The Synthesis and Biological Evaluation of Multifunctionalised Derivatives of Noscapine as Cytotoxic Agents

Noscapine, a phthalideisoquinoline alkaloid derived from Papaver somniferum, is a well‐known antitussive drug that has a relatively safe in vitro toxicity profile. Noscapine is also known to possess weak anticancer efficacy, and since its discovery, efforts have been made to design derivatives with improved potency. Herein, the synthesis of a series of noscapine analogues, which have been modified in the 6′, 9′, 1 and 7‐positions, is described. In a previous study, replacement of the naturally occurring N‐methyl group in the 6′‐position with an N‐ethylaminocarbonyl was shown to promote cell‐cycle arrest and cytotoxicity against three cancer cell lines. Here, this modification has been combined with other structural changes that have previously been shown to improve anticancer activity, namely halo substitution in the 9′‐position, regioselective O‐demethylation to reveal a free phenol in the 7‐position, and reduction of the lactone to the corresponding cyclic ether in the 1‐position. The incorporation of new aryl substituents in the 9′‐position was also investigated. The study identified interesting new compounds able to induce G2/M cell‐cycle arrest and that possess cytotoxic activity against the human prostate carcinoma cell line PC3, the human breast adenocarcinoma cell line MCF‐7, and the human pancreatic epithelioid carcinoma cell line PANC‐1. In particular, the ethyl urea cyclic ether noscapinoids and a compound containing a 6′‐ethylaminocarbonyl along with 9′‐chloro, 7‐hydroxy and lactone moieties exhibited the most promising biological activities, with EC₅₀ values in the low micromolar range against all three cancer cell lines, and these derivatives warrant further investigation.     

Momentum in nonlinear optics

Abstract

Although it is well known that light carries momentum and exerts a pressure on objects, a conservation of momentum principle is apparently rarely used in optics. In nonlinear optics light waves interact and may exchange both energy and momentum. We demonstrate that a conservation of momentum principle holds in these cases and in fact its use is widespread but generally unrecognized in the standard mathematical methods. In both the cases of linear basis waves interacting nonlinearly, e.g. coupled-wave theory and frequency mixing, and fully nonlinear waves, we demonstrate that a governing Hamiltonian is related to momentum. Action principles are used to discuss the generality of these results.     

Organizational Patterns

When we study the literature and the evidence of recent innovation, we see a confusing array of different techniques. The confusion is deepened, because each of these new methods is presented to us as if the embodiment of industrialization itself—in an exclusivist sense. This confusion is hardly surprising, however; no more surprising, indeed, than the arrogance with which each example is promoted. For, while all governments are throwing a similar challenge at their respective building industries, the actual innovative responses occur when some practical and tangible portion of market can be hardened up and made available to any intending innovator. (This is because industrialization presupposes continuity and the risks involved are too great to be left to the market hazards typical of our industry today.)     

Contradictions and Challenges in Managing Design

It is argued that architects are relatively powerless in the overall building design and construction process because they have ignored not only social but also technological and economic concerns that are critical to the effective practice of architecture. This article calls for more collaborative research going beyond the traditional limits of design and construction to investigate the organizational and management processes that link owner, designer, contractor, and supplier.     

Facile Synthesis of Amine-Functionalized Eu3+-Doped La(OH)3 Nanophosphors for Bioimaging

Here, we report a straightforward synthesis process to produce colloidal Eu³⁺-activated nanophosphors (NPs) for use as bioimaging probes. In this procedure, poly(ethylene glycol) serves as a high-boiling point solvent allowing for nanoscale particle formation as well as a convenient medium for solvent exchange and subsequent surface modification. The La(OH)₃:Eu³⁺ NPs produced by this process were ~3.5 nm in diameter as determined by transmission electron microscopy. The NP surface was coated with aminopropyltriethoxysilane to provide chemical functionality for attachment of biological ligands, improve chemical stability and prevent surface quenching of luminescent centers. Photoluminescence spectroscopy of the NPs displayed emission peaks at 597 and 615 nm (λ_ex = 280 nm). The red emission, due to ⁵D₀ → ⁷F₁ and ⁵D₀ → ⁷F₂ transitions, was linear with concentration as observed by imaging with a conventional bioimaging system. To demonstrate the feasibility of these NPs to serve as optical probes in biological applications, an in vitro experiment was performed with HeLa cells. NP emission was observed in the cells by fluorescence microscopy. In addition, the NPs displayed no cytotoxicity over the course of a 48-h MTT cell viability assay. These results suggest that La(OH)₃:Eu³⁺ NPs possess the potential to serve as a luminescent bioimaging probe.     

Impact of oxygen transport properties on the kinetic modeling of polypropylene thermal oxidation. II. Effect of oxygen diffusivity

The kinetic model, established in a previous article (François‐Heude et al., J. Appl. Polym. Sci., in press) to predict the homogeneous oxidation in iPP films typically thinner than 100 µm, is now extended to simulate the oxidation profiles in thicker plates by coupling the oxygen diffusion and its consumption by the chemical reactions. In this perspective, oxygen transport properties (namely oxygen solubility, diffusivity, and permeability) are measured by permeametry on a reference iPP. These values are compared with an exhaustive compilation of literature data to evaluate their variability among the whole iPP family, which one has been reasonably ascribed to initial differences in polymer morphology, but also to evaluate their consistency, especially their temperature dependence between 20 and 140°C. Failing to simulate oxidation profiles, the kinetic model is then used as an inverse resolution method for estimating more satisfactory values of oxygen transport properties. It is thus evidenced that the crystallinity changes induced by thermal oxidation largely explains the dramatic decrease in oxygen penetration toward the sample core just after the induction period. A strategy aimed for introducing the relationship between the polymer crystalline morphology and oxygen transport properties into the kinetic model is given in the graphical abstract, although the effect of polymer polarity remains to be established prior to this implementation. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41562.     

Linked multicontinuum and crack tensor approach for modeling of coupled geomechanics, fluid flow and transport in fractured rock

In this paper, we present a linked multicontinuum and crack tensor approach for modeling of coupled geomechanics, fluid flow, and solute transport in fractured rock. We used the crack tensor approach to calculate effective block-scale properties, including anisotropic permeability and elastic tensors, as well as multicontinuum properties relevant to fracture-matrix interactions and matrix diffusion. In the modeling, we considered stress dependent properties, through stress-induced changes in fracture apertures, to update permeability and elastic tensors. We evaluated the effectiveness and accuracy of our multicon-tinuum approach by comparing our modeling results with that of three independent discrete fracture network (DFN) models. In two of the three alternative DFN models, solute transport was simulated by particle tracking, an approach very different from the standard solute transport used in our multicon-tinuum modeling. We compared the results for flow and solute transport through a 20 m × 20 m model domain of fractured rock, including detailed comparison of total flow rate, its distribution, and solute breakthrough curves. In our modeling, we divided the 20 m × 20 m model domain into regular blocks, or continuum elements. We selected a model discretization of 40 × 40 elements (having a side length of 0.5 m) that resulted in a fluid-flow rate equivalent to that of the DFN models. Our simulation results were in reasonably good agreement with the alternative DFN models, for both advective dominated transport (under high hydraulic gradient) and matrix-diffusion retarded transport (under low hydraulic gradient). However, we found pronounced numerical dispersion when using larger grid blocks, a problem that could be remediated by the use of a finer numerical grid resolution, while maintaining a larger grid for evaluation of equivalent properties, i.e. a property grid overlapping the numerical grid. Finally, we encountered some difficulties in using our approach when element sizes were so small that only one or a few fractures intersect an element-this is an area of possible improvement that will be pursued in future research.     

Urban Development the Pattern and the Background; Concluding Discussion

When We Build Again. A Bournville Village Trust Research Publication. George Allen &; Unwin, Ltd., London, 1941. Pp. xii (16), 138.

Report Relative to Postwar Reconstruction in the City, Prepared by Improvements and Town Planning Committee, published by The Corporation of London, 1944, pp. 66 plus maps and photographs.

The Economic Status of the New York Metropolitan Region in 1944, by The Regional Plan Association, Inc., New York, 1944, xx, 91 pp.