Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of “onco-channelopathy”. Here, we review the contribution of ion channels and transporters in multiple myeloma (MM), a hematological neoplasia characterized by the expansion of tumor plasma cells (MM cells) in the bone marrow (BM). Deregulation of ion channels sustains MM progression by modulating intracellular pathways that promote MM cells’ survival, proliferation, and drug resistance. Finally, we focus on the promising role of ion channels as therapeutic targets for the treatment of MM patients in a combination strategy with currently used anti-MM drugs to improve their cytotoxic activity and reduce adverse effects.     

Failure mechanisms in granular media: a discrete element analysis

This paper attempts to numerically validate the concept of diffuse failure using a discrete element method. First, the theoretical background is reviewed, and it is shown how the kinetic energy of a system, initially at rest after a loading history, is likely to abruptly increase under the effect of disturbances. The vanishing of the second-order work thus constitutes a basic ingredient, related to both the pioneering work of Hill (J Mech Phys Solids (6):236–249, 1958) and the notion of bifurcation applied to geomechanics (Vardoulakis and Sulem in Bifurcation analysis in geomechanics, Chapman & Hall Publisher, London, 1995). Discrete numerical simulations were performed on homogeneous three-dimensional specimens, and the three basic conditions that must be satisfied in order to observe a failure mechanism are numerically checked. Finally, this work illustrates the phenomena that are likely to affect in situ slopes, for instance, when the loading (due to weather conditions or human activities) meets the three basic conditions for a failure mechanism to develop.     

An improved observation model for super-resolution under affine motion.

Super-resolution (SR) techniques make use of subpixel shifts between frames in an image sequence to yield higher resolution images. We propose an original observation model devoted to the case of nonisometric inter-frame motion as required, for instance, in the context of airborne imaging sensors. First, we describe how the main observation models used in the SR literature deal with motion, and we explain why they are not suited for nonisometric motion. Then, we propose an extension of the observation model by Elad and Feuer adapted to affine motion. This model is based on a decomposition of affine transforms into successive shear transforms, each one efficiently implemented by row-by-row or column-by-column one-dimensional affine transforms. We demonstrate on synthetic and real sequences that our observation model incorporated in a SR reconstruction technique leads to better results in the case of variable scale motions and it provides equivalent results in the case of isometric motions.     

Assembly and Characterizations of Bifunctional Fluorescent and Magnetic Microneedles With One Decade Length Tunability

This report presents the fabrication of bifunctional magnetic and fluorescent microneedles (µNDs) made of a ternary mixture of magnetic nanoparticles (NPs), quantum dots (QDs), and polyelectrolyte. The assembly relies on the electrostatic complexation of negatively charged NPs with positively charged polymer strands and is controlled by the charge ratio between the nanoparticle building blocks and the polymer mortar. The resulting 1D objects can be actuated using an external magnetic field and can be imaged using fluorescence microscopy, thanks to the fluorescent and superparamagnetic properties inherited from their NP constituents. Using a combination of core and surface characterizations and a state‐of‐the‐art image analysis algorithm, the dependence of the brightness and length on the ternary composition is thoroughly investigated. In particular, statistics on hundreds of µNDs with a range of compositions show that the µNDs have a log‐lormal length distribution and that their mean length can be robustly tuned in the 5–50 µm range to match the relevant length scales of various applications in micromixing, bioassays or biomechanics.     

Highly Stable Colloidal “Giant” Quantum Dots Sensitized Solar Cells

Colloidal quantum dots (QDs) are widely studied due to their promising optoelectronic properties. This study explores the application of specially designed and synthesized “giant” core/shell CdSe/(CdS)_x QDs with variable CdS shell thickness, while keeping the core size at 1.65 nm, as a highly efficient and stable light harvester for QD sensitized solar cells (QDSCs). The comparative study demonstrates that the photovoltaic performance of QDSCs can be significantly enhanced by optimizing the CdS shell thickness. The highest photoconversion efficiency (PCE) of 3.01% is obtained at optimum CdS shell thickness ≈1.96 nm. To further improve the PCE and fully highlight the effect of core/shell QDs interface engineering, a CdSe_x S_1?x interfacial alloyed layer is introduced between CdSe core and CdS shell. The resulting alloyed CdSe/(CdSe_x S_1?x )₅/(CdS)₁ core/shell QD‐based QDSCs yield a maximum PCE of 6.86%, thanks to favorable stepwise electronic band alignment and improved electron transfer rate with the incorporation of CdSe_x S_1?x interfacial layer with respect to CdSe/(CdS)₆ core/shell. In addition, QDSCs based on “giant” core/CdS‐shell or alloyed core/shell QDs exhibit excellent long‐term stability with respect to bare CdSe‐based QDSCs. The giant core/shell QDs interface engineering methodology offers a new path to improve PCE and the long‐term stability of liquid junction QDSCs.     

Mlcrolasers based on silica microspheres

Light can be confined efficiently in the high-Q, small-volume whispering-gallery-modes observed in silica microspheres. By coupling these microspheres to eroded optical fibers and fiber tips, direct mapping of the whispering-gallery modes has been achieved and the mode numbers have been assessed. The properties of these modes have allowed us to obtain laser action with very low thresholds in Nd-doped silica microspheres. Further projects in the field of non-linear optics and cavity quantum electrodynamics are described.     

Upper bounds for blocking probabilities in large multi‐rate loss networks

In this paper, we consider large loss networks with fixed routing and multirate traffic. We use singlelink formulae and standard results on multidimensional Gaussian distributions to obtain upper bounds for blocking probabilities of new calls under light up to critical loading conditions. This is the loading regime of interest for many practical applications such as admission control in ATM networks. The main advantage of our approach is that the complexity does not scale with the size of the system, making it numerically attractive. Comparison with simulation results show that we get good upper bounds. We conclude by discussing the correlation between links in a network.     

The rise and fall of French Ecological Tax Reform: social acceptability versus political feasibility in the energy tax implementation process

The French government has a 10-year history of negotiations with industry, resulting in voluntary agreements on energy consumption. When implemented, these voluntary agreements produced very few results in terms of global reduction of greenhouse emissions (Politiques et Management Public 11(4) (1993) 47), hence the idea of an energy tax became increasingly attractive for many French decision-makers. Ecological/Environmental Tax Reform (ETR) should have been one of the major political decisions and successes of the past leftwing coalition government. Instead it became one of its major failures as the Constitutional Court decided to terminate the energy tax project in December 2000. Through insights gleaned from focus groups and interviews with business-people and decision-makers, an attempt is made to understand the failure of the energy tax project. Firstly, decision-makers lacked crucial information about public and business opinions and secondly, there were conflicts between the relevant administrations. The fuel revolts of 2000 ended any hope of resolving the conflicts and implementing ETR, which was ultimately found unconstitutional. This paper examines the political controversies raised by the ETR project and the reasons for its eventual collapse, in the hope of contributing new understanding to the body of knowledge on the political difficulties of introducing environmental policy instruments.