948 resultados para actions collectives


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M. T. Schnirer

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2-Chloro-9-(2-deoxy-2-fluoro-$\beta $-D-arabinofuranosyl)adenine(Cl-F-ara-A) is a new deoxyadenosine analogue which is resistant to phosphorolytic cleavage and deamination, and exhibits therapeutic activity for both leukemia and solid tumors in experimental systems. To characterize its mechanism of cytotoxicity, the present study investigated the cellular pharmacology and the biochemical and molecular mechanisms of action of Cl-F-ara-A, from entrance of the drug into the cell, chemical changes to active metabolites, targeting on different cellular enzymes, to final programmed cell death response to the drug treatment.^ Cl-F-ara-A exhibited potent inhibitory action on DNA synthesis in a concentration-dependent and irreversible manner. The mono-, di-, and triphosphates of Cl-F-ara-A accumulated in cells, and their elimination was non-linear with a prolonged terminal phase, which resulted in prolonged dNTP depression. Ribonucleotide reductase activity was inversely correlated with the cellular Cl-F-ara-ATP level, and the inhibition of the reductase was saturated at higher cellular Cl-F-ara-ATP concentrations. The sustained inhibition of ribonucleotide reductase and the consequent depletion of deoxynucleotide triphosphate pools result in a cellular Cl-F-ara-ATP to dATP ratio which favors analogue incorporation into DNA.^ Incubation of CCRF-CEM cells with Cl-F-ara-A resulted in the incorporation of Cl-F-ara-AMP into DNA. A much lesser amount was associated with RNA, suggesting that Cl-F-ara-A is a more DNA-directed compound. The site of Cl-F-ara-AMP in DNA was related to the ratio of the cellular concentrations of the analogue triphosphate and the natural substrate dATP. Clonogenicity assays showed a strong inverse correlation between cell survival and Cl-F-ara-AMP incorporation into DNA, suggesting that the incorporation of Cl-F-ara-A monophosphate into DNA is critical for the cytotoxicity of Cl-F-ara-A.^ Cl-F-ara-ATP competed with dATP for incorporation into the A-site of the extending DNA strand catalyzed by both DNA polymerase $\alpha$ and $\varepsilon$. The incorporation of Cl-F-ara-AMP into DNA resulted in termination of DNA strand elongation, with the most pronounced effect being observed at Cl-F-ara-ATP:dATP ratio $>$1. The presence of Cl-F-ara-AMP at the 3$\sp\prime$-terminus of DNA also resulted in an increased incidence of nucleotide misincorporation in the following nucleotide position. The DNA termination and the nucleotide misincorporation induced by the incorporation of Cl-F-ara-AMP into DNA may contribute to the cytotoxicity of Cl-F-ara-A. ^

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Voluntary environmental actions, such as the adoption of ISO 14001, are gaining increasing attention in developing countries. This study examines the mechanism of ISO 14001 diffusion in a developing economy on the basis of a unique corporate survey of manufacturing sectors in Malaysia. Product-related environmental regulations, such as REACH, are contributing to this diffusion indirectly by promoting quality control standards such as ISO 9001. The importance of foreign direct investment and global value chains for ISO 14001 diffusion is also confirmed.

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Since the Three Mile Island accident, an important focus of pressurized water reactor (PWR) transient analyses has been a small-break loss-of-coolant accident (SBLOCA). In 2002, the discovery of thinning of the vessel head wall at the Davis Besse nuclear power plant reactor indicated the possibility of an SBLOCA in the upper head of the reactor vessel as a result of circumferential cracking of a control rod drive mechanism penetration nozzle - which has cast even greater importance on the study of SBLOCAs. Several experimental tests have been performed at the Large Scale Test Facility to simulate the behavior of a PWR during an upper-head SBLOCA. The last of these tests, Organisation for Economic Co-operation and Development Nuclear Energy Agency Rig of Safety Assessment (OECD/NEA ROSA) Test 6.1, was performed in 2005. This test was simulated with the TRACE 5.0 code, and good agreement with the experimental results was obtained. Additionally, a broad analysis of an upper-head SBLOCA with high-pressure safety injection failed in a Westinghouse PWR was performed taking into account different accident management actions and conditions in order to check their suitability. This issue has been analyzed also in the framework of the OECD/NEA ROSA project and the Code Applications and Maintenance Program (CAMP). The main conclusion is that the current emergency operating procedures for Westinghouse reactor design are adequate for these kinds of sequences, and they do not need to be modified.

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From the water management perspective, water scarcity is an unacceptable risk of facing water shortages to serve water demands in the near future. Water scarcity may be temporary and related to drought conditions or other accidental situation, or may be permanent and due to deeper causes such as excessive demand growth, lack of infrastructure for water storage or transport, or constraints in water management. Diagnosing the causes of water scarcity in complex water resources systems is a precondition to adopt effective drought risk management actions. In this paper we present four indices which have been developed to evaluate water scarcity. We propose a methodology for interpretation of index values that can lead to conclusions about the reliability and vulnerability of systems to water scarcity, as well as to diagnose their possible causes and to propose solutions. The described methodology was applied to the Ebro river basin, identifying existing and expected problems and possible solutions. System diagnostics, based exclusively on the analysis of index values, were compared with the known reality as perceived by system managers, validating the conclusions in all cases

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The paper describes the main features of a technical Recommendation first draft on Seismic Actions on Bridges, promoted by the Spanish Ministry of Public Works (MOPT). Although much more research is needed to clarify the seismic behaviour of the vast class of problems present in port structures the current state of the art allows at least a classificaton of subjects and the establishment of minimum requirements to guide the design. Also the use of more refined methods for specially dangerous situations needs some general guidelines that contribute to mantein the design under reasonable safety margins. The Recommendations of the Spanish MOPT are a first try in those directions.

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The paper describes the main features of a Technical Recommendation first draft on Seismic Action on port structures promoted recently by the Spanish Ministry of Public Works (MOPT). Although much more research is needed to clarify the seismic behaviour of the vast class of problems present in port structures the current state of the art allows at least a classification of subjects and the establishment of minimum requirements to guide the design. Also the use of more refined methods for specially dangerous situations needs some general guidelines that contribute to mantein the design under reasonable safety margins. The Recommendations of the Spanish MOPT are a first try in those directions.

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Aim of study: to review the present state of the art in relation to the main labour risks and the most relevant results of recent studies evaluating the safety and health conditions of the forest harvesting work and better ways to reduce accidents. Area of study: It focuses mainly on developed Countries, where the general concern about work risks prevention, together with the complex idiosyncrasy of forest work in forest harvesting operations, has led to a growing interest from the forest scientific and technical community. Material and Methods: The main bibliographic and Internet references have been identified using common reference analysis tools. Their conclusions and recommendations have been comprehensively summarized. Main results: Collection of the principal references and their most important conclusions relating to the main accident risk factors, their causes and consequences, the means used towards their prevention, both instrumental as well as in the aspects of training and business management, besides the influence of the growing mechanization of logging operations on those risks. Research highlights: Accident risk is higher in forest harvesting than in most other work sectors, and the main risk factors such as experience, age, seasonality, training, protective equipment, mechanization degree, etc. have been identified and studied. The paper summarizes some relevant results, one of the principal being that the proper entrepreneurial risk management is a key factor leading to the success in minimizing labour risks..

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Road traffic is the greatest contributor to the carbon footprint of the transport sector and reducing it has become one of the main targets of sustainable transport policies. An analysis of the main factors influencing greenhouse gas (GHG) emissions is essential for designing new energy- and environmentally efficient strategies for the road transport. This paper addresses this need by (i) identifying factors which influence the carbon footprint, including traffic activity, fuel economy and socioeconomic development; and (ii) proposing a methodological framework which uses Modified Laspeyres Index decomposition to analyze the effect of important drivers on the changes in emissions of road transport in Spain during the period from 1990 to 2010. The results demonstrate that the country׳s economic growth has been closely linked to the rise in GHG emissions. The innovative contribution of this paper is the special analysis of the changes in mobility patterns and GHG emissions during the economic crisis, when, for the first time, Spanish road traffic emissions decreased. The reduction of road transport and improved energy efficiency has been powerful contributors to this decrease, demonstrating the effectiveness of energy-saving measures. On the basis of this analysis, several tailored policy recommendations have been suggested for future implementation.

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Fuel poverty can be defined as “the inability to afford adequate warmth in the home" and it is the result of the combination of three items: low household income, housing lack of energy efficiency and high energy bills. Although it affects a growing number of households within the European Union only some countries have an official definition for it. In 2013, the European Parliament claimed the Commission and Estate Members to develop different policies in order to fight household energy vulnerability. The importance of tackling fuel poverty is based on the critical consequences it has for human health living below certain temperatures. In Spain some advances have been made in this field but main existing studies remain at the statistical level and do not deepen the understanding of the problem from the perspective of dwelling indoor habitability conditions. What is more, this concept is yet to be officially defined. This paper presents the evaluation of fuel poverty in a building block of social housing located in the centre of Zaragoza and how this issue determined the strategies implemented in the energy retrofitting intervention project. At a first step, fuel poverty was appraised through the exploration of indoor thermal conditions. The adaptive thermal comfort (UNE-EN 15251:2008) method was used to establish the appropriate indoor temperatures and consequently to determine what can be called 'comfort gap'. Results were collated and verified with energy bills collection and a survey work that gathered data from neighbours. All this permitted pointing out those households more in need. Results from the social analysis combined with the evaluation of the building thermal performance determined the intervention. The renovation project was aimed at the implementation of passive strategies that improve households thermal comfort in order to alleviate households fuel poverty situation. This research is part of the project NewSolutions4OldHousing (LIFE10 ENV/ES/439) cofounded by the European Commission under the LIFE+ Programme.

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The interest for modelling of human actions acting on structures has been recurrent since the first accidents on suspension bridges in the nineteenth century such as Broughton (1831) in the U.K. or Angers (1850) in France. Stadiums, gymnasiums are other types of structure where human induced vibration is very important. In these structures a particular phenomenon appears such as the interaction personstructure (lock-in), the person-person synchronization, and the influence of the mass and damping of the people in the structural behaviour. This paper focuses on the latter topic. In order to evaluate these property modifications several tests have been carried out on a stand-alone building. For the test an electro-dynamic shaker was installed at a fixed point of the gym slab and different groups of people were located around the shaker. The dynamic characteristics of the structure without people inside have been calculated by two methods: using a three-dimensional finite element model of the building and by operational modal analysis. These calculated experimental and numerical values are the reference values used to evaluate the modifications in the dynamic properties of the structure.

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In this paper we present the tests on a structure designed to be a gymnasium, which has natural frequencies within that range. In these tests the gym slab was instrumented with acceleration sensors and different people jumped on a force plate installed on the floor. The test results have been compared with predictions based on the two existing load modelling alternatives (Sim and SCI Guide) and two new methodologies for modelling jumping loads has been proposed. The results of the force plate trials were analysed in an attempt to better characterize the profile of the jump force and determine how best to approximate it. In the first proposed methodology the study is carried out in the frequency domain using an average power spectral density of the jumps. In the second proposed methodology, the jump force is decomposed into the summation of one peak with a large period and a number of peaks with smaller periods. Utilizing a similar model to that of the Sim model, the approximation will still be comprised of the summation of two quadratic cosine functions.