No description available.

No description available.

No description available.

No description available.

Syftet med detta examensarbete var att validera en metod som kvantitativt bestämmer PFAS ijord, slam och sediment. Valideringen omfattade en del olika tester för att utvärdera metodensrapporteringsgräns, precision, riktighet, mätosäkerhet och specificitet. Excel har använts för attberäkna och sammanställa resultaten från de olika testerna. Blankprover och spikade prover haranalyserats för att undersöka rapporteringsgräns. Kontrollprover har analyserats för attundersöka precision samt specificitet. För att undersöka riktighet har en rad olika tester utförts;ISTD-matchning för några av PFAS-analyter som saknade en direkt ISTD-match, jämförelsermot certifierat referensmaterial, analys av tidigare utförda tester som redan hade analyserats iALS Prag och spikade provmatriser. Mätosäkerheten uppskattade och utvärderades i samrådmed kvalitetsansvarig. Resultatet från metodvalideringen bekräftar att metoden har visat sig vara väl validerad.Samtliga tester som utfördes under valideringsprocessen har konsekvent uppfyllt och överträffatde ställda acceptanskriterium för valideringen. Kriterierna inkluderade bland annat relativstandardavvikelse (RSD), utbyte, bias och halt för olika testparametrar. Den omfattandemetodvalideringen gav starka bevis att metoden är tillförlitlig och kan användas för att genererapålitliga resultat inom PFAS-analys. / The purpose of this thesis was to validate a method for quantitatively determining PFAS in soil,sludge, and sediment. The validation involved a number of different tests to evaluate themethod's reporting limit, precision, accuracy, measurement uncertainty, and specificity. Excelwas used to calculate and summarize the results from the different tests. Blank and spikedsamples were analyzed to investigate the reporting limit. Control samples were analyzed toinvestigate precision and specificity. A variety of tests were performed to investigate accuracy;ISTD matching for some PFAS analytes that lacked a direct ISTD match, comparisons againstcertified reference material, analysis of previously performed tests that had already beenanalyzed at ALS Prague, and spiked sample matrices. The measurement uncertainty wasestimated and evaluated in consultation with the quality manager. The results of the method validation confirm that the method has been shown to be wellvalidated. All tests performed during the validation process have consistently met and exceededthe established acceptance criteria for the validation. Criteria included, among others, relativestandard deviation (RSD), recovery, bias, and concentration for various test parameters. Thecomprehensive method validation provided strong evidence that the method is reliable and canbe used to generate reliable results in PFAS analysis.

The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress. Certain GST loci are polymorphic, demonstrating alleles that are null (GSTMI/GSTT1), encode low activity variants (GSTPI), or are associated with variable inducibility (GSTM3). Interleukin-1 (IL- 1) alpha and beta are cytokines involved in recruitment of inflammatory cells, the process of inflammation, and blood-brain barrier breakdown and nerve regeneration. Polymorphisms of both GST and of a complementary interleukin-1 receptor antagonist have been associated with severity and susceptibility to other inflammatory conditions. This thesis examines the influence of the GST and IL-1 genes on both the susceptibility to Multiple Sclerosis (MS), and the course of disease progression. The population examined consisted of four hundred patients with clinically definite MS. Disease severity was measured using the Kurtzke Expanded Disability Status Scale (EDSS), a robust established ranking scale. PCR-based genotyping was performed using DNA extracted from lymphocytes. Significant associations between genotypes and clinical outcome were corrected for known demographic factors influencing prognosis, these being; gender, onset age, and disease duration using the statistical method of logistic regression. Significant associations, withstanding multiple testing corrections, with certain IL-I genotypes and disease severity were found. There was also a significant trend with the GST isoenzymeM 3 that is expressedin nervous tissue. No robust findings suggest that these genes influence susceptibility to MS, but the results suggest that long-term prognosis is genetically influenced by the modulation of inflammatory cytokines and also by the ability to remove the toxic products of oxidative stress.

No description available.

No description available.

No description available.

Les substances synthétisées par les bactéries du genre Bacillus présentent un grand intérêt en raison de leurs nombreuses activités antimicrobiennes. L’objectif de ce travail a consisté à mettre au point un protocole analytique fiable pour extraire ces substances, et les caractériser par spectrométrie de masse et par leurs activités biologiques. Une première approche par spectrométrie de masse MALDI-ToF ne nous a pas donné de résultats satisfaisants en raison d’un phénomène de suppression spectrale. Une seconde stratégie d’étude combinant deux techniques analytiques a alors été envisagée. Les composés et les familles lipopeptidiques ont d’abord été séparés par chromatographie liquide analytique et analysés en ligne en mode de couplage ESI-IT. Ensuite les fractions collectées ont été caractérisées par spectrométrie de masse MALDI-Q-ToF (et ESI-Q-ToF) pour déterminer les masses exactes et obtenir des spectres de fragmentation complémentaires des premiers. Ce procédé nous a permis d’établir des critères d’identification des composés et des familles de lipopeptides de structures connues. Cette caractérisation est basée sur des temps de rétention en chromatographie, des mesures de masses exactes et sur des schémas de fragmentations. Nous avons fait de même avec les composés non identifiés et ensuite évalué leur activité biologique en réalisant des tests de diffusion sur agar. Cette stratégie d’étude permet de faire un criblage de l’ensemble des biomolécules produites par des souches de Bacillus et de relier une structure à une activité biologique. Ce protocole, mis au point pour des cultures réalisées en milieu liquide, a ensuite été adapté aux cultures sur boîtes de Pétri pour pouvoir analyser les composés produits à l’échelle de la colonie bactérienne. / Compounds produced by Bacillus bacteria present a major interest because of their biological activities. The aim of this work was to develop a reliable analytical methodology to extract these compounds, and to characterize them by mass spectrometry and by their biological activities. A first approach by MALDI-ToF mass spectrometry doesn’t give satisfactory results because of strong spectral suppression effects. Therefore, we have designed a second strategy which combined two analytical technologies. First, compounds and lipopeptides families were separated by analytical liquid chromatography and analysed by ESI-IT. Then, collected fractions were characterized by MALDI-Q-ToF (and ESI-Q-ToF) in order to determine accurate mass measurements and obtain complementary product ion spectra. This process led us to establish identification criteria of compounds and lipopeptides families which have known structures. This characterization is based of retention times in chromatography, accrurate mass measurements and fragmentation schemes. We have achieved the same experiments with non identified compounds and then assessed their biological activity by agar well diffusion test.This strategy allows to obtain a screening of whole of the biomolecules produced by bacillus strains and establishes a link between structure and biological activity. This methodology, designed for cultures in liquid medium, was then adapted to cultures in Petri disches in order to analyse compounds producted at the bacterial colony scale.