Conformation and dynamics of RNA monitored via fluorescent dye molecules

Die vorliegende Arbeit beschäftigt sich mit der Untersuchung der konformationellen und elektronischen Eigenschaften sowie der Dynamik verschiedener RNA-Systeme. Zur Durchführung dieser Experimente wurde zusätzlich zu bereits vorhandenen statischen und zeitaufgelösten Absorptionsspektrometern im Rahmen dieser Arbeit eine Apparatur zur Messung von Fluoreszenzlebensdauern entwickelt, die durch die integrative Verwendung zweier verschiedener, etablierter Technologien (TCSPC und Aufkonvertierung) über einen weiten Zeitbereich von 9 Größenordnungen (100 fs - 0,1 ms) operiert. Mit diesem Aufbau konnten neben den RNA-Studien wichtige Beiträge zum Verständnis der Isomerisierung eines Retinalproteins, des Transportprozess des Membrantransportproteins TbSMR und der im Infraroten liegenden Fluoreszenz des Radikalkations von Astaxanthin gewonnen werden. Der Schwerpunkt der vorliegenden Arbeit liegt auf der Untersuchung verschiedener RNA-Systeme: So werden die optischen Eigenschaften einer 1-Ethinylpyren-modifzierten RNA-Adeninbase allein und in RNA-Strängen eingebunden untersucht. Statische Fluoreszenzmessungen zeigen einen ausgeprägten Ladungstransfercharakter des Chromophors und eine generell große Wechselwirkung zwischen Ethinylpyren und Adenin, die in einer substanziellen Änderung der optischen Eigenschaften des Pyrens resultiert. Die Untersuchung der schnellen Photodynamik von Pyrenadenin zeigt zudem eine Verringerung der Lebensdauer von Pyren um etwa 2 Größenordnungen. Pyrenadenin zeigt sowohl Fluoreszenz eines neutralen (100-200 ps), als auch eines energetisch tiefer liegenden Ladungstransferzustands (1-2 ns). Die Formationszeit des Ladungstransferzustandes fällt mit steigender Polarität des Lösemittels. Eingebunden in Modell-RNA-Stränge ist Fluoreszenzquantenausbeute des Chromophors ein deutlicher Indikator für seine Interkalation. Nur in der stabileren Umgebung von GC-Basenpaaren ist das Pyren in der Lage, sich dauerhaft innerhalb des Duplex aufzuhalten, während in einer flexibleren AU-Umgebung eine Position außerhalb des RNA-Duplex präferiert wird. Transiente Absorptionsmessungen zeigen, dass die Photophysik des in RNA eingebundenen Pyrenadenins nur kleine Variationen im Vergleich zur Photophysik des Labels allein aufweist. Die deutliche Abnahme der Quantenausbeute des interkalierten Chromophors geht hauptsächlich auf Kosten der langlebigeren Ladungstransferfluoreszenz, so dass interkaliertes Pyren insgesamt schneller in den Grundzustand zurückkehrt als nicht interkaliertes. Mit Hilfe eines doppelt modifizierten Duplex, bei dem sich jeweils ein Farbstoff an einem der beiden Stränge befindet, kann nachgewiesen werden, dass aufgrund von Exzimerwechselwirkungen eine Verschiebung des Fluoreszenzmaximums von 35 nm auftritt. Kurzzeitspektroskopische Messungen zeigen Signale, die als Superposition von Monomeren und Exzimeren interpretiert werden können, wobei die Lebensdauer des letzteren mit 18,5 ns die der Monomerkomponente um ein Vielfaches übertrifft. Ein weiterer Teil dieser Arbeit beschäftigt sich mit einer Studie zur Bindung des fluoreszenten Liganden Tetrazyklin an das Tetrazyklin bindende Aptamer. Hier wird auf Basis verschiedener Mutanten mit Hilfe des TCSPC eine Analyse der Stabilität der Bindetasche sowie mit der Stopped-Flow-Methode eine Beobachtung des Bindungsprozesses durchgeführt. Insgesamt folgt die Bindung des Tetrazyklins an das Aptamer einer zweistufigen Kinetik, deren zweiter Schritt irreversibel ist. Die Bindung läuft, verglichen mit anderen Aptameren, sehr schnell ab. Während die Mutationen von A13 und A50,die direkte Kontakte zum Substrat bilden, nur einen leichten Einfluss auf beide Bindungsschritte ausüben, führt eine Mutation der für die Präformation verantwortlichen Base A9 zu einer Verlangsamung des Bindungsprozesses um mehr als einen Faktor 20 durch eine immens gesteigerten Rückreaktionsrate des ersten Bindungsschritts. Hieraus lässt sich schließen, dass bei fehlender Präformation des Aptamers nur wenige Tetrazyklinmoleküle ein für vollständige Bindung geeignetes Aptamer vorfinden. Die Bindung an A13 und A50 geschieht bereits im ersten Schritt des Bindungsprozesses. Ferner konnte anhand von Lebensdauermessungen gezeigt werden, dass nach dem Wildtyp die Mutante A9G die stabilste Bindetasche aufwies. Das Fehlen eines direkten Kontaktes wirkt sich deutlich stärker aus. Insbesondere führt die Abwesenheit der Fixierung des Gegenions durch A50 zu der instabilsten Bindetasche. Wie in dieser Arbeit gezeigt wird, ist die zeitaufgelöste optische Spektroskopie insbesondere in Verbindung mit fluoreszierenden Molekülen ein ausgezeichnetes Mittel zur Beobachtung von Struktur und Dynamik von RNA. Die Empfindlichkeit von Fluoreszenz auf die Veränderung der Umgebung des Chromophors erlaubt es, Konformationsdynamik und elektronische Konfigurationen in Echtzeit zu beobachten.This thesis treats the examination of the conformational and electronic properties, as well as the dynamics of various RNA systems. These experiments were carried out with static and time resolved absorption spectrometers, as well as with a newly developed fluorescence lifetime measurement setup. This setup operates over 9 orders of magnitude in time (100 fs – 0.1 ms) by applying two different established techniques (TCSPC and Upconversion) using the same hardware. With this setup, valuable contributions could be made to the study of the isomerisation of a retinal protein, the transport process of the membrane transporter TbSMR and the infrared fluorescence of the radical cation of astaxanthin. The focus of this thesis lies on the examination of various RNA-systems. The optical properties of a 1-ethynylpyrene-modified RNA-adenine-base, alone and incorporated into RNA strands, are examined. Static fluorescence measurements show a strong charge transfer character of the chromophore and a generally strong interaction between ethynylpyrene and adenine, which results in a substantial change of the optical properties of pyrene. The observation of the fast photodynamics of pyreneadenine shows a shortening of the overall lifetime of pyrene by 2 orders of magnitude. Pyreneadenine exhibits fluorescence of both a neutral (100-200 ps) and a energetically lower lying charge transfer state (1-2 ns). The formation time of the charge transfer state decreases with rising solvent polarity. Incorporated into model-RNA-strands, the fluorescence quantum efficiency of the chromophore is a significant indicator for its intercalation. Only in the more stable surrounding of GC-base pairs, pyrene is able to effectively remain within the duplex, while in a more flexible AU-surrounding, a position outside of the duplex is preferred. Transient absorption measurements show, that the photophysics of the pyreneadenine incorporated into RNA shows only small variations compared to that of the label alone. The strong decrease of quantum efficiency of the intercalated pyrene is mainly attributed to a quenching of the longer-lived charge transfer fluorescence. Thus, the ground state recovery of intercalated pyrene is faster than that of non-intercalated pyrene. With the aid of a doubly modified duplex, where a pyrene is located on each strand, it can be shown, that a shift of the fluorescence maximum of 35 nm occurs due to excimer interactions. Ultrafast spectroscopy shows signals, which can be interpreted as a superposition of monomer and excimer characteristics. The lifetime of the latter was found to be 18.5 ns and thus exceeds that of the monomer components by a multiple. The second part of this work discusses the binding of the fluorescent ligand tetracycline to the tetracycline binding aptamer. Here, on the basis of various mutants, an analysis of the stability of the binding pocket is carried out via TCSPC, and the stopped-flow method is used to monitor the binding process. Generally speaking, the binding of the tetracycline to the aptamer follows a two-step process with a irreversible second step. The binding is fast, compared to that of other aptamers. While the mutations of A13 and A50, which form direct contacts to the substrate, exert only small influences on both binding steps, indicating, that the binding to both bases occurs during the first binding step, the mutation of the base A9, which is responsible for the preformation, leads to a slowing of the binding process by a factor of 20, due to a strongly enhanced backreaction rate of the first step. This leads to the conclusion, that in this case, only few tetracycline molecules are able to find an aptamer, which is suited for complete binding. In addition to this, lifetime measurements showed, that of all mutants, the mutant A9G provides the most stable binding pocket. The mutation of direct contacts lead to more instable binding pockets, the least stable pocket is found in A50U. This may be due to the fact, that the attachment of the tetracycline counterion via A50 imposes the strongest restriction upon the flexibility of the tetracycline. This work shows, that time-resolved optical spectroscopy, especially together with fluorescent molecules, are a valuable tool for monitoring the structure and dynamics of RNA. The sensitivity of fluorescence on environmental factors allows the observation of conformational dynamics and electronic configurations in real time

Übernahme mit Herz und Verstand: Die Integration einer bestehenden Hausarztpraxis in ein neues Gesundheitszentrum für erweiterte Hausmedizin: Herausforderungen, Stolpersteine und Erfolgsfaktoren unter Einbezug des Changemanagements

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Developmental switch of intestinal antimicrobial peptide expression

Paneth cell–derived enteric antimicrobial peptides provide protection from intestinal infection and maintenance of enteric homeostasis. Paneth cells, however, evolve only after the neonatal period, and the antimicrobial mechanisms that protect the newborn intestine are ill defined. Using quantitative reverse transcription–polymerase chain reaction, immunohistology, reverse-phase high-performance liquid chromatography, and mass spectrometry, we analyzed the antimicrobial repertoire in intestinal epithelial cells during postnatal development. Surprisingly, constitutive expression of the cathelin-related antimicrobial peptide (CRAMP) was observed, and the processed, antimicrobially active form was identified in neonatal epithelium. Peptide synthesis was limited to the first two weeks after birth and gradually disappeared with the onset of increased stem cell proliferation and epithelial cell migration along the crypt–villus axis. CRAMP conferred significant protection from intestinal bacterial growth of the newborn enteric pathogen Listeria monocytogenes. Thus, we describe the first example of a complete developmental switch in innate immune effector expression and anatomical distribution. Epithelial CRAMP expression might contribute to bacterial colonization and the establishment of gut homeostasis, and provide protection from enteric infection during the postnatal period

Tiefengeothermie Sachsen

In drei Gebieten Sachsens wurde durch einen Forschungsverbund unter Leitung des LfULG die Nutzung der petrothermalen Geothermie zur Strom- und Wärmegewinnung untersucht. In der Elbezone im Raum Dresden, in Freiberg und Aue-Schneeberg wurden geologische, petrophysikalische und thermische Daten aufgearbeitet und dreidimensionale Modelle bewertet. Die Ergebnisse zeigen, dass eine Stromerzeugung durch Tiefenaufschlüsse bis 5 km Tiefe in allen drei Untersuchungsgebieten möglich ist. Die Temperaturmodelle weisen in 5 km Tiefe Werte zwischen 105 und 190 °C auf. Dabei verfügt das Untersuchungsgebiet Aue-Schneeberg über die besten Voraussetzungen für die Errichtung eines Geothermiekraftwerkes

User Inquiries and Ground Segment Operation Activities

Since the beginning of the operational phase in November 2022, the Environmental Mapping and Analysis Programm (EnMAP) has gathered substantial interest within the Earth Observation community, counting a considerable number of more than 1800 registered users from over 80 different countries across the globe. The EnMAP data archive is also used very frequently by users with ordering and downloading approx. 2000 tiles per months. Any science user can submit its (his/her) own observations request via the EnMAP Instrument Planning Portal (IPP, https://planning.enmap.org/, also reachable through the official website www.enmap.org), by submitting a proposal. The IP portal also provides access links to the entire EnMAP data archive via the EOWEB Geoportal. The number of users requesting future observations varies significantly based on geographic location. Notably, Europe sees the highest demand for the EnMAP mission, leading to challenges such as conflicting orders for areas within the same orbit. This convergence has introduced complexities in data acquisition, particularly for time series and orchestration of field campaigns. To ensure (increase) regular data acquisition and boost mission efficiency, a "Foreground Mission" has been introduced. This entails prioritized acquisition of extended 990-kilometer flightlines (stripes) over Europe, with a specific focus on Germany. This strategic approach aims to improve data coverage in Germany and streamlines recurring acquisitions along key transects. First this informative presentation provides an assessment of ground segment operations, with special attention given to user feedback and inquiries. Along the way, it outlines the most prevalent user concerns and highlights the strategic factors involved in requesting observations. As second part the audience gains deeper insight into the newly implemented Foreground Mission initiative

Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study

Background: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Methods: Using the “functional eicosanoid testing and typing” (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. Results: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14–2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. Conclusions: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD

Human Practice. Digital Ecologies. Our Future. : 14. Internationale Tagung Wirtschaftsinformatik (WI 2019) : Tagungsband

Erschienen bei: universi - Universitätsverlag Siegen. - ISBN: 978-3-96182-063-4Aus dem Inhalt: Track 1: Produktion & Cyber-Physische Systeme Requirements and a Meta Model for Exchanging Additive Manufacturing Capacities Service Systems, Smart Service Systems and Cyber- Physical Systems—What’s the difference? Towards a Unified Terminology Developing an Industrial IoT Platform – Trade-off between Horizontal and Vertical Approaches Machine Learning und Complex Event Processing: Effiziente Echtzeitauswertung am Beispiel Smart Factory Sensor retrofit for a coffee machine as condition monitoring and predictive maintenance use case Stakeholder-Analyse zum Einsatz IIoT-basierter Frischeinformationen in der Lebensmittelindustrie Towards a Framework for Predictive Maintenance Strategies in Mechanical Engineering - A Method-Oriented Literature Analysis Development of a matching platform for the requirement-oriented selection of cyber physical systems for SMEs Track 2: Logistic Analytics An Empirical Study of Customers’ Behavioral Intention to Use Ridepooling Services – An Extension of the Technology Acceptance Model Modeling Delay Propagation and Transmission in Railway Networks What is the impact of company specific adjustments on the acceptance and diffusion of logistic standards? Robust Route Planning in Intermodal Urban Traffic Track 3: Unternehmensmodellierung & Informationssystemgestaltung (Enterprise Modelling & Information Systems Design) Work System Modeling Method with Different Levels of Specificity and Rigor for Different Stakeholder Purposes Resolving Inconsistencies in Declarative Process Models based on Culpability Measurement Strategic Analysis in the Realm of Enterprise Modeling – On the Example of Blockchain-Based Initiatives for the Electricity Sector Zwischenbetriebliche Integration in der Möbelbranche: Konfigurationen und Einflussfaktoren Novices’ Quality Perceptions and the Acceptance of Process Modeling Grammars Entwicklung einer Definition für Social Business Objects (SBO) zur Modellierung von Unternehmensinformationen Designing a Reference Model for Digital Product Configurators Terminology for Evolving Design Artifacts Business Role-Object Specification: A Language for Behavior-aware Structural Modeling of Business Objects Generating Smart Glasses-based Information Systems with BPMN4SGA: A BPMN Extension for Smart Glasses Applications Using Blockchain in Peer-to-Peer Carsharing to Build Trust in the Sharing Economy Testing in Big Data: An Architecture Pattern for a Development Environment for Innovative, Integrated and Robust Applications Track 4: Lern- und Wissensmanagement (e-Learning and Knowledge Management) eGovernment Competences revisited – A Literature Review on necessary Competences in a Digitalized Public Sector Say Hello to Your New Automated Tutor – A Structured Literature Review on Pedagogical Conversational Agents Teaching the Digital Transformation of Business Processes: Design of a Simulation Game for Information Systems Education Conceptualizing Immersion for Individual Learning in Virtual Reality Designing a Flipped Classroom Course – a Process Model The Influence of Risk-Taking on Knowledge Exchange and Combination Gamified Feedback durch Avatare im Mobile Learning Alexa, Can You Help Me Solve That Problem? - Understanding the Value of Smart Personal Assistants as Tutors for Complex Problem Tasks Track 5: Data Science & Business Analytics Matching with Bundle Preferences: Tradeoff between Fairness and Truthfulness Applied image recognition: guidelines for using deep learning models in practice Yield Prognosis for the Agrarian Management of Vineyards using Deep Learning for Object Counting Reading Between the Lines of Qualitative Data – How to Detect Hidden Structure Based on Codes Online Auctions with Dual-Threshold Algorithms: An Experimental Study and Practical Evaluation Design Features of Non-Financial Reward Programs for Online Reviews: Evaluation based on Google Maps Data Topic Embeddings – A New Approach to Classify Very Short Documents Based on Predefined Topics Leveraging Unstructured Image Data for Product Quality Improvement Decision Support for Real Estate Investors: Improving Real Estate Valuation with 3D City Models and Points of Interest Knowledge Discovery from CVs: A Topic Modeling Procedure Online Product Descriptions – Boost for your Sales? Entscheidungsunterstützung durch historienbasierte Dienstreihenfolgeplanung mit Pattern A Semi-Automated Approach for Generating Online Review Templates Machine Learning goes Measure Management: Leveraging Anomaly Detection and Parts Search to Improve Product-Cost Optimization Bedeutung von Predictive Analytics für den theoretischen Erkenntnisgewinn in der IS-Forschung Track 6: Digitale Transformation und Dienstleistungen Heuristic Theorizing in Software Development: Deriving Design Principles for Smart Glasses-based Systems Mirroring E-service for Brick and Mortar Retail: An Assessment and Survey Taxonomy of Digital Platforms: A Platform Architecture Perspective Value of Star Players in the Digital Age Local Shopping Platforms – Harnessing Locational Advantages for the Digital Transformation of Local Retail Outlets: A Content Analysis A Socio-Technical Approach to Manage Analytics-as-a-Service – Results of an Action Design Research Project Characterizing Approaches to Digital Transformation: Development of a Taxonomy of Digital Units Expectations vs. Reality – Benefits of Smart Services in the Field of Tension between Industry and Science Innovation Networks and Digital Innovation: How Organizations Use Innovation Networks in a Digitized Environment Characterising Social Reading Platforms— A Taxonomy-Based Approach to Structure the Field Less Complex than Expected – What Really Drives IT Consulting Value Modularity Canvas – A Framework for Visualizing Potentials of Service Modularity Towards a Conceptualization of Capabilities for Innovating Business Models in the Industrial Internet of Things A Taxonomy of Barriers to Digital Transformation Ambidexterity in Service Innovation Research: A Systematic Literature Review Design and success factors of an online solution for cross-pillar pension information Track 7: IT-Management und -Strategie A Frugal Support Structure for New Software Implementations in SMEs How to Structure a Company-wide Adoption of Big Data Analytics The Changing Roles of Innovation Actors and Organizational Antecedents in the Digital Age Bewertung des Kundennutzens von Chatbots für den Einsatz im Servicedesk Understanding the Benefits of Agile Software Development in Regulated Environments Are Employees Following the Rules? On the Effectiveness of IT Consumerization Policies Agile and Attached: The Impact of Agile Practices on Agile Team Members’ Affective Organisational Commitment The Complexity Trap – Limits of IT Flexibility for Supporting Organizational Agility in Decentralized Organizations Platform Openness: A Systematic Literature Review and Avenues for Future Research Competence, Fashion and the Case of Blockchain The Digital Platform Otto.de: A Case Study of Growth, Complexity, and Generativity Track 8: eHealth & alternde Gesellschaft Security and Privacy of Personal Health Records in Cloud Computing Environments – An Experimental Exploration of the Impact of Storage Solutions and Data Breaches Patientenintegration durch Pfadsysteme Digitalisierung in der Stressprävention – eine qualitative Interviewstudie zu Nutzenpotenzialen User Dynamics in Mental Health Forums – A Sentiment Analysis Perspective Intent and the Use of Wearables in the Workplace – A Model Development Understanding Patient Pathways in the Context of Integrated Health Care Services - Implications from a Scoping Review Understanding the Habitual Use of Wearable Activity Trackers On the Fit in Fitness Apps: Studying the Interaction of Motivational Affordances and Users’ Goal Orientations in Affecting the Benefits Gained Gamification in Health Behavior Change Support Systems - A Synthesis of Unintended Side Effects Investigating the Influence of Information Incongruity on Trust-Relations within Trilateral Healthcare Settings Track 9: Krisen- und Kontinuitätsmanagement Potentiale von IKT beim Ausfall kritischer Infrastrukturen: Erwartungen, Informationsgewinnung und Mediennutzung der Zivilbevölkerung in Deutschland Fake News Perception in Germany: A Representative Study of People’s Attitudes and Approaches to Counteract Disinformation Analyzing the Potential of Graphical Building Information for Fire Emergency Responses: Findings from a Controlled Experiment Track 10: Human-Computer Interaction Towards a Taxonomy of Platforms for Conversational Agent Design Measuring Service Encounter Satisfaction with Customer Service Chatbots using Sentiment Analysis Self-Tracking and Gamification: Analyzing the Interplay of Motivations, Usage and Motivation Fulfillment Erfolgsfaktoren von Augmented-Reality-Applikationen: Analyse von Nutzerrezensionen mit dem Review-Mining-Verfahren Designing Dynamic Decision Support for Electronic Requirements Negotiations Who is Stressed by Using ICTs? A Qualitative Comparison Analysis with the Big Five Personality Traits to Understand Technostress Walking the Middle Path: How Medium Trade-Off Exposure Leads to Higher Consumer Satisfaction in Recommender Agents Theory-Based Affordances of Utilitarian, Hedonic and Dual-Purposed Technologies: A Literature Review Eliciting Customer Preferences for Shopping Companion Apps: A Service Quality Approach The Role of Early User Participation in Discovering Software – A Case Study from the Context of Smart Glasses The Fluidity of the Self-Concept as a Framework to Explain the Motivation to Play Video Games Heart over Heels? An Empirical Analysis of the Relationship between Emotions and Review Helpfulness for Experience and Credence Goods Track 11: Information Security and Information Privacy Unfolding Concerns about Augmented Reality Technologies: A Qualitative Analysis of User Perceptions To (Psychologically) Own Data is to Protect Data: How Psychological Ownership Determines Protective Behavior in a Work and Private Context Understanding Data Protection Regulations from a Data Management Perspective: A Capability-Based Approach to EU-GDPR On the Difficulties of Incentivizing Online Privacy through Transparency: A Qualitative Survey of the German Health Insurance Market What is Your Selfie Worth? A Field Study on Individuals’ Valuation of Personal Data Justification of Mass Surveillance: A Quantitative Study An Exploratory Study of Risk Perception for Data Disclosure to a Network of Firms Track 12: Umweltinformatik und nachhaltiges Wirtschaften Kommunikationsfäden im Nadelöhr – Fachliche Prozessmodellierung der Nachhaltigkeitskommunikation am Kapitalmarkt Potentiale und Herausforderungen der Materialflusskostenrechnung Computing Incentives for User-Based Relocation in Carsharing Sustainability’s Coming Home: Preliminary Design Principles for the Sustainable Smart District Substitution of hazardous chemical substances using Deep Learning and t-SNE A Hierarchy of DSMLs in Support of Product Life-Cycle Assessment A Survey of Smart Energy Services for Private Households Door-to-Door Mobility Integrators as Keystone Organizations of Smart Ecosystems: Resources and Value Co-Creation – A Literature Review Ein Entscheidungsunterstützungssystem zur ökonomischen Bewertung von Mieterstrom auf Basis der Clusteranalyse Discovering Blockchain for Sustainable Product-Service Systems to enhance the Circular Economy Digitale Rückverfolgbarkeit von Lebensmitteln: Eine verbraucherinformatische Studie Umweltbewusstsein durch audiovisuelles Content Marketing? Eine experimentelle Untersuchung zur Konsumentenbewertung nachhaltiger Smartphones Towards Predictive Energy Management in Information Systems: A Research Proposal A Web Browser-Based Application for Processing and Analyzing Material Flow Models using the MFCA Methodology Track 13: Digital Work - Social, mobile, smart On Conversational Agents in Information Systems Research: Analyzing the Past to Guide Future Work The Potential of Augmented Reality for Improving Occupational First Aid Prevent a Vicious Circle! The Role of Organizational IT-Capability in Attracting IT-affine Applicants Good, Bad, or Both? Conceptualization and Measurement of Ambivalent User Attitudes Towards AI A Case Study on Cross-Hierarchical Communication in Digital Work Environments ‘Show Me Your People Skills’ - Employing CEO Branding for Corporate Reputation Management in Social Media A Multiorganisational Study of the Drivers and Barriers of Enterprise Collaboration Systems-Enabled Change The More the Merrier? The Effect of Size of Core Team Subgroups on Success of Open Source Projects The Impact of Anthropomorphic and Functional Chatbot Design Features in Enterprise Collaboration Systems on User Acceptance Digital Feedback for Digital Work? Affordances and Constraints of a Feedback App at InsurCorp The Effect of Marker-less Augmented Reality on Task and Learning Performance Antecedents for Cyberloafing – A Literature Review Internal Crowd Work as a Source of Empowerment - An Empirical Analysis of the Perception of Employees in a Crowdtesting Project Track 14: Geschäftsmodelle und digitales Unternehmertum Dividing the ICO Jungle: Extracting and Evaluating Design Archetypes Capturing Value from Data: Exploring Factors Influencing Revenue Model Design for Data-Driven Services Understanding the Role of Data for Innovating Business Models: A System Dynamics Perspective Business Model Innovation and Stakeholder: Exploring Mechanisms and Outcomes of Value Creation and Destruction Business Models for Internet of Things Platforms: Empirical Development of a Taxonomy and Archetypes Revitalizing established Industrial Companies: State of the Art and Success Principles of Digital Corporate Incubators When 1+1 is Greater than 2: Concurrence of Additional Digital and Established Business Models within Companies Special Track 1: Student Track Investigating Personalized Price Discrimination of Textile-, Electronics- and General Stores in German Online Retail From Facets to a Universal Definition – An Analysis of IoT Usage in Retail Is the Technostress Creators Inventory Still an Up-To-Date Measurement Instrument? Results of a Large-Scale Interview Study Application of Media Synchronicity Theory to Creative Tasks in Virtual Teams Using the Example of Design Thinking TrustyTweet: An Indicator-based Browser-Plugin to Assist Users in Dealing with Fake News on Twitter Application of Process Mining Techniques to Support Maintenance-Related Objectives How Voice Can Change Customer Satisfaction: A Comparative Analysis between E-Commerce and Voice Commerce Business Process Compliance and Blockchain: How Does the Ethereum Blockchain Address Challenges of Business Process Compliance? Improving Business Model Configuration through a Question-based Approach The Influence of Situational Factors and Gamification on Intrinsic Motivation and Learning Evaluation von ITSM-Tools für Integration und Management von Cloud-Diensten am Beispiel von ServiceNow How Software Promotes the Integration of Sustainability in Business Process Management Criteria Catalog for Industrial IoT Platforms from the Perspective of the Machine Tool Industry Special Track 3: Demos & Prototyping Privacy-friendly User Location Tracking with Smart Devices: The BeaT Prototype Application-oriented robotics in nursing homes Augmented Reality for Set-up Processe Mixed Reality for supporting Remote-Meetings Gamification zur Motivationssteigerung von Werkern bei der Betriebsdatenerfassung Automatically Extracting and Analyzing Customer Needs from Twitter: A “Needmining” Prototype GaNEsHA: Opportunities for Sustainable Transportation in Smart Cities TUCANA: A platform for using local processing power of edge devices for building data-driven services Demonstrator zur Beschreibung und Visualisierung einer kritischen Infrastruktur Entwicklung einer alltagsnahen persuasiven App zur Bewegungsmotivation für ältere Nutzerinnen und Nutzer A browser-based modeling tool for studying the learning of conceptual modeling based on a multi-modal data collection approach Exergames & Dementia: An interactive System for People with Dementia and their Care-Network Workshops Workshop Ethics and Morality in Business Informatics (Workshop Ethik und Moral in der Wirtschaftsinformatik – EMoWI’19) Model-Based Compliance in Information Systems - Foundations, Case Description and Data Set of the MobIS-Challenge for Students and Doctoral Candidates Report of the Workshop on Concepts and Methods of Identifying Digital Potentials in Information Management Control of Systemic Risks in Global Networks - A Grand Challenge to Information Systems Research Die Mitarbeiter von morgen - Kompetenzen künftiger Mitarbeiter im Bereich Business Analytics Digitaler Konsum: Herausforderungen und Chancen der Verbraucherinformati

Development and application of analytical methods for quantification of naphthalene metabolites in human urine samples

Naphthalin entsteht im Gemisch mit anderen polyzyklischen aromatischen Kohlenwasserstoffen bei unvollständigen Verbrennungsreaktionen. Durch verschiedenste Emissionsquellen gelangt es in die Umwelt. Die Folge ist eine unvermeidbare ubiquitäre Exposition des Menschen. Durch beruflichen Kontakt mit Naphthalin an industriellen Arbeitsplätzen kann die Naphthalinbelastung weit über die Hintergrundbelastung hinaus ansteigen. Die mögliche Kanzerogenität des Naphthalins ist im Zusammenhang mit dessen ubiquitären Vorkommen von arbeits- und umweltmedizinischer Bedeutung. Um eine Einschätzung des Gesundheitsrisikos vornehmen zu können, ist die Bestimmung der inneren Belastung des Menschen anhand von Naphthalinmetaboliten unerlässlich. Alleinige Luftmessungen unterschätzen das resultierende Gesundheitsrisiko möglicherweise, da Naphthalin zusätzlich über die Haut resorbiert wird. Ziel dieser Arbeit war die Etablierung von Biomarkern, die das kanzerogene Potential des Naphthalins widerspiegeln. Weiterhin sollte ein Beitrag zur Aufklärung des Humanmetabolismus von Naphthalin geleistet werden. Als ultimale Kanzerogene im Naphthalinmetabolismus werden 1,2- und 1,4-Naphthochinon diskutiert. Aus diesen Naphthochinonen könnten durch Michael-Addition von Glutathion die Naphthochinonmerkaptursäuren (NQMA) als unmittelbare Folgeprodukte gebildet werden. Zur Quantifizierung von 1,2- und 1,4-NQMA in Humanurin wurde im Rahmen dieser Arbeit ein empfindliches analytisches Verfahren mit LC-ESI-MS/MS entwickelt und validiert. Bei der Analyse der Urinproben von Personen der Allgemeinbevölkerung sowie von nachweislich beruflich sehr hoch exponierten Beschäftigten konnten weder 1,2- noch 1,4-NQMA nachgewiesen werden. NQMAs können nicht als Parameter zur Abschätzung der inneren Naphthalinbelastung im Rahmen eines Human-Biomonitorings herangezogen werden. Bei den Dihydroxynaphthalinen 1,2- und 1,4-DHN handelt sich um die unmittelbaren Precursoren sowie möglicherweise auch die Reduktionsprodukte der im Gleichgewicht vorliegenden, ultimal kanzerogenen Chinone. Deshalb wurde eine Methode zur Bestimmung von 1,2- und 1,4 DHN im Urin entwickelt. Zusätzlich werden 1,7-, 1,6-, 1,5-, 2,7- und 2,6 DHN erfasst, um einen Beitrag zur Aufklärung des humanen Naphthalinmetabolismus zu leisten. Bei der analytischen Bestimmung werden die sieben Dihydroxynaphthaline unter reduktiven Bedingungen in einer enzymatischen Hydrolyse aus ihren Konjugaten freigesetzt sowie anschließend mittels Festphasenextraktion von der Probenmatrix abgetrennt und aufkonzentriert. Nach Überführung in die entsprechenden Trimethylsilylderivate wird mittels GC-EI-MS quantifiziert. Diese Methode wurde zur Untersuchung von beruflich gegen PAKs exponierten Arbeitern in der Konverterzustellung sowie einem Kontrollkollektiv von Personen der Allgemeinbevölkerung angewandt. 1,2-DHN stellte den Hauptmetaboliten dar und konnte in 98 % aller untersuchten Urinproben quantifiziert werden. Für diesen Parameter werden Maximalwerte von bis zu 6477 µg/l ermittelt. Anhand des 1,2-DHNs konnte gezeigt werden, dass Konverterzusteller eine signifikant höhere innere Naphthalinbelastung aufweisen als die untersuchten Personen der Allgemeinbevölkerung. Weiterhin wurden die Metabolite 1,4-, 1,7-, 2,7- und 2,6-DHN nachgewiesen, allerdings in einem deutlich niedrigeren Konzentrationsbereich als 1,2-DHN (Maximalwerte bis 113 µg/l). Die Bildung von 1,4-, 1,7-, 2,7- und 2,6-DHN spielt eine untergeordnete Rolle im Humanmetabolismus. 1,5- und 1,6-DHN waren in Humanurin nicht detektierbar. Hauptmetabolit von Naphthalin im menschlichen Stoffwechsel ist 1,2 DHN. In hochbelasteten Arbeiterurinen sind etwa 10fach höhere Konzentrationen nachweisbar als die der etablierten Biomarker 1- und 2-Naphthol, während bei niedrigerer Exposition etwa vergleichbare Konzentrationen der Metabolite ausgeschieden werden. Diese von der Expositionshöhe abhängige Metabolisierungsrate kann bisher nicht erklärt werden, hierfür ist die Untersuchung weiterer Kollektive erforderlich. Die erhöhte 1,2-DHN-Ausscheidung erscheint jedoch im Hinblick auf die toxikologische Relevanz des 1,2-DHN als Precursor bzw. Reduktionsprodukt des als ultimal kanzerogenen Metaboliten diskutierten 1,2-Naphthochinons nicht unbedenklich. 1,2-DHN kann als diagnostisch empfindlicher und spezifischer Biomarker zur Bestimmung der inneren Belastung nach einer Naphthalinexposition herangezogen werden. Untersuchungsdaten für den Parameter 1,2-DHN liegen bisher nur aus wenigen Studien vor. Hingegen ist für Naphthole eine Bewertung der Biomonitoring-Ergebnisse im Vergleich zu umfangreichen Literaturdaten von Kollektiven aus dem arbeits- und umweltmedizinischen Bereich möglich. Zur Charakterisierung der inneren Naphthalinbelastung im Rahmen eines Human-Biomonitorings ist die Anaytik verschiedener Biomarker anzustreben, so dass sich die Bestimmung von 1,2-DHN und den etablierten Biomarkern 1- und 2-Naphthol empfiehlt.Naphthalene is generated, combined with other polycyclic aromatic hydrocarbons (PAH), during all incomplete combustion processes. It diffuses in the environment via different sources of emission, leading to an ubiquitary exposure for humans. Occupational contact with naphthalene at industrial workplaces may significantly increase the naphthalene burden beyond the background level. The potentially carcinogenic properties of naphthalene are, regarding to its ubiquitary presence, of occupational-medical and environmental-medical importance. To estimate the health risk, it is essential to determine the internal burden by means of biological monitoring using metabolites in human body fluids. Ambient monitoring alone may underestimate the health risk, because percutaneously absorbed naphthalene is not considered. Main interest of this work was to establish biomarkers reflecting the carcinogenic properties of naphthalene and obtain deeper insights in human naphthalene metabolism. 1,2- and 1,4-naphthoquinone are discussed as ultimate carcinogens in human naphthalene metabolism. A Michael-addition of glutathione to naphthoquinones could lead to naphthoquinone mercapturic acids (NQMA). In the framework of this thesis, an LC-ESI-MS/MS-method for the determination of 1,2- and 1,4-NQMA in human urine was developed and validated. Those metabolites could neither be detected in urine sample of persons without PAH-exposure, nor in persons with known high PAH-exposure. Thus, naphthalene is not converted to 1,2- and 1,4-NQMA in human metabolism. NQMAs are unsuitable as parameters for a human biomonitoring. The dihydroxynaphthalenes 1,2- and 1,4-DHN are the direct precursors of the ultimate carcinogenic quinones. Therefore a method for quantification of 1,2- and 1,4-DHN in human urine was developed. Additionally the dihydroxy¬naphthalenes 1,7 , 1,6 , 1,5 , 2,7 and 2,6 DHN were analysed to provide insights in the human naphthalene metabolism. Briefly, urine is enzymatically hydrolysed for conjugate cleavage. Afterwards solid phase extraction is applied for sample clean-up and analyte concentration. After converting to the corresponding trimethylsilyl-derivates, the analytes are quantified by GC-EI-MS. This method was applied to occupational PAH-exposed workers in converter reconstruction sites as well as controls of the general population, which were all previously analysed for 1- and 2-naphthol. 1,2-DHN is the mayor urinary metabolite of naphthalene. It was quantified in 98 % of the analysed urine samples with maximum concentrations ranging up to remarkable 6477 µg/l. Using 1,2-DHN as biomarker, workers in converter reconstruction show significantly higher internal naphthalene burden than controls of the general population. Furthermore, the metabolites 1,4-, 1,7- 2,7- and 2,6-DHN were detected, but in lower concentration with a maximum of 113 µg/l. The formation of 1,4-, 1,7-, 2,7- and 2,6-DHN is of minor importance in human metabolism. 1,5- and 1,6-DHN were not analysed in human urine. 1,2-DHN is the mayor metabolite of naphthalene in humans. In high exposed workers urine, median-concentrations are about ten times higher than those of the established biomarkers 1 and 2-naphthol, while comparable concentrations of the metabolites are excreted at lower exposure levels. The varying ratios seem to depend on the exposure level. This fact has to be evaluated as not harmless regarding to the toxicological relevance of 1,2-DHN as precursor of the possibly ultimate carcinogenic naphthalene-metabolite 1,2-naphthoquinone. Diagnostically, 1,2-DHN is a susceptible parameter, which is more suitable for differentiation between a collective of occupational against PAH-exposed workers and controls than 1- and 2-naphthol. 1,2-DHN was shown as diagnostically sensitive and specific biomarker for the estimation of the internal burden after naphthalene exposure. Up to now, there are only less studies in literature presenting biomonitoring results for the parameter 1,2-DHN. However, biomonitoring results for 1- and 2-naphthol can be compared and evaluated with considerable data published for collectives in occupational- as well as environmental medicine. In the framework of further human biomonitoring studies, the analysis of different naphthalene-biomarkers is aspired. Thus, 1,2-DHN should be analysed together with the well-established biomarkers 1- and 2-naphthol