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Sample records for metabolic flux control

  1. 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

  2. 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.

  3. 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.

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

    Science.gov (United States)

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

    2017-06-27

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

  5. Flux networks in metabolic graphs

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  6. 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.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  8. 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...

  9. 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.

  10. Regulation of flux through metabolic cycles

    International Nuclear Information System (INIS)

    Walsh, K.

    1984-01-01

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

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

    Science.gov (United States)

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

    2003-11-01

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

  12. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  14. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.

    2016-01-01

    Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat...... is similar to the overflow metabolism observed in many other microorganisms, e.g. ethanol production by Sacchromyces cerevisiae at nitrogen limitation....

  15. Metabolic-flux dependent regulation of microbial physiology.

    Science.gov (United States)

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

    2018-04-01

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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Nielsen Lars K

    2009-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Tim Daniel Rose

    2018-04-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

  20. Neutron flux control systems validation

    International Nuclear Information System (INIS)

    Hascik, R.

    2003-01-01

    In nuclear installations main requirement is to obtain corresponding nuclear safety in all operation conditions. From the nuclear safety point of view is commissioning and start-up after reactor refuelling appropriate period for safety systems verification. In this paper, methodology, performance and results of neutron flux measurements systems validation is presented. Standard neutron flux measuring chains incorporated into the reactor protection and control system are used. Standard neutron flux measuring chain contains detector, preamplifier, wiring to data acquisition unit, data acquisition unit, wiring to display at control room and display at control room. During reactor outage only data acquisition unit and wiring and displaying at reactor control room is verified. It is impossible to verify detector, preamplifier and wiring to data acquisition recording unit during reactor refuelling according to low power. Adjustment and accurate functionality of these chains is confirmed by start-up rate (SUR) measurement during start-up tests after refuelling of the reactors. This measurement has direct impact to nuclear safety and increase operational nuclear safety level. Briefly description of each measuring system is given. Results are illustrated on measurements performed at Bohunice NPP during reactor start-up tests. Main failures and their elimination are described (Authors)

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

    Directory of Open Access Journals (Sweden)

    Nanette R Boyle

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

  2. Thermodynamics of the control of metabolism

    NARCIS (Netherlands)

    Westerhoff, H. V.; Plomp, P. J.; Groen, A. K.; Wanders, R. J.

    1987-01-01

    A theory is presented, describing the control analysis of metabolic systems in terms of Gibbs free energies, extending earlier work of Kacser and Burns (25), and Heinrich and Rapoport (29). It is shown that relationships exist between flux control coefficients (the degree to which enzymes control

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Hyun-Seob Song

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2016-07-11

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

  7. 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.

  8. Dissolved organic matter and lake metabolism: Biogeochemistry and controls of nutrient flux dynamics in lakes: Technical progress report, 1 July 1986-30 June 1987

    International Nuclear Information System (INIS)

    Wetzel, R.G.

    1987-01-01

    Most lakes are small and possess large littoral and wetland components in the interface region between the open water per se and the drainage basin. Not only does the photosynthetic productivity of the surrounding littoral-wetland complex vastly exceed that of the pelagic zone, but the littoral-wetland vegetation and its intensive synthesis and decompositional metabolism regulate loading of inorganic nutrients passing to the open water (functioning as pulsed sources and sinks), and regulate loading of dissolved organic matter and particulate organic matter to the recipient open water, which by numerous complex pathways and mechanisms enhance or suppress pelagic productivity. Research emphasis was placed on the sources, fates, and interactions of dissolved and particulate organic matter in relation to inorganic chemical cycling: allochthonous loading to the lake system; and the coupled nutrient physiology and metabolism of phytoplankton, bacterial populations, macrophytes and attendant sessile algal-bacterial communities. Regulatory mechanisms of growth and rates of carbon and nutrient cycling were evaluated among the inorganic-organic influxes of allochthonous sources as they are controlled by wetland-littoral communities, the littoral photosynthetic producer-decomposer complex, the microflora of the sediment-water interface, and the microflora of the pelagic zone. 28 refs., 13 figs., 2 tabs

  9. 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.

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

    Science.gov (United States)

    Ando, David; Garcia Martin, Hector

    2018-01-01

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

  11. 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...

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

    Directory of Open Access Journals (Sweden)

    Verónica S. Martínez

    2015-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-08-19

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

  14. Maintenance metabolism and carbon fluxes in Bacillus species

    Directory of Open Access Journals (Sweden)

    Decasper Seraina

    2008-06-01

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

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Jordà Joel

    2012-05-01

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

  17. Device for controlling neutron flux

    International Nuclear Information System (INIS)

    Hirukawa, Koji.

    1979-01-01

    Purpose: To separately provide a reflux-type control tube and a scramming control rod, and arrange respective control tube groups concentrically from the core to the outside, and add a monitoring material thereto, thereby simplifying control system, flattening and controlling the core power. Constitution: At the central part of four fuel assemblies there are arranged reflux type control tubes filled with a solution of a neutron control substance, and four of the fundamental units are assembled and scramming control rods and provided at the center of these fundamental units in a freely insertable and removable manner, thereby forming a unit. The units of reflux type control tubes filled with the solutions of the neutron control substances having different concentrations are arranged concentrically from the core to the outside. Further, a monitoring substance such as phosphoric acid or the like, displaying similar behaviors as the solution is added in the solution, and the concentration of the solution is continuously measured. (Sekiya, K.)

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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...

  20. 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

  1. Topological analysis of metabolic control.

    Science.gov (United States)

    Sen, A K

    1990-12-01

    A topological approach is presented for the analysis of control and regulation in metabolic pathways. In this approach, the control structure of a metabolic pathway is represented by a weighted directed graph. From an inspection of the topology of the graph, the control coefficients of the enzymes are evaluated in a heuristic manner in terms of the enzyme elasticities. The major advantage of the topological approach is that it provides a visual framework for (1) calculating the control coefficients of the enzymes, (2) analyzing the cause-effect relationships of the individual enzymes, (3) assessing the relative importance of the enzymes in metabolic regulation, and (4) simplifying the structure of a given pathway, from a regulatory viewpoint. Results are obtained for (a) an unbranched pathway in the absence of feedback the feedforward regulation and (b) an unbranched pathway with feedback inhibition. Our formulation is based on the metabolic control theory of Kacser and Burns (1973) and Heinrich and Rapoport (1974).

  2. 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)

  3. 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.

  4. (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.

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

    Desai, Trunil S; Srivastava, Shireesh

    2018-01-01

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

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

    Science.gov (United States)

    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.

  13. 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.

  14. Precision metabolic engineering: The design of responsive, selective, and controllable metabolic systems.

    Science.gov (United States)

    McNerney, Monica P; Watstein, Daniel M; Styczynski, Mark P

    2015-09-01

    Metabolic engineering is generally focused on static optimization of cells to maximize production of a desired product, though recently dynamic metabolic engineering has explored how metabolic programs can be varied over time to improve titer. However, these are not the only types of applications where metabolic engineering could make a significant impact. Here, we discuss a new conceptual framework, termed "precision metabolic engineering," involving the design and engineering of systems that make different products in response to different signals. Rather than focusing on maximizing titer, these types of applications typically have three hallmarks: sensing signals that determine the desired metabolic target, completely directing metabolic flux in response to those signals, and producing sharp responses at specific signal thresholds. In this review, we will first discuss and provide examples of precision metabolic engineering. We will then discuss each of these hallmarks and identify which existing metabolic engineering methods can be applied to accomplish those tasks, as well as some of their shortcomings. Ultimately, precise control of metabolic systems has the potential to enable a host of new metabolic engineering and synthetic biology applications for any problem where flexibility of response to an external signal could be useful. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-04-21

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

  16. 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...

  17. 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...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Richard A Notebaart

    2008-01-01

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

  20. 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.

  1. 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

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

    Science.gov (United States)

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

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

  3. Flux control through protein phosphorylation in yeast

    DEFF Research Database (Denmark)

    Chen, Yu; Nielsen, Jens

    2016-01-01

    Protein phosphorylation is one of the most important mechanisms regulating metabolism as it can directly modify metabolic enzymes by the addition of phosphate groups. Attributed to such a rapid and reversible mechanism, cells can adjust metabolism rapidly in response to temporal changes. The yeast...... as well as identify mechanisms underlying human metabolic diseases. Here we collect functional phosphorylation events of 41 enzymes involved in yeast metabolism and demonstrate functional mechanisms and the application of this information in metabolic engineering. From a systems biology perspective, we...... describe the development of phosphoproteomics in yeast as well as approaches to analysing the phosphoproteomics data. Finally, we focus on integrated analyses with other omics data sets and genome-scale metabolic models. Despite the advances, future studies improving both experimental technologies...

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

    Science.gov (United States)

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

    2010-04-19

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

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

    Directory of Open Access Journals (Sweden)

    Robert eHeise

    2015-06-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  7. "Active Flux" DTFC-SVM Sensorless Control of IPMSM

    DEFF Research Database (Denmark)

    Boldea, Ion; Codruta Paicu, Mihaela; Gheorghe-Daniel, Andreescu,

    2009-01-01

    This paper proposes an implementation of a motionsensorless control system in wide speed range based on "active flux" observer, and direct torque and flux control with space vector modulation (DTFC-SVM) for the interior permanent magnet synchronous motor (IPMSM), without signal injection....... The concept of "active flux" (or "torque producing flux") turns all the rotor salient-pole ac machines into fully nonsalient-pole ones. A new function for Lq inductance depending on torque is introduced to model the magnetic saturation. Notable simplification in the rotor position and speed estimation...

  8. 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

  9. 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

  10. 13C Metabolic Flux Analysis for systematic metabolic engineering of S. cerevisiae for overproduction of fatty acids.

    Directory of Open Access Journals (Sweden)

    Amit Ghosh

    2016-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Rabus Ralf

    2009-09-01

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

  12. 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.

  13. 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.

  14. 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.

  15. 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)

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

    Science.gov (United States)

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

    2013-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Elad Noor

    2016-11-01

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

  18. Short communication: Assessment of activity patterns of growing rabbits in a flux-controlled chamber

    Directory of Open Access Journals (Sweden)

    Irene Olivas

    2013-06-01

    Full Text Available Flux-controlled and metabolic chambers are often used for nutritional and environmental studies. However, the potential alterations of animal behaviour and welfare are so far not fully understood. In consequence, this study had 2 main objectives: to assess potential alterations of animal activity pattern and time budget inside a flux chamber, and to assess the importance of the “rearing up” behaviour. To this end, 10 growing rabbits of different ages (from 1 to 5 wk of the growing period were housed inside a flux chamber. Their activity was continuously recorded and assessed, determining the frequency and duration of 8 different behaviours: lying, sleeping, sitting, eating, drinking, walking, rearing up and others. Nocturnal rabbit behaviour and time budget were not altered inside the chamber if compared to previously described rabbit activity under conventional cages. In addition, rabbits in this experiment presented a tendency to perform “rearing up” when housed inside the flux chamber.

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

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    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

  20. 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...

  1. 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.

  2. 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.

  3. 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.

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

    Science.gov (United States)

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

    2015-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Francesco Alessandro Massucci

    2013-09-01

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

  6. Feedforward temperature control using a heat flux microsensor

    OpenAIRE

    Lartz, Douglas John

    1993-01-01

    The concept of using heat flux measurements to provide the input for a feedforward temperature control loop is investigated. The feedforward loop is added to proportional and integral feedback control to increase the speed of the response to a disturbance. Comparison is made between the feedback and the feedback plus feedforward control laws. The control law with the feedforward control loop is also compared to the conventional approach of adding derivative control to speed up ...

  7. TORCing up metabolic control in the brain.

    Science.gov (United States)

    Hietakangas, Ville; Cohen, Stephen M

    2008-05-01

    Transducer of regulated CREB activity 2 (TORC2) is a coactivator of CREB and an important regulator of energy balance in mammals through control of gluconeogenesis in the liver. In this issue of Cell Metabolism, Wang and coworkers (2008) report an intriguing role for Drosophila TORC in the neuronal regulation of metabolism.

  8. Controlling the flux dynamics in superconductors by nanostructured magnetic arrays

    Science.gov (United States)

    Kapra, Andrey

    In this thesis we investigate theoretically how the critical current jc of nano-engineered mesoscopic superconducting film can be improved and how one can control the dynamics of the magnetic flux, e.g., the transition from flux-pinned to flux-flow regime, using arrays of magnetic nanostructures. In particularly we investigate: (1) Vortex transport phenomena in superconductors with deposited ferromagnetic structures on top, and the influence of the sample geometry on the critical parameters and on the vortex configurations. Changing geometry of the magnetic bars and magnetization of the bars will affect the critical current jc of the superconducting film. Such nanostructured ferromagnets strongly alter the vortex structure in its neighborhood. The influence of geometry, position and magnetization of the ferromagnet (single bar or regular lattice of the bars) on the critical parameters of the superconductor is investigated. (2) Effect of flux confinement in narrow superconducting channels with zigzag-shaped banks: the flux motion is confined in the transverse (perpendicular) direction of a diamond-cell-shape channel. The matching effect for the magnetic flux is found in the system relevantless of boundary condition. We discuss the dynamics of vortices in the samples and vortex pattern formation in the channel. We show how the inclusion of higher-Tc superconductor into the sample can lead to enhanced properties of the system. By adding an external driving force, we study the vortex dynamics. The different dynamic regimes are discussed. They allowed an effective control of magnetic flux in superconductors.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Saratram Gopalakrishnan

    2015-12-01

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

  11. 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

  12. Very low speed performance of active flux based sensorless control: interior permanent magnet synchronous motor vector control versus direct torque and flux control

    DEFF Research Database (Denmark)

    Paicu, M. C.; Boldea, I.; Andreescu, G. D.

    2009-01-01

    This study is focused on very low speed performance comparison between two sensorless control systems based on the novel ‘active flux' concept, that is, the current/voltage vector control versus direct torque and flux control (DTFC) for interior permanent magnet synchronous motor (IPMSM) drives...... with space vector modulation (SVM), without signal injection. The active flux, defined as the flux that multiplies iq current in the dq-model torque expression of all ac machines, is easily obtained from the stator-flux vector and has the rotor position orientation. Therefore notable simplification...

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

    Directory of Open Access Journals (Sweden)

    Manuel Quirós

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

  15. 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.

  16. 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.

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Picó Jesús

    2007-10-01

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

  19. How to determine control of growth rate in a chemostat. Using metabolic control analysis to resolve the paradox

    DEFF Research Database (Denmark)

    Snoep, Jacky L.; Jensen, Peter Ruhdal; Groeneveld, Philip

    1994-01-01

    how, paradoxically, one can determine control of growth rate, of growth yield and of other fluxes in a chemostat. We develop metabolic control analysis for the chemostat. this analysis does not depend on the particular way in which specific growth rate varies with the concentration of the growth...

  20. Heat and Flux. Enabling the Wind Turbine Controller

    Energy Technology Data Exchange (ETDEWEB)

    Schaak, P. [ECN Wind Energy, Petten (Netherlands)

    2006-09-15

    In the years 1999-2003 ECN invented and patented the technique 'Heat and Flux'. The idea behind Heat and Flux is that tuning turbines at the windward side of a wind farm more transparent than usual, i.e. realising an axial induction factor below the Lanchester-Betz optimum of 1/3, should raise net farm production and lower mechanical turbine loading without causing draw-backs. For scaled farms in a boundary layer wind tunnel this hypothesis has been proved in previous projects. To enable alternative turbine transparencies, the wind turbine controller must support the additional control aim 'desired transparency'. During this study we have determined a general method to design a transparency control algorithm. This method has been implemented in ECN's 'Control Tool' for designing wind turbine control algorithms. The aero-elastic wind turbine code Phatas has been used to verify the resulting control algorithm. Heat and Flux does not fundamentally change the control of horizontal axis variable speed wind turbines. The axial induction can be reduced by an offset on blade pitch or generator torque. Weighing reliability against performance profits, it appeared to be advisable to adapt only blade angle control.

  1. Electric control of the heat flux through electrophononic effects

    Science.gov (United States)

    Seijas-Bellido, Juan Antonio; Aramberri, Hugo; Íñiguez, Jorge; Rurali, Riccardo

    2018-05-01

    We demonstrate a fully electric control of the heat flux, which can be continuously modulated by an externally applied electric field in PbTiO3, a prototypical ferroelectric perovskite, revealing the mechanisms by which experimentally accessible fields can be used to tune the thermal conductivity by as much as 50% at room temperature.

  2. (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.

  3. High quality flux control system for electron gun evaporation

    International Nuclear Information System (INIS)

    Appelbloom, A.M.; Hadley, P.; van der Marel, D.; Mooij, J.E.

    1991-01-01

    This paper reports on a high quality flux control system for electron gun evaporation developed and tested for the MBE growth of high temperature superconductors. The system can be applied to any electron gun without altering the electron gun itself. Essential elements of the system are a high bandwidth mass spectrometer, control electronics and a high voltage modulator to sweep the electron beam over the melt at high frequencies. the sweep amplitude of the electron beam is used to control the evaporation flux at high frequencies. The feedback loop of the system has a bandwidth of over 100 Hz, which makes it possible to grow superlattices and layered structures in a fast and precisely controlled manner

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

    Directory of Open Access Journals (Sweden)

    Akιn Ata

    2007-12-01

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

  5. 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

  6. Soil Carbon Dioxide Production and Surface Fluxes: Subsurface Physical Controls

    Science.gov (United States)

    Risk, D.; Kellman, L.; Beltrami, H.

    Soil respiration is a critical determinant of landscape carbon balance. Variations in soil temperature and moisture patterns are important physical processes controlling soil respiration which need to be better understood. Relationships between soil respi- ration and physical controls are typically addressed using only surface flux data but other methods also exist which permit more rigorous interpretation of soil respira- tion processes. Here we use a combination of subsurface CO_{2} concentrations, surface CO_{2} fluxes and detailed physical monitoring of the subsurface envi- ronment to examine physical controls on soil CO_{2} production at four climate observatories in Eastern Canada. Results indicate that subsurface CO_{2} produc- tion is more strongly correlated to the subsurface thermal environment than the surface CO_{2} flux. Soil moisture was also found to have an important influence on sub- surface CO_{2} production, particularly in relation to the soil moisture - soil profile diffusivity relationship. Non-diffusive profile CO_{2} transport appears to be im- portant at these sites, resulting in a de-coupling of summertime surface fluxes from subsurface processes and violating assumptions that surface CO_{2} emissions are the result solely of diffusion. These results have implications for the study of soil respiration across a broad range of terrestrial environments.

  7. 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.

  8. IPMSM Motion-Sensorless Direct Torque and Flux Control

    DEFF Research Database (Denmark)

    Pitict, Christian Ilie; Andreescu, Gheorghe-Daniel; Blaabjerg, Frede

    2005-01-01

    The paper presents a rather comprehensive implementation of a wide speed motion-sensorless control of IPMSM drives via direct torque and flux control (DTFC) with space vector modulation (SVM). Signal injection with only one D-module vector filter and phase-locked loop (PLL) observer is used at low...... provides for a smooth current waveform even at 1 rpm. The paper demonstrates through ample experiments a 1750 rpm 1 1 rpm speed range full-loaded with sensorless DTFC-SVM....

  9. 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...

  10. 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...

  11. 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

  12. 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....

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

    Directory of Open Access Journals (Sweden)

    Cervantes Duarte, R.

    2016-09-01

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

  14. 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.

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

    Science.gov (United States)

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

    2012-09-15

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

  16. Metabolic gene polymorphism frequencies in control populations

    DEFF Research Database (Denmark)

    Garte, Seymour; Gaspari, Laura; Alexandrie, Anna-Karin

    2001-01-01

    Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1...

  17. Stability and Bifurcation in Magnetic Flux Feedback Maglev Control System

    Directory of Open Access Journals (Sweden)

    Wen-Qing Zhang

    2013-01-01

    Full Text Available Nonlinear properties of magnetic flux feedback control system have been investigated mainly in this paper. We analyzed the influence of magnetic flux feedback control system on control property by time delay and interfering signal of acceleration. First of all, we have established maglev nonlinear model based on magnetic flux feedback and then discussed hopf bifurcation’s condition caused by the acceleration’s time delay. The critical value of delayed time is obtained. It is proved that the period solution exists in maglev control system and the stable condition has been got. We obtained the characteristic values by employing center manifold reduction theory and normal form method, which represent separately the direction of hopf bifurcation, the stability of the period solution, and the period of the period motion. Subsequently, we discussed the influence maglev system on stability of by acceleration’s interfering signal and obtained the stable domain of interfering signal. Some experiments have been done on CMS04 maglev vehicle of National University of Defense Technology (NUDT in Tangshan city. The results of experiments demonstrate that viewpoints of this paper are correct and scientific. When time lag reaches the critical value, maglev system will produce a supercritical hopf bifurcation which may cause unstable period motion.

  18. Flux

    DEFF Research Database (Denmark)

    Ravn, Ib

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

  19. Flux-weakening control methods for hybrid excitation synchronous motor

    Directory of Open Access Journals (Sweden)

    Mingming Huang

    2015-09-01

    Full Text Available The hybrid excitation synchronous motor (HESM, which aim at combining the advantages of permanent magnet motor and wound excitation motor, have the characteristics of low-speed high-torque hill climbing and wide speed range. Firstly, a new kind of HESM is presented in the paper, and its structure and mathematical model are illustrated. Then, based on a space voltage vector control, a novel flux-weakening method for speed adjustment in the high speed region is presented. The unique feature of the proposed control method is that the HESM driving system keeps the q-axis back-EMF components invariable during the flux-weakening operation process. Moreover, a copper loss minimization algorithm is adopted to reduce the copper loss of the HESM in the high speed region. Lastly, the proposed method is validated by the simulation and the experimental results.

  20. 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)

  1. An Autophagic Flux Probe that Releases an Internal Control.

    Science.gov (United States)

    Kaizuka, Takeshi; Morishita, Hideaki; Hama, Yutaro; Tsukamoto, Satoshi; Matsui, Takahide; Toyota, Yuichiro; Kodama, Akihiko; Ishihara, Tomoaki; Mizushima, Tohru; Mizushima, Noboru

    2016-11-17

    Macroautophagy is an intracellular degradation system that utilizes the autophagosome to deliver cytoplasmic components to the lysosome. Measuring autophagic activity is critically important but remains complicated and challenging. Here, we have developed GFP-LC3-RFP-LC3ΔG, a fluorescent probe to evaluate autophagic flux. This probe is cleaved by endogenous ATG4 proteases into equimolar amounts of GFP-LC3 and RFP-LC3ΔG. GFP-LC3 is degraded by autophagy, while RFP-LC3ΔG remains in the cytosol, serving as an internal control. Thus, autophagic flux can be estimated by calculating the GFP/RFP signal ratio. Using this probe, we re-evaluated previously reported autophagy-modulating compounds, performed a high-throughput screen of an approved drug library, and identified autophagy modulators. Furthermore, we succeeded in measuring both induced and basal autophagic flux in embryos and tissues of zebrafish and mice. The GFP-LC3-RFP-LC3ΔG probe is a simple and quantitative method to evaluate autophagic flux in cultured cells and whole organisms. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-03-01

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

  3. 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/.

  4. 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.

  5. The bifunctional autophagic flux by 2-deoxyglucose to control survival or growth of prostate cancer cells

    International Nuclear Information System (INIS)

    Jeon, Jeong Yong; Kim, Seung Won; Park, Ki Cheong; Yun, Mijin

    2015-01-01

    Recent reports using metabolism regulating drugs showed that nutrient deprivation was an efficient tool to suppress cancer progression. In addition, autophagy control is emerging to prevent cancer cell survival. Autophagy breaks down the unnecessary cytoplasmic components into anabolic units and energy sources, which are the most important sources for making the ATP that maintains homeostasis in cancer cell growth and survival. Therefore, the glucose analog 2-deoxyglucose (2DG) has been used as an anticancer reagent due to its inhibition of glycolysis. Prostate cancer cells (PC3) were treated with 2DG for 6 h or 48 h to analyze the changing of cell cycle and autophagic flux. Rapamycin and LC3B overexpressing vectors were administered to PC3 cells for autophagy induction and chloroquine and shBeclin1 plasmid were used to inhibit autophagy in PC3 cells to analyze PC3 cells growth and survival. The samples for western blotting were prepared in each culture condition to confirm the expression level of autophagy related and regulating proteins. We demonstrated that 2DG inhibits PC3 cells growth and had discriminating effects on autophagy regulation based on the different time period of 2DG treatment to control cell survival. Short-term treatment of 2DG induced autophagic flux, which increased microtubule associated protein 1 light chain 3B (LC3B) conversion rates and reduced p62 levels. However, 2DG induced autophagic flux is remarkably reduced over an extended time period of 2DG treatment for 48 h despite autophagy inducing internal signaling being maintained. The relationship between cell growth and autophagy was proved. Increased autophagic flux by rapamycin or LC3B overexpression powerfully reduced cell growth, while autophagy inhibition with shBeclin1 plasmid or chloroquine had no significant effect on regulating cell growth. Given these results, maintaining increased autophagic flux was more effective at inhibiting cancer cell progression than inhibition of

  6. Fourier transform and controlling of flux in scalar hysteresis measurement

    International Nuclear Information System (INIS)

    Kuczmann, Miklos

    2008-01-01

    The paper deals with a possible realization of eliminating the effect of noise in scalar hysteresis measurements. The measured signals have been transformed into the frequency domain, and, after applying digital filter, the spectrums of the filtered signals have been transformed back to the time domain. The proposed technique results in an accurate noise-removal algorithm. The paper illustrates a fast controlling algorithm applying the inverse of the actually measured hysteresis loop, and another proportional one to measure distorted flux pattern. By developing the mentioned algorithms, it aims at the controlling of a more complicated phenomena, i.e. measuring the vector hysteresis characteristics

  7. Metabolic Control of Redox and Redox Control of Metabolism in Plants

    Science.gov (United States)

    Fernie, Alisdair R.

    2014-01-01

    Abstract Significance: Reduction-oxidation (Redox) status operates as a major integrator of subcellular and extracellular metabolism and is simultaneously itself regulated by metabolic processes. Redox status not only dominates cellular metabolism due to the prominence of NAD(H) and NADP(H) couples in myriad metabolic reactions but also acts as an effective signal that informs the cell of the prevailing environmental conditions. After relay of this information, the cell is able to appropriately respond via a range of mechanisms, including directly affecting cellular functioning and reprogramming nuclear gene expression. Recent Advances: The facile accession of Arabidopsis knockout mutants alongside the adoption of broad-scale post-genomic approaches, which are able to provide transcriptomic-, proteomic-, and metabolomic-level information alongside traditional biochemical and emerging cell biological techniques, has dramatically advanced our understanding of redox status control. This review summarizes redox status control of metabolism and the metabolic control of redox status at both cellular and subcellular levels. Critical Issues: It is becoming apparent that plastid, mitochondria, and peroxisome functions influence a wide range of processes outside of the organelles themselves. While knowledge of the network of metabolic pathways and their intraorganellar redox status regulation has increased in the last years, little is known about the interorganellar redox signals coordinating these networks. A current challenge is, therefore, synthesizing our knowledge and planning experiments that tackle redox status regulation at both inter- and intracellular levels. Future Directions: Emerging tools are enabling ever-increasing spatiotemporal resolution of metabolism and imaging of redox status components. Broader application of these tools will likely greatly enhance our understanding of the interplay of redox status and metabolism as well as elucidating and

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

    Indian Academy of Sciences (India)

    2015-09-28

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

  9. 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.

  10. 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

  11. Role of metabolic control on diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Macedo Célia Sperandéo

    2002-01-01

    Full Text Available OBJECTIVE: The aim of this investigation was studying the influence of glucose metabolic control on diabetic nephropathy. The authors observed the effect of acarbose, insulin, and both drugs on the metabolic control and development of mesangial enlargement of kidney glomeruli in alloxan-diabetic rats. METHODS: Five groups of Wistar rats were used: normal rats (N, non-treated alloxan-diabetic rats (D, alloxan-diabetic rats treated with acarbose (AD, alloxan-diabetic rats treated with insulin (ID, and alloxan-diabetic rats treated with insulin plus acarbose (IAD. The following parameters were evaluated: body weight; water and food intake; diuresis; blood and urine glucose levels; and the kidney lesions: mesangial enlargement and tubule cell vacuolization. Renal lesions were analysed using a semi-quantitative score 1, 3, 6, 9, and 12 months after diabetes induction. RESULTS: Diabetic rats showed a marked increase of glycemia, urinary glucose levels, diuresis, water and food intake, and weight loss, while the treated diabetic rats showed significant decreased levels of these parameters. The most satisfactory metabolic control was that of diabetic rats treated with acarbose + insulin. There was a significant mesangial enlargement in diabetic rats compared to normal rats from the third up to the 12th month after diabetes induction, with a significant difference between the animals treated with acarbose + insulin and non-treated diabetic rats. A difference between the animals treated with acarbose or insulin alone and non-treated diabetics rats was not seen. CONCLUSIONS: The authors discuss the results stressing the role of diabetic metabolic control in the prevention of diabetic nephropathy.

  12. 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.

  13. Decoupling Suspension Controller Based on Magnetic Flux Feedback

    Directory of Open Access Journals (Sweden)

    Wenqing Zhang

    2013-01-01

    Full Text Available The suspension module control system model has been established based on MIMO (multiple input and multiple output state feedback linearization. We have completed decoupling between double suspension points, and the new decoupling method has been applied to CMS04 magnetic suspension vehicle in national mid-low-speed maglev experiment field of Tangshan city in China. Double suspension system model is very accurate for investigating stability property of maglev control system. When magnetic flux signal is taken back to the suspension control system, the suspension module’s antijamming capacity for resisting suspension load variety has been proved. Also, the external force interference has been enhanced. As a result, the robustness and stability properties of double-electromagnet suspension control system have been enhanced.

  14. Decoupling suspension controller based on magnetic flux feedback.

    Science.gov (United States)

    Zhang, Wenqing; Li, Jie; Zhang, Kun; Cui, Peng

    2013-01-01

    The suspension module control system model has been established based on MIMO (multiple input and multiple output) state feedback linearization. We have completed decoupling between double suspension points, and the new decoupling method has been applied to CMS04 magnetic suspension vehicle in national mid-low-speed maglev experiment field of Tangshan city in China. Double suspension system model is very accurate for investigating stability property of maglev control system. When magnetic flux signal is taken back to the suspension control system, the suspension module's antijamming capacity for resisting suspension load variety has been proved. Also, the external force interference has been enhanced. As a result, the robustness and stability properties of double-electromagnet suspension control system have been enhanced.

  15. An accurate reactive power control study in virtual flux droop control

    Science.gov (United States)

    Wang, Aimeng; Zhang, Jia

    2017-12-01

    This paper investigates the problem of reactive power sharing based on virtual flux droop method. Firstly, flux droop control method is derived, where complicated multiple feedback loops and parameter regulation are avoided. Then, the reasons for inaccurate reactive power sharing are theoretically analyzed. Further, a novel reactive power control scheme is proposed which consists of three parts: compensation control, voltage recovery control and flux droop control. Finally, the proposed reactive power control strategy is verified in a simplified microgrid model with two parallel DGs. The simulation results show that the proposed control scheme can achieve accurate reactive power sharing and zero deviation of voltage. Meanwhile, it has some advantages of simple control and excellent dynamic and static performance.

  16. Fault tolerant homopolar magnetic bearings with flux invariant control

    International Nuclear Information System (INIS)

    Na, Uhn Joo

    2006-01-01

    The theory for a novel fault-tolerant 4-active-pole homopolar magnetic bearing is developed. If any one coil of the four coils in the bearing actuator fail, the remaining three coil currents change via an optimal distribution matrix such that the same opposing pole, C-core type, control fluxes as those of the un-failed bearing are produced. The homopolar magnetic bearing thus provides unaltered magnetic forces without any loss of the bearing load capacity even if any one coil suddenly fails. Numerical examples are provided to illustrate the novel fault-tolerant, 4-active pole homopolar magnetic bearings

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

    Science.gov (United States)

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

    2017-10-01

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

  18. 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...

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Fabrication of control rods for the High Flux Isotope Reactor

    International Nuclear Information System (INIS)

    Sease, J.D.

    1998-01-01

    The High Flux Isotope Reactor (HFIR) is a research-type nuclear reactor that was designed and built in the early 1960s and has been in continuous operation since its initial criticality in 1965. Under current plans, the HFIR is expected to continue in operation until 2035. This report updates ORNL/TM-9365, Fabrication Procedure for HFIR Control Plates, which was mainly prepared in the early 1970's but was not issued until 1984, and reflects process changes, lessons learned in the latest control rod fabrication campaign, and suggested process improvements to be considered in future campaigns. Most of the personnel involved with the initial development of the processes and in part campaigns have retired or will retire soon. Because their unlikely availability in future campaigns, emphasis has been placed on providing some explanation of why the processes were selected and some discussions about the importance of controlling critical process parameters. Contained in this report is a description of the function of control rods in the reactor, the brief history of the development of control rod fabrication processes, and a description of procedures used in the fabrication of control rods. A listing of the controlled documents and procedures used in the last fabrication campaigns is referenced in Appendix A

  4. Fabrication of control rods for the High Flux Isotope Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Sease, J.D.

    1998-03-01

    The High Flux Isotope Reactor (HFIR) is a research-type nuclear reactor that was designed and built in the early 1960s and has been in continuous operation since its initial criticality in 1965. Under current plans, the HFIR is expected to continue in operation until 2035. This report updates ORNL/TM-9365, Fabrication Procedure for HFIR Control Plates, which was mainly prepared in the early 1970's but was not issued until 1984, and reflects process changes, lessons learned in the latest control rod fabrication campaign, and suggested process improvements to be considered in future campaigns. Most of the personnel involved with the initial development of the processes and in part campaigns have retired or will retire soon. Because their unlikely availability in future campaigns, emphasis has been placed on providing some explanation of why the processes were selected and some discussions about the importance of controlling critical process parameters. Contained in this report is a description of the function of control rods in the reactor, the brief history of the development of control rod fabrication processes, and a description of procedures used in the fabrication of control rods. A listing of the controlled documents and procedures used in the last fabrication campaigns is referenced in Appendix A.

  5. Metabolic control of feed intake: implications for metabolic disease of fresh cows.

    Science.gov (United States)

    Allen, Michael S; Piantoni, Paola

    2013-07-01

    The objective of this article is to discuss metabolic control of feed intake in the peripartum period and its implications for metabolic disease of fresh cows. Understanding how feed intake is controlled during the transition from gestation to lactation is critical to both reduce risk and successfully treat many metabolic diseases. Copyright © 2013. Published by Elsevier Inc.

  6. Molecular, metabolic, and genetic control: An introduction

    Science.gov (United States)

    Tyson, John J.; Mackey, Michael C.

    2001-03-01

    The living cell is a miniature, self-reproducing, biochemical machine. Like all machines, it has a power supply, a set of working components that carry out its necessary tasks, and control systems that ensure the proper coordination of these tasks. In this Special Issue, we focus on the molecular regulatory systems that control cell metabolism, gene expression, environmental responses, development, and reproduction. As for the control systems in human-engineered machines, these regulatory networks can be described by nonlinear dynamical equations, for example, ordinary differential equations, reaction-diffusion equations, stochastic differential equations, or cellular automata. The articles collected here illustrate (i) a range of theoretical problems presented by modern concepts of cellular regulation, (ii) some strategies for converting molecular mechanisms into dynamical systems, (iii) some useful mathematical tools for analyzing and simulating these systems, and (iv) the sort of results that derive from serious interplay between theory and experiment.

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

    Science.gov (United States)

    Unrean, Pornkamol; Nguyen, Nhung H A

    2012-06-01

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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Joel Jordà

    2014-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Lucile Courtial

    2017-08-01

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

  11. Chemical potential and reaction electronic flux in symmetry controlled reactions.

    Science.gov (United States)

    Vogt-Geisse, Stefan; Toro-Labbé, Alejandro

    2016-07-15

    In symmetry controlled reactions, orbital degeneracies among orbitals of different symmetries can occur along a reaction coordinate. In such case Koopmans' theorem and the finite difference approximation provide a chemical potential profile with nondifferentiable points. This results in an ill-defined reaction electronic flux (REF) profile, since it is defined as the derivative of the chemical potential with respect to the reaction coordinate. To overcome this deficiency, we propose a new way for the calculation of the chemical potential based on a many orbital approach, suitable for reactions in which symmetry is preserved. This new approach gives rise to a new descriptor: symmetry adapted chemical potential (SA-CP), which is the chemical potential corresponding to a given irreducible representation of a symmetry group. A corresponding symmetry adapted reaction electronic flux (SA-REF) is also obtained. Using this approach smooth chemical potential profiles and well defined REFs are achieved. An application of SA-CP and SA-REF is presented by studying the Cs enol-keto tautomerization of thioformic acid. Two SA-REFs are obtained, JA'(ξ) and JA'' (ξ). It is found that the tautomerization proceeds via an in-plane delocalized 3-center 4-electron O-H-S hypervalent bond which is predicted to exist only in the transition state (TS) region. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion

    DEFF Research Database (Denmark)

    Anderson, Kristin A; Huynh, Frank K; Fisher-Wellman, Kelsey

    2017-01-01

    in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance....... These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging....

  13. Hematopoietic stem cell fate through metabolic control.

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2018-05-25

    Hematopoietic stem cells (HSCs) maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions, and this damage may eventually compromise the cells' self-renewal capacity. HSC divisions result in either self-renewal or differentiation, with the balance between the two directly impacting hematopoietic homeostasis; but the heterogeneity of available HSC-enriched fractions, together with the technical challenges of observing HSC behavior, has long hindered the analysis of individual HSCs, and prevented the elucidation of this process. However, recent advances in genetic models, metabolomics analyses and single-cell approaches have revealed the contributions made to HSC self-renewal by metabolic cues, mitochondrial biogenesis, and autophagy/mitophagy, which have highlighted mitochondrial quality as a key control factor in the equilibrium of HSCs. A deeper understanding of precisely how specific modes of metabolism control HSC fate at the single cell level is therefore not only of great biological interest, but will have clear clinical implications for the development of therapies for hematological disease. Copyright © 2018. Published by Elsevier Inc.

  14. 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.

  15. Bilateral Diabetic Papillopathy and Metabolic Control

    DEFF Research Database (Denmark)

    Ostri, Christoffer; Lund-Andersen, Henrik; Sander, Birgit

    2010-01-01

    OBJECTIVE: The pathogenesis of diabetic papillopathy largely is unknown, but case reports suggest that it may follow rapidly improved metabolic control. The present study was designed to investigate this hypothesis. DESIGN: Retrospective case-control study. PARTICIPANTS: Two thousand sixty......-six patients with type 1 diabetes. METHODS: Review of clinical, photographic, and clinical chemistry records from a large diabetology and ophthalmology unit between 2001 and 2008. MAIN OUTCOME MEASURES: Simultaneous, bilateral diabetic papillopathy. RESULTS: The mean follow-up was 4.9 years. During 10 020...... patient-years of observation, bilateral diabetic papillopathy developed in 5 patients. During the year preceding this incident, all 5 patients had experienced a decrease in glycosylated hemoglobin A(1c) (HbA(1C)) at a maximum rate of -2.5 (mean) percentage points per quarter year, which was significantly...

  16. Factors Controlling Nitrogen Fluxes in Groundwater in Agricultural Areas

    Science.gov (United States)

    Liao, L.; Green, C. T.; Bekins, B. A.; Bohlke, J. K.

    2010-12-01

    Predictions of effects of land use changes on water quality require identification of the relative importance of geochemical and hydrologic factors. To understand the factors controlling the transport of nitrogen in groundwater, vertical fluxes of water and solutes were estimated for 13 aquifers in agricultural areas located in California, Iowa, Maryland, Minnesota, Mississippi, Nebraska, North Carolina, Texas, and Wisconsin. The aquifers are overlain by unsaturated zones with thicknesses ranging from 2.5 to 100 m. Precipitation ranges from 19 to 132 cm/yr and irrigation ranges from 0 to 120 cm/yr. Main crop types include corn, soybeans, forage, wheat, and cotton. A 1-dimensional mathematical model was developed to estimate vertical N transport in response to N inputs on the land surface from chemical fertilizer, manure and atmospheric deposition. Simulated vertical profiles of O2, NO3-, N2 from denitrification, Cl- and atmospheric age tracers were matched to observations by adjusting parameters for recharge rate, unsaturated zone travel time, N leaching ratio (defined as leaching fraction of N reaching water table of N input at land surface), Cl- leaching ratio, O2 reduction rate and denitrification rate. Results indicated that vertical NO3 fluxes below the water table were affected by both geochemical and physical factors. High vertical NO3 fluxes below the water table are associated with high N input at the land surface. Values of Cl- leaching ratios were less than 1 (0.42 to 1) likely as a result of runoff and exported harvested crops. N leaching ratios were lower (0.1 to 0.6), consistent with additional N losses such as denitrification and volatilization. The sites with high leaching ratios for both N and Cl tended to be those with high recharge rates and low ET loss, defined as the fraction of applied water lost to ET. Modeled zero-order denitrification rates in the saturated zone varied within an order of magnitude with a maximum rate of 1.6 mg

  17. Super-twisting sliding mode control of torque and flux in permanent magnet synchronous machine drives

    DEFF Research Database (Denmark)

    Lascu, Christian; Boldea, Ion; Blaabjerg, Frede

    2013-01-01

    This paper investigates a permanent magnet synchronous motor drive controlled by a second-order variable structure control technique, known as the super-twisting sliding modes (STSM) control. The STSM controller is designed as a direct torque and flux controller and it works in the stator flux...

  18. High Flux Commercial Illumination Solution with Intelligent Controls

    Energy Technology Data Exchange (ETDEWEB)

    Camil Ghiu

    2012-04-30

    This report summarizes the work performed at OSRAM SYLVANIA under US Department of Energy contract DE-EE0003241 for developing a high efficiency LED-based luminaire. A novel light engine module (two versions: standard and super), power supply and luminaire mechanical parts were designed and tested. At steady-state, the luminaire luminous flux is 3156 lumens (lm), luminous efficacy 97.4 LPW and CRI (Ra) 88 at a correlated color temperature (CCT) of 3507K. When the luminaire is fitted with the super version of the light engine the efficacy reaches 130 LPW. In addition, the luminaire is provided with an intelligent control network capable of additional energy savings. The technology developed during the course of this project has been incorporated into a family of products. Recently, the first product in the family has been launched.

  19. 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

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

    Science.gov (United States)

    Wittmann, Christoph; Heinzle, Elmar

    2002-12-01

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

  1. 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

  2. Robust quasi NID current and flux control of an induction motor for position control

    NARCIS (Netherlands)

    van Duijnhoven, M.; Blachuta, M.J.

    1999-01-01

    In the paper, a new control design method called Dynamic Contraction method is applied to the flux and quadrature current robust control of an induction motor operated using the field orientation principle. The resulting input-output decoupled and linearized drive is then used for time-optimal

  3. Metabolic control analysis of xylose catabolism in Aspergillus

    DEFF Research Database (Denmark)

    Prathumpai, Wai; Gabelgaard, J.B.; Wanchanthuek, P.

    2003-01-01

    , and flux control was shown to be dependent on the metabolite levels. Due to thermodynamic constraints, flux control may reside at the first step in the pathway, i.e., at the xylose reductase, even when the intracellular xylitol concentration is high. On the basis of the kinetic analysis, the general dogma...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  5. Extraction of gadolinium from high flux isotope reactor control plates

    International Nuclear Information System (INIS)

    Kohring, M.W.

    1987-04-01

    Gadolinium-153 is an important radioisotope used in the diagnosis of various bone disorders. Recent medical and technical developments in the detection and cure of osteoporosis, a bone disease affecting an estimated 50 million people, have greatly increased the demand for this isotope. The Oak Ridge National Laboratory (ORNL) has produced 153 Gd since 1980 primarily through the irradiation of a natural europium-oxide powder followed by the chemical separation of the gadolinium fraction from the europium material. Due to the higher demand for 153 Gd, an alternative production method to supplement this process has been investigated. This process involves the extraction of gadolinium from the europium-bearing region of highly radioactive, spent control plates used at the High Flux Isotope Reactor (HFIR) with a subsequent re-irradiation of the extracted material for the production of the 153 Gd. Based on the results of experimental and calculational analyses, up to 25 grams of valuable gadolinium (≥60% enriched in 152 Gd) resides in the europium-bearing region of the HFIR control components of which 70% is recoverable. At a specific activity yield of 40 curies of 153 Gd for each gram of gadolinium re-irradiated, 700 one-curie sources can be produced from each control plate assayed

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

    Science.gov (United States)

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

    2011-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Alves Paula M

    2007-01-01

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

  8. It must be my metabolism: Metabolic control of mind

    Directory of Open Access Journals (Sweden)

    Dana M Small

    2014-07-01

    relationship between the reinforcing potency of sugared solutions and the metabolic effects that follow their consumption (16, also see the abstract of I. de Araujo. We therefore hypothesized that metabolic response provides the critical signal necessary to condition preference. To test this prediction in humans we designed a flavor nutrient conditioning study in which participants first rated their liking for novel flavored beverages and then, over a three week-long conditioning protocol, alternately ingested one of the flavored beverages with 112.5 kcal from maltodextrin, a tasteless and odorless polysaccharide that breaks down into glucose, and another flavored beverage with no calories added. Plasma glucose was measured before and after each of the drinks’ consumption as a proxy measure of metabolic response, assuming that glucose oxidation depends upon the level of circulating glucose. For each participant flavor-calorie pairings were held constant but the identity of the conditioned flavors were counterbalanced across participants. Following the exposure phase, participants’ liking of, and brain responses to, non-caloric versions of the flavors were assessed. We predicted that change in plasma glucose produced by beverage consumption during the exposure sessions would be associated with neural responses in dopamine source and target regions to the calorie predictive flavor. As predicted, response in the ventral striatum and hypothalamus to the calorie-predictive flavor (CS+ vs. non the noncaloric-predictive flavor (CS- was strongly associated with the changes in plasma glucose levels produced by ingestion of these same beverages when consumed previously either with (CS+ or without (CS- calories (17. Specifically, the greater the increase in circulating glucose occurring post ingestion of the beverage containing 112.5 kcal from maltodextrin versus the noncaloric drink, the stronger was the brain response to the CS+ compared to the CS- flavor. Importantly, because each

  9. Emotional Learning Based Intelligent Controllers for Rotor Flux Oriented Control of Induction Motor

    Science.gov (United States)

    Abdollahi, Rohollah; Farhangi, Reza; Yarahmadi, Ali

    2014-08-01

    This paper presents design and evaluation of a novel approach based on emotional learning to improve the speed control system of rotor flux oriented control of induction motor. The controller includes a neuro-fuzzy system with speed error and its derivative as inputs. A fuzzy critic evaluates the present situation, and provides the emotional signal (stress). The controller modifies its characteristics so that the critics stress is reduced. The comparative simulation results show that the proposed controller is more robust and hence found to be a suitable replacement of the conventional PI controller for the high performance industrial drive applications.

  10. 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.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  12. Perspectives in metabolic engineering: understanding cellular regulation towards the control of metabolic routes.

    Science.gov (United States)

    Zadran, Sohila; Levine, Raphael D

    2013-01-01

    Metabolic engineering seeks to redirect metabolic pathways through the modification of specific biochemical reactions or the introduction of new ones with the use of recombinant technology. Many of the chemicals synthesized via introduction of product-specific enzymes or the reconstruction of entire metabolic pathways into engineered hosts that can sustain production and can synthesize high yields of the desired product as yields of natural product-derived compounds are frequently low, and chemical processes can be both energy and material expensive; current endeavors have focused on using biologically derived processes as alternatives to chemical synthesis. Such economically favorable manufacturing processes pursue goals related to sustainable development and "green chemistry". Metabolic engineering is a multidisciplinary approach, involving chemical engineering, molecular biology, biochemistry, and analytical chemistry. Recent advances in molecular biology, genome-scale models, theoretical understanding, and kinetic modeling has increased interest in using metabolic engineering to redirect metabolic fluxes for industrial and therapeutic purposes. The use of metabolic engineering has increased the productivity of industrially pertinent small molecules, alcohol-based biofuels, and biodiesel. Here, we highlight developments in the practical and theoretical strategies and technologies available for the metabolic engineering of simple systems and address current limitations.

  13. 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.

  14. Central nervous system control of triglyceride metabolism

    NARCIS (Netherlands)

    Geerling, Johanna Janetta (Janine)

    2013-01-01

    This thesis describes the role of the brain in the regulation of peripheral triglyceride metabolism, in the context of the metabolic syndrome. Based on various pharmacological studies we described the role of two hormones, insulin and glucagon-like peptide-1, in the production and clearance of

  15. Factors controlling vertical fluxes of prrticles in the Arabian Sea

    Digital Repository Service at National Institute of Oceanography (India)

    Nair, T.M.B.; Ramaswamy, V.; Parthiban, G.; Shankar, R.

    )) in the western Arabian Sea. Carbonate contributed mainly by foraminifers and coccolithophorids, are the dominant component in all the traps. Opal fluxes were maximum in the western Arabian Sea. At all the locations, lithogenic percentages increased with depth...

  16. 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.

  17. Simplified Fuzzy Control for Flux-Weakening Speed Control of IPMSM Drive

    Directory of Open Access Journals (Sweden)

    M. J. Hossain

    2011-01-01

    Full Text Available This paper presents a simplified fuzzy logic-based speed control scheme of an interior permanent magnet synchronous motor (IPMSM above the base speed using a flux-weakening method. In this work, nonlinear expressions of d-axis and q-axis currents of the IPMSM have been derived and subsequently incorporated in the control algorithm for the practical purpose in order to implement fuzzy-based flux-weakening strategy to operate the motor above the base speed. The fundamentals of fuzzy logic algorithms as related to motor control applications are also illustrated. A simplified fuzzy speed controller (FLC for the IPMSM drive has been designed and incorporated in the drive system to maintain high performance standards. The efficacy of the proposed simplified FLC-based IPMSM drive is verified by simulation at various dynamic operating conditions. The simplified FLC is found to be robust and efficient. Laboratory test results of proportional integral (PI controller-based IPMSM drive have been compared with the simulated results of fuzzy controller-based flux-weakening IPMSM drive system.

  18. The glycolytic flux in Escherichia coli is controlled by the demand for ATP

    DEFF Research Database (Denmark)

    Købmann, Brian Jensen; Westerhoff, H.V.; Snoep, J.L.

    2002-01-01

    additional ATP hydrolysis, we increased the flux through glycolysis to 1.7 times that of the wild-type flux. The results demonstrate why attempts in the past to increase the glycolytic flux through overexpression of glycolytic enzymes have been unsuccessful: the majority of flux control (> 75%) resides...... not inside but outside the pathway, i.e., with the enzymes that hydrolyze ATP. These data further allowed us to answer the question of whether catabolic or anabolic reactions control the growth of E. coli. We show that the majority of the control of growth rate resides in the anabolic reactions, i...

  19. Adherence to two methods of education and metabolic control in ...

    African Journals Online (AJOL)

    BACKGROUND: Education in diabetes optimizes metabolic control, prevents acute and chronic complications, and improves quality of life. Our main objective was to evaluate if a better metabolic control is achieved in diabetic patients undergoing a program of intensive interactive care than in those with traditional care and ...

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

    Directory of Open Access Journals (Sweden)

    Cheng Zhong

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

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

    Directory of Open Access Journals (Sweden)

    Sergio eRuiz-Halpern

    2014-12-01

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

  2. 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]).

  3. 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...

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Fabien Coze

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Komi Nambou

    2015-12-01

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

  8. 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.

  9. Enhanced production of resveratrol derivatives in tobacco plants by improving the metabolic flux of intermediates in the phenylpropanoid pathway.

    Science.gov (United States)

    Jeong, Yu Jeong; An, Chul Han; Woo, Su Gyeong; Park, Ji Hye; Lee, Ki-Won; Lee, Sang-Hoon; Rim, Yeonggil; Jeong, Hyung Jae; Ryu, Young Bae; Kim, Cha Young

    2016-09-01

    The biosynthesis of flavonoids such as anthocyanin and stilbenes has attracted increasing attention because of their potential health benefits. Anthocyanins and stilbenes share common phenylpropanoid precursor pathways. We previously reported that the overexpression of sweetpotato IbMYB1a induced anthocyanin pigmentation in transgenic tobacco (Nicotiana tabacum) plants. In the present study, transgenic tobacco (Nicotiana tabacum SR1) plants (STS-OX and ROST-OX) expressing the RpSTS gene encoding stilbene synthase from rhubarb (Rheum palmatum L. cv. Jangyeop) and the RpSTS and VrROMT genes encoding resveratrol O-methyltransferase from frost grape (Vitis riparia) were generated under the control of 35S promoter. Phenotypic alterations in floral organs, such as a reduction in floral pigments and male sterility, were observed in STS-OX transgenic tobacco plants. However, we failed to obtain STS-OX and ROST-OX plants with high levels of resveratrol compounds. Therefore, to improve the production of resveratrol derivatives in plants, we cross-pollinated flowers of STS-OX or ROST-OX and IbMYB1a-OX transgenic lines (SM and RSM). Phenotypic changes in vegetative and reproductive development of SM and RSM plants were observed. Furthermore, by HPLC and LC-MS analyses, we found enhanced production of resveratrol derivatives such as piceid, piceid methyl ether, resveratrol methyl ether O-hexoside, and 5-methyl resveratrol-3,4'-O-β-D-diglucopyranoside in SM and RSM cross-pollinated lines. Here, total contents of trans- and cis-piceids ranged from approximately 104-240 µg/g fresh weight in SM (F2). Collectively, we suggest that coexpression of RpSTS and IbMYB1a via cross-pollination can induce enhanced production of resveratrol compounds in plants by increasing metabolic flux into stilbenoid biosynthesis.

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

    Science.gov (United States)

    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

  11. Active control of divertor heat and particle fluxes in EAST towards advanced steady state operations

    Energy Technology Data Exchange (ETDEWEB)

    Wang, L., E-mail: lwang@ipp.ac.cn [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Dalian University of Technology, Dalian 116024 (China); Guo, H.Y. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); General Atomics, P. O. Box 85608, San Diego, CA 92186 (United States); Li, J.; Wan, B.N.; Gong, X.Z.; Zhang, X.D.; Hu, J.S. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Liang, Y. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Association EURATOM-FZJ, D-52425 Jülich (Germany); Xu, G.S. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Zou, X.L. [CEA, IRFM, F-13108 Saint-Paul-lez-Durance (France); Loarte, A. [ITER Organization, Route de Vinon sur Verdon, 13115 St Paul Lez Durance (France); Maingi, R.; Menard, J.E. [Princeton Plasma Physics Laboratory, Princeton, NJ 08543 (United States); Luo, G.N.; Gao, X.; Hu, L.Q.; Gan, K.F.; Liu, S.C.; Wang, H.Q.; Chen, R. [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); and others

    2015-08-15

    Significant progress has been made in EAST towards advanced steady state operations by active control of divertor heat and particle fluxes. Many innovative techniques have been developed to mitigate transient ELM and stationary heat fluxes on the divertor target plates. It has been found that lower hybrid current drive (LHCD) can lead to edge plasma ergodization, striation of the stationary heat flux and lower ELM transient heat and particle fluxes. With multi-pulse supersonic molecular beam injection (SMBI) to quantitatively regulate the divertor particle flux, the divertor power footprint pattern can be actively modified. H-modes have been extended over 30 s in EAST with the divertor peak heat flux and the target temperature being controlled well below 2 MW/m{sup 2} and 250 °C, respectively, by integrating these new methods, coupled with advanced lithium wall conditioning and internal divertor pumping, along with an edge coherent mode to provide continuous particle and power exhaust.

  12. 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....

  13. Sleep Control, GPCRs, and Glucose Metabolism.

    Science.gov (United States)

    Tsuneki, Hiroshi; Sasaoka, Toshiyasu; Sakurai, Takeshi

    2016-09-01

    Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders. Copyright © 2016. Published by Elsevier Ltd.

  14. Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates

    DEFF Research Database (Denmark)

    Nielsen, Jens Bredal

    1997-01-01

    Metabolic control analysis is a powerful technique for the evaluation of flux control within biochemical pathways. Its foundation is the elasticity coefficients and the flux control coefficients (FCCs). On the basis of a thermokinetic description of reaction rates it is here shown...... that the elasticity coefficients can be calculated directly from the pool levels of metabolites at steady state. The only requirement is that one thermodynamic parameter be known, namely the reaction affinity at the intercept of the tangent in the inflection point of the curve of reaction rate against reaction...... of the thermokinetic description of reaction rates to include the influence of effecters. Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations. With this type of rate function it is shown that the approach of Delgado and Liao [Biochem. J. (1992) 282, 919-927] can...

  15. Nitrate addition to groundwater impacted by ethanol-blended fuel accelerates ethanol removal and mitigates the associated metabolic flux dilution and inhibition of BTEX biodegradation

    Science.gov (United States)

    Corseuil, Henry Xavier; Gomez, Diego E.; Schambeck, Cássio Moraes; Ramos, Débora Toledo; Alvarez, Pedro J. J.

    2015-03-01

    A comparison of two controlled ethanol-blended fuel releases under monitored natural attenuation (MNA) versus nitrate biostimulation (NB) illustrates the potential benefits of augmenting the electron acceptor pool with nitrate to accelerate ethanol removal and thus mitigate its inhibitory effects on BTEX biodegradation. Groundwater concentrations of ethanol and BTEX were measured 2 m downgradient of the source zones. In both field experiments, initial source-zone BTEX concentrations represented less than 5% of the dissolved total organic carbon (TOC) associated with the release, and measurable BTEX degradation occurred only after the ethanol fraction in the multicomponent substrate mixture decreased sharply. However, ethanol removal was faster in the nitrate amended plot (1.4 years) than under natural attenuation conditions (3.0 years), which led to faster BTEX degradation. This reflects, in part, that an abundant substrate (ethanol) can dilute the metabolic flux of target pollutants (BTEX) whose biodegradation rate eventually increases with its relative abundance after ethanol is preferentially consumed. The fate and transport of ethanol and benzene were accurately simulated in both releases using RT3D with our general substrate interaction module (GSIM) that considers metabolic flux dilution. Since source zone benzene concentrations are relatively low compared to those of ethanol (or its degradation byproduct, acetate), our simulations imply that the initial focus of cleanup efforts (after free-product recovery) should be to stimulate the degradation of ethanol (e.g., by nitrate addition) to decrease its fraction in the mixture and speed up BTEX biodegradation.

  16. Hypothalamic control of energy and glucose metabolism.

    Science.gov (United States)

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  17. Divertor heat flux control and plasma-material interaction

    International Nuclear Information System (INIS)

    Kikuchi, Yusuke; Nagata, Masayoshi; Sawada, Keiji; Takamura, Shuichi; Ueda, Yoshio

    2014-01-01

    Development of reliable radiative-cooling divertors is essential in DEMO reactor because it uses low-activation materials with low heat removal and the plasma heat flux exhausted from the confined region is 5 times as large as in ITER. It is important to predict precisely the heat and particle flux toward the divertor plate by simulation. In this present article, theoretical and experimental data of the reflection, secondary emission and surface recombination coefficients of the divertor plate by ion bombardment are given and their effects on the power transmission coefficient are discussed. In addition, some topics such as the erosion process of the divertor plate by ELM and the plasma disruption, the thermal shielding due to the vapor layer on the divertor plate and the formation of fuzz structure on W by helium plasma irradiation, are described. (author)

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

    Science.gov (United States)

    Calvetti, Daniela; Cheng, Yougan; Somersalo, Erkki

    2016-12-01

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

  19. Evaluation of statistical protocols for quality control of ecosystem carbon dioxide fluxes

    Science.gov (United States)

    Jorge F. Perez-Quezada; Nicanor Z. Saliendra; William E. Emmerich; Emilio A. Laca

    2007-01-01

    The process of quality control of micrometeorological and carbon dioxide (CO2) flux data can be subjective and may lack repeatability, which would undermine the results of many studies. Multivariate statistical methods and time series analysis were used together and independently to detect and replace outliers in CO2 flux...

  20. Thermodynamic and Probabilistic Metabolic Control Analysis of Riboflavin (Vitamin B₂) Biosynthesis in Bacteria.

    Science.gov (United States)

    Birkenmeier, Markus; Mack, Matthias; Röder, Thorsten

    2015-10-01

    In this study, we applied a coupled in silico thermodynamic and probabilistic metabolic control analysis methodology to investigate the control mechanisms of the commercially relevant riboflavin biosynthetic pathway in bacteria. Under the investigated steady-state conditions, we found that several enzyme reactions of the pathway operate far from thermodynamic equilibrium (transformed Gibbs energies of reaction below about -17 kJ mol(-1)). Using the obtained thermodynamic information and applying enzyme elasticity sampling, we calculated the distributions of the scaled concentration control coefficients (CCCs) and scaled flux control coefficients (FCCs). From the statistical analysis of the calculated distributions, we inferred that the control over the riboflavin producing flux is shared among several enzyme activities and mostly resides in the initial reactions of the pathway. More precisely, the guanosine triphosphate (GTP) cyclohydrolase II activity, and therefore the bifunctional RibA protein of Bacillus subtilis because it catalyzes this activity, appears to mainly control the riboflavin producing flux (mean FCCs = 0.45 and 0.55, respectively). The GTP cyclohydrolase II activity and RibA also exert a high positive control over the riboflavin concentration (mean CCCs = 2.43 and 2.91, respectively). This prediction is consistent with previous findings for microbial riboflavin overproducing strains.

  1. Mitochondrial quality control pathways as determinants of metabolic health

    NARCIS (Netherlands)

    Held, Ntsiki M.; Houtkooper, Riekelt H.

    2015-01-01

    Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  4. Forest canopy temperatures: dynamics, controls, and relationships with ecosystem fluxes

    Science.gov (United States)

    Still, C. J.; Griffith, D.; Kim, Y.; Law, B. E.; Hanson, C. V.; Kwon, H.; Schulze, M.; Detto, M.; Pau, S.

    2017-12-01

    Temperature strongly affects enzymatic reactions, ecosystem biogeochemistry, and species distributions. Although most focus is on air temperature, the radiative or skin temperature of plants is more relevant. Canopy skin temperature dynamics reflect biophysical, physiological, and anatomical characteristics and interactions with the environment, and can be used to examine forest responses to stresses like droughts and heat waves. Thermal infrared (TIR) imaging allows for extensive temporal and spatial sampling of canopy temperatures, particularly compared to spot measurements using thermocouples. We present results of TIR imaging of forest canopies at eddy covariance flux tower sites in the US Pacific Northwest and in Panama. These forests range from an old-growth temperate rainforest to a second growth semi-arid pine forest to a semi-deciduous tropical forest. Canopy temperature regimes at these sites are highly variable. Canopy temperatures at all forest sites displayed frequent departures from air temperature, particularly during clear sky conditions, with elevated canopy temperatures during the day and depressed canopy temperatures at night compared to air temperature. Comparison of canopy temperatures to fluxes of carbon dioxide, water vapor, and energy reveals stronger relationships than those found with air temperature. Daytime growing season net ecosystem exchange at the pine forest site is better explained by canopy temperature (r2 = 0.61) than air temperature (r2 = 0.52). At the semi-deciduous tropical forest, canopy photosynthesis is highly correlated with canopy temperature (r2 = 0.51), with a distinct optimum temperature for photosynthesis ( 31 °C) that agrees with leaf-level measurements. During the peak of one heat wave at an old-growth temperate rainforest, hourly averaged air temperature exceeded 35 °C, 10 °C above average. Peak hourly canopy temperature approached 40 °C, and leaf-to-air vapor pressure deficit exceeded 6 kPa. These extreme

  5. Flux control-based design of furfural-resistance strains of Saccharomyces cerevisiae for lignocellulosic biorefinery.

    Science.gov (United States)

    Unrean, Pornkamol

    2017-04-01

    We have previously developed a dynamic flux balance analysis of Saccharomyces cerevisiae for elucidation of genome-wide flux response to furfural perturbation (Unrean and Franzen, Biotechnol J 10(8):1248-1258, 2015). Herein, the dynamic flux distributions were analyzed by flux control analysis to identify target overexpressed genes for improved yeast robustness against furfural. The flux control coefficient (FCC) identified overexpressing isocitrate dehydrogenase (IDH1), a rate-controlling flux for ethanol fermentation, and dicarboxylate carrier (DIC1), a limiting flux for cell growth, as keys of furfural-resistance phenotype. Consistent with the model prediction, strain characterization showed 1.2- and 2.0-fold improvement in ethanol synthesis and furfural detoxification rates, respectively, by IDH1 overexpressed mutant compared to the control. DIC1 overexpressed mutant grew at 1.3-fold faster and reduced furfural at 1.4-fold faster than the control under the furfural challenge. This study hence demonstrated the FCC-based approach as an effective tool for guiding the design of robust yeast strains.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  7. Seasonal and Intra-annual Controls on CO2 Flux in Arctic Alaska

    Energy Technology Data Exchange (ETDEWEB)

    Oechel, Walter [San Diego State Univ., CA (United States); Kalhori, Aram [San Diego State Univ., CA (United States)

    2015-12-01

    In order to advance the understanding of the patterns and controls on the carbon budget in the Arctic region, San Diego State University has maintained eddy covariance flux towers at three sites in Arctic Alaska, starting in 1997.

  8. Investigation of the low flux servo-controlled limit of a co-phased interferometer

    Science.gov (United States)

    Damé, Luc; Derrien, Marc; Kozlowski, Mathias; Merdjane, Mohamed

    2018-04-01

    This paper, "Investigation of the low flux servo-controlled limit of a co-phased interferometer," was presented as part of International Conference on Space Optics—ICSO 1997, held in Toulouse, France.

  9. Metabolic control of the insecticides safety use

    Directory of Open Access Journals (Sweden)

    L.I. Solomenko

    2016-06-01

    Full Text Available The results of the conducted research affirm that the phosphororganic insecticides utilization can lead to the break in the nitrogen metabolism, breaking the protein formation, reducing the protein molecules renewal, causing the amino acid and amides accumulation in the active state. It has been revealed that the translocation and transformation of the insecticides under consideration are more closely connected with the changes of insoluble protein fraction. The stagnation point of the Phosphamide and Kaunter impact on the plant has been determined. And only the use of the preparation in optimal norms can influence stimulatingly the course of the process under consideration.

  10. Metabolic control by S6 kinases depends on dietary lipids.

    Directory of Open Access Journals (Sweden)

    Tamara R Castañeda

    Full Text Available Targeted deletion of S6 kinase (S6K 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and this effect is not dependent upon amino acids. Comparison of male mice lacking S6K1 and 2 (S6K-dko with wt controls showed that S6K-dko mice are protected against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice fed a high-fat diet had increased energy expenditure, improved glucose tolerance, lower fat mass gain, and changes in markers of lipid metabolism. Importantly, however, these metabolic phenotypes were dependent upon dietary lipids, with no such effects observed in S6K-dko mice fed a fat-free diet. These changes appear to be mediated via modulation of cellular metabolism in skeletal muscle, as shown by the expression of genes involved in energy metabolism. Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism.

  11. Predictive torque and flux control of an induction machine drive ...

    Indian Academy of Sciences (India)

    Finite-state model predictive control; fuzzy decision making; multi-objective optimization; predictive torque control. Abstract. Among the numerous direct torque control techniques, the finite-state predictive torque control (FS-PTC) has emerged as a powerful alternative as it offers the fast dynamic response and the flexibility to ...

  12. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    Science.gov (United States)

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases. © 2014 John Wiley & Sons Ltd.

  13. 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

  14. Application of a controllable degron strategy for metabolic engineering

    DEFF Research Database (Denmark)

    Knuf, Christoph; Maury, Jerome; Jacobsen, Simo Abdessamad

    2014-01-01

    In numerous cases of metabolic engineering, metabolite pools have to be increased in order to obtain flux into heterologous pathways. A simple tool for this would be the deletion of genes that would practically lead to a block of the natural pathway, so that the carbon can flow into the heterolog...... of intermediates of the mevalonate pathway around 2,3-oxidosqualene, which is the precursor for triterpenoids. Many triterpenoids are pharmaceutically relevant compounds which nowadays need to be extracted from plant material through an intricate and resource consuming process....

  15. 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.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

  19. A study of flux control for high-efficiency speed control of variable flux permanent magnet motor

    Directory of Open Access Journals (Sweden)

    Young Hyun Kim

    2018-05-01

    Full Text Available In this study, we evaluate the performance of permanent magnets (PMs. The efficiency of attraction in the high speed region was studied using the variable flux memory motor (VFMM. It is presented in order to analyze the magnetic characteristics of PMs, using the second quadrant plan data with re- and de-magnetization. In addition, this study focuses on the evaluation of operational characteristics relative to the magnetizing directions according to the d-axis currents, by using one of the finite element solutions. The feasibility of application for the VFMM has been experimentally demonstrated.

  20. A study of flux control for high-efficiency speed control of variable flux permanent magnet motor

    Science.gov (United States)

    Kim, Young Hyun; Lee, Seong Soo; Lee, Jung Ho

    2018-05-01

    In this study, we evaluate the performance of permanent magnets (PMs). The efficiency of attraction in the high speed region was studied using the variable flux memory motor (VFMM). It is presented in order to analyze the magnetic characteristics of PMs, using the second quadrant plan data with re- and de-magnetization. In addition, this study focuses on the evaluation of operational characteristics relative to the magnetizing directions according to the d-axis currents, by using one of the finite element solutions. The feasibility of application for the VFMM has been experimentally demonstrated.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-11-15

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

  2. CARBO-CONTROLE. Quantification of the carbon flux and stocks at the european and national scale

    International Nuclear Information System (INIS)

    Ciais, P.

    2007-01-01

    The CARBO-CONTROLE project aims to evaluate the different methodologies to estimate the CO 2 flux at the european, national and regional scale. The strategy is to combine a crumbling, down scaling, of the flux at a big scale, by inverting the atmospheric CO 2 measures with a aggregation, up scaling, of the national stocks and flux from the climatic parameters of a model of ecosystems.They show that with the monthly data of the global network of CO 2 monitoring stations, it is possible to obtain an estimation of the european flux. Meanwhile the errors bond to the leak of continental stations are of the order of the flux average. (A.L.B.)

  3. Environmental control of methane fluxes over a Danish peatland

    Science.gov (United States)

    Herbst, M.; Ringgaard, R.; Friborg, T.; Soegaard, H.

    2009-12-01

    Reducing the greenhouse gas (GHG) emissions from natural and anthropogenic environments has become a key issue over the last decades. In Denmark the management of the wetlands is playing a key role in these attempts. The wetland area of Skjern Meadows in the western part of Denmark is one of the best known examples of peatland restauration in northern Europe. The valley of the Skjern river was restored in 2002, after it had been drained for about 35 years. A micrometeorological instrument mast was erected in the centre of the 2200 ha large area in the summer of 2008, in order to facilitate continuous eddy covariance measurements of the exchange of carbon dioxide and methane between the peatland and the atmosphere. A sonic anemometer (R3, Gill) was used together with a closed-path CO2 analyzer (LI-7000, Li-Cor) and a closed-path CH4 analyzer (DLT-100, Los Gatos). A measurement height of 7 m above the surface ensures that the observed eddy fluxes represent an average signal from the entire peatland. The first year of data collection confirmed the expectation that the area functions as a moderate CO2 sink, whilst it releases methane into the atmosphere. During a 12-months period starting in September 2008, the wetland removed 119 g CO2-C per m2 from the atmosphere and emitted 6 g CH4-C per m2. If the amount of the emitted CH4 is converted into CO2 equivalents, it remained lower than the annual CO2 uptake (188 versus 437 g CO2). This means that the restored peatland functions as a weak greenhouse gas sink, despite its methane production. Whilst the annual CO2 uptake at Skjern Meadows was similar to that reported by Friborg et al. (2003) for a Siberian wetland, the CH4 emission was much lower. The average CO2 and CH4 flux rates were both lower than those estimated for a Dutch wetland by Hendriks et al. (2007). The CH4 emission showed no particular diurnal pattern, but daily rates varied considerably throughout the year. This variability can be correlated to variations

  4. 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

  5. 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.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  7. Nonadiabatic effect on the quantum heat flux control.

    Science.gov (United States)

    Uchiyama, Chikako

    2014-05-01

    We provide a general formula of quantum transfer that includes the nonadiabatic effect under periodic environmental modulation by using full counting statistics in Hilbert-Schmidt space. Applying the formula to an anharmonic junction model that interacts with two bosonic environments within the Markovian approximation, we find that the quantum transfer is divided into the adiabatic (dynamical and geometrical phases) and nonadiabatic contributions. This extension shows the dependence of quantum transfer on the initial condition of the anharmonic junction just before the modulation, as well as the characteristic environmental parameters such as interaction strength and cut-off frequency of spectral density. We show that the nonadiabatic contribution represents the reminiscent effect of past modulation including the transition from the initial condition of the anharmonic junction to a steady state determined by the very beginning of the modulation. This enables us to tune the frequency range of modulation, whereby we can obtain the quantum flux corresponding to the geometrical phase by setting the initial condition of the anharmonic junction.

  8. Hypothalamic control of energy metabolism via the autonomic nervous system

    NARCIS (Netherlands)

    Kalsbeek, A.; Bruinstroop, E.; Yi, C. X.; Klieverik, L. P.; La Fleur, S. E.; Fliers, E.

    2010-01-01

    The hypothalamic control of hepatic glucose production is an evident aspect of energy homeostasis. In addition to the control of glucose metabolism by the circadian timing system, the hypothalamus also serves as a key relay center for (humoral) feedback information from the periphery, with the

  9. Role of glycolytic intermediate in regulation: Improving lycopene production in Escherichia coli by engineering metabolic control

    Energy Technology Data Exchange (ETDEWEB)

    Farmer, W.R.; Liao, J.C.

    2001-06-01

    Metabolic engineering in the postgenomic era is expected to benefit from a full understanding of the biosynthetic capability of microorganisms as a result of the progress being made in bioinformatics and functional genomics. The immediate advantage of such information is to allow the rational design of novel pathways and the elimination of native reactions that are detrimental or unnecessary for the desired purpose. However, with the ability to manipulate metabolic pathways becoming more effective, metabolic engineering will need to face a new challenge: the reengineering of the regulatory hierarchy that controls gene expression in those pathways. In addition to constructing the genetic composition of a metabolic pathway, they propose that it will become just as important to consider the dynamics of pathways gene expression. It has been widely observed that high-level induction of a recombinant protein or pathway leads to growth retardation and reduced metabolic activity. These phenotypic characteristics result from the fact that the constant demands of production placed upon the cell interfere with its changing requirements for growth. They believe that this common situation in metabolic engineering can be alleviated by designing a dynamic controller that is able to sense the metabolic state of the cell and regulate the expression of the recombinant pathway accordingly. This approach, which is termed metabolic control engineering, involves redesigning the native regulatory circuits and applying them to the recombinant pathway. The general goal of such an effort will be to control the flux to the recombinant pathway adaptively according to the cell's metabolic state. The dynamically controlled recombinant pathway can potentially lead to enhanced production, minimized growth retardation, and reduced toxic by-product formation. The regulation of gene expression in response to the physiological state is also essential to the success of gene therapy. Here they

  10. 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.

  11. Control of Flux Pinning in MOD YBCO Coated Conductor

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, W. [American Superconductor Corporation, Westborough, MA; Huang, Y. [American Superconductor Corporation, Westborough, MA; Li, X. [American Superconductor Corporation, Westborough, MA; Kodenkandath, Thomas [American Superconductor Corporation, Westborough, MA; Rupich, Marty [American Superconductor Corporation, Westborough, MA; Schoop, U. [American Superconductor Corporation, Westborough, MA; Verebelyi, D. T. [American Superconductor Corporation, Westborough, MA; Thieme, C. L. H. [American Superconductor Corporation, Westborough, MA; Siegal, E. E. [American Superconductor Corporation, Westborough, MA; Holesinger, T. G. [Los Alamos National Laboratory (LANL); Maiorov, B. [Los Alamos National Laboratory (LANL); Miller, D. J. [Argonne National Laboratory (ANL); Maroni, V. A. [Argonne National Laboratory (ANL); Goyal, Amit [ORNL; Specht, Eliot D [ORNL; Paranthaman, Mariappan Parans [ORNL

    2007-01-01

    Two different types of defect structures have been identified to be responsible for the enhanced pinning in metal organic deposited YBCO films. Rare earth additions result in the formation of nanodots in the YBCO matrix, which form uncorrelated pinning centers, increasing pinning in all magnetic field orientations. 124-type intergrowths, which form as laminar structures parallel to the ab-plane, are responsible for the large current enhancement when the magnetic field is oriented in the ab-plane. TEM studies showed that the intergrowths emanate from cuprous containing secondary phase particles, whose density is partially controlled by the rare earth doping level. Critical process parameters have been identified to control this phase formation, and therefore, control the f 24 intergrowth formation. This work has shown that through process control and proper conductor design, either by adjusting the composition or by multiple coatings of different functional layers, the desired angular dependence can be achieved.

  12. Control of flux pinning in MOD YBCO coated conductor.

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, W.; Huang, Y.; Li, X.; Kodenkandath, T.; Rupich, M. W.; Schoop, U.; Verebelyi, D. T.; Thieme, C. L. H.; Siegal, E.; Holesinger, T. G.; Maiorov, B.; Civale, L.; Miller, D. J.; Maroni, V. A.; Li, J.; Martin, P. M.; Specht, E. D.; Goyal, A.; Paranthaman, M. P.; American Superconductor Corp.; LANL; ORNL

    2007-06-01

    NTwo different types of defect structures have been identified to be responsible for the enhanced pinning in metal organic deposited YBCO films. Rare earth additions result in the formation of nanodots in the YBCO matrix, which form uncorrelated pinning centers, increasing pinning in all magnetic field orientations. 124-type intergrowths, which form as laminar structures parallel to the ab-plane, are responsible for the large current enhancement when the magnetic field is oriented in the ab-plane. TEM studies showed that the intergrowths emanate from cuprous containing secondary phase particles, whose density is partially controlled by the rare earth doping level. Critical process parameters have been identified to control this phase formation, and therefore, control the f 24 intergrowth formation. This work has shown that through process control and proper conductor design, either by adjusting the composition or by multiple coatings of different functional layers, the desired angular dependence can be achieved.

  13. Metabolic control of female puberty: potential therapeutic targets.

    Science.gov (United States)

    Castellano, Juan M; Tena-Sempere, Manuel

    2016-10-01

    The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting. The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress.

  14. Validation of neutron flux redistribution factors in JSI TRIGA reactor due to control rod movements

    International Nuclear Information System (INIS)

    Kaiba, Tanja; Žerovnik, Gašper; Jazbec, Anže; Štancar, Žiga; Barbot, Loïc; Fourmentel, Damien; Snoj, Luka

    2015-01-01

    For efficient utilization of research reactors, such as TRIGA Mark II reactor in Ljubljana, it is important to know neutron flux distribution in the reactor as accurately as possible. The focus of this study is on the neutron flux redistributions due to control rod movements. For analyzing neutron flux redistributions, Monte Carlo calculations of fission rate distributions with the JSI TRIGA reactor model at different control rod configurations have been performed. Sensitivity of the detector response due to control rod movement have been studied. Optimal radial and axial positions of the detector have been determined. Measurements of the axial neutron flux distribution using the CEA manufactured fission chambers have been performed. The experiments at different control rod positions were conducted and compared with the MCNP calculations for a fixed detector axial position. In the future, simultaneous on-line measurements with multiple fission chambers will be performed inside the reactor core for a more accurate on-line power monitoring system. - Highlights: • Neutron flux redistribution due to control rod movement in JSI TRIGA has been studied. • Detector response sensitivity to the control rod position has been minimized. • Optimal radial and axial detector positions have been determined

  15. The extent to which ATP demand controls the glycolytic flux depends strongly on the organism and conditions for growth

    DEFF Research Database (Denmark)

    Købmann, Brian Jensen; Westerhoff, H.V.; Snoep, J.L.

    2002-01-01

    Using molecular genetics we have introduced uncoupled ATPase activity in two different bacterial species, Escherichia coli and Lactococcus lactis, and determined the elasticities of the growth rate and glycolytic flux towards the intracellular [ATP]/[ADP] ratio. During balanced growth in batch...... cultures of E. coli the ATP demand was found to have almost full control on the glycolytic flux (FCC=0.96) and the flux could be stimulated by 70%. In contrast to this, in L. lactis the control by ATP demand on the glycolytic flux was close to zero. However, when we used non-growing cells of L. lactis...... (which have a low glycolytic flux) the ATP demand had a high flux control and the flux could be stimulated more than two fold. We suggest that the extent to which ATP demand controls the glycolytic flux depends on how much excess capacity of glycolysis is present in the cells....

  16. Spatial flux instabilities, and their control in the graphite gas power reactors; Les instabilites spatiales du flux et leur controle dans les reacteurs de puissance graphite-gaz

    Energy Technology Data Exchange (ETDEWEB)

    Cailly, J L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-07-01

    Radial-azimuthal and axial spatial flux instabilities in graphite-gas reactors are studied by means of an analytical approach. Results are checked with those which are given by two dimensional (r, z and r, {theta}) kinetic models programmed for an IBM 7094 computer. At least, conclusions on the control of instabilities obtained from these models are reported. (author) [French] Les instabilites spatiales du flux dans les reacteurs graphite-gaz, radiales et azimutales d'une part, axiales d'autre part, sont etudiees au moyen d'une formulation analytique. Les resultats sont confrontes avec ceux que fournissent des modeles cinetiques a deux dimensions (r, z et r, {theta}) programmes sur IBM 7094. On donne enfin les conclusions relatives au controle de ces instabilites que ces modeles ont permis de degager. (auteur)

  17. 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 .

  18. Digital signal processing control of induction machine`s torque and stator flux utilizing the direct stator flux field orientation method

    Energy Technology Data Exchange (ETDEWEB)

    Seiz, Julie Burger [Union College, Schenectady, NY (United States)

    1997-04-01

    This paper presents a review of the Direct Stator Flux Field Orientation control method. This method can be used to control an induction motor`s torque and flux directly and is the application of interest for this thesis. This control method is implemented without the traditional feedback loops and associated hardware. Predictions are made, by mathematical calculations, of the stator voltage vector. The voltage vector is determined twice a switching period. The switching period is fixed throughout the analysis. The three phase inverter duty cycle necessary to control the torque and flux of the induction machine is determined by the voltage space vector Pulse Width Modulation (PWM) technique. Transient performance of either the flux or torque requires an alternate modulation scheme which is also addressed in this thesis. A block diagram of this closed loop system is provided. 22 figs., 7 tabs.

  19. Sensorless sliding mode torque control of an IPMSM drive based on active flux concept

    Directory of Open Access Journals (Sweden)

    A.A. Hassan

    2012-03-01

    Full Text Available This paper investigates a novel direct torque control of a sensorless interior permanent magnet synchronous motor based on a sliding mode technique. The speed and position of the interior permanent magnet synchronous motor are estimated online based on active flux concept. To overcome the large ripple content associated with the direct torque, a torque/flux sliding mode controller has been employed. Two integral surface functions are used to construct the sliding mode controller. The command voltage is estimated from the torque and flux errors based on the two switching functions. The idea of the total sliding mode is used to eliminate the problem of reaching phase stability. The space vector modulation is combined with the sliding mode controller to ensure minimum torque and flux ripples and provides high resolution voltage control. The proposed scheme has the advantages of simple implementation, and does not require an external signal injection. In addition, it combines the merits of the direct torque control, sliding mode controller, and space vector modulation besides to the sensorless control. Simulation works are carried out to demonstrate the ability of the proposed scheme at different operating conditions. The results confirm the high performance of the proposed scheme at standstill, low and high speeds including load disturbance and parameters variation.

  20. Metabolic sensing neurons and the control of energy homeostasis.

    Science.gov (United States)

    Levin, Barry E

    2006-11-30

    The brain and periphery carry on a constant conversation; the periphery informs the brain about its metabolic needs and the brain provides for these needs through its control of somatomotor, autonomic and neurohumoral pathways involved in energy intake, expenditure and storage. Metabolic sensing neurons are the integrators of a variety of metabolic, humoral and neural inputs from the periphery. Such neurons, originally called "glucosensing", also respond to fatty acids, hormones and metabolites from the periphery. They are integrated within neural pathways involved in the regulation of energy homeostasis. Unlike most neurons, they utilize glucose and other metabolites as signaling molecules to regulate their membrane potential and firing rate. For glucosensing neurons, glucokinase acts as the rate-limiting step in glucosensing while the pathways that mediate responses to metabolites like lactate, ketone bodies and fatty acids are less well characterized. Many metabolic sensing neurons also respond to insulin and leptin and other peripheral hormones and receive neural inputs from peripheral organs. Each set of afferent signals arrives with different temporal profiles and by different routes and these inputs are summated at the level of the membrane potential to produce a given neural firing pattern. In some obese individuals, the relative sensitivity of metabolic sensing neurons to various peripheral inputs is genetically reduced. This may provide one mechanism underlying their propensity to become obese when exposed to diets high in fat and caloric density. Thus, metabolic sensing neurons may provide a potential therapeutic target for the treatment of obesity.

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

    Science.gov (United States)

    Vallino, J J; Stephanopoulos, G

    2000-03-20

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

  2. 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

  3. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

  4. Metabolic control analysis of xylose catabolism in Aspergillus

    NARCIS (Netherlands)

    Prathumpai, W.; Gabelgaard, J.B.; Wanchanthuek, P.; Vondervoort, van de P.J.I.; Groot, de M.J.L.; McIntyre, M.; Nielsen, J.

    2003-01-01

    A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out,

  5. Dynamic optimal metabolic control theory: a cybernetic approach for modelling of the central nitrogen metabolism of S. cerevisiae

    NARCIS (Netherlands)

    Riel, van N.A.W.; Giuseppin, M.L.F.; Verrips, C.T.

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the

  6. Regulation of terpene metabolism. Final technical report, March 15, 1988--March 14, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1996-12-31

    This research focuses on the following topics: the biosynthesis and catabolism of monoterpenes; the organization of monoterpene metabolism; the developmental regulation of monoterpene metabolism; the flux control of precursor supply; and the integration of monoterpene and higher terpenoid metabolism.

  7. Transcriptional switches in the control of macronutrient metabolism.

    Science.gov (United States)

    Wise, Alan

    2008-06-01

    This review shows how some transcription factors respond to alterations in macronutrients. Carbohydrates induce enzymes for their metabolism and fatty acid synthesis. Fatty acids reduce carbohydrate processing, induce enzymes for their metabolism, and increase both gluconeogenesis and storage of fat. Fat stores help control carbohydrate uptake by other cells. The following main transcription factors are discussed: carbohydrate response element-binding protein; sterol regulatory element-binding protein-1c, cyclic AMP response element-binding protein, peroxisome proliferator-activated receptor-alpha, and peroxisome proliferator-activated receptor-gamma.

  8. Control of a Dual-Stator Flux-Modulated Motor for Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Xinhua Guo

    2016-07-01

    Full Text Available This paper presents the control strategies for a novel dual-stator flux-modulated (DSFM motor for application in electric vehicles (EVs. The DSFM motor can be applied to EVs because of its simple winding structure, high reliability, and its use of two stators and rotating modulation steels in the air gap. Moreover, it outperforms conventional brushless doubly-fed machines in terms of control performance. Two stator-current-oriented vector controls with different excitation in the primary winding, direct and alternating current excitation, are designed, simulated, and evaluated on a custom-made DSFM prototype allowing the decoupled control of torque. The stable speed response and available current characteristics strongly validate the feasibility of the two control methods. Furthermore, the proposed control methods can be employed in other applications of flux-modulated motors.

  9. Sleep and metabolic control: waking to a problem?

    Science.gov (United States)

    Trenell, Michael I; Marshall, Nathaniel S; Rogers, Naomi L

    2007-01-01

    1. The aim of the present review is to outline: (i) the association between sleep and metabolism; (ii) how sleep duration influences the development of disease; and (iii) how sex differences, ageing and obesity may potentially influence the relationship between sleep, metabolic control and subsequent disease. 2. Sleep is associated with a number of endocrine changes, including a change in insulin action in healthy young individuals. Sleep duration shows a prospective U-shaped relationship with all-cause mortality, cardiovascular disease and Type 2 diabetes. 3. Chronic sleep restriction is becoming more common. Experimental sleep restriction impedes daytime glucose control and increases appetite. 4. The sex hormones oestrogen and testosterone influence sleep duration and quality and may account for sex differences in the prevalence of sleep-related disorders. 5. Ageing is associated with a decreased sleep duration, decreased muscle mass and impaired insulin action. 6. Obesity impairs insulin action and is associated with the incidence and severity of obstructive sleep apnoea. 7. Sleep plays an integral role in metabolic control. Consequently, insufficient sleep may represent a modifiable risk factor for the development of Type 2 diabetes. The challenge ahead is to identify how sex differences, ageing and obesity could potentially influence the relationship between sleep and metabolism.

  10. Congruent evaporation temperature of GaAs(001) controlled by As flux

    International Nuclear Information System (INIS)

    Zhou, Z. Y.; Zheng, C. X.; Tang, W. X.; Jesson, D. E.; Tersoff, J.

    2010-01-01

    The congruent evaporation temperature T c is a fundamental surface characteristic of GaAs and similar compounds. Above T c the rate of As evaporation exceeds that of Ga during Langmuir (free) evaporation into a vacuum. However, during molecular beam epitaxy (MBE) there is generally an external As flux F incident on the surface. Here we show that this flux directly controls T c . We introduce a sensitive approach to measure T c based on Ga droplet stability, and determine the dependence of T c on F. This dependence is explained by a simple model for evaporation in the presence of external flux. The capability of manipulating T c via changing F offers a means of controlling congruent evaporation with relevance to MBE, surface preparation methods, and droplet epitaxy.

  11. Inhibition of Non-flux-Controlling Enzymes Deters Cancer Glycolysis by Accumulation of Regulatory Metabolites of Controlling Steps.

    Science.gov (United States)

    Marín-Hernández, Álvaro; Rodríguez-Zavala, José S; Del Mazo-Monsalvo, Isis; Rodríguez-Enríquez, Sara; Moreno-Sánchez, Rafael; Saavedra, Emma

    2016-01-01

    Glycolysis provides precursors for the synthesis of macromolecules and may contribute to the ATP supply required for the constant and accelerated cellular duplication in cancer cells. In consequence, inhibition of glycolysis has been reiteratively considered as an anti-cancer therapeutic option. In previous studies, kinetic modeling of glycolysis in cancer cells allowed the identification of the main steps that control the glycolytic flux: glucose transporter, hexokinase (HK), hexose phosphate isomerase (HPI), and glycogen degradation in human cervix HeLa cancer cells and rat AS-30D ascites hepatocarcinoma. It was also previously experimentally determined that simultaneous inhibition of the non-controlling enzymes lactate dehydrogenase (LDH), pyruvate kinase (PYK), and enolase (ENO) brings about significant decrease in the glycolytic flux of cancer cells and accumulation of intermediate metabolites, mainly fructose-1,6-bisphosphate (Fru1,6BP), and dihydroxyacetone phosphate (DHAP), which are inhibitors of HK and HPI, respectively. Here it was found by kinetic modeling that inhibition of cancer glycolysis can be attained by blocking downstream non flux-controlling steps as long as Fru1,6BP and DHAP, regulatory metabolites of flux-controlling enzymes, are accumulated. Furthermore, experimental results and further modeling showed that oxamate and iodoacetate inhibitions of PYK, ENO, and glyceraldehyde3-phosphate dehydrogenase (GAPDH), but not of LDH and phosphoglycerate kinase, induced accumulation of Fru1,6BP and DHAP in AS-30D hepatoma cells. Indeed, PYK, ENO, and GAPDH exerted the highest control on the Fru1,6BP and DHAP concentrations. The high levels of these metabolites inhibited HK and HPI and led to glycolytic flux inhibition, ATP diminution, and accumulation of toxic methylglyoxal. Hence, the anticancer effects of downstream glycolytic inhibitors are very likely mediated by this mechanism. In parallel, it was also found that uncompetitive inhibition of the

  12. Determining the Control Circuitry of Redox Metabolism at the Genome-Scale

    DEFF Research Database (Denmark)

    Federowicz, Stephen; Kim, Donghyuk; Ebrahim, Ali

    2014-01-01

    -scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes...

  13. A passive apparatus for controlled-flux delivery of biocides: hydrogen peroxide as an example

    DEFF Research Database (Denmark)

    Olsen, Stefan Møller; Pedersen, L.T.; Dam-Johansen, Kim

    2010-01-01

    A new test method has been developed to estimate the required release rate of hydrogen peroxide (H2O2) to prevent marine biofouling. The technique exploits a well-defined concentration gradient of biocide across a cellulose acetate membrane. A controlled flux of H2O2, an environmentally friendly ...

  14. Monsoon control on trace metal fluxes in the deep Arabian Sea

    Indian Academy of Sciences (India)

    Monsoon control on trace metal fluxes in the deep Arabian Sea ... at marine boundaries and surface ocean processes: Forcings and feedbacks Volume 115 ... Annual Al fluxes at shallow and deep trap depths were 0.47 and 0.46 gm−2 in the ...

  15. Phosphoglycerate Mutase Is a Highly Efficient Enzyme without Flux Control in Lactococcus lactis

    DEFF Research Database (Denmark)

    Solem, Christian; Petranovic, D.; Købmann, Brian

    2010-01-01

    The glycolytic enzyme phosphoglycerate mutase (PGM), which catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate, was examined in Lactococcus lactis with respect to its function, kinetics and glycolytic flux control. A library of strains with PGM activities ranging between 15-465% ...

  16. A new virtual-flux-vector based droop control strategy for parallel connected inverters in microgrids

    DEFF Research Database (Denmark)

    Hu, Jiefeng; Zhu, Jianguo; Qu, Yanqing

    2013-01-01

    Voltage and frequency droop method is commonly used in microgrids to achieve proper autonomous power sharing without rely on intercommunication systems. This paper proposes a new control strategy for parallel connected inverters in microgrid applications by drooping the flux instead of the invert...

  17. Environmental controls on ozone fluxes in a poplar plantation in Western Europe

    DEFF Research Database (Denmark)

    Zona, D.; Gioli, B.; Fares, S.

    2014-01-01

    development. Largest O-3 uptakes were recorded at the beginning of the growing season in correspondence to a minimum stomatal uptake. Wind speed was the most important control and explained 44% of the variability in the nighttime O-3 fluxes, suggesting that turbulent mixing and the mechanical destruction of O...

  18. Controlling cell-free metabolism through physiochemical perturbations.

    Science.gov (United States)

    Karim, Ashty S; Heggestad, Jacob T; Crowe, Samantha A; Jewett, Michael C

    2018-01-01

    Building biosynthetic pathways and engineering metabolic reactions in cells can be time-consuming due to complexities in cellular metabolism. These complexities often convolute the combinatorial testing of biosynthetic pathway designs needed to define an optimal biosynthetic system. To simplify the optimization of biosynthetic systems, we recently reported a new cell-free framework for pathway construction and testing. In this framework, multiple crude-cell extracts are selectively enriched with individual pathway enzymes, which are then mixed to construct full biosynthetic pathways on the time scale of a day. This rapid approach to building pathways aids in the study of metabolic pathway performance by providing a unique freedom of design to modify and control biological systems for both fundamental and applied biotechnology. The goal of this work was to demonstrate the ability to probe biosynthetic pathway performance in our cell-free framework by perturbing physiochemical conditions, using n-butanol synthesis as a model. We carried out three unique case studies. First, we demonstrated the power of our cell-free approach to maximize biosynthesis yields by mapping physiochemical landscapes using a robotic liquid-handler. This allowed us to determine that NAD and CoA are the most important factors that govern cell-free n-butanol metabolism. Second, we compared metabolic profile differences between two different approaches for building pathways from enriched lysates, heterologous expression and cell-free protein synthesis. We discover that phosphate from PEP utilization, along with other physiochemical reagents, during cell-free protein synthesis-coupled, crude-lysate metabolic system operation inhibits optimal cell-free n-butanol metabolism. Third, we show that non-phosphorylated secondary energy substrates can be used to fuel cell-free protein synthesis and n-butanol biosynthesis. Taken together, our work highlights the ease of using cell-free systems to explore

  19. 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

  20. [Metabolic control in children and adolescents with type 1 diabetes].

    Science.gov (United States)

    Díaz-Cárdenas, Claudia; Wong, Carolina; Vargas Catalán, Nelson A

    2016-01-01

    Type 1 diabetes mellitus (T1D) is an important disease in children and adolescent being a major risk factor for early morbidity and mortality. To know the degree of metabolic control and prevalence of cardiovascular risk factors in T1D patients. Retrospective study including patients under 19 years of age with T1D controlled at a Chilean hospital in 2011. 94 patients were evaluated (average age at diagnosis: 7.3 years; current age: 11,9 years; evolution time: 4.5 years). Seventy-nine percent (79.8%) of patients presented glycated hemoglobin (HbA1c) over the recommended level with an average of 8.9%. The group between 13 and 19 years of age exhibited the worst metabolic control (86% with HbA1c abnormal levels). Overweight or obesity occurred in 26.6% of patients, 20.3% had LDL >100mg/dl and 4.2% had hypertension. Only about twenty percent of patients had adequate metabolic control as measured by HbA1c, although cardiovascular risk profile was acceptable. Therapeutic and educational efforts must be reinforced mainly in adolescents, emphasizing the importance of adequate nutritional management as a primary method to treat this entity. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility.

    Science.gov (United States)

    Navarro, Victor M; Tena-Sempere, Manuel

    2011-09-13

    The neurohormonal control of reproduction involves a hierarchical network of central and peripheral signals in the hypothalamic-pituitary-gonadal (HPG) axis. Development and function of this neuroendocrine system is the result of a lifelong delicate balance between endogenous regulators and environmental cues, including nutritional and metabolic factors. Kisspeptins are the peptide products of KISS1, which operate via the G-protein-coupled receptor GPR54 (also known as Kiss1R). These peptides have emerged as essential upstream regulators of neurons secreting gonadotropin-releasing hormone (GnRH), the major hypothalamic node for the stimulatory control of the HPG axis. They are potent elicitors of gonadotropin secretion in various species and physiological settings. Moreover, Kiss1 neurons in the hypothalamus participate in crucial features of reproductive maturation and function, such as brain-level sex differentiation, puberty onset and the neuroendocrine regulation of gonadotropin secretion and ovulation. Cotransmitters of Kiss1 neurons, such as neurokinin B, with roles in controlling the HPG axis have been identified by genetic, neuroanatomical and physiological studies. In addition, a putative role has been proposed for Kiss1 neurons in transmitting metabolic information to GnRH neurons, although the precise mechanisms are as yet unclear. In this Review, we present the major reproductive features of kisspeptins, especially their interplay with neurokinin B and potential roles in the metabolic control of puberty and fertility, and suggest new avenues for research.

  2. (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

  3. On which timescales do gas transfer velocities control North Atlantic CO2 flux variability?

    OpenAIRE

    Couldrey, Matthew; Oliver, Kevin; Yool, Andrew; Halloran, Paul; Achterberg, Eric

    2016-01-01

    The North Atlantic is an important basin for the global ocean's uptake of anthropogenic and natural carbon dioxide (CO2), but the mechanisms controlling this carbon flux are not fully understood. The air-sea flux of CO2, F, is the product of a gas transfer velocity, k, the air-sea CO2 concentration gradient, ΔpCO2, and the temperature and salinity-dependent solubility coefficient, α. k is difficult to constrain, representing the dominant uncertainty in F on short (instantaneous to interannual...

  4. Climatic and geologic controls on suspended sediment flux in the Sutlej River Valley, western Himalaya

    Directory of Open Access Journals (Sweden)

    H. Wulf

    2012-07-01

    Full Text Available The sediment flux through Himalayan rivers directly impacts water quality and is important for sustaining agriculture as well as maintaining drinking-water and hydropower generation. Despite the recent increase in demand for these resources, little is known about the triggers and sources of extreme sediment flux events, which lower water quality and account for extensive hydropower reservoir filling and turbine abrasion. Here, we present a comprehensive analysis of the spatiotemporal trends in suspended sediment flux based on daily data during the past decade (2001–2009 from four sites along the Sutlej River and from four of its main tributaries. In conjunction with satellite data depicting rainfall and snow cover, air temperature and earthquake records, and field observations, we infer climatic and geologic controls of peak suspended sediment concentration (SSC events. Our study identifies three key findings: First, peak SSC events (≥ 99th SSC percentile coincide frequently (57–80% with heavy rainstorms and account for about 30% of the suspended sediment flux in the semi-arid to arid interior of the orogen. Second, we observe an increase of suspended sediment flux from the Tibetan Plateau to the Himalayan Front at mean annual timescales. This sediment-flux gradient suggests that averaged, modern erosion in the western Himalaya is most pronounced at frontal regions, which are characterized by high monsoonal rainfall and thick soil cover. Third, in seven of eight catchments, we find an anticlockwise hysteresis loop of annual sediment flux variations with respect to river discharge, which appears to be related to enhanced glacial sediment evacuation during late summer. Our analysis emphasizes the importance of unconsolidated sediments in the high-elevation sector that can easily be mobilized by hydrometeorological events and higher glacial-meltwater contributions. In future climate change scenarios, including continuous glacial retreat and

  5. Dynamic performance analysis of permanent magnet contactor with a flux-weakening control strategy

    Science.gov (United States)

    Wang, Xianbing; Lin, Heyun; Fang, Shuhua; Jin, Ping; Wang, Junhua; Ho, S. L.

    2011-04-01

    A new flux-weakening control strategy for permanent magnet contactors is proposed. By matching the dynamic attraction force and the antiforce, the terminal velocity and collision energy of the movable iron in the closing process are significantly reduced. The movable iron displacement is estimated by detecting the closing voltage and current with the proposed control. A dynamic mathematical model is also established under four kinds of excitation scenarios. The attraction force and flux linkage are predicted by finite element method and the dynamics of the closing process is simulated using the 4th-order Runge-Kutta algorithm. Experiments are carried out on a 250A prototype with an intelligent control unit to verify the proposed control strategy.

  6. Design of magnetic flux concentrator of permancent magnet for control rod position indicator of SMART CEDM

    International Nuclear Information System (INIS)

    Yoo, J. Y.; Kim, J. H.; Hur, H.; Kim, J. I.

    2002-01-01

    The reliability and accuracy of the information on control rod position are very important to the reactor safety and the design of the core protection system. A survey on the RSPT(Reed Switch Position Transmitter) type control rod position indication system and its actual implementation in the exiting nuclear power plants in Korea was performed first. The control rod position indicator having the high performance for SMART was developed on the basis of RSPT technology identified through the survey. The arrangement of permanent magnet and reed switches is the most important procedure in the design of control rod position indication. In this study, the magnetic flux concentrator of permanent magnet is introduced and the calculation method for effective flux area for reed switch is presented

  7. Leptin and the central nervous system control of glucose metabolism.

    Science.gov (United States)

    Morton, Gregory J; Schwartz, Michael W

    2011-04-01

    The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders.

  8. 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.

  9. Metabolic control of puberty: roles of leptin and kisspeptins.

    Science.gov (United States)

    Sanchez-Garrido, Miguel A; Tena-Sempere, Manuel

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Reproduction is an energy-demanding function. Accordingly, puberty is metabolically gated, as a means to prevent fertility in conditions of energy insufficiency. In addition, obesity has been shown to impact the timing of puberty and may be among the causes for the earlier trends of pubertal age reported in various countries. The metabolic control of puberty in such a spectrum of situations, ranging from energy deficit to extreme overweight, is the result of the concerted action of different peripheral hormones and central transmitters that sense the metabolic state of the organism and transmit this information to the various elements of the reproductive axis, mainly the GnRH neurons. Among the peripheral signals involved, the adipose hormone, leptin, is known to play an essential role in the regulation of puberty, especially in females. Yet, although it is clear that the effects of leptin on puberty onset are predominantly permissive and mainly conducted at central (hypothalamic) levels, the primary sites and mechanisms of action of leptin within the reproductive brain remain unsolved. In this context, neurons expressing kisspeptins, the products of the Kiss1 gene that have emerged recently as essential upstream regulators of GnRH neurons, operate as key sensors of the metabolic state and funnel of the reproductive effects of leptin. Yet, much debate has arisen recently on whether the putative actions of leptin on the Kiss1 system are actually indirect and/or may primarily target Kiss1-independent pathways, such as those originating from the ventral premmamilary nucleus. Moreover, evidence has been presented for extra-hypothalamic or peripheral actions of leptin, including direct gonadal effects, which may contribute to the metabolic control of reproduction in extreme body weight conditions. In this work, we will critically review the experimental evidence supporting a role of leptin, kisspeptin

  10. Data Quality Assurance and Control for AmeriFlux Network at CDIAC, ORNL

    Science.gov (United States)

    Shem, W.; Boden, T.; Krassovski, M.; Yang, B.

    2014-12-01

    The Carbon Dioxide Information Analysis Center (CDIAC) at the Oak Ridge National Laboratory (ORNL) serves as the long-term data repository for the AmeriFlux network. Datasets currently available include hourly or half-hourly meteorological and flux observations, biological measurement records, and synthesis data products. Currently there is a lack of standardized nomenclature and specifically designed procedures for data quality assurance/control in processing and handling micrometeorological and ecological data at individual flux sites. CDIAC's has bridged this gap by providing efficient and accurate procedures for data quality control and standardization of the results for easier assimilation by the models used in climate science. In this presentation we highlight the procedures we have put in place to scrutinize continuous flux and meteorological data within Ameriflux network. We itemize some basic data quality issues that we have observed over the past years and include some examples of typical data quality issues. Such issues, e.g., incorrect time-stamping, poor calibration or maintenance of instruments, missing or incomplete metadata and others that are commonly over-looked by PI's, invariably impact the time-series observations.

  11. Effects of experimental nitrogen fertilization on planktonic metabolism and CO2 flux in a hypereutrophic hardwater lake.

    Directory of Open Access Journals (Sweden)

    Matthew J Bogard

    Full Text Available Hardwater lakes are common in human-dominated regions of the world and often experience pollution due to agricultural and urban effluent inputs of inorganic and organic nitrogen (N. Although these lakes are landscape hotspots for CO2 exchange and food web carbon (C cycling, the effect of N enrichment on hardwater lake food web functioning and C cycling patterns remains unclear. Specifically, it is unknown if different eutrophication scenarios (e.g., modest non point vs. extreme point sources yield consistent effects on auto- and heterotrophic C cycling, or how biotic responses interact with the inorganic C system to shape responses of air-water CO2 exchange. To address this uncertainty, we induced large metabolic gradients in the plankton community of a hypereutrophic hardwater Canadian prairie lake by adding N as urea (the most widely applied agricultural fertilizer at loading rates of 0, 1, 3, 8 or 18 mg N L-1 week-1 to 3240-L, in-situ mesocosms. Over three separate 21-day experiments, all treatments of N dramatically increased phytoplankton biomass and gross primary production (GPP two- to six-fold, but the effects of N on autotrophs plateaued at ~3 mg N L-1. Conversely, heterotrophic metabolism increased linearly with N fertilization over the full treatment range. In nearly all cases, N enhanced net planktonic uptake of dissolved inorganic carbon (DIC, and increased the rate of CO2 influx, while planktonic heterotrophy and CO2 production only occurred in the highest N treatments late in each experiment, and even in these cases, enclosures continued to in-gas CO2. Chemical effects on CO2 through calcite precipitation were also observed, but similarly did not change the direction of net CO2 flux. Taken together, these results demonstrate that atmospheric exchange of CO2 in eutrophic hardwater lakes remains sensitive to increasing N loading and eutrophication, and that even modest levels of N pollution are capable of enhancing autotrophy and CO

  12. Sense and nonsense in metabolic control of reproduction.

    Science.gov (United States)

    Schneider, Jill E; Klingerman, Candice M; Abdulhay, Amir

    2012-01-01

    An exciting synergistic interaction occurs among researchers working at the interface of reproductive biology and energy homeostasis. Reproductive biologists benefit from the theories, experimental designs, and methodologies used by experts on energy homeostasis while they bring context and meaning to the study of energy homeostasis. There is a growing recognition that identification of candidate genes for obesity is little more than meaningless reductionism unless those genes and their expression are placed in a developmental, environmental, and evolutionary context. Reproductive biology provides this context because metabolic energy is the most important factor that controls reproductive success and gonadal hormones affect energy intake, storage, and expenditure. Reproductive hormone secretion changes during development, and reproductive success is key to evolutionary adaptation, the process that most likely molded the mechanisms that control energy balance. It is likely that by viewing energy intake, storage, and expenditure in the context of reproductive success, we will gain insight into human obesity, eating disorders, diabetes, and other pathologies related to fuel homeostasis. This review emphasizes the metabolic hypothesis: a sensory system monitors the availability of oxidizable metabolic fuels and orchestrates behavioral motivation to optimize reproductive success in environments where energy availability fluctuates or is unpredictable.

  13. Role of Autophagy in the Control of Body Metabolism

    Directory of Open Access Journals (Sweden)

    Wenying Quan

    2013-03-01

    Full Text Available Autophagy plays a crucial role in the maintenance of cellular nutrient balance and the function of organelles such as mitochondria or the endoplasmic reticulum, which are important in intracellular metabolism, insulin release, and insulin sensitivity. In the insulin-producing pancreatic β-cells, autophagy is important in the maintenance of β-cell mass, structure, and function. Mice with deficiencies in β-cell-specific autophagy show reduced β-cell mass and defects in insulin secretion that lead to hypoinsulinemia and hyperglycemia but not diabetes. However, these mice developed diabetes when bred with ob/ob mice, suggesting that autophagy-deficient β-cells have defects in dealing with the increased metabolic stress imposed by obesity. These results also imply that autophagy deficiency in β-cells could be a factor in the progression from obesity to diabetes. Another important function of autophagy is in hypothalamic neurons for the central control of energy expenditure, appetite, and body weight. In addition, mice with autophagy deficiencies in the target tissues of insulin have yielded diverse phenotypes. Taken together, these results suggest that autophagy is important in the control of whole body energy and nutrient homeostasis, and its dysregulation could play a role in the development of metabolic disorders and diabetes.

  14. 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.

  15. Metabolic control of vesicular glutamate transport and release.

    Science.gov (United States)

    Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

    2010-10-06

    Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Effects of ocean acidification and hydrodynamic conditions on carbon metabolism and dissolved organic carbon (DOC) fluxes in seagrass populations.

    Science.gov (United States)

    Egea, Luis G; Jiménez-Ramos, Rocío; Hernández, Ignacio; Bouma, Tjeerd J; Brun, Fernando G

    2018-01-01

    Global change has been acknowledged as one of the main threats to the biosphere and its provision of ecosystem services, especially in marine ecosystems. Seagrasses play a critical ecological role in coastal ecosystems, but their responses to ocean acidification (OA) and climate change are not well understood. There have been previous studies focused on the effects of OA, but the outcome of interactions with co-factors predicted to alter during climate change still needs to be addressed. For example, the impact of higher CO2 and different hydrodynamic regimes on seagrass performance remains unknown. We studied the effects of OA under different current velocities on productivity of the seagrass Zostera noltei, using changes in dissolved oxygen as a proxy for the seagrass carbon metabolism, and release of dissolved organic carbon (DOC) in a four-week experiment using an open-water outdoor mesocosm. Under current pH conditions, increasing current velocity had a positive effect on productivity, but this depended on shoot density. However, this positive effect of current velocity disappeared under OA conditions. OA conditions led to a significant increase in gross production rate and respiration, suggesting that Z. noltei is carbon-limited under the current inorganic carbon concentration of seawater. In addition, an increase in non-structural carbohydrates was found, which may lead to better growing conditions and higher resilience in seagrasses subjected to environmental stress. Regarding DOC flux, a direct and positive relationship was found between current velocity and DOC release, both under current pH and OA conditions. We conclude that OA and high current velocity may lead to favourable growth scenarios for Z. noltei populations, increasing their productivity, non-structural carbohydrate concentrations and DOC release. Our results add new dimensions to predictions on how seagrass ecosystems will respond to climate change, with important implications for the

  17. Effects of ocean acidification and hydrodynamic conditions on carbon metabolism and dissolved organic carbon (DOC fluxes in seagrass populations.

    Directory of Open Access Journals (Sweden)

    Luis G Egea

    Full Text Available Global change has been acknowledged as one of the main threats to the biosphere and its provision of ecosystem services, especially in marine ecosystems. Seagrasses play a critical ecological role in coastal ecosystems, but their responses to ocean acidification (OA and climate change are not well understood. There have been previous studies focused on the effects of OA, but the outcome of interactions with co-factors predicted to alter during climate change still needs to be addressed. For example, the impact of higher CO2 and different hydrodynamic regimes on seagrass performance remains unknown. We studied the effects of OA under different current velocities on productivity of the seagrass Zostera noltei, using changes in dissolved oxygen as a proxy for the seagrass carbon metabolism, and release of dissolved organic carbon (DOC in a four-week experiment using an open-water outdoor mesocosm. Under current pH conditions, increasing current velocity had a positive effect on productivity, but this depended on shoot density. However, this positive effect of current velocity disappeared under OA conditions. OA conditions led to a significant increase in gross production rate and respiration, suggesting that Z. noltei is carbon-limited under the current inorganic carbon concentration of seawater. In addition, an increase in non-structural carbohydrates was found, which may lead to better growing conditions and higher resilience in seagrasses subjected to environmental stress. Regarding DOC flux, a direct and positive relationship was found between current velocity and DOC release, both under current pH and OA conditions. We conclude that OA and high current velocity may lead to favourable growth scenarios for Z. noltei populations, increasing their productivity, non-structural carbohydrate concentrations and DOC release. Our results add new dimensions to predictions on how seagrass ecosystems will respond to climate change, with important

  18. Real time implementation of viable torque and flux controllers and torque ripple minimization algorithm for induction motor drive

    International Nuclear Information System (INIS)

    Vasudevan, M.; Arumugam, R.; Paramasivam, S.

    2006-01-01

    Field oriented control (FOC) and direct torque control (DTC) are becoming the industrial standards for induction motors torque and flux control. This paper aims to give a contribution for a detailed comparison between these two control techniques, emphasizing their advantages and disadvantages. The performance of these two control schemes is evaluated in terms of torque and flux ripple and their transient response to step variations of the torque command. Moreover, a new torque and flux ripple minimization technique is also proposed to improve the performance of the DTC drive. Based on the experimental results, the analysis has been presented

  19. 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.

  20. Superconducting Qubit with Integrated Single Flux Quantum Controller Part I: Theory and Fabrication

    Science.gov (United States)

    Beck, Matthew; Leonard, Edward, Jr.; Thorbeck, Ted; Zhu, Shaojiang; Howington, Caleb; Nelson, Jj; Plourde, Britton; McDermott, Robert

    As the size of quantum processors grow, so do the classical control requirements. The single flux quantum (SFQ) Josephson digital logic family offers an attractive route to proximal classical control of multi-qubit processors. Here we describe coherent control of qubits via trains of SFQ pulses. We discuss the fabrication of an SFQ-based pulse generator and a superconducting transmon qubit on a single chip. Sources of excess microwave loss stemming from the complex multilayer fabrication of the SFQ circuit are discussed. We show how to mitigate this loss through judicious choice of process workflow and appropriate use of sacrificial protection layers. Present address: IBM T.J. Watson Research Center.

  1. Modified Direct Torque Control of Three-Phase Induction Motor Drives with Low Ripple in Flux and Torque

    Directory of Open Access Journals (Sweden)

    Vinay KUMAR

    2011-06-01

    Full Text Available This paper proposes an algorithm for direct flux and torque controlled three phase induction motor drive systems. This method is based on control of slip speed and decoupled between amplitude and angle of reference stator flux for determining required stator voltage vector. In this proposes model, integrator unit is not required to generate the reference stator flux angle for calculating required stator voltage vector, hence it eliminates the initial values problems in real time. Within the given sampling time, flux as well as torque errors are controlled by stator voltage vector which is evaluated from reference stator flux. The direct torque control is achieved by reference stator flux angle which is generates from instantaneous slip speed angular frequency and stator flux angular frequency. The amplitude of the reference stator flux is kept constant at rated value. This technique gives better performance in three-phase induction motor than conventional technique. Simulation results for 3hp induction motor drive, for both proposed and conventional techniques, are presented and compared. From the results it is found that the stator current, flux linkage and torque ripples are decreased with proposed technique.

  2. Global observation-based diagnosis of soil moisture control on land surface flux partition

    Science.gov (United States)

    Gallego-Elvira, Belen; Taylor, Christopher M.; Harris, Phil P.; Ghent, Darren; Veal, Karen L.; Folwell, Sonja S.

    2016-04-01

    Soil moisture plays a central role in the partition of available energy at the land surface between sensible and latent heat flux to the atmosphere. As soils dry out, evapotranspiration becomes water-limited ("stressed"), and both land surface temperature (LST) and sensible heat flux rise as a result. This change in surface behaviour during dry spells directly affects critical processes in both the land and the atmosphere. Soil water deficits are often a precursor in heat waves, and they control where feedbacks on precipitation become significant. State-of-the-art global climate model (GCM) simulations for the Coupled Model Intercomparison Project Phase 5 (CMIP5) disagree on where and how strongly the surface energy budget is limited by soil moisture. Evaluation of GCM simulations at global scale is still a major challenge owing to the scarcity and uncertainty of observational datasets of land surface fluxes and soil moisture at the appropriate scale. Earth observation offers the potential to test how well GCM land schemes simulate hydrological controls on surface fluxes. In particular, satellite observations of LST provide indirect information about the surface energy partition at 1km resolution globally. Here, we present a potentially powerful methodology to evaluate soil moisture stress on surface fluxes within GCMs. Our diagnostic, Relative Warming Rate (RWR), is a measure of how rapidly the land warms relative to the overlying atmosphere during dry spells lasting at least 10 days. Under clear skies, this is a proxy for the change in sensible heat flux as soil dries out. We derived RWR from MODIS Terra and Aqua LST observations, meteorological re-analyses and satellite rainfall datasets. Globally we found that on average, the land warmed up during dry spells for 97% of the observed surface between 60S and 60N. For 73% of the area, the land warmed faster than the atmosphere (positive RWR), indicating water stressed conditions and increases in sensible heat flux

  3. FFTF [Fast Flux Test Facility] performance measurements for safety, productivity and control

    International Nuclear Information System (INIS)

    Newland, D.J.; Praetorius, P.R.; Tomaszewski, T.A.

    1987-05-01

    A useful set of performance measurements for Safety, Productivity and Control has evolved at the Fast Flux Test Facility (FFTF). In response to declining budgets and the resulting need to safely manage a manpower rampdown, an ''Early Warning System'' was developed in 1984. Its purpose was to monitor the effects of the staffing rampdown such that appropriate remedial action could be taken to correct adverse trends before a significant problem occurred. 1 tab

  4. The BWR core simulator COSIMA with 2 group nodal flux expansion and control rod history

    International Nuclear Information System (INIS)

    Hoejerup, C.F.

    1989-08-01

    The boiling water simulator NOTAM has been modified and improved in several aspects: - The ''1 1/2'' energy group TRILUX nodal flux solution method has been exchanged with a 2 group modal expansion method. - Control rod ''history'' has been introduced. - Precalculated instrument factors have been introduced. The paper describes these improvements, which were considered sufficiently large to justify a new name to the programme: COSIMA. (author)

  5. Metabolic Control in Mammalian Fed-Batch Cell Cultures for Reduced Lactic Acid Accumulation and Improved Process Robustness

    Directory of Open Access Journals (Sweden)

    Viktor Konakovsky

    2016-01-01

    Full Text Available Biomass and cell-specific metabolic rates usually change dynamically over time, making the “feed according to need” strategy difficult to realize in a commercial fed-batch process. We here demonstrate a novel feeding strategy which is designed to hold a particular metabolic state in a fed-batch process by adaptive feeding in real time. The feed rate is calculated with a transferable biomass model based on capacitance, which changes the nutrient flow stoichiometrically in real time. A limited glucose environment was used to confine the cell in a particular metabolic state. In order to cope with uncertainty, two strategies were tested to change the adaptive feed rate and prevent starvation while in limitation: (i inline pH and online glucose concentration measurement or (ii inline pH alone, which was shown to be sufficient for the problem statement. In this contribution, we achieved metabolic control within a defined target range. The direct benefit was two-fold: the lactic acid profile was improved and pH could be kept stable. Multivariate Data Analysis (MVDA has shown that pH influenced lactic acid production or consumption in historical data sets. We demonstrate that a low pH (around 6.8 is not required for our strategy, as glucose availability is already limiting the flux. On the contrary, we boosted glycolytic flux in glucose limitation by setting the pH to 7.4. This new approach led to a yield of lactic acid/glucose (Y L/G around zero for the whole process time and high titers in our labs. We hypothesize that a higher carbon flux, resulting from a higher pH, may lead to more cells which produce more product. The relevance of this work aims at feeding mammalian cell cultures safely in limitation with a desired metabolic flux range. This resulted in extremely stable, low glucose levels, very robust pH profiles without acid/base interventions and a metabolic state in which lactic acid was consumed instead of being produced from day 1. With

  6. Development of Anodic Flux and Temperature Controlling System for Micro Direct Methanol Fuel Cell

    International Nuclear Information System (INIS)

    Li, M M; Liu, C; Liang, J S; Wu, C B; Xu, Z

    2006-01-01

    Micro Direct Methanol Fuel Cell (μDMFC) is a kind of newly developed power sources, which effective apparatus for its performance evaluation is still in urgent need at present. In this study, a testing system was established for the purpose of testing the continuous working performance such as micro flux and temperature of μDMFC. In view of the temperature controlling for micro-flux liquid fuel, a heating block with labyrinth-like single pass channel inside for heating up the methanol solution was fabricated. A semiconductorrefrigerating chip was utilized to heat and cool the liquid flow during testing procedures. On the other hand, the two channels of a high accuracy double-channel syringe pump that can suck and pump in turn so as to transport methanol solution continuously was adopted. Based on the requirements of wide-ranged temperature and micro flux controlling, the solenoid valves and the correlative component were used. A hydraulic circuit, which can circulate the fed methanol cold to hot in turn, has also been constructed to test the fatigue life of the μDMFC. The automatic control was actualized by software module written with Visual C++. Experimental results show that the system is perfect in stability and it may provide an important and advanced evaluation apparatus to satisfy the needs for real time performance testing of μDMFC

  7. Brain Ceramide Metabolism in the Control of Energy Balance

    Directory of Open Access Journals (Sweden)

    Céline Cruciani-Guglielmacci

    2017-10-01

    Full Text Available The regulation of energy balance by the central nervous system (CNS is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D. Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate, the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance.

  8. 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.

  9. 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.

  10. NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair.

    Science.gov (United States)

    Wang, Pei; Li, Wen-Lin; Liu, Jian-Min; Miao, Chao-Yu

    2016-06-01

    Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.

  11. Metabolic control of muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher

    2003-01-01

    that combined blockade of NOS and PGI2, and NOS and cytochrome P450, both attenuate exercise-induced hyperemia in humans. Combined vasodilator blockade studies offer the potential to uncover important interactions and compensatory vasodilator responses. The signaling pathways that link metabolic events evoked...... to exert control of muscle vasodilation. Adenosine, nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarization factor (EDHF) are possible mediators of muscle vasodilation during exercise. In humans, adenosine has been shown to contribute to functional hyperemia as blood flow...... by muscle contraction to vasodilatory signals in the local vascular bed remains an important area of study....

  12. Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

    Science.gov (United States)

    van Riel, N A; Giuseppin, M L; Verrips, C T

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

  13. Eddy-current inspection of high flux isotope reactor nuclear control rods

    International Nuclear Information System (INIS)

    Smith, J.H.; Chitwood, L.D.

    1981-07-01

    Inner control rods for the High Flux Isotope Reactor were nondestructively inspected for defects by eddy-current techniques. During these examinations aluminum cladding thickness and oxide thickness on the cladding were also measured. Special application techniques were required because of the high-radiation levels (approx. 10 5 R/h at 30 cm) present and the relatively large temperature gradients that occurred on the surface of the control rods. The techniques used to perform the eddy-current inspections and the methods used to reduce the associated data are described

  14. Flux coupling and transcriptional regulation within the metabolic network of the photosynthetic bacterium Synechocystis sp. PCC6803

    DEFF Research Database (Denmark)

    Montagud, Arnau; Zelezniak, Aleksej; Navarro, Emilio

    2011-01-01

    networks, surrounded by a stable core of pathways leading to biomass building blocks. This analysis identified potential bottlenecks for hydrogen and ethanol production. Integration of transcriptomic data with the Synechocystis flux coupling networks lead to identification of reporter flux coupling pairs...

  15. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  16. Improving understanding of controls on spatial variability in methane fluxes in Arctic tundra

    Science.gov (United States)

    Davidson, Scott J.; Sloan, Victoria; Phoenix, Gareth; Wagner, Robert; Oechel, Walter; Zona, Donatella

    2015-04-01

    The Arctic is experiencing rapid climate change relative to the rest of the globe, and this increase in temperature has feedback effects across hydrological and thermal regimes, plant community distribution and carbon stocks within tundra soils. Arctic wetlands account for a significant amount of methane emissions from natural ecosystems to the atmosphere and with further permafrost degradation under a warming climate, these emissions are expected to increase. Methane (CH4) is an extremely important component of the global carbon cycle with a global warming potential 28.5 times greater than carbon dioxide over a 100 year time scale (IPCC, 2013). In order to validate carbon cycle models, modelling methane at broader landscape scales is needed. To date direct measurements of methane have been sporadic in time and space which, while capturing some key controls on the spatial heterogeneity, make it difficult to accurately upscale methane emissions to the landscape and regional scales. This study investigates what is controlling the spatial heterogeneity of methane fluxes across Arctic tundra. We combined over 300 portable chamber observations from 13 micro-topographic positions (with multiple vegetation types) across three locations spanning a 300km latitudinal gradient in Northern Alaska from Barrow to Ivotuk with synchronous measurements of environmental (soil temperature, soil moisture, water table, active layer thaw depth, pH) and vegetation (plant community composition, height, sedge tiller counts) variables to evaluate key controls on methane fluxes. To assess the diurnal variation in CH4 fluxes, we also performed automated chamber measurements in one study site (Barrow) location. Multiple statistical approaches (regression tree and multiple linear regression) were used to identify key controlling variables and their interactions. Methane emissions across all sites ranged from -0.08 to 15.3 mg C-CH4 m-2 hr-1. As expected, soil moisture was the main control

  17. On which timescales do gas transfer velocities control North Atlantic CO2 flux variability?

    Science.gov (United States)

    Couldrey, Matthew P.; Oliver, Kevin I. C.; Yool, Andrew; Halloran, Paul R.; Achterberg, Eric P.

    2016-05-01

    The North Atlantic is an important basin for the global ocean's uptake of anthropogenic and natural carbon dioxide (CO2), but the mechanisms controlling this carbon flux are not fully understood. The air-sea flux of CO2, F, is the product of a gas transfer velocity, k, the air-sea CO2 concentration gradient, ΔpCO2, and the temperature- and salinity-dependent solubility coefficient, α. k is difficult to constrain, representing the dominant uncertainty in F on short (instantaneous to interannual) timescales. Previous work shows that in the North Atlantic, ΔpCO2 and k both contribute significantly to interannual F variability but that k is unimportant for multidecadal variability. On some timescale between interannual and multidecadal, gas transfer velocity variability and its associated uncertainty become negligible. Here we quantify this critical timescale for the first time. Using an ocean model, we determine the importance of k, ΔpCO2, and α on a range of timescales. On interannual and shorter timescales, both ΔpCO2 and k are important controls on F. In contrast, pentadal to multidecadal North Atlantic flux variability is driven almost entirely by ΔpCO2; k contributes less than 25%. Finally, we explore how accurately one can estimate North Atlantic F without a knowledge of nonseasonal k variability, finding it possible for interannual and longer timescales. These findings suggest that continued efforts to better constrain gas transfer velocities are necessary to quantify interannual variability in the North Atlantic carbon sink. However, uncertainty in k variability is unlikely to limit the accuracy of estimates of longer-term flux variability.

  18. Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

    Science.gov (United States)

    Smith, John K.

    2018-01-01

    This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones, such as glucagon-like peptide 1 and leptin. It provides an insight as to how high intensity exercise may improve homeostatic control in overweight and obese subjects. Finally, it provides suggestions as to how further progress can be made in controlling the current pandemic of obesity and diabetes.

  19. Space Station CMIF extended duration metabolic control test

    Science.gov (United States)

    Schunk, Richard G.; Bagdigian, Robert M.; Carrasquillo, Robyn L.; Ogle, Kathryn Y.; Wieland, Paul O.

    1989-01-01

    The Space Station Extended Duration Metabolic Control Test (EMCT) was conducted at the MSFC Core Module Integration Facility. The primary objective of the EMCT was to gather performance data from a partially-closed regenerative Environmental Control and Life Support (ECLS) system functioning under steady-state conditions. Included is a description of the EMCT configuration, a summary of events, a discussion of anomalies that occurred during the test, and detailed results and analysis from individual measurements of water and gas samples taken during the test. A comparison of the physical, chemical, and microbiological methods used in the post test laboratory analyses of the water samples is included. The preprototype ECLS hardware used in the test, providing an overall process description and theory of operation for each hardware item. Analytical results pertaining to a system level mass balance and selected system power estimates are also included.

  20. 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

  1. Control of particles flux in a tokamak with an events structure; Controle des flux de particules dans un Tokamak au moyen d`une structure a events

    Energy Technology Data Exchange (ETDEWEB)

    Tsitrone, E

    1995-12-01

    Two key problems in the development of a controlled fusion reactor are: -the control of the ashes resulting from the fusion reaction (helium) and of the impurities coming from the wall erosion, which affect the central plasma performances by diluting the fuel and dissipating a part of the produced energy by radiation. - the removal of the heat carried to the walls by charged particles, which is highly concentrated (peak values of several tens of MW per m{sup 2}). Two types of systems are generally used for the plasma-wall interface: throat limiter and axisymmetric divertor. Neither is an ideal candidate to control simultaneously the heat and particle fluxes. This thesis investigates an alternative configuration, the vented limiter, tested for the first time on the Tore Supra tokamak. The vented limiter principle lies on the recycling neutrals collection by slots, in such a way that local thermal overload is avoided. It is shown experimentally that the surface temperature of the prototype installed in Tore Supra remains uniform. As far as the particle collection is concerned, even though the pressure in the vented limiter is lower than the pressure in the throat limiter by a factor 3 for deuterium and 4 helium, it is sufficient to control the plasma density. Moreover, as with a throat limiter, the pressure exhibits a quadratic evolution with the plasma density. To interpret these results, a model describing the plasma recycling on the limiter and the pumping by the slots has been developed. The model has been validated by a comparison with the experimental data. It was then used to propose an optimized version of the prototype with reshaped slots. This should improve the pumping efficiency by a factor 2, in deuterium as well as in helium, but without removing the discrepancy between both pumping efficiencies. (Abstract Truncated)

  2. Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells

    NARCIS (Netherlands)

    Grüning, N.M.; Rinnerthaler, M.; Bluemlein, K.; Mulleder, M.; Wamelink, M.M.C.; Lehrach, H.; Jakobs, C.A.J.M.; Breitenbach, M.; Ralser, M.

    2011-01-01

    In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism

  3. Controllable conditional quantum oscillations and quantum gate operations in superconducting flux qubits

    International Nuclear Information System (INIS)

    Chen Aimin; Cho Samyoung

    2011-01-01

    Conditional quantum oscillations are investigated for quantum gate operations in superconducting flux qubits. We present an effective Hamiltonian which describes a conditional quantum oscillation in two-qubit systems. Rabi-type quantum oscillations are discussed in implementing conditional quantum oscillations to quantum gate operations. Two conditional quantum oscillations depending on the states of control qubit can be synchronized to perform controlled-gate operations by varying system parameters. It is shown that the conditional quantum oscillations with their frequency synchronization make it possible to operate the controlled-NOT and -U gates with a very accurate gate performance rate in interacting qubit systems. Further, this scheme can be applicable to realize a controlled multi-qubit operation in various solid-state qubit systems. (author)

  4. Control of three dimensional particle flux to divertor using rotating RMP in the EAST tokamak

    Science.gov (United States)

    Jia, M.; Sun, Y.; Liang, Y.; Wang, L.; Xu, J.; Gu, S.; Lyu, B.; Wang, H. H.; Yang, X.; Zhong, F.; Chu, N.; Feng, W.; He, K.; Liu, Y. Q.; Qian, J.; Shi, T.; Shen, B.

    2018-04-01

    Controlling the steady state particle and heat flux impinging on the plasma facing components, as one of the main concerns of future fusion reactors, is still necessary when the transient power loads induced by edge localized modes (ELMs) have been eliminated by resonant magnetic perturbations (RMPs) in high confinement tokamak experiments. This is especially true for long pulse operation. One promising solution is to use the rotating perturbed field. Recently rotating and differential phase scans of n  =  1 and 2 RMP fields have been operated for the first time in EAST discharges. The particle flux patterns on the divertor targets change synchronously with both rotating and phasing RMP fields as predicted by the modeled magnetic footprint patterns. The modeling with plasma response, which is calculated by MARS-F, is also carried out. The plasma response shows amplifying or screening effect to n  =  2 perturbations with different spectra. This changes the field line penetration depth rather than the general footprint shape. This has been verified by experimental observations on EAST. These experiments motivate further study of reducing both transient and steady state local power load and particle flux with the help of rotating RMPs in long pulse operation.

  5. 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....

  6. FGF-dependent metabolic control of vascular development

    Science.gov (United States)

    Yu, Pengchun; Alves, Tiago C.; Fang, Jennifer S.; Xie, Yi; Zhu, Jie; Chen, Zehua; De Smet, Frederik; Zhang, Jiasheng; Jin, Suk-Won; Sun, Lele; Sun, Hongye; Kibbey, Richard G.; Hirschi, Karen K.; Hay, Nissim; Carmeliet, Peter; Chittenden, Thomas W.; Eichmann, Anne; Potente, Michael; Simons, Michael

    2017-01-01

    Blood and lymphatic vasculatures are intimately involved in tissue oxygenation and fluid homeostasis maintenance. Assembly of these vascular networks involves sprouting, migration and proliferation of endothelial cells. Recent studies have suggested that changes in cellular metabolism are of importance to these processes1. While much is known about vascular endothelial growth factor (VEGF)-dependent regulation of vascular development and metabolism2,3, little is understood about the role of fibroblast growth factors (FGFs) in this context4. Here we identify FGF receptor (FGFR) signaling as a critical regulator of vascular development. This is achieved by FGF-dependent control of c-MYC (MYC) expression that, in turn, regulates expression of the glycolytic enzyme hexokinase 2 (HK2). A decrease in HK2 levels in the absence of FGF signaling inputs results in decreased glycolysis leading to impaired endothelial cell proliferation and migration. Pan-endothelial- and lymphatic-specific Hk2 knockouts phenocopy blood and/or lymphatic vascular defects seen in Fgfr1/r3 double mutant mice while HK2 overexpression partially rescues the defects caused by suppression of FGF signaling. Thus, FGF-dependent regulation of endothelial glycolysis is a pivotal process in developmental and adult vascular growth and development. PMID:28467822

  7. 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

  8. 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

  9. 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

  10. Speed control of permanent magnet excitation transverse flux linear motor by using adaptive neuro-fuzzy controller

    Energy Technology Data Exchange (ETDEWEB)

    Hasanien, Hany M., E-mail: Hanyhasanien@ieee.or [Dept. of Elec. Power and Machines, Faculty of Eng., Ain-shams Univ. Cairo (Egypt); Muyeen, S.M. [Department of Electrical Engineering, Petroleum Institute, Abu Dhabi (United Arab Emirates); Tamura, Junji [Department of EEE, Kitami Institute of Technology, 165 Koen Cho, Kitami 090-8507, Hokkaido (Japan)

    2010-12-15

    This paper presents a novel adaptive neuro-fuzzy controller applies on transverse flux linear motor for controlling its speed. The proposed controller presents fuzzy logic controller with self tuning scaling factors based on artificial neural network structure. It has two input variables and one control output variable. Firstly the fuzzy logic control rules are described then NN architecture is represented to self tune the output scaling factors of the controller. The application of this control technique represents the novelty of work, where this algorithm has so far not been stated before for this type of drives. This methodology solves the problem of nonlinearities and load changes of TFLM drives. The dynamic response of the motor is studied under the rated load condition as well as load disturbances. The proposed controller ensures fast and accurate dynamic response with an excellent steady state performance. The dynamic response of the motor with the proposed controller is compared with PI and adaptive NN controllers. It is found that the proposed controller gives better and faster response from the viewpoint of overshoot and settling time. Matlab/Simulink tool is used for this dynamic simulation study.

  11. CARBO-CONTROLE. Quantification of the carbon flux and stocks at the european and national scale; CARBO-CONTROLE. Quantification des flux et stocks de carbone au niveau Europeen et national

    Energy Technology Data Exchange (ETDEWEB)

    Ciais, P

    2007-07-01

    The CARBO-CONTROLE project aims to evaluate the different methodologies to estimate the CO{sub 2} flux at the european, national and regional scale. The strategy is to combine a crumbling, down scaling, of the flux at a big scale, by inverting the atmospheric CO{sub 2} measures with a aggregation, up scaling, of the national stocks and flux from the climatic parameters of a model of ecosystems.They show that with the monthly data of the global network of CO{sub 2} monitoring stations, it is possible to obtain an estimation of the european flux. Meanwhile the errors bond to the leak of continental stations are of the order of the flux average. (A.L.B.)

  12. Controls and variability of solute and sedimentary fluxes in Arctic and sub-Arctic Environments

    Science.gov (United States)

    Dixon, John

    2015-04-01

    Six major factors consistently emerge as controls on the spatial and temporal variability in sediment and solute fluxes in cold climates. They are climatic, geologic, physiographic or relief, biologic, hydrologic, and regolith factors. The impact of these factors on sediment and solute mass transfer in Arctic and sub-Arctic environments is examined. Comparison of non-glacierized Arctic vs. subarctic drainage basins reveals the effects of these controls. All drainage basins exhibit considerable variability in rates of sediment and solute fluxes. For the non-glacierized drainage basins there is a consistent increase in sediment mass transfer by slope processes and fluvial processes as relief increases. Similarly, a consistent increase in sediment mass transfer by slope and fluvial processes is observed as total precipitation increases. Similar patterns are also observed with respect to solute transport and relief and precipitation. Lithologic factors are most strongly observed in the contrast between volcanic vs. plutonic igneous bedrock substrates. Basins underlain by volcanic rocks display greater mass transfers than those underlain by plutonic rocks. Biologic influences are most strongly expressed by variations in extent of vegetation cover and the degree of human interference, with human impacted basins generating greater fluxes. For glacierized basins the fundamental difference to non-glacierized basins is an overall increase in mean annual mass transfers of sediment and a generally smaller magnitude solute transfer. The principal role of geology is observed with respect to lithology. Catchments underlain by limestone demonstrate substantially greater solute mass transfers than sediment transfer. The influence of relief is seen in the contrast in mass transfers between upland and lowland drainage basins with upland basins generating greater sediment and solute transfers than lowland basins. For glacierized basins the effects of biology and regolith appear to be

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

    DEFF Research Database (Denmark)

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno

    2017-01-01

    obtained by (13)C-NMR spectroscopy in rodent brain. When simulated data matched experiments as well as biophysical calculations, the stoichiometry for voltage/ligand-gated Na(+) and K(+) fluxes generated by neuronal activity was close to a 1:1 relationship, and specifically 63/58 Na(+)/K(+) ions per...

  14. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

    2016-05-01

    Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

  15. Soil Dissolved Organic Carbon Fluxes are Controlled by both Precipitation and Longer-Term Climate Effects on Boreal Forest Ecosystems

    Science.gov (United States)

    Hotchkiss, E. R.; Ziegler, S. E.; Edwards, K. A.; Bowering, K.

    2017-12-01

    Water acts as a control on the cycling of organic carbon (OC). Forest productivity responses to climate change are linked to water availability while water residence time is a major control on OC loss in aquatic ecosystems. However, controls on the export of terrestrial OC to the aquatic environment remains poorly understood. Transport of dissolved OC (DOC) through soils both vertically to deeper soil horizons and into aquatic systems is a key flux of terrestrial OC, but the climate drivers controlling OC mobilized from soils is poorly understood. We installed zero-tension lysimeters across similar balsam fir forest sites within three regions that span a MAT gradient of 5.2˚C and MAP of 1050-1500 mm. Using soil water collected over all seasons for four years we tested whether a warmer and wetter climate promotes greater DOC fluxes in ecosystems experiencing relatively high precipitation. Variability within and between years was compared to that observed across climates to test the sensitivity of this flux to shorter relative to longer-term climate effects on this flux. The warmest and wettest southern site exhibited the greatest annual DOC flux (25 to 28 g C m-2 y-1) in contrast to the most northern site (8 to 10 g C m -2 y-1). This flux represented 10% of litterfall C inputs across sites and surpassed the DOC export from associated forested headwater streams (1 to 16 g C m-2 y-1) suggesting terrestrial to aquatic interface processing. Historical climate and increased soil C inputs explain the greater DOC flux in the southern region. Even in years with comparable annual precipitation among regions the DOC flux differed by climate region. Furthermore, neither quantity nor form of precipitation could explain inter-annual differences in DOC flux within each region. Region specific relationships between precipitation and soil water flux instead suggest historical climate effects may impact soil water transport efficiency thereby controlling the regional variation in

  16. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  17. Controlled heat flux measurement across a closing nanoscale gap and its comparison to theory

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Y.; Ghafari, A.; Budaev, B. V.; Bogy, D. B., E-mail: dbogy@berkeley.edu [Department of mechanical Engineering, Computer Mechanics Lab, University of California, Berkeley, California 94720 (United States)

    2016-05-23

    We present here a controlled measurement of heat flux across a closing gap that is initially less than 10 nm wide between two solid surfaces at different temperatures. The measured heat transfer is compared with our published theoretical analyses of this phenomenon that show thermal radiation dominates the heat transfer for gaps wider than about 1–2 nm, but phonon conduction dominates between 1 and 2 nm and contact. The experiments employ a thermal actuator mounted on a rocking base block for coarse positioning that supplies Joule heating to an embedded element to cause thermal expansion of a localized region for less than 10 nm spacing control, together with an embedded near-surface resistive temperature sensor to measure its temperature change due to the heat flux across the gap. The measured results are in general agreement with the theoretical predictions, and they also agree with common sense expectations. This paper not only shows nano-scale heat transfer measurement across a closing gap, it also lends additional strong support to the validity of the referenced theoretical developments. The proposed experimental approach can provide support to design of future devices for nano-scale heat transfer measurement.

  18. Method and apparatus for controlling the neutron flux in nuclear reactors

    International Nuclear Information System (INIS)

    Minnick, L.E.

    1979-01-01

    A control rod assembly in a nuclear reactor that automatically scrams the reactor when a loss of coolant flow occurs and that can also control the level of neutron flux in the reactor is described. The control rod assembly includes a separator plate having an orifice through which the reactor coolant flows and a sealing surface around the orifice. The control rod in the assembly has a complementary sealing surface. When the control rod and separator plate are brought into contact, the differential pressure across the separator plate caused by the flow of the primary coolant through the reactor core retains the two sealing surfaces together. If the flow of coolant stops or the differential pressure across the separator plate decreases for any reason, the control rod drops by gravity and the reactor is scrammed. The control rod is also automatically dropped as a result of the lateral vibration of an earthquake or by the downward motion of the rod drive shaft, either of which will open the sealing surfaces and reduce the sealing pressure

  19. Above and belowground connections and species interactions: Controls over ecosystem fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Trowbridge, Amy Marie [Montana State Univ., Bozeman, MT (United States); Phillips, Richard [Indiana Univ., Bloomington, IN (United States); Stoy, Paul Christopher [Montana State Univ., Bozeman, MT (United States)

    2016-11-01

    The ultimate goal of this work was to quantify soil and volatile organic compound fluxes as a function of tree species and associated mycorrhizal associations in an intact forest, but also to describe the physical and biological factors that control these emissions. The results of this research lay the foundation toward an improved mechanistic understanding of carbon pathways, fluxes, and ecosystem function, ultimately improving the representation of forest ecosystems in Earth System models. To this end, a multidisciplinary approach was necessary to fill a critical gap in our understanding of how soil and root processes may influence whole-ecosystem carbon-based volatile fluxes in the face of a rapidly changing climate. We developed a series of novel sampling protocols and coupled a variety of advanced analytical techniques, resulting in findings relevant across disciplines. Furthermore, we leveraged existing infrastructure, research sites, and datasets to design a low-cost exploratory project that links belowground processes, soil volatile emissions, and total ecosystem carbon budgets. Measurements from soil collars installed across a species/mycorrhizal gradient at the DOE-supported Moran Monroe State Forest Ameriflux tower site suggest that leaf litter is the primary source of belowground and forest floor volatile emissions, but the strength of this source is significantly affected not only by leaf litter type, but the strength of the soil as a sink. Results suggest that the strength of the sink is influenced by tree species-specific associated microbial communities that change throughout the season as a function of temperature, soil moisture, leaf litter inputs, and phenology. The magnitude of the observed volatile fluxes from the forest floor is small relative to total aboveground ecosystem flux, but the contribution of these emissions to volatile-mediated ecological interactions and soil processes (e.g. nitrification) varies substantially across the growing

  20. Improved Metabolic Control in Diabetes, HSP60, and Proinflammatory Mediators

    Directory of Open Access Journals (Sweden)

    Claudio Blasi

    2012-01-01

    Full Text Available The diabetes-atherosclerosis relationship remains to be fully defined. Repeated prolonged hyperglycemia, increased ROS production and endothelial dysfunction are important factors. One theory is that increased blood levels of heat shock protein (HSP60 are proinflammatory, through activation of innate immunity, and contribute to the progression of vascular disease. It was hypothesized that improvement of diabetes control in patients presenting with metabolic syndrome would lower HSP60, and anti-HSP60 antibody levels and decrease inflammatory markers. Paired sera of 17 Italian patients, before and after intensive treatment, were assayed for cytokines, HSP60 and anti-HSP60 antibodies. As expected, intensive treatment was associated with a decrease in HgbA1C (P<0.001 and BMI (P<0.001. After treatment, there was a significant decrease in IL-6 (P<0.05. HSP60 levels were before treatment −6.9+1.9, after treatment −7.1+2.0 ng/mL (P=ns. Overall HSP60 concentrations were lower than published reports. Anti-HSP60 antibody titers were high and did not decrease with treatment. In conclusion, improvement of diabetic control did not alter HSP60 concentrations or antiHSP60 antibody titers, but led to a reduction of IL-6 levels.

  1. Spatially Explicit Simulation of Mesotopographic Controls on Peatland Hydrology and Carbon Fluxes

    Science.gov (United States)

    Sonnentag, O.; Chen, J. M.; Roulet, N. T.

    2006-12-01

    A number of field carbon flux measurements, paleoecological records, and model simulations have acknowledged the importance of northern peatlands in terrestrial carbon cycling and methane emissions. An important parameter in peatlands that influences both net primary productivity, the net gain of carbon through photosynthesis, and decomposition under aerobic and anaerobic conditions, is the position of the water table. Biological and physical processes involved in peatland carbon dynamics and their hydrological controls operate at different spatial scales. The highly variable hydraulic characteristics of the peat profile and the overall shape of the peat body as defined by its surface topography at the mesoscale (104 m2) are of major importance for peatland water table dynamics. Common types of peatlands include bogs with a slightly domed centre. As a result of the convex profile, their water supply is restricted to atmospheric inputs, and water is mainly shed by shallow subsurface flow. From a modelling perspective the influence of mesotopographic controls on peatland hydrology and thus carbon balance requires that process-oriented models that examine the links between peatland hydrology, ecosystem functioning, and climate must incorporate some form of lateral subsurface flow consideration. Most hydrological and ecological modelling studies in complex terrain explicitly account for the topographic controls on lateral subsurface flow through digital elevation models. However, modelling studies in peatlands often employ simple empirical parameterizations of lateral subsurface flow, neglecting the influence of peatlands low relief mesoscale topography. Our objective is to explicitly simulate the mesotopographic controls on peatland hydrology and carbon fluxes using the Boreal Ecosystem Productivity Simulator (BEPS) adapted to northern peatlands. BEPS is a process-oriented ecosystem model in a remote sensing framework that takes into account peatlands multi

  2. Control Mechanisms of the Electron Heat Flux in the Solar Wind: Observations in Comparison to Numerical Simulations

    Science.gov (United States)

    Stverak, S.; Hellinger, P.; Landi, S.; Travnicek, P. M.; Maksimovic, M.

    2017-12-01

    Recent understanding of the heat transport and dissipation in the expanding solar wind propose number of complex control mechanisms down to the electron kinetic scales. We investigate the evolution of electron heat flux properties and constraints along the expansion using in situ observations from Helios spacecraft in comparison to numerical kinetic simulations. In particular we focus on the roles of Coulomb collisions and wave-particle interactions in shaping the electron velocity distribution functions and thus controlling the heat transported by the electron heat flux. We show the general evolution of the electron heat flux to be driven namely by the Coulomb collisions. Locally we demonstrate the wave-particle interactions related to the kinetic plasma instabilities to be providing effective constraints in case of extreme heat flux levels.

  3. Sequential cryogen spraying for heat flux control at the skin surface

    Science.gov (United States)

    Majaron, Boris; Aguilar, Guillermo; Basinger, Brooke; Randeberg, Lise L.; Svaasand, Lars O.; Lavernia, Enrique J.; Nelson, J. Stuart

    2001-05-01

    Heat transfer rate at the skin-air interface is of critical importance for the benefits of cryogen spray cooling in combination with laser therapy of shallow subsurface skin lesions, such as port-wine stain birthmarks. With some cryogen spray devices, a layer of liquid cryogen builds up on the skin surface during the spurt, which may impair heat transfer across the skin surface due to relatively low thermal conductivity and potentially higher temperature of the liquid cryogen layer as compared to the spray droplets. While the mass flux of cryogen delivery can be adjusted by varying the atomizing nozzle geometry, this may strongly affect other spray properties, such as lateral spread (cone), droplet size, velocity, and temperature distribution. We present here first experiments with sequential cryogen spraying, which may enable accurate mass flux control through variation of spray duty cycle, while minimally affecting other spray characteristics. The observed increase of cooling rate and efficiency at moderate duty cycle levels supports the above described hypothesis of isolating liquid layer, and demonstrates a novel approach to optimization of cryogen spray devices for individual laser dermatological applications.

  4. Remote Power Control Injection of Grid-Connected Power Converters Based on Virtual Flux

    Directory of Open Access Journals (Sweden)

    Nurul Fazlin Roslan

    2018-02-01

    Full Text Available Renewable Energy Source (RES-based power plants need to control the active and reactive power at the Point of Common Connection (PCC with the grid, in order to comply with the requirements of the Transmission System Operators (TSOs. This point is normally far away from the power converter station, and the cables and step-up transformers have a non-neglectable influence on the delivered power. In order to overcome this drawback, this paper presents a control algorithm that permits one to control remotely the power injected at the PCC, by adjusting the local controller of the Voltage Source Converters (VSCs. In this work, the synchronization with the grid is done based on the Virtual Flux (VF concept. The results reveals that the VF estimation is able to produce a reliable estimation of the grid voltage in any point of the network, and makes it possible to calculate the necessary current reference for injecting a desired active and reactive power at a point that can be some kilometres away. In this paper the main principle for this remote power control is presented. Likewise, the simulation and experimental results will be shown in order to analyse the effectiveness of the proposed system.

  5. Plasma under control: Advanced solutions and perspectives for plasma flux management in material treatment and nanosynthesis

    Science.gov (United States)

    Baranov, O.; Bazaka, K.; Kersten, H.; Keidar, M.; Cvelbar, U.; Xu, S.; Levchenko, I.

    2017-12-01

    Given the vast number of strategies used to control the behavior of laboratory and industrially relevant plasmas for material processing and other state-of-the-art applications, a potential user may find themselves overwhelmed with the diversity of physical configurations used to generate and control plasmas. Apparently, a need for clearly defined, physics-based classification of the presently available spectrum of plasma technologies is pressing, and the critically summary of the individual advantages, unique benefits, and challenges against key application criteria is a vital prerequisite for the further progress. To facilitate selection of the technological solutions that provide the best match to the needs of the end user, this work systematically explores plasma setups, focusing on the most significant family of the processes—control of plasma fluxes—which determine the distribution and delivery of mass and energy to the surfaces of materials being processed and synthesized. A novel classification based on the incorporation of substrates into plasma-generating circuitry is also proposed and illustrated by its application to a wide variety of plasma reactors, where the effect of substrate incorporation on the plasma fluxes is emphasized. With the key process and material parameters, such as growth and modification rates, phase transitions, crystallinity, density of lattice defects, and others being linked to plasma and energy fluxes, this review offers direction to physicists, engineers, and materials scientists engaged in the design and development of instrumentation for plasma processing and diagnostics, where the selection of the correct tools is critical for the advancement of emerging and high-performance applications.

  6. 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

  7. Surface-Air Mercury Fluxes Across Western North America: A Synthesis of Spatial Trends and Controlling Variables.

    Science.gov (United States)

    Eckley, C.; Tate, M.; Lin, C. J.; Gustin, M. S.; Dent, S.; Eagles-Smith, C.; Lutz, M.; Wickland, K.; Wang, B.; Gray, J.; Edwards, G. C.; Krabbenhoft, D. P.; Smith, D. B.

    2016-12-01

    Mercury (Hg) emission and deposition can occur to and from soils and are an important component of the global atmospheric Hg budget. This presentation focuses on synthesizing existing surface-air Hg flux data collected throughout the Western North American region and is part of a series of geographically focused Hg synthesis projects. A database of existing Hg flux data collected using the dynamic flux chamber (DFC) approach from almost a thousand locations was created for the Western North America region. Statistical analysis was performed on the data to identify the important variables controlling Hg fluxes and to allow spatiotemporal scaling. The results indicated that most of the variability in soil-air Hg fluxes could be explained by variations in soil-Hg concentrations, solar radiation, and soil moisture. This analysis also identified that variations in DFC methodological approaches were detectable among the field studies, with the chamber material and sampling flushing flow rate influencing the magnitude of calculated emissions. The spatiotemporal scaling of soil-air Hg fluxes identified that the largest emissions occurred from irrigated agricultural landscapes in California. Vegetation was shown to have a large impact on surface-air Hg fluxes due to both a reduction in solar radiation reaching the soil as well as from direct uptake of Hg in foliage. Despite high soil Hg emissions from some forested and other heavily vegetated regions, the net ecosystem flux (soil flux + vegetation uptake) was low. Conversely, sparsely vegetated regions showed larger net ecosystem emissions, which were similar in magnitude to atmospheric Hg deposition (except for the Mediterranean California region where soil emissions were higher). The net ecosystem flux results highlight the important role of landscape characteristics in effecting the balance between Hg sequestration and (re-)emission to the atmosphere.

  8. Surface-air mercury fluxes across Western North America: A synthesis of spatial trends and controlling variables

    Science.gov (United States)

    Eckley, Chris S.; Tate, Michael T.; Lin, Che-Jen; Gustin, Mae S.; Dent, Stephen; Eagles-Smith, Collin A.; Lutz, Michelle A; Wickland, Kimberly; Wang, Bronwen; Gray, John E.; Edwards, Grant; Krabbenhoft, David P.; Smith, David

    2016-01-01

    Mercury (Hg) emission and deposition can occur to and from soils, and are an important component of the global atmospheric Hg budget. This paper focuses on synthesizing existing surface-air Hg flux data collected throughout the Western North American region and is part of a series of geographically focused Hg synthesis projects. A database of existing Hg flux data collected using the dynamic flux chamber (DFC) approach from almost a thousand locations was created for the Western North America region. Statistical analysis was performed on the data to identify the important variables controlling Hg fluxes and to allow spatiotemporal scaling. The results indicated that most of the variability in soil-air Hg fluxes could be explained by variations in soil-Hg concentrations, solar radiation, and soil moisture. This analysis also identified that variations in DFC methodological approaches were detectable among the field studies, with the chamber material and sampling flushing flow rate influencing the magnitude of calculated emissions. The spatiotemporal scaling of soil-air Hg fluxes identified that the largest emissions occurred from irrigated agricultural landscapes in California. Vegetation was shown to have a large impact on surface-air Hg fluxes due to both a reduction in solar radiation reaching the soil as well as from direct uptake of Hg in foliage. Despite high soil Hg emissions from some forested and other heavily vegetated regions, the net ecosystem flux (soil flux + vegetation uptake) was low. Conversely, sparsely vegetated regions showed larger net ecosystem emissions, which were similar in magnitude to atmospheric Hg deposition (except for the Mediterranean California region where soil emissions were higher). The net ecosystem flux results highlight the important role of landscape characteristics in effecting the balance between Hg sequestration and (re-)emission to the atmosphere.

  9. Surface-air mercury fluxes across Western North America: A synthesis of spatial trends and controlling variables

    Energy Technology Data Exchange (ETDEWEB)

    Eckley, Chris S., E-mail: eckley.chris@epa.gov [US Environmental Protection Agency, Region-10, Seattle, WA 98101 (United States); Tate, Mike T. [US Geological Survey, Middleton, WI 53562 (United States); Lin, Che-Jen [Center for Advances on Water and Air quality, Lamar University, Beaumont, TX 77710 (United States); Gustin, Mae [Department of Natural Resources & Environmental Science, University of Nevada, Reno, NV 89557 (United States); Dent, Stephen [CDM Smith, Portland, OR 97205 (United States); Eagles-Smith, Collin [US Geological Survey, Corvallis, OR 97331 (United States); Lutz, Michelle A. [US Geological Survey, Middleton, WI 53562 (United States); Wickland, Kimberly P. [US Geological Survey Boulder, CO 80303 (United States); Wang, Bronwen [US Geological Survey, Anchorage, AK 99508 (United States); Gray, John E. [US Geological Survey, Denver, CO 80225 (United States); Edwards, Grant C. [Department of Environment and Geography, Macquarie University, North Ryde, NSW 2109 (Australia); Krabbenhoft, Dave P. [US Geological Survey, Middleton, WI 53562 (United States); Smith, David B. [US Geological Survey, Denver, CO 80225 (United States)

    2016-10-15

    Mercury (Hg) emission and deposition can occur to and from soils, and are an important component of the global atmospheric Hg budget. This paper focuses on synthesizing existing surface-air Hg flux data collected throughout the Western North American region and is part of a series of geographically focused Hg synthesis projects. A database of existing Hg flux data collected using the dynamic flux chamber (DFC) approach from almost a thousand locations was created for the Western North America region. Statistical analysis was performed on the data to identify the important variables controlling Hg fluxes and to allow spatiotemporal scaling. The results indicated that most of the variability in soil-air Hg fluxes could be explained by variations in soil-Hg concentrations, solar radiation, and soil moisture. This analysis also identified that variations in DFC methodological approaches were detectable among the field studies, with the chamber material and sampling flushing flow rate influencing the magnitude of calculated emissions. The spatiotemporal scaling of soil-air Hg fluxes identified that the largest emissions occurred from irrigated agricultural landscapes in California. Vegetation was shown to have a large impact on surface-air Hg fluxes due to both a reduction in solar radiation reaching the soil as well as from direct uptake of Hg in foliage. Despite high soil Hg emissions from some forested and other heavily vegetated regions, the net ecosystem flux (soil flux + vegetation uptake) was low. Conversely, sparsely vegetated regions showed larger net ecosystem emissions, which were similar in magnitude to atmospheric Hg deposition (except for the Mediterranean California region where soil emissions were higher). The net ecosystem flux results highlight the important role of landscape characteristics in effecting the balance between Hg sequestration and (re-)emission to the atmosphere. - Highlights: • Soil-air Hg fluxes are an important component of the

  10. Surface-air mercury fluxes across Western North America: A synthesis of spatial trends and controlling variables

    International Nuclear Information System (INIS)

    Eckley, Chris S.; Tate, Mike T.; Lin, Che-Jen; Gustin, Mae; Dent, Stephen; Eagles-Smith, Collin; Lutz, Michelle A.; Wickland, Kimberly P.; Wang, Bronwen; Gray, John E.; Edwards, Grant C.; Krabbenhoft, Dave P.; Smith, David B.

    2016-01-01

    Mercury (Hg) emission and deposition can occur to and from soils, and are an important component of the global atmospheric Hg budget. This paper focuses on synthesizing existing surface-air Hg flux data collected throughout the Western North American region and is part of a series of geographically focused Hg synthesis projects. A database of existing Hg flux data collected using the dynamic flux chamber (DFC) approach from almost a thousand locations was created for the Western North America region. Statistical analysis was performed on the data to identify the important variables controlling Hg fluxes and to allow spatiotemporal scaling. The results indicated that most of the variability in soil-air Hg fluxes could be explained by variations in soil-Hg concentrations, solar radiation, and soil moisture. This analysis also identified that variations in DFC methodological approaches were detectable among the field studies, with the chamber material and sampling flushing flow rate influencing the magnitude of calculated emissions. The spatiotemporal scaling of soil-air Hg fluxes identified that the largest emissions occurred from irrigated agricultural landscapes in California. Vegetation was shown to have a large impact on surface-air Hg fluxes due to both a reduction in solar radiation reaching the soil as well as from direct uptake of Hg in foliage. Despite high soil Hg emissions from some forested and other heavily vegetated regions, the net ecosystem flux (soil flux + vegetation uptake) was low. Conversely, sparsely vegetated regions showed larger net ecosystem emissions, which were similar in magnitude to atmospheric Hg deposition (except for the Mediterranean California region where soil emissions were higher). The net ecosystem flux results highlight the important role of landscape characteristics in effecting the balance between Hg sequestration and (re-)emission to the atmosphere. - Highlights: • Soil-air Hg fluxes are an important component of the

  11. Enhanced control of DFIG wind turbine based on stator flux decay compensation

    DEFF Research Database (Denmark)

    Zhu, Rongwu; Deng, Fujin; Chen, Zhe

    2016-01-01

    For the doubly-fed induction generator (DFIG)- based wind energy conversion system (WECS), the decaying flux and negative flux are the main reasons to cause the DFIG rotor overcurrent, during grid faults. The stator decaying flux characteristics versus the depth and instant of the stator voltage...

  12. 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...

  13. The voltage—current relationship and equivalent circuit implementation of parallel flux-controlled memristive circuits

    International Nuclear Information System (INIS)

    Bao Bo-Cheng; Feng Fei; Dong Wei; Pan Sai-Hu

    2013-01-01

    A flux-controlled memristor characterized by smooth cubic nonlinearity is taken as an example, upon which the voltage—current relationships (VCRs) between two parallel memristive circuits — a parallel memristor and capacitor circuit (the parallel MC circuit), and a parallel memristor and inductor circuit (the parallel ML circuit) — are investigated. The results indicate that the VCR between these two parallel memristive circuits is closely related to the circuit parameters, and the frequency and amplitude of the sinusoidal voltage stimulus. An equivalent circuit model of the memristor is built, upon which the circuit simulations and experimental measurements of both the parallel MC circuit and the parallel ML circuit are performed, and the results verify the theoretical analysis results

  14. A new design approach for control circuits of pipelined single-flux-quantum microprocessors

    International Nuclear Information System (INIS)

    Yamanashi, Y; Akimoto, A; Yoshikawa, N; Tanaka, M; Kawamoto, T; Kamiya, Y; Fujimaki, A; Terai, H; Yorozu, S

    2006-01-01

    A novel method of design for controllers of pipelined microprocessors using single-flux-quantum (SFQ) logic has been proposed. The proposed design approach is based on one hot encoding and is very suitable for designing a finite state machine using SFQ logic circuits, where each internal state of the microprocessor is represented by a flip-flop. In this approach, decoding of the internal state can be performed instantaneously, in contrast to the case in the conventional method using a binary state register. Moreover, pipelining is effectively implemented without increasing the circuit size because no pipeline registers are required in the one hot encoding. By using this method, we have designed a controller for our new SFQ microprocessors, which employs pipelining. The number of Josephson junctions of the newly designed controller is 1067, while the previous version without pipelining contains 1721 Josephson junctions. These results indicate that the proposed design approach is very effective for pipelined SFQ microprocessors. We have implemented a new controller using the NEC 2.5 kA cm -2 Nb standard process and confirmed its correct operation experimentally

  15. Role of hexose transport in control of glycolytic flux in Saccharomyces cerevisiae.

    Science.gov (United States)

    Elbing, Karin; Larsson, Christer; Bill, Roslyn M; Albers, Eva; Snoep, Jacky L; Boles, Eckhard; Hohmann, Stefan; Gustafsson, Lena

    2004-09-01

    The yeast Saccharomyces cerevisiae predominantly ferments glucose to ethanol at high external glucose concentrations, irrespective of the presence of oxygen. In contrast, at low external glucose concentrations and in the presence of oxygen, as in a glucose-limited chemostat, no ethanol is produced. The importance of the external glucose concentration suggests a central role for the affinity and maximal transport rates of yeast's glucose transporters in the control of ethanol production. Here we present a series of strains producing functional chimeras between the hexose transporters Hxt1 and Hxt7, each of which has distinct glucose transport characteristics. The strains display a range of decreasing glycolytic rates resulting in a proportional decrease in ethanol production. Using these strains, we show for the first time that at high glucose levels, the glucose uptake capacity of wild-type S. cerevisiae does not control glycolytic flux during exponential batch growth. In contrast, our chimeric Hxt transporters control the rate of glycolysis to a high degree. Strains whose glucose uptake is mediated by these chimeric transporters will undoubtedly provide a powerful tool with which to examine in detail the mechanism underlying the switch between fermentation and respiration in S. cerevisiae and will provide new tools for the control of industrial fermentations.

  16. Zooplankton biomass and metabolism through image analysis systems: from the development and testing of metabolic equations to the assessment of carbon fluxes

    OpenAIRE

    Garijo, Juan Carlos

    2016-01-01

    Programa de Doctorado en Oceanografía Zooplankton plays an important role in the biogeochemical cycles in the ocean. Due to their central position in the ocean’s food web, they recycle and redistribute energy and matter, not only at different levels of the trophic web, but also horizontally and vertically in the water column. Understanding the role of zooplankton in the biological pump and the ocean carbon cycle requires accurate estimates of community biomass and metabolism at large spati...

  17. Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

    National Research Council Canada - National Science Library

    Randall, Lisa

    1998-01-01

    ... (Diabetes control and Complications Trial, 1993). Nurses' understanding of diabetes management coupled with a holistic view of person makes them the optimal professionals to facilitate patient movement toward tight metabolic control...

  18. Enhancing sediment flux control and natural hazard risk mitigation through a structured conceptual planning approach

    Science.gov (United States)

    Simoni, S.; Vignoli, G.; Mazzorana, B.

    2017-08-01

    Sediment fluxes from mountain rivers contribute to shape the geomorphologic features of lowland rivers and to establish the physical basis for an optimal set of ecosystem functions and related services to people. Through significant public funding, the hydro-morphological regimes of mountain rivers in the European Alps have been progressively altered over the last century, with the aim to provide a safe dwelling space, to boost transport, mobility and to support economic growth. We claim that the underlying planning weaknesses contribute to determine these inefficient resource allocations, since flood risk is still high and the ecosystem services are far from being optimal. Hence, with the overall aim to enhance sediment flux control and hazard risk mitigation in such heavily modified alpine streams, we propose a structured design workflow which guides the planner through system analysis and synthesis. As a first step the proposed workflow sets the relevant planning goals and assesses the protection structure functionality. Then a methodology is proposed to achieve the goals. This methodology consists in characterising the hydrologic basin of interest and the sediment availability and determining the sediment connectivity to channels. The focus is set on the detailed analysis of existing river cross sections where the sediment continuity is interrupted (e.g. slit and check dams). By retaining relevant sediment volumes these structures prevent the reactivation of hydro-morphological and associated ecological functionalities. Since their actual performance can be unsatisfying with respect to flood risk mitigation (e.g. mainly old structures), we introduce specific efficiency indicators as a support for the conceptual design stage to quantify effects related to sediment flux control and risk management. The proposed planning approach is then applied to the Gadria system (stream, slit dam, retention basin and culvert), located in South Tyrol, Italy. This case study

  19. Changes of in vivo fluxes through central metabolic pathways during the production of nystatin by Streptomyces noursei in batch culture

    DEFF Research Database (Denmark)

    Jonsbu, E.; Christensen, Bjarke; Nielsen, Jens

    2001-01-01

    The central carbon metabolism of the nystatin-producing strain Streptomyces noursei ATCC 11455 was evaluated by C-13-labelling experiments. A batch fermentation was examined during the idiophase by GC-MS measurements of the labelling patterns of amino acids in the biomass. The labelling patterns...

  20. Physiological response to extreme fasting in subantarctic fur seal (Arctocephalus tropicalis) pups: metabolic rates, energy reserve utilization, and water fluxes.

    Science.gov (United States)

    Verrier, Delphine; Groscolas, René; Guinet, Christophe; Arnould, John P Y

    2009-11-01

    Surviving prolonged fasting requires various metabolic adaptations, such as energy and protein sparing, notably when animals are simultaneously engaged in energy-demanding processes such as growth. Due to the intermittent pattern of maternal attendance, subantarctic fur seal pups have to repeatedly endure exceptionally long fasting episodes throughout the 10-mo rearing period while preparing for nutritional independence. Their metabolic responses to natural prolonged fasting (33.4 +/- 3.3 days) were investigated at 7 mo of age. Within 4-6 fasting days, pups shifted into a stage of metabolic economy characterized by a minimal rate of body mass loss (0.7%/day) and decreased resting metabolic rate (5.9 +/- 0.1 ml O(2)xkg(-1)xday(-1)) that was only 10% above the level predicted for adult terrestrial mammals. Field metabolic rate (289 +/- 10 kJxkg(-1)xday(-1)) and water influx (7.9 +/- 0.9 mlxkg(-1)xday(-1)) were also among the lowest reported for any young otariid, suggesting minimized energy allocation to behavioral activity and thermoregulation. Furthermore, lean tissue degradation was dramatically reduced. High initial adiposity (>48%) and predominant reliance on lipid catabolism likely contributed to the exceptional degree of protein sparing attained. Blood chemistry supported these findings and suggested utilization of alternative fuels, such as beta-hydroxybutyrate and de novo synthesized glucose from fat-released glycerol. Regardless of sex and body condition, pups tended to adopt a convergent strategy of extreme energy and lean body mass conservation that appears highly adaptive for it allows some tissue growth during the repeated episodes of prolonged fasting they experience throughout their development.

  1. Spatial variability and controls over biomass stocks, carbon fluxes, and resource-use efficiencies across forest ecosystems

    NARCIS (Netherlands)

    Fernández-Martínez, Marcos; Vicca, Sara; Janssens, Ivan A.; Luyssaert, Sebastiaan; Campioli, Matteo; Sardans, Jordi; Estiarte, Marc; Peñuelas, Josep

    2014-01-01

    Key message: Stand age, water availability, and the length of the warm period are the most influencing controls of forest structure, functioning, and efficiency. We aimed to discern the distribution and controls of plant biomass, carbon fluxes, and resource-use efficiencies of forest ecosystems

  2. Integration of Environmental and Developmental (or Metabolic) Control of Seed Mass by Sugar and Ethylene Metabolisms in Arabidopsis.

    Science.gov (United States)

    Meng, Lai-Sheng; Xu, Meng-Ke; Wan, Wen; Wang, Jing-Yi

    2018-04-04

    In higher plants, seed mass is an important to evolutionary fitness. In this context, seedling establishment positively correlates with seed mass under conditions of environmental stress. Thus, seed mass constitutes an important agricultural trait. Here, we show loss-of-function of YODA (YDA), a MAPKK Kinase, and decreased seed mass, which leads to susceptibility to drought. Furthermore, we demonstrate that yda disrupts sugar metabolisms but not the gaseous plant hormone, ethylene. Our data suggest that the transcription factor EIN3 (ETHYLENE-INSENSITIVE3), integral to both sugar and ethylene metabolisms, physically interacts with YDA. Further, ein3-1 mutants exhibited increased seed mass. Genetic analysis indicated that YDA and EIN3 were integral to a sugar-mediated metabolism cascade which regulates seed mass by maternally controlling embryo size. It is well established that ethylene metabolism leads to the suppression of drought tolerance by the EIN3 mediated inhibition of CBF1, a transcription factor required for the expression genes of abiotic stress. Our findings help guide the synthesis of a model predicting how sugar/ethylene metabolisms and environmental stress are integrated at EIN3 to control both the establishment of drought tolerance and the production of seed mass. Collectively, these insights into the molecular mechanism underpinning the regulation of plant seed size may aid prospective breeding or design strategies to increase crop yield.

  3. Landscape Controls of CH4 Fluxes in a Catchment of the Forest Tundra in Northern Siberia

    Science.gov (United States)

    Flessa, H.; Rodionov, A.; Guggenberger, G.; Fuchs, H.; Magdon, P.; Shibistova, O.; Zrazhevskaya, G.; Kasansky, O.; Blodau, C.

    2007-12-01

    Soils have the capacity to both produce and consume atmospheric methane. The direction and the size of net- CH4 exchange between soils and atmosphere is mainly controlled by the soil aeration, temperature and the amount of bioavailable organic matter. All these factors are strongly influenced by distribution and seasonal dynamics of permafrost. Thus, distribution of permafrost and the thickness of the active layer can exert strong influence on CH4 dynamics in artic and northern boreal ecosystems. We analyzed the spatial and temporal variability of net-CH4 exchange within a catchment located in the Siberian forest tundra at the eastern shore of the lower Yenissej River to constrain the current function of this region as a sink or source of atmospheric CH4 and to gain insight into the potential for climatic change to alter the rate and form of carbon cycling and CH4 fluxes in this region. Net-fluxes of CH4 were measured from July to November 2003 and from August 2006 to July 2007 on representative soils of the catchment (mineral soils with different thawing depth, soils of bog plateaux) and on a thermokarst pond. In addition, dissolved CH4 in the stream draining the catchment was determined. Field observations, classification of landscape structures from satellite images and flux measurements were combined to estimate total catchment CH4 exchange. Nearly all soils of the catchment were net-sinks of atmospheric CH4 with annual CH4-C uptake rates ranging between 1.2 and 0.2 kg ha-1 yr-1. The active layer depth was the main factor determining the size of CH4 uptake. Total net-exchange of CH4 from the catchment was dominated by ponds that covered only about 2% of the catchment area. Due to high CH4 emission from these aquatic systems, the catchment was a net source of atmospheric CH4 with a mean annual emission of approximately 170 kg CH4-C ha-1. CH4 concentration in streams draining the catchment can help to identify areas with high CH4 production. The results suggest

  4. The LMJ project - status of our knowledge in hohlraum energetics physics: production and control of the radiation flux

    International Nuclear Information System (INIS)

    Dattolo, E.

    2001-09-01

    CEA-DAM in France is working on Inertial controlled Fusion (ICF) since the beginning of nineties. In an indirect drive scheme, the laser light is converted in X-ray in a hohlraum made with an high-Z material. Part of this radiation flux is absorbed by a micro-balloon filled with DT, placed in the center of the hohlraum, and generates its implosion, ignition and burn. This paper gives the status of our knowledge and studies for production and control of the radiation flux in the hohlraum, in the perspective of the Laser MegaJoule (LMJ). (authors)

  5. Physical and biological controls over patterns of methane flux from wetland soils

    Science.gov (United States)

    Owens, S. M.; von Fischer, J. C.

    2006-12-01

    While methane (CH4) production and plant-facilitated gas transport both contribute to patterns of CH4 emissions from wetlands, the relative importance of each mechanism is uncertain. In flooded wetland soils, CH4 is produced by anaerobic methanogenic bacteria. In the absence of competing oxidizers (i.e. SO42-, NO3-, O2), CH4 production is limited by the availability of labile carbon, which is supplied from recent plant primary production (e.g. as root exudates) and converted by anaerobic fermenting bacteria into methanogenic substrate (e.g. acetate). Because diffusion of gases through saturated soils is extremely slow, the aerenchymous tissues of wetland plants provide the primary pathway for CH4 emissions in systems dominated by emergent vascular vegetation. Aerenchyma also function to shuttle atmospheric oxygen to belowground plant tissues for respiration. Consequentially, root radial oxygen loss results in an oxidized rhizosphere, which limits CH4 production and provides habitat for aerobic methanotrophic bacteria, potentially reducing CH4 emissions. To test the contribution of recent photosynthates on CH4 emissions, a shading experiment was conducted in a Juncus-dominated wetland in the Colorado Front Range. Shade treatments significantly reduced net ecosystem production (NEE) and gross primary production (GPP) compared to control plots (p=0.0194 and p=0.0551, respectively). While CH4 emissions did not significantly differ between treatments, CH4 flux rates were strongly correlated with NEE (p=0.0063) and GPP (p=0.0020), in support of the hypothesis that labile carbon from recent photosynthesis controls patterns of CH4 emissions. The relative importance of plant gas transport and methane consumption rates on CH4 emissions is not known. Methane flux is more tightly correlated with NEE than GPP, which may be explained by increased CH4 consumption or decreased CH4 production as a result of rhizospheric oxidation. The ability to predict future emissions of this

  6. Simultaneously estimation for surface heat fluxes of steel slab in a reheating furnace based on DMC predictive control

    International Nuclear Information System (INIS)

    Li, Yanhao; Wang, Guangjun; Chen, Hong

    2015-01-01

    The predictive control theory is utilized for the research of a simultaneous estimation of heat fluxes through the upper, side and lower surface of a steel slab in a walking beam type rolling steel reheating furnace. An inverse algorithm based on dynamic matrix control (DMC) is established. That is, each surface heat flux of a slab is simultaneously estimated through rolling optimization on the basis of temperature measurements in selected points of its interior by utilizing step response function as predictive model of a slab's temperature. The reliability of the DMC results is enhanced without prior assuming specific functions of heat fluxes over a period of future time. The inverse algorithm proposed a respective regularization to effectively improve the stability of the estimated results by considering obvious strength differences between the upper as well as lower and side surface heat fluxes of the slab. - Highlights: • The predictive control theory is adopted. • An inversion scheme based on DMC is established. • Upper, side and lower surface heat fluxes of slab are estimated based DMC. • A respective regularization is proposed to improve the stability of results

  7. Direct Torque Control with Full Order Stator Flux Observer for Dual-Three Phase Induction Motor Drives

    Science.gov (United States)

    Farina, Francesco; Bojoi, Radu; Tenconi, Alberto; Profumo, Francesco

    A Direct Torque Control (DTC) strategy for dual-three phase induction motor drives is discussed in this paper. The induction machine has two sets of stator three-phase windings spatially shifted by 30 electrical degrees with isolated neutral points. The proposed control strategy is based on Proportional Integral (PI) regulators implemented in the stator flux synchronous reference frame. To improve the flux estimation, an Adaptive Stator Flux Observer (ASFO) has been used. Doing so, besides a better flux estimation in contrast to open-loop flux estimators, it is possible to use the observed currents to compensate the inverter non-linear behavior (such as dead-time effects), improving the drive performance at low speed. This is particularly important for low voltage/high current applications, as the drive considered in this paper. The advantages of the discussed control strategy are: constant inverter switching frequency, good transient and steady-state performance and less distorted machine currents in contrast to DTC schemes with variable switching frequency. Experimental results are presented for a 10kW dual three-phase induction motor drive prototype.

  8. Significance of family and peer support for metabolic control of type 1 diabetes in adolescents

    Directory of Open Access Journals (Sweden)

    Đurović Dušanka

    2009-01-01

    Full Text Available The aim of the paper was to explore the significance of family and peer support for metabolic control of Type 1 diabetes in adolescents. Metabolic control refers to maintenance of acceptable blood glucose level thus diminishing risk for chronic complications. It involves regular insulin shots, measuring blood glucose and keeping diary, as the daily based self-control. Regular visits to endocrinologist and screening for chronic complications are compulsory. The sample comprised 79 adolescents age 10-17 years with diagnose of Type 1 diabetes and properly treated at the institute. The sample was divided in two groups - with good (N=40 and poor (N=39 metabolic control. A criterium for good metabolic control was glycosilated hemoglobin less than 7,6%. Social support was measured by Social Support Scale consisting of two parts - the first for estimation of registered family support (based upon modified Perceived Social Support Family Scale and the second for estimation of registered friends' support (modified Perceived Social Support Friend Scale. Adolescents with good metabolic control referred statistically more significant social support in the family, unlike the group with poor metabolic control. Considering peer social support, there was no statistically significant difference. Positive family history for diabetes also appeared to be directly linked to good metabolic control.

  9. Complex controls on nitrous oxide flux across a large-elevation gradient in the tropical Peruvian Andes

    Directory of Open Access Journals (Sweden)

    T. Diem

    2017-11-01

    Full Text Available Current bottom–up process models suggest that montane tropical ecosystems are weak atmospheric sources of N2O, although recent empirical studies from the southern Peruvian Andes have challenged this idea. Here we report N2O flux from combined field and laboratory experiments that investigated the process-based controls on N2O flux from montane ecosystems across a large-elevation gradient (600–3700 m a.s.l. in the southern Peruvian Andes. Nitrous oxide flux and environmental variables were quantified in four major habitats (premontane forest, lower montane forest, upper montane forest and montane grassland at monthly intervals over a 30-month period from January 2011 to June 2013. The role of soil moisture content in regulating N2O flux was investigated through a manipulative, laboratory-based 15N-tracer experiment. The role of substrate availability (labile organic matter, NO3− in regulating N2O flux was examined through a field-based litter-fall manipulation experiment and a laboratory-based 15N–NO3− addition study, respectively. Ecosystems in this region were net atmospheric sources of N2O, with an unweighted mean flux of 0.27 ± 0.07 mg N–N2O m−2 d−1. Weighted extrapolations, which accounted for differences in land surface area among habitats and variations in flux between seasons, predicted a mean annual flux of 1.27 ± 0.33 kg N2O–N ha−1 yr−1. Nitrous oxide flux was greatest from premontane forest, with an unweighted mean flux of 0.75 ± 0.18 mg N–N2O m−2 d−1, translating to a weighted annual flux of 0.66 ± 0.16 kg N2O–N ha−1 yr−1. In contrast, N2O flux was significantly lower in other habitats. The unweighted mean fluxes for lower montane forest, montane grasslands, and upper montane forest were 0.46 ± 0.24 mg N–N2O m−2 d−1, 0.07 ± 0.08 mg N–N2O m−2 d−1, and 0.04 ± 0.07 mg N–N2O m−2 d−1

  10. Metabolic flux analysis of the phenylpropanoid pathway in wound-healing potato tuber tissue using stable isotope-labeled tracer and LC-MS spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Fumio; Morino, Keiko; Miyashita, Masahiro; Miyagawa, Hisashi [Kyoto Univ. (Japan). Department of Agriculture

    2003-05-01

    The metabolic flux of two phenylpropanoid metabolites, N-p-coumaroyloctopamine (p-CO) and chlorogenic acid (CGA), in the wound-healing potato tuber tissue was quantitatively analyzed by a newly developed method based upon the tracer experiment using stable isotope-labeled compounds and LC-MS. Tuber disks were treated with aqueous solution of L-phenyl-d{sub 5}-alanine, and the change in the ratio of stable isotope-labeled compound to non-labeled (isotope abundance) was monitored for p-CO and CGA in the tissue extract by LC-MS. The time-dependent change in the isotope abundance of each metabolite was fitted to an equation that was derived from the formation and conversion kinetics of each compound. Good correlations were obtained between the observed and calculated isotope abundances for both p-CO and CGA. The rates of p-CO formation and conversion (i.e. fluxes) were 1.15 and 0.96 nmol (g FW){sup -1}h{sup -1}, respectively, and for CGA, the rates 4.63 and 0.42 nmol (g FW){sup -1}h{sup -1}, respectively. This analysis enabled a direct comparison of the biosynthetic activity between these two compounds. (author)

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

    Science.gov (United States)

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

    2014-03-01

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

  12. Flight muscle enzymes and metabolic flux rates during hovering flight of the nectar bat, Glossophaga soricina: further evidence of convergence with hummingbirds.

    Science.gov (United States)

    Suarez, R K; Welch, K C; Hanna, S K; Herrera M, L G

    2009-06-01

    Given their high metabolic rates, nectarivorous diet, and ability to directly fuel their energetically-expensive flight using recently-ingested sugar, we tested the hypothesis that Pallas long tongued nectar bats (Glossophaga soricina) possess flight muscles similar to those of hummingbirds with respect to enzymatic flux capacities in bioenergetic pathways. In addition, we compared these biochemical capacities with flux rates achieved in vivo during hovering flight. Rates of oxygen consumption (V(O(2))) were measured during hover-feeding and used to estimate rates of ATP turnover, glucose and long-chain fatty acid oxidation per unit mass of flight muscle. Enzyme V(max) values at key steps in glucose and fatty acid oxidation obtained in vitro from pectoralis muscle samples exceed those found in the locomotory muscles of other species of small mammals and resemble data obtained from hummingbird flight muscles. The ability of nectar bats and hummingbirds to hover in fed and fasted states, fueled almost exclusively by carbohydrate or fat, respectively, allowed the estimation of fractional velocities (v/V(max)) at both the hexokinase and carnitine palmitoyltransferase-2 steps in glucose and fatty acid oxidation, respectively. The results further support the hypothesis of convergent evolution in biochemical and physiological traits in nectar bats and hummingbirds.

  13. Whole-system metabolism and CO2 fluxes in a Mediterranean Bay dominated by seagrass beds (Palma Bay, NW Mediterranean

    Directory of Open Access Journals (Sweden)

    F. Gazeau

    2005-01-01

    Full Text Available Planktonic and benthic incubations (bare and Posidonia oceanica vegetated sediments were performed at monthly intervals from March 2001 to October 2002 in a seagrass vegetated area of the Bay of Palma (Mallorca, Spain. Results showed a contrast between the planktonic compartment, which was on average near metabolic balance (−4.6±5.9 mmol O2 m-2 d-1 and the benthic compartment, which was autotrophic (17.6±8.5 mmol O2 m-2 d-1. During two cruises in March and June 2002, planktonic and benthic incubations were performed at several stations in the bay to estimate the whole-system metabolism and to examine its relationship with partial pressure of CO2 (pCO2 and apparent oxygen utilisation (AOU spatial patterns. Moreover, during the second cruise, when the residence time of water was long enough, net ecosystem production (NEP estimates based on incubations were compared, over the Posidonia oceanica meadow, to rates derived from dissolved inorganic carbon (DIC and oxygen (O2 mass balance budgets. These budgets provided NEP estimates in fair agreement with those derived from direct metabolic estimates based on incubated samples over the Posidonia oceanica meadow. Whereas the seagrass community was autotrophic, the excess organic carbon production therein could only balance the planktonic heterotrophy in shallow waters relative to the maximum depth of the bay (55 m. This generated a horizontal gradient from autotrophic or balanced communities in the shallow seagrass-covered areas, to strongly heterotrophic communities in deeper areas of the bay. It seems therefore that, on an annual scale in the whole bay, the organic matter production by the Posidonia oceanica may not be sufficient to fully compensate the heterotrophy of the planktonic compartment, which may require external organic carbon inputs, most likely from land.

  14. Nucleotide Metabolism and its Control in Lactic Acid Bacteria

    DEFF Research Database (Denmark)

    Kilstrup, Mogens; Hammer, Karin; Jensen, Peter Ruhdal

    2005-01-01

    Most metabolic reactions are connected through either their utilization of nucleotides or their utilization of nucleotides or their regulation by these metabolites. In this review the biosynthetic pathways for pyrimidine and purine metabolism in lactic acid bacteria are described including...... the interconversion pathways, the formation of deoxyribonucleotides and the salvage pathways for use of exogenous precursors. The data for the enzymatic and the genetic regulation of these pathways are reviewed, as well as the gene organizations in different lactic acid bacteria. Mutant phenotypes and methods...... for manipulation of nucleotide pools are also discussed. Our aim is to provide an overview of the physiology and genetics of nucleotide metabolism and its regulation that will facilitate the interpretation of data arising from genetics, metabolomics, proteomics, and transcriptomics in lactic acid bacteria....

  15. Interaction Between the Central and Peripheral Effects of Insulin in Controlling Hepatic Glucose Metabolism in the Conscious Dog

    Science.gov (United States)

    Ramnanan, Christopher J.; Kraft, Guillaume; Smith, Marta S.; Farmer, Ben; Neal, Doss; Williams, Phillip E.; Lautz, Margaret; Farmer, Tiffany; Donahue, E. Patrick; Cherrington, Alan D.; Edgerton, Dale S.

    2013-01-01

    The importance of hypothalamic insulin action to the regulation of hepatic glucose metabolism in the presence of a normal liver/brain insulin ratio (3:1) is unknown. Thus, we assessed the role of central insulin action in the response of the liver to normal physiologic hyperinsulinemia over 4 h. Using a pancreatic clamp, hepatic portal vein insulin delivery was increased three- or eightfold in the conscious dog. Insulin action was studied in the presence or absence of intracerebroventricularly mediated blockade of hypothalamic insulin action. Euglycemia was maintained, and glucagon was clamped at basal. Both the molecular and metabolic aspects of insulin action were assessed. Blockade of hypothalamic insulin signaling did not alter the insulin-mediated suppression of hepatic gluconeogenic gene transcription but blunted the induction of glucokinase gene transcription and completely blocked the inhibition of glycogen synthase kinase-3β gene transcription. Thus, central and peripheral insulin action combined to control some, but not other, hepatic enzyme programs. Nevertheless, inhibition of hypothalamic insulin action did not alter the effects of the hormone on hepatic glucose flux (production or uptake). These data indicate that brain insulin action is not a determinant of the rapid (<4 h) inhibition of hepatic glucose metabolism caused by normal physiologic hyperinsulinemia in this large animal model. PMID:23011594

  16. Metabolic Engineering of Chemical Defence Pathways in Plant Disease Control

    DEFF Research Database (Denmark)

    Rook, Frederik

    2016-01-01

    on each topic. The chapter reviews the some of the scientific and technical challenges in metabolic engineering and the new possibilities emerging from recent technological developments. It concludes by discussing the outlook for bioengineered chemical defences as part of crop protection strategies, also...... with antimicrobial properties for use in crop protection. It presents an overview of the metabolic engineering efforts made in the area of plant chemical defence. For in-depth information on the characteristics of a specific class of chemical defence compounds, the reader is referred to the specialized reviews...

  17. Controls of evapotranspiration and CO2 fluxes from scots pine by surface conductance and abiotic factors.

    Directory of Open Access Journals (Sweden)

    Tianshan Zha

    Full Text Available Evapotranspiration (E and CO2 flux (Fc in the growing season of an unusual dry year were measured continuously over a Scots pine forest in eastern Finland, by eddy covariance techniques. The aims were to gain an understanding of their biological and environmental control processes. As a result, there were obvious diurnal and seasonal changes in E, Fc , surface conductance (gc , and decoupling coefficient (Ω, showing similar trends to those in radiation (PAR and vapour pressure deficit (δ. The maximum mean daily values (24-h average for E, Fc , gc , and Ω were 1.78 mmol m(-2 s(-1, -11.18 µmol m(-2 s(-1, 6.27 mm s(-1, and 0.31, respectively, with seasonal averages of 0.71 mmol m(-2 s(-1, -4.61 µmol m(-2 s(-1, 3.3 mm s(-1, and 0.16. E and Fc were controlled by combined biological and environmental variables. There was curvilinear dependence of E on gc and Fc on gc . Among the environmental variables, PAR was the most important factor having a positive linear relationship to E and curvilinear relationship to Fc , while vapour pressure deficit was the most important environmental factor affecting gc . Water use efficiency was slightly higher in the dry season, with mean monthly values ranging from 6.67 to 7.48 μmol CO2 (mmol H2O(-1 and a seasonal average of 7.06 μmol CO2 (μmol H2O(-1. Low Ω and its close positive relationship with gc indicate that evapotranspiration was sensitive to surface conductance. Mid summer drought reduced surface conductance and decoupling coefficient, suggesting a more biotic control of evapotranspiration and a physiological acclimation to dry air. Surface conductance remained low and constant under dry condition, supporting that a constant value of surface constant can be used for modelling transpiration under drought condition.

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

    Science.gov (United States)

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

    2016-09-01

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

  19. [Characteristics of mercury exchange flux between soil and atmosphere under the snow retention and snow melting control].

    Science.gov (United States)

    Zhang, Gang; Wang, Ning; Ai, Jian-Chao; Zhang, Lei; Yang, Jing; Liu, Zi-Qi

    2013-02-01

    Jiapigou gold mine, located in the upper Songhua River, was once the largest mine in China due to gold output, where gold extraction with algamation was widely applied to extract gold resulting in severe mercury pollution to ambient environmental medium. In order to study the characteristics of mercury exchange flux between soil (snow) and atmosphere under the snow retention and snow melting control, sampling sites were selected in equal distances along the slope which is situated in the typical hill-valley terrain unit. Mercury exchange flux between soil (snow) and atmosphere was determined with the method of dynamic flux chamber and in all sampling sites the atmosphere concentration from 0 to 150 cm near to the earth in the vertical direction was measured. Furthermore, the impact factors including synchronous meteorology, the surface characteristics under the snow retention and snow melting control and the mercury concentration in vertical direction were also investigated. The results are as follows: During the period of snow retention and melting the air mercury tends to gather towards valley bottom along the slope and an obvious deposit tendency process was found from air to the earth's surface under the control of thermal inversion due to the underlying surface of cold source (snow surface). However, during the period of snow melting, mercury exchange flux between the soil and atmosphere on the surface of the earth with the snow being melted demonstrates alternative deposit and release processes. As for the earth with snow covered, the deposit level of mercury exchange flux between soil and atmosphere is lower than that during the period of snow retention. The relationship between mercury exchange flux and impact factors shows that in snow retention there is a remarkable negative linear correlation between mercury exchange flux and air mercury concentration as well as between the former and the air temperature. In addition, in snow melting mercury exchange

  20. Control of alanine metabolism in rat liver by transport processes or cellular metabolism.

    OpenAIRE

    Fafournoux, P; Rémésy, C; Demigné, C

    1983-01-01

    1. Factors governing hepatic utilization of alanine were studied in vivo and in vitro in rats adapted to increasing dietary protein. 2. Hepatic alanine utilization was enhanced 5-fold with a 90%-casein diet, compared with a 13%-casein diet. The increased uptake resulted from enhanced fractional extraction in the presence of high concentrations of alanine in the portal vein. 3. The increase in alanine metabolism on high-protein diets was associated with an increase in alanine aminotransferase ...

  1. Practical Wide-speed-range Sensorless Control System for Permanent Magnet Reluctance Synchronous Motor Drives via Active Flux Model

    DEFF Research Database (Denmark)

    Ancuti, Mihaela Codruta; Tutelea, Lucian; Andreescu, Gheorghe-Daniel

    2014-01-01

    This article introduces a control strategy to obtain near-maximum available torque in a wide speed range with sensorless operation via the active flux concept for permanent magnet-reluctance synchronous motor drives. A new torque dq current reference calculator is proposed, with reference torque...

  2. Active-flux based motion sensorless vector control of biaxial excitation generator/motor for automobiles (BEGA)

    DEFF Research Database (Denmark)

    Coroban-Schramel, Vasile; Boldea, Ion; Andreescu, Gheorghe-Daniel

    2009-01-01

    This paper proposes a novel, active-flux based, motion-sensorless vector control structure for biaxial excitation generator for automobiles (BEGA) for wide speed range operation. BEGA is a hybrid excited synchronous machine having permanent magnets on q-axis and a dc excitation on daxis. Using th...... electrical degrees in less than 2 ms test time....

  3. Controlling Lipid Fluxes at Glycerol-3-phosphate Acyltransferase Step in Yeast

    Science.gov (United States)

    Marr, Nancy; Foglia, Julena; Terebiznik, Mauricio; Athenstaedt, Karin; Zaremberg, Vanina

    2012-01-01

    The ability to channel excess fatty acids into neutral lipids like triacylglycerol (TAG) is a critical strategy used by cells to maintain lipid homeostasis. Upon activation to acyl-CoA, fatty acids become readily available as substrates for acyltransferases involved in neutral lipid synthesis. Neutral lipids are then packed into organelles derived from the endoplasmic reticulum called lipid particles (LPs). The first acylation step in the de novo pathway for TAG synthesis is catalyzed by glycerol-3-phosphate acyltransferases (GPATs). Two isoforms, Gat1p/Gpt2p and Gat2p/Sct1p, are present in the yeast Saccharomyces cerevisiae. Previous evidence indicated that these enzymes contribute differentially to the synthesis of TAG in actively growing cells. In this work we studied the role of the yeast GPATs in the formation of LPs induced by a surplus of oleic acid. Yeast lacking Gat1p (but not Gat2p) were sensitive to oleate and failed to accumulate LPs induced by this unsaturated fatty acid. It is shown that oleate induces dephosphorylation of Gat1p as well as an increment in its levels. Most importantly, we identified novel Gat1p crescent structures that are formed in the presence of oleate. These structures are connected with the endoplasmic reticulum and are intimately associated with LPs. No such structures were observed for Gat2p. A crucial point of control of lipid fluxes at the GPAT step is proposed. PMID:22267742

  4. Controls on methane concentrations and fluxes in streams draining human-dominated landscapes

    Science.gov (United States)

    Crawford, John T.; Stanley, Emily H.

    2016-01-01

    Streams and rivers are active processors of carbon, leading to significant emissions of CO2 and possibly CH4 to the atmosphere. Patterns and controls of CH4 in fluvial ecosystems remain relatively poorly understood. Furthermore, little is known regarding how major human impacts to fluvial ecosystems may be transforming their role as CH4 producers and emitters. Here, we examine the consequences of two distinct ecosystem changes as a result of human land use: increased nutrient loading (primarily as nitrate), and increased sediment loading and deposition of fine particles in the benthic zone. We did not find support for the hypothesis that enhanced nitrate loading down-regulates methane production via thermodynamic or toxic effects. We did find strong evidence that increased sedimentation and enhanced organic matter content of the benthos lead to greater methane production (diffusive + ebullitive flux) relative to pristine fluvial systems in northern Wisconsin (upper Midwest, USA). Overall, streams in a human-dominated landscape of southern Wisconsin were major regional sources of CH4 to the atmosphere, equivalent to ~20% of dairy cattle emissions, or ~50% of a landfill’s annual emissions. We suggest that restoration of the benthic environment (reduced fine deposits) could lead to reduced CH4 emissions, while decreasing nutrient loading is likely to have limited impacts to this ecosystem process.

  5. Tensile and impact testing of an HFBR [High Flux Beam Reactor] control rod follower

    International Nuclear Information System (INIS)

    Czajkowski, C.J.; Schuster, M.H.; Roberts, T.C.; Milian, L.W.

    1989-08-01

    The Materials Technology Group of the Department of Nuclear Energy (DNE) at Brookhaven National Laboratory (BNL) undertook a program to machine and test specimens from a control rod follower from the High Flux Beam Reactor (HFBR). Tensile and Charpy impact specimens were machined and tested from non-irradiated aluminum alloys in addition to irradiated 6061-T6 from the HFBR. The tensile test results on irradiated material showed a two-fold increase in tensile strength to a maximum of 100.6 ksi. The impact resistance of the irradiated material showed a six-fold decrease in values (3 in-lb average) compared to similar non-irradiated material. Fracture toughness (K I ) specimens were tested on an unirradiated compositionally and dimensionally similar (to HFBR follower) 6061 T-6 material with K max values of 24.8 ± 1.0 Ksi√in (average) being obtained. The report concludes that the specimens produced during the program yielded reproducible and believable results and that proper quality assurance was provided throughout the program. 9 figs., 6 tabs

  6. Self-Efficacy, Self-Care, and Metabolic Control in Persons with Type 2, Diet and Exercised Controlled Diabetes

    National Research Council Canada - National Science Library

    Randall, Lisa

    1998-01-01

    .... psychological determinants of self-care and metabolic control must be explored. Self-efficacy (Bandura, 1977) has demonstrated its importance in behavioral modification but has been minimally investigated in diabetes...

  7. A real-time control system of gene expression using ligand-bound nucleic acid aptamer for metabolic engineering.

    Science.gov (United States)

    Wang, Jing; Cui, Xun; Yang, Le; Zhang, Zhe; Lv, Liping; Wang, Haoyuan; Zhao, Zhenmin; Guan, Ningzi; Dong, Lichun; Chen, Rachel

    2017-07-01

    Artificial control of bio-functions through regulating gene expression is one of the most important and attractive technologies to build novel living systems that are useful in the areas of chemical synthesis, nanotechnology, pharmacology, cell biology. Here, we present a novel real-time control system of gene regulation that includes an enhancement element by introducing duplex DNA aptamers upstream promoter and a repression element by introducing a RNA aptamer upstream ribosome binding site. With the presence of ligands corresponding to the DNA aptamers, the expression of the target gene can be potentially enhanced at the transcriptional level by strengthening the recognition capability of RNAP to the recognition region and speeding up the separation efficiency of the unwinding region due to the induced DNA bubble around the thrombin-bound aptamers; while with the presence of RNA aptamer ligand, the gene expression can be repressed at the translational level by weakening the recognition capability of ribosome to RBS due to the shielding of RBS by the formed aptamer-ligand complex upstream RBS. The effectiveness and potential utility of the developed gene regulation system were demonstrated by regulating the expression of ecaA gene in the cell-free systems. The realistic metabolic engineering application of the system has also tested by regulating the expression of mgtC gene and thrombin cDNA in Escherichia coli JD1021 for controlling metabolic flux and improving thrombin production, verifying that the real-time control system of gene regulation is able to realize the dynamic regulation of gene expression with potential applications in bacterial physiology studies and metabolic engineering. Copyright © 2017. Published by Elsevier Inc.

  8. Biological control of trace metal and organometal benthic fluxes in a eutrophic lagoon (Thau Lagoon, Mediterranean Sea, France)

    Science.gov (United States)

    Point, D.; Monperrus, M.; Tessier, E.; Amouroux, D.; Chauvaud, L.; Thouzeau, G.; Jean, F.; Amice, E.; Grall, J.; Leynaert, A.; Clavier, J.; Donard, O. F. X.

    2007-04-01

    of photosynthetic activity in controlling benthic exchanges. Significant changes in benthic flux intensity and/or direction were reported for all redox sensitive elements (Cd, Co, Cu, Mn, Pb, U, and iHg). For MMHg and organotin species, other complimentary processes such as photodegradation/uptake and hydrophobic absorption/desorption need to be considered. This work demonstrates that the processes governing benthic exchanges are complex and that benthic organisms play a major role in the significant seasonal, diurnal and spatial variability of trace metals and organometals benthic fluxes in the lagoon.

  9. A new lattice hydrodynamic model based on control method considering the flux change rate and delay feedback signal

    Science.gov (United States)

    Qin, Shunda; Ge, Hongxia; Cheng, Rongjun

    2018-02-01

    In this paper, a new lattice hydrodynamic model is proposed by taking delay feedback and flux change rate effect into account in a single lane. The linear stability condition of the new model is derived by control theory. By using the nonlinear analysis method, the mKDV equation near the critical point is deduced to describe the traffic congestion. Numerical simulations are carried out to demonstrate the advantage of the new model in suppressing traffic jam with the consideration of flux change rate effect in delay feedback model.

  10. Active-Flux-Based, V/f-with-Stabilizing-Loops Versus Sensorless Vector Control of IPMSM Drives

    DEFF Research Database (Denmark)

    Moldovan, Ana; Blaabjerg, Frede; Boldea, Ion

    2011-01-01

    . By this control strategy, a fast dynamic speed response, without steady state error and without speed or current regulators, for all AC machines is obtained. The second control method is a sensorless vector control strategy which also has been implemented and tested, just for comparison.......This paper proposes two control methods for Interior Permanent Magnet Synchronous Motor (IPMSM) Drives. The first one is a V/f control with two stabilizing loops: one loop based on active flux balance for voltage magnitude correction and a second, based on speed error, with voltage phase correction...

  11. Controls on gross fluxes of nitrous oxide and methane from an active agricultural ecosystem

    Science.gov (United States)

    Yang, W. H.; Silver, W. L.

    2013-12-01

    Agricultural soils can be a significant source of greenhouse gas emissions. Most research on the dynamics of these gases measure net fluxes across the soil-atmosphere interface. This approach limits our ability to determine driving variables because production and consumption processes occur simultaneously, and may be controlled by different factors. We used the trace gas stable isotope pool dilution technique to simultaneously measure field rates of gross production and consumption of N2O and CH4 during the growing season in a corn field located in the Sacramento-San Joaquin Delta, California. We also measured net nitrogen (N) mineralization and nitrification rates, soil temperature, soil moisture, and soil carbon dioxide (CO2) emissions to explore their role as drivers of greenhouse gas fluxes. Across five sampling dates spanning from seeding to senescence, net N2O fluxes ranged from 0 - 4.5 mg N m-2 d-1 and averaged 1.6 × 0.2 mg N m-2 d-1 (n = 112). Gross N2O production ranged from 0.09 - 6.6 mg N m-2 d-1 and gross N2O reduction rates ranged from 0.00 - 0.95 mg N m-2 d-1. The N2O yield averaged 0.68 × 0.02 (n = 40). At peak growth (days after seeding 59 and 94), 89 % of the variability in gross N2O production rates was predicted by the combination of soil moisture, soil temperature, net N mineralization, and CO2 emissions (n = 15, p seeding 11, 24, and 171), gross N2O production was most strongly correlated with soil temperature (R2 = 0.20, n = 24, p = 0.03), and gross N2O reduction rates were best predicted by CO2 emissions (R2 = 0.80, n =24, p production in 36 out of 37 measurements. Gross CH4 production reached as high as 5.4 mg C m-2 d-1 with rates trending higher throughout the growing season. Gross CH4 production rates were marginally significantly higher in rows than in inter-rows (p = 0.10). Gross CH4 oxidation did not differ significantly among sampling dates (Figure 2b), averaging 1.1 × 0.2 mg C m-2 d-1 across all measurements (n = 37). However

  12. Stage-Specific Fatty Acid Fluxes Play a Regulatory Role in Glycerolipid Metabolism during Seed Development in Jatropha curcas L.

    Science.gov (United States)

    Chaitanya, Bharatula Sri Krishna; Kumar, Sumit; Kaki, Shiva Shanker; Balakrishna, Marrapu; Karuna, Mallampalli Sri Lakshmi; Prasad, Rachapudi Badari Narayana; Sastry, Pidaparty Seshadri; Reddy, Attipalli Ramachandra

    2015-12-23

    The present study describes the changes in lipid profile as well as fatty acid fluxes during seed development in Jatropha curcas L. Endosperm from 34, 37, and 40 days after anthesis (DAA), incubated with [(14)C]acetate, showed significant synthesis of phosphatidylcholine (PC) at seed maturation. The fatty acid methyl ester profile showed PC from 34 DAA was rich in palmitic acid (16:0), whereas PC from 37 and 40 DAA was rich in oleic acid (18:1n-9). Molecular species analysis of diacylglycerol (DAG) indicated DAG (16:0/18:2n-6) was in abundance at 34 DAA, whereas DAG (18:1n-9/18:2n-6) was significantly high at 40 DAA. Triacylglycerol (TAG) analysis revealed TAG (16:0/18:2n-6/16:0) was abundant at 34 DAA, whereas TAG (18:1n-9/18:2n-6/18:1n-9) formed the majority at 40 DAA. Expression of two types of diacylglycerol acyltransferases varied with seed maturation. These data demonstrate stage-specific distinct pools of PC and DAG synthesis during storage TAG accumulation in Jatropha seed.

  13. Resistive flux saving and current profile control during lower hybrid waves assisted current rise in TORE SUPRA

    International Nuclear Information System (INIS)

    van Houtte, D.; Hoang, G.T.; Joffrin, E.; Lecoustey, P.; Moreau, D.; Parlange, F.; Tonon, G.; Vallet, J.C.

    1992-01-01

    Resistive flux saving at densities n e = (1 - 2) x 10 19 m -3 has been studied. High flux saving efficiency (0.7 x 10 13 Wb/J/m -1 ) can be achieved for a low rf power (P LH = 0.5 MW) due to the beneficial effect of the electric field on the suprathermal electrons. However for power higher than 1 MW, the efficiency is 0.25 x 10 13 Wb/J/m -1 . This flux saving efficiency is comparable to the one obtained during the flat top phase. The application of the LH power during a low density current ramp-up tends to peak the electron temperature and current density profiles. The rf power level, the parallel wavenumber and the current ramp rate allow to control the trajectories of the plasma discharges during the current rise inside the MHD stable domain

  14. Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.

    Science.gov (United States)

    Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo

    2015-04-20

    Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.

  15. Diamond Microchannel Heat Sink Designs For High Heat Flux Thermal Control

    National Research Council Canada - National Science Library

    Corbin, Michael

    2002-01-01

    .... Many investigators have suggested the use of diamond heat spreaders to reduce flux levels at or near to its source, and some have suggested that diamond microchannel heat sinks ultimately may play...

  16. Control of particles flux in a tokamak with an events structure

    International Nuclear Information System (INIS)

    Tsitrone, E.

    1995-01-01

    Two key problems in the development of a controlled fusion reactor are: -the control of the ashes resulting from the fusion reaction (helium) and of the impurities coming from the wall erosion, which affect the central plasma performances by diluting the fuel and dissipating a part of the produced energy by radiation. - the removal of the heat carried to the walls by charged particles, which is highly concentrated (peak values of several tens of MW per m 2 ). Two types of systems are generally used for the plasma-wall interface: throat limiter and axisymmetric divertor. Neither is an ideal candidate to control simultaneously the heat and particle fluxes. This thesis investigates an alternative configuration, the vented limiter, tested for the first time on the Tore Supra tokamak. The vented limiter principle lies on the recycling neutrals collection by slots, in such a way that local thermal overload is avoided. It is shown experimentally that the surface temperature of the prototype installed in Tore Supra remains uniform. As far as the particle collection is concerned, even though the pressure in the vented limiter is lower than the pressure in the throat limiter by a factor 3 for deuterium and 4 helium, it is sufficient to control the plasma density. Moreover, as with a throat limiter, the pressure exhibits a quadratic evolution with the plasma density. To interpret these results, a model describing the plasma recycling on the limiter and the pumping by the slots has been developed. The model has been validated by a comparison with the experimental data. It was then used to propose an optimized version of the prototype with reshaped slots. This should improve the pumping efficiency by a factor 2, in deuterium as well as in helium, but without removing the discrepancy between both pumping efficiencies. As a consequence, even if the thermal behaviour of the vented limiter is satisfactory, its suitability for a future strongly depends on whether it is possible or

  17. Control design for axial flux permanent magnet synchronous motor which operates above the nominal speed

    Directory of Open Access Journals (Sweden)

    Xuan Minh Tran

    2017-04-01

    Full Text Available The axial flux permanent magnet synchronous motor (AFPM motor using magnet bearings instead of ball-bearings at both two shaft ends could allow rotational speed of shaft much greater than nominal speed. One of the solutions to increase motor speed higher than its nameplate speed is reducing rotor’s pole magnetic flux of rotor (Yp. This paper proposes a method to boost the speed of AFPM motor above nominal speed by adding a reversed current isd of (Yp.

  18. Use of Principal Components Analysis to Explain Controls on Nutrient Fluxes to the Chesapeake Bay

    Science.gov (United States)

    Rice, K. C.; Mills, A. L.

    2017-12-01

    The Chesapeake Bay watershed, on the east coast of the United States, encompasses about 166,000-square kilometers (km2) of diverse land use, which includes a mixture of forested, agricultural, and developed land. The watershed is now managed under a Total Daily Maximum Load (TMDL), which requires implementation of management actions by 2025 that are sufficient to reduce nitrogen, phosphorus, and suspended-sediment fluxes to the Chesapeake Bay and restore the bay's water quality. We analyzed nutrient and sediment data along with land-use and climatic variables in nine sub watersheds to better understand the drivers of flux within the watershed and to provide relevant management implications. The nine sub watersheds range in area from 300 to 30,000 km2, and the analysis period was 1985-2014. The 31 variables specific to each sub watershed were highly statistically significantly correlated, so Principal Components Analysis was used to reduce the dimensionality of the dataset. The analysis revealed that about 80% of the variability in the whole dataset can be explained by discharge, flux, and concentration of nutrients and sediment. The first two principal components (PCs) explained about 68% of the total variance. PC1 loaded strongly on discharge and flux, and PC2 loaded on concentration. The PC scores of both PC1 and PC2 varied by season. Subsequent analysis of PC1 scores versus PC2 scores, broken out by sub watershed, revealed management implications. Some of the largest sub watersheds are largely driven by discharge, and consequently large fluxes. In contrast, some of the smaller sub watersheds are more variable in nutrient concentrations than discharge and flux. Our results suggest that, given no change in discharge, a reduction in nutrient flux to the streams in the smaller watersheds could result in a proportionately larger decrease in fluxes of nutrients down the river to the bay, than in the larger watersheds.

  19. Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

    OpenAIRE

    John K. Smith

    2018-01-01

    This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones...

  20. Metabolic control analysis of Aspergillus niger L-arabinose catabolism

    DEFF Research Database (Denmark)

    de Groot, M.J.L.; Prathumpai, Wai; Visser, J.

    2005-01-01

    A mathematical model of the L-arabinose/D-xylose catabolic pathway of Aspergillus niger was constructed based on the kinetic properties of the enzymes. For this purpose L-arabinose reductase, L-arabitol dehydrogenase and D-xylose reductase were purified using dye-affinity chromatography...... aiming at either flux or metabolite level optimization of the L-arabinose catabolic pathway of A. niger. Faster L-arabinose utilization may enhance utilization of readily available organic waste containing hemicelluloses to be converted into industrially interesting metabolites or valuable enzymes...

  1. Metabolic syndrome and atypical antipsychotics: Possibility of prediction and control.

    Science.gov (United States)

    Franch Pato, Clara M; Molina Rodríguez, Vicente; Franch Valverde, Juan I

    Schizophrenia and other psychotic disorders are associated with high morbidity and mortality, due to inherent health factors, genetic factors, and factors related to psychopharmacological treatment. Antipsychotics, like other drugs, have side-effects that can substantially affect the physical health of patients, with substantive differences in the side-effect profile and in the patients in which these side-effects occur. To understand and identify these risk groups could help to prevent the occurrence of the undesired effects. A prospective study, with 24 months follow-up, was conducted in order to analyse the physical health of severe mental patients under maintenance treatment with atypical antipsychotics, as well as to determine any predictive parameters at anthropometric and/or analytical level for good/bad outcome of metabolic syndrome in these patients. There were no significant changes in the physical and biochemical parameters individually analysed throughout the different visits. The baseline abdominal circumference (lambda Wilks P=.013) and baseline HDL-cholesterol levels (lambda Wilks P=.000) were the parameters that seem to be more relevant above the rest of the metabolic syndrome constituents diagnosis criteria as predictors in the long-term. In the search for predictive factors of metabolic syndrome, HDL-cholesterol and abdominal circumference at the time of inclusion were selected, as such that the worst the baseline results were, the higher probability of long-term improvement. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Metabolic Control and Academic Achievement over Time among Adolescents with Type 1 Diabetes

    Science.gov (United States)

    Winnick, Joel B.; Berg, Cynthia A.; Wiebe, Deborah J.; Schaefer, Barbara A.; Lei, Pui-Wa; Butner, Jonathan E.

    2017-01-01

    The relation between metabolic control (HbA1c) and achievement (grade point average [GPA]) was examined over a period of 2.5 years (every 6 months) employing a dynamical systems approach that allowed for the examination of whether HbA1c was associated with change in subsequent GPA and vice versa. Metabolic control tends to deteriorate (i.e., with…

  3. Establishing research strategies, methodologies and technologies to link genomics and proteomics to seagrass productivity, community metabolism, and ecosystem carbon fluxes.

    Science.gov (United States)

    Mazzuca, Silvia; Björk, M; Beer, S; Felisberto, P; Gobert, S; Procaccini, G; Runcie, J; Silva, J; Borges, A V; Brunet, C; Buapet, P; Champenois, W; Costa, M M; D'Esposito, D; Gullström, M; Lejeune, P; Lepoint, G; Olivé, I; Rasmusson, L M; Richir, J; Ruocco, M; Serra, I A; Spadafora, A; Santos, Rui

    2013-01-01

    A complete understanding of the mechanistic basis of marine ecosystem functioning is only possible through integrative and interdisciplinary research. This enables the prediction of change and possibly the mitigation of the consequences of anthropogenic impacts. One major aim of the European Cooperation in Science and Technology (COST) Action ES0609 "Seagrasses productivity. From genes to ecosystem management," is the calibration and synthesis of various methods and the development of innovative techniques and protocols for studying seagrass ecosystems. During 10 days, 20 researchers representing a range of disciplines (molecular biology, physiology, botany, ecology, oceanography, and underwater acoustics) gathered at The Station de Recherches Sous-marines et Océanographiques (STARESO, Corsica) to study together the nearby Posidonia oceanica meadow. STARESO is located in an oligotrophic area classified as "pristine site" where environmental disturbances caused by anthropogenic pressure are exceptionally low. The healthy P. oceanica meadow, which grows in front of the research station, colonizes the sea bottom from the surface to 37 m depth. During the study, genomic and proteomic approaches were integrated with ecophysiological and physical approaches with the aim of understanding changes in seagrass productivity and metabolism at different depths and along daily cycles. In this paper we report details on the approaches utilized and we forecast the potential of the data that will come from this synergistic approach not only for P. oceanica but for seagrasses in general.

  4. Establishing research strategies, methodologies and technologies to link genomics and proteomics to seagrass productivity, community metabolism and ecosystem carbon fluxes

    Directory of Open Access Journals (Sweden)

    Silvia eMazzuca

    2013-03-01

    Full Text Available A complete understanding of the mechanistic basis of marine ecosystem functioning is only possible through integrative and interdisciplinary research. This enables the prediction of change and possibly the mitigation of the consequences of anthropogenic impacts. One major aim of the COST Action ES0609 Seagrasses productivity. From genes to ecosystem management, is the calibration and synthesis of various methods and the development of innovative techniques and protocols for studying seagrass ecosystems.During ten days, twenty researchers representing a range of disciplines (molecular biology, physiology, botany, ecology, oceanography, underwater acoustics gathered at the marine station of STARESO (Corsica to study together the nearby Posidonia oceanica meadow. The Station de Recherches Sous-marine et Océanographiques (STARESO is located in an oligotrophic area classified as "pristine site" where environmental disturbances caused by anthropogenic pressure are exceptionally low. The healthy P. oceanica meadow, that grows in front of the lab, colonizes the sea bottom from the surface to 37 m depth. During the study, genomic and proteomic approaches were integrated with ecophysiological and physical approaches with the aim of understanding changes in seagrass productivity and metabolism at different depths and along daily cycles. In this paper we report details on the approaches utilized and we forecast the potential of the data that will come from this synergistic approach not only for P. oceanica but for seagrasses in general.

  5. Improvement of open-type magnetically shielded room composed of magnetic square cylinders by controlling flux path

    International Nuclear Information System (INIS)

    Hirosato, S.; Yamazaki, K.; Tsuruta, T.; Haraguchi, Y.; Kosaka, M.; Gao, Y.; Muramatsu, K.; Kobayashi, K.

    2011-01-01

    We have developed an open-type magnetically shielded room composed of magnetic square cylinders that has been used for an actual MRI in a hospital. To improve shielding performance, we propose here a method to control the path of the magnetic flux in the wall composed of the magnetic square cylinders by changing the magnetic permeability in each direction of the square cylinders spatially. First, we discuss a method to control the magnetic permeability in each direction of the square cylinders independently by inserting slits without changing the outside dimensions of the square cylinders, by using 3-D magnetic field analysis. Then, the effectiveness of the design of controlling the flux pass was shown by magnetic field analysis and experiments. (author)

  6. The calcium feedback loop and T cell activation: how cytoskeleton networks control intracellular calcium flux.

    Science.gov (United States)

    Joseph, Noah; Reicher, Barak; Barda-Saad, Mira

    2014-02-01

    During T cell activation, the engagement of a T cell with an antigen-presenting cell (APC) results in rapid cytoskeletal rearrangements and a dramatic increase of intracellular calcium (Ca(2+)) concentration, downstream to T cell antigen receptor (TCR) ligation. These events facilitate the organization of an immunological synapse (IS), which supports the redistribution of receptors, signaling molecules and organelles towards the T cell-APC interface to induce downstream signaling events, ultimately supporting T cell effector functions. Thus, Ca(2+) signaling and cytoskeleton rearrangements are essential for T cell activation and T cell-dependent immune response. Rapid release of Ca(2+) from intracellular stores, e.g. the endoplasmic reticulum (ER), triggers the opening of Ca(2+) release-activated Ca(2+) (CRAC) channels, residing in the plasma membrane. These channels facilitate a sustained influx of extracellular Ca(2+) across the plasma membrane in a process termed store-operated Ca(2+) entry (SOCE). Because CRAC channels are themselves inhibited by Ca(2+) ions, additional factors are suggested to enable the sustained Ca(2+) influx required for T cell function. Among these factors, we focus here on the contribution of the actin and microtubule cytoskeleton. The TCR-mediated increase in intracellular Ca(2+) evokes a rapid cytoskeleton-dependent polarization, which involves actin cytoskeleton rearrangements and microtubule-organizing center (MTOC) reorientation. Here, we review the molecular mechanisms of Ca(2+) flux and cytoskeletal rearrangements, and further describe the way by which the cytoskeletal networks feedback to Ca(2+) signaling by controlling the spatial and temporal distribution of Ca(2+) sources and sinks, modulating TCR-dependent Ca(2+) signals, which are required for an appropriate T cell response. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters

  7. Strain improvement and metabolic flux analysis in the wild-type and a mutant Lactobacillus lactis strain for L(+)-lactic acid production.

    Science.gov (United States)

    Bai, Dong-Mei; Zhao, Xue-Ming; Li, Xin-Gang; Xu, Shi-Min

    2004-12-20

    The effects of initial glucose concentration and calcium lactate concentration on the lactic acid production by the parent strain, Lactobacillus lactis BME5-18, were studied. The results of the experiments indicated that glucose and lactate repressed the cell growth and the lactic acid production by Lactobacillus lactis BME5-18. A L(+)-lactic acid overproducing strain, Lactobacillus lactis BME5-18M, was screened by mutagenizing the parent strain with ultraviolet (UV) light irradiation and selecting the high glucose and lactate calcium concentration repression resistant mutant. Starting with a concentration of 100g L(-1) glucose, the mutant produced 98.6 g L(-1) lactic acid after 60 h in flasks, 73.9% higher than that of the parent strain. The L(+)-lactic acid purity was 98.1% by weight based on the amount of total lactic acid. The culture of the parent strain could not be analyzed well by conventional metabolic flux analysis techniques, since some pyruvate were accumulated intracellularly. Therefore, a revised flux analysis method was proposed by introducing intracellular pyruvate pool. Further studies demonstrate that there is a high level of NADH oxidase activity (12.11 mmol mg(-1) min(-1)) in the parent strain. The molecular mechanisms of the strain improvement were proposed, i.e., the high level of NADH oxidase activity was eliminated and the uptake rate of glucose was increased from 82.1 C-mmol (g DW h)(-1) to 98.9 C-mmol (g DW h)(-1) by mutagenizing the parent strain with UV, and therefore the mutant strain converts mostly pyruvate to lactic acid with a higher productivity (1.76 g L(-1) h(-1)) than the parent strain (0.95 g L(-1) h(-1)).

  8. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    Science.gov (United States)

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  9. The solar wind control of electron fluxes in geostationary orbit during magnetic storms

    International Nuclear Information System (INIS)

    Popov, G.V.; Degtyarev, V.I.; Sheshukov, S.S.; Chudnenko, S.E.

    1999-01-01

    The dynamics of electron fluxes (with energies from 30 to 1360 keV) in geostationary orbit during magnetic storms was investigated on the basis of LANL spacecraft 1976-059 and 1977-007 data. Thirty-seven magnetic storms with distinct onsets from the time interval July 1976-December 1978 were used in the analysis. A treatment of experimental data involved the moving averaging and the overlapping epoch method. The smoothed component of electron fluxes represents mainly trapped electrons and shows their strong dependence on the solar wind velocity. The time lag between a smoothed electron flux and the solar wind velocity increases with electron energy reflecting dynamics of the inner magnetosphere filling with trapped energetic electrons originating from substorm injection regions located not far outside geostationary orbit

  10. Stratigraphic controls on fluid and solute fluxes across the sediment-water interface of an estuary

    Science.gov (United States)

    Sawyer, Audrey H.; Lazareva, Olesya; Kroeger, Kevin D.; Crespo, Kyle; Chan, Clara S.; Stieglitz, Thomas; Michael, Holly A.

    2014-01-01

    Shallow stratigraphic features, such as infilled paleovalleys, modify fresh groundwater discharge to coastal waters and fluxes of saltwater and nutrients across the sediment–water interface. We quantify the spatial distribution of shallow surface water–groundwater exchange and nitrogen fluxes near a paleovalley in Indian River Bay, Delaware, using a hand resistivity probe, conventional seepage meters, and pore-water samples. In the interfluve (region outside the paleovalley) most nitrate-rich fresh groundwater discharges rapidly near the coast with little mixing of saline pore water, and nitrogen transport is largely conservative. In the peat-filled paleovalley, fresh groundwater discharge is negligible, and saltwater exchange is deep (∼1 m). Long pore-water residence times and abundant sulfate and organic matter promote sulfate reduction and ammonium production in shallow sediment. Reducing, iron-rich fresh groundwater beneath paleovalley peat discharges diffusely around paleovalley margins offshore. In this zone of diffuse fresh groundwater discharge, saltwater exchange and dispersion are enhanced, ammonium is produced in shallow sediments, and fluxes of ammonium to surface water are large. By modifying patterns of groundwater discharge and the nature of saltwater exchange in shallow sediments, paleovalleys and other stratigraphic features influence the geochemistry of discharging groundwater. Redox reactions near the sediment–water interface affect rates and patterns of geochemical fluxes to coastal surface waters. For example, at this site, more than 99% of the groundwater-borne nitrate flux to the Delaware Inland Bays occurs within the interfluve portion of the coastline, and more than 50% of the ammonium flux occurs at the paleovalley margin.

  11. Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*.

    Science.gov (United States)

    Carrer, Michele; Liu, Ning; Grueter, Chad E; Williams, Andrew H; Frisard, Madlyn I; Hulver, Matthew W; Bassel-Duby, Rhonda; Olson, Eric N

    2012-09-18

    Obesity and metabolic syndrome are associated with mitochondrial dysfunction and deranged regulation of metabolic genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional coactivator that regulates metabolism and mitochondrial biogenesis through stimulation of nuclear hormone receptors and other transcription factors. We report that the PGC-1β gene encodes two microRNAs (miRNAs), miR-378 and miR-378*, which counterbalance the metabolic actions of PGC-1β. Mice genetically lacking miR-378 and miR-378* are resistant to high-fat diet-induced obesity and exhibit enhanced mitochondrial fatty acid metabolism and elevated oxidative capacity of insulin-target tissues. Among the many targets of these miRNAs, carnitine O-acetyltransferase, a mitochondrial enzyme involved in fatty acid metabolism, and MED13, a component of the Mediator complex that controls nuclear hormone receptor activity, are repressed by miR-378 and miR-378*, respectively, and are elevated in the livers of miR-378/378* KO mice. Consistent with these targets as contributors to the metabolic actions of miR-378 and miR-378*, previous studies have implicated carnitine O-acetyltransferase and MED13 in metabolic syndrome and obesity. Our findings identify miR-378 and miR-378* as integral components of a regulatory circuit that functions under conditions of metabolic stress to control systemic energy homeostasis and the overall oxidative capacity of insulin target tissues. Thus, these miRNAs provide potential targets for pharmacologic intervention in obesity and metabolic syndrome.

  12. Iron metabolism in critically ill patients developing anemia of inflammation: a case control study.

    Science.gov (United States)

    Boshuizen, Margit; Binnekade, Jan M; Nota, Benjamin; van de Groep, Kirsten; Cremer, Olaf L; Tuinman, Pieter R; Horn, Janneke; Schultz, Marcus J; van Bruggen, Robin; Juffermans, Nicole P

    2018-05-02

    Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients. Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters. In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score. The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.

  13. Real time magnetic field and flux measurements for tokamak control using a multi-core PCI Express system

    International Nuclear Information System (INIS)

    Giannone, L.; Schneider, W.; McCarthy, P.J.; Sips, A.C.C.; Treutterer, W.; Behler, K.; Eich, T.; Fuchs, J.C.; Hicks, N.; Kallenbach, A.; Maraschek, M.; Mlynek, A.; Neu, G.; Pautasso, G.; Raupp, G.; Reich, M.; Schuhbeck, K.H.; Stober, J.; Volpe, F.; Zehetbauer, T.

    2009-01-01

    The existing real time system for the position and shape control in ASDEX Upgrade has been extended to calculate magnetic flux surfaces in real time using a multi-core PCI Express system running LabVIEW RT. The availability of reflective memory for LabVIEW RT will allow this system to be connected to the control system and other diagnostics in a multi-platform real time network. The measured response of each magnetic probe to the individual poloidal field coil currents in the absence of plasma current is compared to the calculated value. Prior to a tokamak discharge this comparison can be used to check for failure of the magnetic probe, flux loop or integrator.

  14. Mammalian iron metabolism and its control by iron regulatory proteins☆

    Science.gov (United States)

    Anderson, Cole P.; Shen, Lacy; Eisenstein, Richard S.; Leibold, Elizabeth A.

    2013-01-01

    Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22610083

  15. Determination of the neutron flux for a possible way of controlling a fast reactor through the reflector

    International Nuclear Information System (INIS)

    Souza, A.W.A. de.

    1979-08-01

    The determination of time dependent flux is made in a fast reactor with the core embraced by a perfect reflector. The fuel burnup is taken in account establishing a nonlinear diffusion problem. A stable numeric scheme is done and the integration of two limit cases is obtained. Finally, one possibility of reactor control through the variation between two cases is discussed. (E.G.) [pt

  16. Determining the control circuitry of redox metabolism at the genome-scale.

    Directory of Open Access Journals (Sweden)

    Stephen Federowicz

    2014-04-01

    Full Text Available Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs, ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r(2 (p<1e-6 correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.

  17. Heart over mind: metabolic control of white adipose tissue and liver.

    Science.gov (United States)

    Nakamura, Michinari; Sadoshima, Junichi

    2014-12-01

    Increasing evidence suggests that the heart controls the metabolism of peripheral organs. Olson and colleagues previously demonstrated that miR‐208a controls systemic energy homeostasis through the regulation of MED13 in cardiomyocytes (Grueter et al, 2012). In their follow‐up study in this issue of EMBO Molecular Medicine, white adipose tissue (WAT) and liver are identified as the physiological targets of cardiac MED13 signaling, most likely through cardiac‐derived circulating factors, which boost energy consumption by upregulating metabolic gene expression and increasing mitochondrial numbers (Baskin et al, 2014). In turn, increased energy expenditure in WAT and the liver confers leanness. These findings strengthen the evidence of metabolic crosstalk between the heart and peripheral tissues through cardiokines and also set the stage for the development of novel treatments for metabolic syndrome.

  18. High Flux Microchannel Receiver Development with Adap-tive Flow Control

    Energy Technology Data Exchange (ETDEWEB)

    Drost, Kevin [Oregon State Univ., Corvallis, OR (United States)

    2015-08-15

    This project is focused on the demonstration of a microchannel-based solar receiver (MSR). The MSR concept consists of using a modular arrangement of arrayed microchannels to heat a working fluid in a concentrating solar receiver, allowing a much higher solar flux on the receiver and consequently a significant reduction in thermal losses, size, and cost.

  19. Methyl halide fluxes from tropical plants under controlled radiation and temperature regimes

    Science.gov (United States)

    Blei, Emanuel; Yokouchi, Yoko; Saito, Takuya; Nozoe, Susumu

    2015-04-01

    Methyl halides (CH3Cl, CH3Br, CH3I) contribute significantly to the halogen burden of the atmosphere and have the potential to influence the stratospheric ozone layer through their catalytic effect in the Chapman cycle. As such they have been studied over the years, and many plants and biota have been examined for their potential to act as a source of these gases. One of the potentially largest terrestrial sources identified was tropical vegetation such as tropical ferns and Dipterocarp trees. Most of these studies concentrated on the identification and quantification of such fluxes rather than their characteristics and often the chambers used in these studies were either opaque or only partially transparent to the full solar spectrum. Therefore it is not certain to which degree emissions of methyl halides are innate to the plants and how much they might vary due to radiation or temperature conditions inside the enclosures. In a separate development it had been proposed that UV-radiation could cause live plant materials to be become emitters of methane even under non-anoxic conditions. As methane is chemically very similar to methyl halides and had been proposed to be produced from methyl-groups ubiquitously found in plant cell material there is a relatively good chance that such a production mechanism would also apply to methyl halides. To test whether radiation can affect elevated emissions of methyl halides from plant materials and to distinguish this from temperature effects caused by heat build-up in chambers a set of controlled laboratory chamber enclosures under various radiation and temperature regimes was conducted on four different tropical plant species (Magnolia grandiflora, Cinnamonum camphora, Cyathea lepifera, Angiopteris lygodiifolia), the latter two of which had previously been identified as strong methyl halide emitters. Abscised leaf samples of these species were subjected to radiation treatments such UV-B, UV-A and broad spectrum radiation

  20. Association between metabolic control and oral health in adolescents with type 1 diabetes mellitus.

    Science.gov (United States)

    Saes Busato, Ivana Maria; Bittencourt, Mônica Sommer; Machado, Maria Angela Naval; Grégio, Ana Maria Trindade; Azevedo-Alanis, Luciana Reis

    2010-03-01

    The aim of this study was to evaluate the association between metabolic control and oral health of adolescents with type 1 diabetes mellitus (DM1). A case-control epidemiologic study was performed on adolescents allocated between 2 groups: DM1 group composed of 51 with DM1, and control group composed of 51 without diabetes. In the DM1 group, metabolic control data were observed (glycosylated hemoglobin (GHb) and capillary glucose), whereby GHb 8.0% poor metabolic control (DM1-B). Oral mucosal abnormalites, Community Periodontal Index (CPI), and decayed, missing, and filled (DMF) index were documented. Salivary flow was evaluated by means of stimulated saliva collection (SSFR). Glycosylated hemoglobin values of 8.0% (DM1-B) in 34 (76%) of the subjects. The average DMF indexes were 1.5 (control) and 3.3 (DM1-group) (P < or = .05). The average CPIs were 0.2 (control), 1.4 (DM1-A), and 2.0 (DM1-B) (P < or = .05). Average SSFRs were 0.997 (DM1-A), 0.903 (DM1-B), and 1.224 (control) mL/min. Oral health of adolescents with DM1 was impaired regardless of metabolic control. Copyright 2010 Mosby, Inc. All rights reserved.

  1. Dynamical and biogeochemical control on the decadal variability of ocean carbon fluxes

    Directory of Open Access Journals (Sweden)

    R. Séférian

    2013-04-01

    Full Text Available Several recent observation-based studies suggest that ocean anthropogenic carbon uptake has slowed down due to the impact of anthropogenic forced climate change. However, it remains unclear whether detected changes over the recent time period can be attributed to anthropogenic climate change or rather to natural climate variability (internal plus naturally forced variability alone. One large uncertainty arises from the lack of knowledge on ocean carbon flux natural variability at the decadal time scales. To gain more insights into decadal time scales, we have examined the internal variability of ocean carbon fluxes in a 1000 yr long preindustrial simulation performed with the Earth System Model IPSL-CM5A-LR. Our analysis shows that ocean carbon fluxes exhibit low-frequency oscillations that emerge from their year-to-year variability in the North Atlantic, the North Pacific, and the Southern Ocean. In our model, a 20 yr mode of variability in the North Atlantic air-sea carbon flux is driven by sea surface temperature variability and accounts for ~40% of the interannual regional variance. The North Pacific and the Southern Ocean carbon fluxes are also characterised by decadal to multi-decadal modes of variability (10 to 50 yr that account for 20–40% of the interannual regional variance. These modes are driven by the vertical supply of dissolved inorganic carbon through the variability of Ekman-induced upwelling and deep-mixing events. Differences in drivers of regional modes of variability stem from the coupling between ocean dynamics variability and the ocean carbon distribution, which is set by large-scale secular ocean circulation.

  2. Aeolian controls of soil geochemistry and weathering fluxes in high-elevation ecosystems of the Rocky Mountains, Colorado

    Science.gov (United States)

    Lawrence, Corey R.; Reynolds, Richard L.; Kettterer, Michael E.; Neff, Jason C.

    2013-01-01

    When dust inputs are large or have persisted for long periods of time, the signature of dust additions are often apparent in soils. The of dust will be greatest where the geochemical composition of dust is distinct from local sources of soil parent material. In this study the influence of dust accretion on soil geochemistry is quantified for two different soils from the San Juan Mountains of southwestern Colorado, USA. At both study sites, dust is enriched in several trace elements relative to local rock, especially Cd, Cu, Pb, and Zn. Mass-balance calculations that do not explicitly account for dust inputs indicate the accumulation of some elements in soil beyond what can be explained by weathering of local rock. Most observed elemental enrichments are explained by accounting for the long-term accretion of dust, based on modern isotopic and geochemical estimates. One notable exception is Pb, which based on mass-balance calculations and isotopic measurements may have an additional source at one of the study sites. These results suggest that dust is a major factor influencing the development of soil in these settings and is also an important control of soil weathering fluxes. After accounting for dust inputs in mass-balance calculations, Si weathering fluxes from San Juan Mountain soils are within the range observed for other temperate systems. Comparing dust inputs with mass-balanced based flux estimates suggests dust could account for as much as 50–80% of total long-term chemical weathering fluxes. These results support the notion that dust inputs may sustain chemical weathering fluxes even in relatively young continental settings. Given the widespread input of far-traveled dust, the weathering of dust is likely and important and underappreciated aspect of the global weathering engine.

  3. Aeolian controls of soil geochemistry and weathering fluxes in high-elevation ecosystems of the Rocky Mountains, Colorado

    Science.gov (United States)

    Lawrence, Corey R.; Reynolds, Richard L.; Ketterer, Michael E.; Neff, Jason C.

    2013-04-01

    When dust inputs are large or have persisted for long periods of time, the signature of dust additions are often apparent in soils. The of dust will be greatest where the geochemical composition of dust is distinct from local sources of soil parent material. In this study the influence of dust accretion on soil geochemistry is quantified for two different soils from the San Juan Mountains of southwestern Colorado, USA. At both study sites, dust is enriched in several trace elements relative to local rock, especially Cd, Cu, Pb, and Zn. Mass-balance calculations that do not explicitly account for dust inputs indicate the accumulation of some elements in soil beyond what can be explained by weathering of local rock. Most observed elemental enrichments are explained by accounting for the long-term accretion of dust, based on modern isotopic and geochemical estimates. One notable exception is Pb, which based on mass-balance calculations and isotopic measurements may have an additional source at one of the study sites. These results suggest that dust is a major factor influencing the development of soil in these settings and is also an important control of soil weathering fluxes. After accounting for dust inputs in mass-balance calculations, Si weathering fluxes from San Juan Mountain soils are within the range observed for other temperate systems. Comparing dust inputs with mass-balanced based flux estimates suggests dust could account for as much as 50-80% of total long-term chemical weathering fluxes. These results support the notion that dust inputs may sustain chemical weathering fluxes even in relatively young continental settings. Given the widespread input of far-traveled dust, the weathering of dust is likely and important and underappreciated aspect of the global weathering engine.

  4. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  5. 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.

  6. Optimal determination of the parameters controlling biospheric CO{sub 2} fluxes over Europe using eddy covariance fluxes and satellite NDVI measurements

    Energy Technology Data Exchange (ETDEWEB)

    Aalto, Tuula [Finnish Meteorological Inst., Helsinki (Finland). Air Quality Research; Ciais, Philippe; Moulin, Cyril [UMR CEA-CNRS, Gif-sur-Yvette (France). Laboratoire des Sciences du Climat et de l' Environnement; Chevillard, Anne [CEA, Fontenay-aux-Roses (France). DPRE/SERGD/LEIRPA

    2004-04-01

    Ecosystem CO{sub 2} flux measurements using the eddy covariance method were compared with the biospheric CO{sub 2} exchange estimates of a regional scale atmospheric model. The model described the seasonal patterns quite well, but underestimated the amplitude of the fluxes, especially at the northern sites. Two model parameters, photosynthetic efficiency for light use and Q{sub 10} for soil respiration, were re-evaluated on a diurnal and seasonal basis using the results from flux measurements. In most cases the photosynthetic efficiency was higher than the earlier estimate. The resulting flux was very sensitive to the value of photosynthetic efficiency, while changes in Q{sub 10} did not have a significant effect.

  7. On-line iron loss resistance identification by a state observer for rotor-flux-oriented control of induction motor

    International Nuclear Information System (INIS)

    Barrera, Pablo M. de la; Bossio, Guillermo R.; Solsona, Jorge A.; Garcia, Guillermo O.

    2008-01-01

    A rotor flux state observer considering iron loss, for an Induction Motor (IM), is proposed. The aim of this proposal is to avoid detuning caused by the IM iron loss on a field-oriented control (FOC). An adaptive scheme for the K Fe , a parameter that represents the IM iron loss, is also proposed. The main objective of this scheme is to improve the dynamic response of control by compensating the variations of iron losses due to possible variations in the stator core characteristics. Simulation results demonstrated that the observer and the adaptive scheme showed a good performance fulfilling then the objectives

  8. Combined Flux Observer With Signal Injection Enhancement for Wide Speed Range Sensorless Direct Torque Control of IPMSM Drives

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Andreescu, G.-D.; Pitic, C.I.

    2008-01-01

    voltage-current model with PI compensator for low-speed operations. As speed increases, the observer switches gradually to a PI compensated closed-loop voltage model, which is solely used at high speeds. High-frequency rotating-voltage injection with a single D-module bandpass vector filter and a phase......This paper proposes a motion-sensorless control system using direct torque control with space vector modulation for interior permanent magnet synchronous motor (IPMSM) drives, for wide speed range operation, including standstill. A novel stator flux observer with variable structure uses a combined...

  9. Filtration behavior of casein glycomacropeptide (CGMP) in an enzymatic membrane reactor: fouling control by membrane selection and threshold flux operation

    DEFF Research Database (Denmark)

    Luo, Jianquan; Morthensen, Sofie Thage; Meyer, Anne S.

    2014-01-01

    . In this study, the filtration performance and fouling behavior during ultrafiltration (UF) of CGMP for the enzymatic production of 3′-sialyllactose were investigated. A 5kDa regenerated cellulose membrane with high anti-fouling performance, could retain CGMP well, permeate 3′-sialyllactose, and was found...... to be the most suitable membrane for this application. Low pH increased CGMP retention but produced more fouling. Higher agitation and lower CGMP concentration induced larger permeate flux and higher CGMP retention. Adsorption fouling and pore blocking by CGMP in/on membranes could be controlled by selecting...... a highly hydrophilic membrane with appropriate pore size. Operating under threshold flux could minimize the concentration polarization and cake/gel/scaling layers, but might not avoid irreversible fouling caused by adsorption and pore blocking. The effects of membrane properties, pH, agitation and CGMP...

  10. Active Power and Flux Control of a Self-Excited Induction Generator for a Variable-Speed Wind Turbine Generation

    Energy Technology Data Exchange (ETDEWEB)

    Na, Woonki; Muljadi, Eduard; Leighty, Bill; Kim, Jonghoon

    2017-05-11

    A Self-Excited Induction Generation (SEIG) for a variable speed wind turbine generation(VS-WG) is normally considered to be a good candidate for implementation in stand-alone applications such as battery charging, hydrogenation, water pumping, water purification, water desalination, and etc. In this study, we have examined a study on active power and flux control strategies for a SEIG for a variable speed wind turbine generation. The control analysis for the proposed system is carried out by using PSCAD software. In the process, we can optimize the control design of the system, thereby enhancing and expediting the control design procedure for this application. With this study, this control design for a SEIG for VS-WG can become the industry standard for analysis and development in terms of SEIG.

  11. How interactions between top-down and bottom-up controls on carbon cycling affect fluxes within and from lakes

    Science.gov (United States)

    Sadro, S.; Piovia-Scott, J.; Nelson, C.; Sickman, J. O.; Knapp, R.

    2017-12-01

    While the role of inland waters in global carbon cycling has grown clearer in recent decades, the extent to which top-down and bottom-up mechanisms interact to regulate dynamics at the catchment scale is not well understood. The degree to which lakes process, export, or store terrestrial carbon is influenced by hydrological variability, variation in the magnitude of terrestrial organic matter (t-OM) entering a system, the efficiency with which such material is metabolized by bacterioplankton, the extent to which it is incorporated into secondary consumer biomass, and by the effects of food-web structure, such as the presence or absence of top predators. However, how these processes interact to mediate carbon fluxes between terrestrial, aquatic, and atmospheric reservoirs remains unclear. We develop a conceptual model that explores how interactions among these factors ultimately affects carbon dynamics using data from lakes located in the Sierra Nevada mountains of California. The Sierra are an excellent system for studies of carbon cycling because elevation-induced landscape gradients in soil development and vegetation cover provide large natural variation in terrestrial inputs to lakes, while variation in confounding factors such as lake morphometry or trophic state is comparatively small. Dissolved organic carbon concentrations increase 100 fold in lakes spanning the alpine to montane elevation gradient found in the Sierra, and fluorescence characteristics reflect an increasingly terrestrial signature with decreasing elevation. Bacterioplankton make up a large proportion of total ecosystem metabolism in these systems, and their metabolic efficiency is tightly coupled to the composition of dissolved organic matter. Stable isotope food web data (δ13C, Δ14C, and δ2H) and measurements of pCO2 from lakes indicate the magnitude of allochthony, rates if carbon cycling, and ecosystem heterotrophy all increase with the increasingly terrestrial signature of dissolved

  12. Diabetes in children and adolescents from ethnic minorities: barriers to education, treatment and good metabolic control

    DEFF Research Database (Denmark)

    Povlsen, Lene; Olsen, Birthe; Ladelund, Steen

    2005-01-01

    AIM: This paper reports an investigation to establish whether metabolic control is different in children and adolescents from ethnic minorities with type 1 diabetes compared with young Danish patients, and to learn about factors affecting their opportunities to achieve good metabolic control....... BACKGROUND: The prevalence of diabetes in children and adolescents from ethnic minorities in Denmark is increasing. Having a different ethnic background has frequently been described as a risk factor for poor metabolic control, but whether the risk is represented by the ethnicity and immigration itself...... the centres provided limited specialized knowledge and support. The questionnaires completed by the parents revealed limited schooling, lack of professional education and a major need for interpreters; these characteristics were especially prevalent among the mothers. CONCLUSIONS: Young patients from ethnic...

  13. A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

    Science.gov (United States)

    Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A

    2017-04-11

    Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .

  14. 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.

  15. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine-K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor

  16. Roles for Orexin/Hypocretin in the Control of Energy Balance and Metabolism.

    Science.gov (United States)

    Goforth, Paulette B; Myers, Martin G

    The neuropeptide hypocretin is also commonly referred to as orexin, since its orexigenic action was recognized early. Orexin/hypocretin (OX) neurons project widely throughout the brain and the physiologic and behavioral functions of OX are much more complex than initially conceived based upon the stimulation of feeding. OX most notably controls functions relevant to attention, alertness, and motivation. OX also plays multiple crucial roles in the control of food intake, metabolism, and overall energy balance in mammals. OX signaling not only promotes food-seeking behavior upon short-term fasting to increase food intake and defend body weight, but, conversely, OX signaling also supports energy expenditure to protect against obesity. Furthermore, OX modulates the autonomic nervous system to control glucose metabolism, including during the response to hypoglycemia. Consistently, a variety of nutritional cues (including the hormones leptin and ghrelin) and metabolites (e.g., glucose, amino acids) control OX neurons. In this chapter, we review the control of OX neurons by nutritional/metabolic cues, along with our current understanding of the mechanisms by which OX and OX neurons contribute to the control of energy balance and metabolism.

  17. Metabolic Control and Illness Perceptions in Adolescents with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Line Wisting

    2016-01-01

    Full Text Available Background. Disturbed eating behavior and psychosocial variables have been found to influence metabolic control, but little is known about how these variables interact or how they influence metabolic control, separately and combined. Objective. To explore associations between metabolic control (measured by HbA1c and eating disorder psychopathology, coping strategies, illness perceptions, and insulin beliefs in adolescents with type 1 diabetes. Methods. A total of 105 patients (41.9% males with type 1 diabetes (12–20 years were interviewed with the Child Eating Disorder Examination. In addition, self-report psychosocial questionnaires were completed. Clinical data, including HbA1c, was obtained from the Norwegian Childhood Diabetes Registry. Results. Significant gender differences were demonstrated. Among females, HbA1c correlated significantly with eating restriction (.29, p < .05, the illness perception dimensions consequences, personal control, coherence, and concern (ranging from .33 to .48, and the coping strategy ventilating negative feelings (−.26, p < .05. Illness perception personal control contributed significantly to HbA1c in a regression model, explaining 23% of the variance among females (β .48, p < .001. None of the variables were significantly associated with HbA1c among males. Conclusions. Illness perceptions appear to be important contributors to metabolic control in females, but not males, with type 1 diabetes.

  18. Role of Parenting Style in Achieving Metabolic Control in Adolescents With Type 1 Diabetes

    OpenAIRE

    Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

    2011-01-01

    OBJECTIVE To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA1c values. RESULTS An authoritative paternal parenting style predicted better glycemic control and...

  19. Control of Hepatic Glucose Metabolism by the Oral Hypoglycemic Sulfonylureas

    Science.gov (United States)

    1984-05-11

    diphosphate, 0.2 mM; 2,3 diphosphoglycerate , 0.1 mM; NADH, 0.2 mM; and 0.60 ml of deprotelnized sample. Pyruvate was measured by following the oxidation...J,; Rodgrlgues, L,M,; Whitton, P,A, and Hems, D,A, (1980) Control mechanisms in the acceleration of hepatic glycogen degradation during anoxia

  20. Modified metabolic syndrome and second cancers in women: A case control study.

    Science.gov (United States)

    Ortiz-Mendoza, Carlos-Manuel; Pérez-Chávez, Ernesto; Fuente-Vera, Tania-Angélica De-la

    2016-01-01

    According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. To find out the implication of the modified metabolic syndrome in women with second cancers. This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases) and age-matched women with only one neoplasm (controls). The analysis comprised: Tumor (s), anthropometric features, and body mass index (BMI); moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 ) was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1). Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.

  1. Modified metabolic syndrome and second cancers in women: A case control study

    Directory of Open Access Journals (Sweden)

    Carlos-Manuel Ortiz-Mendoza

    2016-01-01

    Full Text Available Background: According to some studies, the metabolic syndrome causes diverse primary cancers; however, there is no evidence about metabolic syndrome impact on second cancers development in women. Aim: To find out the implication of the modified metabolic syndrome in women with second cancers. Materials and Methods: This was a case-control study, at a general hospital in Mexico City, in women with second cancers (cases and age-matched women with only one neoplasm (controls. The analysis comprised: Tumor (s, anthropometric features, and body mass index (BMI; moreover, presence of diabetes mellitus, hypertension, and fasting serum levels of total cholesterol, triglycerides and glucose. Results: The sample was of nine cases and 27 controls. In cases, the metabolic syndrome (diabetes mellitus or glucose > 99 mg/dL + hypertension or blood pressure ≥ 135/85 mm Hg + triglycerides > 149 mg/dL or BMI ≥ 30 kg/m 2 was more frequent (odds ratio 20.8, 95% confidence interval: 1.9-227.1. Conclusion: Our results suggest that in women, the modified metabolic syndrome may be a risk factor for second cancers.

  2. Control of Hepatic Glucose Metabolism by Islet and Brain

    Science.gov (United States)

    Rojas, Jennifer M.; Schwartz, Michael W.

    2014-01-01

    Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP), both contribute to hyperglycemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver, but also via a mechanism involving the brain. Yet the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice investigating whether the direct hepatic action of insulin is necessary for normal HGP: when hepatic insulin signaling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. PMID:25200294

  3. Superconducting Qubit with Integrated Single Flux Quantum Controller Part II: Experimental Characterization

    Science.gov (United States)

    Leonard, Edward, Jr.; Beck, Matthew; Thorbeck, Ted; Zhu, Shaojiang; Howington, Caleb; Nelson, Jj; Plourde, Britton; McDermott, Robert

    We describe the characterization of a single flux quantum (SFQ) pulse generator cofabricated with a superconducting quantum circuit on a single chip. Resonant trains of SFQ pulses are used to induce coherent qubit rotations on the Bloch sphere. We describe the SFQ drive characteristics of the qubit at the fundamental transition frequency and at subharmonics (ω01 / n , n = 2 , 3 , 4 , ⋯). We address the issue of quasiparticle poisoning due to the proximal SFQ pulse generator, and we characterize the fidelity of SFQ-based rotations using randomized benchmarking. Present address: IBM T.J. Watson Research Center.

  4. The relative contribution of insulin secretory capacity, insulin action, and incretins to metabolic control after islet transplantation in dogs

    NARCIS (Netherlands)

    van der Burg, MPM; van Suylichem, PTR; Guicherit, OR; Frolich, M; Lemkes, HHPJ; Gooszen, HG

    Adequate metabolic control is central to the concept of islet transplantation, but has received limited attention. We studied metabolic control in 8 dogs at 6-9 months after intrasplenic autografting of similar to 25% of the normal mass islets - as compared to 30 controls. A similar posttransplant

  5. Comprehensive assessment of variables affecting metabolic control in patients with type 2 diabetes mellitus in Jordan.

    Science.gov (United States)

    Qteishat, Rola Reyad; Ghananim, Abdel Rahman Al

    2016-01-01

    The aim of the study was to identify variables affecting metabolic control among diabetic patients treated at diabetes and endocrine clinic in Jordan. A total of 200 patients were studied by using a cross sectional study design. Data were collected from patients' medical records, glycemic control tests and prestructured questionnaires about variables that were potentially important based on previous researches and clinical judgment: Adherence evaluation, Patients' knowledge about drug therapy and non-pharmacological therapy, Anxiety and depression, Beliefs about diabetes treatment (benefits and barriers of treatment), Knowledge about treatment goals, Knowledge about diabetes, Self efficacy, and Social support. The mean (±SD) age was 53.5 (±10.38) years and mean HbA1c was 8.4 (±1.95). In the multivariate analysis, education level, and self efficacy found to have significantly independent association with metabolic control (Pknowledge and high self efficacy was significant in patients with good metabolic control. Emphasizing the importance of continuous educational programs and improving the self efficacy as well, could warrant achieving good metabolic control. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  6. Quality control of CarboEurope flux data - Part 1: Coupling footprint analyses with flux data quality assessment to evaluate sites in forest ecosystems

    DEFF Research Database (Denmark)

    Göckede, M.; Foken, T.; Aubinet, M.

    2008-01-01

    We applied a site evaluation approach combining Lagrangian Stochastic footprint modeling with a quality assessment approach for eddy-covariance data to 25 forested sites of the CarboEurope-IP network. The analysis addresses the spatial representativeness of the flux measurements, instrumental...... of the surrounding terrain, while the latent heat flux is subject to instrumentation-related problems. The Planar-Fit coordinate rotation proved to be a reliable tool for the majority of the sites using only a single set of rotation angles. Overall, we found a high average data quality for the CarboEurope-IP network...... effects on data quality, spatial patterns in the data quality, and the performance of the coordinate rotation method. Our findings demonstrate that application of a footprint filter could strengthen the CarboEurope-IP flux database, since only one third of the sites is situated in truly homogeneous...

  7. A dual control mechanism synchronizes riboflavin and sulphur metabolism in Bacillus subtilis

    Science.gov (United States)

    Pedrolli, Danielle Biscaro; Kühm, Christian; Sévin, Daniel C.; Vockenhuber, Michael P.; Sauer, Uwe; Suess, Beatrix; Mack, Matthias

    2015-01-01

    Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for biosynthesis and/or transport of riboflavin (rib genes). Cytoplasmic riboflavin is rapidly and almost completely converted to FMN by flavokinases. When cytoplasmic levels of FMN are sufficient (“high levels”), FMN binding to FMN riboswitches leads to a reduction of rib gene expression. We report here that the protein RibR counteracts the FMN-induced “turn-off” activities of both FMN riboswitches in Bacillus subtilis, allowing rib gene expression even in the presence of high levels of FMN. The reason for this secondary metabolic control by RibR is to couple sulfur metabolism with riboflavin metabolism. PMID:26494285

  8. [Metabolic control in the critically ill patient an update: hyperglycemia, glucose variability hypoglycemia and relative hypoglycemia].

    Science.gov (United States)

    Pérez-Calatayud, Ángel Augusto; Guillén-Vidaña, Ariadna; Fraire-Félix, Irving Santiago; Anica-Malagón, Eduardo Daniel; Briones Garduño, Jesús Carlos; Carrillo-Esper, Raúl

    Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  9. Synthetic control of a fitness tradeoff in yeast nitrogen metabolism

    Directory of Open Access Journals (Sweden)

    Lee Jack J

    2009-01-01

    Full Text Available Abstract Background Microbial communities are involved in many processes relevant to industrial and medical biotechnology, such as the formation of biofilms, lignocellulosic degradation, and hydrogen production. The manipulation of synthetic and natural microbial communities and their underlying ecological parameters, such as fitness, evolvability, and variation, is an increasingly important area of research for synthetic biology. Results Here, we explored how synthetic control of an endogenous circuit can be used to regulate a tradeoff between fitness in resource abundant and resource limited environments in a population of Saccharomyces cerevisiae. We found that noise in the expression of a key enzyme in ammonia assimilation, Gdh1p, mediated a tradeoff between growth in low nitrogen environments and stress resistance in high ammonia environments. We implemented synthetic control of an endogenous Gdh1p regulatory network to construct an engineered strain in which the fitness of the population was tunable in response to an exogenously-added small molecule across a range of ammonia environments. Conclusion The ability to tune fitness and biological tradeoffs will be important components of future efforts to engineer microbial communities.

  10. Multilayer four-flux model for the optical degradation of thermal control coatings in space

    Science.gov (United States)

    Tonon, C.; Rozé, C.; Girasole, T.; Duvignacq, Carole

    2017-11-01

    The aim of this paper is to generalize the four-flux radiative transfer model to the case of a multilayer medium. An application is presented with the study of the optical degradation of a white paint in simulated space environment. This paint is constituted of a mixing a zinc oxide and a silicone resin. A sample was irradiated with 45 keV protons and reflectance measurements were achieved in situ after each step of irradiation in order to see the evolution of the thermo-optical properties of the coating. These tests were completed after irradiation by Scanning Electron Microscopy (SEM) in order to characterize the structure of the material and to detect possible structural changes due to the irradiation. This experimental investigation allowed us to define hypothesis to be introduced in the model. In particular, we assume that the optical degradation centered on 410 nm is due to a variation a-/+ of the imaginary part of the refractive index of zinc oxide in the damaged layer. The generalized four-flux model was validated by comparing numerical calculation with experiment.

  11. Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

    Science.gov (United States)

    Mitch, William E.; Sands, Jeff M.

    2015-01-01

    Renal nitrogen metabolism primarily involves urea and ammonia metabolism, and is essential to normal health. Urea is the largest circulating pool of nitrogen, excluding nitrogen in circulating proteins, and its production changes in parallel to the degradation of dietary and endogenous proteins. In addition to serving as a way to excrete nitrogen, urea transport, mediated through specific urea transport proteins, mediates a central role in the urine concentrating mechanism. Renal ammonia excretion, although often considered only in the context of acid-base homeostasis, accounts for approximately 10% of total renal nitrogen excretion under basal conditions, but can increase substantially in a variety of clinical conditions. Because renal ammonia metabolism requires intrarenal ammoniagenesis from glutamine, changes in factors regulating renal ammonia metabolism can have important effects on glutamine in addition to nitrogen balance. This review covers aspects of protein metabolism and the control of the two major molecules involved in renal nitrogen excretion: urea and ammonia. Both urea and ammonia transport can be altered by glucocorticoids and hypokalemia, two conditions that also affect protein metabolism. Clinical conditions associated with altered urine concentrating ability or water homeostasis can result in changes in urea excretion and urea transporters. Clinical conditions associated with altered ammonia excretion can have important effects on nitrogen balance. PMID:25078422

  12. Determination of homogenization factors in the simulation in the azymuthal flux unit distribution in the control ring of a experimental fast reactor

    International Nuclear Information System (INIS)

    Jachic, J.

    1987-01-01

    The azimuthal neutronic flux distribution in the control ring region for a low power fast reactor is simulated using a plate and rectangular smash models for one dimensional calculations under periodic boundary conditions in the frontier. (E.G.) [pt

  13. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock

    DEFF Research Database (Denmark)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.

    2014-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-s...

  14. The effect of metabolic control on hemodynamics in short-term insulin-dependent diabetic patients

    DEFF Research Database (Denmark)

    Mathiesen, E R; Hilsted, J; Feldt-Rasmussen, B

    1985-01-01

    Hemodynamics variables (heart rate, arterial blood pressure, cardiac output, hepato-splanchnic blood flow, forearm blood flow, and plasma catecholamines) were measured during good (median blood glucose 4.7 mmol/L) and poor (median blood glucose 16.3 mmol/L) metabolic control in eight young, short...

  15. The role of the autonomic nervous liver innervation in the control of energy metabolism

    NARCIS (Netherlands)

    Yi, Chun-Xia; la Fleur, Susanne E.; Fliers, Eric; Kalsbeek, Andries

    2010-01-01

    Despite a longstanding research interest ever since the early work by Claude Bernard, the functional significance of autonomic liver innervation, either sympathetic or parasympathetic, is still ill defined. This scarcity of information not only holds for the brain control of hepatic metabolism, but

  16. Carbon-carbon composite and copper-composite bond damages for high flux component controlled fusion

    International Nuclear Information System (INIS)

    Chevet, G.

    2010-01-01

    Plasma facing components constitute the first wall in contact with plasma in fusion machines such as Tore Supra and ITER. These components have to sustain high heat flux and consequently elevated temperatures. They are made up of an armour material, the carbon-carbon composite, a heat sink structure material, the copper chromium zirconium, and a material, the OFHC copper, which is used as a compliant layer between the carbon-carbon composite and the copper chromium zirconium. Using different materials leads to the apparition of strong residual stresses during manufacturing, because of the thermal expansion mismatch between the materials, and compromises the lasting operation of fusion machines as damage which appeared during manufacturing may propagate. The objective of this study is to understand the damage mechanisms of the carbon-carbon composite and the composite-copper bond under solicitations that plasma facing components may suffer during their life. The mechanical behaviours of carbon-carbon composite and composite-copper bond were studied in order to define the most suitable models to describe these behaviours. With these models, thermomechanical calculations were performed on plasma facing components with the finite element code Cast3M. The manufacturing of the components induces high stresses which damage the carbon-carbon composite and the composite-copper bond. The damage propagates during the cooling down to room temperature and not under heat flux. Alternative geometries for the plasma facing components were studied to reduce damage. The relation between the damage of the carbon-carbon composite and its thermal conductivity was also demonstrated. (author) [fr

  17. Vulnerability to stress, anxiety and depressive symptoms and metabolic control in Type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Gois Carlos

    2012-06-01

    Full Text Available Abstract Background Vulnerability to stress has been associated to distress, emotional distress symptoms and metabolic control in type 2 diabetes mellitus (T2DM patients as well. Furthermore some conflicting results were noticed. We aimed to evaluate the effect over metabolic control in what concerns vulnerability to stress beyond depressive and anxiety symptoms. Findings This cross-sectional study assessed 273 T2DM patients with depressive and anxiety symptoms using the Hospital Anxiety Depression Scale (HADS and the 23 Questions to assess Vulnerability to Stress (23QVS, along with demographic and clinical diabetes-related variables. Hierarchical logistic regression models were used to investigate predictors of poor glycemic control. The results showed an association of depressive symptoms (odds ratio = 1.12, 95%CI = 1.01-1.24, P = 0.030 with increased risk of poor glycemic control. Anxiety symptoms and vulnerability to stress on their own were not predictive of metabolic control, respectively (odds ratio = 0.92, 95%CI = 0.84-1.00, P = 0.187 and odds ratio = 0.98, 95%CI = 0.95-1.01, P = 0.282. Conclusions Our data suggested that vulnerability to stress was not predictive of poor glycemic control in T2DM, but depressive symptoms were.

  18. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    Science.gov (United States)

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-(18)FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. Copyright © 2015 the authors 0270-6474/15/353248-08$15.00/0.

  19. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    International Nuclear Information System (INIS)

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis we compared the effects of alcohol intoxication (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) and 23 healthy controls each of whom underwent four PET- 18 FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p=0.04); that alcohol (compared to placebo) decreased metabolism more in HD (20±13%) than controls (9±11%, p=0.005) and in proportion to daily alcohol consumption (r=0.36, p=0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10±12%) compared to NS in both groups (15±13%, p=0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e. acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in heavy drinkers, which might make them vulnerable to energy deficits during withdrawal

  20. Combined Effects of Ezetimibe and Phytosterols on Cholesterol Metabolism: A Randomized, Controlled Feeding Study in Humans

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B.; Lefevre, Michael; Ma, Lina; Spearie, Catherine Anderson; Steger-May, Karen; Ostlund, Richard E.

    2011-01-01

    Background Both ezetimibe and phytosterols inhibit cholesterol absorption. We tested the hypothesis that ezetimibe combined with phytosterols is more effective than ezetimibe alone in altering cholesterol metabolism. Methods and Results Twenty-one mildly hypercholesterolemic subjects completed a randomized, double-blind, placebo-controlled, triple crossover study. Each subject received a phytosterol-controlled diet plus (1) ezetimibe placebo + phytosterol placebo, (2) 10 mg ezetimibe/day + phytosterol placebo, and (3) 10 mg ezetimibe/day + 2.5 g phytosterols/day, for 3 weeks each. All meals were prepared in a metabolic kitchen. Primary outcomes were intestinal cholesterol absorption, fecal cholesterol excretion, and LDL cholesterol levels. The combined treatment resulted in significantly lower intestinal cholesterol absorption (598 mg/day, 95% CI 368 to 828) relative to control (2161 mg/day, 1112 to 3209) and ezetimibe alone (1054 mg/day, 546 to 1561, both P phytosterols averaged 129 (95% CI: 116 to 142), 108 (97 to 119), and 101 (90 to 112) mg/dL (P phytosterols to ezetimibe significantly enhanced the effects of ezetimibe on whole-body cholesterol metabolism and plasma LDL cholesterol. The large cumulative action of combined dietary and pharmacologic treatment on cholesterol metabolism emphasizes the potential importance of dietary phytosterols as adjunctive therapy for the treatment of hypercholesterolemia. PMID:21768544

  1. A New Adaptive Control for Five-Phase Fault-Tolerant Flux-Switching Permanent Magnet Motor

    Directory of Open Access Journals (Sweden)

    Hongyu Tang

    2016-01-01

    Full Text Available The five-phase fault-tolerant flux-switching permanent magnet (FT-FSPM motor can offer high efficiency and high fault-tolerant capability. In this paper, its operation principle is presented briefly and its mathematical model is derived. Further, a new adaptive control for an FT-FSPM motor, based on the backstepping method and the sliding mode control strategy, is proposed. According to the backstepping method, the current controllers and voltage control laws are designed to track the speed and minimize the current static error, which enhance the dynamic response and the ability to suppress external disturbances. In order to overcome the influence of parameter variations, according to sliding mode control theory, the virtual control variables and the adaptive algorithm are utilized to approach uncertainty terms. Three Lyapunov functions are designed, and the stability of the closed-loop system is analyzed in detail. Finally, both simulation and experimental results are presented to verify the proposed control method.

  2. Determination of transient temperature and heat flux on the surface of a reactor control rod based on temperature measurements at the interior points

    International Nuclear Information System (INIS)

    Cebula, Artur; Taler, Jan

    2014-01-01

    The paper presents heat transfer calculation results concerning a control rod of nuclear power plant. Apart from numerical calculation results, experimental heat transfer measurements of the control rod model are also presented. The control rod that is the object of interest is surrounded by a mixing region of hot and cold streams and, as a consequence, is subjected to thermal fluctuations. The paper describes a method based on the solution of the inverse heat conduction problem (IHCP) for determining heat flux on the outer surface of the rod. Numerical tests were conducted to validate the method by comparison of the results with the time changes of surface temperature and heat flux which were obtained from the computational fluid dynamics (CFD) simulation of the mixing process. A measuring instrument was designed to measure the heat flux at the outer surface of the control rod model. In addition, the principle of operation and construction of heat flux meter is presented in detail. -- Highlights: • Temperature and heat flux estimation during cooling of control rod are presented. • The inverse technique is based on the space marching method. • The instrument for surface heat flux measurement was manufactured and tested. • CFD simulations were used to validate the developed inverse technique. • Actual data were used to demonstrate practical applicability of the method

  3. G0S2: A small giant controller of lipolysis and adipose-liver fatty acid flux.

    Science.gov (United States)

    Zhang, Xiaodong; Heckmann, Bradlee L; Campbell, Latoya E; Liu, Jun

    2017-10-01

    The discovery of adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) provided a major paradigm shift in the understanding of intracellular lipolysis in both adipocytes and nonadipocyte cells. The subsequent discovery of G0/G1 switch gene 2 (G0S2) as a potent endogenous inhibitor of ATGL revealed a unique mechanism governing lipolysis and fatty acid (FA) availability. G0S2 is highly conserved in vertebrates, and exhibits cyclical expression pattern between adipose tissue and liver that is critical to lipid flux and energy homeostasis in these two tissues. Biochemical and cell biological studies have demonstrated that a direct interaction with ATGL mediates G0S2's inhibitory effects on lipolysis and lipid droplet degradation. In this review we examine evidence obtained from recent in vitro and in vivo studies that lends support to the proof-of-principle concept that G0S2 functions as a master regulator of tissue-specific balance of TG storage vs. mobilization, partitioning of metabolic fuels between adipose and liver, and the whole-body adaptive energy response. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Lactate turnover in fast-moving vertebrates: The control of plasma metabolite fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Weber, J.M.

    1987-01-01

    The goals of this thesis were: (1) to investigate the major factors involved in the regulation of plasma metabolite turnover at the whole-organism level-using lactate as a model, and (2) to determine whether endurance-adapted animals can support higher lactate turnover rates than sedentary animals. Lactate turnover was measured by bolus injection of (U{sup {minus}14}C)lacetate in skipjack tuna, Katsuwonus pelamis, and in thoroughbred race horses, Equus caballus. In tuna, turnover rates ranged from 112 to 431 umol min{sup {minus}1} kg{sup {minus}1}, and they were positively correlated with (lactate). These rates were higher than expected for a mammal of equivalent size. Plots of resting lactate and glucose turnover rates vs body mass on a log-log scale were linear for a wide range mammalian body sizes, and they showed the same slope as the classic body mass vs metabolic rate relationship.

  5. Robust Non-Linear Direct Torque and Flux Control of Adjustable Speed Sensorless PMSM Drive Based on SVM Using a PI Predictive Controller

    Directory of Open Access Journals (Sweden)

    F. Naceri

    2010-01-01

    Full Text Available This paper presents a new sensorless direct torque control method for voltage inverter – fed PMSM. The control methodis used a modified Direct Torque Control scheme with constant inverter switching frequency using Space Vector Modulation(DTC-SVM. The variation of stator and rotor resistance due to changes in temperature or frequency deteriorates theperformance of DTC-SVM controller by introducing errors in the estimated flux linkage and the electromagnetic torque.As a result, this approach will not be suitable for high power drives such as those used in tractions, as they require goodtorque control performance at considerably lower frequency. A novel stator resistance estimator is proposed. The estimationmethod is implemented using the Extended Kalman Filter. Finally extensive simulation results are presented to validate theproposed technique. The system is tested at different speeds and a very satisfactory performance has been achieved.

  6. Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: impact on thyroid function, metabolic control and pregnancy outcome

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Nielsen, Lene Ringholm; Rasmussen, Åse Krogh

    2008-01-01

    In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome.......In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti-TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome....

  7. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

    Directory of Open Access Journals (Sweden)

    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  8. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Bart eEverts

    2014-05-01

    Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

  9. Metabolism and the Control of Cell Fate Decisions and Stem Cell Renewal

    Science.gov (United States)

    Ito, Kyoko; Ito, Keisuke

    2016-01-01

    Although the stem cells of various tissues remain in the quiescent state to maintain their undifferentiated state, they also undergo cell divisions as required, and if necessary, even a single stem cell is able to provide for lifelong tissue homeostasis. Stem cell populations are precisely controlled by the balance between their symmetric and asymmetric divisions, with their division patterns determined by whether the daughter cells involved retain their self-renewal capacities. Recent studies have reported that metabolic pathways and the distribution of mitochondria are regulators of the division balance of stem cells and that metabolic defects can shift division balance toward symmetric commitment, which leads to stem cell exhaustion. It has also been observed that in asymmetric division, old mitochondria, which are central metabolic organelles, are segregated to the daughter cell fated to cell differentiation, whereas in symmetric division, young and old mitochondria are equally distributed between both daughter cells. Thus, metabolism and mitochondrial biology play important roles in stem cell fate decisions. As these decisions directly affect tissue homeostasis, understanding their regulatory mechanisms in the context of cellular metabolism is critical. PMID:27482603

  10. A critique of the molecular target-based drug discovery paradigm based on principles of metabolic control: advantages of pathway-based discovery.

    Science.gov (United States)

    Hellerstein, Marc K

    2008-01-01

    Contemporary drug discovery and development (DDD) is dominated by a molecular target-based paradigm. Molecular targets that are potentially important in disease are physically characterized; chemical entities that interact with these targets are identified by ex vivo high-throughput screening assays, and optimized lead compounds enter testing as drugs. Contrary to highly publicized claims, the ascendance of this approach has in fact resulted in the lowest rate of new drug approvals in a generation. The primary explanation for low rates of new drugs is attrition, or the failure of candidates identified by molecular target-based methods to advance successfully through the DDD process. In this essay, I advance the thesis that this failure was predictable, based on modern principles of metabolic control that have emerged and been applied most forcefully in the field of metabolic engineering. These principles, such as the robustness of flux distributions, address connectivity relationships in complex metabolic networks and make it unlikely a priori that modulating most molecular targets will have predictable, beneficial functional outcomes. These same principles also suggest, however, that unexpected therapeutic actions will be common for agents that have any effect (i.e., that complexity can be exploited therapeutically). A potential operational solution (pathway-based DDD), based on observability rather than predictability, is described, focusing on emergent properties of key metabolic pathways in vivo. Recent examples of pathway-based DDD are described. In summary, the molecular target-based DDD paradigm is built on a naïve and misleading model of biologic control and is not heuristically adequate for advancing the mission of modern therapeutics. New approaches that take account of and are built on principles described by metabolic engineers are needed for the next generation of DDD.

  11. Monitoring and robust adaptive control of fed-batch cultures of microorganisms exhibiting overflow metabolism [abstract

    Directory of Open Access Journals (Sweden)

    Vande Wouwer, A.

    2010-01-01

    Full Text Available Overflow metabolism characterizes cells strains that are likely to produce inhibiting by-products resulting from an excess of substrate feeding and a saturated respiratory capacity. The critical substrate level separating the two different metabolic pathways is generally not well defined. Monitoring of this kind of cultures, going from model identification to state estimation, is first discussed. Then, a review of control techniques which all aim at maximizing the cell productivity of fed-batch fermentations is presented. Two main adaptive control strategies, one using an estimation of the critical substrate level as set-point and another regulating the by-product concentration, are proposed. Finally, experimental investigations of an adaptive RST control scheme using the observer polynomial for the regulation of the ethanol concentration in Saccharomyces cerevisiae fed-batch cultures ranging from laboratory to industrial scales, are also presented.

  12. Microbial controls on metal mobility under the low nutrient fluxes found throughout the subsurface

    International Nuclear Information System (INIS)

    Boult, Stephen; Hand, Victoria L.; Vaughan, David J.

    2006-01-01

    Laboratory simulations and field studies of the shallow subsurface have shown that microbes and their extracellular products can influence the mobility of toxic metals from waste disposal sites. Modelling the transport of contaminants in groundwater may, therefore, require the input of microbial ecology data in addition to geochemical data, thus increasing the costs and the uncertainty of predictions. However, whether microbial effects on contaminant mobility occur extensively in the natural subsurface is unknown because the conditions under which they have been observed hitherto are generally unrepresentative of the average subsurface environment. Here, we show that microbial activity affects the mobility of a toxic trace metal (Cu) under the relatively low nutrient fluxes that dominate subsurface systems. More particularly, we show that under these low nutrient conditions, microbes and microbial products can immobilize metal but may themselves be subject to subsequent mobilization, thus complicating the pattern of metal storage and release. Our results show that the capability of microbes in the subsurface to change both the capacity of porous media to store metal, and the behaviour of metal that is released, is not restricted to the well researched environments close to sites of waste disposal. We anticipate our simulations will be a starting point for generating input data for transport models, and specifying the mechanism of metal remobilisation in environments more representative of the subsurface generally

  13. 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.

  14. 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.

  15. On the Control of Solute Mass Fluxes and Concentrations Below Fields Irrigated With Low-Quality Water: A Numerical Study

    Science.gov (United States)

    Russo, David

    2017-11-01

    The main goal of this study was to test the capability of irrigation water-based and soil-based approaches to control nitrate and chloride mass fluxes and concentrations below the root zone of agricultural fields irrigated with treated waste water (TWW). Using numerical simulations of flow and transport in relatively a fine-textured, unsaturated, spatially heterogeneous, flow domain, scenarios examined include: (i) irrigating with TWW only (REF); (ii) irrigation water is substituted between TWW and desalinized water (ADW); (iii) soil includes a capillary barrier (CB) and irrigating with TWW only (CB + TWW); and (iv) combination of (ii) and a CB (CB + ADW). Considering groundwater quality protection, plausible goals are: (i) to minimize solute discharges leaving the root zone, and, (ii) to maximize the probability that solute concentrations leaving the root zone will not exceed a prescribed, critical value. Results of the analyses suggest that in the case of a seasonal crop (a corn field) subject to irrigations only, with respect to the first goal, the CB + TWW and CB + ADW scenarios provide similar, excellent results, better than the ADW scenario; with respect to the second goal, however, the CB + ADW scenario gave substantially better results than the CB + TWW scenario. In the case a multiyear, perennial crop (a citrus orchard), subject to a sequence of irrigation and rainfall periods, for both solutes, and, particularly, nitrate, with respect to the two goals, both the ADW and CB + ADW scenarios perform better than the CB + TWW scenario. As compared with the REF and CB + TWW scenarios, the ADW and CB + ADW scenarios substantially reduce nitrogen mass fluxes to the groundwater and to the atmosphere, and, essentially, did not reduce nitrogen mass fluxes to the trees. Similar results, even better, were demonstrated for a relatively coarse-textured, spatially heterogeneous soil.

  16. Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.

    Science.gov (United States)

    Hicks, Julie A; Porter, Tom E; Liu, Hsiao-Ching

    2017-09-05

    The transition from embryonic to posthatch development in the chicken represents a massive metabolic switch from primarily lipolytic to primarily lipogenic metabolism. This metabolic switch is essential for the chick to successfully transition from the metabolism of stored egg yolk to the utilization of carbohydrate-based feed. However, regulation of this metabolic switch is not well understood. We hypothesized that microRNAs (miRNAs) play an important role in the metabolic switch that is essential to efficient growth of chickens. We used high-throughput RNA sequencing to characterize expression profiles of mRNA and miRNA in liver during late embryonic and early posthatch development of the chicken. This extensive data set was used to define the contributions of microRNAs to the metabolic switch during development that is critical to growth and nutrient utilization in chickens. We found that expression of over 800 mRNAs and 30 miRNAs was altered in the embryonic liver between embryonic day 18 and posthatch day 3, and many of these differentially expressed mRNAs and miRNAs are associated with metabolic processes. We confirmed the regulation of some of these mRNAs by miRNAs expressed in a reciprocal pattern using luciferase reporter assays. Finally, through the use of yeast one-hybrid screens, we identified several proteins that likely regulate expression of one of these important miRNAs. Integration of the upstream regulatory mechanisms governing miRNA expression along with monitoring the downstream effects of this expression will ultimately allow for the construction of complete miRNA regulatory networks associated with the hepatic metabolic switch in chickens. Our findings support a key role for miRNAs in controlling the metabolic switch that occurs between embryonic and posthatch development in the chicken.

  17. The Role of Monoaminergic Neurotransmission for Metabolic Control in the Fruit Fly Drosophila Melanogaster

    Directory of Open Access Journals (Sweden)

    Yong Li

    2017-08-01

    Full Text Available Hormones control various metabolic traits comprising fat deposition or starvation resistance. Here we show that two invertebrate neurohormones, octopamine (OA and tyramine (TA as well as their associated receptors, had a major impact on these metabolic traits. Animals devoid of the monoamine OA develop a severe obesity phenotype. Using flies defective in the expression of receptors for OA and TA, we aimed to decipher the contributions of single receptors for these metabolic phenotypes. Whereas those animals impaired in octß1r, octß2r and tar1 share the obesity phenotype of OA-deficient (tβh-deficient animals, the octß1r, octß2r deficient flies showed reduced insulin release, which is opposed to the situation found in tβh-deficient animals. On the other hand, OAMB deficient flies were leaner than controls, implying that the regulation of this phenotype is more complex than anticipated. Other phenotypes seen in tβh-deficient animals, such as the reduced ability to perform complex movements tasks can mainly be attributed to the octß2r. Tissue-specific RNAi experiments revealed a very complex interorgan communication leading to the different metabolic phenotypes observed in OA or OA and TA-deficient flies.

  18. Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: a case control study.

    Science.gov (United States)

    Wee, Bee S; Poh, Bee K; Bulgiba, Awang; Ismail, Mohd N; Ruzita, Abdul T; Hills, Andrew P

    2011-05-18

    With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome. Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic

  19. Getting the Dimensions Right - Human Nutrition as Key for the Control of Regional Nitrogen Fluxes

    Science.gov (United States)

    Zessner, M.; Thaler, S.; Ruzicka, K.; Natho, S.

    2009-04-01

    The western society is rested upon a strong animal-based (meat, eggs, milk) nutrition, which is far of a healthy balanced diet. Furthermore, the production of animal based food consumes five to six times more resources (e.g.: area, fertilizer) compared to plant-based food and is closely connected to environmental pollution (e.g.: emission of greenhouse gases, water pollution). Especially the regional nitrogen turnover is highly driven by the request from human nutrition on agricultural production. While the efficiency of the transfer of applied nitrogen into the product is 60 - 70 % for vegetarian food, it is 15 - 25 % for animal based food. This contribution is going to demonstrate the most important nitrogen fluxes on national scale in Austria calculated using a national material flow analysis. The national nitrogen balance is driven by the production of nitrogen fertiliser and import of fooder. The airborne transport of reactive nitrogen (NOX and NHX) plays a decisive role within this balance. The main losses into the environment occur during the agricultural production process. Losses to the atmosphere exceed losses to groundwater and surface waters. After introduction of nitrogen removal at treatment plants, emissions to surface waters are dominated by land use driven fluxes via groundwater. The influence of nitrogen depositions on land (agricultural area, forest and mountain regions) on nitrogen emissions to the water system is in the same order of magnitude as the direct emissions due to fertiliser application - especially in a country as Austria with high shares of mountainous and silvicultural areas. Sources for depositions of reactive nitrogen are mainly NH3 emissions to the air from animal husbandry and NOX emissions to the air from traffic. Both substance are matter of transboundary transport and thus are highly influenced by activities outside a specific country or river catchment. Management of nitrogen on a national or catchment scale has therefore

  20. Controls for multi-scale temporal variation in methane flux of a subtropical tidal salt marsh

    Science.gov (United States)

    Li, H.

    2016-12-01

    Coastal wetlands provide critical carbon sequestration benefits, yet the production of methane (CH4) from these ecosystems can vary by an order of magnitude based on environmental and biological factors. Eddy covariance (EC) measurements for methane flux (FCH4) were performed in a subtropical tidal salt marsh of eastern China over 20 months. Spectral analysis techniques including the continuous wavelet transform, the wavelet coherence, the partial wavelet coherence and the multiple wavelet coherence were employed to analyze the periodicities and the main regulating factors of FCH4 in the tidal salt marsh. The annual budget of methane was 17.8 g C-CH4 m-2 yr-1, which was relatively high compared to those of most reported from inland wetland sites. In non-growing season, release of ebullition was the dominant driving mechanism for variability of FCH4 from hourly to monthly scales. There was no single dominant factor at short-term scale (half-day to 1-day) in growing season. It is worthwhile to note that tide was one of the most important factors regulating FCH4 at short time scale (half-day to 1-day). In comparison, the contribution of temperature to FCH4 at a short time scale (half-day to 1-day) was small due to its narrow range. In addition, plant-modulated transport and gross primary production also contributed to FCH4 at multiple temporal scales in this densely vegetated marsh, especially at weekly to monthly scales. Due to the complex interactive influences of tidal dynamics, temperature fluctuation, plant productivity, plant-mediated transport and release of ebullition on FCH4 exhibited no clear pattern of diurnal variation, but instead was highly variable.

  1. Flux control analysis of mitochondrial oxidative phosphorylation in rat skeletal muscle: pyruvate and palmitoyl-carnitine as substrates give different control patterns

    DEFF Research Database (Denmark)

    Fritzen, Anette J; Grunnet, Niels; Quistorff, Bjørn

    2007-01-01

    was associated with the ADP-generating system, i.e., 0.58 +/- 0.05 with pyruvate, but significantly lower, 0.40 +/- 0.05, with palmitoyl-carnitine as substrate. The flux control coefficients of complex I, III and IV, the ATP synthase, the ATP/ADP carrier and the P(i) carrier were 0.070 +/- 0.03, 0.083 +/- 0.......04, 0.054 +/- 0.01, 0.11 +/- 0.03, 0.090 +/- 0.03 and 0.026 +/- 0.01, respectively, with pyruvate as substrate. With palmitoyl-carnitine all control coefficients were significantly different, except for the P(i) carrier (i.e., 0.024 +/- 0.001, 0.036 +/- 0.01, 0.052 +/- 0.02, 0.020 +/- 0.002, 0.034 +/- 0.......02 and 0.012 +/- 0.002, respectively), probably caused by the shift from NADH to FADH(2) oxidation. The sum of flux control coefficients was not significantly different from unity with pyruvate, while only 0.58 with palmitoyl-carnitine, indicating significant control contributions from the enzymes involved...

  2. Flux stability and power control in the Soviet RBMK-1000 reactors

    International Nuclear Information System (INIS)

    Meriwether, G.H.; McNeece, J.P.

    1993-08-01

    As a result of the Chernobyl accident, the Soviets have studied and implemented various design changes to improve the safety of the RBMK reactors. The safety measurements include modifications of the control rod configuration, fuel enrichment increase from 2.0 to 2.4 weight percent U-235, and installation of additional supplemental absorbers. The purpose of this study is to investigate the effects of increased fuel enrichment, different control rod positions, and supplemental absorber loadings on reactivity control, power distribution within the large RBMK core, and relative stability against power oscillations

  3. Hybrid Heat Pipes for High Heat Flux Spacecraft Thermal Control, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Grooved aluminum/ammonia Constant Conductance Heat Pipes (CCHPs) are the standard for thermal control in zero-gravity. Unfortunately, they are limited in terms of...

  4. Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype.

    Science.gov (United States)

    Lang, Jason E; Holbrook, Janet T; Mougey, Edward B; Wei, Christine Y; Wise, Robert A; Teague, W Gerald; Lima, John J

    2015-06-01

    Gastric acid blockade in children with asymptomatic acid reflux has not improved asthma control in published studies. There is substantial population variability regarding metabolism of and response to proton pump inhibitors based on metabolizer phenotype. How metabolizer phenotype affects asthma responses to acid blockage is not known. To determine how metabolizer phenotype based on genetic analysis of CYP2C19 affects asthma control among children treated with a proton pump inhibitor. Asthma control as measured by the Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month clinical trial of lansoprazole in children with asthma was analyzed for associations with surrogates of lansoprazole exposure (based on treatment assignment and metabolizer phenotype). Groups included placebo-treated children; lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes. Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two wild-type alleles were extensive metabolizers (EMs). Asthma control through most of the treatment period was unaffected by lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P = 0.02) and placebo-treated children (+0.16 vs. -0.23; P lansoprazole-treated PMs. Children with the PM phenotype developed worse asthma control after 6 months of lansoprazole treatment for poorly controlled asthma. Increased exposure to proton pump inhibitor may worsen asthma control by altering responses to respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00604851).

  5. Use of Plant Hydraulic Theory to Predict Ecosystem Fluxes Across Mountainous Gradients in Environmental Controls and Insect Disturbances

    Science.gov (United States)

    Ewers, B. E.; Pendall, E.; Reed, D. E.; Barnard, H. R.; Whitehouse, F.; Frank, J. M.; Massman, W. J.; Brooks, P. D.; Biederman, J. A.; Harpold, A. A.; Naithani, K. J.; Mitra, B.; Mackay, D. S.; Norton, U.; Borkhuu, B.

    2011-12-01

    While mountainous areas are critical for providing numerous ecosystem benefits at the regional scale, the strong gradients in environmental controls make predictions difficult. A key part of the problem is quantifying and predicting the feedback between mountain gradients and plant function which then controls ecosystem cycling. The emerging theory of plant hydraulics provides a rigorous yet simple platform from which to generate testable hypotheses and predictions of ecosystem pools and fluxes. Plant hydraulic theory predicts that plant controls over carbon, water, energy and nutrient fluxes can be derived from the limitation of plant water transport from the soil through xylem and out of stomata. In addition, the limit to plant water transport can be predicted by combining plant structure (e.g. xylem diameters or root-to-shoot ratios) and plant function (response of stomatal conductance to vapor pressure deficit or root vulnerability to cavitation). We evaluate the predictions of the plant hydraulic theory by testing it against data from a mountain gradient encompassing sagebrush steppe through subalpine forests (2700 to 3400 m). We further test the theory by predicting the carbon, water and nutrient exchanges from several coniferous trees in the same gradient that are dying from xylem dysfunction caused by blue-stain fungi carried by bark beetles. The common theme of both of these data sets is a change in water limitation caused by either changing precipitation along the mountainous gradient or lack of access to soil water from xylem-occluding fungi. Across all of the data sets which range in scale from individual plants to hillslopes, the data fit the predictions of plant hydraulic theory. Namely, there was a proportional tradeoff between the reference canopy stomatal conductance to water vapor and the sensitivity of that conductance to vapor pressure deficit that quantitatively fits the predictions of plant hydraulic theory. Incorporating this result into

  6. Defining a novel leptin–melanocortin–kisspeptin pathway involved in the metabolic control of puberty

    Directory of Open Access Journals (Sweden)

    Maria Manfredi-Lozano

    2016-10-01

    Full Text Available Objective: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction. However, its role in the metabolic regulation of puberty and interplay with kisspeptin, an essential puberty-regulating neuropeptide encoded by Kiss1, remain largely unknown. We aim here to unveil the potential contribution of central α-MSH signaling in the metabolic control of puberty by addressing its role in mediating the pubertal effects of leptin and its potential interaction with kisspeptin. Methods: Using wild type and genetically modified rodent models, we implemented pharmacological studies, expression analyses, electrophysiological recordings, and virogenetic approaches involving DREADD technology to selectively inhibit Kiss1 neurons, in order to interrogate the physiological role of a putative leptin→α-MSH→kisspeptin pathway in the metabolic control of puberty. Results: Stimulation of central α-MSH signaling robustly activated the reproductive axis in pubertal rats, whereas chronic inhibition of melanocortin receptors MC3/4R, delayed puberty, and prevented the permissive effect of leptin on puberty onset. Central blockade of MC3/4R or genetic elimination of kisspeptin receptors from POMC neurons did not affect kisspeptin effects. Conversely, congenital ablation of kisspeptin receptors or inducible, DREADD-mediated inhibition of arcuate nucleus (ARC Kiss1 neurons resulted in markedly attenuated gonadotropic responses to MC3/4R activation. Furthermore, close appositions were observed between

  7. Photoperiodism and enzyme activity: towards a model for the control of circadian metabolic rhythms in the crassulacean Acid metabolism.

    Science.gov (United States)

    Queiroz, O; Morel, C

    1974-04-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system.

  8. Changes in the isozymic pattern of phosphoenolpyruvate : An early step in photoperiodic control of crassulacean acid metabolism level.

    Science.gov (United States)

    Brulfert, J; Arrabaça, M C; Guerrier, D; Queiroz, O

    1979-01-01

    Two major isofunctional forms of phosphoenolpyruvate carboxylase (EC 4.1.1.31) have been separated from the leaves of Kalanchoe blossfeldiana Poelln. Tom Thumb by acrylamide gel electrophoresis and diethylaminoethyl cellulose techniques: one of the forms prevails under long-day treatment (low crassulacean acid metabolism level), the other develops under short-day treatment (high Crassulacean acid metabolism level). Molecular weights are significantly different: 175·10(3) and 186·10(3), respectively. These results indicate that two populations of phosphoenolyruvate carboxylase are present in the plant, one of which is responsible for Crassulacean acid metabolism activity under the control of photoperiod.The Crassulacean acid metabolism appears to depend on the same endogenous clock that governs other photoperiodically controlled events (e.g. flowering). The metabolic and energetic significance of this feature is discussed. It is suggested that modification in isozymic composition could be an early step in the response to photoperiodism at the metabolic level.

  9. Determination of the theoretical feasibility for the transmutation of europium isotopes from high flux isotope reactor control cylinders

    International Nuclear Information System (INIS)

    Elam, K.R.; Reich, W.J.

    1995-09-01

    The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory (ORNL) is a 100 MWth light-water research reactor designed and built in the 1960s primarily for the production of transuranic isotopes. The HFIR is equipped with two concentric cylindrical blade assemblies, known as control cylinders, that are used to control reactor power. These control cylinders, which become highly radioactive from neutron exposure, are periodically replaced as part of the normal operation of the reactor. The highly radioactive region of the control cylinders is composed of europium oxide in an aluminum matrix. The spent HFIR control cylinders have historically been emplaced in the ORNL Waste Area Grouping (WAG) 6. The control cylinders pose a potential radiological hazard due to the long lived radiotoxic europium isotopes 152 Eu, 154 Eu, and 155 Eu. In a 1991 health evaluation of WAG 6 (ERD 1991) it was shown that these cylinders were a major component of the total radioactivity in WAG 6 and posed a potential exposure hazard to the public in some of the postulated assessment scenarios. These health evaluations, though preliminary and conservative in nature, illustrate the incentive to investigate methods for permanent destruction of the europium radionuclides. When the cost of removing the control cylinders from WAG 6, performing chemical separations and irradiating the material in HFIR are factored in, the option of leaving the control cylinders in place for decay must be considered. Other options, such as construction of an engineered barrier around the disposal silos to reduce the chance of migration, should also be analyzed

  10. Hypoglycemia in pregnant women with type 1 diabetes - Predictors and role of metabolic control

    DEFF Research Database (Denmark)

    Nielsen, L.R.; Johansen, M.; Pedersen-Bjergaard, U.

    2008-01-01

    OBJECTIVE- In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, Vomiting, and other potential predictors of occurrence of severe hypoglycemia. RESEARCH DESIGN AND METHODS- A prospective...... awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia. CONCLUSIONS - In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors...... observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild...

  11. 3D microwave cavity with magnetic flux control and enhanced quality factor

    Energy Technology Data Exchange (ETDEWEB)

    Reshitnyk, Yarema [The University of Queensland, School of Mathematics and Physics, St Lucia (Australia); Jerger, Markus [The University of Queensland, ARC Centre of Excellence for Engineered Quantum Systems, 4072 (Australia); Fedorov, Arkady [The University of Queensland, School of Mathematics and Physics, St Lucia (Australia); The University of Queensland, ARC Centre of Excellence for Engineered Quantum Systems, 4072 (Australia)

    2016-12-15

    Three-dimensional (3D) microwave cavities have been extensively used for coupling and interacting with superconducting quantum bits (qubits), providing a versatile platform for quantum control experiments and for realizing hybrid quantum systems. While having high quality factors (>10{sup 6}) superconducting cavities do not permit magnetic field control of qubits. In contrast, cavities made of normal metals are transparent to magnetic fields, but experience lower quality factors (∝10{sup 4}). We have created a hybrid cavity which is primarily composed of aluminium but also contains a small copper insert reaching the internal quality factor of ≅10{sup 5}, an order of magnitude improvement over all previously tested normal metal cavities. In order to demonstrate precise magnetic control, we performed spectroscopy of three superconducting qubits, where individual control of each qubit's frequency was exerted with small external wire coils. An improvement in quality factor and magnetic field control makes this 3D hybrid cavity an attractive new element for circuit quantum electrodynamics experiments. (orig.)

  12. Role of parenting style in achieving metabolic control in adolescents with type 1 diabetes.

    Science.gov (United States)

    Shorer, Maayan; David, Ravit; Schoenberg-Taz, Michal; Levavi-Lavi, Ifat; Phillip, Moshe; Meyerovitch, Joseph

    2011-08-01

    To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes. Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA(1c) values. An authoritative paternal parenting style predicted better glycemic control and adherence in the child; a permissive maternal parenting style predicted poor adherence. A higher sense of helplessness in both parents predicted worse glycemic control and lesser adherence to treatment. Parental sense of helplessness was a significant predictor of diabetes control after correcting for other confounders (patient age, sex, and treatment method). An authoritative nonhelpless parenting style is associated with better diabetes control in adolescents. Paternal involvement is important in adolescent diabetes management. These results have implications for psychological interventions.

  13. Cardiovascular and metabolic syndrome risk among men with and without erectile dysfunction: case-control study

    OpenAIRE

    Zambon, João Paulo; Mendonça, Rafaela Rosalba de; Wroclawski, Marcelo Langer; Karam Junior, Amir; Santos, Raul D.; Carvalho, José Antonio Maluf de; Wroclawski, Eric Roger

    2010-01-01

    CONTEXT AND OBJECTIVE: Erectile dysfunction has been associated with cardiovascular diseases. The aim here was to evaluate cardiovascular risk through the Framingham Risk Score (FRS) criteria, C-reactive protein (CRP) assays and presence of metabolic syndrome (MS) in men with and without erectile dysfunction diagnosed within a healthcare program. DESIGN AND SETTING: A retrospective case-control study was conducted. The patients were selected from a healthcare program at the Hospital Israelita...

  14. Heat flux and temperature determination on the control rod outer surface

    International Nuclear Information System (INIS)

    Taler, J.; Cebula, A.; Marcinkiewicz, J.; Tinoco, H.

    2011-01-01

    The paper presents heat transfer calculation results concerning a control rod of Unit 3 of Forsmark Nuclear Power Plant (NPP). The part of the control rod, which is the object of interest, is surrounded by a mixing region of hot and cold flows and, as a consequence, is subjected to thermal fluctuations. The paper describes a numerical test which validates the method based on the solution of the inverse heat conduction problem (IHCP). The comparison of the results achieved by two methods, CFD and IHCP, including a description of the IHCP method used in the calculation process, shows a very good agreement between the methods. (author)

  15. Verification of heat flux and temperature calculation on the control rod outer surface

    Science.gov (United States)

    Taler, Jan; Cebula, Artur

    2011-12-01

    The paper presents heat transfer calculation results concerning a control rod of Forsmark Nuclear Power Plant (NPP). The part of the control rod, which is the object of interest, is surrounded by a mixing region of hot and cold flows and, as a consequence, is subjected to thermal fluctuations. The paper describes a numerical test which validates the method based on the solution of the inverse heat conduction problem (IHCP). The comparison of the results achieved by two methods, computational fluid dynamics (CFD) simulations and IHCP, including a description of the IHCP method used in the calculation process, shows a very good agreement between the methods.

  16. Plant lighting system with five wavelength-band light-emitting diodes providing photon flux density and mixing ratio control

    Directory of Open Access Journals (Sweden)

    Yano Akira

    2012-11-01

    Full Text Available Abstract Background Plant growth and development depend on the availability of light. Lighting systems therefore play crucial roles in plant studies. Recent advancements of light-emitting diode (LED technologies provide abundant opportunities to study various plant light responses. The LED merits include solidity, longevity, small element volume, radiant flux controllability, and monochromaticity. To apply these merits in plant light response studies, a lighting system must provide precisely controlled light spectra that are useful for inducing various plant responses. Results We have developed a plant lighting system that irradiated a 0.18 m2 area with a highly uniform distribution of photon flux density (PFD. The average photosynthetic PFD (PPFD in the irradiated area was 438 micro-mol m–2 s–1 (coefficient of variation 9.6%, which is appropriate for growing leafy vegetables. The irradiated light includes violet, blue, orange-red, red, and far-red wavelength bands created by LEDs of five types. The PFD and mixing ratio of the five wavelength-band lights are controllable using a computer and drive circuits. The phototropic response of oat coleoptiles was investigated to evaluate plant sensitivity to the light control quality of the lighting system. Oat coleoptiles irradiated for 23 h with a uniformly distributed spectral PFD (SPFD of 1 micro-mol m–2 s–1 nm–1 at every peak wavelength (405, 460, 630, 660, and 735 nm grew almost straight upwards. When they were irradiated with an SPFD gradient of blue light (460 nm peak wavelength, the coleoptiles showed a phototropic curvature in the direction of the greater SPFD of blue light. The greater SPFD gradient induced the greater curvature of coleoptiles. The relation between the phototropic curvature (deg and the blue-light SPFD gradient (micro-mol m–2 s–1 nm–1 m–1 was 2 deg per 1 micro-mol m–2 s–1 nm–1 m–1. Conclusions The plant lighting system, with a computer with a

  17. Interaction of Pubertal Development and Metabolic Control in Adolescents with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    M. Plamper

    2017-01-01

    Full Text Available Background. In T1DM, delayed pubertal development and reduced final height are associated with inadequate metabolic control. Objective. To assess whether T1DM affects pubertal growth spurt and whether metabolic control during puberty is gender-related. Methods. Using a large multicentre database, longitudinal data from 1294 patients were analysed. Inclusion criteria: complete records of height and HbA1c from the age of seven to 16 years. Exclusion criteria: other significant chronic diseases and medications, T1DM duration less than three months, and initial BMI 97th percentile. Results. Growth velocity (GV was impaired with a significant reduction of peak GV by 1.2 cm in boys. HbA1c increase during male puberty was lower except for a period of 1.5 years. The highest HbA1c increase in boys coincided with maximum growth spurt. In girls, the highest HbA1c increase was observed during late puberty. Even though there is impaired GV, both sexes reach a height at 16 years of age which corresponds to the background population height. Conclusion. Worsening of metabolic control is sex-discordant and associated with gender-specific alterations of GV. However, the vast majority of boys and girls with T1DM seems to reach normal height at the age of 16 years.

  18. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

    Science.gov (United States)

    Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

    2014-01-01

    The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

  19. Mechanisms controlling the air–sea CO2 flux in the North Sea

    NARCIS (Netherlands)

    Prowe, A.E.F.; Thomas, Helmuth; Pätsch, Johannes; Kühn, Wilfried; Bozec, Yann; Schiettecatte, Laure-Sophie; Borges, Alberto V.; Baar, Hein J.W. de; Paetsch, J; Kuehn, W

    2009-01-01

    The mechanisms driving the air–sea exchange of carbon dioxide (CO2) in the North Sea are investigated using the three-dimensional coupled physical–biogeochemical model ECOHAM (ECOlogical-model, HAMburg). We validate our simulations using field data for the years 2001–2002 and identify the controls

  20. Shallow soil moisture – ground thaw interactions and controls – Part 2: Influences of water and energy fluxes

    Directory of Open Access Journals (Sweden