Facultad EMPRESARIALES

sectores primario y secundario de la economía XI. PROTECCIÓN DEL MEDIO AMBIENTE Y ACTUACIONES ESPECÍFICAS RESPECTO A LOS SECTORES AGRÍCOLA, FORESTAL, PECUARIO, MINERO Y DEL ESPACIO MARÍTIMO Y AÉREO Protección del medio ambiente: normativa dispersa e inorgánica PARTE QUINTA Actuaciones del Estado respecto al sector terciario de la economía XV. COMERCIO INTERNO, TRANSPORTE, CONTRATACIÓN PÚBLICA Y SERVICIOS BÁSICOS Fases de la actividad del Estado en el sector terciario Comercio interno -Transporte

Model checking is a well known method to carry out formal verification of distributed systems. This method needs a model representing the behaviour of the system to be verified. The size of this model depends on the complexity of the system. To be able to verify real life systems, it is necessary to use techniques allowing to take advantage of all the available storage space, to reduce the amount of information needed for the verification and to speed up computation time. But the expressiveness of the languages used to describe the system and its expected behaviours (properties) limit the possible reductions. We present in this paper our choices for an automatic verification tool by using model checking. The preliminary results obtained from its use for the verification of a real life protocol allow us to make some estimations about the limits of model checking methods.

Research on formal description techniques during the last years has revealed new trends on the description of distributed systems. Nevertheless, the application of these techniques to real and complex systems is not straightforward and there are not many case studies in this area. This paper presents an experience in protocol building area, by involving a close interaction between protocol design and formal verification, and shows off its application in the design of a real distributed system: a network independent atomic multicast protocol.

We report a kindred with autosomal recessive interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency in 3 fourth-degree relatives. A diagnosis of IRAK-4 deficiency should be considered in families with invasive bacterial disease, even if the individuals affected are only distantly related, which falsely suggests multigenic or dominant inheritance with low penetrance.

Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma.

Genetic engineering of metabolic pathways is a standard strategy to increase the production of metabolites of economic interest. However, such flux increases could very likely lead to undesirable changes in metabolite concentrations, producing deleterious perturbations on other cellular processes. These negative effects could be avoided by implementing a balanced increase of enzyme concentrations according to the Universal Method [Kacser and Acerenza (1993) Eur J Biochem 216:361–367]. Exact application of the method usually requires modification of many reactions, which is difficult to achieve in practice. Here, improvement of threonine production via pyruvate kinase deletion in Escherichia coli is used as a case study to demonstrate a partial application of the Universal Method, which includes performing sensitivity analysis. Our analysis predicts that manipulating a few reactions is sufficient to obtain an important increase in threonine production without major perturbations of metabolite concentrations. Biotechnol. Bioeng. 2009;103: 609–620. © 2009 Wiley Periodicals, Inc.

OBJECTIVES. Inborn defects in Toll-like receptor signaling are recently described primary immunodeficiencies that predispose affected children to life-threatening infections. Patients with interleukin-1 receptor-associated kinase-4 deficiency are prone to invasive pneumococcal disease, and patients with UNC-93B deficiency are prone to herpes simplex virus encephalitis. These genetic disorders are underdiagnosed, partly because diagnosis currently requires expensive and time-consuming techniques available at only a few specialized centers worldwide. We, therefore, aimed to develop a cheap and fast test for the detection of defects in Toll-like receptor signaling.

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