32 research outputs found
Endogenous TRAIL-R4 critically impacts apoptotic and non-apoptotic TRAIL-induced signaling in cancer cells
Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. In addition, TRAIL has been shown to preferentially kill tumor cells, raising hope for the development of targeted anti-cancer therapies. Apart from death-inducing receptors, TRAIL also binds to TRAIL-R3 and TRAIL-R4. Whereas TRAIL-R3 is lacking an intracellular domain entirely, TRAIL-R4 contains a truncated death domain but still a signaling-competent intracellular part. It is assumed that these receptors have anti-apoptotic, yet still not well understood regulatory functions. To analyze the significance of the endogenous levels of TRAIL-R4 for TRAIL-induced signaling in cancer cells, we stably knocked down this receptor in Colo357 and MDA-MB-231 cells and analyzed the activation of apoptotic and non-apoptotic pathways in response to treatment with TRAIL. We found that TRAIL-R4 affects a plethora of signaling pathways, partly in an opposite way. While knockdown of TRAIL-R4 in Colo357 strongly increased apoptosis and reduced clonogenic survival, it inhibited cell death and improved clonogenic survival of MDA-MB-231 cells after TRAIL treatment. Furthermore, TRAIL-R4 turned out to be an important regulator of the expression of a variety of anti-apoptotic proteins in MDA-MB-231 cells since TRAIL-R4-KD reduced the cellular levels of FLIPs, XIAP and cIAP2 but upregulated the levels of Bcl-xL. By inhibiting Bcl-xL with Navitoclax, we could finally show that this protein mainly accounts for the acquired resistance of MDA-MB-231 TRAIL-R4-KD cells to TRAIL-induced apoptosis. Analyses of non-apoptotic signaling pathways revealed that in both cell lines TRAIL-R4-KD resulted in a constitutively increased activity of AKT and ERK, while it reduced AKT activity after TRAIL treatment
CDK4/6 Inhibitors in Advanced HR+/HER2 - Breast Cancer: A Multicenter Real-World Data Analysis
CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy are considered standard-of-care for first-line therapy of patients with hormone receptor positive, HER2 negative, advanced breast cancer (HR+/HER2- ABC). Superiority of combination therapy over endocrine monotherapy has been demonstrated in a multitude of randomized controlled trials (RCTs) in phase III and IV. However, RCTs reflect clinical reality only to a limited extent, as narrow inclusion criteria lead to a selected patient collective. Here, we present real-world data (RWD) on CDK4/6i treatment in patients with HR+/HER2- ABC at four certified German university breast cancer centers.This study was supported by Novartis Pharma GmbH as part of the “ERIC” (“Excellent Researchers in Breast Cancer”) project
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
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
Are administrative data valid when measuring patient safety in hospitals? A comparison of data collection methods using a chart review and administrative data
Objective: To evaluate the validity and reliability of German Diagnosis Related Group administrative data to measure indicators of patient safety in comparison to clinical records. Design: A cross-sectional study was conducted using chart review (CR) as gold standard and screening of associated administrative data based on DRG coding. Setting: Three German somatic acute care hospitals for adults. Participants: A total of 3000 cases treated between May and December, 2010. Main outcome measures: Eight indicators were used to analyse the incidence of associated adverse events (AEs): pressure ulcers, catheter-related infections, respiratory failure, deep vein thromboses, hospital-acquired pneumonia, acute renal failure, acute myocardial infarction and wound infections. We calculated sensitivity, specificity, positive predictive value (PPV) and Cohen's Kappa with 95% confidence intervals. Results: Screening of administrative data identified 171 AEs and 456 were identified by CR. A number of 135 identical events were identified by both methods. Sensitivities for the detection of AEs using administrative data ranged from 6 to 100%. Specificities ranged from 99 to 100%. PPV were 33 to 100% and reliabilities were 12 to 85%. Conclusions: Indicators based on German administrative data deviate widely from indicators based on clinical data. Therefore, hospitals should be cautious to use indicators based on administrative data for quality assurance. However, some might be useful for case findings and quality improvement. The precision of the evaluated indicators needs further development to detect AEs by the valid use of administrative data
Mathematical model of micro turning process
In recent years, significant advances in turning process have been achieved greatly due to the emergent technologies for precision machining. Turning operations are common in the automotive and aerospace industries where large metal workpieces are reduced to a fraction of their original weight when creating complex thin structures. The analysis of forces plays an important role in characterizing the cutting process, as the tool wear and surface texture, depending on the forces. In this paper, the objective is to show how our understanding of the micro turning process can be utilized to predict turning behavior such as the real feed rate and the real cutting depth, as well as the cutting and feed forces. The machine cutting processes are studied with a different model compared to that recently introduced for grinding process by Malkin and Guo (2006). The developed two-degrees-of-freedom model includes the effects of the process kinematics and tool edge serration. In this model, the input feed is changing because of current forces during the turning process, and the feed rate will be reduced by elastic deflection of the work tool in the opposite direction to the feed. Besides this, using the forces and material removal during turning, we calculate the effective cross-sectional area of cut to model material removal. With this model, it is possible for a machine operator, using the aforementioned turning process parameters, to obtain a cutting model at very small depths of cut. Finally, the simulated and experimental results prove that the developed mathematical model predicts the real position of the tool tip and the cutting and feed forces of the micro turning process accurately enough for design and implementation of a cutting strategy for a real task. © 2009 Springer-Verlag London Limited
Construction of a highly flexible and comprehensive gene collection representing the ORFeome of the human pathogen <it>Chlamydia pneumoniae</it>
<p>Abstract</p> <p>Background</p> <p>The Gram-negative bacterium <it>Chlamydia pneumoniae</it> (Cpn) is the leading intracellular human pathogen responsible for respiratory infections such as pneumonia and bronchitis. Basic and applied research in pathogen biology, especially the elaboration of new mechanism-based anti-pathogen strategies, target discovery and drug development, rely heavily on the availability of the entire set of pathogen open reading frames, the ORFeome. The ORFeome of Cpn will enable genome- and proteome-wide systematic analysis of Cpn, which will improve our understanding of the molecular networks and mechanisms underlying and governing its pathogenesis.</p> <p>Results</p> <p>Here we report the construction of a comprehensive gene collection covering 98.5% of the 1052 predicted and verified ORFs of Cpn (<it>Chlamydia pneumoniae</it> strain CWL029) in Gateway® ‘entry’ vectors. Based on genomic DNA isolated from the vascular chlamydial strain CV-6, we constructed an ORFeome library that contains 869 unique Gateway® entry clones (83% coverage) and an additional 168 PCR-verified ‘pooled’ entry clones, reaching an overall coverage of ~98.5% of the predicted CWL029 ORFs. The high quality of the ORFeome library was verified by PCR-gel electrophoresis and DNA sequencing, and its functionality was demonstrated by expressing panels of recombinant proteins in <it>Escherichia coli</it> and by genome-wide protein interaction analysis for a test set of three Cpn virulence factors in a yeast 2-hybrid system. The ORFeome is available in different configurations of resource stocks, PCR-products, purified plasmid DNA, and living cultures of <it>E. coli</it> harboring the desired entry clone or pooled entry clones. All resources are available in 96-well microtiterplates.</p> <p>Conclusion</p> <p>This first ORFeome library for Cpn provides an essential new tool for this important pathogen. The high coverage of entry clones will enable a systems biology approach for Cpn or host–pathogen analysis. The high yield of recombinant proteins and the promising interactors for Cpn virulence factors described here demonstrate the possibilities for proteome-wide studies.</p
Maternal and fetal cord blood lipids in intrauterine growth restriction
Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses