Linear Model Selection Based on Risk Estimation

The problem of selecting one model from a family of linear models to describe a normally distributed observed data vector is considered. The notion of the model of given dimension nearest to the observation vector is introduced and methods of estimating the risk associated with such a nearest model are discussed. This leads to new model selection criteria one of which, called the "partial bootstrap", seems particularly promising. The methods are illustrated by specializing to the problem of estimating the non-zero components of a parameter vector on which noisy observations are available.     

An ABC transporter with a secondary-active multidrug translocator domain

Multidrug resistance, by which cells become resistant to multiple unrelated pharmaceuticals, is due to the extrusion of drugs from the cell's interior by active transporters such as the human multidrug resistance P-glycoprotein. Two major classes of transporters mediate this extrusion. Primary-active transporters are dependent on ATP hydrolysis, whereas secondary-active transporters are driven by electrochemical ion gradients that exist across the plasma membrane. The ATP-binding cassette (ABC) transporter LmrA is a primary drug transporter in Lactococcus lactis that can functionally substitute for P-glycoprotein in lung fibroblast cells. Here we have engineered a truncated LmrA protein that lacks the ATP-binding domain. Surprisingly, this truncated protein mediates a proton-ethidium symport reaction without the requirement for ATP. In other words, it functions as a secondary-active multidrug uptake system. These findings suggest that the evolutionary precursor of LmrA was a secondary-active substrate translocator that acquired an ATP-binding domain to enable primary-active multidrug efflux in L. lactis.