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A temporary seismic network composed of 11 stations was installed in the city of Potenza (Southern Italy) to record local and regional seismicity within the context of a national project funded by the Italian Department of Civil Protection (DPC). Some stations were moved after a certain time in order to increase the number of measurement points, leading to a total of 14 sites within the city by the end of the experiment. Recordings from 26 local earthquakes (M-l 2.2-3.8 ) were analyzed to compute the site responses at the 14 sites by applying both reference and non-reference site techniques. Furthermore, the Spectral Intensity (SI) for each local earthquake, as well as their ratios with respect to the values obtained at a reference site, were also calculated. In addition, a field survey of 233 single station noise measurements within the city was carried out to increase the information available at localities different from the 14 monitoring sites. By using the results of the correlation analysis between the horizontal-to-vertical spectral ratios computed from noise recordings (NHV) at the 14 selected sites and those derived by the single station noise measurements within the town as a proxy, the spectral intensity correction factors for site amplification obtained from earthquake analysis were extended to the entire city area. This procedure allowed us to provide a microzonation map of the urban area that can be directly used when calculating risk scenarios for civil defence purposes. The amplification factors estimated following this approach show values increasing along the main valley toward east where the detrital and alluvial complexes reach their maximum thickness.
The safe upper limit for inclusion of vitamin A in complete diets for growing dogs is uncertain, with the result that current recommendations range from 5.24 to 104.80 mu mol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy (ME). The aim of the present study was to determine the effect of feeding four concentrations of vitamin A to puppies from weaning until 1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever and Miniature Schnauzer, were randomly assigned to one of four treatment groups. Following weaning at 8 weeks of age, puppies were fed a complete food supplemented with retinyl acetate diluted in vegetable oil and fed at 1ml oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 mu mol retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME. Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36 and 52 weeks of age and analysed for markers of vitamin A metabolism and markers of safety including haematological and biochemical variables, bone-specific alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I collagen and dual-energy X-ray absorptiometry. Clinical examinations were conducted every 4 weeks. Data were analysed by means of a mixed model analysis with Bonferroni corrections for multiple endpoints. There was no effect of vitamin A concentration on any of the parameters, with the exception of total serum retinyl esters, and no effect of dose on the number, type and duration of adverse events. We therefore propose that 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the formulation of diets designed for puppy growth.
The reaction of the German labor market to the Great Recession 2008/09 was relatively mild – especially compared to other countries. The reason lies not only in the specific type of the recession – which was favorable for the German economy structure – but also in a series of labor market reforms initiated between 2002 and 2005 altering, inter alia, labor supply incentives. However, irrespective of the mild response to the Great Recession, there are a number of substantial future challenges the German labor market will soon have to face. Female labor supply still lies well below that of other countries and a massive demographic change over the next 50 years will have substantial effects on labor supply as well as the pension system. In addition, due to a skill-biased technological change over the next decades, firms will face problems of finding employees with adequate skills. The aim of this paper is threefold. First, we outline why the German labor market reacted in such a mild fashion, describe current economic trends of the labor market in light of general trends in the European Union, and reveal some of the main associated challenges. Thereafter, the paper analyzes recent reforms of the main institutional settings of the labor market which influence labor supply. Finally, based on the status quo of these institutional settings, the paper gives a brief overview of strategies to combat adequately the challenges in terms of labor supply and to ensure economic growth in the future.
Dynamic regulatory on/off minimization for biological systems under internal temporal perturbations
(2012)
Background: Flux balance analysis (FBA) together with its extension, dynamic FBA, have proven instrumental for analyzing the robustness and dynamics of metabolic networks by employing only the stoichiometry of the included reactions coupled with adequately chosen objective function. In addition, under the assumption of minimization of metabolic adjustment, dynamic FBA has recently been employed to analyze the transition between metabolic states.
Results: Here, we propose a suite of novel methods for analyzing the dynamics of (internally perturbed) metabolic networks and for quantifying their robustness with limited knowledge of kinetic parameters. Following the biochemically meaningful premise that metabolite concentrations exhibit smooth temporal changes, the proposed methods rely on minimizing the significant fluctuations of metabolic profiles to predict the time-resolved metabolic state, characterized by both fluxes and concentrations. By conducting a comparative analysis with a kinetic model of the Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate that the principle of regulatory on/off minimization coupled with dynamic FBA can accurately predict the changes in metabolic states.
Conclusions: Our methods outperform the existing dynamic FBA-based modeling alternatives, and could help in revealing the mechanisms for maintaining robustness of dynamic processes in metabolic networks over time.
Cell-level kinetic models for therapeutically relevant processes increasingly benefit the early stages of drug development. Later stages of the drug development processes, however, rely on pharmacokinetic compartment models while cell-level dynamics are typically neglected. We here present a systematic approach to integrate cell-level kinetic models and pharmacokinetic compartment models. Incorporating target dynamics into pharmacokinetic models is especially useful for the development of therapeutic antibodies because their effect and pharmacokinetics are inherently interdependent. The approach is illustrated by analysing the F(ab)-mediated inhibitory effect of therapeutic antibodies targeting the epidermal growth factor receptor. We build a multi-level model for anti-EGFR antibodies by combining a systems biology model with in vitro determined parameters and a pharmacokinetic model based on in vivo pharmacokinetic data. Using this model, we investigated in silico the impact of biochemical properties of anti-EGFR antibodies on their F(ab)-mediated inhibitory effect. The multi-level model suggests that the F(ab)-mediated inhibitory effect saturates with increasing drug-receptor affinity, thereby limiting the impact of increasing antibody affinity on improving the effect. This indicates that observed differences in the therapeutic effects of high affinity antibodies in the market and in clinical development may result mainly from Fc-mediated indirect mechanisms such as antibody-dependent cell cytotoxicity.
Parafoveal preview benefit (PB) is an implicit measure of lexical activation in reading. PB has been demonstrated for orthographic and phonological but not for semantically related information in English. In contrast, semantic PB is obtained in German and Chinese. We propose that these language differences reveal differential resource demands and timing of phonological and semantic decoding in different orthographic systems.
This study provides a detailed analysis of the mid-Holocene to present-day precipitation change in the Asian monsoon region. We compare for the first time results of high resolution climate model simulations with a standardised set of mid-Holocene moisture reconstructions. Changes in the simulated summer monsoon characteristics (onset, withdrawal, length and associated rainfall) and the mechanisms causing the Holocene precipitation changes are investigated. According to the model, most parts of the Indian subcontinent received more precipitation (up to 5 mm/day) at mid-Holocene than at present-day. This is related to a stronger Indian summer monsoon accompanied by an intensified vertically integrated moisture flux convergence. The East Asian monsoon region exhibits local inhomogeneities in the simulated annual precipitation signal. The sign of this signal depends on the balance of decreased pre-monsoon and increased monsoon precipitation at mid-Holocene compared to present-day. Hence, rainfall changes in the East Asian monsoon domain are not solely associated with modifications in the summer monsoon circulation but also depend on changes in the mid-latitudinal westerly wind system that dominates the circulation during the pre-monsoon season. The proxy-based climate reconstructions confirm the regional dissimilarities in the annual precipitation signal and agree well with the model results. Our results highlight the importance of including the pre-monsoon season in climate studies of the Asian monsoon system and point out the complex response of this system to the Holocene insolation forcing. The comparison with a coarse climate model simulation reveals that this complex response can only be resolved in high resolution simulations.