NILC_USP: an improved hybrid system for sentiment analysis in Twitter messages.

This paper describes the NILC USP system that participated in SemEval-2014 Task 9: Sentiment Analysis in Twitter, a re-run of the SemEval 2013 task under the same name. Our system is an improved version of the system that participated in the 2013 task. This system adopts a hybrid classification process that uses three classification approaches: rule-based, lexiconbased and machine learning. We suggest a pipeline architecture that extracts the best characteristics from each classifier. In this work, we want to verify how\ud this hybrid approach would improve with better classifiers. The improved system achieved an F-score of 65.39% in the Twitter message-level subtask for 2013 dataset (+ 9.08% of improvement) and 63.94% for 2014 dataset.FAPESPSAMSUN

Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus

Maitotoxins (MTXs) are among the most potent toxins known. These toxins are produced by epi-benthic dinoflagellates of the genera Gambierdiscus and Fukuyoa and may play a role in causing the symptoms associated with Ciguatera Fish Poisoning. A recent survey revealed that, of the species tested, the newly described species from the Canary Islands, G. excentricus, is one of the most maitotoxic. The goal of the present study was to characterize MTX-related compounds produced by this species. Initially, lysates of cells from two Canary Island G. excentricus strains VGO791 and VGO792 were partially purified by (i) liquid-liquid partitioning between dichloromethane and aqueous methanol followed by (ii) size-exclusion chromatography. Fractions from chromatographic separation were screened for MTX toxicity using both the neuroblastoma neuro-2a (N2a) cytotoxicity and Ca2+ flux functional assays. Fractions containing MTX activity were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to pinpoint potential MTX analogs. Subsequent non-targeted HRMS analysis permitted the identification of a novel MTX analog, maitotoxin-4 (MTX4, accurate mono-isotopic mass of 3292.4860 Da, as free acid form) in the most toxic fractions. HRMS/MS spectra of MTX4 as well as of MTX are presented. In addition, crude methanolic extracts of five other strains of G. excentricus and 37 other strains representing one Fukuyoa species and ten species, one ribotype and one undetermined strain/species of Gambierdiscus were screened for the presence of MTXs using low resolution tandem mass spectrometry (LRMS/MS). This targeted analysis indicated the original maitotoxin (MTX) was only present in one strain (G. australes S080911_1). Putative maitotoxin-2 (p-MTX2) and maitotoxin-3 (p-MTX3) were identified in several other species, but confirmation was not possible because of the lack of reference material. Maitotoxin-4 was detected in all seven strains of G. excentricus examined, independently of their origin (Brazil, Canary Islands and Caribbean), and not detected in any other species. MTX4 may therefore serve as a biomarker for the highly toxic G. excentricus in the Atlantic area

Industrialisation d'un nouveau vaccin au sein d'un service formulation de la Mise Sous Forme Pharmaceutique Sanofi Pasteur

Le développement d'un médicament se déroule en plusieurs étapes. Les lots industriels de conformité produits pour obtenir l'autorisation de mise sur le marché sont réalisés en fin de Phase III du développement clinique. Grâce à ces lots de conformité, le procédé de fabrication du nouveau médicament peut être validé. L'objectif de cette thèse est de montrer la démarche suivie pour valider le processus de fabrication d'un nouveau vaccin au sein du service formulation afin de le produire en routine. L'équipe projet du bâtiment est responsable de cette action en collaboration avec le service développement.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Traitement de l'infection à Pseudomonas aeruginosa dans la mucoviscidose (état actuel et perspectives)

La mucoviscidose est une maladie génétique mortelle due à une viscosité anormale des sécrétions muqueuses par suite d'une mutation sur le gène CFTR qui code pour la protéine CFTR, canal chlorure exprimé à la surface des cellules épithéliales. L'atteinte est multiviscérale avec une prédominance respiratoire. Pseudomonas aeruginosa, bactérie opportuniste, est responsable d'une infection respiratoire chez la grande majorité des patients. Cette infection évolue vers la chronicité et conduit généralement au décès. Les antibiotiques par voie orale, intraveineuse ou inhalée ont permis d'augmenter la durée de vie des patients. Néanmoins, dès lors que l'infection chronique est installée, l'éradication de la bactérie est impossible et les médecins sont de plus en plus confrontés aux résistances bactériennes. De nouveaux traitements antibactériens sont indispensables pour améliorer la prise en charge. Les traitements actuellement en développement sont essentiellement des formes inhalées d'antibiotiques largement utilisés qui amélioreront la qualité de vie des patients, mais ne permettront pas d'éliminer la bactérie. D'autres traitements plus innovants, comme une solution d'anticorps polyclonaux dirigés contre Pseudomonas aeruginosa, n'en sont qu'aux premiers stades de développement mais pourraient apporter un réel progrès thérapeutique en raison de leurs mécanismes d'action nouveaux.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Etudes biologiques et chimiques de Melochia Odorata L.f.

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Tuberculose et terpènes antimycobactériens (étude de l'huile essentielle de Myoporom crassifolium (Myoporacées))

BESANCON-BU Médecine pharmacie (250562102) / SudocSudocFranceF

Etudes métabolique, analytique et biologique des quinoléines antileishmaniennes, en vue de la détermination de leur biodisponibilité

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Apport de nouvelles phases stationnaires dans le contrôle qualité des peptides à visée thérapeutique

La production de peptides-médicaments et de protéines recombinantes est en plein essor dans l industrie pharmaceutique. La synthèse des peptides en phase solide conduit à la formation de substances apparentées de structure proche du peptide d intérêt, d où la nécessité d un contrôle qualité rigoureux. En ce qui concerne les protéines recombinantes, leur contrôle qualité est généralement effectué par l établissement d une carte peptidique, qui correspond à l analyse des fragments peptidiques issus de la digestion enzymatique de la protéine à l aide d une méthode séparative. Pour la détection des substances apparentées ou issus de la dégradation des peptides, des méthodes analytiques capables de distinguer des formes structurellement très proches doivent être proposées pour le contrôle qualité, à toutes les étapes du développement du produit. La chromatographie liquide haute performance (CLHP) en phase inverse est la méthode la plus utilisée pour la détermination de la pureté des peptides synthétiques ou l établissement de la carte peptidique d une protéine. Le but de ce travail de thèse était d évaluer l apport de nouvelles phases stationnaires dans l analyse des peptides. Différents types de phases stationnaires particulaires ou monolithiques ont été étudiés : phases mixtes, d interactions hydrophiles et d échange d ions. Des peptides de caractère physicochimique différents ou de structure proche (les enképhalines) ont été étudiés. L application à la séparation d un peptide d intérêt (dalargine) de ses impuretés de synthèse a été réalisée.The production of peptide-drug and recombinant proteins is growing in the pharmaceutical industry. The solid phase synthesis of peptides leads to the formation of related substances of similar structure of the target peptide, hence the need for rigorous quality control. Regarding the recombinant proteins, their quality control is generally performed by peptide mapping, which corresponds to the analysis of peptide fragments resulted from the enzymatic digestion of the protein. For the detection of related substances or degradation products of peptides, analytical methods able to distinguish similar structurally products should be proposed for quality control at all stages of product development. Reversed phase high-performance liquid chromatography (HPLC-RP) is the most common method used either for determining the purity of synthetic peptides or for the peptide mapping of a protein. The aim of this thesis was to evaluate the contribution of new stationary phases in peptide analysis. Different types of particulate or monolithic stationary phases were studied: mixed, hydrophilic interaction and ion-exchange phases. Peptides of different physico-chemical properties or of closed structure (enkephalins) have been studied. Application to the separation of a target peptide (dalargin) from its synthetic impurities has been performed.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Production and Isolation of Azaspiracid-1 and -2 from Azadinium spinosum Culture in Pilot Scale Photobioreactors

Azaspiracid (AZA) poisoning has been reported following consumption of contaminated shellfish, and is of human health concern. Hence, it is important to have sustainable amounts of the causative toxins available for toxicological studies and for instrument calibration in monitoring programs, without having to rely on natural toxin events. Continuous pilot scale culturing was carried out to evaluate the feasibility of AZA production using Azadinium spinosum cultures. Algae were harvested using tangential flow filtration or continuous centrifugation. AZAs were extracted using solid phase extraction (SPE) procedures, and subsequently purified. When coupling two stirred photobioreactors in series, cell concentrations reached 190,000 and 210,000 cell·mL−1 at steady state in bioreactors 1 and 2, respectively. The AZA cell quota decreased as the dilution rate increased from 0.15 to 0.3 day−1, with optimum toxin production at 0.25 day−1. After optimization, SPE procedures allowed for the recovery of 79 ± 9% of AZAs. The preparative isolation procedure previously developed for shellfish was optimized for algal extracts, such that only four steps were necessary to obtain purified AZA1 and -2. A purification efficiency of more than 70% was achieved, and isolation from 1200 L of culture yielded 9.3 mg of AZA1 and 2.2 mg of AZA2 of >95% purity. This work demonstrated the feasibility of sustainably producing AZA1 and -2 from A. spinosum cultures

Metabolomic approach for the analysis of micro-algae : direct analysis versus passive sampling

By 2014, the new targeted LC-MS/MS reference method for the detection of lipophilic toxins will replace the mouse bioassay (MBA). This bioassay, which has the advantage of being a rapid and global toxicity test, can not be used for toxin identification purposes. Furthermore, it has appeared that, in some cases, the mouse bioassay could reveal uncharacterized toxicities that could not be elucidated by targeted mass spectrometry methods. Therefore, moving from the global toxicity assessment test to a targeted technique leads to a lack of information on emerging toxins. Objectives: - Beside targeted methods, develop metabolomic approaches to screen for known and unknown emerging toxins - Develop passive sampling devices suitable for toxins of varying polarities, as a tool complementary to traditional monitoring - Compare metabolomic profiles of passively sampled algal constituents to those of algae themselves (footprint versus fingerprint