¿Favorece la publicación en abierto el impacto de los artículos científicos? Un estudio empírico en el ámbito de la medicina intensiva

Peer-reviewed

Quantitative modelling of transcription factor binding sites

Abstract One of the most important issues in molecular biology is to understand regulatory mechanisms that control gene expression. Gene expression is often regulated by proteins, called transcription factors which bind to short (5 to 20 base pairs),degenerate segments of DNA. Experimental efforts towards understanding the sequence specificity of transcription factors is laborious and expensive, but can be substantially accelerated with the use of computational predictions. This thesis describes the use of algorithms and resources for transcriptionfactor binding site analysis in addressing quantitative modelling, where probabilitic models are built to represent binding properties of a transcription factor and can be used to find new functional binding sites in genomes. Initially, an open-access database(HTPSELEX) was created, holding high quality binding sequences for two eukaryotic families of transcription factors namely CTF/NF1 and LEFT/TCF. The binding sequences were elucidated using a recently described experimental procedure called HTP-SELEX, that allows generation of large number (> 1000) of binding sites using mass sequencing technology. For each HTP-SELEX experiments we also provide accurate primary experimental information about the protein material used, details of the wet lab protocol, an archive of sequencing trace files, and assembled clone sequences of binding sequences. The database also offers reasonably large SELEX libraries obtained with conventional low-throughput protocols.The database is available at http://wwwisrec.isb-sib.ch/htpselex/ and and ftp://ftp.isrec.isb-sib.ch/pub/databases/htpselex. The Expectation-Maximisation(EM) algorithm is one the frequently used methods to estimate probabilistic models to represent the sequence specificity of transcription factors. We present computer simulations in order to estimate the precision of EM estimated models as a function of data set parameters(like length of initial sequences, number of initial sequences, percentage of nonbinding sequences). We observed a remarkable robustness of the EM algorithm with regard to length of training sequences and the degree of contamination. The HTPSELEX database and the benchmarked results of the EM algorithm formed part of the foundation for the subsequent project, where a statistical framework called hidden Markov model has been developed to represent sequence specificity of the transcription factors CTF/NF1 and LEF1/TCF using the HTP-SELEX experiment data. The hidden Markov model framework is capable of both predicting and classifying CTF/NF1 and LEF1/TCF binding sites. A covariance analysis of the binding sites revealed non-independent base preferences at different nucleotide positions, providing insight into the binding mechanism. We next tested the LEF1/TCF model by computing binding scores for a set of LEF1/TCF binding sequences for which relative affinities were determined experimentally using non-linear regression. The predicted and experimentally determined binding affinities were in good correlation.

UPCommons: global access to Universitat Politècnica de Catalunya (UPC) knowledge

Programa de mà lliurat en la presentació del pòster 'UPCommons', exposat al primer COMMUNIA Workshop on Technology and the Public Domain, celebrat a Torí (Itàlia) el 18 de gener de 2008.

eggNOG v4.0: nested orthology inference across 3686 organisms

With the increasing availability of various 'omics data, high-quality orthology assignment is crucial for evolutionary and functional genomics studies. We here present the fourth version of the eggNOG database (available at http://eggnog.embl.de) that derives nonsupervised orthologous groups (NOGs) from complete genomes, and then applies a comprehensive characterization and analysis pipeline to the resulting gene families. Compared with the previous version, we have more than tripled the underlying species set to cover 3686 organisms, keeping track with genome project completions while prioritizing the inclusion of high-quality genomes to minimize error propagation from incomplete proteome sets. Major technological advances include (i) a robust and scalable procedure for the identification and inclusion of high-quality genomes, (ii) provision of orthologous groups for 107 different taxonomic levels compared with 41 in eggNOGv3, (iii) identification and annotation of particularly closely related orthologous groups, facilitating analysis of related gene families, (iv) improvements of the clustering and functional annotation approach, (v) adoption of a revised tree building procedure based on the multiple alignments generated during the process and (vi) implementation of quality control procedures throughout the entire pipeline. As in previous versions, eggNOGv4 provides multiple sequence alignments and maximum-likelihood trees, as well as broad functional annotation. Users can access the complete database of orthologous groups via a web interface, as well as through bulk download.

Systematic review protocol to define classical IgE-associated diseases from birth to adolescence: the MeDALL study

BACKGROUND: Classical disease phenotypes are mainly based on descriptions of symptoms and the hypothesis that a given pattern of symptoms provides a diagnosis. With refined technologies there is growing evidence that disease expression in patients is much more diverse and subtypes need to be defined to allow a better targeted treatment. One of the aims of the Mechanisms of the Development of Allergy Project (MeDALL,FP7) is to re-define the classical phenotypes of IgE-associated allergic diseases from birth to adolescence, by consensus among experts using a systematic review of the literature and identify possible gaps in research for new disease markers. This paper describes the methods to be used for the systematic review of the classical IgE-associated phenotypes applicable in general to other systematic reviews also addressing phenotype definitions based on evidence. METHODS/DESIGN: Eligible papers were identified by PubMed search (complete database through April 2011). This search yielded 12,043 citations. The review includes intervention studies (randomized and clinical controlled trials) and observational studies (cohort studies including birth cohorts, case-control studies) as well as case series. Systematic and non-systematic reviews, guidelines, position papers and editorials are not excluded but dealt with separately. Two independent reviewers in parallel conducted consecutive title and abstract filtering scans. For publications where title and abstract fulfilled the inclusion criteria the full text was assessed. In the final step, two independent reviewers abstracted data using a pre-designed data extraction form with disagreements resolved by discussion among investigators. DISCUSSION: The systematic review protocol described here allows to generate broad,multi-phenotype reviews and consensus phenotype definitions. The in-depth analysis of the existing literature on the classification of IgE-associated allergic diseases through such a systematic review will 1) provide relevant information on the current epidemiologic definitions of allergic diseases, 2) address heterogeneity and interrelationships and 3) identify gaps in knowledge.

MANAGING STRATEGIC CHANGE:New Business Models Applying Wireless Technology as a Source of Competitive Edge

The diffusion of mobile telephony began in 1971 in Finland, when the first car phones, called ARP1 were taken to use. Technologies changed from ARP to NMT and later to GSM. The main application of the technology, however, was voice transfer. The birth of the Internet created an open public data network and easy access to other types of computer-based services over networks. Telephones had been used as modems, but the development of the cellular technologies enabled automatic access from mobile phones to Internet. Also other wireless technologies, for instance Wireless LANs, were also introduced. Telephony had developed from analog to digital in fixed networks and allowed easy integration of fixed and mobile networks. This development opened a completely new functionality to computers and mobile phones. It also initiated the merger of the information technology (IT) and telecommunication (TC) industries. Despite the arising opportunity for firms' new competition the applications based on the new functionality were rare. Furthermore, technology development combined with innovation can be disruptive to industries. This research focuses on the new technology's impact on competition in the ICT industry through understanding the strategic needs and alternative futures of the industry's customers. The change speed inthe ICT industry is high and therefore it was valuable to integrate the DynamicCapability view of the firm in this research. Dynamic capabilities are an application of the Resource-Based View (RBV) of the firm. As is stated in the literature, strategic positioning complements RBV. This theoretical framework leads theresearch to focus on three areas: customer strategic innovation and business model development, external future analysis, and process development combining these two. The theoretical contribution of the research is in the development of methodology integrating theories of the RBV, dynamic capabilities and strategic positioning. The research approach has been constructive due to the actual managerial problems initiating the study. The requirement for iterative and innovative progress in the research supported the chosen research approach. The study applies known methods in product development, for instance, innovation process in theGroup Decision Support Systems (GDSS) laboratory and Quality Function Deployment (QFD), and combines them with known strategy analysis tools like industry analysis and scenario method. As the main result, the thesis presents the strategic innovation process, where new business concepts are used to describe the alternative resource configurations and scenarios as alternative competitive environments, which can be a new way for firms to achieve competitive advantage in high-velocity markets. In addition to the strategic innovation process as a result, thestudy has also resulted in approximately 250 new innovations for the participating firms, reduced technology uncertainty and helped strategic infrastructural decisions in the firms, and produced a knowledge-bank including data from 43 ICT and 19 paper industry firms between the years 1999 - 2004. The methods presentedin this research are also applicable to other industries.

Cambio social y homogamia educativa

A partir de una amplia revisión bibliográfica y basándose en los datos de un estudio realizado sobre una muestra representativa de la provincia de Lérida (N=1.219) se analiza en este artículo la persistencia de la homogamia educativa en un contexto de expansión de la escolarización, en especial, de las cohortes femeninas españolas nacidas con posterioridad a 1955. Más allá de la controversia de la homogamia frente a la heterogamia los autores interpretan los resultados como ejemplo de los límites al cambio de modelo de enlace matrimonial.

Secure many-to-one communications in wireless sensor networks

Wireless Sensor Networks (WSN) are formed by nodes with limited computational and power resources. WSNs are finding an increasing number of applications, both civilian and military, most of which require security for the sensed data being collected by the base station from remote sensor nodes. In addition, when many sensor nodes transmit to the base station, the implosion problem arises. Providing security measures and implosion-resistance in a resource-limited environment is a real challenge. This article reviews the aggregation strategies proposed in the literature to handle the bandwidth and security problems related to many-to-one transmission in WSNs. Recent contributions to secure lossless many-to-one communication developed by the authors in the context of several Spanish-funded projects are surveyed. Ongoing work on the secure lossy many-to-one communication is also sketched.

In silico pathway reconstruction: Iron-sulfur cluster biogenesis in Saccharomyces cerevisiae

Background: Current advances in genomics, proteomics and other areas of molecular biology make the identification and reconstruction of novel pathways an emerging area of great interest. One such class of pathways is involved in the biogenesis of Iron-Sulfur Clusters (ISC). Results: Our goal is the development of a new approach based on the use and combination of mathematical, theoretical and computational methods to identify the topology of a target network. In this approach, mathematical models play a central role for the evaluation of the alternative network structures that arise from literature data-mining, phylogenetic profiling, structural methods, and human curation. As a test case, we reconstruct the topology of the reaction and regulatory network for the mitochondrial ISC biogenesis pathway in S. cerevisiae. Predictions regarding how proteins act in ISC biogenesis are validated by comparison with published experimental results. For example, the predicted role of Arh1 and Yah1 and some of the interactions we predict for Grx5 both matches experimental evidence. A putative role for frataxin in directly regulating mitochondrial iron import is discarded from our analysis, which agrees with also published experimental results. Additionally, we propose a number of experiments for testing other predictions and further improve the identification of the network structure. Conclusion: We propose and apply an iterative in silico procedure for predictive reconstruction of the network topology of metabolic pathways. The procedure combines structural bioinformatics tools and mathematical modeling techniques that allow the reconstruction of biochemical networks. Using the Iron Sulfur cluster biogenesis in S. cerevisiae as a test case we indicate how this procedure can be used to analyze and validate the network model against experimental results. Critical evaluation of the obtained results through this procedure allows devising new wet lab experiments to confirm its predictions or provide alternative explanations for further improving the models.

Minimization of biosynthetic costs in adaptive gene expression responses of yeast to environmental changes

Yeast successfully adapts to an environmental stress by altering physiology and fine-tuning metabolism. This fine-tuning is achieved through regulation of both gene expression and protein activity, and it is shaped by various physiological requirements. Such requirements impose a sustained evolutionary pressure that ultimately selects a specific gene expression profile, generating a suitable adaptive response to each environmental change. Although some of the requirements are stress specific, it is likely that others are common to various situations. We hypothesize that an evolutionary pressure for minimizing biosynthetic costs might have left signatures in the physicochemical properties of proteins whose gene expression is fine-tuned during adaptive responses. To test this hypothesis we analyze existing yeast transcriptomic data for such responses and investigate how several properties of proteins correlate to changes in gene expression. Our results reveal signatures that are consistent with a selective pressure for economy in protein synthesis during adaptive response of yeast to various types of stress. These signatures differentiate two groups of adaptive responses with respect to how cells manage expenditure in protein biosynthesis. In one group, significant trends towards downregulation of large proteins and upregulation of small ones are observed. In the other group we find no such trends. These results are consistent with resource limitation being important in the evolution of the first group of stress responses.

Asociaciones entre la red social y la discapacidad al comienzo de la vejez en las ciudades de Madrid y Barcelona en 2005

La pérdida de autonomía a edades avanzadas no se asocia únicamente con el envejecimiento sino también con características del entorno físico y social. Investigaciones recientes han demostrado que la red social, la integración social y la participación, actúan como predictores de la discapacidad en la vejez. El objetivo de este trabajo es nalizar el efecto de la red social sobre el nivel de autonomía(en términos de discapacidad instrumental y básica) en etapas iniciales de la vejez.

Financial convergence in transition economies: EU enlargement

This paper analyses the financial impact of the enlargement of the European Union (EU) to include 10 new Central and Eastern European Nations (CEEN) on firms’ business and financial structures. To this end, we employ quantitative analytic techniques and financial ratios. In this context, we hope to discover whether firms in the new EU member States tend to converge with business in the Europe of the 15 in terms of the structure of firms’ financial statements. We examine the extent to which the increasing integration of the former may foster the convergence of productive structures. The methodology followed consists of an analysis of the evolution of 12 financial ratios in a sample of firms obtained from the AMADEUS data base. To that end, we perform a Dynamic Factor Analysis that identifies the determining factors of the joint evolution of deviations in the financial ratios with respect to the average value of firms in the EU-15. This analysis allows us to analyse the convergence in each of the CEEN nations with respect to the EU-15.

Prevalencia de la discapacidad en España por comunidades autónomas: el papel de los factores individuales y del entorno geográfico en su variabilidad

Fundamento: La prevalencia de discapacidad en la población general presenta una gran variabilidad geográfica, de manera que identificar aquellos factores que pudieran explicarla será importante para la planificación de políticas sociales. En este trabajo se analiza la variabilidad de la discapacidad por comunidades autónomas desde una doble vertiente, los factores individuales y del entorno. Métodos: Los datos proceden principalmente de la Encuesta de Discapacidad, Deficiencias y Estado de Salud de 1999 y del Inebase, ambas del Instituto Nacional de Estadística (INE). Se calculó la prevalencia de discapacidad simple y ajustada por edad de las CCAA. Se analizan los factores individuales asociados a la discapacidad mediante una regresión logística y los factores individuales y de la comunidad autónoma conjuntamente con una regresión logística de dos niveles. Resultados: La prevalencia de discapacidad muestra una diferencia máxima de 5,75 puntos entre las comunidades autónomas. En la regresión logística la comunidad de residencia fue estadísticamente significativa (OR: 3,35 en la de mayor prevalencia respecto a la de menor) junto con otras variables individuales: edad (OR de 40-64= 1,78 OR de 65-79= 1,87 y OR de >79= 3,34), sexo (OR mujer= 0,66), situación laboral (OR sin trabajo=2,25 OR amas casa/estudiante=1,39 y OR otros=2,03), estado de salud (OR regular= 1,69 OR malo/muy malo= 2,05) y enfermedades crónicas (OR 1-3=1,56 OR4-6=1,82 OR>6=2,59). En la regresión de dos niveles las variables individuales explican poca varianza (s=0,261) y ninguna de las variables relativas a las CCAA mejora el modelo. Conclusiones: Las características individuales no explican suficientemente la variabilidad de la discapacidad entre CCAA y no se han identificado variables del entorno que sean significativas.

Prevalencia de la infección tuberculosa y por el VIH en los usuarios de un programa de reducción de riesgos para usuarios de drogas por vía parenteral (UDVP)

FUNDAMENTO: Determinar la prevalencia de la infección tuberculosa y por el VIH, así como los factores asociados, en la población de usuarios del programa de reducción de riesgos de la ciudad de Lleida. MÉTODOS: La muestra la formaron los nuevos usuarios del programa en el período abril-junio de 1996, entre los los cuales se realizó un cuestionario para la recogida de datos de las variables: edad, sexo, resultado de la prueba de la tuberculina, vacunación BCG, conocimiento de la serología frente al VIH, ingreso en prisión y años de consumo de heroína. Se calculó la prevalencia de la infección tuberculosa y por el VIH, con el intervalo de confianza (IC) del 95%. La asociación de ambas variables con el resto de variables del estudio se determinó mediante la odds ratio (OR) y su IC del 95% . RESULTADOS: Acudieron 150 pacientes diferentes, de los cuales 45 eran nuevos usuarios. De ellos, el 80,0% eran varones, con una edad media de 31,1 años. La prevalencia de la coinfección fue del 8,9% (IC 95% 2,8-22,1). La prevalencia de la infección tuberculosa fue de 27,3% (IC 95% 12,4-43,0), siendo superior en los que tenían antecedentes de ingreso en prisión (OR=3,4; IC 95% 0,5-27,4). La prevalencia de la infección por el VIH fue del 36,1% (IC 95% 21,3-53,8), siendo superior en los que tenían una antigüedad, en el consumo de heroína, superior a los 11 años ( OR = 7,3; IC 95% 1,0-65,9). CONCLUSIONES: El antecedente de ingreso en prisión es el principal factor de riesgo de la infección tuberculosa. Los años de consumo se asocian con la infección por el VIH, especialmente a partir de los 11 años. Los programas de reducción de riesgos de nuestro país deberían realizar actividades de control de la infección tuberculosa y por VIH.

The effect of age at the first mating and herd size on the lifetime productivity of sows

The effect of age at the first mating and herd size were evaluated in the reference Spanish Databank (BDporc) of 37 698 sows born between 1991 and 1995 and with individual lifetime records. The data included dates of births at entrance and culling, first mating, repetitive mating and conception, first farrowing and weaning records. Individual records were validated before the analysis by screening them through a tolerance “filter” in order to eliminate the extreme values from the analysis. The total database of the sows was classified in 7 classes according to age at the first mating (< 210, 210–220, 221–230, 231–240, 241–250, 251–270, and > 270 days) and in 6 classes of herd size (< 200, 200–300, 301–400, 401–600, 601–800, and > 800 sows). The total number of litters and number of weaned piglets obtained from each sow during the lifetime production were significantly (P < 0.05) greater for gilts between 221 and 240 d of age at the first mating. There was a significant (P < 0.001) effect of the herd size on the reproductive performance of the sow, and the best performance was obtained with herds with 401 to 600 sows compared to < 200 or > 800 sow-herds. Furthermore, a significant (P < 0.001) interaction between age at the first mating and herd size was detected and can be associated with a particular pattern for the herd size class 401–600 sows with the best performances obtained for the sows first mated at less than 200 days. For the other herd sizes, the results indicated that sows mated for the first time at the right age, 221–240 days, are more productive, both in the number and size of the parities throughout lifetime production.