Dissertationen zum Thema „AlSb LCQ“

La détection sensible et sélective des BTEX et du propane présente un grand intérêt pour les applications environnementales, biomédicales et pétrochimiques. Cependant, la détection de ces composés est compliquée à cause des interférences potentielles, soit entre eux, soit avec d'autres composés. Ce problème peut être résolu par la spectroscopie laser à de grandes longueurs d'onde (13-15 µm), où ils présentent des caractéristiques d'absorption très discriminantes. Pourtant, cette gamme spectrale est pratiquement inexplorée en raison du manque de sources appropriées. Cette thèse vise à combler cette lacune en développant des LCQ émettant à des grandes longueurs d'onde élevées et en exploitant le QEPAS pour une détection ultra-sensible et sélective.Un nouveau design est proposé pour améliorer les performances des LCQ à base d'InAs de grande longueurs d'onde. Cette conception nous a permis de démontrer une densité de courant de seuil record de 0,6 kA/cm2 à 300 K. En outre, une nouvelle technique d'isolation utilisant le SOG est également proposée pour améliorer les problèmes de stabilité du dispositif provoqués par l'altération des propriétés de l'isolation de la résine photosensible (généralement utilisée pour les QCL à base d'InAs) à des températures élevées. Par la suite, des QCL DFB monomodes avec un SMSR > 20 dB et une puissance de sortie optique de l'ordre du mW ont été développé, ciblant les lignes d'absorption de ces gaz. En utilisant ces lasers, un système de détection basé sur le QEPAS a été développé, calibré et caractérisé pour la détection du toluène, du benzène et du propane. Des limites de détection exceptionnellement basses de 113 ppb, 3 ppb et 3 ppm sont atteintes dans une matrice d'azote pur sur un temps d'intégration de 10 secondes. Le système conserve sa sélectivité et sa robustesse, même dans des mélanges de gaz complexes. Enfin, une QCL de 13,71 µm est couplée avec succès à un HCW, où les conditions optimales de couplage, la qualité du faisceau et la perte sont explorées. L'étude confirme la transmission efficace d'une telle longueur d'onde à travers le HCW avec une perte minimale et une qualité de faisceau spatial améliorée
Sensitive and selective sensing of BTEX and Propane is of great interest for environmental, biomedical, and petrochemical applications. However, detecting these compounds poses unique challenges due to potential interferences, either among themselves or from other compounds. This issue can be resolved by using laser spectroscopy in the long-wavelength mid-infrared spectral region (13-15 µm), where they exhibit highly discriminating absorption features. Yet, this wavelength range is almost unexplored due to the lack of suitable sources. This thesis aims to bridge this gap by developing high-performing long-wavelength QCLs and leveraging QEPAS for ultra-sensitive and selective detection.A novel design is proposed to improve the performance of long-wavelength InAs-based QCLs, which allowed us to demonstrate a record-breaking low threshold current density of 0.6 kA/cm2 at 300 K. Additionally, a novel insulation technique using SOG is also proposed to improve device stability issues provoked by the alteration of properties of photoresist insulation (typically used for InAs-based QCLs) at elevated temperatures. Subsequently, single-frequency DFB QCLs with SMSR > 20 dB and optical output power in the mW range operating in the continuous wave regime are developed, targeting the absorption lines of these gasses. Using these DFBs, a sensing system based on QEPAS is developed, calibrated, and characterized for Toluene, Benzene, and Propane detection. Exceptionally low detection limits of 113 ppb, 3 ppb, and 3 ppm are achieved in a pure nitrogen matrix over a 10-second integration time. The system maintains selectivity and robustness, even in complex gas mixtures. Finally, a 13.71 µm QCL is successfully coupled with a HCW, where optimal coupling conditions, beam quality, and loss are explored. The study confirms the efficient transmission of such wavelength through HCW with minimal loss and improved spatial beam quality

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
MicroRNAs (miRNAs) are emerging as a primary mediator of gene regulation in many different cell types. There is increasing evidence that specific subsets of miRNA play a prominent role in the nervous system, both in development and in specific neurodegenerative diseases. This study aims to elucidate the role of microRNA in selective motor neuron death that is the hallmark of amyotrophic Lateral sclerosis (ALS). Pre-symptomatic time-point was chosen since the levels of miRNAs are highly likely to be altered as a secondary consequence of cell injury and death in ALS. Laser capture microdissection (LCM) was used to study miRNA profiles in motor neurons of spinal cord tissue from SOD1G93A mice, the best characterized model of ALS. In preliminary work, using miRNA specific chips we have identified 2 miRNAs which are dramatically upregulated before disease onset. In this study, high RNA quality was achieved from laser captured cells, which consist in a major advance towards obtaining meaningful results of these miRNAs expression in downstream applications. Despite LCM technology has become increasingly sophisticated; rapidly obtaining enough amount of starting material for downstream applications is still extremely challenging. The combination of this optimized technique with microarrays, followed by RT-qPCR may provide insights into potential contribution of microRNAs to progression of neurodegeneration of motor neurons in ALS.

CHARGE syndrome is a common cause of congenital deafblindness, but it has been contended individuals with CHARGE form a distinct group within the broader deafblind population. This thesis explores the education of learners with CHARGE and what the similarities and differences between these two groups might be. A review of literature identifies reported anomalies that may impact upon learning and development, and establishes very limited research-based evidence is available with regard to educational practice with this group of learners. Cycle 1 of this investigation involved document analysis of educational reports, revealing internal factors considered to influence learning and development, and external factors including assessment, support from external professionals and teaching strategies. These were explored further in Cycle 2 involving a questionnaire to teachers of a child with CHARGE and interviews of practitioners in an overseas educational establishment. Commonalities and distinctions between learners with CHARGE and the wider deafblind population were found, and also that established educational deafblind practice is applicable to learners with CHARGE, but that strategies may be alternatively employed and additional strategies also required. A variation in educational provision was also found according to the type of placement attended. In conclusion it was considered that, in a broad sense, educationally there is something unique and distinct in learners with CHARGE.

Wir fanden konservierte molekulare Signaturen der Regulation durch Δ7-DA und Ascarosid bei Dauer- und infektiösen Larven. Danach wurde die hohe Konservierung durch unsere Analyse in Dauer- und Postdauer-Stadium zwischen den zwei nah verwandten freilebenden Arten C. elegans und C. briggsae identifiziert. Das heißt, dass die relative Veränderung auf mRNA- oder Protein- Ebene zwischen zwei Arten stark korreliert ist. Aber die relative Veränderung innerhalb derselben Art zeigt keine hochgradige Korrelation zwischen mRNA- und Protein-Ebene. Unsere Ergebnisse zeigen in C. elegans Dauerlarven die signifikante Reduzierung der RNA-Mengen in 20 Stoffwechselwegen. Im Gegensatz dazu speicherten Dauerlarven reichlich RNA-Mengen in GO Termen wie Ribosome und Aminoacyl-tRNA biosynthesis. Auf Protein-Ebene sind die Stoffwechselwege von Proteinsynthese und Proteinverarbeitung im endoplasmatischen Retikulum in Dauerlarven herunterreguliert und GO Terme wie Lysosome sind hochreguliert. Durch die Zeitreihenanalyse der Proteom-Remodellierung der molekularen Signaturen beim Austritt aus dem Dauer-Stadium fand wir, dass GO Terme wie metal ion binding signifikant herunterreguliert sind und der Proteinabbau hochreguliert ist. Unsere Ergebnisse vom pSILAC Experiment deuten an, dass die Proteine für Energieerzeugung und Chaperone/Proteinfaltung beim Daueraustritt schnell verbraucht sind und wieder hergestellt werden. Zum Schluss haben wir als Erste den popomR-Assay in C. elegans etabliert und ein Screening der vermeintlichen Proteinbindestellen auf poly-A-RNA durchgeführt, um in der Zukunft die konservierten Mechanismen der post-transkriptionellen Regulation durch RBPs im Dauer-Stadium zu analysieren.
We found the conservation of molecular signatures by regulating with Δ7-DA and Ascarosid in dauer larvae and infective larvae. Then by our comparative analysis, the high degree of conservation between two closely related free-living species C. elegans and C. briggsae was identified in dauer and post-dauer stages. This means that the relative changes are strongly correlated on the mRNA or the protein level between two species. But the relative changes in the same species don’t show any strong correlation between the mRNA and the protein levels. Our results showed a significantly reduced amount of RNA in 20 metabolic pathways in C. elegans dauer larvae. In contrast, dauer larvae stored a large amount of RNA in GO terms such as ribosome and aminoacyl-tRNA biosynthesis. On the protein level, the metabolic pathways of protein synthesis and protein processing in endoplasmic reticulum were downregulated in dauer larvae and the term of lysosome was up-regulated. Due to time course analysis for proteome remodeling of molecular signatures during exit process from dauer stage, we found that GO terms such as metal ion binding were significantly downregulated during dauer exit and at the same time the protein degradation was up-regulated. Our results of pSILAC experiment suggest that the proteins for energy generation and chaperone/protein folding are quickly spent and rebuilded during dauer exit. Finally, we were the first to establish the popomR assay in C. elegans and performed a screening of the putative protein binding sites on poly-A RNA to analyze the conserved mechanisms of post-transcriptional regulation by RBPs in dauer larvae in the future.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)
Esta tese de doutorado ? um aporte te?rico-pr?tica para o desenvolvimento de estudos que utilizem a bioanal?tica, particulamente materiais biol?gicos provenientes de bact?rias, podendo estes ser isolados, DNA, entre outros, em conjunto com ferramentas quimiom?ticas de an?lise. Para isso, buscou-se identificar diferen?as bacterianas quando submetidas a uma fonte de estresse a partir de diferentes t?cnicas anal?ticas. A primeira abordagem foi realizada partindo da bioespectroscopia, utilizando-se de dados espectrosc?picos obtidos na regi?o do infravermelho. A bioespectroscopia na regi?o do infravermelho ? descrita como uma t?cnica n?o invasiva, de alto rendimento, baixo custo (quando comparado com t?cnica padr?es de an?lise) e objetivas, e que possui um enorme potencial na an?lise de bact?rias, complementando ou mesmo substituindo m?todos de diagn?stico de doen?as convencionalmente conduzidos por especialistas atrav?s de m?todos padr?es de an?lises de alto custo e que necessitam de reagentes espec?ficos. Os dados obtidos a partir da bioespectroscopia em amostras bacterianas s?o complexos e apresentam muitas bandas de sobreposi??o sendo necess?ria a aplica??o de ferramentas matem?ticas para superar estas dificuldades. Para isso, algumas ferramentas matem?ticas, como os m?todos de sele??o de vari?veis, que utilizam a an?lise discriminante linear com Algoritmo de Proje??o Sucessiva (SPA-LDA) e Algoritmo Gen?tico (GA-LDA), geralmente s?o utilizadas com a finalidade de facilitando a extra??o de informa??es relevantes. A espectroscopia na regi?o do infravermelho, em espec?fico infravermelho pr?ximo (NIR) e infravermelho com trasformata de Fourier e reflect?ncia total atenuada (ATR-FTIR), em conjunto com m?todos de sele??o de vari?veis (SPA-LDA e GA-LDA) foram utilizadas na discrimina??o de amostras de bact?rias (Sthaphylococcus aureus, Klebsiella pneumoneae e Pseudomonas aeruginosa). Foram identificados prov?veis biomarcadores como lip?deos e prote?nas em ~1550 cm-1 e 1400 cm-1 e vibra??es de DNA em ~1080 cm-1. Valores de sensibilidade de 75% e 95% para modelos de SPA-LDA e 100% e 93% para modelos GA-LDA foram encontrados. Com base nesses resultados, pode-se concluir que o SPA-LDA e GA-LDA em conjunto com a espectroscopia na regi?o do infravermelho mostraram-se ferramentas eficientes melhorando o tempo e custo de diagn?stico possibilitando o tratamento mais r?pido em rela??o aos m?todos padr?es de diagn?stico e, consequentemente, sendo poss?vel evitar a evolu??o de uma poss?vel infec??o. A segunda abordagem foi avaliar poss?veis mudan?as no perfil lipid?mico de bact?rias resultante de sua exposi??o a uma fonte de estresse externa (Ars?nio (III)), utilizando as cianobact?rias Anabaena sp. e Planktothrix agardhii. Os dados foram obtidos a partir a Cromatografia L?quida- Espectrometria de Massas (LC-MS) que por gerar uma matriz de dados muito extensa foi necess?ria a utiliza??o de uma estrat?gia de sele??o proposta recentemente, definida como ROI (do ingl?s regions of interests) que diminui significativamente o tamanho da matriz de dados obtidas por LC-MS. Resolu??o Multivariada de Curvas com M?nimos Quadrados Alternantes (MCR-ALS) foi utilizado como m?todo de resolu??o das fontes de varia??o, recuperando as informa??es de seus componentes puros que se encontravam misturadas. As massas majorit?rias encontradas, sendo algumas delas 766.54, 565.40 e 871.56 (m/z), determinam que as cianobact?rias estudadas, ao serem submetidas a As(III), sofrem mudan?as relacionadas a estruturas que comp?em os processos fotossint?ticos das mesmas.
This doctoral thesis is a theoretical-practical contribution for the development of studies that use bioanalytical, particularly biological materials from bacteria, which can be isolated, DNA, among others, in conjunction with chemistry analysis tools. For this, it was sought to identify bacterial differences when submitted to a source of stress from different analytical techniques. The first approach was based on biospectroscopy, using spectroscopic data obtained in the infrared region. Biospectroscopy in the infrared region is described as a non-invasive, high-throughput, low-cost (when compared with standard analytical techniques) and objective techniques, and has a huge potential in the analysis of bacteria, complementing or even replacing diagnostic methods of diseases conventionally conducted by skilled persons by standard methods of expensive analyzes and requiring specific reagents. The data obtained from biospectroscopy in bacterial samples are complex and have many overlapping bands and it is necessary to apply mathematical tools to overcome these difficulties. For this, some mathematical tools, such as variable selection methods, using Linear Discriminant Analysis with Successive Projection Algorithm (SPA-LDA) and Genetic Algorithm (GA-LDA), are generally used for the purpose of solving these data, facilitating the extraction of information. Infrared spectroscopy, in specific Near Infrared (NIR) and infrared spectroscopy with Fourier transform and Attenuated Total Reflectance (ATR- FTIR), in conjunction with variable selection methods (SPA-LDA and GA-LDA) was used in the discrimination of bacterial samples (Sthaphylococcus aureus, Klebsiella pneumoneae and Pseudomonas aeruginosa). Possible biomarkers such as lipids and proteins were identified at ~ 1550 cm -1 and 1400 cm -1 and DNA vibrations at ~ 1080 cm -1. Sensitivity values of 75% and 95% for SPA-LDA models and 100% and 93% for GA-LDA models were found. Based on these results, it can be concluded that the SPA-LDA and GA- LDA in conjunction with the infrared spectroscopy showed efficient tools improving the time and cost of diagnosis allowing the treatment faster than the standard methods of diagnosis, and consequently, it is possible to avoid the evolution of a possible infection. The second approach was to evaluate possible changes in the lipid profile of bacteria resulting from its exposure to an external stress source (Arsenic (III)), using the cyanobacteria Anabaena sp. and Planktothrix agardhii. The data were obtained from Liquid Chromatography-Mass Spectrometry (LC-MS), which, in order to generate a very extensive data matrix, required the use of a recent selection strategy, defined as ROI (regions of interest), which significantly decreased the Size of the data matrix obtained by LC-MS. Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS) was used as a method to solve variation sources, retrieving the information of its pure components that were mixed. The majority masses found, such as 766.54, 565.40 and 871.56 (m/z), determine that the studied cyanobacteria, when subjected to As (III), undergo changes related to structures that make up the photosynthetic processes of the same.

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In der vorliegenden Arbeit wurde die transkriptionelle Regulation des proximalen Promotors der lymphozytenspezifischen Proteintyrosinkinase lck untersucht. Das Hauptaugenmerk richtete sich auf die Beteiligung der Familie der NF-AT-Transkriptionsfaktoren an der Kontrolle der Promotoraktivität. Es konnte zunächst gezeigt werden, dass NF-ATs aus Zellkulturzellen sowie aus frisch isolierten Thymozyten spezifisch an Sequenzmotive in der regulatorischen Region des lck-Typ-I-Promotors binden. Die NF-AT-Bindungsstellen mit der höchsten Affinität wurden in Pos. –480/–476 (NF-AT-I lck) und in Pos. –216/–212 (NF-AT-II lck) identifiziert. Eine Mutation in den Bindungsmotiven verhinderte dementsprechend die Ausbildung von NF-AT-Komplexen mit der DNA. Darüber hinaus wurde nachgewiesen, dass NF-AT-Faktoren den proximalen lck-Promotor allein und zusammen mit Faktoren der Ets-Familie bzw. c-Myb aktivieren können. Die Untersuchung der Interaktion von NF-AT und c-Myb ergab, dass die beiden Transkriptionsfaktoren unmittelbar benachbart an die DNA binden. Unter Berücksichtigung dieses Bindungsverhaltens und der Kooperation in der Transaktivierung des Promotors konnten wir somit eine neue Form eines NF-AT-"composite elements" beschreiben. Bei der Untersuchung von NF-AT-"knock out"-Mäusen auf Anzeichen einer lck-Bildungsstörung zeigte sich eine deutliche Reduktion der lck-Typ-I-Transkripte in NF-AT1/NF-AT4 doppelt defizienten Tieren. Dies belegt die Relevanz der NF-AT-Faktoren für die Aktivität des proximalen lck-Promotors in vivo
The presented thesis covers the investigation of the transcriptional regulation of the proximal promotor of the lymphocyte specific protein tyrosine kinase lck. The main aspect is focused on the role of NF-AT family of transcription factors in the control of the promotor activity. It was shown that NF-ATs in cell culture cells as well as in freshly isolated murine thymocytes show specific binding to sequence motifs in the regulatory sequence of the lck type I promotor. The NF-AT binding sites with the strongest affinity were located in pos. -480/-476 (NF-ATI lck) and pos. -216/-212 (NF-AT II lck). Mutations in the binding motifs did therefore not allow any complex formation inbetween NF-AT an DNA. Moreover it was shown that NF-AT factors were able to activate the proximal lck-promotor by themselves and together with c-Myb and members of the Ets-family. The investigation of the interaction between NF-At and c-Myb revealed that the two factors bind the DNA in close proximity. Taking this into account and the fact that the two factors cooperate in the transactivation of the proximal lck promotor we were able to describe a new NF-AT "composite element". Examining NF-AT knock out mice for signs of lck-deprevation we saw a significant reduction of lck-type I transcripts in NF-AT1/NF-AT4-double negative animals. This stresses the relevance of NF-AT factors for the activity of the proximal lck-promotor in vivo

Library 2.0 - a concept based on blogs, wikis, RSS, social bookmarking or other - can provide a new future for libraries. Are the librarians ready for this shift? Are the users ready for it? Is it something for now or for much later? This thesis tries to answer these questions.

Metabonomics bildet das Ende der Omics-Kaskade und stellt eine top-down-Strategie zur Erfassung und Interpretation des Metaboloms, d. h. der Gesamtheit aller niedermolekularen Metaboliten in einem intakten Organismus, dar. Ziel der Technik ist es, mittels geeigneter ungerichteter Screeningverfahren in nicht-invasiv zu gewinnenden biologischen Proben wie Urin oder Blut charakteristische Metabolitenprofile zu bestimmen. Im Kontext des Metabonomics wurde in Anlehnung an den Geno- bzw. Phänotyp hierfür der Begriff „Metabotyp“ geprägt. Durch biostatistische Methoden, die auf Mustererkennung (pattern recognition) basieren, können Signaturen gegenübergestellt und auf diesem Weg gruppenspezifische Metaboliten, d. h. Biomarker bzw. Metabolitenmuster, extrahiert werden. Metabonomics kann folglich als Fusion klassischer bioanalytischer und biostatistischer Verfahren aufgefasst werden. Seit der Einführung im Jahr 1999 hat sich das Konzept des Metabonomics in mehrere Richtungen weiterentwickelt. So gab es Bestrebungen, die Technik, die ursprünglich zur Prädiktion von toxischen Effekten bei der Arzneistoffentwicklung etabliert wurde, auf Fragestellungen zu übertragen, die den Menschen im Mittelpunkt haben. Neben präklinischen Anwendungen verfolgt man mit Metabonomics zunehmend das Ziel, einer personalisierten Medizin und Ernährung einen Schritt näher zu kommen. Da sich die ursprünglich eingesetzte NMR-Technik als zu unempfindlich und die resultierenden Metabolitenprofile als zu anfällig gegenüber biologischen und analytischen Einflussgrößen (Confoundern) erwiesen haben, wurde parallel auf sensitivere Verfahren wie die Massenspektrometrie gesetzt. Insbesondere die Kopplung mit der Hochdruckflüssigchromatographie erwies sich hierbei für das Metabolitenscreening als geeignet. Schnell wurde allerdings klar, dass aus den klassischen full scan/TOF-Methoden Datensätze resultierten, die häufig zu komplex waren, um mit nachgeschalteten chemometrischen Verfahren die „Spreu vom Weizen trennen“ zu können. Da sich Metabolitendatenbanken bisher noch im Aufbau befinden, ist die Identifizierung der Marker mit zusätzlichen Schwierigkeiten verbunden und bedarf aufwändiger analytischer Verfahren. Eine Strategie stellt daher die Beschränkung auf ein Metabolitensubset dar. Indem man sich auf Metabolitenklassen fokussiert, die einen Bezug zum untersuchten Mechanismus haben, können die Erfolgsaussichten bei der Identifizierung charakteristischer Biomarker deutlich erhöht werden. Aufgrund zahlreicher exogener und endogener Faktoren (Arzneistoffe, Industriechemikalien, Nahrungsbestandteile, Tabakrauchbestandteile, Produkte der Lipidperoxidation etc.) ist der menschliche Organismus stets einer Vielzahl an elektrophilen Verbindungen ausgesetzt. Oxidative Schädigungen an Strukturen wie der DNA, Proteinen und Lipiden werden mit einer Reihe von Krankheitsbildern in Zusammenhang gebracht, darunter Parkinson, Alzheimer, Krebs und Volkskrankheiten wie Arteriosklerose, Allergien und koronare Herzerkrankungen. Mit dem Glutathionsystem verfügt der Körper über einen wirksamen Detoxifizierungsmechanismus. Das Tripeptid Glutathion reagiert als Nukleophil mit den exogen oder endogen gebildeten elektrophilen Intermediaten. Endprodukte sind Merkaptursäuren (N-Acetyl-L-Cystein-Addukte) bzw. deren Sulfoxide, die in erster Linie mit dem Urin ausgeschieden werden. Folglich besteht zwischen diesen Merkaptursäurederivaten und der elektrophilen Belastung eines Organismus ein direkter Zusammenhang. Vor diesem Hintergrund war es das Ziel der Arbeit, einen nicht-invasiven Metabonomicsansatz zur Anwendung am Menschen zu entwickeln. Durch die Fokussierung des Metabolitenscreenings auf die Effekt-, Dosis- und Suszeptibilitätsmarkerklasse der Merkaptursäuren sollten hierbei die Erfolgsaussichten im Hinblick auf die Identifizierung potentieller Biomarker für diverse toxikologische sowie medizinische Endpunkte erhöht werden
Metabonomics forms the end of the omics-cascade and represents a top-down strategy for the interpretation of the metabolome, i. e. all the low molecular weight metabolites in an intact organism. The aim of the approach is to analyse characteristic metabolite profiles by suitable untargeted screening methods in biological samples like urine or blood that can be obtained in a non-invasive manner. In the context of metabonomics, the term “metabotype” was defined according to the geno- and phenotype, respectively. Biostatistical methods based on pattern recognition techniques allow comparing metabolic signatures and extracting group specific metabolites and biomarkers. Therefore, metabonomics can be regarded as the fusion of bioanalytical and biostatistical techniques. Since its introduction in 1999, the concept of metabonomics has permanently gained importance in many fields of scientific research. One aim was to transfer the methodology, which was originally established to predict toxic effects in drug development processes, to human issues. Apart from preclinical questions, metabonomics is increasingly applied in the area of personalised medicine and nutrition. As the NMR technique used by pioneers of the field was too insensitive and the resulting metabolite profiles were too susceptible to biological and analytical confounders, more sensitive techniques like mass spectrometry were more and more applied. Especially mass spectrometry in combination with high performance liquid chromatography showed great promise for the screening of metabolites. However, after a very short time, it was clear that the data sets resulting from full scan/TOF-methods were too complex to “separate the wheat from the chaff” with chemometric procedures. Metabolite databases are still under construction, and therefore marker identification is challenging and requires complex analytical techniques. Thus, one strategy is to concentrate on a certain metabolite subset. The focus on a metabolite class with a close relation to the mechanism under investigation can considerably increase the prospects of success in the biomarker identification process. Due to a variety of exogenous and endogenous factors (drugs, industrial chemicals, food ingredients, and tobacco smoke) the human organism is steadily confronted with a multitude of electrophilic compounds. Oxidative damage of the DNA, proteins, and lipids is associated with the development of diseases like Parkinson’s, Alzheimer’s, cancer and widespread diseases like arteriosclerosis, allergies and coronary heart diseases. With the glutathione system the human organism is equipped with an efficient detoxification mechanism. The tripeptide glutathione reacts as nucleophile with exogenously and endogenously formed electrophilic intermediates. End products are mercapturic acids (N-acetyl-L-cysteine-adducts) and respective sulfoxides that are predominantly excreted with urine. Therefore, there is a close relationship between these mercapturic acid patterns and the electrophilic burden of an organism. In this context, the aim of this thesis was to develop a non-invasive human metabonomics approach that focuses the metabolite screening on the effect, dose and susceptibility marker class of the mercapturic acids. Thus, the prospects of success regarding the identification of potential biomarkers for various toxicological and pathological endpoints should be increased