Herstellung eines Phaffia rhodozyma : Stamms mit verstärkter Astaxanthin-Synthese über gezielte genetische Modifikation chemisch mutagenisierter Stämme

Ziel dieser Arbeit war es erstmals durch eine Kombination aus chemischer Mutagenese und gezielter genetischer Modifikation (hier: „metabolic engineering“) einen Phaffia-Stamm herzustellen, welcher über die Mutagenese hinaus über eine weiter verstärkte Astaxanthin-Synthese verfügt. Die von „DSM Nutritional Products“ bereitgestellten chemischen Mutanten wurden analysiert und über einen Selektionsprozess auf Pigmentstabilität und Wachstum hin optimiert, da die Stämme aus cryogenisierter Dauerkultur starke Pigmentinstabilitäten und ein verzögertes Wachstum aufwiesen. Über eine exploratorische Phase wurde die Carotinoidsynthese analysiert und festgestellt, dass in den Mutanten keine Einzelreaktionen betroffen sind, welche für die Heraufregulierung der Carotinoidsynthese in den Mutanten verantwortlich sind. Hierbei wurden Limitierungen identifiziert und diese durch Transformation von Expressionsplasmiden mit geeigneten Genen aufgehoben, um damit eine noch effizientere Metabolisierung von Astaxanthin-Vorstufen hin zu Astaxanthin zu erreichen. Eine Überexpression der Phytoensynthase/Lycopinzyklase crtYB resultierte in einem gesteigerten Carotinoidgehalt bei gleichbleibendem Astaxanthin- Anteil. Durch eine zweite Transformation mit einer Expressionskassette für die Astaxanthin-Synthase asy konnte der Carotinoidgehalt weiter gesteigert und zusätzlich eine Limitierung der Metabolisierung von Astaxanthin-Vorstufen behoben werden, sodass die Transformante nahezu alle Intermediate der Astaxanthinsynthese zu Astaxanthin metabolisieren konnte (Gassel et al. 2013). Es konnte gezeigt werden, dass auch in den Mutanten, aus Experimenten mit dem Wildtyp bekannte, Limitierungen identifiziert und ausgeglichen werden konnten

A Call to Arms: Revisiting Database Design

Good database design is crucial to obtain a sound, consistent database, and - in turn - good database design methodologies are the best way to achieve the right design. These methodologies are taught to most Computer Science undergraduates, as part of any Introduction to Database class. They can be considered part of the "canon", and indeed, the overall approach to database design has been unchanged for years. Moreover, none of the major database research assessments identify database design as a strategic research direction. Should we conclude that database design is a solved problem? Our thesis is that database design remains a critical unsolved problem. Hence, it should be the subject of more research. Our starting point is the observation that traditional database design is not used in practice - and if it were used it would result in designs that are not well adapted to current environments. In short, database design has failed to keep up with the times. In this paper, we put forth arguments to support our viewpoint, analyze the root causes of this situation and suggest some avenues of research.Comment: Removed spurious column break. Nothing else was change

Conceptual Modelling and The Quality of Ontologies: Endurantism Vs. Perdurantism

Ontologies are key enablers for sharing precise and machine-understandable semantics among different applications and parties. Yet, for ontologies to meet these expectations, their quality must be of a good standard. The quality of an ontology is strongly based on the design method employed. This paper addresses the design problems related to the modelling of ontologies, with specific concentration on the issues related to the quality of the conceptualisations produced. The paper aims to demonstrate the impact of the modelling paradigm adopted on the quality of ontological models and, consequently, the potential impact that such a decision can have in relation to the development of software applications. To this aim, an ontology that is conceptualised based on the Object-Role Modelling (ORM) approach (a representative of endurantism) is re-engineered into a one modelled on the basis of the Object Paradigm (OP) (a representative of perdurantism). Next, the two ontologies are analytically compared using the specified criteria. The conducted comparison highlights that using the OP for ontology conceptualisation can provide more expressive, reusable, objective and temporal ontologies than those conceptualised on the basis of the ORM approach

Towards an Indexical Model of Situated Language Comprehension for Cognitive Agents in Physical Worlds

We propose a computational model of situated language comprehension based on the Indexical Hypothesis that generates meaning representations by translating amodal linguistic symbols to modal representations of beliefs, knowledge, and experience external to the linguistic system. This Indexical Model incorporates multiple information sources, including perceptions, domain knowledge, and short-term and long-term experiences during comprehension. We show that exploiting diverse information sources can alleviate ambiguities that arise from contextual use of underspecific referring expressions and unexpressed argument alternations of verbs. The model is being used to support linguistic interactions in Rosie, an agent implemented in Soar that learns from instruction.Comment: Advances in Cognitive Systems 3 (2014

Controlled vocabularies and semantics in systems biology

The use of computational modeling to describe and analyze biological systems is at the heart of systems biology. Model structures, simulation descriptions and numerical results can be encoded in structured formats, but there is an increasing need to provide an additional semantic layer. Semantic information adds meaning to components of structured descriptions to help identify and interpret them unambiguously. Ontologies are one of the tools frequently used for this purpose. We describe here three ontologies created specifically to address the needs of the systems biology community. The Systems Biology Ontology (SBO) provides semantic information about the model components. The Kinetic Simulation Algorithm Ontology (KiSAO) supplies information about existing algorithms available for the simulation of systems biology models, their characterization and interrelationships. The Terminology for the Description of Dynamics (TEDDY) categorizes dynamical features of the simulation results and general systems behavior. The provision of semantic information extends a model's longevity and facilitates its reuse. It provides useful insight into the biology of modeled processes, and may be used to make informed decisions on subsequent simulation experiments

Proceedings ICPW'07: 2nd International Conference on the Pragmatic Web, 22-23 Oct. 2007, Tilburg: NL

Proceedings ICPW'07: 2nd International Conference on the Pragmatic Web, 22-23 Oct. 2007, Tilburg: N

Polysemy and word meaning: an account of lexical meaning for different kinds of content words

There is an ongoing debate about the meaning of lexical words, i.e., words that contribute with content to the meaning of sentences. This debate has coincided with a renewal in the study of polysemy, which has taken place in the psycholinguistics camp mainly. There is already a fruitful interbreeding between two lines of research: the theoretical study of lexical word meaning, on the one hand, and the models of polysemy psycholinguists present, on the other. In this paper I aim at deepening on this ongoing interbreeding, examine what is said about polysemy, particularly in the psycholinguistics literature, and then show how what we seem to know about the representation and storage of polysemous senses affects the models that we have about lexical word meaning