Membrane transporters in drug development

Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling. © 2010 Macmillan Publishers Limited

Complexity revealed in the greening of the Arctic

As the Arctic warms, vegetation is responding, and satellite measures indicate widespread greening at high latitudes. This 'greening of the Arctic' is among the world’s most important large-scale ecological responses to global climate change. However, a consensus is emerging that the underlying causes and future dynamics of so-called Arctic greening and browning trends are more complex, variable and inherently scale-dependent than previously thought. Here we summarize the complexities of observing and interpreting high-latitude greening to identify priorities for future research. Incorporating satellite and proximal remote sensing with in-situ data, while accounting for uncertainties and scale issues, will advance the study of past, present and future Arctic vegetation change

Enhanced Stiffness of Amorphous Polymer Surfaces under Confinement of Localized Contact Loads

The apparent stiffness of various amorphous polymer surfaces at room temperature was measured in response to five maximum indentation loads imposed through two well-characterized conospherical diamond probes. These maximum loads correspond to indentation contact depths hc, ranging from 5nm to >100nm from the free surface. The enhanced apparent stiffness near the surface is recognized as a result of an interface formed at the contact surface confined between the polymers and the diamond probe. Four different processing and thermal history routes were employed, including compression molding (CM), injection molding (IM), spin coating (SC), and annealing after spin coating (SC-A) for PS and PMMA. The results provide the basis for isolating the effects of mechanical compression/confinement and of probe surface chemistry in the mechanical behavior of polymer surfaces under localized contact