<p>Natural products, along with natural product derivatives, are known to be at the root of the development of many pharmaceuticals, oftentimes showing unique bioactivity against interesting targets. Specifically, natural products containing furans show activity against a variety of diseases including fungal infections, and cancers. It is hypothesized that unknown natural products containing furans could show more potent or other biological activities. However, it is challenging to discover and isolate these small molecules from cell supernatant. The work described herein showcases the development of a molecular probe that can covalently attach to furan moieties via a [4 + 2] Diels-Alder cycloaddition, making them easily identifiable on liquid chromatography mass spectroscopy (LC-MS). The molecular probe, which undergoes this reaction with a variety of furans, was designed with both a UV-tag and a mass tag to enable easy identification. The probe has been tested with a variety of purified furans, including natural products, methylenomycin furan (MMF) hormones, and MMF derivatives. Moreover, work has begun to test the molecular probe in cell supernatants. </p>

Der betriebliche Einsatz von Smart Glasses zur Unterstützung von manuellen Dienstleistungsprozessen bietet viele Vorteile, die mit anderen Technologien nicht erreicht werden können. Insbesondere im Bereich der Logistik kann von der Informationsversorgung bei gleichzeitiger Mobilität Gebrauch gemacht werden. Um dieses Potenzial auszunutzen, bedarf es allerdings Softwarelösungen, die auf die jeweiligen Anforderungen zugeschnitten sind. In dieser Forschungsarbeit wird daher untersucht, wie Smart-Glasses-basierte Informationssysteme zur Unterstützung der Logistik zu gestalten und zu implementieren sind. Die Forschungsarbeit folgt dabei zwei Zielen: (A) Die Unterstützung von Logistikprozessen durch Smart-Glasses-basierte Informationssysteme wird im Hinblick auf Anforderungen, Herausforderungen und Gestaltungsprinzipien untersucht, und (B) wird der Entwicklungsprozess zur Gestaltung und Implementierung von derartigen Informationssystemen im Rahmen eines Forschungsprojekts konzipiert und evaluiert. Das Vorgehen wird durch methodische Betrachtungen von Gestaltungsanforderungen und -prinzipien geleitet und entspricht so dem gestaltungsorientierten Forschungsansatz der Wirtschaftsinformatik. Die genauere Beantwortung der gestellten Forschungsfrage erfolgt in drei Schritten: (1) Methoden zur Initiierung von agilen Softwareprojekten und der Integration von Softwareentwicklung und -betrieb werden basierend auf der Wissensbasis agiler Methoden, Praktiken und Ansätze abgeleitet, (2) Grundlagen zur thematischen Fokussierung auf die Technologie Smart Glasses und die Anwendungsdomäne der Logistik werden durch multimethodische Studien geschaffen, und (3) werden entsprechende Systeme zur Mitarbeiterunterstützung instanziiert, evaluiert und die Forschungsergebnisse in ein Vorgehensframework zur Durchführung von Implementierungsprojekten überführt. Die vorliegende Dissertation trägt somit zur Wissensbasis der gestaltungsorientierten Wirtschaftsinformatik durch die erreichten Erkenntnisse zur Initiierung und Durchführung von Softwareentwicklungsprojekten zur Unterstützung von betrieblichen Prozessen durch Smart-Glasses-basierte Informationssysteme bei. Darüber hinaus bietet die Arbeit durch die bewusst praxisnahe Orientierung mit dem generierten Gestaltungswissen einen Mehrwert für Praktiker aus den betrachteten Bereichen, insbesondere für Stakeholder für die Einführung mobiler Informationssysteme in betrieblichen Umfeldern.

Microbial natural products have been a source for new drugs for many decades and are unrivaled in their capacity to generate not only future therapeutic agents, but also providing key agents for agricultural and industrial use. LC-MS/MS based metabolomic tools and technologies have been developed that can rapidly dereplicate nonribosomal peptides and statistically identify related congeners in an automated nontargeted process from complex natural product extracts with nanogram sensitivity. This data-base search approach is designed to handle linear, cyclic and cyclic-branched nonribosomal peptides from proteinogenic and nonproteinogenic amino acids without genomic data or traditional bioactivity directed fractionation. Chemometric work-flows combined with a comprehensive metabolomic guided discovery strategy were used to profile the chemical space of a diverse collection of understudied fungal endophytes from fruiting plants. This approach allowed for the prioritization of unique isolates and for the focused discovery, isolation and characterization of distinct outlier metabolites by LC-SPE, 1D and 2D NMR, HRMS and single crystal X-ray analysis. These metabolomic tools and strategies have led to the discovery and characterization of 35 new and over 40 known natural products, many of which are biologically active. This thesis with enabling metabolomic tools and novel discoveries has demonstrated the utility of these analytical methodologies as an effective strategy for the untargeted discovery of new natural products from bacteria and endophytic fungi. / Thesis / Doctor of Philosophy (PhD)

[pt] Esse trabalho investiga o papel da descoberta de produto na demanda por jogos eletrônicos. Nós mostramos que o padrão de vendas para jogos eletrônicos é bastante variado, com alguns jogos tendo suas vendas imediatamente depois de seus lançamentos, e outros com caldas de venda maiores. Para entender essas diferenças nós propomos um modelo de demanda em que consumidores são periodicamente informados sobre a existência de um jogo e exploramos o padrão de vendas que isso implica. Em seguida aplicamos o modelo aos dados usando dados de preços e vendas da plataforma digital Steam e dados e busca online do google trends. Nossos resultados sugerem que vendas três meses depois do lançamento são em média metade do que seria caso consumidores tivessem informação completa. / [en] This paper investigates the role of product discovery in the demand for video games. We show that the lifetime sales patterns for video games vary widely, with some games selling most of their units in the first months after launch and others having longer tails. To understand these differences we propose a demand model in which consumers are periodically informed about the existence of a game and explore the lifetime sales patterns that this implies. We then take it to the data using price and sales figures from the Steam digital platform and web search figures from google trends. Our results imply that sales three months after launch are on average half of what they should be were consumers fully informed.