Inhibition of the multidrug resistance P-glycoprotein: Time for a change of strategy?

P-glycoprotein (P-gp) is a key player in the multidrug-resistant phenotype in cancer. The protein confers resistance by mediating the ATP-dependent efflux of an astonishing array of anticancer drugs. Its broad specificity has been the subject of numerous attempts to inhibit the protein and restore the efficacy of anticancer drugs. The general strategy has been to develop compounds that either compete with anticancer drugs for transport or act as direct inhibitors of P-gp. Despite considerable in vitro success, there are no compounds currently available to "block" P-gp-mediated resistance in the clinic. The failure may be attributed to toxicity, adverse drug interaction, and numerous pharmacokinetic issues. This review provides a description of several alternative approaches to overcome the activity of P-gp in drug-resistant cells. These include 1) drugs that specifically target resistant cells, 2) novel nanotechnologies to provide high-dose, targeted delivery of anticancer drugs, 3) compounds that interfere with nongenomic transfer of resistance, and 4) approaches to reduce the expression of P-gp within tumors. Such approaches have been developed through the pursuit of greater understanding of resistance mediators such as P-gp, and they show considerable potential for further application. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics

Structural properties of crumpled cream layers

The cream layer is a complex heterogeneous material of biological origin which forms spontaneously at the air-milk interface. Here, it is studied the crumpling of a single cream layer packing under its own weight at room temperature in three-dimensional space. The structure obtained in these circumstances has low volume fraction and anomalous fractal dimensions. Direct means and noninvasive NMR imaging technique are used to investigate the internal and external structure of these systems.Comment: 9 pages, 4 figures, accepted in J. Phys. D: Appl. Phy

Spin-glass state of vortices in YBa2Cu3Oy and La2-xSrxCuO4 below the metal-to-insulator crossover

Highly disordered magnetism confined to individual weakly interacting vortices is detected by muon spin rotation in two different families of high-transition-temperature superconductors, but only in samples on the low-doping side of the low-temperature normal state metal-to-insulator crossover (MIC). The results support an extended quantum phase transition (QPT) theory of competing magnetic and superconducting orders that incorporates the coupling between CuO2 planes. Contrary to what has been inferred from previous experiments, the static magnetism that coexists with superconductivity near the field-induced QPT is not ordered. Our findings unravel the mystery of the MIC and establish that the normal state of high-temperature superconductors is ubiquitously governed by a magnetic quantum critical point in the superconducting phase.Comment: 9 pages, 9 figure

Design study of the deepsky ultraviolet survey telescope

Preliminary mechanical design and specifications are presented for a wide field ultraviolet telescope and detector to be carried as a Spacelab payload. Topics discussed include support structure stiffness (torsional and bending), mirror assembly, thermal control, optical alignment, attachment to the instrument pointing pallet, control and display, power requirements, acceptance and qualification test plans, cost analysis and scheduling. Drawings are included

EIT and diffusion of atomic coherence

We study experimentally the effect of diffusion of Rb atoms on Electromagnetically Induced Transparency (EIT) in a buffer gas vapor cell. In particular, we find that diffusion of atomic coherence in-and-out of the laser beam plays a crucial role in determining the EIT resonance lineshape and the stored light lifetime.Comment: 5 pages, 8 figure

A network-based dynamical ranking system for competitive sports

From the viewpoint of networks, a ranking system for players or teams in sports is equivalent to a centrality measure for sports networks, whereby a directed link represents the result of a single game. Previously proposed network-based ranking systems are derived from static networks, i.e., aggregation of the results of games over time. However, the score of a player (or team) fluctuates over time. Defeating a renowned player in the peak performance is intuitively more rewarding than defeating the same player in other periods. To account for this factor, we propose a dynamic variant of such a network-based ranking system and apply it to professional men's tennis data. We derive a set of linear online update equations for the score of each player. The proposed ranking system predicts the outcome of the future games with a higher accuracy than the static counterparts.Comment: 6 figure

Hole doping dependences of the magnetic penetration depth and vortex core size in YBa2Cu3Oy: Evidence for stripe correlations near 1/8 hole doping

We report on muon spin rotation measurements of the internal magnetic field distribution n(B) in the vortex solid phase of YBa2Cu3Oy (YBCO) single crystals, from which we have simultaneously determined the hole doping dependences of the in-plane Ginzburg-Landau (GL) length scales in the underdoped regime. We find that Tc has a sublinear dependence on 1/lambda_{ab}^2, where lambda_{ab} is the in-plane magnetic penetration depth in the extrapolated limits T -> 0 and H -> 0. The power coefficient of the sublinear dependence is close to that determined in severely underdoped YBCO thin films, indicating that the same relationship between Tc and the superfluid density is maintained throughout the underdoped regime. The in-plane GL coherence length (vortex core size) is found to increase with decreasing hole doping concentration, and exhibit a field dependence that is explained by proximity-induced superconductivity on the CuO chains. Both the magnetic penetration depth and the vortex core size are enhanced near 1/8 hole doping, supporting the belief by some that stripe correlations are a universal property of high-Tc cuprates.Comment: 12 pages, 13 figure