Chemical-genetic screen identifies riluzole as an enhancer of Wnt/β-catenin signaling in melanoma

To identify new protein and pharmacological regulators of Wnt/β-catenin signaling, we used a cell-based reporter assay to screen a collection of 1857 human-experienced compounds for their ability to enhance activation of the β-catenin reporter by a low concentration of WNT3A. This identified 44 unique compounds, including the FDA-approved drug riluzole, which is presently in clinical trials for treating melanoma. We found that treating melanoma cells with riluzole in?vitro enhances the ability of WNT3A to regulate gene expression, to promote pigmentation, and to decrease cell proliferation. Furthermore riluzole, like WNT3A, decreases metastases in a mouse melanoma model. Interestingly, siRNAs targeting the metabotropic glutamate receptor, GRM1, a reported indirect target of riluzole, enhance β-catenin signaling. The unexpected regulation of β-catenin signaling by both riluzole and GRM1 has implications for the future uses of this drug.     

Study of the Light‐Induced Spin Crossover Process of the [FeII(bpy)3]2+ Complex

Ab initio calculations have been performed on [Fe^II(bpy)₃]²⁺ (bpy=bipyridine) to establish the variation of the energy of the electronic states relevant to light‐induced excited‐state spin trapping as a function of the Fe? ligand distance. Light‐induced spin crossover takes place after excitation into the singlet metal‐to‐ligand charge‐transfer (MLCT) band. We found that the corresponding electronic states have their energy minimum in the same region as the low‐spin (LS) state and that the energy dependence of the triplet MLCT states are nearly identical to the ¹MLCT states. The high‐spin (HS) state is found to cross the MLCT band near the equilibrium geometry of the MLCT states. These findings give additional support to the hypothesis of a fast singlet–triplet interconversion in the MLCT manifold, followed by a ³MLCT–HS (⁵T₂) conversion accompanied by an elongation of the Fe? N distance.     

Mixed-width aisle configurations for order picking in distribution centers

Space required for the order picking area and labor required to perform the picking activity are two significant costs for a distribution center (DC). Traditionally, DCs employ either entirely wide or entirely narrow aisles in their picking systems. Wide aisles allow pickers to pass each other, which reduces blocking, and requires fewer pickers than their narrow-aisle counterpart for the same throughput. However, the amount of space required for wide-aisle configurations is high. Narrow aisles utilize less space than wide aisles, but are less efficient because of the increased likelihood of congestion experienced by pickers. We propose a variation to the traditional orthogonal aisle designs where both wide and narrow aisles are mixed within the configuration, with a view that mixed-width aisles may provide a compromise between space and labor. To analyze these new mixed-width aisle configurations, we develop analytical models for space and travel time considering randomized storage and traversal routing policies. Through a cost-based optimization model, we identify system parameters for which mixed-width aisle configurations are optimal. Experimental results indicate that annual cost savings of up to $48,000 can be realized over systems with pure wide or narrow aisle configurations.     

Effect of electrostatic spray on human pulmonary epithelial cells

Aerosolization techniques for delivery of gene therapies to the lungs decrease activity of these treatments. The low transfection is attributed to loss in molecular integrity. Electrosprays can aerosolize DNA without structural loss. Electrospray affects on human pulmonary cells are unknown. This study is to assess toxicity, inflammatory response, and transfection of DNA mixtures delivered via electrospray to human pulmonary cells. EpiAirway? cells are cultured on air–liquid interfaces and simulate in vivo. All conditions examined (except PEI/DNA 10:1) showed no toxic or inflammation response. Transfection was not observed. In vitro results indicate that electrosprays have potential for administering DNA therapeutics pulmonarily.     

Degradation Thermique des Polystyrenes et du Polychlorure de Vinyle : Application d'une Matrice d'experiences a l'etude de l'influence des Parametres de l'analyse Thermomanometrique. Partie I : Exploitation des résultats par traitement mathématique

Thermal degradation of polystyrene and polyvinylchloride was studied by thermomanometric analysis. A design of experiments was used to quantify the influence of 8 physico-chemical parameters on the responses of the analyser and on the different types of degradation compounds. This revised version was published online in July 2006 with corrections to the Cover Date.     

Parametric processes in microstructured and highly nonlinear optical fibres

Optical parametric amplification is an important nonlinear process in photonic crystal fibres driven by the small effective area and the special dispersion characteristics of these fibres. Aside from its role in supercontinuum generation, parametric amplification can lead to efficient wavelength conversion, limited primarily by the uniformity of the diameter of currently available fibres. The related Bragg scattering process can be used for both wavelength conversion and optical switching, again limited by the physical characteristics of the fibres used.     

A Ca2+‐, Mg2+‐, and Zn2+‐Based Dendritic Contractile Nanodevice with Two pH‐Dependent Motional Functions

A contractile dendritic motional device is reported where metal ions with biological importance—Ca²⁺ (the main regulatory and signaling species of the natural muscles), Mg²⁺, and Zn²⁺—initiate two kinds of motional functions. The first motional function is the metal‐ion‐induced contraction of a linear strand into a Z‐shaped dinuclear complex, and the second one is the change of the height of Z‐shaped complexes via transmetalation. By means of the pH‐dependent counterligand tren, the two motional features of the machine can depend on alternate additions of acid and base. An optical response is associated with the conversion of the linear form (which is yellow) into the metalated Z‐shaped one (which is red).