Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases

Tyrosine hydroxylase (TyrOH) catalyzes the conversion of tyrosine to L-DOPA, the rate-limiting step in the biosynthesis of the catecholamines dopamine, adrenaline, and noradrenaline. TyrOH is highly homologous in terms of both protein sequence and catalytic mechanism to phenylalanine hydroxylase (PheOH) and tryptophan hydroxylase (TrpOH). The crystal structure of the catalytic and tetramerization domains of TyrOH reveals a novel alpha-helical basket holding the catalytic iron and a 40 A long anti-parallel coiled coil which forms the core of the tetramer. The catalytic iron is located 10 A below the enzyme surface in a 17 A deep active site pocket and is coordinated by the conserved residues His 331, His 336 and Glu 376. The structure provides a rationale for the effect of point mutations in TyrOH that cause L-DOPA responsive parkinsonism and Segawa's syndrome. The location of 112 different point mutations in PheOH that lead to phenylketonuria (PKU) are predicted based on the TyrOH structure.     

Choice of B-splines with free parameters in the flexible discriminant analysis context

Flexible discriminant analysis (FDA) is a general methodology which aims at providing tools for multigroup non linear classification. It consists in a nonparametric version of discriminant analysis by replacing linear regression by any nonparametric regression method. A new option for FDA, consisting in a nonparametric regression method based on B-spline functions, will be introduced. The relevance of the transformation (hence the discrimination) depends on the parameters defining the spline functions: degree, number and location of the knots for each continuous variable. This method called FDA-FKBS (Free Knot B-Splines) allows to determine all these parameters without the necessity of many prior parameters. It is inspired by Reversible Jumps Monte Carlo Markov Chains but the objective function is different and the Bayesian aspect is put aside.     

A new genetic algorithm in proteomics: Feature selection for SELDI-TOF data

Mass spectrometry from clinical specimens is used in order to identify biomarkers in a diagnosis. Thus, a reliable method for both feature selection and classification is required. A novel method is proposed to find biomarkers in SELDI-TOF in order to perform robust classification.The feature selection is based on a new genetic algorithm. Concerning the classification, a method which takes into account the great variability on intensity by using decision stumps has been developed. Moreover, as the samples are often small, it is more appropriate to use the decision stumps simultaneously than building a complete tree. The thresholds of the decision stumps are determined in the same genetic algorithm. Finally, the method was generalized to more than two groups based on pairwise coupling. The obtained algorithm was applied on two data sets: a publicly available one containing two groups allowing a comparison with other methods from the literature and a new one containing three groups.     

Influence of a dielectric buffer layer on the field distribution in an electrooptic guided-wave device

An analytical solution to the field distribution for coplanar electrodes incorporating a buffer layer is obtained by using the method of images. The accuracy of the present analysis is found to be comparable to that obtained from a numerical solution, the finite element technique, The solution is applied to practical integrated optical devices incorporating waveguides with stripe geometry in order to directly estimate the overlap integral between optical and electric fields.     

Wideband omnidirectional microstrip array

A compact broadband antenna having a far-field pattern similar to that of a magnetic dipole with horizontal polarisation has been designed and tested. The dimensions of this printed antenna, etched on low permittivity substrate, are 130×130 mm. The measured bandwidth, which is 52% for a VSWR of less than 2, is achieved through the utilisation of nonresonant elements     

Comparison between linear and nonlinear PLS methods to explain overall liking from sensory characteristics

The influence of sensory characteristics on overall liking can be statistically studied with Partial Least Squares (PLS) regression methods. To correctly model nonlinear dependence relationships, some nonlinear PLS extensions are useful. The purpose of the present paper is to compare performances and results of three PLS methods, using a real data set: regular PLS with sensory attributes as explanatory variables; PLS with attributes and their respective squares; and a new nonlinear PLS extension, called ASPLS. In case of a nonlinear dependence relationship between sensory characteristics and hedonic responses, this last method is shown to be worth considering.     

Chromosomal aberrations induced in human lymphocytes by high-LET irradiation

The affinity of a DNA sequence for the histone octamer in a core nucleosome depends on the intrinsic flexibility of the DNA. This parameter can be affected both by the sequence-dependent conformational preferences of individual base steps and by the nature and location of the exocyclic groups of the DNA bases. By adopting highly preferred conformations particular types of base step can influence the rotational positioning of the DNA on the surface of the histone octamer. The asymmetry of the next higher order of chromatin structure is determined in part by the asymmetric binding of the globular domain of histone H5 to the core nucleosome.     

Interfaces en langage naturel : du traitement du non attendu à la composition de phrases assistée

We survey the different kinds of errors that happen with natural language interfaces. We present different techniques of their treatment, and the incidences on interface architectures. We show the interest of an approach in which sentence reformulation is favoured. The generalization of this approach leads to an interesting mode of communication, the aided sentences composition. We give the principles of this mode.