THE DEVELOPMENT OF AN EDUCATIONAL SYSTEM FOR A LONG TERM TRAINING ON SEISMIC AND VOLCANIC RISK

One of the tasks of the European Project UPStrat-MAFA (Urban Prevention Strategies using MAcroseimic Fields and FAult Sources) is to develop an educational system aimed at long-term training, mainly on seismic hazard and risk. This task will be carried out by sharing the expertise of partners of the project to set different actions, encompassing programs and educational material for students, teachers and general public, and to design an interactive travelling educational path. Starting from the Icelandic educational program tested on schools in the last decade by EERC (Earthquake Engineering Research Centre), the task will develop educational tools especially designed for children, and also new tools using the most spread information channels, in order to outreach information on seismic risk and how to cope with earthquakes. The interactive travelling educational path on earthquakes and volcanoes, aimed at risk-reduction by increasing awareness, is an interactive experience using a multimedia approach, in order to have a very flexible, easy-to-share and appealing set of educational tools (video, simulations, games…) also developed for “edutainment”. The educational path, which is also a travelling exhibition, has to deal with issues related to seismic and volcanoes hazard and risks, especially in urban areas. The whole education-information system developed in the framework of UPStrat-MAFA project is structured to represent both a way to convey project results to the scientific community and to strengthen people’s risk awareness and their training to face up to seismic and/or volcanic events.Co-financed by the EU - Civil Protection Financial Instrument, in the framework the European project ”Urban disaster Prevention Strategies using MAcroseismic Fields and FAult Sources” (UPStrat-MAFA - Num. 230301/2011/613486/SUB/A5), DG ECHO Unit A5. http://ec.europa.eu/echo/funding/cp_projects2011_en.htmUnpublished19-24 August 2012 in Moscow, Russia.5.9. Formazione e informazioneope

THE DEVELOPMENT OF AN EDUCATIONAL SYSTEM FOR A LONG TERM TRAINING ON SEISMIC AND VOLCANIC RISK

One of the tasks of the European Project UPStrat-MAFA (Urban Prevention Strategies using MAcroseimic Fields and FAult Sources) is to develop an educational system aimed at long-term training, mainly on seismic hazard and risk. This task will be carried out by sharing the expertise of partners of the project to set different actions, encompassing programs and educational material for students, teachers and general public, and to design an interactive travelling educational path. Starting from the Icelandic educational program tested on schools in the last decade by EERC (Earthquake Engineering Research Centre), the task will develop educational tools especially designed for children, and also new tools using the most spread information channels, in order to outreach information on seismic risk and how to cope with earthquakes. The interactive travelling educational path on earthquakes and volcanoes, aimed at risk-reduction by increasing awareness, is an interactive experience using a multimedia approach, in order to have a very flexible, easy-to-share and appealing set of educational tools (video, simulations, games…) also developed for “edutainment”. The educational path, which is also a travelling exhibition, has to deal with issues related to seismic and volcanoes hazard and risks, especially in urban areas. The whole education-information system developed in the framework of UPStrat-MAFA project is structured to represent both a way to convey project results to the scientific community and to strengthen people’s risk awareness and their training to face up to seismic and/or volcanic events

Plasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development.

The viability of Mycobacterium tuberculosis (Mtb) depends on energy generated by its respiratory chain. Cytochrome bc1-aa3 oxidase and type-2 NADH dehydrogenase (NDH-2) are respiratory chain components predicted to be essential, and are currently targeted for drug development. Here we demonstrate that an Mtb cytochrome bc1-aa3 oxidase deletion mutant is viable and only partially attenuated in mice. Moreover, treatment of Mtb-infected marmosets with a cytochrome bc1-aa3 oxidase inhibitor controls disease progression and reduces lesion-associated inflammation, but most lesions become cavitary. Deletion of both NDH-2 encoding genes (Δndh-2 mutant) reveals that the essentiality of NDH-2 as shown in standard growth media is due to the presence of fatty acids. The Δndh-2 mutant is only mildly attenuated in mice and not differently susceptible to clofazimine, a drug in clinical use proposed to engage NDH-2. These results demonstrate the intrinsic plasticity of Mtb's respiratory chain, and highlight the challenges associated with targeting the pathogen's respiratory enzymes for tuberculosis drug development

Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations.

Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common 'metastatic precursor'. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination

Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences

Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer

Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia

Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P 1�4 2.15 � 10 � 120) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis. We then perform whole-genome sequencing on 21 samples from the case cohort, and identify several novel loss-of-function mutations within the associated loci. Our results provide new insights into genetic background of craniofacial microsomia

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Urban Disaster-Prevention Strategies Using Macroseismic Fields and Fault Sources

This contribution presents the general framework of the European project UPStrat-MAFA "Urban disaster Prevention Strategies using MAcroseismic Fields and FAult Sources" and its ongoing activities. A unique probabilistic procedure is being used for seismic hazard evaluation, using both macroseismic fields and characteristics of fault sources for the analysis of data from volcanic and tectonic areas: Mt. Etna, Mt. Vesuvius and Campi Flegrei (Italy), Azores Islands (Portugal), South Iceland (Iceland), Alicante-Murcia (Spain), and mainland and offshore Portugal. An improvement of urban scale vulnerability information on building and network systems (typologies, schools, strategic buildings, lifelines, and others) is proposed in the form of a global Disruption Index, with the objective to provide a systematic way of measuring earthquake impact in urbanized areas considered as complex networks. Disaster prevention strategies are considered based on an education information system, another effective component of the disaster risk reduction given by long-term activities.Co-financed by the EU - Civil Protection Financial Instrument, in the framework the European project ”Urban disaster Prevention Strategies using MAcroseismic Fields and FAult Sources (Acronym: UPStrat-MAFA, Grant Agreement N. 23031/2011/613486/SUB/A5). http://ec.europa.eu/echo/funding/cp_projects2011_en.htmPublishedLisbon - Portugal4.1. Metodologie sismologiche per l'ingegneria sismicaope