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Disaster risk is not only associated with the occurrence of intense hazard events but also with the vulnerability conditions that facilitate disasters when such events occur. Vulnerability is closely linked to social processes and governance weaknesses in disaster-prone areas, and is usually related to a set of fragilities, susceptibilities, and issues regarding the lack of resilience of the exposed human settlements. The holistic risk assessment aims to reflect risk from a comprehensive perspective by using, in one hand, the physical risk or potential physical damage directly linked to the occurrence of hazard events and, on the other hand by capturing how underlying risk drivers or amplifiers –social, economic, environmental issues, non-hazard dependent elements, worsen the current existing physical risk conditions in terms of lack of capacity to anticipate or resist, or to respond and recover from adverse impacts. This article presents the results of the holistic evaluation of risk as well as of the implications of risk for development obtained at global level in the framework of the UN Atlas-GAR: Unveiling Disaster Risk, using the probabilistic physical risk results, obtained from the multi-hazard Global Risk Assessment 2015, socioeconomic indicators and macroeconomic flow variables available in worldwide databases for more than 200 countries and territories. These results are useful to identify risk drivers that are associated not only to the physical vulnerability of countries’ assets but also to social, economic and financial issues that should be examined and tackled in a comprehensive way

Despite the effectiveness of classic treatments and available diagnostic tools, cancer continues to be a leading world health problem, with devastating cancer-related death rates. Advances in oncolytic virotherapy have shown promise as potentially effective treatment options in the fight against cancer. The poxviruses have many features that make them an attractive platform for the development of oncolytic vectors, with some candidates currently in clinical trials. Here, we report the design and generation of a new oncolytic vector based on the vaccinia virus Western Reserve (WR) strain. We show that the WR-Δ4 virus, with the combined deletion of four specific viral genes that act on metabolic, proliferation, and signaling pathways (A48R, B18R, C11R, and J2R), has effective anti-tumor capabilities in vivo. In WR-Δ4-infected mice, we observed strong viral attenuation, reduced virus dissemination, and efficient tumor cell growth control in the B16F10 syngeneic melanoma model, with enhanced neutrophil migration and activation of tumor antigen-specific immune responses. This approach provides an alternative strategy toward ongoing efforts to develop an optimal oncolytic poxvirus vector. Keywords: oncolytic vectors, vaccinia virus, virotherapy, immune responses

Biomolecules are advantageous scaffolds for the synthesis and ordering of metallic nanoparticles. Rotavirus VP6 nanotubes possess intrinsic affinity to metal ions, a property that has been exploited to synthesize gold nanoparticles over them. The resulting nanobiomaterials have unique properties useful for novel applications. However, the formed nanobiomaterials lack of colloidal stability and flocculate, limiting their functionality. Here we demonstrate that it is possible to synthesize thiol-protected gold nanoparticles over VP6 nanotubes, which resulted in soluble nanobiomaterials. With this strategy, it was possible to modulate the size, colloidal stability, and surface plasmon resonance of the synthesized nanoparticles by controlling the content of the thiolated ligands. Two types of water-soluble ligands were tested, a small linear ligand, sodium 3-mercapto-1-propanesulfonate (MPS), and a bulky ligand, 5-mercaptopentyl β-D-glucopyranoside (GlcC5SH). The synthesized nanobiomaterials had a higher stability in suspension, as determined by Z-potential measurements. To the extent of our knowledge, this is the first time that a rational strategy is developed to modulate the particular properties of metal nanoparticles in situ synthesized over a protein bioscaffold through thiol coating, achieving a high spatial and structural organization of nanoparticles in a single integrative hybrid structure.

Disaster risk is most detailed at a micro-social or territorial scale. As we aggregate and work at more macro scales, details are lost. However, decision-making and information needs at each level are quite different, as are the social actors and stakeholders. This means that appropriate evaluation tools are necessary to make it easy to understand the problem and guide the decision-making process. It is fundamentally important to understand how vulnerability is generated, how it increases and how it accumulates. Performance benchmarks are also needed to facilitate decision makers’ access to relevant information as well as the identification and proposal of effective policies and actions. The Disaster Risk Management Indicators Program for the Americas meets this need and the results obtained for most countries of the Americas are presented. Four components or composite indicators have been designed to represent the main elements of vulnerability and show each country’s progress in managing risk. They are the ‘Disaster Deficit Index’, the ‘Local Disaster Index’, the ‘Prevalent Vulnerability Index’, and the ‘Risk Management Index’. These indicators reflect the organizational, development, capacity and institutional actions taken to reduce vulnerability and losses, to prepare for crisis and to recover efficiently from disasters. In this way, the system of indicators covers different areas of the risk problem, taking into account issues such as: potential damages and losses resulting from extreme events; recurrent disasters or losses; social and environmental conditions that make particular countries or regions more disaster prone; the capacity of the economy to recover; the operation of key services; institutional capacity and the effectiveness of basic risk management instruments (such as risk identification, prevention and mitigation measures, financial mechanisms and risk transfer); emergency response levels; and preparedness and recovery capacity. The system of indicators proposed for the Inter-American Development Bank (IDB) and applied to the countries of the Americas permits a systematic and quantitative benchmarking of each country during different periods between 1980 and 2008.

It has been assumed that oxidative phosphorylation (OxPhos) in solid tumors is severely reduced due to cytochrome c oxidase substrate restriction, although the measured extracellular oxygen concentration in hypoxic areas seems not limiting for this activity. To identify alternative hypoxia-induced OxPhos depressing mechanisms, an integral analysis of transcription, translation, enzyme activities and pathway fluxes was performed on glycolysis and OxPhos in HeLa and MCF-7 carcinomas. In both neoplasias exposed to hypoxia, an early transcriptional response was observed after 8h (two times increased glycolysis-related mRNA synthesis promoted by increased HIF-1alpha levels). However, major metabolic remodeling was observed only after 24h hypoxia: increased glycolytic protein content (1-5-times), enzyme activities (2-times) and fluxes (4-6-times). Interestingly, in MCF-7 cells, 24h hypoxia decreased OxPhos flux (4-6-fold), and 2-oxoglutarate dehydrogenase and glutaminase activities (3-fold), with no changes in respiratory complexes I and IV activities. In contrast, 24h hypoxia did not significantly affect HeLa OxPhos flux; neither mitochondria related mRNAs, protein contents or enzyme activities, although the enhanced glycolysis became the main ATP supplier. Thus, prolonged hypoxia (a) targeted some mitochondrial enzymes in MCF-7 but not in HeLa cells, and (b) induced a transition from mitochondrial towards a glycolytic-dependent energy metabolism in both MCF-7 and HeLa carcinomas.

It is thought that glycolysis is the predominant energy pathway in cancer, particularly in solid and poorly vascularized tumors where hypoxic regions develop. To evaluate whether glycolysis does effectively predominate for ATP supply and to identify the underlying biochemical mechanisms, the glycolytic and oxidative phosphorylation (OxPhos) fluxes, ATP/ADP ratio, phosphorylation potential, and expression and activity of relevant energy metabolism enzymes were determined in multi-cellular tumor spheroids, as a model of human solid tumors. In HeLa and Hek293 young-spheroids, the OxPhos flux and cytochrome c oxidase protein content and activity were similar to those observed in monolayer cultured cells, whereas the glycolytic flux increased two- to fourfold; the contribution of OxPhos to ATP supply was 60%. In contrast, in old-spheroids, OxPhos, ATP content, ATP/ADP ratio, and phosphorylation potential diminished 50-70%, as well as the activity (88%) and content (3 times) of cytochrome c oxidase. Glycolysis and hexokinase increased significantly (both, 4 times); consequently glycolysis was the predominant pathway for ATP supply (80%). These changes were associated with an increase (3.3 times) in the HIF-1alpha content. After chronic exposure, both oxidative and glycolytic inhibitors blocked spheroid growth, although the glycolytic inhibitors, 2-deoxyglucose and gossypol (IC(50) of 15-17 nM), were more potent than the mitochondrial inhibitors, casiopeina II-gly, laherradurin, and rhodamine 123 (IC(50) > 100 nM). These results suggest that glycolysis and OxPhos might be considered as metabolic targets to diminish cellular proliferation in poorly vascularized, hypoxic solid tumors.

A fully probabilistic risk assessment of Santo Domingo –National District–, Dominican Republic, was conducted using a building by building resolution. A national seismic hazard assessment was developed in order to generate a set of stochastic scenarios for the probabilistic evaluation of seismic risk using the CAPRA platform. Different building classes and vulnerability functions were used to assess damages and losses using probabilistic metrics. Risk premiums of economic loss and casualties were obtained and aggregated by neighborhoods, based on the official cadastral information of the city. Seismic risk was also evaluated from a holistic perspective; i.e. taking into account the expected physical losses as well as the social fragility and lack of resilience conditions, which would increase the second order effects when a strong earthquake strikes the city. Indicators were used to capture the aggravating conditions of the direct physical impact, as well as second order and intangible impact of future earthquakes at urban level. A Urban Seismic Risk Index has been obtained for each neighborhood of the city in order to communicate risk to the stakeholders and decision makers and to identify the areas that will be particularly problematic in case of earthquake and the main social causes of seismic vulnerability.

Reducing risk that emerges from hazards of natural origin and societal vulnerability is a key challenge for the development of more resilient communities and the overall goal of sustainable development. The following chapter outlines a framework for multidimensional, holistic vulnerability assessment that is understood as part of risk evaluation and risk management in the context of Disaster Risk Management (DRM) and Climate Change Adaptation (CCA). As a heuristic, the framework is a thinking tool to guide systematic assessments of vulnerability and to provide a basis for comparative indicators and criteria development to assess key factors and various dimensions of vulnerability, particularly in regions in Europe, however, it can also be applied in other world regions. The framework has been developed within the context of the research project MOVE (Methods for the Improvement of Vulnerability Assessment in Europe; ) sponsored by the European Commission within the framework of the FP 7 program.

Biological molecules that self-assemble in the nanoscale range are useful multifunctional materials. Rotavirus VP6 protein self-assembles into tubular structures in the absence of other rotavirus proteins. Here, we present strategies for selectively directing metal functionalization to the lumen of VP6 nanotubes. The specific in situ metal reduction in the inner surface of nanotube walls was achieved by the simple modification of a method previously reported to functionalize the nanotube outer surface. Silver nanorods and nanowires as long as 1.5 μm were formed inside the nanotubes by coalescence of nanoparticles. Such one-dimensional structures were longer than others previously obtained using bioscaffolds. The interactions between silver ions and the nanotube were simulated to understand the conditions that allowed nanowire formation. Molecular docking showed that a naturally occurring arrangement of aspartate residues enabled the stabilization of silver ions on the internal surface of the VP6 nanotubes. This is the first time that such a spatial arrangement has been proposed for the nucleation of silver nanoparticles, opening the possibility of using such an array to direct functionalization of other biomolecules. These results demonstrate the natural capabilities of VP6 nanotubes to function as a versatile biotemplate for nanomaterials.

Después de ocurrido el terremoto de Lorca, el 11 de mayo de 2011, el Institut Geològic de Catalunya (IGC), la Universidad Politécnica de Cataluña (UPC) y la Asociación Española de Ingeniería Sísmica (AEIS) organizaron, junto con las asociaciones de ingeniería sísmica francesa (AFPS) y portuguesa (SPES), una visita técnica con el objeto de realizar observaciones que permitieran calibrar, verificar y validar los métodos utilizados en las evaluaciones de riesgo sísmico en zonas urbanas. Este artículo resume los aspectos más destacados en cuanto a la observación de la vulnerabilidad de edificios de vivienda, así como de edificios de especial importancia como son hospitales y escuelas. After the earthquake of Lorca, May 11, 2011, the Geological Institute of Catalonia (IGC), the Technical University of Catalonia (UPC) and the Spanish Association for Earthquake Engineering (AEIS) organized a technical visit in order to compile information that allow to calibrate, to verify and to validate the methods used in seismic risk assessments in urban areas. This article summarizes the highlights regarding the vulnerability of residential buildings and buildings of special importance such as hospitals and schools

Risk is defined, for management purposes, as the potential economic, social and environmental consequences of hazardous events that may occur in a specified period of time. From the perspective of this paper, risk requires a multidisciplinary evaluation that takes into account not only the expected physical damage, the number and type of casualties or economic losses, but also the conditions related to social fragility and lack of resilience conditions, which favour the second order effects when a hazard event strike an urban centre. The proposed general method of urban risk evaluation uses the fuzzy sets theory in order to manage qualitative concepts and variables involved in the evaluation. Finally, the method is applied in its single hazard version to the holistic seismic risk evaluation for the cities of Barcelona (Spain) and Bogotá (Colombia).

The main purpose of this review is to update and analyze the effect of several antineoplastic drugs (adriamycin, apoptodilin, casiopeinas, cisplatin, clotrimazole, cyclophosphamide, ditercalinium, NSAIDs, tamoxifen, taxol, 6-mercaptopurine, and alpha-tocopheryl succinate) and energy metabolism inhibitors (2-DOG, gossypol, delocalized lipophilic cations, and uncouplers) on tumor development and progression. The possibility that these antineoplastic drugs currently used in in vitro cancer models, in chemo-therapy, or under study in phase I to III clinical trials induce tumor cellular death by altering also metabolite concentration (i.e., ATP), enzyme activities, and/or energy metabolism fluxes is assessed. It is proposed that the use of energy metabolic therapy, as an alternative or complementary strategy, might be a promising novel approach in the treatment of cancer.

Glycolytic activity during the transition period from anaerobic to aerobic metabolism has been demonstrated to be critical for heart recovery in isolated reperfused hearts. The purpose of this work was to investigate the relevance of the glycolytic pathway in preserving the cardiac function of post-conditioned hearts.The activation of the glycolytic pathway in post-conditioned hearts was evaluated by measuring GLUT-4 insertion, glucose consumption and lactate production. Iodoacetic acid and 2-deoxy-D-glucose were administrated to the working hearts to evaluate the effect of glycolytic inhibition in the post-conditioning protective effect.Post-conditioning maneuvers applied to isolated rat hearts, after prolonged ischemia and before reperfusion, promoted recovery of cardiac mechanical function with sustained increase of GLUT-4 translocation and activation of the glycolytic pathway during ischemia and early reperfusion. Iodoacetate inhibited the protective effect of post-conditioning, without affecting the mitochondrial oxidative capacity. Glycolysis contribution to maintain mechanical function at early reperfusion was observed in post-conditioned hearts perfused with 2-deoxy-D-glucose and in hearts in which iodoacetate was administered only during reperfusion.It is concluded that in the post-conditioned heart, a functional compartmentation of anaerobic energy metabolism, at early reperfusion, plays a significant role in cardiac protection against reperfusion damage.

El presente libro integra una coleccion de articulos que en su conjunto muestran la gestion del riesgo como un reto para las administraciones municipales, argumentando la necesidad de integrar dicho esfuerzo como parte de una estrategia estatal con fuerte liderazgo local, a fin de promover y proteger el desarrollo de los municipios y sus comunidades. Los capitulos, escritos por expertos de America Latina, exploran las opciones institucionales y de politicas, metodologias de evaluacion del riesgo en el territorio y en la infraestructura critica, y de mitigacion de perdidas probables en el patrimonio y los servicios municipales. Con el objetivo de hacer accesible informacion y experiencias replicables en el corto plazo, el libro expone estudios de caso que han sido elaborados por los principales involucrados en los acontecimientos mismos. Se incluyen las experiencias de tres municipalidades colombianas -Manizales, Medellin y Bogota- lideres en el tema, cada una presentada por un servidor publico, protagonista de primera mano: el senor alcalde, el planificador en gestion ambiental y el oficial de la Direccion de Prevencion y Atencion de Emergencias en sus respetivas municipalidades. Estos casos, junto con los de otros municipios centroamericanos, ilustran posibles caminos hacia un desarrollo mas seguro y sostenible para los ciudadanos de la region.

New technologies require the development of novel nanomaterials that need to be fully characterized to achieve their potential. High-resolution low-voltage scanning transmission electron microscopy (STEM) has proven to be a very powerful technique in nanotechnology, but its use for the characterization of nanobiomaterials has been limited. Rotavirus VP6 self-assembles into nanotubular assemblies that possess an intrinsic affinity for Au ions. This property was exploited to produce hybrid nanobiomaterials by the in situ functionalization of recombinant VP6 nanotubes with gold nanoparticles. In this work, Raman spectroscopy and advanced analytical electron microscopy imaging with spherical aberration-corrected (Cs) STEM and nanodiffraction at low-voltage doses were employed to characterize nanobiomaterials. STEM imaging revealed the precise structure and arrangement of the protein templates, as well as the nanostructure and atomic arrangement of gold nanoparticles with high spatial sub-Angstrom resolution and avoided radiation damage. The imaging was coupled with backscattered electron imaging, ultra-high resolution scanning electron microscopy and x-ray spectroscopy. The hybrid nanobiomaterials that were obtained showed unique properties as bioelectronic conductive devices and showed enhanced Raman scattering by their precise arrangement into superlattices, displaying the utility of viral assemblies as functional integrative self-assembled nanomaterials for novel applications.

La estructura y selección de temas de la presente publicación responde, en su mayor parte, a un diagnóstico de crecimiento para Guatemala realizado en 2007, donde se identificaron un conjunto de factores que afectan las posibilidades de desarrollo del país. A lo largo de estas páginas hay un reconocimiento tácito de que, si bien todos los desafíos de desarrollo de una economía son importantes en sí mismos, las principales restricciones al crecimiento varían de país a país. Lo principal radica en priorizarlas como objeto de acción de políticas públicas. Este libro consta de cuatro partes que abarcan desde la identificación de limitantes, agregados y sectoriales, al crecimiento económico de Guatemala hasta el planteamiento de reflexiones y propuestas en el área social que invitan a un diálogo fructífero que permita conducir al país por la senda de más crecimiento con más equidad. No sólo se asume la existencia de importantes retos fiscales, comerciales y sociales, y problemas de exclusión por atender en Guatemala, sino que también se dan propuestas y recomendaciones de política. Sin pretender agotar la discusión sobre los desafíos de desarrollo del país, esta publicación intenta revelar las distintas aristas económicas y sociales que encierran la dinámica de crecimiento y equidad de Guatemala.