Targeting lactate transport suppresses in vivo breast tumour growth.

BACKGROUND Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as "Warburg effect". Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment. RESULTS The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth. CONCLUSIONS This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.

A review of sustainable approaches in transport infrastructure geotechnics

Transportation geotechnics associated with constructing and maintaining properly functioning transportation infrastructure is a very resource intensive activity. Large amounts of materials and natural resources are required, consuming proportionately large amounts of energy and fuel. Thus, the implementation of the principles of sustainability is important to reduce energy consumption, carbon footprint, greenhouse gas emissions, and to increase material reuse/recycling, for example. This paper focusses on some issues and activities relevant to sustainable earthwork construction aimed at minimising the use of energy and the production of CO2 while improving the in-situ ground to enable its use as a foundation without the consumption of large amounts of primary aggregate as additional foundation layers. The use of recycled materials is discussed, including steel slag and tyre bales, alongside a conceptual framework for evaluating the utility of applications for recycled materials in transportation infrastructure.

Electronic tongue: a versatile tool for mineral and fruit-flavored waters recognition

Natural mineral waters (still), effervescent natural mineral waters (sparkling) and aromatized waters with fruit-flavors (still or sparkling) are an emerging market. In this work, the capability of a potentiometric electronic tongue, comprised with lipid polymeric membranes, to quantitatively estimate routinely quality physicochemical parameters (pH and conductivity) as well as to qualitatively classify water samples according to the type of water was evaluated. The study showed that a linear discriminant model, based on 21 sensors selected by the simulated annealing algorithm, could correctly classify 100 % of the water samples (leave-one out cross-validation). This potential was further demonstrated by applying a repeated K-fold cross-validation (guaranteeing that at least 15 % of independent samples were only used for internal-validation) for which 96 % of correct classifications were attained. The satisfactory recognition performance of the E-tongue could be attributed to the pH, conductivity, sugars and organic acids contents of the studied waters, which turned out in significant differences of sweetness perception indexes and total acid flavor. Moreover, the E-tongue combined with multivariate linear regression models, based on sub-sets of sensors selected by the simulated annealing algorithm, could accurately estimate waters pH (25 sensors: R 2 equal to 0.99 and 0.97 for leave-one-out or repeated K-folds cross-validation) and conductivity (23 sensors: R 2 equal to 0.997 and 0.99 for leave-one-out or repeated K-folds cross-validation). So, the overall satisfactory results achieved, allow envisaging a potential future application of electronic tongue devices for bottled water analysis and classification.

Particle transport in fouling caused by kaolin-water suspensions on copper tubes

Particulate fouling tests were carried out using kaolin-water suspensions flowing through an annular heat exchanger with a copper inner tube. The flow rate was changed from test to test, but the fluid temperature and pH, as well as the particle concentration, were maintained constant. In the lower range of fluid velocities (<0.5 m/s), the deposition process seemed to be controlled by mass transfer. The corresponding experimental transport fluxes were compared to the predictions obtained with several models, showing that diffusion governed particle transport. The absolute values of the mass transfer fluxes and their dependences on the Reynolds number were satisfactorily predicted by some of the models.