Idées, réseaux et politiques européennes dans la résistance et en exil (1940-1945) en Belgique, au Luxembourg et aux Pays-Bas

Doctoral thesis (2010)

Identical Binding Energies and Work Functions for Distinct Adsorption Structures: Olympicenes on the Cu(111) Surface

in The Journal of Physical Chemistry Letters (2016), 7(6), 1022-1027

Identificación y control en cascada mediante inversión de no linealidades del cuatrirrotor para el Concurso de Ingeniería de Control CEA IFAC 2012

in RIAI - Revista Iberoamericana de Automatica e Informatica Industrial (2013), 10(3),

Identification and Characterization of Variant Intolerant Sites across Human Protein 3-Dimensional Structures

in Biophysical Journal (2018, February 02), 114(3, Suppl. 1), 664

The functional interpretation of genetic variation in disease-associated genes is far outpaced by data generation. Existing algorithms for prediction of variant consequences do not adequately distinguish ... [more ▼]

The functional interpretation of genetic variation in disease-associated genes is far outpaced by data generation. Existing algorithms for prediction of variant consequences do not adequately distinguish pathogenic variants from benign rare variants. This lack of statistical and bioinformatics analyses, accompanied by an ever-increasing number of identified variants in biomedical research and clinical applications, has become a major challenge. Established methods to predict the functional effect of genetic variation use the degree of amino acid conservation across species in linear protein sequence alignment. More recent methods include the spatial distribution pattern of known patient and control variants. Here, we propose to combine the linear conservation and spatial constrained based scores to devise a novel score that incorporates 3-dimensional structural properties of amino acid residues, such as the solvent-accessible surface area, degree of flexibility, secondary structure propensity and binding tendency, to quantify the effect of amino acid substitutions. For this study, we develop a framework for large-scale mapping of established linear sequence-based paralog and ortholog conservation scores onto the tertiary structures of human proteins. This framework can be utilized to map the spatial distribution of mutations on solved protein structures as well as homology models. As a proof of concept, using a homology model of the human Nav1.2 voltage-gated sodium channel structure, we observe spatial clustering in distinct domains of mutations, associated with Autism Spectrum Disorder (>20 variants) and Epilepsy (>100 variants), that exert opposing effects on channel function. We are currently characterizing all variants (>300k individuals) found in ClinVar, the largest disease variant database, as well as variants identified in >140k individuals from general population. The variant mapping framework and our score, informed with structural information, will be useful in identifying structural motifs of proteins associated with disease risk. [less ▲]

Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease.

in Human molecular genetics (2003), 12(11), 1223-31

Synphilin-1 is linked to the pathogenesis of Parkinson's disease (PD) based on its identification as an alpha-synuclein (PARK1) and parkin (PARK2) interacting protein. Moreover, synphilin-1 is a component ... [more ▼]

Synphilin-1 is linked to the pathogenesis of Parkinson's disease (PD) based on its identification as an alpha-synuclein (PARK1) and parkin (PARK2) interacting protein. Moreover, synphilin-1 is a component of Lewy bodies (LB) in brains of sporadic PD patients. Therefore, we performed a detailed mutation analysis of the synphilin-1 gene in 328 German familial and sporadic PD patients. In two apparently sporadic PD patients we deciphered a novel C to T transition in position 1861 of the coding sequence leading to an amino acid substitution from arginine to cysteine in position 621 (R621C). This mutation was absent in a total of 702 chromosomes of healthy German controls. To define a possible role of mutant synphilin-1 in the pathogenesis of PD we performed functional analyses in SH-SY5Y cells. We found synphilin-1 capable of producing cytoplasmic inclusions in transfected cells. Moreover we observed a significantly reduced number of inclusions in cells expressing C621 synphilin-1 compared with cells expressing wild-type (wt) synphilin-1, when subjected to proteasomal inhibition. C621 synphilin-1 transfected cells were more susceptible to staurosporine-induced cell death than cells expressing wt synphilin-1. Our findings argue in favour of a causative role of the R621C mutation in the synphilin-1 gene in PD and suggest that the formation of intracellular inclusions may be beneficial to cells and that a mutation in synphilin-1 that reduces this ability may sensitize neurons to cellular stress. [less ▲]

Identification des besoins plurilingues en contexte professionnel

in Derivry-Plard, Martine; Suzuki, Elli (Eds.) La didactique plurilingue et pluriculturelle à l’épreuve du terrain éducatif. contraintes, résistances, tensions (2014)

Une entreprise aéronautique européenne est dans les faits un lieu hautement multilingue en raison de la localisation d’un de ses sites à Hambourg en Allemagne, de son siège social en France et des ... [more ▼]

Une entreprise aéronautique européenne est dans les faits un lieu hautement multilingue en raison de la localisation d’un de ses sites à Hambourg en Allemagne, de son siège social en France et des communications régulières avec des sites dans des zones hispanophones. Cette multinationale a officiellement recours à l’anglais comme lingua franca en interne et en externe, mais elle propose des services multilingues tels que les Newsletters, les services informatiques et des cours de langues à ses employés. L’objectif de cette étude est d’identifier les ressentis des apprenants par rapports aux situations plurilingues quotidiennes professionnelles. Le corpus d’analyse est composé de 576 questionnaires diffusés auprès des salariés de l’entreprise aéronautique avant de commencer une formation en anglais, en allemand, en français ou en espagnol. [less ▲]

L’IDENTIFICATION DES VICTIMES DE LA TRAITE DES ÊTRES HUMAINS LORS DES PROCÉDURES DE PROTECTION INTERNATIONALE ET DE RETOUR FORCÉ

Report (2017)

La note de synthèse présente les principaux résultats de l’étude réalisée en 2013 et actualisée en 2017 par le point de contact luxembourgeois du European Migration Network sur «L’identification des ... [more ▼]

La note de synthèse présente les principaux résultats de l’étude réalisée en 2013 et actualisée en 2017 par le point de contact luxembourgeois du European Migration Network sur «L’identification des victimes de la traite des êtres humains lors des procédures de protection internationale et de retour forcé». [less ▲]

Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome.

in American Journal of Human Genetics (2007), 80(1), 1-11

Bardet-Biedl syndrome (BBS) is primarily an autosomal recessive ciliopathy characterized by progressive retinal degeneration, obesity, cognitive impairment, polydactyly, and kidney anomalies. The disorder ... [more ▼]

Bardet-Biedl syndrome (BBS) is primarily an autosomal recessive ciliopathy characterized by progressive retinal degeneration, obesity, cognitive impairment, polydactyly, and kidney anomalies. The disorder is genetically heterogeneous, with 11 BBS genes identified to date, which account for ~70% of affected families. We have combined single-nucleotide-polymorphism array homozygosity mapping with in silico analysis to identify a new BBS gene, BBS12. Patients from two Gypsy families were homozygous and haploidentical in a 6-Mb region of chromosome 4q27. FLJ35630 was selected as a candidate gene, because it was predicted to encode a protein with similarity to members of the type II chaperonin superfamily, which includes BBS6 and BBS10. We found pathogenic mutations in both Gypsy families, as well as in 14 other families of various ethnic backgrounds, indicating that BBS12 accounts for approximately 5% of all BBS cases. BBS12 is vertebrate specific and, together with BBS6 and BBS10, defines a novel branch of the type II chaperonin superfamily. These three genes are characterized by unusually rapid evolution and are likely to perform ciliary functions specific to vertebrates that are important in the pathophysiology of the syndrome, and together they account for about one-third of the total BBS mutational load. Consistent with this notion, suppression of each family member in zebrafish yielded gastrulation-movement defects characteristic of other BBS morphants, whereas simultaneous suppression of all three members resulted in severely affected embryos, possibly hinting at partial functional redundancy within this protein family. [less ▲]

Identification of amino acid residues crucial for chemokine receptor dimerization.

in Nature immunology (2004), 5(2), 216-23

Chemokines coordinate leukocyte trafficking by promoting oligomerization and signaling by G protein-coupled receptors; however, it is not known which amino acid residues of the receptors participate in ... [more ▼]

Chemokines coordinate leukocyte trafficking by promoting oligomerization and signaling by G protein-coupled receptors; however, it is not known which amino acid residues of the receptors participate in this process. Bioinformatic analysis predicted that Ile52 in transmembrane region-1 (TM1) and Val150 in TM4 of the chemokine receptor CCR5 are key residues in the interaction surface between CCR5 molecules. Mutation of these residues generated nonfunctional receptors that could not dimerize or trigger signaling. In vitro and in vivo studies in human cell lines and primary T cells showed that synthetic peptides containing these residues blocked responses induced by the CCR5 ligand CCL5. Fluorescence resonance energy transfer showed the presence of preformed, ligand-stabilized chemokine receptor oligomers. This is the first description of the residues involved in chemokine receptor dimerization, and indicates a potential target for the modification of chemokine responses. [less ▲]

Identification of Berezin-Toeplitz deformation quantization,

in Journal für die Reine und Angewandte Mathematik (2001), 540