miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

Multidrug resistance (MDR) remains one of the most significant obstacles in breast cancer treatment, and this process often involves dysregulation of a great number of microRNAs (miRNAs). Some miRNAs are indicators of drug resistance and confer resistance to chemotherapeutic drugs, although our understanding of this complex process is still incomplete. We have used a combination of miRNA profiling and real-time PCR in two drug-resistant derivatives of MCF-7 and Cal51 cells. Experimental modulation of miR expression has been obtained by retroviral transfection. Taxol and doxorubicin IC50 values were obtained by short-term drug sensitivity assays. Apoptosis was determined by flow cytometry after annexin V staining, by caspase 3/7 and caspase 9 activity assays and the levels of apoptosis-related proteins bcl-2 and bax by real-time PCR and Western blot. miR target was studied using transient transfection of luciferase constructs with the 3 untranslated regions (UTR) of target mRNAs. Small interfering RNA-mediated genetic knock-down was performed in MDR cells and its modulatory effect on apoptosis examined. The effect of miRNA on tumorigenicity and tumor drug response was studied in mouse xenografts. miRNA profiling of two drug-resistant breast cancer cell models indicated that miR-218 was down-regulated in both MCF-7/A02 and CALDOX cells. Ectopic expression of miR-218 resensitized both drug-resistant cell lines to doxorubicin and taxol due to an increase in apoptosis. miR-218 binds survivin (BIRC5) mRNA 3-UTR and down-regulated reporter luciferase activity. Experimental down-regulation of survivin by RNA interference in drug-resistant cells did mimic the sensitization observed when miRNA-218 was up-regulated. In addition, resensitization to taxol was also observed in mouse tumor xenografts from cells over-expressing miR-218. miR-218 is involved in the development of MDR in breast cancer cells via targeting survivin and leading to evasion of apoptosis. Targeting miR-218 and survivin may thus provide a potential strategy for reversing drug resistance in breast cancer

Geometry, thermodynamics, and finite-size corrections in the critical Potts model

We establish an intriguing connection between geometry and thermodynamics in the critical q-state Potts model on two-dimensional lattices, using the q-state bond-correlated percolation model (QBCPM) representation. We find that the number of clusters of the QBCPM has an energy-like singularity for q different from 1, which is reached and supported by exact results, numerical simulation, and scaling arguments. We also establish that the finite-size correction to the number of bonds, has no constant term and explains the divergence of related quantities as q --> 4, the multicritical point. Similar analyses are applicable to a variety of other systems.Comment: 12 pages, 6 figure

Universal scaling functions for bond percolation on planar random and square lattices with multiple percolating clusters

Percolation models with multiple percolating clusters have attracted much attention in recent years. Here we use Monte Carlo simulations to study bond percolation on $L_{1}\times L_{2}$ planar random lattices, duals of random lattices, and square lattices with free and periodic boundary conditions, in vertical and horizontal directions, respectively, and with various aspect ratio $L_{1}/L_{2}$. We calculate the probability for the appearance of $n$ percolating clusters, $W_{n},$ the percolating probabilities, $P$, the average fraction of lattice bonds (sites) in the percolating clusters, $_{n}$ ($_{n}$), and the probability distribution function for the fraction $c$ of lattice bonds (sites), in percolating clusters of subgraphs with $n$ percolating clusters, $f_{n}(c^{b})$ ($f_{n}(c^{s})$). Using a small number of nonuniversal metric factors, we find that $W_{n}$, $P$, $_{n}$ ($_{n}$), and $f_{n}(c^{b})$ ($f_{n}(c^{s})$) for random lattices, duals of random lattices, and square lattices have the same universal finite-size scaling functions. We also find that nonuniversal metric factors are independent of boundary conditions and aspect ratios.Comment: 15 pages, 11 figure

Positive and copositive spline approximation in Lp[0, 1]

AbstractThe order of positive and copositive spline approximation in the Lp-norm, 1 ≤ p < ∞, is studied; the main results are 1.(1) the error of positive approximation by splines is bounded by Cω2(f, 1n)p if f has a nonnegative extension;2.(2) the order deteriorates to ω1 if f does not have such an extension;3.(3) the error of copositive spline approximation is bounded by Cω(f, 1n)p;4.(4) if f is also continuous, the error in (3) can be estimated in terms of the third τ-modulus τ3(f, 1n)p.All constants in the error bounds are absolute

Finite-size scaling for the Ising model on the Moebius strip and the Klein bottle

We study the finite-size scaling properties of the Ising model on the Moebius strip and the Klein bottle. The results are compared with those of the Ising model under different boundary conditions, that is, the free, cylindrical, and toroidal boundary conditions. The difference in the magnetization distribution function $p(m)$ for various boundary conditions is discussed in terms of the number of the percolating clusters and the cluster size. We also find interesting aspect-ratio dependence of the value of the Binder parameter at $T=T_c$ for various boundary conditions. We discuss the relation to the finite-size correction calculations for the dimer statistics.Comment: 4 pages including 5 eps figures, RevTex, to appear in Phys. Rev. Let

Some symmetry properties of spin currents and spin polarizations in multi-terminal mesoscopic spin-orbit coupled systems

We study theoretically some symmetry properties of spin currents and spin polarizations in multi-terminal mesoscopic spin-orbit coupled systems. Based on a scattering wave function approach, we show rigorously that in the equilibrium state no finite spin polarizations can exist in a multi-terminal mesoscopic spin-orbit coupled system (both in the leads and in the spin-orbit coupled region) and also no finite equilibrium terminal spin currents can exist. By use of a typical two-terminal mesoscopic spin-orbit coupled system as the example, we show explicitly that the nonequilibrium terminal spin currents in a multi-terminal mesoscopic spin-orbit coupled system are non-conservative in general. This non-conservation of terminal spin currents is not caused by the use of an improper definition of spin current but is intrinsic to spin-dependent transports in mesoscopic spin-orbit coupled systems. We also show that the nonequilibrium lateral edge spin accumulation induced by a longitudinal charge current in a thin strip of \textit{finite} length of a two-dimensional electronic system with intrinsic spin-orbit coupling may be non-antisymmetric in general, which implies that some cautions may need to be taken when attributing the occurrence of nonequilibrium lateral edge spin accumulation induced by a longitudinal charge current in such a system to an intrinsic spin Hall effect.Comment: 11 pages, 6 figure