Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

Electrochemical methods for speciation of trace elements in marine waters. Dynamic aspects

The contribution of electrochemical methods to the knowledge of dynamic speciation of toxic trace elements in marine waters is critically reviewed. Due to the importance of dynamic considerations in the interpretation of the electrochemical signal, the principles and recent developments of kinetic features in the interconversion of metal complex species will be presented. As dynamic electrochemical methods, only stripping techniques (anodic stripping voltammetry and stripping chronopotentiometry) will be used because they are the most important for the determination of trace elements. Competitive ligand ex- change-adsorptive cathodic stripping voltammetry, which should be considered an equilibrium technique rather than a dynamic method, will be also discussed because the complexing parameters may be affected by some kinetic limitations if equilibrium before analysis is not attained and/or the flux of the adsorbed complex is in fluenced by the lability of the natural complexes in the water sample. For a correct data interpretation and system characterization the comparison of results obtained from different techniques seems essential in the articulation of a serious discussion of their meaning

Spatial aggregation of land uses allocation and pesticide efficiency at landscape level A Multi-ware production approach

We extend the single-stage framework of damage-control inputs like pesticides to a multi-ware framework where four technologies are considered. The economic technologies describe the production and the damages due to pests while the ecological technologies represent the dynamics of pests and predators populations. To account for the possibilities of spatial effects of land uses (crop and non-crop habitats), we consider an analysis at the landscape level and try to find the optimal allocation of the land uses that help minimizing pesticides. To this aim we rely on a prey-predator simulation model. We assess pesticides performance considering nonparametric production frontier techniques. Our results indicate that pesticides can be reduced by 7.7% without reducing the landscape production. In terms of land uses we found that grasslands areas should be increased by more than twice and croplands with medium levels of pesticides unchanged. Croplands with zero and high levels of pesticides should be reduced. In terms of trade-offs between pesticides and the landscape production we found that the spillover effect is very high and result in a negative trade-off because of the destruction of predators by pesticides. Pesticides inefficiency can be reduced when treated areas are spatially aggregated and when grasslands are subsidized. Acknowledgement

Luenberger and Malmquist Productivity Indices: Theoretical Comparisons and Empirical Illustration

http://www.blackwell-synergy.com/toc/boer/55/4International audienceThis contribution establishes, from a theoretical viewpoint, the relations between the Malmquist productivity indices, that measure in either input or output orientations, and the Luenberger productivity indices, that can simultaneously contract inputs and expand outputs, but that can also measure in either input or output orientations. The main result is that a Malmquist productivity index overestimates productivity changes, since it provides productivity measures that are nearly twice those given by the Luenberger productivity index looking for simultaneous contractions of inputs and expansions of outputs. This relationship is empirically illustrated using data from 20 OECD countries over the 1974–97 period