124 research outputs found

    Probabilistic model for the representation of the reservoir water level of concrete dams during normal operation periods

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    The dam’s reservoir water level varies over the year according to the water inflow and outflow, as a function of environmental events but also of dam exploitation management policy and human decisions. In the Portuguese dam safety regulation (RSB 2007), the normal water level (NWL) is considered as the optimum exploitation level. However, as proved by the continuous monitoring over the lifetime of a set of dams, the NWL is occasionally exceeded for non-negligible time periods. The reservoir water level, to which the water pressure on the upstream face is related, is a fundamental parameter for the safety and reliability analysis of concrete dams. When water-induced actions are considering the leading loads, only the maximum reservoir water level, usually associated with a high-return-period flood, is relevant. However, for other combinations, in particular, earthquake scenarios, the consideration of the variability of the water level over time is crucial. In reliability analysis of concrete dams, the reservoir water level has been considered either as a deterministic variable, once the loading scenario analyzed assume water-induced actions as leading loads (Westberg 2010), or as a random variable defined using hydrological site information of a specific study case (Altarejos et al. Structural Safety 36-37:1–13 2012). This work proposes a probabilistic model of the reservoir water level of any new dam based only on its geometrical properties, which provides a low-cost alternative to in-depth hydrological analysis. The proposed model can be useful in two stages of the lifecycle of dams: (i) initial design and feasibility stages, and (ii) routine safety assessment of existing structures, as in both stages the costs of a complete hydrological analysis is too high for the level of detail required. For that, the recorded reservoir water level of 27 Portuguese large concrete dams is used. A normalized sinusoidal model, with annual period, is adjusted to the reservoir water level annual history of those dams by beta regression. Generally, a good agreement between observations and the proposed model, for most of the annual adjustments, was achieved. The distribution parameters of the random variables were estimated through the maximum likelihood estimation (MLE) method. The physical, model and statistical uncertainties were quantified and can now be included in a reliability analysis procedur

    Motives for corporate cash holdings:the CEO optimism effect

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    We examine the chief executive officer (CEO) optimism effect on managerial motives for cash holdings and find that optimistic and non-optimistic managers have significantly dissimilar purposes for holding more cash. This is consistent with both theory and evidence that optimistic managers are reluctant to use external funds. Optimistic managers hoard cash for growth opportunities, use relatively more cash for capital expenditure and acquisitions, and save more cash in adverse conditions. By contrast, they hold fewer inventories and receivables and their precautionary demand for cash holdings is less than that of non-optimistic managers. In addition, we consider debt conservatism in our model and find no evidence that optimistic managers’ cash hoarding is related to their preference to use debt conservatively. We also document that optimistic managers hold more cash in bad times than non-optimistic managers do. Our work highlights the crucial role that CEO characteristics play in shaping corporate cash holding policy

    Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process

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    A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies
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