Der Ruf : Aus: Actions and reactions

Wolfgang Weisl

Die Erwiderung des Actions-Comités auf den Bericht Dr. Nathans

Aktionskomitee

Rechenschaftsbericht des Actions-Comités

M. T. Schnirer

Metabolism and actions of 2 -chloro-2$\sp\prime$-fluoro-arabinosyladenine

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. ^

John Rziha, Perfecting human actions: St. Thomas Aquinas on human participation in eternal law, Catholic University of America Press, Washington, 2009; 300 p., ISBN 978-0-8132-1672-0.

Fil: Peretó Rivas, Rubén.

Product-related environmental regulation and voluntary environmental actions : impacts of RoHS and REACH in Malaysia

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.

Accident Management Actions In An Upper-Head Small-Break Loss-Of-Coolant Accident With High-Pressure Safety Injection Failed

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.

Diagnosing Causes of Water Scarcity in Complex Water Resources Systems and Identifying Risk Management Actions

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

Recommendations on seismic actions on bridges

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.

Recommendations on seismic actions on port structures

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.

Safety and health in forest harvesting operations. Diagnosis and preventive actions. A review

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..

On the Use of Situational and Body Information in Goalkeeper Actions during a Soccer Penalty Kick

Artículo Experimental