A physical model of cell metabolism

Cell metabolism is characterized by three fundamental energy demands: to sustain cell maintenance, to trigger aerobic fermentation and to achieve maximum metabolic rate. The transition to aerobic fermentation and the maximum metabolic rate are currently understood based on enzymatic cost constraints. Yet, we are lacking a theory explaining the maintenance energy demand. Here we report a physical model of cell metabolism that explains the origin of these three energy scales. Our key hypothesis is that the maintenance energy demand is rooted on the energy expended by molecular motors to fluidize the cytoplasm and counteract molecular crowding. Using this model and independent parameter estimates we make predictions for the three energy scales that are in quantitative agreement with experimental values. The model also recapitulates the dependencies of cell growth with extracellular osmolarity and temperature. This theory brings together biophysics and cell biology in a tractable model that can be applied to understand key principles of cell metabolism

Characterizing steady states of genome-scale metabolic networks in continuous cell cultures

We present a model for continuous cell culture coupling intra-cellular metabolism to extracellular variables describing the state of the bioreactor, taking into account the growth capacity of the cell and the impact of toxic byproduct accumulation. We provide a method to determine the steady states of this system that is tractable for metabolic networks of arbitrary complexity. We demonstrate our approach in a toy model first, and then in a genome-scale metabolic network of the Chinese hamster ovary cell line, obtaining results that are in qualitative agreement with experimental observations. More importantly, we derive a number of consequences from the model that are independent of parameter values. First, that the ratio between cell density and dilution rate is an ideal control parameter to fix a steady state with desired metabolic properties invariant across perfusion systems. This conclusion is robust even in the presence of multi-stability, which is explained in our model by the negative feedback loop on cell growth due to toxic byproduct accumulation. Moreover, a complex landscape of steady states in continuous cell culture emerges from our simulations, including multiple metabolic switches, which also explain why cell-line and media benchmarks carried out in batch culture cannot be extrapolated to perfusion. On the other hand, we predict invariance laws between continuous cell cultures with different parameters. A practical consequence is that the chemostat is an ideal experimental model for large-scale high-density perfusion cultures, where the complex landscape of metabolic transitions is faithfully reproduced. Thus, in order to actually reflect the expected behavior in perfusion, performance benchmarks of cell-lines and culture media should be carried out in a chemostat

The quantum Arnold transformation

By a quantum version of the Arnold transformation of classical mechanics, all quantum dynamical systems whose classical equations of motion are non-homogeneous linear second-order ordinary differential equations, including systems with friction linear in velocity, can be related to the quantum free-particle dynamical system. This transformation provides a basic (Heisenberg-Weyl) algebra of quantum operators, along with well-defined Hermitian operators which can be chosen as evolution-like observables and complete the entire Schr\"odinger algebra. It also proves to be very helpful in performing certain computations quickly, to obtain, for example, wave functions and closed analytic expressions for time-evolution operators.Comment: 19 pages, minor changes, references update

Temperature modelling and model predictive control of a pilot-scale batch reaction system

The temperature control equipment on a pilot scale batch reaction system located at EAFIT University in Medelln, Colombia, is modeled and a new controller is designed aiming at using it in the reactor current PLC-based control system. Some mathematical models are developed from experimental data to describe the system behavior and using them several model based predictive controllers are designed. The simplest, yet reliable, model obtained is an ARX polynomial model of order (1,1,1) that yields a four states ane model for which an explicit MPC was calculated. This controller has a reduced mathematical complexity and can probably be used directly on the existing control system.Preprin

Existence of multiple solutions for a quasilinear elliptic problem

In this paper we prove the existence of multiple solutions for a quasilinear elliptic boundary value problem, when the p-derivative at zero and the p-derivative at infinity of the nonlinearity are greater than the first eigenvalue of the p-Laplace operator. Our proof uses bifurcation from infinity and bifurcation from zero to prove the existence of unbounded branches of positive solutions (resp. of negative solutions). We show the existence of multiple solutions and we provide qualitative properties of these solutions

Fomento público a la creación de empresas: caso Chocó 2009 - 2014

El Departamento de Chocó Es sujeto de derecho de la normatividad estatal que le debe brindar la oportunidad de acceder a programas, proyectos y estrategias del orden nacional que buscan fomentar la Creación de Empresas en todo el territorio Colombiano al igual que los otros 31 departamentos que integran esta Nación -- Aun así sigue ocupando según el DANE, los mayores índices de pobreza extrema, severidad de la pobreza y necesidades básicas insatisfechas en Colombia, no cuenta con un Sector Empresarial desarrollado y son pocas las fuentes de empleo para sus habitantes -- En este artículo se presenta un acercamiento a la realidad empresarial del departamento de Chocó, resultado de un análisis descriptivo de la base de datos de empresas registradas en la Cámara de comercio de Chocó entre los años 2009 y 2014 como respuesta a la implementación de la Política Nacional de Competitividad y Productividad “CONPES 3527” del 23 de junio de 2008 -- La información se obtuvo por medio de acercamiento a la oficina de planeación de la Cámara de Comercio de Chocó y a la consulta de normas y reglamentaciones encaminadas al fomento público para la creación de empresas en ColombiaThe Department of Chocó is the subject of law of state regulations that should be given the opportunity to access programs, projects and strategies at the national level that seek to promote Entrepreneurship throughout the Colombian territory like the other 31 departments that make this Nation -- Still remains high according to DANE, the highest rates of extreme poverty, severity of poverty and unmet basic needs in Colombia, does not have a developed business sector and few jobs for its inhabitants -- In this paper an approach to business reality department collided, resulting from a descriptive analysis of the database registered in the Chamber of Commerce Chocó between 2009 and 2014 companies in response to the implementation of the policy presented national Competitiveness and Productivity "COMPES 3527" from June 23, 2008 -- The information was obtained by means of approach to the planning office of the Chamber of Commerce and Choco consultation of rules and regulations designed to promote public entrepreneurship in Colombi