CAESAR models for developmental toxicity

Background

The new REACH legislation requires assessment of a large number of chemicals in the European market for several endpoints. Developmental toxicity is one of the most difficult endpoints to assess, on account of the complexity, length and costs of experiments. Following the encouragement of QSAR (in silico) methods provided in the REACH itself, the CAESAR project has developed several models.

Results

Two QSAR models for developmental toxicity have been developed, using different statistical/mathematical methods. Both models performed well. The first makes a classification based on a random forest algorithm, while the second is based on an adaptive fuzzy partition algorithm. The first model has been implemented and inserted into the CAESAR on-line application, which is java-based software that allows everyone to freely use the models.

Conclusions

The CAESAR QSAR models have been developed with the aim to minimize false negatives in order to make them more usable for REACH. The CAESAR on-line application ensures that both industry and regulators can easily access and use the developmental toxicity model (as well as the models for the other four endpoints).

     

Synthesis and Study of the Photophysical Properties of a New Eu<Superscript>3+</Superscript> Complex with 3-Hydroxypicolinamide

This work reports on the synthesis and characterization of a new complex of Eu³⁺ with the 3-hydroxypicolinamide ligand (Hhpa). Here we present an approach for obtaining bis[2-carbamoyl(κO)pyridin-3-olato(κO’)] lanthanide complexes, which were characterized through elemental analysis, thermal analysis, infrared and photoluminescence spectroscopies (emission, excitation, luminescence lifetimes, quantum efficiencies, Judd-Ofelt parameters and quantum yields). Although hpa can act as a bidentate ligand in different conformations, the results attest for the occurrence of a unique coordination site of low symmetry for the Eu³⁺ ions, in which two anionic hpa ligands coordinate the cations through an O/O chelating system. The phosphorescence of the synthesized gadolinium complex provides the energy of the triplet state, which is determined to be at 20,830 cm^-1 over the ground state. This makes the Hhpa ligand very adequate for sensitizing the Eu³⁺ luminescence, which leads to a very efficient antenna effect and opens a wide range of applications for the complex in light emitting organic-inorganic devices.     

3D features of modified photostructurable glass-ceramic with infrared femtosecond laser pulses

The exclusive ability of laser radiation to be focused inside transparent materials makes lasers a unique tool to process inner parts of them unreachable with other techniques. Hence, laser direct-write can be used to create 3D structures inside bulk materials. Infrared femtosecond lasers are especially indicated for this purpose because a multiphoton process is usually required for absorption and high resolution can be attained. This work studies the modifications produced by 450 fs laser pulses at 1027 nm wavelength focused inside a photostructurable glass-ceramic (Foturan^®) at different depths. Irradiated samples were submitted to standard thermal treatment and subsequent soaking in HF solution to form the buried microchannels and thus unveil the modified material. The voxel dimensions of modified material depend on the laser pulse energy and the depth at which the laser is focused. Spherical aberration and self-focusing phenomena are required to explain the observed results.     

The other natural two Higgs doublet model

We characterize models where electroweak symmetry breaking is driven by two light Higgs doublets arising as pseudo-Nambu-Goldstone bosons of new dynamics above the weak scale. They represent the simplest natural two Higgs doublet alternative to supersymmetry. We construct their low-energy effective Lagrangian making only few specific assumptions about the strong sector. These concern their global symmetries, their patterns of spontaneous breaking and the sources of explicit breaking. In particular we assume that all the explicit breaking is associated with the couplings of the strong sector to the Standard Model fields, that is gauge and (proto)-Yukawa interactions. Under those assumptions the scalar potential is determined at lowest order by very few free parameters associated to the top sector. Another crucial property of our scenarios is the presence of a discrete symmetry, in addition to custodial SO(4), that controls the T-parameter. That can either be simple CP or a Z₂ that distinguishes the two Higgs doublets. Among various possibilities we study in detail models based on SO(6)/SO(4) × SO(2), focussing on their predictions for the structure of the scalar spectrum and the deviations of their couplings from those of a generic renormalizable two Higgs doublet model.     

The Dirichlet problem for the fractional Laplacian: Regularity up to the boundary

We study the regularity up to the boundary of solutions to the Dirichlet problem for the fractional Laplacian. We prove that if u   is a solution of (−Δ)^su=g${(-\mathrm{\Delta })}^{s}u=g$ in Ω  , u≡0$u\equiv 0$ in Rⁿ\Ω${\mathbb{R}}^n\backslash \Omega$, for some s∈(0,1)$s\in (0,1)$ and g∈L^∞(Ω)$g\in L^{\infty }(\Omega )$, then u   is C^s(Rⁿ)$C^s({\mathbb{R}}^n)$ and u/δ^s_|Ω$u/{\delta }^s{|}_{\Omega }$ is C^α$C^{\alpha }$ up to the boundary ∂Ω   for some α∈(0,1)$\alpha \in (0,1)$, where δ(x)=dist(x,∂Ω)$\delta (x)=\mathrm{dist}(x,\partial \Omega )$. For this, we develop a fractional analog of the Krylov boundary Harnack method.     

Nanotubes from misfit layered compounds

Abstract

First, the mechanisms leading to the formation of nanotubes from layered (2-D) materials are briefly discussed. Two main mechanisms are evoked: (1) The asymmetry of the layer along the c-axis, which leads to spontaneous folding, as revealed first by Pauling in 1930; (2) The seaming of the layer due to the abundance of dangling bonds in the rim atoms of the 2-D nanoclusters. This mechanism was discussed first in connection with carbon fullerenes and carbon nanotubes, some 30 years ago and was further extended to inorganic 2-D materials in 1992. In the second part of this work, the formation mechanism of nanotubes from misfit layered compounds (MLC) is deliberated. Here, the two forces are shown to work in synergy leading to facile formation of nanotubes from ternary misfit compounds. This synergy is demonstrated through the versatile chemistry, which has been employed to synthesize MLC nanotubes. Furthering in complexity, few recent examples of nanotubes from quaternary chalcogenide-based MLC are briefly discussed.     

The synthesis of tetradentate salens derived from (3R,4R)-N-substituted-3,4-diaminopyrrolidines and their application in the enantioselective trimethylsilylcyanation of aromatic aldehydes

The in situ formed Ti(IV) complexes of pyrrolidine-based chiral salen ligands derived from natural l-tartaric acid were evaluated as catalysts in the enantioselective trimethylsilylcyanation of aromatic aldehydes. The different activity and selectivity of the catalysts in the formation of the products were found to be dependent on the N-substituent of the pyrrolidine.     

A unifying approach to abstract matrix algebra preconditioning

In earlier papers Tyrtyshnikov [42] and the first author [14] considered the analysis of clustering properties of the spectra of specific Toeplitz preconditioned matrices obtained by means of the best known matrix algebras. Here we generalize this technique to a generic Banach algebra of matrices by devising general preconditioners related to “convergent” approximation processes [36]. Finally, as case study, we focus our attention on the Tau preconditioning by showing how and why the best matrix algebra preconditioners for symmetric Toeplitz systems can be constructed in this class. Received April 25, 1997 / Revised version received March 13, 1998