Idealismus

in Schrenk, Markus (Ed.) Handbuch Metaphysik (2017)

Idealizations and the decomposability of models in science

Presentation (2019, August 06)

Idéation suicidaire – Les tendances et les groupes à risque chez les adolescents au Luxembourg

Conference given outside the academic context (2018)

Le suicide est l'une des principales causes de décès chez les jeunes et l'adolescence est une période à risque pour le développement des idées suicidaires. L’objectif de cette communication est de ... [more ▼]

Le suicide est l'une des principales causes de décès chez les jeunes et l'adolescence est une période à risque pour le développement des idées suicidaires. L’objectif de cette communication est de présenter les tendances et les groupes à risque chez les adolescents au Luxembourg. Les résultats montrent que le sexe, le niveau socioéconomique, la structure familiale, le type d'école, l'âge et le harcèlement, entre autres sont des variables associés aux idées et comportement suicidaires. [less ▲]

L’idée de citoyenneté : De quoi parle-t-on ?

Poster (2001, January 31)

Die Ideenfabrik. Universitäten als Produzenten von Wissen

Article for general public (2018)

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 ▲]