Evaluation and improvement of QSAR predictions of skin sensitization for pesticides

In vivo skin sensitization assays have to be provided by applicants to the competent authorities in the European Union for the approval of active substances (AS) in pesticides. This study aimed to test the practicability of in silico predictions for AS by freely available (Q)SAR tools to evaluate their use as a time- and cost-effective alternative to animal testing in the context of the 3R concept. Predictions of skin sensitization for 48 selected sensitizing and non-sensitizing AS by the software programs CAESAR, Toxtree, OECD (Q)SAR Toolbox, CASE Ultra, Leadscope and SciQSAR were collected and compared. Different data evaluation methodologies (score definition, mean, weighted mean, threshold score definition) were applied to optimize the predictions. The calculation methods were internally cross-validated and further validated with an additional validation set of 80 AS. Although the presented calculation methodologies are not suitable as a stand-alone method, this study has shown weaknesses and strengths of some prominent (Q)SAR programs and diverse combinatorial options in the prediction of skin sensitization by pesticidal AS. The present study will help to foster discussions on in silico alternatives to animal testing in the pesticide area.     

Complexes of atmospheric alpha-dicarbonyls with water: FTIR matrix isolation and theoretical study

The complexes of glyoxal (Gly), methylglyoxal (MGly), and diacetyl (DAc) with water have been studied using Fourier transform infrared (FTIR) matrix isolation spectroscopy and MP2 calculations with 6-311++G(2d,2p) basis set. The analysis of the experimental spectra of the Gly(MGly,DAc)/H2O/Ar matrixes indicates formation of one Gly...H2O complex, three MGly...H2O complexes, and two DAc...H2O ones. All the complexes are stabilized by the O-H...O(C) hydrogen bond between the water molecule and carbonyl oxygen as evidenced by the strong perturbation of the O-H, C=O stretching vibrations. The blue shift of the CH stretching vibration in the Gly...H2O complex and in two MGly...H2O ones suggests that these complexes are additionally stabilized by the improper C-H...O(H2) hydrogen bonding. The theoretical calculations confirm the experimental findings. They evidence the stability of three hydrogen-bonded Gly...H2O and DAc...H2O complexes and six MGly...H2O ones stabilized by the O-H...O(C) hydrogen bond. The calculated vibrational frequencies and geometrical parameters indicate that one DAc..H2O complexes, two Gly...H2O, and three MGly...H2O ones are additionally stabilized by the improper hydrogen bonding between the C-H group and water oxygen. The comparison of the theoretical frequencies with the experimental ones allowed us to attribute the calculated structures to the complexes present in the matrixes.     

A Model for the Evolution of Laminates

We study the time evolution of a generalized standard material in elastoplasticity. Of our particular interest are the formation and the evolution of microstructure. Our aim is to prove the existence of solutions. This is a challenging task, since the presence of microstructure comes along with a lack of convexity and, hence, compactness arguments cannot be applied to prove the existence of solutions. In order to overcome this problem, we will incorporate information on the microstructure into the internal variable, which is still compatible with the notion of generalized standard materials. More precisely, we shall allow such forms of microstructure that are given by simple laminates. We will consider a model for the evolution of these laminates and we will state a result on the existence of solutions to the time-incremental minimization problem. (© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Universal Monos in Partial Morphism Categories

In this paper the category, C\mathcal{C} with respect to a certain class D\mathcal{D} of subobjects of C\mathcal{C} is formed and the universality of monomorphisms of ${\overset{\lower0.5em\hbox{${\overset{\lower0.5em\hbox{ is investigated. The main result characterizes ${\overset{\lower0.5em\hbox{${\overset{\lower0.5em\hbox{-universality of monos, in terms of C\mathcal{C}-universality of monos and the existence of local C\mathcal{C}-implications.     

Emergence of rate-independent dissipation from viscous systems with wiggly energies

We consider the passage from viscous systems to rate-independent system in the limit of vanishing viscosity and for wiggly energies. Our new convergence approach is based on the ${(\mathcal{R},\mathcal{R}^*)}$ formulation of De Giorgi, where we pass to the Γ limit in the dissipation functional. The difficulty is that the type of dissipation changes from a quadratic functional to one that is homogeneous of degree 1, thus leading to hysteresis. The analysis uses the decomposition of the restoring force into a macroscopic part and a fluctuating part, where the latter is handled via homogenization.     

On interfaces between incompatible wells and elastic deformations of infinite cylinders

We consider the minimization problem for the functional where is an infinitely long cylinder. The density is polyconvex and assumed to be 0 on a set of wells and positive elsewhere. We show that the gradients of solutions with finite energy have to approach one component for and one component for , if the number of components is finite (among other conditions). Moreover, for certain pairs of distinct components we construct nontrivial minimizers within the class of solutions approaching the given components. We follow ideas developed in the variational study of heteroclinic connections for Lagrangian systems and we put special emphasis on multiplicity of such interface solutions. We discuss an application in the theory of nonlinear elasticity, where such solutions are called semi-necks. When a two-dimensional infinite hyperelastic strip is stretched along its infinite direction it may occur that for a given tensile load many homogeneous deformations are possible. In such a case we show by infimizing the energy functional the existence of configurations that tend asymptotically to two different homogeneous deformations. Received: 1 March 2000 / Accepted: 4 December 2000 / Published online: 4 May 2001     

Photo-Induced Reactions between Glyoxal and Hydroxylamine in Cryogenic Matrices

In this paper, the photochemistry of glyoxal–hydroxylamine (Gly–HA) complexes is studied using FTIR matrix isolation spectroscopy and ab initio calculations. The irradiation of the Gly–HA complexes with the filtered output of a mercury lamp (λ > 370 nm) leads to their photoconversion to hydroxyketene–hydroxylamine complexes and the formation of hydroxy(hydroxyamino)acetaldehyde with a hemiaminal structure. The first product is the result of a double hydrogen exchange reaction between the aldehyde group of Gly and the amino or hydroxyl group of HA. The second product is formed as a result of the addition of the nitrogen atom of HA to the carbon atom of one aldehyde group of Gly, followed by the migration of the hydrogen atom from the amino group of hydroxylamine to the oxygen atom of the carbonyl group of glyoxal. The identification of the products is confirmed by deuterium substitution and by MP2 calculations of the structures and vibrational spectra of the identified species.     

Flow equations for the spin-boson problem

Using continuous unitary transformations recently introduced by Wegner [1], we obtain flow equations for the parameters of the spin-boson Hamiltonian. Interactions not contained in the original Hamiltonian are generated by this unitary transformation. Within an approximation that neglects additional interactions quadratic in the bath operators, we can close the flow equations. Applying this formalism to the case of Ohmic dissipation at zero temperature, we calculate the renormalized tunneling frequency. We find a transition from an untrapped to trapped state at the critical coupling constant α _c =1. We also obtain the static susceptibility via the equilibrium spin correlation function. Our results are both consistent with results known from the Kondo problem and those obtained from mode-coupling theories. Using this formalism at finite temperature, we find a transition from coherent to incoherent tunneling atT ₂ ^* ≈2T ₁ ^* , whereT ₁ ^* is the crossover temperature of the dynamics known from the NIBA.