0000000000300218
AUTHOR
Jesús Picó
MCR-ALS on metabolic networks: Obtaining more meaningful pathways
[EN] With the aim of understanding the flux distributions across a metabolic network, i.e. within living cells, Principal Component Analysis (PCA) has been proposed to obtain a set of orthogonal components (pathways) capturing most of the variance in the flux data. The problems with this method are (i) that no additional information can be included in the model, and (ii) that orthogonality imposes a hard constraint, not always reasonably. To overcome these drawbacks, here we propose to use a more flexible approach such as Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) to obtain this set of biological pathways through the network. By using this method, different constraint…
Metabolic flux understanding of Pichia pastoris grown on heterogenous culture media
[EN] Within the emergent field of Systems Biology, mathematical models obtained from physical chemical laws (the so-called first principles-based models) of microbial systems are employed to discern the principles that govern cellular behaviour and achieve a predictive understanding of cellular functions. The reliance on this biochemical knowledge has the drawback that some of the assumptions (specific kinetics of the reaction system, unknown dynamics and values of the model parameters) may not be valid for all the metabolic possible states of the network. In this uncertainty context, the combined use of fundamental knowledge and data measured in the fermentation that describe the behaviour…
Controller Design Under Fuzzy Pole-Placement Specifications: An Interval Arithmetic Approach
This paper discusses fuzzy specifications for robust controller design, as a way to define different specification levels for different plants in a family and allow the control of performance degradation. Controller synthesis will be understood as mapping a fuzzy plant onto a desired fuzzy set of closed-loop specifications. In this context, a fuzzy plant is considered as a possibility distribution on a given plant space. In particular, pole placement in linear plants with fuzzy parametric uncertainty is discussed, although the basic idea is general and could be applied to other settings. In the case under consideration, the controller coefficients are the solution of a fuzzy linear system o…
Estimation of recombinant protein production in Pichia pastoris base don a constraint-based model
[EN] A previously validated constraint based model and possibilistic MFA have been used to design a simple estimator of protein production rate in Pichia pastoris cultures. A structured model of the yeast P. pastoris metabolism is used to predict the balance of key energetic equivalents such as ATP from available measurements, mainly substrate consumption, gases exchange rates and biomass specific growth. It has been shown that ATP flux can be related to biomass growth and protein productivity specific rates by linear regression. Cross-validation has been applied for robust parameter fitting on the basis of chemostat, steady-state experimental conditions. In this way, protein estimation can…
Guaranteed tuning of PID controllers for parametric uncertain systems
This paper presents a methodology for tuning the controller of a parametric uncertain plant in order to guarantee the satisfaction of specifications. These specifications are defined by means of an interval reference model that represents the set of satisfactory time or frequency behaviors. The controller synthesis is then formulated as a set-inclusion problem in the frequency domain. Interval techniques for the solution of constraint satisfaction problems are applied to design fixed-structure controllers in a guaranteed manner. In particular, PID controllers are considered since they are widely used in industry.
Comprehensive pharmacokinetic model of insulin Glargine and other insulin formulations.
In this paper, a comprehensive pharmacokinetic model for different insulin formulations including insulin Glargine is developed based on the model proposed by Trajanoski et al. (1993). Current models show limitations for insulin Glargine due to the appearance of an uncharacteristic peak in the concentration-time evolution of plasma insulin that does not coincide with real experimental data. This important limitation has been solved in this paper by introducing a new virtual insulin state called the bound state, in addition to the dimeric and hexameric ones. Trying to describe the retarded action of insulin Glargine, the modeling idea behind this approach is that immediately after the subcut…
Partial stability for specific growth rate control biotechnological fed-batch processes
In this paper, the problem of the specific growth rate control in biological reactions in fed-batch mode is dealt with. It is assumed that only part of the state is measurable on-line, namely biomass and volume. Moreover, no estimation of the specific growth rate is used. An unbounded manifold is tracked using a partial state feedback. Then, techniques for partial stability, i.e., only with respect to part of the variables, are used in order to analyze the problem.