Application de la modélisation moléculaire à de nouvelles approches thérapeutiques du cancer [Application of molecular modeling to new therapeutic cancer approaches].

Recent progress in the experimental determination of protein structures allow to understand, at a very detailed level, the molecular recognition mechanisms that are at the basis of the living matter. This level of understanding makes it possible to design rational therapeutic approaches, in which effectors molecules are adapted or created de novo to perform a given function. An example of such an approach is drug design, were small inhibitory molecules are designed using in silico simulations and tested in vitro. In this article, we present a similar approach to rationally optimize the sequence of killer T lymphocytes receptors to make them more efficient against melanoma cells. The architecture of this translational research project is presented together with its implications both at the level of basic research as well as in the clinics.

MAMOT: hidden Markov modeling tool.

Hidden Markov models (HMMs) are probabilistic models that are well adapted to many tasks in bioinformatics, for example, for predicting the occurrence of specific motifs in biological sequences. MAMOT is a command-line program for Unix-like operating systems, including MacOS X, that we developed to allow scientists to apply HMMs more easily in their research. One can define the architecture and initial parameters of the model in a text file and then use MAMOT for parameter optimization on example data, decoding (like predicting motif occurrence in sequences) and the production of stochastic sequences generated according to the probabilistic model. Two examples for which models are provided are coiled-coil domains in protein sequences and protein binding sites in DNA. A wealth of useful features include the use of pseudocounts, state tying and fixing of selected parameters in learning, and the inclusion of prior probabilities in decoding. AVAILABILITY: MAMOT is implemented in C++, and is distributed under the GNU General Public Licence (GPL). The software, documentation, and example model files can be found at http://bcf.isb-sib.ch/mamot

Aplicació especialitza en la cerca de feines que es puguin realitzar des de casa

El projecte consisteix en la creació d'una aplicació WEB construïda sota arquitectura J2EE, aquesta aplicació consistirà en mostrar ofertes laborals definides per empresa, categories, hores de treball i condicions contractuals amb un objectiu molt clar, el que totes les ofertes presentades és puguin realitzar des de casa.

Aplicaciones Web para trabajo colaborativo: Diseño y prototipo de un sofware para la replicación de ficheros en sistemas de trabajo en grupo P2P

Aplicación para trabajar en un entorno colaborativo con el fin de compartir ficheros xml. Dicho entorno colaborativo se basa en una red peer to peer.

Task-dependent influence of genetic architecture and mating frequency on division of labour in social insect societies.

Division of labour is one of the most prominent features of social insects. The efficient allocation of individuals to different tasks requires dynamic adjustment in response to environmental perturbations. Theoretical models suggest that the colony-level flexibility in responding to external changes and internal perturbation may depend on the within-colony genetic diversity, which is affected by the number of breeding individuals. However, these models have not considered the genetic architecture underlying the propensity of workers to perform the various tasks. Here, we investigated how both within-colony genetic variability (stemming from variation in the number of matings by queens) and the number of genes influencing the stimulus (threshold) for a given task at which workers begin to perform that task jointly influence task allocation efficiency. We used a numerical agent-based model to investigate the situation where workers had to perform either a regulatory task or a foraging task. One hundred generations of artificial selection in populations consisting of 500 colonies revealed that an increased number of matings always improved colony performance, whatever the number of loci encoding the thresholds of the regulatory and foraging tasks. However, the beneficial effect of additional matings was particularly important when the genetic architecture of queens comprised one or a few genes for the foraging task's threshold. By contrast, a higher number of genes encoding the foraging task reduced colony performance with the detrimental effect being stronger when queens had mated with several males. Finally, the number of genes encoding the threshold for the regulatory task only had a minor effect on colony performance. Overall, our numerical experiments support the importance of mating frequency on efficiency of division of labour and also reveal complex interactions between the number of matings and genetic architecture.

The fine-scale architecture of structural variants in 17 mouse genomes.

BACKGROUND: Accurate catalogs of structural variants (SVs) in mammalian genomes are necessary to elucidate the potential mechanisms that drive SV formation and to assess their functional impact. Next generation sequencing methods for SV detection are an advance on array-based methods, but are almost exclusively limited to four basic types: deletions, insertions, inversions and copy number gains. RESULTS: By visual inspection of 100 Mbp of genome to which next generation sequence data from 17 inbred mouse strains had been aligned, we identify and interpret 21 paired-end mapping patterns, which we validate by PCR. These paired-end mapping patterns reveal a greater diversity and complexity in SVs than previously recognized. In addition, Sanger-based sequence analysis of 4,176 breakpoints at 261 SV sites reveal additional complexity at approximately a quarter of structural variants analyzed. We find micro-deletions and micro-insertions at SV breakpoints, ranging from 1 to 107 bp, and SNPs that extend breakpoint micro-homology and may catalyze SV formation. CONCLUSIONS: An integrative approach using experimental analyses to train computational SV calling is essential for the accurate resolution of the architecture of SVs. We find considerable complexity in SV formation; about a quarter of SVs in the mouse are composed of a complex mixture of deletion, insertion, inversion and copy number gain. Computational methods can be adapted to identify most paired-end mapping patterns.

Anàlisi. Disseny i implementació d'una utilitat de Workflow aplicat a una web de gestió d'un centre de Reclamacions i Queixes mitjançant J2EE : una solució amb Struts i EJBs

El treball final de carrera està compost de l¿anàlisi, disseny i implementació d'una utilitat de Workflow que dóna servei a una web per gestionar les reclamacions i queixes d'una empresa. La part del Workflow s'ha pensat per ser totalment configurable a les particularitats d'un determinat aplicatiu i per donar servei a tantes aplicacions com faci falta simultàniament.L'anàlisi i el disseny s'han basat en la metodologia UML dins el paradigma de l'Orientació a Objectes juntament amb diversos patrons de disseny com pot ser el MVC que ha permès separar completament la lògica de negoci (Workflow) de la presentació (Web). Per les 2 parts: Workflow i web s¿ha fet ús d'una arquitectura distribuïda.

The heterotetrameric architecture of the epithelial sodium channel (ENaC).

The epithelial sodium channel (ENaC) is a key element for the maintenance of sodium balance and the regulation of blood pressure. Three homologous ENaC subunits (alpha, beta and gamma) assemble to form a highly Na+-selective channel. However, the subunit stoichiometry of ENaC has not yet been solved. Quantitative analysis of cell surface expression of ENaC alpha, beta and gamma subunits shows that they assemble according to a fixed stoichiometry, with alpha ENaC as the most abundant subunit. Functional assays based on differential sensitivities to channel blockers elicited by mutations tagging each alpha, beta and gamma subunit are consistent with a four subunit stoichiometry composed of two alpha, one beta and one gamma. Expression of concatameric cDNA constructs made of different combinations of ENaC subunits confirmed the four subunit channel stoichiometry and showed that the arrangement of the subunits around the channel pore consists of two alpha subunits separated by beta and gamma subunits.

Xat segur

L'objectiu d'aquest treball de final de carrera és crear un programari de missatgeria instantània deslligada de qualsevol servidor, de manera que cada usuari tingui un programa client/servidor amb el qual pugui rebre 'trucades' o fer-ne, en aquest últim cas indicant prèviament l'adreça IP del destinatari.

Gestión de proyectos de cooperativa de iniciativa social

Desenvolupament d'una aplicació d'empresa d'estructura distribuïda utilitzant la web com a interfície. Per això s'ha utilitzat l'arquitectura J2EE, que és un estàndard per al desenvolupament distribuït d'aplicacions empresarials a Internet. L'aplicació seguirà el patró MVC (model, vista, controlador) així com altres patrons, frameworks, tecnologies utilitzades en entorns web o en l'accés a dades, així com un sistema gestor de base de dades relacional.