Knowledge Bases Integration

The IBC (“Intégration de Bases de Connaissance” - Knowledge Bases Integration) project addresses the question of ontology based data integration, in the context of the MMT (Man Machine Teaming) initiative. It aims at combining data residing in different actors (aircraft, drone, sattelite, … ) during an air mission scenario and providing users with a unified view of all available data, in a communication constrained environment

CNS Delivery Via Adsorptive Transcytosis

Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of medicines across the blood-brain barrier (BBB). The BBB is readily equipped for the AMT process: it provides both the potential for binding and uptake of cationic molecules to the luminal surface of endothelial cells, and then for exocytosis at the abluminal surface. The transcytotic pathways present at the BBB and its morphological and enzymatic properties provide the means for movement of the molecules through the endothelial cytoplasm. AMT-based drug delivery to the brain was performed using cationic proteins and cell-penetrating peptides (CPPs). Protein cationization using either synthetic or natural polyamines is discussed and some examples of diamine/polyamine modified proteins that cross BBB are described. Two main families of CPPs belonging to the Tat-derived peptides and Syn-B vectors have been extensively used in CPP vector-mediated strategies allowing delivery of a large variety of small molecules as well as proteins across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from several limitations such as toxicity and immunogenicity—like the cationization strategy—as well as the instability of peptide vectors in biological media. The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Commissioning and performance of the CMS silicon strip tracker with cosmic ray muons

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPDuring autumn 2008, the Silicon Strip Tracker was operated with the full CMS experiment in a comprehensive test, in the presence of the 3.8 T magnetic field produced by the CMS superconducting solenoid. Cosmic ray muons were detected in the muon chambers and used to trigger the readout of all CMS sub-detectors. About 15 million events with a muon in the tracker were collected. The efficiency of hit and track reconstruction were measured to be higher than 99% and consistent with expectations from Monte Carlo simulation. This article details the commissioning and performance of the Silicon Strip Tracker with cosmic ray muons.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

La cationisation, un procédé de vectorisation des anticorps dans le système nerveux central

Le système nerveux central est isolé du reste de l’organisme par la barrière hémato-encéphalique. La présence de cette barrière empêche la pénétration cérébrale de nombreuses molécules, comme les anticorps, ce qui rend difficile leur utilisation pour le traitement de maladies du système nerveux, telles que le tétanos et le botulisme. Ces deux maladies sont provoquées par des bactéries du genre Clostridium qui libèrent des toxines dont le neurotropisme est maintenant bien connu. Dès lors qu’elles ont pénétré le système nerveux central, ces toxines deviennent inaccessibles à des anticorps spécifiques, alors que ces molécules sont efficaces dans le traitement des risques tétanique et botulique, c’est à dire lorsque les toxines sont localisées en périphérie. Différentes techniques neurochirurgicales peuvent être utilisées pour délivrer les anticorps dans le cerveau. Néanmoins, les stratégies de délivrance fondées sur l’utilisation de mécanismes ou de systèmes de transport existant naturellement au niveau des cellules de la barrière hémato-encéphalique sont plus prometteuses. La cationisation des protéines est un procédé chimique qui consiste à augmenter la densité de charges positives de ces molécules afin de favoriser leurs interactions avec les charges négatives présentes à l’intrados des capillaires cérébraux. Appliqué aux anticorps, ce procédé de vectorisation permet la pénétration de ces macromolécules dans le cerveau par un mécanisme de transcytose médiée par adsorption. Les études in vivo et in vitro réalisées avec une grande variété d’anticorps cationisés font apparaître de nombreuses difficultés pour la mise en place de stratégies d’immunothérapie fondées sur l’utilisation de ces molécules. Ces difficultés concernent, entre autres, une possible altération de la fonction des anticorps due à la cationisation, et une modification de la cinétique et de la distribution tissulaire des anticorps cationisés due au radiomarquage de ces molécules et/ou leur fixation à des facteurs sériques. Plusieurs types de vecteurs aminés (hexaméthylènediamine, polyamines naturelles) sont utilisés pour cationiser les anticorps. Les résultats de capture cérébrale obtenus avec une variété de protéines cationisées par ces différentes amines semblent indiquer l’existence d’une plus grande spécificité cérébrale pour les molécules modifiées par les polyamines naturelles que pour celles modifiées par l’hexaméthylènediamine. La mise en place de modèles expérimentaux permettant de vérifier l’efficacité thérapeutique des anticorps cationisés, une fois ceux-ci vectorisés dans le cerveau, s’avère nécessaire. Malgré l’existence de nombreuses difficultés, les études décrites dans cette synthèse, ainsi que les acquis dans le domaine de l’ingénierie et de la fragmentation des anticorps, permettent d’envisager de nouvelles orientations thérapeutiques des intoxications provoquées par les neurotoxines clostridiales

Ontology-based data integration in a distributed context of coalition air missions

International audienceThe IBC (Knowledge Base Integration) project addresses an issue of ontology-based data integration. It aims at combining data residing in different actors (aircraft, drone, satellite...) during an air mission scenario and providing users with a unified view of all available data, in a communication constrained environment. We describe the solution we have implemented based on mediation. We use rule languages to process queries using an OWL2 domain ontology and RDF triples to store data. We also give a performance analysis of our prototype

Ribosomal RNA (rRNA) sequences from 33 globally distributed mosquito species for improved metagenomics and species identification

International audienceTotal RNA sequencing (RNA-seq) is an important tool in the study of mosquitoes and the RNA viruses they vector as it allows assessment of both host and viral RNA in specimens. However, there are two main constraints. First, as with many other species, abundant mosquito ribosomal RNA (rRNA) serves as the predominant template from which sequences are generated, meaning that the desired host and viral templates are sequenced far less. Second, mosquito specimens captured in the field must be correctly identified, in some cases to the sub-species level. Here, we generate mosquito ribosomal RNA (rRNA) datasets which will substantially mitigate both of these problems. We describe a strategy to assemble novel rRNA sequences from mosquito specimens and produce an unprecedented dataset of 234 full-length 28S and 18S rRNA sequences of 33 medically important species from countries with known histories of mosquito-borne virus circulation (Cambodia, the Central African Republic, Madagascar, and French Guiana). These sequences will allow both physical and computational removal of rRNA from specimens during RNAseq protocols. We also assess the utility of rRNA sequences for molecular taxonomy and compare phylogenies constructed using rRNA sequences versus those created using the gold standard for molecular species identification of specimens-the mitochondrial cytochrome c oxidase I (COI) gene. We find that rRNA- and COI-derived phylogenetic trees are incongruent and that 28S and concatenated 28S+18S rRNA phylogenies reflect evolutionary relationships that are more aligned with contemporary mosquito systematics. This significant expansion to the current rRNA reference library for mosquitoes will improve mosquito RNA-seq metagenomics by permitting the optimization of species-specific rRNA depletion protocols for a broader range of species and streamlining species identification by rRNA sequence and phylogenetics

Ribosomal RNA (rRNA) sequences from 33 globally distributed mosquito species for improved metagenomics and species identification

Total RNA sequencing (RNA-seq) is an important tool in the study of mosquitoes and the RNA viruses they vector as it allows assessment of both host and viral RNA in specimens. However, there are two main constraints. First, as with many other species, abundant mosquito ribosomal RNA (rRNA) serves as the predominant template from which sequences are generated, meaning that the desired host and viral templates are sequenced far less. Second, mosquito specimens captured in the field must be correctly identified, in some cases to the sub-species level. Here, we generate mosquito rRNA datasets which will substantially mitigate both of these problems. We describe a strategy to assemble novel rRNA sequences from mosquito specimens and produce an unprecedented dataset of 234 full-length 28S and 18S rRNA sequences of 33 medically important species from countries with known histories of mosquito-borne virus circulation (Cambodia, the Central African Republic, Madagascar, and French Guiana). These sequences will allow both physical and computational removal of rRNA from specimens during RNA-seq protocols. We also assess the utility of rRNA sequences for molecular taxonomy and compare phylogenies constructed using rRNA sequences versus those created using the gold standard for molecular species identification of specimens—the mitochondrial cytochrome c oxidase I (COI) gene. We find that rRNA- and COI-derived phylogenetic trees are incongruent and that 28S and concatenated 28S+18S rRNA phylogenies reflect evolutionary relationships that are more aligned with contemporary mosquito systematics. This significant expansion to the current rRNA reference library for mosquitoes will improve mosquito RNA-seq metagenomics by permitting the optimization of species-specific rRNA depletion protocols for a broader range of species and streamlining species identification by rRNA sequence and phylogenetics

B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice

Wiskott Aldrich syndrome (WAS) is caused by mutations in the WAS gene that encodes for a protein (WASp) involved in cytoskeleton organization in hematopoietic cells. Several distinctive abnormalities of T, B, and natural killer lymphocytes; dendritic cells; and phagocytes have been found in WASp-deficient patients and mice; however, the in vivo consequence of WASp deficiency within individual blood cell lineages has not been definitively evaluated. By conditional gene deletion we have generated mice with selective deficiency ofWASp in the B-cell lineage (B/WcKO mice). We show that this is sufficient to cause a severe reduction of marginal zone B cells and inability to respond to type II T-independent Ags, thereby recapitulating phenotypic features of complete WASp deficiency. In addition, B/WcKO mice showed prominent signs of B-cell dysregulation, as indicated by an increase in serum IgM levels, expansion of germinal center B cells and plasma cells, and elevated autoantibody production. These findings are accompanied by hyperproliferation of WASp-deficient follicular and germinal center B cells in heterozygous B/WcKO mice in vivo and excessive differentiation of WASp-deficient B cells into class-switched plasmablasts in vitro, suggesting that WASp-dependent B cell-intrinsic mechanisms critically contribute to WAS-associated autoimmunity