Synthesis and biological evaluation of several 3‐(coumarin‐4‐yl)tetrahydroisoxazole and 3‐(coumarin‐4‐yl)dihydropyrazole derivatives

A series of novel 3‐(coumarin‐4‐yl)tetrahydroisoxazoles 5a,b, 7, 9 and 3‐(coumarin‐4‐yl)dihydropyra‐zoles 13a‐d, 14,15a,b were synthesized from coumarin‐4‐carboxaldehyde 1 via the intermediate N‐methyl nitrone 3 and N‐phenyl or N‐methyl hydrazones 11a,b . These coumarin derivatives were isolated, characterized and evaluated in vitro for their ability to inhibit trypsin, β‐glucuronidase, soybean lipoxygenase and to interact with the stable radical 1,1‐diphenyl‐2‐picrylhydrazyl. The compounds were tested in vivo as anti‐inflammatory agents in the rat carrageenin paw edema assay. Compound 15a seems to be a lead molecule to be modified in order to improve the lipoxygenase inhibition. The results are discussed in terms of structural characteristics.     

Airy plasmons: non‐diffracting optical surface waves

Airy beams represent an important class of non‐diffracting waves which can be realized on a flat surface. Being generated in the form of surface‐plasmon polaritons, such Airy plasmons demonstrate many remarkable properties: they do not diffract while propagating along parabolic trajectories, and they recover their shape after passing through obstacles. This paper reviews the basic physics of Airy plasmons in both paraxial and non‐paraxial cases, and describes the experimental methods for generation of Airy surface waves on metal surfaces, including a control of their trajectories, as well as the interference of Airy plasmons and hot‐spot generation. Many unusual properties of Airy plasmons can be utilized for useful applications, including plasmonic circuitry and surface tweezers. Picture: Observation of two colliding Airy plasmons.     

On aspects of the dynamic behavior of persistent chemicals in a multimedia environment related to exposure-based hazard assessment

The present research study focuses on the analysis and characterization of certain aspects of the dynamic behavior displayed by persistent chemicals in a multimedia environment (chemodynamics), which is jointly determined by the inherent physicochemical properties of the chemical substance under consideration, as well as underlying environmental processes such as degradation in different phases/media (soil, water and air) coupled with intermedia transport (interphase mass transfer). In particular, dynamic multimedia environmental models are considered with constant source terms describing steady chemical release/discharge rates into various environmental media of interest, and key risk-related aspects of the dynamic behavior of persistent chemicals are analyzed using perturbation theory techniques under conditions where degradation rates in different media are considerably slower than intermedia transport rates. Under the above conditions, the problem of defining physically meaningful and practical quantitative measures of overall persistence of chemicals in a multimedia environment is revisited, given its role as a key exposure-based indicator within all major chemical risk assessment frameworks, and a proof is provided that rigorously establishes equivalence between two important and popular persistence measures, namely the characteristic time at steady state and the inverse of the associated chemodynamics overall decay rate (slowest chemodynamic mode).     

Chiral flavanones from Amygdalus lycioides Spach: structural elucidation and identification of TNFalpha inhibitors by bioactivity-guided fractionation

Phytochemical investigation on the Amygdalus lycioides Spach branchelets resulted in the isolation of four chiral flavanones: (2R,3R)-Taxifolin, (2R,3R)-aromadendrin, (S)-5,7,3',5'-tetrahydroxyflavanone and (S)-naringenin. The flavanones were isolated by semi-preparative HPLC, their structures elucidated based on spectroscopic data and their absolute configuration assigned. As a part of our ethnobotanical-directed search for novel TNFα inhibitors, the bioassay-guided fractionation of the n-hexane-acetone (n-Hex-Ac, 1:1 v/v) Amygdalus lycioides Spach branchelets extract was performed. In this way, (S)-naringenin was identified as the constituent responsible for the TNFα blocking effect, being effective in vitro and in vivo after oral administration. This is the first investigation on bioactive secondary metabolites of Amygdalus lycioides Spach branchelets.     

Charged cosmic strings interacting with gravitational and electromagnetic waves

Under a particular choice of the Ernst potential, we solve analytically the Einstein–Maxwell equations to derive a new exact solution depending on five parameters: the mass, the angular-momentum (per unit mass), α, the electromagnetic-field strength, k, the parameter-p and the Kerr-NUT parameter, l. This (Petrov Type D) solution is cylindrically symmetric and represents the curved background around a charged, rotating cosmic string, surrounded by gravitational and electromagnetic waves, under the influence of the Kerr-NUT parameter. A C-energy study in the radiation zone suggests that both the incoming and the outgoing radiation is gravitational, strongly focused around the null direction and preserving its profile. In this case, the absence of the k-parameter from the C-energy implies that, away from the linear defect the electromagnetic field is too weak to contribute to the energy-content of the cylindrically symmetric space-time under consideration. In order to explain this result, we have evaluated the Weyl and the Maxwell scalars near the axis of the linear defect and at the spatial infinity. Accordingly, we have found that the electromagnetic field is concentrated (mainly) in the vicinity of the axis, while falling-off prominently at large radial distances. However, as long as k ≠ 1, the non-zero Kerr-NUT parameter enhances those scalars, both near the axis and at the spatial infinity, introducing some sort of gravitomagnetic contribution.     

PIFA-mediated synthesis of novel pyrazoloquinolin-4-ones as potential ligands for the estrogen receptor

A facile and efficient preparation of pyrazoloquinolin-4-ones, as potential ligands for the estrogen receptor, via a PIFA [phenyliodine(III)bis(trifluoroacetate)] promoted cyclization reaction with overall yields up to 29% over six steps is described. The employed strategy, based on an electrophilic amidation reaction as the key step of the synthesis, allows the generation of a diverse array of derivatives.     

Biological Properties of New Chiral 2-Methyl-5,6,7,8-tetrahydroquinolin-8-amine-based Compounds

The synthesis of a small library of 8-substituted 2-methyl-5,6,7,8-tetrahydroquinoline derivatives is presented. All the compounds were tested for their antiproliferative activity in non-cancer human dermal microvascular endothelial cells (HMEC-1) and cancer cells: human T-lymphocyte cells (CEM), human cervix carcinoma cells (HeLa), human dermal microvascular endothelial cells (HMEC-1), colorectal adenocarcinoma (HT-29), ovarian carcinoma (A2780), and biphasic mesothelioma (MSTO-211H). Compounds 3a, 5a, and 2b, showing significant IC₅₀ values against the whole panel of the selected cells, were further synthesized and tested as pure enantiomers in order to shed light on how their stereochemistry might impact on the related biological effect. The most active compound (R)-5a was able to affect cell cycle phases and to induce mitochondrial membrane depolarization and cellular ROS production in A2780 cells.     

On the regularity of spherically symmetric wave maps

Wave maps are critical points U: M → N of the Lagrangian ??[U] = ∞_M ‖dU‖², where M is an Einsteinian manifold and N a Riemannian one. For the case M = ?^2,1 and U a spherically symmetric map, it is shown that the solution to the Cauchy problem for U with smooth initial data of arbitrary size is smooth for all time, provided the target manifold N satisfies the two conditions that: (1) it is either compact or there exists an orthonormal frame of smooth vectorfields on N whose structure functions are bounded; and (2) there are two constants c and C such that the smallest eigenvalue λ and the largest eigenvalue λ of the second fundamental form k_AB of any geodesic sphere Σ(p, s) of radius s centered at p ? N satisfy sλ ≧ c and s A ≦ C(1 + s). This is proved by first analyzing the energy-momentum tensor and using the second condition to show that near the first possible singularity, the energy of the solution cannot concentrate, and hence is small. One then proves that for targets satisfying the first condition, initial data of small energy imply global regularity of the solution. © 1993 John Wiley & Sons, Inc.     

Understanding Social Reforms: A Conceptual Analysis

We attempt here to explain why reforming social systems is not an easy job and what can be done about it. Vickers' concept of ‘appreciative systems’ is re-examined and further developed. It is argued that appreciative systems are socially established ways of perceiving, consisting of a set of cognitive categories, values and interests which are grounded on social practices. The latter are constituted by certain historically developed self-understandings shared by individuals. Social practices are self-referential and, therefore, particularly resistant to reform. It is argued that the role of policy makers should be seen as consisting of two components. First, inventing and supplying social systems with new appreciative systems, and secondly, regularly providing social systems with information about their own functioning as well as the functioning of other systems. That information, spread throughout a system, has potentially reforming effects. These claims are illustrated with examples from UK and American public life.