The economic basis of periodic enzyme dynamics

Periodic enzyme activities can improve the metabolic performance of cells. As an adaptation to periodic environments or by driving metabolic cycles that can shift fluxes and rearrange metabolic processes in time to increase their efficiency. To study what benefits can ensue from rhythmic gene expression or posttranslational modification of enzymes, I propose a theory of optimal enzyme rhythms in periodic or static environments. The theory is based on kinetic metabolic models with predefined metabolic objectives, scores the effects of harmonic enzyme oscillations, and determines amplitudes and phase shifts that maximise cell fitness. In an expansion around optimal steady states, the optimal enzyme profiles can be computed by solving a quadratic optimality problem. The formulae show how enzymes can increase their efficiency by oscillating in phase with their substrates and how cells can benefit from adapting to external rhythms and from spontaneous, intrinsic enzyme rhythms. Both types of behaviour may occur different parameter regions of the same model. Optimal enzyme profiles are not passively adapted to existing substrate rhythms, but shape them actively to create opportunities for further fitness advantage: in doing so, they reflect the dynamic effects that enzymes can exert in the network. The proposed theory combines the dynamics and economics of metabolic systems and shows how optimal enzyme profiles are shaped by network structure, dynamics, external rhythms, and metabolic objectives. It covers static enzyme adaptation as a special case, reveals the conditions for beneficial metabolic cycles, and predicts optimally combinations of gene expression and posttranslational modification for creating enzyme rhythms

Intangibles mismeasurements, synergy, and accounting numbers : a note.

For the last two decades, authors (e.g. Ohlson, 1995; Lev, 2000, 2001) have regularly pointed out the enforcement of limitations by traditional accounting frameworks on financial reporting informativeness. Consistent with this claim, it has been then argued that accounting finds one of its major limits in not allowing for direct recognition of synergy occurring amongst the firm intangible and tangible items (Casta, 1994; Casta & Lesage, 2001). Although the firm synergy phenomenon has been widely documented in the recent accounting literature (see for instance, Hand & Lev, 2004; Lev, 2001) research hitherto has failed to provide a clear approach to assess directly and account for such a henceforth fundamental corporate factor. The objective of this paper is to raise and examine, but not address exhaustively, the specific issues induced by modelling the synergy occurring amongst the firm assets whilst pointing out the limits of traditional accounting valuation tools. Since financial accounting valuation methods are mostly based on the mathematical property of additivity, and consequently may occult the perspective of regarding the firm as an organized set of assets, we propose an alternative valuation approach based on non-additive measures issued from the Choquet's (1953) and Sugeno's (1997) framework. More precisely, we show how this integration technique with respect to a non-additive measure can be used to cope with either positive or negative synergy in a firm value-building process and then discuss its potential future implications for financial reporting.Financial reporting; accounting goodwill; assets synergy; non-additive measures; Choquet’s framework;

Synergy Modelling and Financial Valuation : the contribution of Fuzzy Integrals.

Les méthodes d’évaluation financière utilisent des opérateurs d’agrégation reposant sur les propriétés d’additivité (sommations, intégrales de Lebesgue). De ce fait, elles occultent les phénomènes de renforcement et de synergie (ou de redondance) qui peuvent exister entre les éléments d’un ensemble organisé. C’est particulièrement le cas en ce qui concerne le problème d’évaluation financière du patrimoine d’une entreprise : en effet, en pratique, il est souvent mis en évidence une importante différence de valorisation entre l’approche « valeur de la somme des éléments » (privilégiant le point de vue financier) et l’approche « somme de la valeur des différents éléments » (privilégiant le point de vue comptable). Les possibilités offertes par des opérateurs d’agrégation comme les intégrales floues (Sugeno, Grabisch, Choquet) permettent, au plan théorique, de modéliser l’effet de synergie. La présente étude se propose de valider empiriquement les modalités d’implémentation opérationnelle de ce modèle à partir d’un échantillon d’entreprises cotées ayant fait l’objet d’une évaluation lors d’une OPA.Financial valuation methods use additive aggregation operators. But a patrimony should be regarded as an organized set, and additivity makes it impossible for these aggregation operators to formalize such phenomena as synergy or mutual inhibition between the patrimony’s components. This paper considers the application of fuzzy measure and fuzzy integrals (Sugeno, Grabisch, Choquet) to financial valuation. More specifically, we show how integration with respect to a non additive measure can be used to handle positive or negative synergy in value construction.Fuzzy measure; Fuzzy integral; Aggregation operator; Synergy; Financial valuation;

Comparing System Dynamics and Agent-Based Simulation for Tumour Growth and its Interactions with Effector Cells

There is little research concerning comparisons and combination of System Dynamics Simulation (SDS) and Agent Based Simulation (ABS). ABS is a paradigm used in many levels of abstraction, including those levels covered by SDS. We believe that the establishment of frameworks for the choice between these two simulation approaches would contribute to the simulation research. Hence, our work aims for the establishment of directions for the choice between SDS and ABS approaches for immune system-related problems. Previously, we compared the use of ABS and SDS for modelling agents' behaviour in an environment with nomovement or interactions between these agents. We concluded that for these types of agents it is preferable to use SDS, as it takes up less computational resources and produces the same results as those obtained by the ABS model. In order to move this research forward, our next research question is: if we introduce interactions between these agents will SDS still be the most appropriate paradigm to be used? To answer this question for immune system simulation problems, we will use, as case studies, models involving interactions between tumour cells and immune effector cells. Experiments show that there are cases where SDS and ABS can not be used interchangeably, and therefore, their comparison is not straightforward.Comment: 8 pages, 8 figures, 2 tables, International Summer Computer Simulation Conference 201

Robust Processing of Natural Language

Previous approaches to robustness in natural language processing usually treat deviant input by relaxing grammatical constraints whenever a successful analysis cannot be provided by ``normal'' means. This schema implies, that error detection always comes prior to error handling, a behaviour which hardly can compete with its human model, where many erroneous situations are treated without even noticing them. The paper analyses the necessary preconditions for achieving a higher degree of robustness in natural language processing and suggests a quite different approach based on a procedure for structural disambiguation. It not only offers the possibility to cope with robustness issues in a more natural way but eventually might be suited to accommodate quite different aspects of robust behaviour within a single framework.Comment: 16 pages, LaTeX, uses pstricks.sty, pstricks.tex, pstricks.pro, pst-node.sty, pst-node.tex, pst-node.pro. To appear in: Proc. KI-95, 19th German Conference on Artificial Intelligence, Bielefeld (Germany), Lecture Notes in Computer Science, Springer 199

Muscle Synergies Facilitate Computational Prediction of Subject-Specific Walking Motions.

Researchers have explored a variety of neurorehabilitation approaches to restore normal walking function following a stroke. However, there is currently no objective means for prescribing and implementing treatments that are likely to maximize recovery of walking function for any particular patient. As a first step toward optimizing neurorehabilitation effectiveness, this study develops and evaluates a patient-specific synergy-controlled neuromusculoskeletal simulation framework that can predict walking motions for an individual post-stroke. The main question we addressed was whether driving a subject-specific neuromusculoskeletal model with muscle synergy controls (5 per leg) facilitates generation of accurate walking predictions compared to a model driven by muscle activation controls (35 per leg) or joint torque controls (5 per leg). To explore this question, we developed a subject-specific neuromusculoskeletal model of a single high-functioning hemiparetic subject using instrumented treadmill walking data collected at the subject's self-selected speed of 0.5 m/s. The model included subject-specific representations of lower-body kinematic structure, foot-ground contact behavior, electromyography-driven muscle force generation, and neural control limitations and remaining capabilities. Using direct collocation optimal control and the subject-specific model, we evaluated the ability of the three control approaches to predict the subject's walking kinematics and kinetics at two speeds (0.5 and 0.8 m/s) for which experimental data were available from the subject. We also evaluated whether synergy controls could predict a physically realistic gait period at one speed (1.1 m/s) for which no experimental data were available. All three control approaches predicted the subject's walking kinematics and kinetics (including ground reaction forces) well for the model calibration speed of 0.5 m/s. However, only activation and synergy controls could predict the subject's walking kinematics and kinetics well for the faster non-calibration speed of 0.8 m/s, with synergy controls predicting the new gait period the most accurately. When used to predict how the subject would walk at 1.1 m/s, synergy controls predicted a gait period close to that estimated from the linear relationship between gait speed and stride length. These findings suggest that our neuromusculoskeletal simulation framework may be able to bridge the gap between patient-specific muscle synergy information and resulting functional capabilities and limitations

A Neural Network Model for Cursive Script Production

This article describes a neural network model, called the VITEWRITE model, for generating handwriting movements. The model consists of a sequential controller, or motor program, that interacts with a trajectory generator to move a. hand with redundant degrees of freedom. The neural trajectory generator is the Vector Integration to Endpoint (VITE) model for synchronous variable-speed control of multijoint movements. VITE properties enable a simple control strategy to generate complex handwritten script if the hand model contains redundant degrees of freedom. The proposed controller launches transient directional commands to independent hand synergies at times when the hand begins to move, or when a velocity peak in a given synergy is achieved. The VITE model translates these temporally disjoint synergy commands into smooth curvilinear trajectories among temporally overlapping synergetic movements. The separate "score" of onset times used in most prior models is hereby replaced by a self-scaling activity-released "motor program" that uses few memory resources, enables each synergy to exhibit a unimodal velocity profile during any stroke, generates letters that are invariant under speed and size rescaling, and enables effortless. connection of letter shapes into words. Speed and size rescaling are achieved by scalar GO and GRO signals that express computationally simple volitional commands. Psychophysical data concerning band movements, such as the isochrony principle, asymmetric velocity profiles, and the two-thirds power law relating movement curvature and velocity arise as emergent properties of model interactions.National Science Foundation (IRI 90-24877, IRI 87-16960); Office of Naval Research (N00014-92-J-1309); Air Force Office of Scientific Research (F49620-92-J-0499); Defense Advanced Research Projects Agency (90-0083