SBMLsqueezer: A CellDesigner plug-in to generate kinetic rate equations for biochemical networks

<p>Abstract</p> <p>Background</p> <p>The development of complex biochemical models has been facilitated through the standardization of machine-readable representations like SBML (Systems Biology Markup Language). This effort is accompanied by the ongoing development of the human-readable diagrammatic representation SBGN (Systems Biology Graphical Notation). The graphical SBML editor CellDesigner allows direct translation of SBGN into SBML, and vice versa. For the assignment of kinetic rate laws, however, this process is not straightforward, as it often requires manual assembly and specific knowledge of kinetic equations.</p> <p>Results</p> <p>SBMLsqueezer facilitates exactly this modeling step via automated equation generation, overcoming the highly error-prone and cumbersome process of manually assigning kinetic equations. For each reaction the kinetic equation is derived from the stoichiometry, the participating species (e.g., proteins, mRNA or simple molecules) as well as the regulatory relations (activation, inhibition or other modulations) of the SBGN diagram. Such information allows distinctions between, for example, translation, phosphorylation or state transitions. The types of kinetics considered are numerous, for instance generalized mass-action, Hill, convenience and several Michaelis-Menten-based kinetics, each including activation and inhibition. These kinetics allow SBMLsqueezer to cover metabolic, gene regulatory, signal transduction and mixed networks. Whenever multiple kinetics are applicable to one reaction, parameter settings allow for user-defined specifications. After invoking SBMLsqueezer, the kinetic formulas are generated and assigned to the model, which can then be simulated in CellDesigner or with external ODE solvers. Furthermore, the equations can be exported to SBML, LaTeX or plain text format.</p> <p>Conclusion</p> <p>SBMLsqueezer considers the annotation of all participating reactants, products and regulators when generating rate laws for reactions. Thus, for each reaction, only applicable kinetic formulas are considered. This modeling scheme creates kinetics in accordance with the diagrammatic representation. In contrast most previously published tools have relied on the stoichiometry and generic modulators of a reaction, thus ignoring and potentially conflicting with the information expressed through the process diagram. Additional material and the source code can be found at the project homepage (URL found in the Availability and requirements section).</p

Barriers To Entry For New PlayersIn First-Person Games : The issues that new players encounter and possible ways to solve them

This paper studies how new players approach first-person games using a controller. By observingthe behaviour of five mostly inexperienced individuals as they play through the first few levelsof the game Portal 2 , the following patterns for barriers to entry can be observed:The game presumes common knowledge of its player that new players lack.Uninitiated have a hard time using buttons and sticks simultaneously for complicatedmaneuvers.New players primarily use the buttons that they can see with a casual glance, causingsome buttons to be less used.Misunderstanding due to not clearly have been shown possibilities in the gameworld.New players are unaware of the Options menu.Players find navigation and orientation difficult when lacking all the senses of a physicalbody.The fear of not being good enough causes distress.Players find it a waste of time to redo previously conquered challenges or not makingprogress fast enough.The paper then discusses possible solutions to these problems.Denna rapport studerar hur nya spelare närmar sig förstapersonsspel som kontrolleras medhandkontroll. Genom att observera beteendet hos fem till mestadels oerfarna individer medan despelar igenom några av de första få banorna i spelet Portal 2 kan följande mönster som hindrardem från att börja spela urskiljas:Spelet förutsätter att dess spelare har en gemensam allmän kunskap. Kunskap som nyaspelare saknar.Oinvigda har svårt att använda både knappar och spakar simultant för att utförakomplicerade manövrar.Nya spelare använder primärt knapparna som de kan se vid en flyktig blick, vilketorsakar att vissa knappar blir mindre frekvent använda än andra.Missförstånd på grund av att icke klart och tydligt blivit meddelade spelvärldenmöjligheter.Nya spelare är omedvetna om Options-menyn.Spelare finner att röra sig i spelvärlden är svårt när de inte har tillgång till alla sinnen enfysisk kropp har.Rädslan för att inte vara bra nog orsakar oro.Spelare finner att det är slöseri med tid att göra om tidigare erövrade utmaningar eller attinte göra framsteg i tillräckligt hög fart.Denna rapport diskuterar möjliga lösningar på dessa problem

Stability analysis of membrane-reinforced curved earth retaining walls, using a multiphase approach

International audienceThe stability analysis of curved earth retaining walls, stabilized by reinforcing membranes, is investigated by means of a multiphase model developed in the framework of the yield design approach. This model is an extension of that previously developed for soils reinforced by linear inclusions. It combines the advantage of a homogenization approach in terms of improved computational efficiency, with its capability to account for a specific soil-reinforcement failure condition, in a rational and systematic way. Application of this model is performed on the illustrative example of a cylindrical reinforced retaining wall by means of the kinematic approach of yield design, which provides upper bound estimates for the retaining wall stability factor. Non dimensional charts are finally presented assessing the influence of relevant parameters such as the curvature of the wall, the length of the reinforcing membranes or the reinforcement pull-out resistance The stability analysis of curved earth retaining walls, stabilized by reinforcing membranes, is investigated by means of a multiphase model developed in the framework of the yield design approach. This model is an extension of that previously developed for soils reinforced by linear inclusions. It combines the advantage of a homogenization approach in terms of improved computational efficiency, with its capability to account for a specific soil-reinforcement failure condition, in a rational and systematic way. Application of this model is performed on the illustrative example of a cylindrical reinforced retaining wall by means of the kinematic approach of yield design, which provides upper bound estimates for the retaining wall stability factor. Non dimensional charts are finally presented assessing the influence of relevant parameters such as the curvature of the wall, the length of the reinforcing membranes or the reinforcement pull-out resistanc