Turnover of inositol polyphosphate pyrophosphates in pancreatoma cells

There is little information concerning the intracellular function of inositol 1,3,4,5,6-pentakis- and hexakisphosphate, despite their being the most abundant inositol polyphosphates. Current opinions that they play passive roles as antioxidants (Graf, E., Mahoney, J. R., Bryant, R. G., and Eaton, J. W. (1987) J. Biol. Chem. 259, 3620-3624) or "housekeeping" molecules (Berridge, M. J., and Irvine, R. F. (1989) Nature 341, 197-205) arises from belief in their metabolic lethargy. However, we have discovered that cell homogenates, incubated with 5 mM fluoride and 5 mM ATP, converted both inositol hexakisphosphate (Km = 2 +/- 0.5 microM, Vmax = 9 +/- 2 pmol/mg of protein/min) and inositol 1,3,4,5,6-pentakisphosphate (Km = 13 +/- 4 microM, Vmax = 11 +/- 5 pmol/mg of protein/min) to more polar products. These reactions were also observed in intact cells treated with 0.5-20 mM fluoride, and the precursor/product relationships were confirmed by comparing the effects of fluoride on cells differentially labeled with [3H]inositol in either short-term or pulse-chase protocols. The novel products were determined to be inositol pyrophosphates because of their relatively specific hydrolysis by tobacco pyrophosphatase and alkaline phosphatase. The pyrophosphates were metabolized rapidly by cell homogenates back to their pentakisphosphate and hexakisphosphate precursors. This endogenous pyrophosphatase activity was inhibited by up to 99% by 5 mM fluoride in vitro. In intact cells incubated with 10 mM fluoride, about 20% of the inositol 1,3,4,5,6-pentakisphosphate pool, and 50% of the inositol hexakisphosphate pool were each converted to pyrophosphate derivatives within 1 h.     

Secure Network Management Within an Open-Source Mobile Agent Framework

Mobile agents (MAs) have been proposed for decentralized network management. This paper explains how Aglets, a Java open-source MA framework, not a proprietary system, can be used for security-enhanced network management, complementing the security of the Simple Network Management Protocol (SNMP) version 3. The solution prototyped is a hybrid environment where network management applications use MAs that interact locally with SNMP agents via the SNMP protocol. The implemented class libraries extend the security infrastructure of Aglets, by incorporating cryptographic functions through the Java Cryptography Extension. The extension enables data fields to be encrypted, while code is to be digitally signed. Legacy SNMPv1 and v2 enabled devices, with elementary security, can also be upgraded through this approach, which can effectively avoid a range of attacks. Consideration has been given to auxiliary functionality such as responding to SNMP traps, key distribution, logging, and secure clock synchronization.     

Corrosion in alkanolamine used for acid gas removal: From natural gas processing to CO2 capture

The aim of this paper is to review some of the parameters influencing the corrosivity of alkanolamine solvents used for natural gas purification or for CO₂ capture. In the light of literature data and of new experimental results, the influences of temperature and of acid gas loading are discussed. These two parameters appear to have a strong impact on corrosion rates of carbon steel, with extrapolated corrosion rates of several tens of mm/year for the highest temperature and acid gas loading condition. It is then proposed to discuss about similarities and differences between natural gas processing and CO₂ capture from flue gas. For both applications, alkanolamine processes are used. Still, differences can be found in operating parameters. The most significant gap concerns the lean amine sections. In acid gas treatment, the regeneration of the solvent is often performed down to zero loading. Under these conditions, an extremely low corrosivity of the lean solvent is expected. On the contrary, CO₂ capture from flue gas requires only a partial stripping of the CO₂ in the regeneration section, due to energy efficiency reasons. Then, the lean solvent still contains some acid gas, and subsequently a higher corrosivity. Finally, the general principles for material selection for the different parts of acid gas removal units are discussed, considering both cases of natural gas processing or CO₂ capture.     

The European construction industry and its competitiveness: a construct of the European Commission

The 'European construction industry' is a fiction that tends to obscure its heterogeneous character and to mar studies and policies of the European Commission aimed at improving the internal and external 'competitiveness' of the sector. In order to assess the process of integration in Europe under the impact of its own dynamics as well as Union policies, this paper looks at the dynamics of the sector from three different aspects: as investment, production and labour process. It shows, in particular, the persistent regional and social disparities dividing the industry into separate entities. Political attention tends to focus on a small number of construction companies competing for a few projects which represent the European dimension. Yet, these companies still rely on their respective national bases and local labour from the place where construction is carried out. Persistent divisions between the states are also reflected in the low level of transnational organization of the construction industry. The policy of the European Commission generally ignores these divisions and attempts to establish principles intended to make a whole sector more 'competitive', while its component parts, operating at hugely different levels of productivity, do not even meet on the same market. This paper argues that, instead of trying in vain to introduce a 'knock-out' system of competition in the EU Member States, a targeted approach might help raise productivity in lagging regions and thus improve the basis of competitiveness on global markets.     

Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.