Knowledge management for systems biology a general and visually driven framework applied to translational medicine

Background: To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined. Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature. Existing knowledge such as genotype - phenotype relations or signal transduction pathways must be semantically integrated and dynamically organised into structured networks that are connected with clinical and experimental data. Different approaches to this challenge exist but so far none has proven entirely satisfactory. Results: To address this challenge we previously developed a generic knowledge management framework, BioXM™, which allows the dynamic, graphic generation of domain specific knowledge representation models based on specific objects and their relations supporting annotations and ontologies. Here we demonstrate the utility of BioXM for knowledge management in systems biology as part of the EU FP6 BioBridge project on translational approaches to chronic diseases. From clinical and experimental data, text-mining results and public databases we generate a chronic obstructive pulmonary disease (COPD) knowledge base and demonstrate its use by mining specific molecular networks together with integrated clinical and experimental data. Conclusions: We generate the first semantically integrated COPD specific public knowledge base and find that for the integration of clinical and experimental data with pre-existing knowledge the configuration based set-up enabled by BioXM reduced implementation time and effort for the knowledge base compared to similar systems implemented as classical software development projects. The knowledgebase enables the retrieval of sub-networks including protein-protein interaction, pathway, gene - disease and gene - compound data which are used for subsequent data analysis, modelling and simulation. Pre-structured queries and reports enhance usability; establishing their use in everyday clinical settings requires further simplification with a browser based interface which is currently under development.

Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

Background: The arrangement of regulatory motifs in gene promoters, or promoterarchitecture, is the result of mutation and selection processes that have operated over manymillions of years. In mammals, tissue-specific transcriptional regulation is related to the presence ofspecific protein-interacting DNA motifs in gene promoters. However, little is known about therelative location and spacing of these motifs. To fill this gap, we have performed a systematic searchfor motifs that show significant bias at specific promoter locations in a large collection ofhousekeeping and tissue-specific genes.Results: We observe that promoters driving housekeeping gene expression are enriched inparticular motifs with strong positional bias, such as YY1, which are of little relevance in promotersdriving tissue-specific expression. We also identify a large number of motifs that show positionalbias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specificmotifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis,as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictionsfor 559 tissue-specific motifs in mouse gene promoters.Conclusion: The study shows that motif positional bias is an important feature of mammalianproximal promoters and that it affects both general and tissue-specific motifs. Motif positionalconstraints define very distinct promoter architectures depending on breadth of expression andtype of tissue.

The communicative dimension of landscape. A theoretical and applied proposal

The fusion of knowledge, the interrelationship of disciplines and, finally, the interaction of learning fields, provides new challenges for an auto denominated global society. The contemporary value of landscape, linked to the patent commodification of culture, the commercial construction of identities, the triumph of inauthenticity, of the induced representation or the economy of symbolism, open up great prospects for studying the symbolic value of landscape. The rapprochement of geographical praxis to the study of space intangibles, linked to the discovery of emotional geographies, besides the growing interest of communicational sciences on the territorial discourse, allow us to envisage a communicative study of landscape based on a fusion of geographical and communicational knowledge. The balancing of the variables: geography, landscape, emotion and communication, enables the progress towards analysing the emotionalisation of space to discern its intangible value, which emerges from the application of different communication techniques.

Análisis de la enseñanza-aprendizaje y evaluación de competencias transversales en general, y de la competencia de la comunicación escrita en particular, en currículos TIC

Este Proyecto Fin de Carrera, pertenece al área de 'Competencias profesionales' y tiene como objetivo el análisis de diversas experiencias de enseñanza-aprendizaje y de evaluación de competencias transversales, haciendo hincapié en la competencia de la comunicación escrita, dentro de la formación de currículos TIC. El análisis se centra en los planes de estudios del Grado en Ingeniería Informática de 10 universidades españolas representativas (públicas, privadas y a distancia) como representación de la "nueva" formación de currículos TIC en nuestra sociedad.

Del discurso a la lexicografía: propuesta de aplicación para los conectores reformulativos

This paper aims at defending the necessity of creating applicationsfrom studies on discourse, so that applied linguistics becomes auseful tool for the society. This work explains briefly what reformulation connectors are and it shows the electronic prototype (than can be consulted by internet) of a tool designed to make the work of lexicographerseasy concerning the entrance of connectors in the dictionaries (ALCOR), by making emphasis on the theoretical base on which it is sustained and on the decisions of application that have been taken into account.

Stationarity analysis of historical flood series in France and Spain (14th-20th centuries)

Interdisciplinary frameworks for studying natural hazards and their temporal trends have an important potential in data generation for risk assessment, land use planning, and therefore the sustainable management of resources. This paper focuses on the adjustments required because of the wide variety of scientific fields involved in the reconstruction and characterisation of flood events for the past 1000 years. The aim of this paper is to describe various methodological aspects of the study of flood events in their historical dimension, including the critical evaluation of old documentary and instrumental sources, flood-event classification and hydraulic modelling, and homogeneity and quality control tests. Standardized criteria for flood classification have been defined and applied to the Isère and Drac floods in France, from 1600 to 1950, and to the Ter, the Llobregat and the Segre floods, in Spain, from 1300 to 1980. The analysis on the Drac and Isère data series from 1600 to the present day showed that extraordinary and catastrophic floods were not distributed uniformly in time. However, the largest floods (general catastrophic floods) were homogeneously distributed in time within the period 1600¿1900. No major flood occurred during the 20th century in these rivers. From 1300 to the present day, no homogeneous behaviour was observed for extraordinary floods in the Spanish rivers. The largest floods were uniformly distributed in time within the period 1300-1900, for the Segre and Ter rivers.

Decay of unstable states in the presence of colored noise and random initial conditions. I. Theory of nonlinear relaxation times

The general theory of nonlinear relaxation times is developed for the case of Gaussian colored noise. General expressions are obtained and applied to the study of the characteristic decay time of unstable states in different situations, including white and colored noise, with emphasis on the distributed initial conditions. Universal effects of the coupling between colored noise and random initial conditions are predicted.

RNA interference: a new and powerful tool for functional genomic analysis.

In many species, the introduction of double-stranded RNA induces potent and specific gene silencing, referred to as RNA interference. This phenomenon, which is based on targeted degradation of mRNAs and occurs in almost any eukaryote, from trypanosomes to mice including plants and fungi, has sparked general interest from both applied and fundamental standpoints. RNA interference, which is currently used to investigate gene function in a variety of systems, is linked to natural resistance to viruses and transposon silencing, as if it were a primitive immune system involved in genome surveillance. Here, we review the mechanism of RNA interference in post-transcriptional gene silencing, its function in nature, its value for functional genomic analysis, and the modifications and improvements that may make it more efficient and inheritable. We also discuss the future directions of this versatile technique in both fundamental and applied science.

Asymptotic analysis of stock price densities and implied volatilities in mixed stochastic models

In this paper, we obtain sharp asymptotic formulas with error estimates for the Mellin con- volution of functions de ned on (0;1), and use these formulas to characterize the asymptotic behavior of marginal distribution densities of stock price processes in mixed stochastic models. Special examples of mixed models are jump-di usion models and stochastic volatility models with jumps. We apply our general results to the Heston model with double exponential jumps, and make a detailed analysis of the asymptotic behavior of the stock price density, the call option pricing function, and the implied volatility in this model. We also obtain similar results for the Heston model with jumps distributed according to the NIG law.

Asymmetries in the capacity-inflation trade-off

This paper analyzes the joint dynamics of two key macroeconomic variables for the conduct of monetary policy: inflation and the aggregate capacity utilization rate. An econometric procedure useful for estimating dynamic rational expectation models with unobserved components is developed and applied in this context. The method combines the flexibility of the unobserved components approach, based on the Kalman recursion, with the power of the general method of moments estimation procedure. A 'hyb id' Phillips curve relating inflation to the capacity utilization gap and incorporating forward and backward looking components is estimated. The results show that such a relationship in non-linear: the slope of the Phillips curve depends significantly on the magnitude of the capacity gap. These findings provide support for studying the implications of asymmetricmonetary policy rules.

Contractive probability metrics and asymptotic behavior of dissipative kinetic equations

The present notes are intended to present a detailed review of the existing results in dissipative kinetic theory which make use of the contraction properties of two main families of probability metrics: optimal mass transport and Fourier-based metrics. The first part of the notes is devoted to a self-consistent summary and presentation of the properties of both probability metrics, including new aspects on the relationships between them and other metrics of wide use in probability theory. These results are of independent interest with potential use in other contexts in Partial Differential Equations and Probability Theory. The second part of the notes makes a different presentation of the asymptotic behavior of Inelastic Maxwell Models than the one presented in the literature and it shows a new example of application: particle's bath heating. We show how starting from the contraction properties in probability metrics, one can deduce the existence, uniqueness and asymptotic stability in classical spaces. A global strategy with this aim is set up and applied in two dissipative models.

Point-occurrence self-similarity in crackling-noise systems and in other complex systems

It has been recently found that a number of systems displaying crackling noise also show a remarkable behavior regarding the temporal occurrence of successive events versus their size: a scaling law for the probability distributions of waiting times as a function of a minimum size is fulfilled, signaling the existence on those systems of self-similarity in time-size. This property is also present in some non-crackling systems. Here, the uncommon character of the scaling law is illustrated with simple marked renewal processes, built by definition with no correlations. Whereas processes with a finite mean waiting time do not fulfill a scaling law in general and tend towards a Poisson process in the limit of very high sizes, processes without a finite mean tend to another class of distributions, characterized by double power-law waiting-time densities. This is somehow reminiscent of the generalized central limit theorem. A model with short-range correlations is not able to escape from the attraction of those limit distributions. A discussion on open problems in the modeling of these properties is provided.

Relationship between technological progress, capital elasticity and emissions of industrial pollutants for the production sectors in Catalonia

As is known, the Kyoto Protocol proposes to reinforce national policies for emission reduction and, furthermore, to cooperate with other contracting parties. In this context, it would be necessary to assess these emissions, both in general and specifically, by pollutants and/or among productive sectors. The object of this paper is precisely to estimate the polluting emissions of industrial origin in Catalonia in the year 2001, in a multivariate context which explicitly allows a distinction to be made between the polluter and/or the productive sector causing this emission. Six pollutants considered, four directly related to greenhouse effect. A multi-level model, with two levels, pollutants and productive sectors, was specified. Both technological progress and elasticity of capital were introduced as random effects. Hence, it has been permitted that these coefficients vary according to one or other level. The most important finding in this paper is that elasticity of capital has been estimated as very non-elastic, with a range which varies between 0.162 (the paper industry) and 0.556 (commerce). In fact, and generally speaking, the greater capital the sector has, the less elasticity of capital has been estimated. Key words: Kyoto protocol, multilevel model, technological progress

Paraphrasing : scope and typology : a computational approach

This PhD project aims to study paraphrasing, initially understood as the different ways in which the same content is expressed linguistically. We will go into that concept in depth trying to define and delimit its scope more accurately. In that sense, we also aim to discover which kind of structures and phenomena it covers. Although there exist some paraphrasing typologies, the great majority of them only apply to English, and focus on lexical and syntactic transformations. Our intention is to go further into this subject and propose a paraphrasing typology for Spanish and Catalan combining lexical, syntactic, semantic and pragmatic knowledge. We apply a bottom-up methodology trying to collect evidence of this phenomenon from the data. For this purpose, we are initially using the Spanish Wikipedia as our corpus. The internal structure of this encyclopedia makes it a good resource for extracting paraphrasing examples for our investigation. This empirical approach will be complemented with the use of linguistic knowledge, and by comparing and contrasting our results to previously proposed paraphrasing typologies in order to enlarge the possible paraphrasing forms found in our corpus. The fact that the same content can be expressed in many different ways presents a major challenge for Natural Language Processing (NLP) applications. Thus, research on paraphrasing has recently been attracting increasing attention in the fields of NLP and Computational Linguistics. The results obtained in this investigation would be of great interest in many of these applications.

Activem la filosofia del llenguatge

En el projecte de millora de la qualitat docent “Activem al filosofia del llenguatge” hi han participat 11 professors i professores de la Universitat de Barcelona, la Universitat Autònoma de Barcelona, la Universitat de Girona i la Universitat Rovira i Virgili. Aquest grup de docents constitueixen la pràctica totalitat del professors que imparteixen regularment matèries de filosofia del llenguatge en les universitats catalanes. Aquest projecte ha consistit en dissenyar, elaborar i aplicar diferents eines que tenen per objectiu ajudar als alumnes a passar d’una actitud passiva de receptors de classes, a una actitud activa vers els continguts dels cursos troncals de filosofia del llenguatge. La contribució al canvi d’actitud del “rebre” al “fer” s’ha buscat amb la combinació de diferents propostes: la selecció de textos clàssics breus, importants i clars que els estudiants tenien que llegir i rellegir amb deteniment relacionats amb cadascun dels temes tractats en el curs i, vinculat a això, l’elaboració de “preguntes per a guiar la lectura” que ajuden als estudiants a centrar la atenció en els aspectes més pertinents i importants de cadascun d’aquests textos, l’elaboració de dossiers electrònics vinculats a cadascun dels diferents temes que es tracten en aquests cursos, l’elaboració per a cadascun dels temes de diferents exercicis i “preguntes de discussió”, la creació d’un fòrum de discussió electrònic, i la celebració de “jornades de debat” que es centraven en algunes de les “preguntes de discussió”. Hem pogut constatar la necessitat de trobar en el futur maneres d’aplicar les diferents eines que hem dissenyat de forma que els estudiants facin ús de forma encara més general d’aquestes eines.