The ability of aluminium to inhibit the (Na+/K+)ATPase activity has been observed by several authors. During chronic dietary exposure to AlCl3, brain (Na+/K+)ATPase activity drops, even if no alterations of catalytic subunit protein expression and of energy charge potential are observed. The aluminium effect on (Na+/K+)ATPase activity seems to implicate the reduction of interacting protomers within the oligomeric ensemble of the membrane-bound (Na+/K+)ATPase. The activity of (Na+/K+)ATPase is altered by the microviscosity of lipid environment. We studied if aluminium inhibitory effect on (Na+/K+)ATPase is modified by alterations in synaptosomal membrane cholesterol content. Adult male Wistar rats were submitted to chronic dietary AlCl3exposure (0.03 g/day of AlCl3) and/or to colestipol, a hypolidaemic drug (0.31 g/day) during 4 months. The activity of (Na+/K+)ATPase was studied in brain cortex synaptosomes with different cholesterol contents. Additionally, we incubate synaptosomes with methyl-β-cyclodextrin for both enrichment and depletion of membrane cholesterol content, with or without 300 μM AlCl3. This enzyme activity was significantly reduced by micromolar AlCl3added in vitro and when aluminium was orally administered to rats. The oral administration of colestipol reduced the cholesterol content and concomitantly inhibited the (Na+/K+)ATPase. The aluminium inhibitory effect on synaptosomal (Na+/K+)ATPase was reduced by cholesterol depletion both in vitro and in vivo.

Aluminium is neurotoxic in humans and has been implicated in several neurological disorders. Chronic use of buffered aspirins, as aspegic, would likely constitute the major human aluminium uptake source. Low-dose aspirin is beneficial in secondary prevention of cardiovascular events, so it is widely used for long periods of time. We studied if oral administration of aspegic to rats modified the aluminium inhibitory effect on brain (Na+/K+)ATPase due to alteration in synaptosomal membrane aluminium content. Adult male Wistar rats were submitted to sub-acute (1.00 g/day during 10 days) and chronic (0.03 g/day during 4 months) dietary AlCl3 exposure and/or to aspegic (0.11 g/day). The exposure protocol increased the synaptosomal aluminium content especially after a long-term exposure to aluminium and aspegic. Although no alterations were observed in rat body weight gain and adenylate energy charge, the (Na+/K+)ATPase activity was significantly reduced when aluminium was orally administered to rats. The oral administration of aspegic increased the synaptosomal aluminium content and concomitantly enhanced the (Na+/K+)ATPase inhibition. In our exposure protocol the increase in synaptosomal aluminium content correlates with the reduction of the (Na+/K+)ATPase activity.

The ability of aluminum to inhibit the (Na+/K+)ATPase activity has been observed by several investigators. The (Na+/K+)ATPase is characterized by a complex molecular heterogeneity that results from the expression and differential association of multiple isoforms of both catalytic (alpha) and regulatory (beta) subunits. For instance, three main alpha (alpha(1), alpha(2) and alpha(3)) and three beta (beta(1), beta(2) and beta(3)) subunit isoforms exist in vertebrate nervous tissue, whereas only alpha(1) and beta(1) have been identified in kidney. However, no studies have focused on determining the change in (Na+/K+)ATPase isoforms caused by chronic exposure to aluminum and its relation with aluminum toxicity. In this study, adult male Wistar rats were submitted to chronic dietary AlCl3 exposure (0.03 g/day of AlCl3 for 4 months), and the activity and protein expression of (Na+/K+)ATPase isozymes were studied in brain cortex synaptosomes and in kidney homogenates. The intracellular levels of adenine nucleotides, plasma membrane integrity, and aluminum accumulation were also studied in brain synaptosomes. Aluminum accumulation upon chronic dietary AlCl3 administration significantly decreased the (Na+/K+)ATPase activity measured in the presence of nonlimiting Mg-ATP concentrations, without compromising protein expression of alpha-subunit isoforms in brain and kidney. Aluminum-induced synaptosomal (Na+/K+)ATPase inhibition was due to a reduction in the activity of isozymes containing alpha(1)-alpha(2) and alpha(3)-subunits. The onset of enzyme inhibition was accompanied by a decrease of the (Na+/K+)ATPase sensitivity to submicromolar concentrations of ouabain, and it preceded major damage in plasma membrane integrity and energy supply, as revealed by the analysis of lactate dehydrogenase leakage and endogenous adenine nucleotides. The data suggest that, during chronic dietary exposure to AlCl3, brain (Na+/K+)ATPase activity drops, even if no significant alterations of catalytic subunit protein expression, cellular energy depletion, and changes in cell membrane integrity are observed. Implications regarding underlying mechanisms of aluminum neurotoxicity are discussed.

Risk analysis is a critical link in the reduction of casualties and damages due to earthquakes. Recognition of this relation has led to a rapid rise in demand for accurate, reliable and flexible risk assessment software. However, there is a significant disparity between the high quality scientific data developed by researchers and the availability of versatile, open and user-friendly risk analysis tools to meet the demands of end-users. In the past few years several open-source software have been developed that play an important role in the seismic research, such as OpenSHA and OpenSEES. There is however still a gap when it comes to open-source risk assessment tools and software. In order to fill this gap, the Global Earthquake Model (GEM) has been created. GEM is an internationally sanctioned program initiated by the OECD that aims to build independent, open standards to calculate and communicate earthquake risk around the world. This initiative started with a one-year pilot project named GEM1, during which an evaluation of a number of existing risk software was carried out. After a critical review of the results it was concluded that none of the software were adequate for GEM requirements and therefore, a new object-oriented tool was to be developed. This paper presents a summary of some of the most well known applications used in risk analysis, highlighting the main aspects that were considered for the development of this risk platform. The research that was carried out in order to gather all of the necessary information to build this tool was distributed in four different areas: information technology approach, seismic hazard resources, vulnerability assessment methodologies and sources of exposure data. The main aspects and findings for each of these areas will be presented as well as how these features were incorporated in the up-to-date risk engine. Currently, the risk engine is capable of predicting human or economical losses worldwide considering both deterministic and probabilistic-based events, using vulnerability curves. A first version of GEM will become available at the end of 2013. Until then the risk engine will continue to be developed by a growing community of developers, using a dedicated open-source platform.

The recognition of fragility and vulnerability functions as a fundamental tool in seismic risk assessment has led to the development of more and more complex and elaborate procedures for their computation. Although these functions have been traditionally produced using observed damage and loss data, more recent studies propose the employment of analytical methodologies as a way to overcome the frequent lack of post-earthquake data. The variation of the structural modelling approach on the estimation of building capacity has been the target of many studies in the past; however, its influence on the resulting vulnerability model for classes of buildings, the impact in loss estimations or propagation of the uncertainty to the seismic risk calculations has so far been the object of limited scrutiny. In this paper, an extensive study of static and dynamic procedures for estimating the nonlinear response of buildings has been carried out to evaluate the impact of the chosen methodology on the resulting capacity, fragility, vulnerability and risk outputs. Moreover, the computational effort and numerical stability provided by each approach have been evaluated and conclusions drawn regarding the optimal balance between accuracy and complexity. Copyright © 2013 John Wiley & Sons, Ltd.

This paper presents a new procedure to derive fragility functions for populations of buildings that relies on the displacement-based earthquake loss assessment (DBELA) methodology. The recent developments in this methodology are also presented herein, such as the development of new formulae for the calculation of the yield period or the consideration of infilled frame structures. In the fragility method proposed herein, thousands of synthetic buildings have been produced considering probabilistic distributions describing the variability in their geometrical and material properties. Then, their nonlinear capacity has been estimated using the DBELA method and their performance against a large set of ground motion records has been calculated. Global limit states are used to estimate the distribution of buildings in each damage state for different levels of ground motion, and a regression algorithm is applied to derive fragility functions for each limit state. The proposed methodology is demonstrated for the case of ductile and non-ductile Turkish reinforced concrete buildings with and without masonry infill walls, and compared with results obtained using nonlinear dynamic procedures and with the results from previous studies.

The recognition of fragility functions as a fundamental tool in seismic risk assessment has led to the development of more and more complex and elaborate procedures for their computation. Although vulnerability functions have been traditionally produced using observed damage and loss data, more recent studies propose the employment of analytical methodologies as a way to overcome the frequent lack of post-earthquake data. The variation of the structural modelling approaches on the estimation of building capacity has been the target of many studies in the past, however, its influence in the resulting vulnerability model, impact in loss estimations or propagation of the uncertainty to the seismic risk calculations has so far been the object of restricted scrutiny. Hence, in this paper, an extensive study of static and dynamic procedures for estimating the nonlinear response of buildings has been carried out in order to evaluate the impact of the chosen methodology on the resulting vulnerability and risk outputs. Moreover, the computational effort and numerical stability provided by each approach were evaluated and conclusions were obtained regarding which one offers the optimal balance between accuracy and complexity.

This paper presents a new procedure to derive fragility functions for populations of buildings that relies on the displacement-based earthquake loss assessment (DBELA) methodology. In the method proposed herein, thousands of synthetic buildings have been produced considering the probabilistic distribution describing the variability in geometrical and material properties. Then, their nonlinear capacity has been estimated using the DBELA method and their response against a large set of ground motion records has been estimated. Global limit states are used to estimate the distribution of buildings in each damage state for different levels of ground motion, and a regression algorithm is applied to derive fragility functions for each limit state. The proposed methodology is demonstrated for the case of ductile and non-ductile Turkish reinforced concrete frames with masonry infills.

Risk analysis has a critical role in the reduction of casualties and damages due to earthquakes. Recognition of this relation has led to a rapid rise in demand for accurate, reliable and flexible risk assessment numerical tools and software. As a response to this need, the Global Earthquake Model (GEM) started the development of an open source platform called OpenQuake, for calculating seismic hazard and risk at different scales. Along with this framework, also several other tools to support users creating their own models and visualizing their results are currently being developed, and will be made available as a Modelers Tool Kit (MTK). In this paper, a description of the architecture of OpenQuake is provided, highlighting the current data model, workflow of the calculators and the main challenges raised when running this type of calculations in a global scale. In addition, a case study is presented using the Marmara Region (Turkey) for the calculations, in which the losses for a single event are estimated, as well as probabilistic risk for a 50 years time span.