Erythropoietin inhibits chemotherapy-induced cell death and promotes a senescence-like state in leukemia cells

There are conflicting reports on the adverse effects of erythropoietin (EPO) for the management of cancer-associated anemia. The recognition that erythropoietin receptors (EPORs) are expressed outside the erythroid lineage and concerns that erythropoiesis-stimulating agents (ESAs) may cause tumors to grow and increase the risk of venous thromboembolism have resulted in substantially fewer cancer patients receiving ESA therapy to manage myelosuppressive chemotherapy. In this study, we found that EPO suppresses p53-dependent apoptosis induced by genotoxic (daunorubicin, doxorubicin, and γ-radiation) and non-genotoxic (nutlin-3a) agents and induces a senescence-like state in myeloid leukemia cells. EPO interferes with stress-dependent Mdm2 downregulation and leads to the destabilization of p53 protein. EPO selectively modulates the expression of p53 target genes in response to DNA damage preventing the induction of a number of noncoding RNAs (ncRNAs) previously associated with p53-dependent apoptosis. EPO also enhances the expression of the cyclin-dependent kinase inhibitor p21WAF1 and promotes recruitment of p53 to the p21 promoter. In addition, EPO antagonizes Mcl-1 protein degradation in daunorubicin-treated cells. Hence, EPO signaling targets Mcl-1 expression and the p53-Mdm2 network to promote tumor cell survival.York University Librarie

Fashion, Novelty and Optimality: An application from Physics

We apply a physical based model to describe the clothes fashion market. Every time a new outlet appears on the market, it can invade the market under certain specific conditions. Hence, the "old'' outlet can be completely dominated and disappears. Each creator competes for a finite population of agents. Fashion phenomena are shown to result from a collective phenomenon produced by local individual imitation effects. We assume that, in each step of the imitation process, agents only interact with a subset rather than with the whole set of agents. People are actually more likely to influence (and be influenced by) their close ''neighbours''. Accordingly we discuss which strategy is best fitted for new producers when people are either simply organised into anonymous reference groups or when they are organised in social groups hierarchically ordered. While counterfeits are shown to reinforce the first strategy, creating social leaders can permit to avoid them.Comment: 24 pages, 7 figure

Numerical framework for transcritical real-fluid reacting flow simulations using the flamelet progress variable approach

An extension to the classical FPV model is developed for transcritical real-fluid combustion simulations in the context of finite volume, fully compressible, explicit solvers. A double-flux model is developed for transcritical flows to eliminate the spurious pressure oscillations. A hybrid scheme with entropy-stable flux correction is formulated to robustly represent large density ratios. The thermodynamics for ideal-gas values is modeled by a linearized specific heat ratio model. Parameters needed for the cubic EoS are pre-tabulated for the evaluation of departure functions and a quadratic expression is used to recover the attraction parameter. The novelty of the proposed approach lies in the ability to account for pressure and temperature variations from the baseline table. Cryogenic LOX/GH2 mixing and reacting cases are performed to demonstrate the capability of the proposed approach in multidimensional simulations. The proposed combustion model and numerical schemes are directly applicable for LES simulations of real applications under transcritical conditions.Comment: 55th AIAA Aerospace Sciences Meeting, Dallas, T

Refractometry of organosilica microspheres

The refractive index of novel organosilica (nano/micro)material is determined using two methods. The first method is based on analysis of optical extinction efficiency of organosilica beads versus wavelength, which is obtained by a standard laboratory spectrometer. The second method relies on the measurable trapping potential of these beads in the focused light beam (laser tweezers). Polystyrene beads were used to test these methods, and the determined dispersion curves of refractive index values have been found accurate. The refractive index of organosilica beads has been determined to range from 1.60-1.51 over the wavelength range of 300-1100 nm.Comment: 9 pages, 8 figure

A Dual Read-Out Assay to Evaluate the Potency of Compounds Active against Mycobacterium tuberculosis

PMCID: PMC3617142This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Molecular Tilt on Monolayer-Protected Nanoparticles

The structure of the tilted phase of monolayer-protected nanoparticles is investigated by means of a simple Ginzburg-Landau model. The theory contains two dimensionless parameters representing the preferential tilt angle and the ratio (epsilon) between the energy cost due to spatial variations in the tilt of the coating molecules and that of the van der Waals interactions which favors uniform tilt. We analyze the model for both spherical and octahedral particles. On spherical particles, we find a transition from a tilted phase, at small (epsilon), to a phase where the molecules spontaneously align along the surface normal and tilt disappears. Octahedral particles have an additional phase at small characterized by the presence of six topological defects. These defective configurations provide preferred sites for the chemical functionalization of monolayer-protected nanoparticles via place-exchange reactions and their consequent linking to form molecules and\ud bulk materials

Rapid acceleration of electrons in the magnetosphere by fast-mode MHD waves

During major megnetic storms, enhanced flux of relativistic electrons in the inner magnetosphere have been observed to correleated with ULF waves. The enhancements can take place over a period of several hours. In order to account for such a rapid generation of relativistic electrons, we examine the mechanism of transit-time acceleration of electrons by low-frequency fast-mode MHD waves, here the assumed form of ULF waves. Calcaulations of the acceleration timescales in the model show that fast-mode waves in the Pc4 to Pc5 frequency range, with typically observed wave amplitudes 10--20 nT, can accelerate the seed electrons to energies of order MeV in a period of a few hours.Comment: 9 pages, 3 figures, Accepted to J. Geophys. Re