Disseny i implementació de la base de dades d'un sistema de control energètic

Implementació d'un sistema de base de dades per donar resposta a la necessitat de control energètic plantejada a nivell europeu. La base de dades ha de guardar informació relacionada amb el consum energètic i permetre la generació de dades estadístiques sobre l'ús de l'energia.

The Universal Protein Resource (UniProt) in 2010.

The primary mission of UniProt is to support biological research by maintaining a stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces freely accessible to the scientific community. UniProt is produced by the UniProt Consortium which consists of groups from the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics (SIB) and the Protein Information Resource (PIR). UniProt is comprised of four major components, each optimized for different uses: the UniProt Archive, the UniProt Knowledgebase, the UniProt Reference Clusters and the UniProt Metagenomic and Environmental Sequence Database. UniProt is updated and distributed every 3 weeks and can be accessed online for searches or download at http://www.uniprot.org.

The sustainability of a Spanish Regional Virtual Library

Objectives: The Andalusian Health e-Library (BV-SSPA) is the National Health Library in the region of Andalusia (Spain). It is a corporate hospital library created in 2006. The year 2012 is a turning point for the Spanish economy, and the BV-SSPA has to demonstrate that it is cost-effective and sustainable. Methods: Andalusia is a wide Spanish region with more than 8 million inhabitants, more than 100,000 health professionals for 41 hospitals, 1,500 primary health care centers, and 28 centers for nonmedical attention purposes, and the BV-SSPA was created to cover all these health services. It was appointed the only intermediary for contracting electronic resources destined to the Andalusian Health System. Hospitals are not allowed to subscribe any resources, and the same services are offered for the whole system. Results: In 2011, the BV-SSPA reached the biggest electronic health sciences resource collection in Spain: a total amount of 2,431 subscribed titles, besides 8 databases and other scientific information resources. The following goals were also achieved: • Cost-effectiveness: In 2011, the BV-SSPA represented a saving percentage of 25.42% compared to the individual hospital subscription costs if they would have continued their contracting. • Efficiency: Central purchasing has meant for the Andalusian health professionals, the democracy of research resource access. Some services were also created: • integrated and safe remote access to all the library resources independent of the user’s location • citizenship website, where the resources for citizenship are grouped • Centralized Document Supply Service, focusing all the article orders from and for the Andalusian Health System • institutional repository, which contains the whole intellectual, scientific production generated by the Andalusian health professionals • computer application to study the Andalusian health system scientific production • Social media as instrument for communicating with users • science web, a defined space for researchers. Conclusions: Although Andalusia is facing a dreadful economic situation, the BV-SSPA has demonstrated its sustainability: • For 2012 renewals, it carried out a statistics study allowing obtaining enough data for deciding which titles were not being discharged by users. • Titles with no discharges or without impact factor were rejected after strong negotiation with suppliers, as the BV-SSPA after 6 years on, is considered a strong dealer by them. • This meant savings of 14% from the original budget for 2012, which allowed the continuity of the BV-SSPA without decreasing the quality offered to their users.

Update of the FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation.

The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments. The primary and unique technique is cap analysis of gene expression (CAGE), sequencing mRNA 5'-ends with a second-generation sequencer to quantify promoter activities even in the absence of gene annotation. Additional genome-wide experiments complement the setup including short RNA sequencing, microarray gene expression profiling on large-scale perturbation experiments and ChIP-chip for epigenetic marks and transcription factors. All the experiments are performed in a differentiation time course of the THP-1 human leukemic cell line. Furthermore, we performed a large-scale mammalian two-hybrid (M2H) assay between transcription factors and monitored their expression profile across human and mouse tissues with qRT-PCR to address combinatorial effects of regulation by transcription factors. These interdependent data have been analyzed individually and in combination with each other and are published in related but distinct papers. We provide all data together with systematic annotation in an integrated view as resource for the scientific community (http://fantom.gsc.riken.jp/4/). Additionally, we assembled a rich set of derived analysis results including published predicted and validated regulatory interactions. Here we introduce the resource and its update after the initial release.

Trends in yearly prevalence of third-generation cephalosporin and fluoroquinolone resistant Enterobacteriaceae infections and antimicrobial use in Spanish hospitals, Spain, 1999 to 2010.

Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. are a major cause of infections in hospitalised patients. The aim of our study was to evaluate rates and trends of resistance to third-generation cephalosporins and fluoroquinolones in infected patients, the trends in use for these antimicrobials, and to assess the potential correlation between both trends. The database of national point prevalence study series of infections and antimicrobial use among patients hospitalised in Spain over the period from 1999 to 2010 was analysed. On average 265 hospitals and 60,000 patients were surveyed per year yielding a total of 19,801 E. coli, 3,004 K. pneumoniae and 3,205 Enterobacter isolates. During the twelve years period, we observed significant increases for the use of fluoroquinolones (5.8%-10.2%, p<0.001), but not for third-generation cephalosporins (6.4%-5.9%, p=NS). Resistance to third-generation cephalosporins increased significantly for E. coli (5%-15%, p<0.01) and for K. pneumoniae infections (4%-21%, p<0.01) but not for Enterobacter spp. (24%). Resistance to fluoroquinolones increased significantly for E. coli (16%30%, p<0.01), for K. pneumoniae (5%-22%, p<0.01), and for Enterobacter spp. (6%-15%, p<0.01). We found strong correlations between the rate of fluoroquinolone use and the resistance to fluoroquinolones, third-generation cephalosporins, or co-resistance to both, for E. coli (R=0.97, p<0.01, R=0.94, p<0.01, and R=0.96, p<0.01, respectively), and for K. pneumoniae (R=0.92, p<0.01, R=0.91, p<0.01, and R=0.92, p<0.01, respectively). No correlation could be found between the use of third-generation cephalosporins and resistance to any of the latter antimicrobials. No significant correlations could be found for Enterobacter spp.. Knowledge of the trends in antimicrobial resistance and use of antimicrobials in the hospitalised population at the national level can help to develop prevention strategies.

Disseny i implementació de la base de dades: Sistema de votació ciutadana a nivell Europeu a través d'Internet

La Unió Europea necessita i per tant ens encarrega, un disseny de base de dades per tald'emmagatzemar la informació de futures eleccions ciutadanes a través d'Internet.

Induction of protective T-helper 1 immune responses against Echinococcus granulosus in mice by a multi-T-cell epitope antigen based on five proteins

In this study, we designed an experiment to predict a potential immunodominant T-cell epitope and evaluate the protectivity of this antigen in immunised mice. The T-cell epitopes of the candidate proteins (EgGST, EgA31, Eg95, EgTrp and P14-3-3) were detected using available web-based databases. The synthesised DNA was subcloned into the pET41a+ vector and expressed in Escherichia coli as a fusion to glutathione-S-transferase protein (GST). The resulting chimeric protein was then purified by affinity chromatography. Twenty female C57BL/6 mice were immunised with the antigen emulsified in Freund's adjuvant. Mouse splenocytes were then cultured in Dulbecco's Modified Eagle's Medium in the presence of the antigen. The production of interferon-γ was significantly higher in the immunised mice than in the control mice (> 1,300 pg/mL), but interleukin (IL)-10 and IL-4 production was not statistically different between the two groups. In a challenge study in which mice were infected with 500 live protoscolices, a high protectivity level (99.6%) was demonstrated in immunised BALB/C mice compared to the findings in the control groups [GST and adjuvant (Adj) ]. These results demonstrate the successful application of the predicted T-cell epitope in designing a vaccine against Echinococcus granulosus in a mouse model.

Identification of new MHC class I-restricted human tumor antigens for immunotherapy

Summary Cancer is a leading cause of morbidity and mortality in Western countries (as an example, colorectal cancer accounts for about 300'000 new cases and 200'000 deaths each year in Europe and in the USA). Despite that many patients with cancer have complete macroscopic clearance of their disease after resection, radiotherapy and/or chemotherapy, many of these patients develop fatal recurrence. Vaccination with immunogenic peptide tumor antigens has shown encouraging progresses in the last decade; immunotherapy might therefore constitute a fourth therapeutic option in the future. We dissect here and critically evaluate the numerous steps of reverse immunology, a forecast procedure to identify antigenic peptides from the sequence of a gene of interest. Bioinformatic algorithms were applied to mine sequence databases for tumor-specific transcripts. A quality assessment of publicly available sequence databanks allowed defining strengths and weaknesses of bioinformatics-based prediction of colon cancer-specific alternative splicing: new splice variants could be identified, however cancer-restricted expression could not be significantly predicted. Other sources of target transcripts were quantitatively investigated by polymerase chain reactions, as cancer-testis genes or reported overexpressed transcripts. Based on the relative expression of a defined set of housekeeping genes in colon cancer tissues, we characterized a precise procedure for accurate normalization and determined a threshold for the definition of significant overexpression of genes in cancers versus normal tissues. Further steps of reverse immunology were applied on a splice variant of the Melan¬A gene. Since it is known that the C-termini of antigenic peptides are directly produced by the proteasome, longer precursor and overlapping peptides encoded by the target sequence were synthesized chemically and digested in vitro with purified proteasome. The resulting fragments were identified by mass spectroscopy to detect cleavage sites. Using this information and based on the available anchor motifs for defined HLA class I molecules, putative antigenic peptides could be predicted. Their relative affinity for HLA molecules was confirmed experimentally with functional competitive binding assays and they were used to search patients' peripheral blood lymphocytes for the presence of specific cytolytic T lymphocytes (CTL). CTL clones specific for a splice variant of Melan-A could be isolated; although they recognized peptide-pulsed cells, they failed to lyse melanoma cells in functional assays of antigen recognition. In the conclusion, we discuss advantages and bottlenecks of reverse immunology and compare the technical aspects of this approach with the more classical procedure of direct immunology, a technique introduced by Boon and colleagues more than 10 years ago to successfully clone tumor antigens.

Disseny i implementació de la base de dades d'un sistema de control energètic

La Comunitat Econòmica Europea ha plantejat la necessitat d'assolir un control exhaustiu de la gestió i el consum que a la comunitat es fa de l'energia, sigui quina sigui la seva naturalesa. És per això que requereix el disseny d'una base de dades que proporcioni la capacitat d'emmagatzemar tota la informació necessària, i que faciliti l'obtenció de llistats i dades estadístiques referents a aquest ús de l'energia. Aquest treball pretén implementar la base de dades que donarà resposta a aquestes necessitats, un cop valorats els requeriments i la viabilitat del projecte.

Analysis of Centrosome duplication in "Caenorhabditis elegans" : the role of "sas" genes

Abstract: The centrosome is the major microtubule organizing center (MTOC) of most animal cells. As such, it is essential for a number of processes, including polarized secretion or bipolar spindle assembly. Hence, centrosome number needs to be controlled precisely in coordination with DNA replication. Cells early in the cell cycle contain one centrosome that duplicates during S-phase to give rise to two centrosomes that organize a bipolar spindle during mitosis. A failure in this process is likely to engage the spindle assembly checkpoint and threaten genome stability. Despite its importance for normal and uncontrolled proliferation the mechanisms underlying centrosome duplication are still unclear. The Caenorhabditis elegans embryo is well suited to study the mechanisms of centrosome duplication. It allows for the analysis of cellular processes with high temporal and spatial resolution. Gene identification and inactivation techniques are very powerful and a wide set of mutant and transgenic strains facilitates analysis. My thesis project consisted of characterizing three sas-genes: sas-4, sas-5 and sas-¬6. Embryos lacking these genes fail to form a bipolar spindle, hence their name (spindle assembly). I established that sas-4(RNAi) and sas-6(RNAi) embryos do not form daughter centrioles and thus do not duplicate their centrosomes. Furthermore, I showed that both proteins localize to the cytoplasm and are strikingly enriched at centrioles throughout the cell cycle. By performing fluorescent recovery after photobleaching (FRAP) experiments and differentially labeling centrioles, I established that both proteins are recruited to centrioles once per cell cycle when daughter centrioles form. In contrast, SAS-5, PLK-1 and SPD-2 shuttle permanently between the cytoplasm and centrioles. By showing that SAS-5 and SAS-6 interact in vivo, I established a functional relationship between the proteins. Testing the putative human homologue of SAS-6 (HsSAS-6) and a distant relative of SAS-4 (CPAP), I was able to show that these proteins are required for centrosome duplication in human cells. In addition I found that overexpression of GFP¬HsSAS-6 leads to formation of extra centrosomes. In conclusion, we identified and gained important insights into proteins required for centrosome duplication in C. elegans and in human cells. Thus, our work contributes to further elucidate an important step of cell division in normal and malignant tissues. Eventually, this may allow for the development of novel diagnostic or therapeutic reagents to treat cancer patients. Résumé: Le centrosome est le principal centre organisateur des microtubules dans les cellules animales. De ce fait, il est essentiel pour un certain nombre de processus, comme l'adressage polarisé ou la mise en place d'un fuseau bipolaire. Le nombre de centrosome doit être contrôlé de façon précise et en coordination avec la réplication de l'ADN. Au début du cycle cellulaire, les cellules n'ont qu'un seul centrosome qui se duplique au cours de la phase S pour donner naissance à deux centrosomes qui forment le fuseau bipolaire pendant la mitose. Des défauts dans ce processus déclencheront probablement le "checkpoint" d'assemblage du fuseau et menaceront la stabilité du génome. Malgré leurs importances pour la prolifération normale ou incontrôlée des cellules, les mécanismes gouvernant la duplication des centrosomes restent obscures. L'embryon de Caenorhabditis elegans est bien adapté pour étudier les mécanismes de duplication des centrosomes. Il permet l'analyse des processus cellulaires avec une haute résolution spatiale et temporelle. L'identification des gènes et les techniques d'inactivation sont très puissantes et de larges collections de mutants et de lignées transgéniques facilitent les analyses. Mon projet de thèse a consisté à caractérisé trois gènes: sas-4, sas-5 et sas-6. Les embryons ne possédant pas ces gènes ne forment pas de fuseaux bipolaires, d'où leur nom (spindle assembly). J'ai établi que les embryons sas-4(RNAi) et sas-6(RNAi) ne forment pas de centrioles fils, et donc ne dupliquent pas leur centrosome. De plus, j'ai montré que les deux protéines sont localisées dans le cytoplasme et sont étonnamment enrichies aux centrioles tout le long du cycle cellulaire. En réalisant des expériences de FRAP (fluorscence recovery after photobleaching) et en marquant différentiellement les centrioles, j'ai établi que ces deux protéines sont recrutées une fois par cycle cellulaire aux centrioles, au moment de la duplication. Au contraire, SAS-5, PLK-1 et SPD-2 oscillent en permanence entre le cytoplasme et les centrioles. En montrant que SAS-5 et SAS-6 interagissent in vivo, j'ai établi une relation fonctionnelle entre les deux protéines. En testant les homologues humains putatifs de SAS-6 (HsSAS-6) et de SAS-4 (CPAP), j'ai été capable de montrer que ces protéines étaient aussi requises pour la duplication des centrosomes dans les cellules humaines. De plus, j'ai montré que la surexpression de GFP-HsSAS-6 entrainait la formation de centrosomes surnuméraires. En conclusion, nous avons identifié et progressé dans la compréhension de protéines requises pour la duplication des centrosomes chez C. elegans et dans les cellules humaines. Ainsi, notre travail contribue à mieux élucider une étape importante du la division cellulaire dans les cellules normales et malignes. A terme, ceci devrait aider au développement de nouveaux diagnostics ou de traitements thérapeuthiques pour soigner les malades du cancer.

Subclinical hypothyroidism and the risk of coronary heart disease and mortality.

CONTEXT: Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. OBJECTIVE: To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. DATA EXTRACTION: Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. RESULTS: Among 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.

Evolutionary simulations to detect functional lineage-specific genes.

MOTIVATION: Supporting the functionality of recent duplicate gene copies is usually difficult, owing to high sequence similarity between duplicate counterparts and shallow phylogenies, which hamper both the statistical and experimental inference. RESULTS: We developed an integrated evolutionary approach to identify functional duplicate gene copies and other lineage-specific genes. By repeatedly simulating neutral evolution, our method estimates the probability that an ORF was selectively conserved and is therefore likely to represent a bona fide coding region. In parallel, our method tests whether the accumulation of non-synonymous substitutions reveals signatures of selective constraint. We show that our approach has high power to identify functional lineage-specific genes using simulated and real data. For example, a coding region of average length (approximately 1400 bp), restricted to hominoids, can be predicted to be functional in approximately 94-100% of cases. Notably, the method may support functionality for instances where classical selection tests based on the ratio of non-synonymous to synonymous substitutions fail to reveal signatures of selection. Our method is available as an automated tool, ReEVOLVER, which will also be useful to systematically detect functional lineage-specific genes of closely related species on a large scale. AVAILABILITY: ReEVOLVER is available at http://www.unil.ch/cig/page7858.html.

Magatzems de dades en el context de la web semàntica

L'objecte del projecte és estudiar en profunditat els sistemes gestors de bases de dates en l'àmbit de la web semàntica. Aquests sistemes són gestors de bases de dades especialitzats en l'emmagatzematge i tractament de dades semàntiques, tot tenint en compte les peculiaritats d'aquestes. Per tal d'aprofundir en la matèria, el projecte es divideix en dues parts principals. En la primera es recerca l'estat de l'art, fent un estudi comparatiu entre els magatzems semàntics més coneguts en l'actualitat. En la segona part s'estudia en profunditat un d'aquests magatzems (Virtuoso Universal Server).

XML y web semántica : Bases de datos en el contexto de la web semántica

Este trabajo define qué es una base de datos semántica, qué ventajas ofrece, cómo se utiliza y en qué tipo de proyectos o sistemas tiene sentido usarla. Además, en él se estudia en detalle una de ellas, OWLIM 1, de la empresa Ontotext, para evaluar la dificultad de usarla, su rendimiento y sus capacidades específicas.

Sistema de control energètic

La Comunitat Europea, dins de la partida pressupostària destinada a controlar l'ús de la energia, ha decidit obrir un concurs públic per a rebre propostes sobre el disseny d'una base de dades. Aquesta els hi servirà de magatzem de la informació per a la futura aplicació que volem implementar per permetre la generació de dades estadístiques sobre l'ús de l'energia.