Saturation Transfer Difference-NMR (STD-NMR) spectroscopy has emerged as a powerful screening tool and a straightforward way to study the binding epitopes of active compounds in early stage lead discovery in pharmaceutical research. Here we report the application of STD NMR to characterize the binding of the anti-inflammatory drugs ibuprofen, diclofenac and ketorolac to COX-1 and COX-2. Using well-studied COX inhibitors and by comparing STD signals with crystallographic structures we show that there is a relation between the orientations of ibuprofen and diclofenac in the COX-2 active site and the relative STD responses detected in the NMR experiments. Based on this analysis we propose that ketorolac should bind to the COX-2 active site in similar orientation as that of diclofenac. We also show that the combination of STD NMR with competition experiments constitutes a valuable tool to address the recently proposed behavior of COX-2 as functional heterodimers and complement enzyme activity studies in the effort to rationalize COX inhibition mechanisms.

Summary: We consider various classes of monoids of transformations on a finite chain, in particular of transformations that preserve or reverse either the order or the orientation. Being finite monoids we are naturally interested in computing both their cardinals and their idempotent numbers. Fibonacci and Lucas numbers play an essential role in the last computations.

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For r≥3, a clique-extension of order r+1 is a connected graph that consists of a Kr plus another vertex adjacent to at most r-1 vertices of Kr. In this paper we consider the problem of finding the smallest number t such that any graph G of order n admits a decomposition into edge disjoint copies of a fixed graph H and single edges with at most t elements. Here we solve the case when H is a fixed clique-extension of order r+1, for all r≥3 and will also obtain all extremal graphs. This work extends results proved by Bollobás [Math.\ Proc.\ Cambridge Philosophical Soc 79 (1976) 19--24] for cliques.

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In the last few decades there has been a massive growth in the Waste of Electric and ElectronicEquipment (WEEE). Part of these residues was already properly treated in some countries, but the lack of environmentally friendly options forced the European Union (EU) to take action. Two EU directives were created based on reduction, reutilization and recycling of WEEE. The need to properly designrecoverynetworks for such products appears as mandatory, where not only the economic aspects should be accounted for but also the environmental ones. The present paper addresses this problem and presents a generic optimization model for the design and planning of a recovery and treatment network of WEEE, minimizing both the costs and the environmental impacts that arise from the activity performed.

The model is applied to the real case of Amb3E, the Portuguese Association for the Management of Waste of Electric and ElectronicEquipment. Since its formation, in 2006, this organization has been registering an immense growth in the volume of residue collected, and faces now the necessity of reformulating its recoverynetwork. Both the actual cost structure and the best possible cost structure for Amb3E, given by the optimization of the model, are analyzed. These two scenarios are compared in order to turn clear the differences between them and to assess how the recoverynetwork of Amb3E can be improved through optimization. A similar analysis is performed from an environmental impacts perspective.

Software transactional memory is a promising programming model that adapts many concepts borrowed from the databases world to control concurrent accesses to main memory (RAM). This paper discusses how to support revertible operations, such as memory allocation and release, within software libraries that will be used in software memory transactional contexts. The proposal is based in the extension of the transaction life cycle state diagram with new states associated to the execution of user-defined handlers. The proposed approach is evaluated in terms of functionality and performance by way of a use case study and performance tests. Results demonstrate that the proposal and its current implementation are flexible, generic and efficient

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