Proteome-Wide Structural Computations Provide Insights into Empirical Amino Acid Substitution Matrices

The relative contribution of mutation and selection to the amino acid substitution rates observed in empirical matrices is unclear. Herein, we present a neutral continuous fitness-stability model, inspired by the Arrhenius law (qij=aije−|ΔΔGij| ). The model postulates that the rate of amino acid substitution (i→j ) is determined by the product of a pre-exponential factor, which is influenced by the genetic code structure, and an exponential term reflecting the relative fitness of the amino acid substitutions. To assess the validity of our model, we computed changes in stability of 14,094 proteins, for which 137,073,638 in silico mutants were analyzed. These site-specific data were summarized into a 20 square matrix, whose entries, |ΔΔGij| , were obtained after averaging through all the sites in all the proteins. We found a significant positive correlation between these energy values and the disease-causing potential of each substitution, suggesting that the exponential term accurately summarizes the fitness effect. A remarkable observation was that amino acids that were highly destabilizing when acting as the source, tended to have little effect when acting as the destination, and vice versa (source → destination). The Arrhenius model accurately reproduced the pattern of substitution rates collected in the empirical matrices, suggesting a relevant role for the genetic code structure and a tuning role for purifying selection exerted via protein stability.Partial funding for open access charge: Universidad de Málag

Inequality and megaprojects: the Panama Canal expansion

Cuando el control y gestión del Canal de Panamá pasó al estado panameño a finales de 1999, el gobierno comenzó a preparar un plan para su modernización. Este plan incluía la construcción de nuevas esclusas para que pudieran atravesarlo un mayor número de barcos y que admitiese los nuevos buques Post-Panamax de gran tamaño. El proyecto de Ampliación del Canal se ha seleccionado como ejemplo paradigmático de Grandes Obras Públicas (GOP) por su impacto ambiental, económico y social. Este caso de estudio nos servirá para reflexionar sobre las relaciones que existen entre desigualdad, desarrollo y medio ambiente. El artículo se estructura como sigue: 1) se hará una rápida presentación del Canal y de su funcionamiento; 2) se analizarán las diferentes propuestas y alternativas de modernización y ampliación que se han hecho desde el órgano gestor del Canal la Autoridad del Canal de Panamá (ACP); 3) se describirá la forma en que la ACP está gestionando socialmente el proyecto; 4) por último, se llevará a cabo una reflexión sobre las relaciones entre GOP, desigualdad, poder y riesgo.The Panama Canal is one of the fundamental global transoceanic routes. In 1999 and after the management of the Canal was returned to the state of Panama, the PCA, a public/private organism, was formalised. The PCA is in charge of the management of boat traffic as well as the maintenance of this infrastructure. In 1999 a Master Plan was developed with the aim of modernizing the Canal to adapt it to the necessities of global maritime traffic as the carrying capacity of very large boats increased. The final output of the project is the construction of two new and larger locks. This case study has been selected as a paradigmatic example of megaprojects due to its huge environmental, economic and social impacts. Its analysis will improve the knowledge about the relationship among inequality, development and environment.This article is divided into the following parts: 1) a brief presentation of the Canal and its technical management; 2) an analysis of the different alternatives offered for its enlargement proposed by PCA; 3) a description of the social management of the project and 4) an analysis of the relationship among megaprojects, inequalities, power and risk

The Codazzi Equation for Surfaces

In this paper we develop an abstract theory for the Codazzi equation on surfaces, and use it as an analytic tool to derive new global results for surfaces in the space forms {\bb R}^3, {\bb S}^3 and {\bb H}^3. We give essentially sharp generalizations of some classical theorems of surface theory that mainly depend on the Codazzi equation, and we apply them to the study of Weingarten surfaces in space forms. In particular, we study existence of holomorphic quadratic differentials, uniqueness of immersed spheres in geometric problems, height estimates, and the geometry and uniqueness of complete or properly embedded Weingarten surfaces

You communicate, therefore exist? A critique to the ideology of the communication

Este artículo se aproxima al impacto que las diversas posibilidades y usos que ofrecen los medios tecnológicos de la comunicación, insertos en el marco de una cultura de consumo, tienen respecto a determinadas categorías existenciales y éticas. Comunicas,Tthis article deals with the impact that, in relation with certain existential and ethical categories, has the diverse uses and possibilities that new technologies applied to communication and mass media grant to us today. You communicate, so you exist

Digital Background Self-Calibration Technique for Compensating Transition Offsets in Reference-less Flash ADCs

This Dissertation focusses on proving that background calibration using adaptive algorithms are low-cost, stable and effective methods for obtaining high accuracy in flash A/D converters. An integrated reference-less 3-bit flash ADC circuit has been successfully designed and taped out in UMC 180 nm CMOS technology in order to prove the efficiency of our proposed background calibration. References for ADC transitions have been virtually implemented built-in in the comparators dynamic-latch topology by a controlled mismatch added to each comparator input front-end. An external very simple DAC block (calibration bank) allows control the quantity of mismatch added in each comparator front-end and, therefore, compensate the offset of its effective transition with respect to the nominal value. In order to assist to the estimation of the offset of the prototype comparators, an auxiliary A/D converter with higher resolution and lower conversion speed than the flash ADC is used: a 6-bit capacitive-DAC SAR type. Special care in synchronization of analogue sampling instant in both ADCs has been taken into account. In this thesis, a criterion to identify the optimum parameters of the flash ADC design with adaptive background calibration has been set. With this criterion, the best choice for dynamic latch architecture, calibration bank resolution and flash ADC resolution are selected. The performance of the calibration algorithm have been tested, providing great programmability to the digital processor that implements the algorithm, allowing to choose the algorithm limits, accuracy and quantization errors in the arithmetic. Further, systematic controlled offset can be forced in the comparators of the flash ADC in order to have a more exhaustive test of calibration