Multivalent interaction and selectivities in selectin binding of functionalized gold colloids decorated with carbohydrate mimetics

Colloidal gold particles with functionalized organic shells were applied as novel selectin binders. The ligand shell was terminated with different monocyclic carbohydrate mimetics as simplified analogs of the sLe(x) unit found in biological selectin ligands. The multivalent presentation of the sulfated selectin binding epitopes on the gold particles led to extremely high binding affinities towards L- and P-selectin and IC(50) values in the subnanomolar range. Depending on the ring size of the sulfated carbohydrate mimetic, its substitution pattern and its configuration, different selectivities for either L-selectin or P-selectin were obtained. These selectivities were not found for gold particles with simple acyclic sulfated alcohols, diols and triols in the ligand shell. In addition, the influence of the particle size and the thickness of the hydrophobic organic shell were systematically investigated

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

Inhibition of the adhesion receptor L-selectin - Characterization of inhibitory oligosaccharides and glycomimetics

Titelblatt und Inhaltsverzeichnis Einleitung Material und Methoden Ergebnisse Diskussion Zusammenfassung Summary Literaturverzeichnis AnhangL-Selektin vermittelt zusammen mit seinen endothelialen Liganden das Rollen von Leukozyten auf dem Gefäßendothel und leitet hiermit den ersten Schritt einer Adhäsionskaskade ein, die zum Auswandern der Leukozyten in das perivaskuläre Gewebe führt. L-Selektin ist daher einerseits essentiell für die physiologische Immunabwehr. Andererseits ist L-Selektin an pathologischen Entzündungsreaktionen, beispielsweise an der Transplantatabstoßung oder an Autoimmunkrankheiten beteiligt. Es stellt somit eine Zielstruktur für antiinflammatorische Wirkstoffe dar, die durch Blockade von L-Selektin die Rekrutierung von Leukozyten in entzündetes Gewebe hemmen. Ziel der vorliegenden Arbeit war es, die Hemmung der Bindung von L-Selektin an seine Liganden durch synthetische multivalente Liganden auf der Basis von Sialyl Lewis x, Glykomimetika und rekombinanten Glykoproteinen zu untersuchen. Diese Untersuchungen sollten auf der Ebene einzelner Moleküle und auf der Ebene intakter Zellen unter Flussbedingungen erfolgen und somit der Scherstressabhängigkeit der Bindungsfunktion von L-Selektin Rechnung tragen. Für die Untersuchung unterschiedlicher Inhibitoren wurde ein standardisiertes Testsystem entwickelt, bei dem die Bindung von rekombinantem divalenten L -Selektin-IgG an den synthetischen Liganden SiaLex-PAA-sTyr mittels Oberflächenplasmonenresonanz gemessen wurde. Weiterhin wurde ein Flusskammer- Assay für die Untersuchungen von Inhibitoren adaptiert, bei dem das Rollen und die Adhäsion transfizierter NALM-6-Zellen, die L-Selektin auf ihrer Oberfläche exprimieren, an aktivierte HUVECs gemessen wurde. Mit beiden Verfahren wurde die inhibitorische Aktivität von multivalenten Formen von Sialyl Lewis x, Sialyl Lewis a und Tyrosinsulfat kovalent gebunden an den Träger Polyacrylamid im Vergleich zu den monovalenten Formen dieser Liganden gemessen. Die Untersuchungen zeigten, dass Multivalenz zu einer außerordentlichen Steigerung der inhibitorischen Aktivität führt und die Hemmwirkung der multivalenten Inhibitoren mit zunehmendem Scherstress zunimmt. Mit Polyglycerolsulfat-Dendrimeren wurde eine zweite Klasse multivalenter Inhibitoren untersucht. Die Ergebnisse zeigten eine außerordentlich starke Hemmwirkung dieser multivalenten Inhibitoren. Polyglycerolsulfat-Dendrimere hemmten spezifisch L- und P-Selektin, dagegen nicht die Funktion von E-Selektin. Mit dem Makrolid Efomycin M wurde drittens ein Glykomimetikum auf seine inhibitorische Aktivität untersucht. Efomycin M hemmte selektiv die Bindungsfunktion von L-Selektin, jedoch nicht die von E- und P-Selektin. Diese Untersuchungen zeigten, dass auch monovalente Inhibitoren starke Hemmwirkung besitzen können. Auf der Basis des physiologischen Liganden PSGL-1 und von Hsc70, von dem kürzlich eine Zelloberflächenform, die L-Selektin bindet, beschrieben wurde, wurden zwei potentielle inhibitorische Glykoproteine als Fusionsproteine konstruiert: PSGL-1-IgG als Fusionsprotein des N-Terminus von PSGL-1 mit drei Tyrosinresten und einem O-Glykan, welche das L-Selektin- Bindungsmotiv von PSGL-1 darstellen, und Hsc70-IgG als Fusionsprotein des Sequenzabschnitts 279-299 von Hsc70, welcher Ähnlichkeit zum PSGL-1-Bindungsmotiv aufweist. Die Expression erfolgte in der für Glykosylierung und Sulfatierung geeigneten humanen Zelllinie KG1a. Untersuchungen mittels Oberflächenplasmonenresonanz zeigten eine vergleichbar starke Bindung von PSGL-1-IgG und Hsc70-IgG an L-Selektin. Dieses Ergebnis wies darauf hin, dass die rekombinanten Glykoproteine PSGL-1-IgG und Hsc70-IgG zumindest in ihrer divalenten Form potente Inhibitoren der L-Selektin-Funktion sind. Die Ergebnisse der vorliegenden Arbeit zeigen, dass für die Hemmung der Bindungsfunktion von L-Selektin multi- und monovalente Inhibitoren zur Verfügung stehen, die die Entwicklung neuer therapeutischer Strategien der medikamentösen antiinflammatorischen Therapie eröffnen.Together with its endothelial ligands, L-selectin mediates leukocyte rolling on vascular endothelium, thereby initiating the first step of an adhesion cascade that leads to transmigration of leukocytes into the perivascular tissue. On the one hand, L-selectin is thus essential for physiological immune defense; on the other hand, it is involved in pathological inflammatory reactions, e.g. transplant rejection or autoimmune diseases. It is therefore a target structure for antiinflammatory agents that inhibit leukocyte recruitment into inflamed tissue by L-selectin blockade. The aim of this study was to examine the inhibition of L-selectin binding to its ligands by synthetic multivalent ligands on the basis of Sialyl Lewis x, glycomimetics and recombinant glycoproteins. These examinations were performed on the level of individual molecules and that of intact cells under flow conditions in order to take into account the shear stress dependence of L-selectin binding. Different inhibitors were examined by developing a standardized test system that measured the binding of recombinant divalent L-selectin-IgG to the synthetic ligand SiaLex-PAA-sTyr by means of surface plasmon resonance. In addition, inhibitors were examined by adapting a flow chamber assay to measure the rolling and adhesion of transfected L-selectin-expressing NALM-6 cells on activated HUVECs. Both procedures were used to measure the inhibitory activity of multivalent forms of Sialyl Lewis x, Sialyl Lewis a and tyrosine sulfate covalently bound to the carrier polyacrylamide in comparison to the monovalent forms of these ligands. The examinations showed that multivalence markedly enhances the inhibitory activity, and increasing shear stress intensifies the inhibitory effect of multivalent inhibitors. Polyglycerol sulfate dendrimers were used to examine a second class of multivalent inhibitors. The results showed a remarkably strong inhibitory effect of these multivalent inhibitors. Polyglycerol sulfate dendrimers were specific for L- and P-selectin but did not inhibit the function of E-selectin. Third, the macrolide efomycine M was used to examine the inhibitory activity of a glycomimetic. Efomycine M was specific for L-selectin but did not inhibit E- or P-selectin binding. These examinations showed that even monovalent inhibitors exert a strong inhibitory effect. Two potential inhibitory glycoproteins were constructed as fusion proteins on the basis of the physiological ligand PSGL-1 and Hsc70, for which an L-selectin-binding cell surface form was recently described: PSGL-1-IgG as the fusion protein of the N-terminus of PSGL-1 with three tyrosine residues and one O-glycan, which represent the L-selectin binding motive of PSGL-1, and Hsc70-IgG as the fusion protein of a sequence segment of Hsc70 of the position 279-299, which shows similarity to the PSGL-1 binding motive. The expression took place in the human cell line KG1a, which is suitable for glycosylation and sulfatation. Examinations utilizing surface plasmon resonance showed a comparably strong binding of PSGL-1-IgG and Hsc70-IgG to L-selectin. This result indicated that the recombinant glycoproteins PSGL-1-IgG and Hsc70-IgG are potent inhibitors of L-selectin function, at least in their divalent form. The results of this study document the availability of multi- and monovalent inhibitors of L-selectin binding that open up prospects for the development of new anti- inflammatory drug strategies

Geophysical Signal Analysis

xiv, 466 Hal.; 23 C