Mass conserved elementary kinetics is sufficient for the existence of a non-equilibrium steady state concentration

Living systems are forced away from thermodynamic equilibrium by exchange of mass and energy with their environment. In order to model a biochemical reaction network in a non-equilibrium state one requires a mathematical formulation to mimic this forcing. We provide a general formulation to force an arbitrary large kinetic model in a manner that is still consistent with the existence of a non-equilibrium steady state. We can guarantee the existence of a non-equilibrium steady state assuming only two conditions; that every reaction is mass balanced and that continuous kinetic reaction rate laws never lead to a negative molecule concentration. These conditions can be verified in polynomial time and are flexible enough to permit one to force a system away from equilibrium. In an expository biochemical example we show how a reversible, mass balanced perpetual reaction, with thermodynamically infeasible kinetic parameters, can be used to perpetually force a kinetic model of anaerobic glycolysis in a manner consistent with the existence of a steady state. Easily testable existence conditions are foundational for efforts to reliably compute non-equilibrium steady states in genome-scale biochemical kinetic models.Comment: 11 pages, 2 figures (v2 is now placed in proper context of the excellent 1962 paper by James Wei entitled "Axiomatic treatment of chemical reaction systems". In addition, section 4, on "Utility of steady state existence theorem" has been expanded.

MetaboTools: A comprehensive toolbox for analysis of genome-scale metabolic models

Metabolomic data sets provide a direct read-out of cellular phenotypes and are increasingly generated to study biological questions. Our previous work revealed the potential of analyzing extracellular metabolomic data in the context of the metabolic model using constraint-based modeling. Through this work, which consists of a protocol, a toolbox, and tutorials of two use cases, we make our methods available to the broader scientific community. The protocol describes, in a step-wise manner, the workflow of data integration and computational analysis. The MetaboTools comprise the Matlab code required to complete the workflow described in the protocol. Tutorials explain the computational steps for integration of two different data sets and demonstrate a comprehensive set of methods for the computational analysis of metabolic models and stratification thereof into different phenotypes. The presented workflow supports integrative analysis of multiple omics data sets. Importantly, all analysis tools can be applied to metabolic models without performing the entire workflow. Taken together, this protocol constitutes a comprehensive guide to the intra-model analysis of extracellular metabolomic data and a resource offering a broad set of computational analysis tools for a wide biomedical and non-biomedical research community

Conditions for duality between fluxes and concentrations in biochemical networks

Mathematical and computational modelling of biochemical networks is often done in terms of either the concentrations of molecular species or the fluxes of biochemical reactions. When is mathematical modelling from either perspective equivalent to the other? Mathematical duality translates concepts, theorems or mathematical structures into other concepts, theorems or structures, in a one-to-one manner. We present a novel stoichiometric condition that is necessary and sufficient for duality between unidirectional fluxes and concentrations. Our numerical experiments, with computational models derived from a range of genome-scale biochemical networks, suggest that this flux-concentration duality is a pervasive property of biochemical networks. We also provide a combinatorial characterisation that is sufficient to ensure flux-concentration duality. That is, for every two disjoint sets of molecular species, there is at least one reaction complex that involves species from only one of the two sets. When unidirectional fluxes and molecular species concentrations are dual vectors, this implies that the behaviour of the corresponding biochemical network can be described entirely in terms of either concentrations or unidirectional fluxes

Transthyretin familial amyloid polyneuropathy impact on health-related quality of life

info:eu-repo/semantics/publishedVersio

Lifecycle CO2 emissions from US bioethanol production with CCS

There is growing consensus that carbon dioxide removal (CDR) technologies – also referred to as “negative emissions” technologies (NETs) – will be part of the portfolio of strategies and technologies needed to hold the increase in the global average temperature to “well below 2 °C” (1), as agreed by parties to the Paris Agreement. The production of bioenergy with carbon capture and sequestration (BECCS) is one class of CDR technology (2), involving the capture and geologic storage of CO2 (CCS) that would otherwise be emitted to the atmosphere from use of biomass as a fuel for electricity generation or feedstock for production of liquid fuels. Use of CCS typically imposes two energy penalties that can diminish its benefits: energy is needed to separate CO2 from dilute CO2-containing mixtures (e.g. flue gas), and to liquefy CO2 so that it can be transported and injected into geologic formations. The predominant biofuel production pathway in the United States (U.S.) today is conversion of corn starch to ethanol, which generates relatively high-concentration CO2 from fermentation and dilute-CO2 from fuel combustion for process heat. In 2015, the U.S. produced approximately 53 billion liters of bioethanol from nearly 200 facilities (3) releasing approximately 40 MtCO2 of CO2 from fermentation and a further 20 MtCO2 from process heat (4). The climate benefit of applying CCS to biofuel production – and BECCS more generally – can only be accurately assessed in the context of emissions over the entire fuel production pathway, including the biomass supply chain. Few prior studies have quantified the carbon intensity of biofuels, such as ethanol, produced from processes including CCS (5–8). While previous studies consider a range of feedstocks (i.e., sugar cane, beets, and corn), none consider the emissions from direct and indirect land-use change associated with feedstock production and some use dated assumptions for key parameters, such as corn and ethanol yields (7,8). However, all conclude that, with the addition of CCS, GHG intensity of produced fuels decreases and can become negative (even without credit for displacement). In this paper, we quantify the life-cycle emissions of several corn-ethanol production pathways coupled with CCS at different process steps. Specifically, we assess the lifecycle emissions for dry-mill ethanol production with and without CCS for fermentation process emissions and for onsite boiler or cogeneration emissions. We run these scenarios for representative U.S. corn ethanol plants, and include recent estimates of indirect land use change. Finally, we do a detailed parametric sensitivity analysis of our results. 1. Sanderson BM, O’Neill BC, Tebaldi C. What would it take to achieve the Paris temperature targets? Geophys Res Lett. 2016 Jul 16;43(13):7133–42. 2. The Royal Society. Geoengineering the climate: science, governance and uncertainty [Internet]. London, UK: The Royal Society; 2009. Available from: https://royalsociety.org/topics- policy/publications/2009/geoengineering-climate/ 3. U.S. DOE. Renewable & Alternative Fuels - Data [Internet]. U.S. Energy Information Administration (EIA). [cited 2017 Jan 14]. Available from: http://www.eia.gov/renewable/data.cfm#alternative 4. U.S. EPA. EPA Facility Level GHG Emissions Data [Internet]. [cited 2017 Jan 14]. Available from: https://ghgdata.epa.gov/ghgp/main.do 5. Lindfeldt EG, Westermark MO. System study of carbon dioxide (CO2) capture in bio-based motor fuel production. 19th Int Conf Effic Cost Optim Simul Environ Impactof Energy Syst 2006. 2008 Feb;33(2):352–61. 6. Laude A, Ricci O, Bureau G, Royer-Adnot J, Fabbri A. CO2 capture and storage from a bioethanol plant: Carbon and energy footprint and economic assessment. Int J Greenh Gas Control. 2011;5(5):1220–31. 7. Möllersten K, Yan J, R. Moreira J. Potential market niches for biomass energy with CO2 capture and storage--Opportunities for energy supply with negative CO2 emissions. Biomass Bioenergy. 2003;25(3):273–85. 8. Kheshgi HS, Prince RC. Sequestration of fermentation CO2 from ethanol production. Energy. 2005 Jul;30(10):1865–71

Tindak Tutur Komunikasi Dalam Aktivitas Outbound Call Program Indihome Triple Play Oleh Virtual Account Manager PT Telekomunikasi Indonesia

Penelitian ini membahas unit terkecil yang terdapat dalam komunikasi bahasa yaitu Tindak Tutur. Tujuan penelitian ini adalah untuk menelaah bagaimana tindak tutur komunikasi yang ada dalam aktivitas outbound call program IndiHome Triple Play. Penelitian ini menggunakan metode deskriptif kualitatif dengan pendekatan analisis percapakan. Hasil penelitian ini menyatakan bahwa Lokusi ditemukan pada seluruh tuturan Agent. Ilokusi ditemukan sebagai ‘Arti' dari apa yang disampaikan Agent. Agent menstimuli sebuah makna dari apa yang ia sampaikan kepada lawan bicaranya. Dan pelanggan dapat memaknai ketika lokusi sudah disampaikan. Perlokusi secara sempurna ditemukan karena ilokusi nya sudah sampai pada pelanggan, makna dari apa yang kita sampaikan sudah dirasa oleh pelanggan dan secara langsung melihat efek dari apa yang kita sampaikan kepada pelanggan

Protectors or Traitors: The Roles of PON2 and PON3 in Atherosclerosis and Cancer

Cancer and atherosclerosis are major causes of death in western societies. Deregulated cell death is common to both diseases, with significant contribution of inflammatory processes and oxidative stress. These two form a vicious cycle and regulate cell death pathways in either direction. This raises interest in antioxidative systems. The human enzymes paraoxonase-2 (PON2) and PON3 are intracellular enzymes with established antioxidative effects and protective functions against atherosclerosis. Underlying molecular mechanisms, however, remained elusive until recently. Novel findings revealed that both enzymes locate to mitochondrial membranes where they interact with coenzyme Q10 and diminish oxidative stress. As a result, ROS-triggered mitochondrial apoptosis and cell death are reduced. From a cardiovascular standpoint, this is beneficial given that enhanced loss of vascular cells and macrophage death forms the basis for atherosclerotic plaque development. However, the same function has now been shown to raise chemotherapeutic resistance in several cancer cells. Intriguingly, PON2 as well as PON3 are frequently found upregulated in tumor samples. Here we review studies reporting PON2/PON3 deregulations in cancer, summarize most recent findings on their anti-oxidative and antiapoptotic mechanisms, and discuss how this could be used in putative future therapies to target atherosclerosis and cancer