1,229 research outputs found
Joint Transmit and Receive Filter Optimization for Sub-Nyquist Delay-Doppler Estimation
In this article, a framework is presented for the joint optimization of the
analog transmit and receive filter with respect to a parameter estimation
problem. At the receiver, conventional signal processing systems restrict the
two-sided bandwidth of the analog pre-filter to the rate of the
analog-to-digital converter to comply with the well-known Nyquist-Shannon
sampling theorem. In contrast, here we consider a transceiver that by design
violates the common paradigm . To this end, at the receiver, we
allow for a higher pre-filter bandwidth and study the achievable
parameter estimation accuracy under a fixed sampling rate when the transmit and
receive filter are jointly optimized with respect to the Bayesian
Cram\'{e}r-Rao lower bound. For the case of delay-Doppler estimation, we
propose to approximate the required Fisher information matrix and solve the
transceiver design problem by an alternating optimization algorithm. The
presented approach allows us to explore the Pareto-optimal region spanned by
transmit and receive filters which are favorable under a weighted mean squared
error criterion. We also discuss the computational complexity of the obtained
transceiver design by visualizing the resulting ambiguity function. Finally, we
verify the performance of the optimized designs by Monte-Carlo simulations of a
likelihood-based estimator.Comment: 15 pages, 16 figure
Recovery of scandium from acidic waste solutions by means of polymer inclusion membranes
Scandium is a raw material with properties that promise considerable potential for application in alloys to enable aviation fuel savings and as dopants for use in sustainable energy production using solid oxide fuel cells. Despite these attractive properties, scandium is rarely used due to its scarcity and unreliable supply. Therefore, new strategies for scandium recovery are of economic priority. In this study, polymer inclusion membranes (PIMs) consisting of PVDF-HFP, 2-NPOE and DEHPA, were optimised for selective scandium separation from real TiO2 production waste. With the optimised system, >60% of the scandium was recovered with high selectivity, resulting in scandium mole fraction at more than two orders of magnitude higher in the receiving phase than in the original waste. This suggests PIMs may be an effective way to recover scandium from bulk waste, thus easing the scarcity and insecurity that currently limit its bulk application
Organic solvent free PbIâ recycling from perovskite solar cells using hot water
Perovskite solar cells represent an emerging and highly promising renewable energy technology. However, the most efficient perovskite solar cells critically depend on the use of lead. This represents a possible environmental concern potentially limiting the technologiesĂąEurotm commercialization. Here, we demonstrate a facile recycling process for PbI2, the most common lead-based precursor in perovskite absorber material. The process uses only hot water to effectively extract lead from synthetic precursor mixes, plastic- and glass-based perovskites (92.6 ĂąEuro" 10
A new method for post-translationally labeling proteins in live cells for fluorescence imaging and tracking
This work was funded by the Raymond and Beverley Sackler Institute for Biological, Physical, and Engineering sciences [to L.R.]; the National Institute of Health [Grant nos. GM118528 and CA209992 to M. H. and L. R.]; the Medical Research Council [Grant no. MR/K001485 to U.S.L. and J. M. E.]; a Leverhulme Trust Visiting Professorship [to L. R.]; and Royal Society of Edinburgh [Caledonian Scholarship to O.K.M.].We present a novel method to fluorescently label proteins, post-translationally, within live Saccharomycescerevisiae. The premise underlying this work is that fluorescent protein (FP) tags are less disruptive to normal processing and function when they are attached post-translationally, because target proteins are allowed to fold properly and reach their final subcellular location before being labeled. We accomplish this post-translational labeling by expressing the target protein fused to a short peptide tag (SpyTag), which is then covalently labeled in situ by controlled expression of an open isopeptide domain (SpyoIPD, a more stable derivative of the SpyCatcher protein) fused to an FP. The formation of a covalent bond between SpyTag and SpyoIPD attaches the FP to the target protein. We demonstrate the general applicability of this strategy by labeling several yeast proteins. Importantly, we show that labeling the membrane protein Pma1 in this manner avoids the mislocalization and growth impairment that occur when Pma1 is genetically fused to an FP. We also demonstrate that this strategy enables a novel approach to spatiotemporal tracking in single cells and we develop a Bayesian analysis to determine the proteinâs turnover time from such data.PostprintPeer reviewe
Auf dem Weg zur klimaneutralen Industrie - Herausforderungen und Strategien
Der Beitrag beleuchtet die Herausforderungen und Strategien fĂŒr die Industrie in Deutschland im Rahmen der Energiewende. Der Fokus liegt hierbei auf den Themen Kreislaufwirtschaft, Wasserstoffnutzung, Erneuerbare ProzesswĂ€rme und Bioenergie sowie auf den sich darausergebenden Herausforderungen an die Infrastruktur und die Politik
The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer
Background:
In the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups.
Methods:
Primary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, â„65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics.
Results:
Eight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged â„65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59â0.81; P = 0.0001). Median OS in the three regions was 6.5â7.8 months in the trifluridine/tipiracil arm and 4.3â6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34â0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48â0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57â1.00; P = 0.0470). Median PFS was 2.0â2.8 months for trifluridine/tipiracil and 1.7â1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability.
Conclusions:
Trifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status
System-wide profiling of RNA-binding proteins uncovers key regulators of virus infection
International audienceGraphical Abstract Highlights d A quarter of the RBPome changes upon SINV infection d Alterations in RBP activity are largely explained by changes in RNA availability d Altered RBPs are crucial for viral infection efficacy d GEMIN5 binds to the 5 0 end of SINV RNAs and regulates viral gene expressio
Human Practice. Digital Ecologies. Our Future. : 14. Internationale Tagung Wirtschaftsinformatik (WI 2019) : Tagungsband
Erschienen bei: universi - UniversitÀtsverlag 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 SystemsâWhatâs the difference? Towards a Unified Terminology
Developing an Industrial IoT Platform â 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 Customersâ Behavioral Intention to Use Ridepooling Services â 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 â On the Example of Blockchain-Based Initiatives for the Electricity Sector
Zwischenbetriebliche Integration in der Möbelbranche: Konfigurationen und Einflussfaktoren
Novicesâ Quality Perceptions and the Acceptance of Process Modeling Grammars
Entwicklung einer Definition fĂŒr 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 â A Literature Review on necessary Competences in a Digitalized Public Sector
Say Hello to Your New Automated Tutor â 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 â 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 â 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 â 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 â Boost for your Sales?
EntscheidungsunterstĂŒtzung 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 fĂŒr 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 â Harnessing Locational Advantages for the Digital Transformation of Local Retail Outlets: A Content Analysis
A Socio-Technical Approach to Manage Analytics-as-a-Service â Results of an Action Design Research Project
Characterizing Approaches to Digital Transformation: Development of a Taxonomy of Digital Units
Expectations vs. Reality â 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 Platformsâ A Taxonomy-Based Approach to Structure the Field
Less Complex than Expected â What Really Drives IT Consulting Value
Modularity Canvas â 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 fĂŒr 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 Membersâ Affective Organisational Commitment
The Complexity Trap â 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 â An Experimental Exploration of the Impact of Storage Solutions and Data Breaches
Patientenintegration durch Pfadsysteme
Digitalisierung in der StressprĂ€vention â eine qualitative Interviewstudie zu Nutzenpotenzialen
User Dynamics in Mental Health Forums â A Sentiment Analysis Perspective
Intent and the Use of Wearables in the Workplace â 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 Usersâ 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 KontinuitÀtsmanagement
Potentiale von IKT beim Ausfall kritischer Infrastrukturen: Erwartungen, Informationsgewinnung und Mediennutzung der Zivilbevölkerung in Deutschland
Fake News Perception in Germany: A Representative Study of Peopleâs 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 â 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 Individualsâ 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
KommunikationsfĂ€den im Nadelöhr â Fachliche Prozessmodellierung der Nachhaltigkeitskommunikation am Kapitalmarkt
Potentiale und Herausforderungen der Materialflusskostenrechnung
Computing Incentives for User-Based Relocation in Carsharing
Sustainabilityâs 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 â A Literature Review
Ein EntscheidungsunterstĂŒtzungssystem zur ökonomischen Bewertung von Mieterstrom auf Basis der Clusteranalyse
Discovering Blockchain for Sustainable Product-Service Systems to enhance the Circular Economy
Digitale RĂŒckverfolgbarkeit 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
âShow Me Your People Skillsâ - 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 â 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: GeschÀftsmodelle 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 â 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 fĂŒr 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 âNeedminingâ 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 fĂŒr Ă€ltere 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 â EMoWIâ19)
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 kĂŒnftiger Mitarbeiter im Bereich Business Analytics
Digitaler Konsum: Herausforderungen und Chancen der Verbraucherinformati
The European Hematology Association Roadmap for European Hematology Research: a consensus document
The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at âŹ23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.
The EHA Roadmap identifies nine âsectionsâ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.
The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients
Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.
Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes
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