Sample records for architecture hla federation

  1. An HLA based flight simulation architecture

    Huiskamp, W.; Jense, G.J.; Janssen, H.G.M.


    Modern distributed simulation concepts such as the US DoD High Level Architecture (HLA) support interoperability between heterogeneous simulations, thus enabling the development of flexible, re-usable simulation Federations. Based on the principles of HLA, the Dutch national collaborative project 'S

  2. Architecture of HLA Based Distributed Virtual Geographic Environment

    XU Bingli; LIN Hui; GONG Jianhua


    Integrating the theory of distributed virtual geographic environment (DVGE) and high level architecture(HLA), the architecture of DVGE based on HLA is designed. The data flow and the object models of the architecture are also discussed. The architecture basically meets the need of DVGE in real-time communication, distribution, collaboration, reusing and interoperation, expansion, and standard.

  3. High level architecture evolved modular federation object model

    Wang, Wenguang; Chen, Xin; Li, Qun; Wang, Weiping


    To improve the agility, dynamics, composability, reusability, and development efficiency restricted by monolithic Federation Object Model (FOM), a modular FOM was proposed by High Level Architecture (HLA) Evolved product development group. This paper reviews the state-of-the-art of HLA Evolved modular FOM. In particular, related concepts, the overall impact on HLA standards, extension principles, and merging processes are discussed. Also permitted and restricted combinations, and merging rules are provided, and the influence on HLA interface specification is given. The comparison between modular FOM and Base Object Model (BOM) is performed to illustrate the importance of their combination. The applications of modular FOM are summarized. Finally, the significance to facilitate composable simulation both in academia and practice is presented and future directions are pointed out.

  4. An HLA/RTI Architecture Based on Multi-thread Processing

    GUAN Li; ZOU Ru-ping; ZHU Bin; HAO Chong-yang


    In order to improve the real-time performance of the real-time HLA (high level architecture) in the application of massive data communication volume, multi-thread processing was adopted, thread pool structure was introduced into the system, different threads to handle corresponding message queues was utilized to respond different message requests. Fur-thermore, an allocation strategy of semi-complete deprivation of priority was adopted, which reduces thread switching cost and processing burden in the system, provided that the message requests with high priority can be responded in time, thus improves the system's overall performance. The design and experiment results indicate that the method proposed in this pa-per can improve the real-time performance of HLA in distributed system applications greatly.

  5. Avoiding another Green Elephant - A Proposal for the Next Generation HLA based on the Model Driven Architecture

    Tolk, Andreas


    When looking through the proceedings of the recent Simulation Interoperability Workshops, a lot of papers - some of them even awarded by the committee - are dealing with alternative concepts outside or beyond the High Level Architecture (HLA): Web Services, the extensible Markup Language (XML), Java Beans, Simple Object Access Protocol (SOAP), etc. Similarly, requirements driven by interoperability issues have resulted in the need to use meta modeling, adaptive models, and common repositories. The use of the Unified Modeling Language (UML) as a model description language is also rapidly becoming a standard. All these concepts have relations to the HLA, but they are not part of it. There seems to be the danger that HLA is overrun by respective developments of the free market and will become irrelevant finally. ... This paper introduces the MDA concept and shows, how the HLA can be integrated to become a standard stub for simulation applications of legacy systems, systems under development, and systems of the f...

  6. Service-oriented high level architecture

    Wang, Wenguang; Yu, Wenguang; Li, Qun; Wang, Weiping; Liu, Xichun


    Service-oriented High Level Architecture (SOHLA) refers to the high level architecture (HLA) enabled by Service-Oriented Architecture (SOA) and Web Services etc. techniques which supports distributed interoperating services. The detailed comparisons between HLA and SOA are made to illustrate the importance of their combination. Then several key enhancements and changes of HLA Evolved Web Service API are introduced in comparison with native APIs, such as Federation Development and Execution Pr...

  7. Design of a service-oriented architecture for federated systems

    Calegari, Daniel; Viera, Marcos; Motz, Regina


    A Federated System is a collection of independent, cooperative, possibly heterogeneous and autonomous computer systems (usually database systems) which allows sharing all or some of its data. A Service-Oriented Architecture is an application architecture whose functionalities are defined as independent services which offer transparent communication between physically distributed components, possibly heterogeneous and autonomous. In this context, it is interesting to analyze how a Federated Sy...

  8. 基于语义联邦的HLA对象模型生成方法%Novel HLA Object Model Generation Method Based on Semantic Federation

    李犁; 肖田元; 马成


    To assure the semantic consistency in collaborative simulation for complex product development, a novel HLA object model generation method was given based on semantic federation. In HLA, the proposed method reused and organized domain ontologies in semantic federation by publish/subscribe mode, and achieved the mutual understanding among federates while the independence of domain ontology was well reserved. HLA object model for simulation federations could be created dynamically on the basis of semantic federation and user's control, therefore the efficiency of creating simulation federation was improved and the semantic consistency was ensured. A prototype of semantic based collaborative simulation and an industrial case were well established to demonstrate the feasibility of this method.%为提升复杂产品协同仿真过程中的语义一致性,提出了一种基于语义联邦的高层体系结构(High Level Architecture,HLA)对象模型生成方法.该方法在HLA的范畴内,通过建立语义联邦完成各联邦成员间的互理解,以发布和订购的方式实现各联邦成员间本体的概念匹配,在保持领域本体独立性的基础上形成了不同领域本体概念间的概念匹配对,并以此为基础动态生成具体仿真应用联邦的HLA对象模型,从而保证了协同仿真应用联邦建立的效率和语义的一致性.本研究还建立了基于语义联邦协同仿真平台原型系统,并通过实例验证了方法的可行性.

  9. Federated Accounting Management System Architecture for Multimedia Service Usage Management

    Bhushan, Bharat; Gringel, T.; Ryan, Conor; Leray, Eric; de Leastar, Eamonn; Cloney, James


    This white paper reports on the progress and achievements that has been made in the area of federated accounting management since the beginning of FORM project. Thus far, an architecture of federated accounting management system and information model has been design and specified using UML and XML. These both aim to be both open and adaptable, and are based on concepts and recommendations laid down by TMForum (TeleManagement Forum), IPDR (IP Detail Record), OMG (Object Management ...

  10. Architecture of a federated query engine for heterogeneous resources.

    Bradshaw, Richard L; Matney, Susan; Livne, Oren E; Bray, Bruce E; Mitchell, Joyce A; Narus, Scott P


    The Federated Utah Research and Translational Health e-Repository (FURTHeR) is a Utah statewide informatics platform for the new Center for Clinical and Translational Science at the University of Utah. We have been working on one of FURTHeR's key components, a federated query engine for heterogeneous resources, that we believe has the potential to meet some of the fundamental needs of translational science to access and integrate diverse biomedical data and promote discovery of new knowledge. The architecture of the federated query engine for heterogeneous resources is described and demonstrated. PMID:20351825

  11. Federated querying architecture with clinical & translational health IT application.

    Livne, Oren E; Schultz, N Dustin; Narus, Scott P


    We present a software architecture that federates data from multiple heterogeneous health informatics data sources owned by multiple organizations. The architecture builds upon state-of-the-art open-source Java and XML frameworks in innovative ways. It consists of (a) federated query engine, which manages federated queries and result set aggregation via a patient identification service; and (b) data source facades, which translate the physical data models into a common model on-the-fly and handle large result set streaming. System modules are connected via reusable Apache Camel integration routes and deployed to an OSGi enterprise service bus. We present an application of our architecture that allows users to construct queries via the i2b2 web front-end, and federates patient data from the University of Utah Enterprise Data Warehouse and the Utah Population database. Our system can be easily adopted, extended and integrated with existing SOA Healthcare and HL7 frameworks such as i2b2 and caGrid. PMID:21537849

  12. Parasol: An Architecture for Cross-Cloud Federated Graph Querying

    Lieberman, Michael; Choudhury, Sutanay; Hughes, Marisa; Patrone, Dennis; Hider, Sandy; Piatko, Christine; Chapman, Matthew; Marple, JP; Silberberg, David


    Large scale data fusion of multiple datasets can often provide in- sights that examining datasets individually cannot. However, when these datasets reside in different data centers and cannot be collocated due to technical, administrative, or policy barriers, a unique set of problems arise that hamper querying and data fusion. To ad- dress these problems, a system and architecture named Parasol is presented that enables federated queries over graph databases residing in multiple clouds. Parasol’s design is flexible and requires only minimal assumptions for participant clouds. Query optimization techniques are also described that are compatible with Parasol’s lightweight architecture. Experiments on a prototype implementation of Parasol indicate its suitability for cross-cloud federated graph queries.

  13. Study of hierarchical federation architecture using multi-resolution modeling

    HAO Yan-ling; SHEN Dong-hui; QIAN Hua-ming; DENG Ming-hui


    This paper aims at finding a solution to the problem aroused in complex system simulation, where a specific functional federation is coupled with other simulation systems. In other words, the communication information within the system may be received by other federates that participated in this united simulation. For the purpose of ensuring simulation system unitary character, a hierarchical federation architecture (HFA) is taken. Also considering the real situation, where federates in a complicated simulation system can be made simpler to an extent, a multi-resolution modeling (MRM) method is imported to implement the design of hierarchical federation. By utilizing the multiple resolution entity (MRE) modeling approach, MRE for federates are designed out. When different level training simulation is required, the appropriate MRE at corresponding layers can be called. The design method realizes the reuse feature of the simulation system and reduces simulation complexity and improves the validity of system Simulation Cost (SC). Taking submarine voyage training simulator (SVTS) for instance, a HFA for submarine is constructed inthis paper, which approves the feasibility of studied approach.

  14. Service-oriented high level architecture

    Wang, Wenguang; Li, Qun; Wang, Weiping; Liu, Xichun


    Service-oriented High Level Architecture (SOHLA) refers to the high level architecture (HLA) enabled by Service-Oriented Architecture (SOA) and Web Services etc. techniques which supports distributed interoperating services. The detailed comparisons between HLA and SOA are made to illustrate the importance of their combination. Then several key enhancements and changes of HLA Evolved Web Service API are introduced in comparison with native APIs, such as Federation Development and Execution Process, communication mechanisms, data encoding, session handling, testing environment and performance analysis. Some approaches are summarized including Web-Enabling HLA at the communication layer, HLA interface specification layer, federate interface layer and application layer. Finally the problems of current research are discussed, and the future directions are pointed out.

  15. Architecture of a mediator for a bioinformatics database federation.

    Kemp, Graham J L; Angelopoulos, Nicos; Gray, Peter M D


    Developments in our ability to integrate and analyze data held in existing heterogeneous data resources can lead to an increase in our understanding of biological function at all levels. However, supporting ad hoc queries across multiple data resources and correlating data retrieved from these is still difficult. To address this, we are building a mediator based on the functional data model database, P/FDM, which integrates access to heterogeneous distributed biological databases. Our architecture makes use of the existing search capabilities and indexes of the underlying databases, without infringing on their autonomy. Central to our design philosophy is the use of schemas. We have adopted a federated architecture with a five-level schema, arising from the use of the ANSI-SPARC three-level schema to describe both the existing autonomous data resources and the mediator itself. We describe the use of mapping functions and list comprehensions in query splitting, producing execution plans, code generation, and result fusion. We give an example of cross-database querying involving data held locally in P/FDM systems and external data in SRS. PMID:12075665

  16. A federated design for a neurobiological simulation engine: the CBI federated software architecture.

    Cornelis, Hugo; Coop, Allan D; Bower, James M


    Simulator interoperability and extensibility has become a growing requirement in computational biology. To address this, we have developed a federated software architecture. It is federated by its union of independent disparate systems under a single cohesive view, provides interoperability through its capability to communicate, execute programs, or transfer data among different independent applications, and supports extensibility by enabling simulator expansion or enhancement without the need for major changes to system infrastructure. Historically, simulator interoperability has relied on development of declarative markup languages such as the neuron modeling language NeuroML, while simulator extension typically occurred through modification of existing functionality. The software architecture we describe here allows for both these approaches. However, it is designed to support alternative paradigms of interoperability and extensibility through the provision of logical relationships and defined application programming interfaces. They allow any appropriately configured component or software application to be incorporated into a simulator. The architecture defines independent functional modules that run stand-alone. They are arranged in logical layers that naturally correspond to the occurrence of high-level data (biological concepts) versus low-level data (numerical values) and distinguish data from control functions. The modular nature of the architecture and its independence from a given technology facilitates communication about similar concepts and functions for both users and developers. It provides several advantages for multiple independent contributions to software development. Importantly, these include: (1) Reduction in complexity of individual simulator components when compared to the complexity of a complete simulator, (2) Documentation of individual components in terms of their inputs and outputs, (3) Easy removal or replacement of unnecessary or

  17. 41 CFR 102-76.25 - What standards must Federal agencies meet in providing architectural and interior design services?


    ... applicable to Federal buildings in 10 CFR part 435. ... Federal agencies meet in providing architectural and interior design services? 102-76.25 Section 102-76.25... What standards must Federal agencies meet in providing architectural and interior design...

  18. 41 CFR 102-77.10 - What basic Art-in-Architecture policy governs Federal agencies?


    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What basic Art-in... PROPERTY 77-ART-IN-ARCHITECTURE General Provisions § 102-77.10 What basic Art-in-Architecture policy governs Federal agencies? Federal agencies must incorporate fine arts as an integral part of the...

  19. A Federated Approach to Enterprise Architecture Model Maintenance

    Fischer, Ronny; Aier, Stephan; Winter, Robert


    Enterprise architecture is gaining acceptance as an approach to manage change and foster IT/business alignment by (1) propagating strategy and process changes to the software and infrastructure level, by (2) supporting consistent business transformation enabled by technology innovations, and by (3) decoupling business-oriented and technology-oriented architectures. Due to constant change in business as well as in technology, enterprise architecture management is a permanent process rather tha...

  20. CONTRAIL - Architecture design and QoS constraints matching algorithms in Federations

    Coppola, Massimo; Dazzi, Patrizio; Carlini, Emanuele; Righetti, Giacomo; et al, ...


    This deliverable analyses both functionality and algorithms for Contrail Federations and provides an architectural design which takes into account aspects of Identity management and Security. The Federation plays a central role in Contrail: users access Contrail resources through the Federation, which is one the main selling points of Contrail. A Federation can be seen as a bridge between cloud users and cloud providers, since it mediates between users' requests and providers owning the resou...

  1. UFRA: a UIMA-based Approach to Federated Language Resource Architecture

    Del Gratta, Riccardo; Bartolini, Roberto; Caselli, Tommaso; Monachini, Monica; Soria, Claudia; Calzolari, Nicoletta


    In this paper we address the issue of developing an interoperable infrastructure for language resources and technologies. In our approach, called UFRA, we extend the Federate Database Architecture System adding typical functionalities caming from UIMA. In this way, we capitalize the advantages of a federated architecture, such as autonomy, heterogeneity and distribution of components, monitored by a central authority responsible for checking both the integration of components and user rights ...

  2. Evaluating the Effectiveness of Reference Models in Federating Enterprise Architectures

    Wilson, Jeffery A.


    Agencies need to collaborate with each other to perform missions, improve mission performance, and find efficiencies. The ability of individual government agencies to collaborate with each other for mission and business success and efficiency is complicated by the different techniques used to describe their Enterprise Architectures (EAs).…

  3. 基于MOM的HLA/RTI管理盟员的设计与实现%Design and Implementation of HLA/RTI Management Federate Based on MOM

    季利春; 姚益平


    为了在仿真运行过程中对联盟、盟员以及RTI进行监控,HLA中引入了管理对象模型(MOM),该模型是HLA/RTI架构中的重要组成部分.该文介绍了IEEE1516规范中定义的MOM,并在此基础上对其进行了扩展.结合我们StarLink RTI的开发实践,提出了通过代理盟员实现MOM的设计方案,在该RTI中实现了对MOM的支持.最后在此基础上,设计并实现了管理盟员StarFM.

  4. Architecture of a Federated Query Engine for Heterogeneous Resources

    Bradshaw, Richard L.; Matney, Susan; Livne, Oren E.; Bray, Bruce E; Mitchell, Joyce A.; Narus, Scott P


    The Federated Utah Research and Translational Health e-Repository (FURTHeR) is a Utah statewide informatics platform for the new Center for Clinical and Translational Science at the University of Utah. We have been working on one of FURTHeR’s key components, a federated query engine for heterogeneous resources, that we believe has the potential to meet some of the fundamental needs of translational science to access and integrate diverse biomedical data and promote discovery of new knowledge....

  5. 41 CFR 102-77.25 - Do Federal agencies have responsibilities to provide national visibility for Art-in-Architecture?


    ... responsibilities to provide national visibility for Art-in-Architecture? 102-77.25 Section 102-77.25 Public... MANAGEMENT REGULATION REAL PROPERTY 77-ART-IN-ARCHITECTURE Art-in-Architecture § 102-77.25 Do Federal agencies have responsibilities to provide national visibility for Art-in-Architecture? Yes,...

  6. FIGARO ( Future Internet Gateway-based Architecture of Residential Networks ) D5.2: Architecture for service federation in residential networks

    Hartog, F.T.H. den; Hillen, B.A.G.; Tijmes, M.R.


    This document defines the preliminary version of the FIGARO architectural solution for federation within residential networks. The architecture is derived from use cases from the domains of e-health, energy management, domotics and social community services and thus supports requirements from each of these domains. This deliverable describes and validates the architecture and its main components.

  7. Template Driven Code Generator for HLA Middleware

    Jansen, R.E.J.; Prins, L.M.; Huiskamp, W.


    HLA is the accepted standard for simulation interoperability. However, the HLA services and the API that is provided for these services are relatively complex from the user point of view. Since the early days of HLA, federate developers have attempted to simplify their task by using middleware that

  8. PlanetDR, a scalable architecture for federated repositories supporting IMS Learning Design

    Blat, Josep; Griffiths, David; Navarrete, Toni; Santos, José Luis; García, Pedro; Pujol, Jordi


    Please, cite this publication as: Blat, J., Griffiths, D., Navarrete, T., Santos, J.L., García, P., & Pujol, J. (2006). PlanetDR, a scalable architecture for federated repositories supporting IMS Learning Design. Proceedings of International Workshop in Learning Networks for Lifelong Competence Deve

  9. Scalable Architecture for Federated Translational Inquiries Network (SAFTINet) Technology Infrastructure for a Distributed Data Network

    Schilling, Lisa M; Kwan, Bethany M.; Drolshagen, Charles T.; Hosokawa, Patrick W.; Brandt, Elias; Pace, Wilson D.; Uhrich, Christopher; Kamerick, Michael; Bunting, Aidan; Payne, Philip R.O.; Stephens, William E.; George, Joseph M.; Vance, Mark; Giacomini, Kelli; Braddy, Jason


    Introduction: Distributed Data Networks (DDNs) offer infrastructure solutions for sharing electronic health data from across disparate data sources to support comparative effectiveness research. Data sharing mechanisms must address technical and governance concerns stemming from network security and data disclosure laws and best practices, such as HIPAA. Methods: The Scalable Architecture for Federated Translational Inquiries Network (SAFTINet) deploys TRIAD grid technology, a common data mod...

  10. PlanetDR, a scalable architecture for federated repositories supporting IMS Learning Design

    Blat, Josep; Griffiths, David; Navarrete, Toni; Santos, José Luis; García, Pedro; Pujol, Jordi


    This paper discusses PlanetDR, whose architecture supports very large federated educational digital repositories. It is based on the implementation of current open specifications for interoperability (such as IEEE Learning Object Metadata and IMS Digital Repositories Interoperability, in its Edusour

  11. Virtual simulation of operation and control of PWR based on high level architecture

    Considering the function of PWR primary loop system, an architecture and federations design of primary loop system operation and control simulation based on High Level Architecture(HLA) is presented, MAK's VR-Link and RTI is used to construct a distributed network for simulation. The implementation of math model reckon federation, 3-dimensional primary visual federation and 2-dimensional state federations are researched by the compilation of VC++ programs, MATLAB and Vega. The HLA is well extended and reused, so the system can be extended to implement the simulation of the whole nuclear power system. (authors)

  12. Real-time Scheduling of HLA Simulator Components

    Jansen, R.E.J.; Huiskamp, W.; Boomgaardt, J.J.; Brasse, M.


    For several years TNO has done research on the use of component based HLA federates. An individual simulator, participating in an HLA federation, can itself be composed of various components interacting through the same HLA interface as the overall federation. Simulator components communicate via a

  13. FIGARO ( Future Internet Gateway-based Architecture of Residential Networks ) D5.2: Architecture for service federation in residential networks

    Hartog, F.T.H. den; Hillen, B.A.G.; Tijmes, M.R.


    This document defines the preliminary version of the FIGARO architectural solution for federation within residential networks. The architecture is derived from use cases from the domains of e-health, energy management, domotics and social community services and thus supports requirements from each o

  14. Architecture for a Federated Drug Reference in a managed care environment.

    Ketchell, D. S.; Ibrahim, K. N.; Murri, N. A.; Wareham, P. S.; Bell, D. M.; Jankowski, T A


    We describe a model of drug information query management that supports the integration of various types of pharmaceutical information and the delivery of that information through a common interface. Our prototype drug reference system makes use of the World Wide Web client/server architecture as a front-end to federate this data. Although originally intended as an electronic Hospital Formulary, the system has been redefined as a result of input from physicians to include formularies of multip...

  15. Structural modeling of HLA-B*1502/peptide/carbamazepine/T-cell receptor complex architecture: implication for the molecular mechanism of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

    Zhou, Peng; Zhang, Shilei; Wang, Yewang; Yang, Chao; Huang, Jian


    Drug-induced adverse reactions are a significant problem in healthcare worldwide and are estimated to cost billions of dollars annually in the United States. A portion of such reactions is observed to strongly associate with certain human leukocyte antigen (HLA) alleles; one of the strongest associations is the HLA-B*1502 protein with carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) - the odds ratio value can even be higher than one thousand. The particularly strong association in CBZ-induced SJS/TEN suggests that the HLA-B*1502 is not only a genetic marker but also a participant in the pathogenesis of the disease. In the current study, we attempt to computationally model the atomic-level structure of the complete HLA-B*1502/peptide/CBZ/T-cell receptor (TCR) complex architecture based on prior knowledge obtained from epidemiological investigations as well as in vitro and in vivo assays. The model tells a different story about the molecular mechanism of CBZ-induced SJS/TEN from that previously reported for abacavir (ABC)-induced hypersensitivity (HSR); the CBZ molecule is located at the interface between HLA-B*1502/peptide and TCR, directly contacts the P3-P6 residues of antigen peptide, and bound within a pocket region encompassed by two TCR CDR3 fingers. Molecular dynamics simulation and binding energy analysis further reveal that the CBZ shows considerably high affinity to TCR over HLA-B*1502/peptide, which can tightly interact with the former rather than the latter. From the model, two hypotheses are proposed that can well explain most previous observations and are expected to guide next wet-lab experiments. This study could help to promote our understanding of the molecular mechanism and pathological implication underlying CBZ-induced SJS/TEN. PMID:26488421

  16. HLA Evolved规范研究分析%Research and Analysis of HLA Evolved Specification

    钟蔚; 龚建兴; 郝建国; 黄柯棣


    As the next generation HLA specification which is about to accepted by IEEE,HLA Evolved stands for a newest road ahead for HLA.By comparing HLA 1516-2000 with HLA Evolved,important technical innovation and great changes were summarized and analyzed,which discovered that HLA Evolved had a more powerful function and more strengthen mechanism than HLA 1516-2000.Then,a initial research was put forward on how to develop and immigrate federates under HLA Evolved,being a good start for applying and spreading of HLA Evolved.%HLA Evolved作为即将被IEEE通过和接受的下一代HLA规范,代表了HLA体系的最新发展方向。综合比较了HLA 1516-2000与HLA Evolved,概括分析了模块化FOM、动态库兼容API、智能更新率降低、容错处理、Web支持的HLA等重大技术改进和主要变动,揭示了HLA Evolved更为强大的功能和更加健壮的机制。初步研究了HLA Evolved下成员开发和移植工作,为HLAEvolved规范的应用和推广奠定了基础。

  17. Architecture for a Federated Drug Reference in a managed care environment.

    Ketchell, D S; Ibrahim, K N; Murri, N A; Wareham, P S; Bell, D M; Jankowski, T A


    We describe a model of drug information query management that supports the integration of various types of pharmaceutical information and the delivery of that information through a common interface. Our prototype drug reference system makes use of the World Wide Web client/server architecture as a front-end to federate this data. Although originally intended as an electronic Hospital Formulary, the system has been redefined as a result of input from physicians to include formularies of multiple managed care plans. The underlying database is designed for integration with an electronic medical record as well as education and research resources for faculty and students in an academic medical center environment. PMID:8947699

  18. Federal Data Repository Research: Recent Developments in Mercury Search System Architecture

    Devarakonda, R.


    New data intensive project initiatives needs new generation data system architecture. This presentation will discuss the recent developments in Mercury System [1] including adoption, challenges, and future efforts to handle such data intensive projects. Mercury is a combination of three main tools (i) Data/Metadata registration Tool (Online Metadata Editor): The new Online Metadata Editor (OME) is a web-based tool to help document the scientific data in a well-structured, popular scientific metadata formats. (ii) Search and Visualization Tool: Provides a single portal to information contained in disparate data management systems. It facilitates distributed metadata management, data discovery, and various visuzalization capabilities. (iii) Data Citation Tool: In collaboration with Department of Energy's Oak Ridge National Laboratory (ORNL) Mercury Consortium (funded by NASA, USGS and DOE), established a Digital Object Identifier (DOI) service. Mercury is a open source system, developed and managed at Oak Ridge National Laboratory and is currently being funded by three federal agencies, including NASA, USGS and DOE. It provides access to millions of bio-geo-chemical and ecological data; 30,000 scientists use it each month. Some recent data intensive projects that are using Mercury tool: USGS Science Data Catalog (, Next-Generation Ecosystem Experiments (, Carbon Dioxide Information Analysis Center (, Oak Ridge National Laboratory - Distributed Active Archive Center (, SoilSCAPE ( References: [1] Devarakonda, Ranjeet, et al. "Mercury: reusable metadata management, data discovery and access system." Earth Science Informatics 3.1-2 (2010): 87-94.

  19. Technology Reference Model (TRM) Reports: Federal Enterprise Architecture (FEA) Mapping Report

    Department of Veterans Affairs — The One VA Enterprise Architecture (OneVA EA) is a comprehensive picture of the Department of Veterans Affairs' (VA) operations, capabilities and services and the...

  20. Technology Reference Model (TRM) Reports: Federal Enterprise Architecture (FEA) Category Count Report

    Department of Veterans Affairs — The One VA Enterprise Architecture (OneVA EA) is a comprehensive picture of the Department of Veterans Affairs' (VA) operations, capabilities and services and the...

  1. LC Data QUEST: A Technical Architecture for Community Federated Clinical Data Sharing.

    Stephens, Kari A; Lin, Ching-Ping; Baldwin, Laura-Mae; Echo-Hawk, Abigail; Keppel, Gina A; Buchwald, Dedra; Whitener, Ron J; Korngiebel, Diane M; Berg, Alfred O; Black, Robert A; Tarczy-Hornoch, Peter


    The University of Washington Institute of Translational Health Sciences is engaged in a project, LC Data QUEST, building data sharing capacity in primary care practices serving rural and tribal populations in the Washington, Wyoming, Alaska, Montana, Idaho region to build research infrastructure. We report on the iterative process of developing the technical architecture for semantically aligning electronic health data in primary care settings across our pilot sites and tools that will facilitate linkages between the research and practice communities. Our architecture emphasizes sustainable technical solutions for addressing data extraction, alignment, quality, and metadata management. The architecture provides immediate benefits to participating partners via a clinical decision support tool and data querying functionality to support local quality improvement efforts. The FInDiT tool catalogues type, quantity, and quality of the data that are available across the LC Data QUEST data sharing architecture. These tools facilitate the bi-directional process of translational research. PMID:22779052

  2. HLA框架分析和当前应用中的问题%Analyis on the Architecture of HLA and the Problems in Current Applications

    张兵; 吴彬



  3. A New HLA-Based Distributed Control Architecture for Agricultural Teams of Robots in Hybrid Applications with Real and Simulated Devices or Environments

    Martínez, Rafael J.; Joaquín Torres-Sospedra; Patricio Nebot


    The control architecture is one of the most important part of agricultural robotics and other robotic systems. Furthermore its importance increases when the system involves a group of heterogeneous robots that should cooperate to achieve a global goal. A new control architecture is introduced in this paper for groups of robots in charge of doing maintenance tasks in agricultural environments. Some important features such as scalability, code reuse, hardware abstraction and data distribution h...

  4. Promoting A-Priori Interoperability of HLA-Based Simulations in the Space Domain: The SISO Space Reference FOM Initiative

    Moller, Bjorn; Garro, Alfredo; Falcone, Alberto; Crues, Edwin Z.; Dexter, Daniel E.


    Distributed and Real-Time Simulation plays a key-role in the Space domain being exploited for missions and systems analysis and engineering as well as for crew training and operational support. One of the most popular standards is the 1516-2010 IEEE Standard for Modeling and Simulation (M&S) High Level Architecture (HLA). HLA supports the implementation of distributed simulations (called Federations) in which a set of simulation entities (called Federates) can interact using a Run-Time Infrastructure (RTI). In a given Federation, a Federate can publish and/or subscribes objects and interactions on the RTI only in accordance with their structures as defined in a FOM (Federation Object Model). Currently, the Space domain is characterized by a set of incompatible FOMs that, although meet the specific needs of different organizations and projects, increases the long-term cost for interoperability. In this context, the availability of a reference FOM for the Space domain will enable the development of interoperable HLA-based simulators for related joint projects and collaborations among worldwide organizations involved in the Space domain (e.g. NASA, ESA, Roscosmos, and JAXA). The paper presents a first set of results achieved by a SISO standardization effort that aims at providing a Space Reference FOM for international collaboration on Space systems simulations.

  5. An Investigation of Influencing Factors for Adopting Federated Identity Authentication in Service-Oriented Architecture (SOA)

    Tadesse, Yohannes


    The importance of information security has made many organizations to invest and utilize effective information security controls within the information systems (IS) architecture. An organization's strategic decisions to secure enterprise-wide services often associated with the overall competitive advantages that are attained through the process of…

  6. A Multi-Level Investigation into the Antecedents of Enterprise Architecture (EA) Assimilation in the U.S. Federal Government: A Longitudinal Mixed Methods Research Study

    Makiya, George K.


    This dissertation reports on a multi-dimensional longitudinal investigation of the factors that influence Enterprise Architecture (EA) diffusion and assimilation within the U.S. federal government. The study uses publicly available datasets of 123 U.S. federal departments and agencies, as well as interview data among CIOs and EA managers within…

  7. LC Data QUEST: A Technical Architecture for Community Federated Clinical Data Sharing

    Stephens, Kari A.; Lin, Ching-Ping; Baldwin, Laura-Mae; Echo-Hawk, Abigail; Keppel, Gina A.; Buchwald, Dedra; Whitener, Ron J.; Korngiebel, Diane M.; Berg, Alfred O.; Black, Robert A.; Tarczy-Hornoch, Peter


    The University of Washington Institute of Translational Health Sciences is engaged in a project, LC Data QUEST, building data sharing capacity in primary care practices serving rural and tribal populations in the Washington, Wyoming, Alaska, Montana, Idaho region to build research infrastructure. We report on the iterative process of developing the technical architecture for semantically aligning electronic health data in primary care settings across our pilot sites and tools that will facili...

  8. Design and Implementation of Simulation Environment for HLA-Compliant Torpedo Weapon System

    TANG Kai; KANG Feng-ju; GU Hao; SONG Zhi-ming


    A novel scheme for HLA(high level architecture)-compliant reconfigurable open architecture for the torpedo weapon system simulation is proposed. In addition, a kind of applied software framework for federate members based on the reusable software is put forward. The automation of time management strategy drafting and publish-subscribe declaration, and the consistent interface between RTI (run-time infrastructure) and simulation models are solved effectively. Furthermore, in order to simulate the fluctuant seabed, twinkle light spots, air bubbles, muddy effect, etc, an extended module, called as Underwater Space Vega, is developed. Finally, a distributed interactive simulation environment for underwater vehicles is set up with the aid of the software pRTI1.3. The preliminary experiment results indicate that this system friendly features GUI, reusable models and competence for real-time simulation.

  9. Systems Analysis and Design for Service Oriented Architecture Projects: A Case Study at the Federal Financial Institutions Examinations Council (FFIEC

    Chon Abraham


    Full Text Available Problems with consolidating, disseminating, and ensuring integrity of corporate data management continues to confront the information systems leadership in organizations. To address these problems some organizations are employing Service Oriented Architectures (SOA as a paradigm, which is enhanced by the use of Web services to provide a lightweight means of leveraging resources. The Federal Financial Institutions Examinations Council (FFIEC is one such organization. In this paper, we have used the traditional systems analysis and design (SAD principles to frame how the FFIEC employed SOA as a new paradigm of conducting business with Web services enabled by a particular XML based instantiation: eXtensible Business Reporting Language (XBRL. Using qualitative methods, we provide a methodological guide in the form of questions organizations should address in SOA projects that particularizes SAD principles for SOA. The questions derive from merging analysis of the data collected regarding the SAD efforts at the FFIEC coupled with principles asserted in traditional SAD literature. We also present lessons learned by the FFIEC while progressing through the planning, analysis, design, and implementation phases to achieve quality and flexibility in its information supply chain.

  10. HLA in bone marrow transplantation

    It has been well understood that human major histocompatibility antigen system, HLA is the most important role in the allo transplantation. Therefore, the structure of HLA genes was presented by the recent information (1987). Moreover, their functions in vitro and in vivo also were described. Finally, bone marrow transplantation and HLA network system in Japan against HLA mismatched case was proposed. It is eagerly expected that functional and clinical bone marrow transplantation in Japan could be succeeded. (author)

  11. Integrated Mission Simulation (IMSim): Multiphase Initialization Design with Late Joiners, Rejoiners and Federation Save & Restore

    Dexter, Daniel E.; Varesic, Tony E.


    This document describes the design of the Integrated Mission Simulation (IMSim) federate multiphase initialization process. The main goal of multiphase initialization is to allow for data interdependencies during the federate initialization process. IMSim uses the High Level Architecture (HLA) IEEE 1516 [1] to provide the communication and coordination between the distributed parts of the simulation. They are implemented using the Runtime Infrastructure (RTI) from Pitch Technologies AB. This document assumes a basic understanding of IEEE 1516 HLA, and C++ programming. In addition, there are several subtle points in working with IEEE 1516 and the Pitch RTI that need to be understood, which are covered in Appendix A. Please note the C++ code samples shown in this document are for the IEEE 1516-2000 standard.

  12. Federation Agreements - Observations, Considerations and Proposals out of the NATO MSG-052 Working Group - Knowledge Network for Federation Architecture and Design

    Huiskamp, W.; Loper, M.; Cutts, D.E.


    Designing and managing distributed simulation systems is a complex process requiring extensive experience, in-depth knowledge, and unique skills to construct a federation which meets a myriad of operational, functional and technical requirements. Unfortunately, the practical knowledge gained in the

  13. Polymorphism of HLA-A and HLA-B in pre-eclampsia%HLA-A和HLA-B的多态性与先兆子痫

    张展; 贾莉婷; 张琳琳


    Objective: To investigate the association between the polymorphism of HLA-A, HLA-B genes and pre-eclampsia. Methods: HLA-A, HLA-B genotyping was performed by polymerase chain reaction sequence-specific primer (PCR-SSP) in 119 preeclampsia patients, 117 normal pregnant women and their neonates. Results: The study showed that 16 HLA-A and 39 HLA-B alleles were obtained in pre-eclamptic patients and normal pregnant women. 15 HLA-A and 37 HLA-B alleles were obtained in their neonates. No significant difference was found in maternal or neonatal HLA-A, HLA-B alleles be-tween pre-eclampsia group and control group (Pc>0. 05). The frequencies of HLA-A11, HLA-A24,HLA-B13, HLA-B14, HLA-B15, HLA-B52 maternal/fetus genetic assoications were significantly different between pre-eclampsia group and control group (P<0. 05). Conclusion: Some HLA-A, HLA-B maternal/fetus special bindings may be associated with the susceptibility or protective of pre-eclampsia.

  14. HLA-B27 antigen

    ... colitis Psoriatic arthritis (arthritis associated with psoriasis) Reactive arthritis Sacroiliitis (inflammation of the sacroiliac joint) Uveitis If there are symptoms or signs of an autoimmune disease, a positive HLA-B27 test may confirm the diagnosis. However, HLA-B27 ...

  15. Predicted Indirectly Recognizable HLA Epitopes Presented by HLA-DRB1 Are Related to HLA Antibody Formation During Pregnancy

    Geneugelijk, K; Hönger, G; van Deutekom, H W M; Thus, K A; Kesmir, C.; Hösli, I; Schaub, S; Spierings, E


    Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes pres

  16. Predicted indirectly recognizable HLA epitopes presented by HLA-DRB1 are related to HLA antibody formation during pregnancy

    Geneugelijk, K.; Hönger, G.; Van Deutekom, H. W M; Thus, K. A.; Keşmir, C.; Hösli, I.; Schaub, S.; Spierings, E.


    Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes pres

  17. 基于HLA的高炮营作战仿真系统%Simulation system of A-A gun battalion based on HLA

    刘云龙; 卢昱; 陈立云; 孔德金


    根据防空作战的特点、要求以及高炮营的构成,设计开发了基于高层体系结构(HLA)的高炮营作战仿真系统.分析了HLA的意义,对基于VR-Link的HLA系统相比其他HLA系统的改进方面和不同点进行了说明.介绍了所开发系统的体系结构,并对联邦成员的组成、实现功能进行了阐述与分析.采用VC7以及MAK公司的RTI,VR-Link,VR-Forces和Stealth实现各联邦成员的功能,最后给出了视景仿真成员的效果.从实际使用来看,仿真程序运行良好,画面流畅,仿真结果比较接近真实作战.%According to the characteristics and requirements of air defense warfare and the constitution of A-A(anti-air) gun battalion, a simulation system of A-A gun battalion based on High Level Architecture(HLA) is developed. This paper analyses the significance of HLA in the development of simulation system, and gives a brief introduction on the improvements and differences of HLA system based on VR-Link compared with others. It also introduces the structure of the simulation system, and implements the federate with VC7, MAK RTI,VR-Link,VR-Forees and Stealth. The effects of VR simulation federate is given. The result shows that the system is reasonable and reliable, which approaches to the true process of warfare.

  18. HLA antigens in chronic inflammatory demyelinating polyneuropathy.

    Feeney, D J; Pollard, J D; McLeod, J G; Stewart, G. J.; Doran, T J


    HLA typing of 71 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) showed an overall increase in frequencies of HLA-A3, -B7, -DR2 as well as concomitantly decreased frequencies of HLA-44 and DR7. The strongest associations were seen with HLA-DR2, -DR7 and -B44 in CIDP overall, although they did not reach statistical significance.

  19. A novel load balancing method for hierarchical federation simulation system

    Bin, Xiao; Xiao, Tian-yuan


    In contrast with single HLA federation framework, hierarchical federation framework can improve the performance of large-scale simulation system in a certain degree by distributing load on several RTI. However, in hierarchical federation framework, RTI is still the center of message exchange of federation, and it is still the bottleneck of performance of federation, the data explosion in a large-scale HLA federation may cause overload on RTI, It may suffer HLA federation performance reduction or even fatal error. Towards this problem, this paper proposes a load balancing method for hierarchical federation simulation system based on queuing theory, which is comprised of three main module: queue length predicting, load controlling policy, and controller. The method promotes the usage of resources of federate nodes, and improves the performance of HLA simulation system with balancing load on RTIG and federates. Finally, the experiment results are presented to demonstrate the efficient control of the method.

  20. Integrated Battlefield Environment Simulation Based on Multi-Agent and HLA%基于Multi-Agent和HLA的综合战场环境仿真

    苏春梅; 奚宏明; 王玮; 茅文浩


    针对综合战场环境仿真系统在仿真实现中存在的不足,提出将基于多Agent(multi-agent)的复杂系统建模思想和基于高层体系结构(high level architecture,HLA)的仿真技术结合起来的思路.首先用基于多Agent的思想对综合战场环境仿真系统进行分解建模,然后采用基于HLA的分布式仿真技术来实现仿真系统.结果表明,该技术既能降低仿真系统模型的复杂度,又能使仿真成员具有一定的智能性.%Aiming at the shortcomings from the implementation of the integrated battlefield environment simulation system in the simulation, the ideas of combining the modeling methods of complex systems based on Multi-Agent and technologies of distributed interactive simulation based on HLA. Firstly, the methods based on Multi-Agent is used to design the inner models of the integrated battlefield environment simulation system, and then the technologies of distributed interactive simulation based on HLA is used to implement the simulating system, the result indicates that it reduces the complexity of system modeling and provides the federations with intelligence.

  1. Federated Aggregate Cohort Estimator (FACE): an easy to deploy, vendor neutral, multi-institutional cohort query architecture.

    Wyatt, Matthew C; Hendrickson, R Curtis; Ames, Michael; Bondy, Jessica; Ranauro, Paul; English, Thomas M; Bobitt, Keith; Davidson, Arthur; Houston, Thomas K; Embi, Peter J; Berner, Eta S


    Cross-institutional data sharing for cohort discovery is critical to enabling future research. While particularly useful in rare diseases, the ability to target enrollment and to determine if an institution has a sufficient number of patients is valuable in all research, particularly in the initiation of projects and collaborations. An optimal technology solution would work with any source database with minimal resource investment for deployment and would meet all necessary security and confidentiality requirements of participating organizations. We describe a platform-neutral reference implementation to meet these requirements: the Federated Aggregate Cohort Estimator (FACE). FACE was developed and implemented through a collaboration of The University of Alabama at Birmingham (UAB), The Ohio State University (OSU), the University of Massachusetts Medical School (UMMS), and the Denver Health and Hospital Authority (DHHA) a clinical affiliate of the Colorado Clinical and Translational Sciences Institute. The reference implementation of FACE federated diverse SQL data sources and an i2b2 instance to estimate combined research subject availability from three institutions. It used easily-deployed virtual machines and addressed privacy and security concerns for data sharing. PMID:24316052

  2. Sourcing the megalithic stones of Nan Madol : an XRF study of architectural basalt stone from Pohnpei, Federated States of Micronesia

    Nan Madol is a massive 81 hectare prehistoric administrative and ceremonial complex made up of 93 constructed islets on the high volcanic island of Pohnpei. Built between Ad 900 and 1650 over earlier settlement remains along the southern coast of Temwen Island within the fringing reef, the site is noted for its distinctive use of columnar basalt and large boulders. XRF analysis presented here suggests the site's builders favoured columnar basalt from the island's main shield building stage (7-8 mya) over post-shield material. Boulders incorporated in the architecture are primarily from post-shield stage Temwen Island but supplemented by some main shield boulders from mainland Pohnpei. Preliminary findings further suggest that there were shifts in the relative frequency of quarries used to construct different structures. These shifts could relate to exhaustion of accessible stone from specific sources or perhaps changing preferences for stone from different sources due to social or political imperatives. (author). 23 refs., 6 figs., 4 tabs.

  3. 基于HLA的导弹仿真系统%Missile simulation system based on HLA

    王利; 赵振南; 张亮


    计算机仿真是解决导弹装备研发过程中遇到难题的有效方法.设计了基于高层体系结构(HLA)分布式协议的仿真框架,给出了搭建系统的实施方案,具体介绍了系统联邦成员的构成及功能,分析设计了主要联邦成员的对象类和交互类,最后给出了整个系统的仿真流程及主要代码实现.该系统是一个模块化、通用化、易扩展、形象直观的导弹仿真系统,可以进行多种想定条件下导弹飞行仿真和性能评估,为导弹装备的论证、定型、验证提供了支撑平台.%The computer simulation is an effective way to solve the missile R&D process problems encountered.The article designs the simulation framework based on High Level Architecture (HLA),gives out the build system solutions,introduces the structure and function of the system of the federal member,analyzes and designs the main federal members of the object class and interaction class,finally present the simulation process and code implementation of the entire system.The system is a modular,extensible,general-purpose,image intuitive missile simulation system,can do many kinds of scenario conditions missile flight simulation and performance evaluation for missile equipment,provides support platform for missile equipment demonstration,qualitative and verify.

  4. Classification of human leukocyte antigen (HLA) supertypes

    Wang, Mingjun; Claesson, Mogens H


    Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However, the...... barrier to the development of peptide-based vaccines with maximum population coverage is that the restricting HLA genes are extremely polymorphic resulting in a vast diversity of peptide-binding HLA specificities and a low population coverage for any given peptide-HLA specificity. One way to reduce this...... complexity is to group thousands of different HLA molecules into several so-called HLA supertypes: a classification that refers to a group of HLA alleles with largely overlapping peptide binding specificities. In this chapter, we focus on the state-of-the-art classification of HLA supertypes including HLA...

  5. The integration of engineering and architecture: A perspective on natural ventilation for the new San Francisco Federal Building

    A description of the in-progress design of a new Federal Office Building for San Francisco is used to illustrate a number of issues arising in the design of large, naturally ventilated office buildings. These issues include the need for an integrated approach to design involving the architects, mechanical and structural engineers, lighting designers and specialist simulation modelers. In particular, the use of natural ventilation, and the avoidance of air-conditioning, depends on the high degree of exposed thermal mass made possible by the structural scheme and by the minimization of solar heat gains while maintaining the good daylighting that results from optimization of the facade. Another issue was the need for a radical change in interior space planning in order to enhance the natural ventilation; all the individual enclosed offices are located along the central spine of each floorplate rather than at the perimeter. The role of integration in deterring the undermining of the design through value engineering is discussed. The comfort criteria for the building were established based on the recent extension to the ASHRAE comfort standard based on the adaptive model for naturally ventilated buildings. The building energy simulation program EnergyPlus was used to compare the performance of different natural ventilation strategies. The results indicate that, in the San Francisco climate, wind-driven ventilation provides sufficient nocturnal cooling to maintain comfortable conditions and that external chimneys do not provide significant additional ventilation at times when it when it would be beneficial

  6. Research advances of HLA-F%HLA-F研究进展

    徐丹萍; 林爱芬; 颜卫华


    人类白细胞抗原(human leucocyte antigen,HLA)复合体是人体中基因多态性最高的基因复合体,其多态性与疾病遗传易感性显著相关.人类白细胞抗原-F (human leucocyte antigen-F,HLA-F)属于非经典HLAI类分子中的一员,与HLA-E、-G在结构上十分相似,具有有限的多态性.近年来多数学者聚焦于HLA-F基因转录及分子表达调控、HLA-F表达与临床相关性及HLA-F抗体研制,且取得了重要成果.就HLA-F的研究进展作一综述.%Human leukocyte antigen complex with the highest gene polymorphisms in human, is significantly associated with genetic susceptibility to diseases. Human leukocyte antigen-F belongs to the non-classical HLA I molecules. HLA-F, HLA-E and HLA-G have a similar structure and a limited polymorphism. In recent years, transcription regulation of HLA-F, expression regulation of HLA-F in cell surface, clinical relevance of HLA-F and the preparation of anti-HLA-F, are widely studied and have achieved important results. In the present review, the research advances on HLA-F are discussed.

  7. Interconnexion de simulations distribuées HLA

    Bréholée, Benoît


    Cette thèse s’inscrit dans le contexte de HLA, une architecture de simulation distribuée dont l'objectif est de permettre l'interopérabilité et la réutilisation d’applications de simulation. L'ONERA a développé une plate-forme de simulation distribuée compatible HLA (appelée CERTI). L'objectif de cette thèse est d'étendre le travail entrepris sur CERTI en se basant sur l'introduction de la notion classique de domaine. Nous étudions différentes techniques impliquant cette notion et dont les ob...

  8. Influence of HLA-A, HLA-B, and HLA-DR matching on rejection of random corneal grafts using corneal tissue for retrospective DNA HLA typing

    M.C. Bartels (Marjolijn); H.G. Otten; B.E. van Gelderen; A. van der Lelij (Allegonda)


    textabstractAIM: To establish if coincidental HLA-A, HLA-B, and HLA-DR tissue matching is associated with a reduced likelihood of corneal graft rejection. METHODS: Organ culture preserved random donor corneas were used for penetrating keratoplasty (PKP). Corneal tissue from all gra

  9. Idiopathic focal segmental glomerulosclerosis and HLA antigens

    M. Gerbase-DeLima


    Full Text Available The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS. HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P<0.05. In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease

  10. The HLA-DRA*0102 allele: correct nucleotide sequence and associated HLA haplotypes.

    Kralovicova, J; Marsh, S G E; Waller, M J; Hammarstrom, L; Vorechovsky, I


    Here we correct the nucleotide sequence of a single known variant of the HLA-DRA gene. We show that the coding regions of the HLA-DRA*0101 and HLA-DRA*0102 alleles do not differ at two codons as reported previously, but only in codon 217. Using nucleotide sequencing and DNA samples from individuals homozygous in the major histocompatibility complex, we found that the variant, leucine 217-encoding HLA-DRA*0102 allele was present on the haplotypes HLA-B*0801, DRB1*03011, DQB1*0201 (ancestral haplotype AH8.1), HLA-B*07021, DRB1*15011, DQB1*0602 (AH7.1), HLA-B*1501, DRB1*15011, DQB1*0602, HLA-B*1501, DRB1*1402, DQB1*03011 and HLA-A3, B*07021, DRB1*1301, DQB1*0603. The HLA-DRA*0101 allele coding for valine 217 was observed on the haplotypes HLA-B*5701, DRB1*0701, DQB1*03032 (AH57.1), HLA-DRB1*04011, DQB1*0302, HLA-DRB1*0701, DQB1*0202, and HLA-DRB1*0101, DQB1*05011. PMID:12445311

  11. HLA typing in systemic sclerosis

    M. Faré


    Full Text Available Objective: the aim of the study was to investigate the relationship between Systemic Sclerosis (SSc and HLA antigens, and to correlate these antigens with the clinical manifestations of the disease. Materials and methods: 55 patients were stratified according a to the cutaneous involvement b to the positivity of Scl- 70 and anticentromere antibody and c to the internal organ involvement, in particular we used HRCT to demonstrate lung fibrosis, echocardiography for the diagnosis of pulmonary hypertension, blood creatinine, urinalysis and arterial hypertension to demonstrate renal failure, and esophagus double-countrast barium swallow for the diagnosis of esophagopathy. The control group consisting of 2000 healthy Caucasian subjects was recruited from the same population. Results: the frequency of the antigens A23 (p=0.003, RR=3.69, B18 (p<0.0001, RR=3.57, and DR11 (p<0.0001, RR=6.18 was statistically increased in the patients population compared with the healthy controls. Although there is no any significant correlation between HLA antigens and different clinical subsets of scleroderma, antigens B18 and DR11 could be associated with more severe clinical features. Conclusions: the presence of a significant association between SSc and specific HLA antigens (A23, B18, and DR11 could link the HLA system with SSc.

  12. HLA-DP, HLA-DQ, and HLA-DR-restricted epitopes in GRA5 of toxoplasma gondii strains

    Haryati, S.; Sari, Y.; APrasetyo, A.; Sariyatun, R.


    The dense granular (GRA) proteins of Toxoplasma gondii(T. gondii) have been demonstrated as potential sources of T. gondii vaccine antigens. However, data of the GRA5 protein are limited. This study analyzed twenty-one complete GRA5 sequences of T. gondii GT1, RH, ME49, VEG, MAS, RUB, FOU, p89, VAND, and GAB2-2007-GAL-DOM2 strains to identify potential epitopes restricted by Major Histocompatibility Complex class II (MHC- II) molecules (human leukocyte antigen (HLA)-DP, HLA-DQ, and HLA-DR) in the protein. In all T. gondii strains, peptides positioned at amino acid (aa) 15-29, 16-30, 17-31, 18-32, 19-33, 83-97, 84-98, 86-100, 87-101, 89-103, and 90-104 were predicted to pose high affinity and binding with HLA-DRB1*0101, HLA-DRB1*0301 (DR17), HLA-DRB1*0401 (DR4Dw4), HLA-DRB1*0701, HLA-DRB1*1101, HLA-DRB1*1501 (DR2b), and/or HLA-DRB5*0101. Considering the epitope's affinity, ligation strength, and hydrophilicity, LRLLRRRRRRAIQEE sequence (aa 90-104) restricted by HLA-DRB1*0101, HlA- DRB1*0301 (DR17), and HLA-DRB1*0401 (DR4Dw4) was considered as the most potential MHC-II epitope in GRA5 of T. gondii. These results would be useful for studies concerning in developing T. gondii vaccine and diagnostic method.

  13. Software Architecture: Architecture Constraints

    Tibermacine, Chouki


    International audience In this chapter, we introduce an additional, yet essential, concept in describing software architectures : architecture constraints. We explain the precise role of these entities and their importance in object-oriented, component-based or service-oriented software engi-neering. We then describe the way in which they are specified and interpreted. An architect can define architecture constraints and then associate them to architectural descriptions to limit their stru...

  14. Architecture on Architecture

    Olesen, Karen


    how recognising the autonomy of architecture, not as an esoteric concept but as a valid source of information in a pragmatic design practice, may help us overcome the often-proclaimed dichotomy between formal autonomy and a societally committed architecture. It follows that in architectural education...

  15. Multi-population classical HLA type imputation.

    Alexander Dilthey

    Full Text Available Statistical imputation of classical HLA alleles in case-control studies has become established as a valuable tool for identifying and fine-mapping signals of disease association in the MHC. Imputation into diverse populations has, however, remained challenging, mainly because of the additional haplotypic heterogeneity introduced by combining reference panels of different sources. We present an HLA type imputation model, HLA*IMP:02, designed to operate on a multi-population reference panel. HLA*IMP:02 is based on a graphical representation of haplotype structure. We present a probabilistic algorithm to build such models for the HLA region, accommodating genotyping error, haplotypic heterogeneity and the need for maximum accuracy at the HLA loci, generalizing the work of Browning and Browning (2007 and Ron et al. (1998. HLA*IMP:02 achieves an average 4-digit imputation accuracy on diverse European panels of 97% (call rate 97%. On non-European samples, 2-digit performance is over 90% for most loci and ethnicities where data available. HLA*IMP:02 supports imputation of HLA-DPB1 and HLA-DRB3-5, is highly tolerant of missing data in the imputation panel and works on standard genotype data from popular genotyping chips. It is publicly available in source code and as a user-friendly web service framework.

  16. Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

    Romanos, Jihane; Rosén, Anna; Kumar, Vinod; Trynka, Gosia; Franke, Lude; Szperl, Agata; Gutierrez-Achury, Javier; van Diemen, Cleo C; Kanninga, Roan; Jankipersadsing, Soesma A; Steck, Andrea; Eisenbarth, Georges; van Heel, David A; Cukrowska, Bozena; Bruno, Valentina; Mazzilli, Maria Cristina; Núñez, Concepcion; Bilbao, Jose Ramon; Mearin, M Luisa; Barisani, Donatella; Rewers, Marian; Norris, Jill M; Ivarsson, Anneli; Boezen, H Marieke; Liu, Edwin; Wijmenga, Cisca


    Background The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective We explored whether CD risk prediction can be improved by adding non-HLA-susceptible variants to common HLA testing. Design We developed an average weighted genetic risk score with 10, 26 and 57 single nucleotide polymorphisms (SNP) in 2675 cases and 2815 controls and assessed the improvement in risk prediction provided by the non-HLA SNP. Moreover, we assessed the transferability of the genetic risk model with 26 non-HLA variants to a nested case–control population (n=1709) and a prospective cohort (n=1245) and then tested how well this model predicted CD outcome for 985 independent individuals. Results Adding 57 non-HLA variants to HLA testing showed a statistically significant improvement compared to scores from models based on HLA only, HLA plus 10 SNP and HLA plus 26 SNP. With 57 non-HLA variants, the area under the receiver operator characteristic curve reached 0.854 compared to 0.823 for HLA only, and 11.1% of individuals were reclassified to a more accurate risk group. We show that the risk model with HLA plus 26 SNP is useful in independent populations. Conclusions Predicting risk with 57 additional non-HLA variants improved the identification of potential CD patients. This demonstrates a possible role for combined HLA and non-HLA genetic testing in diagnostic work for CD. PMID:23704318

  17. The IMGT/HLA sequence database.

    Robinson, J; Marsh, S G


    The IMGT/HLA database ( specialises in sequences of the polymorphic genes of the HLA system, the humanmajor histocompatibility complex (MHC). This complex is located within the 6p213 region on the short arm of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and these include the 21 highly polymorphic HLA genes, which influence the outcome of clinical transplantation and confer susceptibility to a wide range of non-infectious diseases. The database contains sequences for all HLA alleles officially recognised by the WHO Nomenclature Committee for Factors of the HLA System and provides users with online tools and facilities for their retrieval and analysis. These include allele reports, alignment tools, and detailed descriptions of the source cells. The online submission tool allows both new and confirmatory sequences to be submitted directly to the WHO Nomenclature Committee. The latest version (release 1.10.0 April 2001) contains 1329 HLA alleles, 61 HLA related sequences, derived from around 3350 component sequences from the EMBL/ GenBank/DDBJ databases. The IMGT/HLA database provides a model that will be extended to provide specialist databases for polymorphic MHC genes of other species. PMID:12361093

  18. Complement activation and HLA-B27.

    Meri, S.; Partanen, J; Leirisalo-Repo, M; Repo, H


    The efficiency of complement activation was studied in sera from HLA-B27 positive and negative subjects (27 with previous yersinia arthritis and 35 controls). Activation of complement with zymosan induced higher mean levels of the anaphylatoxin C3a in HLA-B27 positive sera (mean (SD) 7.40 (1.66) mg/l) than in HLA-B27 negative sera (6.41 (1.79) mg/l). Similarly, higher levels of C3d,g, another C3 breakdown fragment, were obtained in HLA-B27 positive sera after Escherichia coli 0111:B4 lipopoly...

  19. Derivation of HLA types from shotgun sequence datasets

    Warren, Rene; Choe, Gina; Freeman, Douglas; Castellarin, Mauro; Munro, Sarah; Moore, Richard; Holt, Robert


    The human leukocyte antigen (HLA) is key to many aspects of human physiology and medicine. All current sequence-based HLA typing methodologies are targeted approaches requiring the amplification of specific HLA gene segments. Whole genome, exome and transcriptome shotgun sequencing can generate prodigious data but due to the complexity of HLA loci these data have not been immediately informative regarding HLA genotype. We describe HLAminer, a computational method for identifying HLA alleles d...

  20. Architecture on Architecture

    Olesen, Karen


    This paper will discuss the challenges faced by architectural education today. It takes as its starting point the double commitment of any school of architecture: on the one hand the task of preserving the particular knowledge that belongs to the discipline of architecture, and on the other hand...... the obligation to prepare students to perform in a profession that is largely defined by forces outside that discipline. It will be proposed that the autonomy of architecture can be understood as a unique kind of information: as architecture’s self-reliance or knowledge-about itself. A knowledge that...... is not scientific or academic but is more like a latent body of data that we find embedded in existing works of architecture. This information, it is argued, is not limited by the historical context of the work. It can be thought of as a virtual capacity – a reservoir of spatial configurations that...

  1. HLA-G polymorphisms and HLA-G expression in sarcoidosis

    Hviid, TVF; Milman, N; Hylenius, S;


    BACKGROUND: The MHC class Ib molecule Human Leukocyte Antigen (HLA)-G may be important in induction and maintenance of immunological tolerance, and HLA-G expression may have a role in different cancers, in certain diseases with associations to HLA, and in organ transplantation. Sarcoidosis is a...... systemic granulomatous disease with unknown etiology but at the molecular level several studies have shown HLA associations. METHODS: In the present study, HLA-G alleles/polymorphisms were studied in sarcoidosis patients (n = 47) and controls (n = 129) by PCR techniques and HLA-G protein expression was...... investigated in granulomas from sarcoidosis patients with the use of immunohistochemistry. RESULTS: The HLA-G*010102/-G*0106 alleles were observed more often in sarcoidosis patients (39.4%) than in controls (26.4%), p = 0.025 (Fisher's exact test); however, not significant after correction (p(c) = 0.15). When...

  2. Digital Earth Watch (DEW): How Mobile Apps Are Paving The Way Towards A Federated Web-Services Architecture For Citizen Science

    Carrera, F.; Schloss, A. L.; Guerin, S.; Beaudry, J.; Pickle, J.


    interacts with the UNH server via APIs (Application Programming Interfaces) that were created to allow bi-directional machine-to-machine interaction between the mobile device and the web site. Thus, the principal functions that a user can perform on the web site, such as finding post sites on a map and viewing and adding picture sets, are available on the smartphone. The development of the APIs makes it now possible not only to communicate with our own mobile app, but, more importantly, it opens the door for other computer systems to directly interact with our server. Our ongoing discussions with the National Phenology Network and Project Budburst, have highlighted the potential (and perhaps the need) for the creation of a distributed web-service architecture whereby each national program exposes its key functionalities not only to their own mobile phone apps, but also to other organizations, in a federated system of servers, all supporting citizen-based digital earth watch programs.

  3. Class II HLA interactions modulate genetic risk for multiple sclerosis

    Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H;


    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17......,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles...... (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01-HLA-DRB1*15:01 and HLA-DQB1*03:01-HLA...

  4. HLA typing in acute optic neuritis

    Frederiksen, J L; Madsen, H O; Ryder, L P;


    frequency of HLA-DR15 was significantly increased in patients with ON + CDMS (52%) and ON (47%) compared with control subjects (31%). The frequency of HLA-DR17 was almost equal in the ON + CDMS (18%), ON (23%), and control (23%) groups. The frequencies of HLA-DQA-1B (55% in ON + CDMS, 58% in ON) and HLA......-DQB-1B (49% in ON + CDMS, 59% in ON) were significantly increased compared with control subjects (41%, HLA-DQA-1B; 37%, HLA-DQB-1B). Brain MRI was abnormal in 48 of 56 examined patients with ON + CDMS and in 64 of 120 examined patients with ON (P < .001). In contrast, the frequencies of HLA alleles did...... not differ between patients with and without demyelinating lesions. However, patients with ON and normal MRI findings did not show association with HLA-DR15. CONCLUSIONS: The frequencies of alleles were similar in patients with ON and ON + CDMS, confirming that they are not 2 immunogenetically...

  5. 麻风病与HLA-A、HLA-B、HLA-DRB1、HLA-DQ等位基因关联性分析%Analysis of the association of HLA-A, HLA-B, HLA-DRB1, HLA-DQ alleles with leprosy

    赵宝泉; 俞宙; 杨菲; 蔡志坚; 周迎; 于德宝; 李娟; 王建莉; 渠鹏程


    目的 探讨中国山东人群HLA-A、HLA-B、HLA-DRB1、HLA-DQ等位基因与麻风病的相关性.方法 采用序列特异性引物聚合酶链反应法(PCR-SSP)对40例麻风病患者及20例健康对照者进行HLA-A、B、DRB1、DQ等位基因分型,x2检验基因频率差异.结果 麻风病患者HLA-B*13(x2=7.067,P=0.008)、DQ*02(x2 =4.156,P=0.041)基因频率较健康对照组低,有统计学意义(P<0.05).LL型麻风患者HLA-B* 13(x2=7.159,P=0.007)等位基因频率降低、HLA-DRB1*15(x2=4.073,P=0.044)等位基因频率升高,与健康对照组相比均具有统计学意义(P<0.05).TT型麻风病患者HLA-B *40(P =0.037)、DQ *05(x2 =5.147,P=0.023)等位基因频率高于健康对照组,差异具有统计学意义(P<0.05).结论 HLA-B * 13、DQ*02基因可能对麻风病易感性有拮抗作用,可能是保护基因;HLA-B* 13可能是LL型拮抗基因、DRB1*15可能是LL型的易感基因;HLA-B* 40、DQ *05可能是TT型的易感基因.%Objective To explore the association of HLA-A,HLA-B,HLA-DRB1,HLA-DQ alleles with leprosy in population of Jinan.Methods PCR-SSP was used to analyse the type of HLA-A,HLA-B,HLA-DRB1 and HLA-DQ alleles in 40 patients with leprosy and 20 healthy controls.SPSS 11.5 software package was used to analyze the data.Results The allele frequencies of HLA-B * 13 (x2 =7.067,P =0.008)and DQ * 02 (x2 =4.156,P =0.041 ) were lower in leprosy patients than those in healthy controls( P < 0.05 ).The allele frequencies of HLA-B * 13 (x2 =7.159,P =0.007 )was lower than that in controls and the frequencies of HLA- DRB 1 * 15 (x2 =4.073,P =0.044) was higher in LL leprosy patients ( P < 0.05 ).The allele frequencies of HLA-B * 40 ( P =0.037 ) and DQ * 05 (x2 =5.147,P =0.023 ) were higher in TT leprosy patients (P<0.05).Conclusion HLA-B * 13 and DQ *02 possibly play protective roles in leprosy patients.B * 13 has also protective roles and DRB1 * 15 was a susceptibility gene in LL leprosy patients.B *40,DQ *05 may be

  6. Complementarity of Binding Motifs is a General Property of HLA-A and HLA-B Molecules and Does Not Seem to Effect HLA Haplotype Composition.

    Rao, Xiangyu; De Boer, Rob J; van Baarle, Debbie; Maiers, Martin; Kesmir, Can


    Different human leukocyte antigen (HLA) haplotypes (i.e., the specific combinations of HLA-A, -B, -DR alleles inherited together from one parent) are observed in different frequencies in human populations. Some haplotypes, like HLA-A1-B8, are very frequent, reaching up to 10% in the Caucasian population, while others are very rare. Numerous studies have identified associations between HLA haplotypes and diseases, and differences in haplotype frequencies can in part be explained by these associations: the stronger the association with a severe (autoimmune) disease, the lower the expected HLA haplotype frequency. The peptide repertoires of the HLA molecules composing a haplotype can also influence the frequency of a haplotype. For example, it would seem advantageous to have HLA molecules with non-overlapping binding specificities within a haplotype, as individuals expressing such an haplotype would present a diverse set of peptides from viruses and pathogenic bacteria on the cell surface. To test this hypothesis, we collect the proteome data from a set of common viruses, and estimate the total ligand repertoire of HLA class I haplotypes (HLA-A-B) using in silico predictions. We compare the size of these repertoires to the HLA haplotype frequencies reported in the National Marrow Donor Program (NMDP). We find that in most HLA-A and HLA-B pairs have fairly distinct binding motifs, and that the observed haplotypes do not contain HLA-A and -B molecules with more distinct binding motifs than random HLA-A and HLA-B pairs. In addition, the population frequency of a haplotype is not correlated to the distinctness of its HLA-A and HLA-B peptide binding motifs. These results suggest that there is a not a strong selection pressure on the haplotype level favoring haplotypes having HLA molecules with distinct binding motifs, which would result the largest possible presented peptide repertoires in the context of infectious diseases. PMID:24294213

  7. Human thymic epithelial cells express functional HLA-DP molecules

    Jørgensen, A; Röpke, C; Nielsen, M;


    HLA-DP molecules function as restriction elements in the presentation of foreign antigens to T cells by antigen presenting cells and certain HLA-DP molecules confer susceptibility to autoimmune disease. Because HLA molecules play an essential role in thymic selection and elimination of autoreactive...... T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DQ but lower than that of HLA-DR. Upon IFN-gamma treatment, HLA-DP expression was strongly upregulated. Since HLA-DQ and DR expression was upregulated in parallel, the hierarchy between MHC class II isotypes remained unchanged following interferon treatment. TEC elicited significant...

  8. HLA diversity in the 1000 genomes dataset.

    Pierre-Antoine Gourraud

    Full Text Available The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation by sequencing at a level that should allow the genome-wide detection of most variants with frequencies as low as 1%. However, in the major histocompatibility complex (MHC, only the top 10 most frequent haplotypes are in the 1% frequency range whereas thousands of haplotypes are present at lower frequencies. Given the limitation of both the coverage and the read length of the sequences generated by the 1000 Genomes Project, the highly variable positions that define HLA alleles may be difficult to identify. We used classical Sanger sequencing techniques to type the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genes in the available 1000 Genomes samples and combined the results with the 103,310 variants in the MHC region genotyped by the 1000 Genomes Project. Using pairwise identity-by-descent distances between individuals and principal component analysis, we established the relationship between ancestry and genetic diversity in the MHC region. As expected, both the MHC variants and the HLA phenotype can identify the major ancestry lineage, informed mainly by the most frequent HLA haplotypes. To some extent, regions of the genome with similar genetic or similar recombination rate have similar properties. An MHC-centric analysis underlines departures between the ancestral background of the MHC and the genome-wide picture. Our analysis of linkage disequilibrium (LD decay in these samples suggests that overestimation of pairwise LD occurs due to a limited sampling of the MHC diversity. This collection of HLA-specific MHC variants, available on the dbMHC portal, is a valuable resource for future analyses of the role of MHC in population and disease studies.

  9. Nomenclature for factors of the HLA system, 1980*


    This article outlines the decisions made by the WHO nomenclature committee on leukocyte antigens at a meeting held after the 8th International Workshop on Histocompatibility Testing. Particular attention is given to new designations for provisional HLA-B and HLA-DR specificities and the upgrading of certain HLA-D and HLA-DR specificities to full HLA status. The existence of supertypic cross-reacting specificities was confirmed and extended.

  10. The peptide-binding specificity of HLA-A*3001 demonstrates membership of the HLA-A3 supertype

    Lamberth, K; Røder, G; Harndahl, M;


    Human leukocyte antigen class I (HLA-I) molecules are highly polymorphic peptide receptors, which select and present endogenously derived peptide epitopes to CD8+ cytotoxic T cells (CTL). The specificity of the HLA-I system is an important component of the overall specificity of the CTL immune...... system. Unfortunately, the large and rapidly increasing number of known HLA-I molecules seriously complicates a comprehensive analysis of the specificities of the entire HLA-I system (as of June 2008, the international HLA registry holds >1,650 unique HLA-I protein entries). In an attempt to reduce this...... complexity, it has been suggested to cluster the different HLA-I molecules into "supertypes" of largely overlapping peptide-binding specificities. Obviously, the HLA supertype concept is only valuable if membership can be assigned with reasonable accuracy. The supertype assignment of HLA-A*3001, a common HLA...

  11. Identification of a new HLA-G allele, HLA-G*01:19, by cloning and phasing.

    Wang, W Y; Tian, W


    A new HLA-G allelic variant, HLA-G*01:19, was identified in a southern Chinese Han population by polymerase chain reaction-sequence-based typing (PCR-SBT), cloning and phasing. HLA-G*01:19 differs from HLA-G*01:04:01 by a nonsynonymous cytosine at position 99 in exon 2, resulting in amino acid change from valine to leucine at codon 34 of the mature HLA-G molecule. PMID:27277539

  12. Service orientation for the design of HLA federations

    Cramp, A.J.; Berg, T.W. van den; Huiskamp, W.


    Service oriented modeling and simulation (M&S) is being pursued by many nations and organizations. Approaches being taken span from the provision of M&S tools and applications via -as-a-Service cloud computing technologies to the actual construction of M&S via service oriented techniques. Often thes

  13. Seronegative pauciarticular arthritis and HLA B27.

    Eastmond, C J; Rajah, S M; D. Tovey; Wright, V.


    Twenty-six patients with a pauciarticular arthritis have been studied clinically, radiologically and with histocompatibility typing. An increased frequency of HLA B27 was found (p = 1.87 x 10(-12)). Low back and buttock pain, Achilles tendinitis and dactylitis of the toes were more frequent in HLA-B27 positive patients. It is suggested that histocompatibility testing may be of some value in diagnosis and in the investigation of the possible 'reactive' nature of this type of arthritis.

  14. Architectural Slicing

    Christensen, Henrik Bærbak; Hansen, Klaus Marius


    Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context of...... architectural prototyping since experiments with full systems are complex and expensive and thus architectural learn- ing is hindered. In this paper, we propose a novel technique for harvest- ing architectural prototypes from existing systems, \\architectural slic- ing", based on dynamic program slicing. Given a...... system and a slicing criterion, architectural slicing produces an architectural prototype that contain the elements in the architecture that are dependent on the ele- ments in the slicing criterion. Furthermore, we present an initial design and implementation of an architectural slicer for Java....

  15. HLA-E expression in cervical adenocarcinomas: association with improved long-term survival

    Spaans Vivian M


    Full Text Available Abstract Background Cervical cancer is the third most common cancer in women worldwide. The most common histopathological subtype is cervical squamous cell carcinoma (SCC, 75-80%, followed by adenocarcinoma (AC and adenosquamous carcinoma (ASC; together 15-20%. Rising incidence rates of AC have been observed relative and absolute to SCC and evidence is accumulating that cervical AC is a distinct clinical entity. Cervical SCC, ASC, and AC are caused by a persistent infection with high-risk human papillomavirus (HPV and failed control of the immune system plays a pivotal role in the carcinogenesis of all three histopathological subtypes. Human leukocyte antigen E (HLA-E, a non-classical HLA class Ib molecule, plays an important role in immune surveillance and immune escape of virally infected cells. In this study we investigated HLA-E expression in three well-defined cohorts of cervical AC, ASC, and SCC patients, and determined whether HLA-E expression was associated with histopathological parameters and patient survival. Methods and results HLA-E expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections of 79 SCC, 38 ASC, and 75 AC patients. All patients included were International Federation of Gynaecology and Obstetrics stage I-II and underwent radical hysterectomy with lymphadenectomy as primary treatment. Significant differences between the histopathological subgroups were detected for age distribution, HPV positivity, HPV type distribution, tumour size, tumour infiltration depth, lymph-vascular space invasion, and adjuvant radiotherapy. High expression of HLA-E was found in 107/192 (56% cervical carcinomas, with significantly more overexpression in cervical AC compared to SCC and ASC (37/79 SCC, 18/38 ASC, and 52/75 AC; P = 0.010. High HLA-E expression in cervical AC was associated with favourable long term disease-specific and recurrence-free survival (P = 0.005 and P = 0

  16. HLA-E polymorphism and soluble HLA-E plasma levels in chronic hepatitis B patients.

    Zidi, I; Laaribi, A B; Bortolotti, D; Belhadj, M; Mehri, A; Yahia, H B; Babay, W; Chaouch, H; Zidi, N; Letaief, A; Yacoub, S; Boukadida, J; Di Luca, D; Hannachi, N; Rizzo, R


    Chronic hepatitis B virus (HBV) infection occurs in association to a deregulation of immune system. Human leukocyte antigen E (HLA-E) is an immune-tolerant nonclassical HLA class I molecule that could be involved in HBV progression. To measure soluble (s) HLA-E in patients with chronic HBV hepatitis (CHB). We tested the potential association of HLA-E*01:01/01:03 A > G gene polymorphism to CHB. Our cohort consisted of 93 Tunisian CHB patients (stratified in CHB with high HBV DNA levels and CHB with low HBV DNA levels) and 245 healthy donors. Plasma sHLA-E was determined using enzyme-linked immunosorbent assay (ELISA). Genotyping was performed using polymerase chain reaction sequence-specific primer. No association between HLA-E*01:01/01:03 A > G polymorphism and HBV DNA levels in CHB patients was found. G/G genotype is less frequent in CHB patients without significance. sHLA-E is significantly enhanced in CHB patients compared with healthy controls (P = 0.0017). Stratification according to HBV DNA levels showed that CHB patients with low HBV DNA levels have higher sHLA-E levels compared with CHB patients with high HBV DNA levels. CHB patients with G/G genotype have enhanced sHLA-E levels compared with other genotypes (P = 0.037). This significant difference is maintained only for CHB women concerning G/G genotypes (P = 0.042). Finally, we reported enhanced sHLA-E in CHB patients with advanced stages of fibrosis (P = 0.032). We demonstrate, for the first time, the association of sHLA-E to CHB. Owing to the positive correlation of HLA-E*01:01/01:03 A > G polymorphism and the association of sHLA-E to advanced fibrosis stages, HLA-E could be a powerful predictor for CHB progression. Further investigations will be required to substantiate HLA-E role as a putative clinical biomarker of CHB. PMID:26956431

  17. Describing the Peptide Binding Specificity of HLA-C

    Rasmussen, Michael; Harndahl, Mikkel Nors; Nielsen, Morten;

    for 5 HLA-C molecules and for all, but one, molecule we find a high frequency of binders, >70%, among these peptides. To extend the examined peptide space, we use bioinformatic prediction tools to search for additional binders. Finally, we update our prediction tool, NetMHCpan, with the HLA-C affinity......Human leukocyte antigen (HLA) presents peptides to T-cells for immune scrutiny. Whereas HLA-A and -B have been described in great detail, HLA-C has received much less attention. Here, to increase the coverage of HLA-C and the accuracy of the corresponding tools, we have generated HLA-C molecules......; peptide-binding assays, data and predictors; and tetramers; representing the most prevalent HLA-C molecules. We have combined positional scanning combinatorial peptide library (PSCPL) with a homogenous high-throughput dissociation assay and generated specificity matrices for 11 different HLA-C molecules...

  18. HLA-B27 subtypes among the Chukotka native groups

    Krylov, M.Y.; Alexeeva, L.I.; Erdesz, S.; Benevolenskaya, L.I. [Akademiya Meditsinskikh Nauk SSSR, Moscow (Russian Federation). Inst. Revmatizma; Reveille, J.D.; Arnett, F.C. [Texas Univ., Houston, TX (United States). Health Science Center


    The purpose of this study was to assess the relative frequency of the known HLA-B27 subtypes in HLA-B27 positive Chukotka natives, which have higher frequencies of HLA-B27 (to 40%) and spondylarthropathies (to 2%) than the Russian Caucasian population. Using oligotyping of the polymerase-chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-B27 positive individuals were successfully typed. All had HLA-B*2705, including 4 patients with Reiter`s syndrome and 5 with ankylosing spondyloarthritis, except one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. With respect to HLA-B27 subtypes the indigenous populations from the eastern part of the Chukotka Peninsula are genetically more closely related to Caucasians than to Orientals. (author). 18 refs, 1 fig., 2 tabs.

  19. Polymorphism of HLA-B27: 105 subtypes currently known.

    Khan, Muhammad Asim


    HLA-B27 has a high degree of genetic polymorphism, with 105 known subtypes, named HLA-B*27:01 to HLA-B*27:106, encoded by 132 alleles. The most common subtypes associated with ankylosing spondylitis are HLA-B*27:05 (Caucasians), HLA-B*27:04 (Chinese), and HLA-B*27:02 (Mediterranean populations). For Chinese populations, HLA-B*27:04 is associated with a greater ankylosing spondylitis risk than HLA-B*27:05. Two subtypes, HLA-B27*06 and HLA-B27*09, seem to have no disease association. These differential disease associations of HLA-B27 subtypes, and the recent discovery that ERAP1 is associated with ankylosing spondylitis for patients with HLA-B27, have increased attempts to determine the function of HLA-B27 in disease pathogenesis by studying hemodynamic features of its protein structure, alterations of its peptidome, aberrant peptide handling, and associated molecular events. However, after 40 years we still do not fully know how HLA-B27 predisposes to ankylosing spondylitis and related spondyloarthritis. PMID:23990399

  20. HLA-B73: An atypical HLA-B molecule carrying a Bw6-epitope motif variant and a B pocket identical to HLA-B27

    Vilches, C.; Pablo, R. de; Herrero, M.J.; Moreno, M.E.; Kreisler, M. [Hospital Puerta de Hierro, Madrid (Spain)


    HLA-B73, first described by Mayr and Kirnbauer (1981), is a poorly characterized allospecificity, serologically related to the B7-CREG. We polymerase chain reaction-amplified, cloned and sequenced the HLA-B alleles of the B-LCL LE023, established from a Spanish Caucasoid individual expressing HLA-B73. 5 refs., 2 figs.

  1. Analysis of HLA-A, HLA-B, HLA-DRB1 allelic, genotypic, and haplotypic frequencies in colombian population

    Yazmin Rocío Árias-Murillo


    Full Text Available Introduction: The high polymorphism of the HLA system allows its typification to be used as valuable tool in establishing association to various illnesses, immune and genetic profiles; it also provides a guide to identifying compatibility among donors and receptors of organs transplants.Objective: To establish HLA-A, HLA-B, and HLA.DRB1 allele, genotype and haplotype frequencies among patients treated at Clinica Colsanitas SA.Methods: 561 patients coming from different regions in Colombia, who were attended in 8 centers of the clinical laboratory of the Clinica Colsanitas in different cities of the country from January 2004 to August 2008, were included in this study. All were HLA-A,-B, and -DRB1 typified via SSP PCR. Allele, genotype and haplotype frequencies were estimated with STATA Software Version 9.0 and the GENEPOP genetic analysis package.Results: 19, 28, and 15 different alleles were identified for loci HLA-A,-B and -DRB1, respectively. Alleles found most frequently were A*24 (26.2%, A*02 (26%, B*35(22.7%, and DRB1*04 (24%. The most frequent genotypes were A*02,24 (14.2%, B*07,35 (5.5%, DRB1*01,04, and DRB1*04,04 (6.9%; while most the frequent haplotypes were HLA A*24, B*35 (9.2%, A*24, DRB1*04 (8.1%; B*35, DRB1*04 (7.8%, A*2 DRB1*04 (7.4%.Conclusion: The results obtained provide a useful reference framework for the population studied, allowing compatibility probability calculations to be performed for organ transplants.

  2. HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703

    Matthews, Philippa C; Adland, Emily; Listgarten, Jennifer;


    The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C......-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1...... disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag...

  3. A NOVel ELISPOT assay to quantify HLA-specific B cells in HLA-immunized individuals

    Heidt, S.; Roelen, D.L.; Vaal, Y.J. de; Kester, M.G.; Eijsink, C.; Thomas, S.; Besouw, N.M. van; Volk, H.D.; Weimar, W.; Claas, F.H.; Mulder, A.


    Quantification of the humoral alloimmune response is generally achieved by measuring serum HLA antibodies, which provides no information about the cells involved in the humoral immune response. Therefore, we have developed an HLA-specific B-cell ELISPOT assay allowing for quantification of B cells p

  4. HLA-DPB1 and HLA class I confer risk of and protection from narcolepsy

    Ollila, Hanna M; Ravel, Jean-Marie; Han, Fang;


    Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza...... H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA...... loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and...

  5. HLA associations and HLA sharing in recurrent miscarriage : A systematic review and meta-analysis

    Meuleman, Tess; Lashley, Lisa E L O; Dekkers, Olaf M.; van Lith, Jan M M; Claas, Frans H J; Bloemenkamp, Kitty W M


    Problem: The aim of this meta-analysis was to evaluate whether specific maternal HLA alleles and HLA sharing of couples are associated with the occurrence of recurrent miscarriage (RM). Method of study: A systematic literature search was performed for studies that evaluated the association between H

  6. Some Basic Aspects of HLA-G Biology

    Estibaliz Alegre


    Full Text Available Human leukocyte antigen-G (HLA-G is a low polymorphic nonclassical HLA-I molecule restrictively expressed and with suppressive functions. HLA-G gene products are quite complex, with seven HLA-G isoforms, four membrane bound, and other three soluble isoforms that can suffer different posttranslational modifications or even complex formations. In addition, HLA-G has been described included in exosomes. In this review we will focus on HLA-G biochemistry with special emphasis to the mechanisms that regulate its expression and how the protein modifications affect the quantification in biological fluids.

  7. Heart conduction disturbance: an HLA-B27 associated disease.

    Peeters, A J; ten Wolde, S; Sedney, M.I.; de Vries, R R; Dijkmans, B A


    In recent studies from Sweden an increased prevalence of HLA-B27 associated diseases and of HLA-B27 was found in an unselected group of men with permanently implanted pacemakers and with a heart block. Furthermore, a significantly increased prevalence of HLA-B27 was found in men with a pacemaker who had no clinical or radiological signs of HLA-B27 associated disease. To obtain more insight into the association between HLA-B27 and heart block, and the possible role of HLA-B27 in causing this b...

  8. Architectural Prototyping

    Bardram, Jakob; Christensen, Henrik Bærbak; Hansen, Klaus Marius


    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights that...

  9. Architectural prototyping

    Bardram, Jakob Eyvind; Christensen, Henrik Bærbak; Hansen, Klaus Marius


    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights that...

  10. Rapid assessment of the antigenic integrity of tetrameric HLA complexes by human monoclonal HLA antibodies.

    Eijsink, Chantal; Kester, Michel G D; Franke, Marry E I; Franken, Kees L M C; Heemskerk, Mirjam H M; Claas, Frans H J; Mulder, Arend


    The ability of tetrameric major histocompatibility complex (MHC) class I-peptide complexes (tetramers) to detect antigen-specific T lymphocyte responses has yielded significant information about the generation of in vivo immunity in numerous antigenic systems. Here we present a novel method for rapid validation of tetrameric HLA molecules based on the presence of allodeterminants. Human monoclonal antibodies (mAbs) recognizing polymorphic determinants on HLA class I were immobilized on polystyrene microparticles and used to probe the structural integrity of tetrameric HLA class I molecules by flow cytometry. A total of 22 tetramers, based on HLA-A1, A2, A3, A24, B7 and B8 were reactive with their counterpart mAbs, thus confirming their antigenic integrity. A positive outcome of this mAb test ensures that tetrameric HLA class I can be used with greater confidence in subsequent functional assays. PMID:16973172

  11. HLA and non-HLA genes in Behçet’s disease: a multicentric study in the Spanish population

    Montes-Cano, Marco A.; Conde-Jaldón, Marta; García-Lozano, José R.; Ortiz-Fernández, Lourdes; Ortego-Centeno, Norberto; Castillo-Palma, María J.; Espinosa, Gerard; Graña-Gil, Genaro; Miguel A. González-Gay; Barnosi-Marín, Ana C.; Solans, Roser; Fanlo, Patricia; Camps, Teresa; Castañeda, Santos; Sánchez-Bursón, Juan


    Abstract Introduction According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet’s disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD...

  12. Povezanost mikrosatelita HLA i gena HLA-B*27 u bolesnika s psorijatičnim artritisom u hrvatskoj populaciji

    Štimac, Davor; Grubić, Zorana; Štingl, Katarina; Perić, Porin; Ćurković, Božidar; Žunec, Renata


    Istraživana je raznovrsnost četiri mikrosatelita HLA (D6S248, D6S2674, D6S2811 i D6S273) u skupini bolesnika s psorijatičnim artritisom (PsA) (N=22) i zdravim osobama (K; N=94) pozitivnima za gen HLA-B*27, te povezanost haplotipskih veza gena HLA-B*27 s PsA. Svi ispitanici bili su prethodno tipizirani za gene HLA-A i -B metodom PCR-SSP i bili su HLA-B*27 pozitivni. Mikrosateliti HLA su analizirani metodom PCR-STR i elektroforezom u ALFexpress sekvenceru. Analiza raspodjele alela mikrosatelita...

  13. Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis.

    Okada, Yukinori; Suzuki, Akari; Ikari, Katsunori; Terao, Chikashi; Kochi, Yuta; Ohmura, Koichiro; Higasa, Koichiro; Akiyama, Masato; Ashikawa, Kyota; Kanai, Masahiro; Hirata, Jun; Suita, Naomasa; Teo, Yik-Ying; Xu, Huji; Bae, Sang-Cheol; Takahashi, Atsushi; Momozawa, Yukihide; Matsuda, Koichi; Momohara, Shigeki; Taniguchi, Atsuo; Yamada, Ryo; Mimori, Tsuneyo; Kubo, Michiaki; Brown, Matthew A; Raychaudhuri, Soumya; Matsuda, Fumihiko; Yamanaka, Hisashi; Kamatani, Yoichiro; Yamamoto, Kazuhiko


    Despite the progress in human leukocyte antigen (HLA) causal variant mapping, independent localization of major histocompatibility complex (MHC) risk from classical HLA genes is challenging. Here, we conducted a large-scale MHC fine-mapping analysis of rheumatoid arthritis (RA) in a Japanese population (6,244 RA cases and 23,731 controls) population by using HLA imputation, followed by a multi-ethnic validation study including east Asian and European populations (n = 7,097 and 23,149, respectively). Our study identified an independent risk of a synonymous mutation at HLA-DOA, a non-classical HLA gene, on anti-citrullinated protein autoantibody (ACPA)-positive RA risk (p = 1.4 × 10(-9)), which demonstrated a cis-expression quantitative trait loci (cis-eQTL) effect on HLA-DOA expression. Trans-ethnic comparison revealed different linkage disequilibrium (LD) patterns in HLA-DOA and HLA-DRB1, explaining the observed HLA-DOA variant risk heterogeneity among ethnicities, which was most evident in the Japanese population. Although previous HLA fine-mapping studies have identified amino acid polymorphisms of the classical HLA genes as driving genetic susceptibility to disease, our study additionally identifies the dosage contribution of a non-classical HLA gene to disease etiology. Our study contributes to the understanding of HLA immunology in human diseases and suggests the value of incorporating additional ancestry in MHC fine-mapping. PMID:27486778

  14. Design and Validation of Conditional Ligands for HLA-B*08:01, HLA-B*15:01, HLA-B*35:01, and HLA-B*44:05

    Frøsig, Thomas Mørch; Yap, Jiawei; Seremet, Tina;


    We designed conditional ligands restricted to HLA-B*08:01, 2B*35:01, and 2B*44:05 and proved the use of a conditional ligand previously designed for HLA-B*15:02 together with HLA-B*15:01. Furthermore, we compared the detection capabilities of specific HLA-B*15:01-restricted T cells using the HLA......-B*15:01 and HLA-B*15:02 major histocompatibility complex (MHC) multimers and found remarkable differences in the staining patterns detected by flow cytometry. These new conditional ligands greatly add to the application of MHC-based technologies in the analyses of T-cell recognition as they represent...... frequently expressed HLA-B molecules. This expansion of conditional ligands is important to allow T-cell detection over a wide range of HLA restrictions, and provide comprehensive understanding of the T-cell recognition in a given context....

  15. Human leukocyte antigen (HLA)-G during pregnancy part II

    Dahl, Mette; Klitkou, Louise; Christiansen, Ole B;


    Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent...... miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood...... plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing...

  16. Future Network Architectures

    Wessing, Henrik; Bozorgebrahimi, Kurosh; Belter, Bartosz;


    This study identifies key requirements for NRENs towards future network architectures that become apparent as users become more mobile and have increased expectations in terms of availability of data. In addition, cost saving requirements call for federated use of, in particular, the optical...

  17. Extended HLA-D region haplotype associated with celiac disease

    Howell, M.D.; Smith, J.R.; Austin, R.K.; Kelleher, D.; Nepom, G.T.; Volk, B.; Kagnoff, M.F.


    Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. The authors previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II ..beta..-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. They now report the isolation of this ..beta..-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP ..beta..-chain. This celiac disease-associated HLA-DP ..beta..-chain gene was flanked by HLA-DP ..cap alpha..-chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP..cap alpha..-chain genes of celiac disease patients also were studied by RFLP analysis. Celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP ..cap alpha..- and ..beta..-chain gene RFLPs. Within the celiac-disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion.

  18. Multiple HLA Epitopes Contribute to Type 1 Diabetes Susceptibility

    Roark, Christina L.; Anderson, Kirsten M.; Simon, Lucas J.; Schuyler, Ronald P.; Aubrey, Michael T; Freed, Brian M.


    Disease susceptibility for type 1 diabetes is strongly associated with the inheritance of specific HLA alleles. However, conventional allele frequency analysis can miss HLA associations because many alleles are rare. In addition, disparate alleles that have similar peptide-binding sites, or shared epitopes, can be missed. To identify the HLA shared epitopes associated with diabetes, we analyzed high-resolution genotyping for class I and class II loci. The HLA epitopes most strongly associated...

  19. A web resource for mining HLA associations with adverse drug reactions: HLA-ADR.

    Ghattaoraya, Gurpreet S; Dundar, Yenal; González-Galarza, Faviel F; Maia, Maria Helena Thomaz; Santos, Eduardo José Melo; da Silva, Andréa Luciana Soares; McCabe, Antony; Middleton, Derek; Alfirevic, Ana; Dickson, Rumona; Jones, Andrew R


    Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: PMID:27189608

  20. sHLA-G1 and HLA-G5 levels are decreased in Tunisian women with multiple abortion.

    Zidi, Inès; Rizzo, Roberta; Bouaziz, Aicha; Laaribi, Ahmed Baligh; Zidi, Nour; Di Luca, Dario; Tlili, Henda; Bortolotti, Daria


    Pregnancy is associated with increased levels of soluble (s) human leukocyte antigen (HLA)-G molecules, while during abortion these molecules are decreased. To date, little is known about the role of sHLA-G isoforms during abortion. In this study, we investigated the levels of total sHLA-G and its isoforms: HLA-G1 (membrane shedded isoform) and alternative spliced HLA-G5 in plasma samples obtained from 55 women who had experienced spontaneous abortion, 108 pregnant healthy women and 56 non pregnant healthy women. We found that pregnant women exhibited higher amounts of sHLA-G compared to either non pregnant women or women with abortion. Among women who had experienced spontaneous abortion, women with recurrent abortions (RSA) had lower sHLA-G than women with only one abortion. In particular, RSA women were characterized by the absence of sHLA-G1 isoform, suggesting a possible implication in abortion event. PMID:26812178

  1. HLA-DP specific responses in allogeneic stem cell transplantation

    Rutten, Caroline Elisabeth


    Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated

  2. Effect of HLA-A, B genotype on the content of soluble HLA classⅠantigen%HLA-A,B基因型别对可溶性HLA Ⅰ类抗原含量的影响

    倪宏英; 陈长荣; 裴斌


    目的了解HLA-A,B基因型别对可溶性HLA Ⅰ类抗原含量的影响.方法 HLA-A,B基因型别用反相PCR-SSO技术检测,可溶性HLA I类抗原的含量用夹心ELISA方法测定.结果在福建省汉族人群中基因型别为HLA-A*24的个体,可溶性HLA Ⅰ类抗原的含量显著高于平均水平;HLA-A*2和A*33基因的携带者可溶性HLA Ⅰ类抗原的含量显著低于平均水平;HLA-A*11、B*15、B*40和B*58的个体可溶性HLA Ⅰ类抗原的含量与平均水平比较无显著差异.结论 HLA-A基因型别的不同可能造成可溶性HLA Ⅰ类抗原含量的差异.

  3. Association study between HLA-DRB, HLA-DQA1, HLA-DQB1 and breast cancer in Iranian women

    Amirzargar AA


    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Based on the reports, high frequency of special alleles of HLA class II genes might be associated with susceptibility to or protective from a particular cancer. These alleles might vary depending on the geographical region. Here we investigate the association between alleles of HLA class II genes and breast cancer in Iranian women."n"nMethods: 100 patients with pathologically proved breast cancer who referred to Cancer Institute, Tehran University of Medical Sciences in Tehran, Iran, were divided to two groups based on ages (40 years old and less/ or more than 40 years old and were randomly selected and compared with a group of 80 healthy blood donor subjects. HLA class II alleles were determined by amplification of DNA with polymerase chain reaction (PCR method followed by HLA-typing using sequence-specific primer (SSP for each allele."n"nResults: The most frequent alleles in the DR and DQ regions in group 1 (40 years old and less in comparison with control group were HLA-DQA1*0301 (p=0.002 and HLA-DQB1*0302 (p>0.05. In contrast HLA-DQA1*0505 (p=0.004 had significantly lower frequency in this group compared with control group. Patients of group two (more than 40 years old had a higher frequencies of HLA

  4. Architectural Contestation

    Merle, J.


    This dissertation addresses the reductive reading of Georges Bataille's work done within the field of architectural criticism and theory which tends to set aside the fundamental ‘broken’ totality of Bataille's oeuvre and also to narrowly interpret it as a mere critique of architectural form, consequently presenting it either as the negation of all form of architecture or as the critique of 'classical' architectural forms. Against this ‘appropriation’, i.e. this reductive reading and the subse...

  5. Architectural Theatricality

    Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning


    and recovery through the architecture framing eating experiences, this article examines, from a theoretical perspective, two less debated concepts relating to hospitality called food design and architectural theatricality. In architectural theory the nineteenth century German architect Gottfried...... Semper is known for his writings on theatricality, understood as a holistic design approach emphasizing the contextual, cultural, ritual and social meanings rooted in architecture. Relative hereto, the International Food Design Society recently argued, in a similar holistic manner, that the methodology...

  6. VLSI architecture

    Randell, B.; Treleaven, P.C.


    This book is a collection of course papers which discusses the latest (1982) milestone of electronic building blocks and its effect on computer architecture. Contributions range from selecting a VLSI process technology to Japan's Fifth Generation Computer Architecture. Contents, abridged: VLSI and machine architecture. Graphic design aids: HED and FATFREDDY. On the LUCIFER system. Clocking of VLSI circuits. Decentralised computer architectures for VLSI. Index.

  7. Architecture & Environment

    Erickson, Mary; Delahunt, Michael


    Most art teachers would agree that architecture is an important form of visual art, but they do not always include it in their curriculums. In this article, the authors share core ideas from "Architecture and Environment," a teaching resource that they developed out of a long-term interest in teaching architecture and their fascination with the…

  8. HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels

    Hviid, Thomas Vauvert F; Hylenius, Sine; Rørbye, Christina;


    During pregnancy, the human extra-villous trophoblast in the contact zone between maternal and fetal tissue in the placenta does not express the classical MHC class I and II molecules. Instead, HLA-G and -C, and possibly HLA-E, are expressed. HLA-G may modulate the immunological relationship...... between mother and fetus in several ways. Finally, the expression of membrane-bound HLA-G and soluble HLA-G has been proposed to influence the outcome of pregnancy, and an aberrant HLA-G expression in pre-eclamptic placentas and spontaneous abortions has been reported. Here, an association between certain...... HLA-G polymorphisms and the mRNA levels of the different alternatively spliced HLA-G isoforms in first trimester trophoblast cell populations is reported. Several alternatively spliced HLA-G mRNA isoforms, including a 14-bp polymorphism in the 3'UTR end (exon 8) of the HLA-G gene, are expressed at a...

  9. Architectural Theatricality

    Tvedebrink, Tenna Doktor Olsen

    This PhD thesis is motived by a personal interest in the theoretical, practical and creative qualities of architecture. But also a wonder and curiosity about the cultural and social relations architecture represents through its occupation with both the sciences and the arts. Inspired by present...... initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture, is...... the current building of a series of Danish ‘super hospitals’ and an increased focus among architectural practices on research-based knowledge produced with the architectural sub-disciplines Healing Architecture and Evidence-Based Design. The problem is that this research does not focus on patient...

  10. Architectural Barriers Removal: Resource Guide.

    Office of Human Development (DHEW), Washington, DC. Office for Handicapped Individuals.

    The guide presents information on resources for eliminating architectural barriers for handicapped persons. Entries are grouped according to information resources, funding sources, and publications available from the federal government. Seven organizations are described in terms of agency goals, publications, and materials. Federal programs…

  11. Distribution of HLA-DRB1 and HLA-DQB1 alleles in Lak population of Iran.

    Varzi, Ali Mohammad; Shahsavar, Farhad; Tarrahi, Mohammad Javad


    Human leukocyte antigen (HLA) genes are the most polymorphic loci in the human genome and encode the highly polymorphic molecules critically involved in immune responses. Anthropological studies based on highly polymorphic HLA genes provide useful information for bone marrow donor registry, forensic medicine, disease association studies, as well as designing peptide vaccines against tumors, and infectious or autoimmune diseases. The aim of this study was to determine the HLA-DRB1 and HLA-DQB1 allele frequencies in 100 unrelated Lak individuals from Lorestan province of Iran. Finally, we compared the results with those previously described in four other Iranian populations. Commercial HLA-Type kits were used for determination of the HLA-DRB1 and HLA-DQB1 allele frequencies. Differences between populations in the distribution of HLA-DRB1 and HLA-DQB1 alleles were estimated by χ2 test with Yate's correction and Fisher's exact test. The most frequent HLA-DRB1 alleles were (*)1103=4 (23%), (*)1502 (9.5%), (*)0701 (9%), (*)0301 (8.5%), (*)1101 (7.5%) and (*)1501 (6%) while HLA-DQB1(*)0301 (40%), (*)0201 (15%), (*)0502 (10.5%), (*)0303 (10%), (*)0602=3 (9.5%), and (*)0501 (7.5%) were the most frequent alleles in Lak population. HLA-DRB1(*)0409, (*)0804, (*)1102, (*)1112, (*)1405, and HLA-DQB1(*)0503, (*)0604 were the least observed frequencies in Lak population. Our results based on HLA-DRB1 and HLA-DQB1 allele frequencies showed that the Lak population possesses the previously reported general features of the Lur and Kurd populations but still with unique, decreased or increased frequencies of several alleles. In other words, the Lak population is close to Lurs Khorramabadi and Kurd but far from Lurs Kohkiloyeh/Boyerahmad and Bakhtiari. PMID:27189628

  12. Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

    Romanos, Jihane; Rosen, Anna; Kumar, Vinod; Trynka, Gosia; Franke, Lude; Szperl, Agata; Gutierrez-Achury, Javier; van Diemen, Cleo C.; Kanninga, Roan; Jankipersadsing, Soesma A; Steck, Andrea; Eisenbarth, Georges; Van Heel, David A.; Cukrowska, Bozena; Bruno, Valentina


    Background The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective We explored whether CD risk prediction can be improved by adding non-HLA-susceptible varian...

  13. Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants

    Romanos, Jihane; Rosén, Anna; Kumar, Vinod; Trynka, Gosia; Franke, Lude; Szperl, Agata; Gutierrez-Achury, Javier; van Diemen, Cleo C.; Kanninga, Roan; Jankipersadsing, Soesma A; Steck, Andrea; Eisenbarth, Georges; Van Heel, David A.; Cukrowska, Bozena; Bruno, Valentina


    Background: The majority of coeliac disease (CD) patients are not being properly diagnosed and therefore remain untreated, leading to a greater risk of developing CD-associated complications. The major genetic risk heterodimer, HLA-DQ2 and DQ8, is already used clinically to help exclude disease. However, approximately 40% of the population carry these alleles and the majority never develop CD. Objective: We explored whether CD risk prediction can be improved by adding non-HLA-susceptible vari...

  14. Clinical implication of HLA class I expression in breast cancer

    Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified. A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed. The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval. The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system

  15. HLA-G molecule as inductor of immunotolerance

    HLA-G are molecules are (non-classic) class I antigens from main histocompatibility system. There are sis isoforms of HLA-G antigen codifying four proteins united to a membrane (HLA-G1, HLA-G2, HLA-G3, HLA-G4), and three soluble isoforms (HLA-G5, HLA-G6, HLA-G7). The first ones are expressed in cells of placental extravillous cytotrophoblast (Langhans' layer), amnios epithelial cells, fetal endothelial cells, mesenchymal macrophages of chorionic villi, and in epithelial cells of thymus medulla; the second ones in amniotic fluid, in maternal peripheral blood and that of the umbilical cord. There was a HLA-G expression in some types of tumors, stroma cells under inflammation conditions, virus-infected cells and in serum of transplant patients. There are strong evidences of HLA-G molecules role in tolerance induction to these physiological and pathological situations through suppression of lithic activity of NK cells and of cytotoxic T lymphocytes. This knowledge may be very useful in future therapeutical management of these entities as well as to favor the success of tissue and organ transplant

  16. HLA-DR expression and disease activity in ulcerative colitis

    Poulsen, L O; Elling, P; Sørensen, Flemming Brandt;


    In 12 patients with active ulcerative colitis (UC) the rectal epithelial cells were analyzed for HLA-DR antigens by an immunohistochemical technique. The clinical, rectoscopic, and histologic stages were also determined. The investigations were carried out at the beginning of the study and 2 weeks...... and 3 months later. The rectal epithelial cells were HLA-DR-positive in all patients at the first two examinations. After 3 months five patients had changed to an HLA-DR-negative stage, whereas the other seven patients remained HLA-DR-positive. Closer analyses showed that expression/nonexpression of...... HLA-DR antigens on rectal epithelial cells of patients with UC could not be predicted from the clinical, rectoscopic, or histologic findings. HLA-DR expression is normally restricted to immunocompetent cells. The presence of HLA-DR antigens on epithelial cells may be a consequence of immunological...

  17. Analysis of HLA-B15 and HLA-B27 in spondyloarthritis with peripheral and axial clinical patterns

    Londono, John; Santos, Ana Maria; Peña, Paola; Calvo, Enrique; Espinosa, Luis R; John D Reveille; Vargas-Alarcon, Gilberto; Jaramillo, Carlos A.; Valle-Oñate, Rafael; Avila, Mabel; Romero, Consuelo; Medina, Juan F.


    Objective Human leucocyte antigen (HLA) B27 and HLA-B15 are associated with spondyloarthritis (SpA). Recent Assessment of SpondyloArthritis international Society (ASAS) criteria emphasise a distinction between SpA with axial and peripheral patterns. We analysed whether HLA-A, HLA-B and HLA-DRB1 alleles could associate with these patterns. Methods We studied 100 healthy individuals and 178 patients with SpA according to European Spondyloarthropathy Study Group (ESSG) criteria. Patients were th...

  18. Architectural freedom and industrialised architecture

    Vestergaard, Inge


    Architectural freedom and industrialized architecture. Inge Vestergaard, Associate Professor, Cand. Arch. Aarhus School of Architecture, Denmark Noerreport 20, 8000 Aarhus C Telephone +45 89 36 0000 E-mai l Based on the repetitive architecture from the "building boom" 1960...... to 1973 it is discussed how architects can handle these Danish element and montage buildings through the transformation to upgraded aesthetical, functional and energy efficient architecture. The method used is analysis of cases, parallels to literature studies and producer interviews. This analysis...... compares "best practice" in Denmark and "best practice" in Austria. The modern architects accepted the fact that industrialized architecture told the storey of repetition and monotonous as basic condition. This article aims to explain that architecture can be thought as a complex and diverse design through...

  19. The Expression of Non-Classical HLA Class I Molecules (HLA-Gand HLA-E)in Human Tumor Cell Lines and the Regulatory Effect of IFN-γ%非经典hla Ⅰ类分子(hla-g和hla-e)在人肿瘤细胞系的表达及ifn-γ的调节作用

    张彩; 田志刚; 魏海明; 冯进波; 许晓群; 张建华; 孙汭


    目的:探讨非经典hla Ⅰ类分子在人肿瘤细胞系的表达及ifn-γ的调节作用。方法:用rt-pcr法检测12种肿瘤细胞系和人脑胶质瘤组织及妊娠妇女滋养层组织标本hla-g和hla-e mrna的表达。结果:人脑胶质瘤组织及妊娠妇女滋养层组织均有hla-g和hla-e mrna的表达;12株肿瘤细胞中仅人t细胞淋巴瘤karpas存在hla-g3的mrna表达,经ifn-γ处理后,karpas出现hla-g1/g5和hla-g2/g4的表达,宫颈癌hela细胞、黑色素瘤m21细胞和膀胱癌t24细胞出现hla-g3 mrna的表达;12株肿瘤细胞中有9株表达hla-e mrna。结论:肿瘤存在hla-g和hla-e mrna的表达,ifn-γ可促进hla-g mrna的表达。肿瘤细胞hla-g和hla-e的表达可能是肿瘤逃避免疫系统监视的机制之一。

  20. HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus

    Rizzo, R; Hviid, T V F; Govoni, M;


    increased frequency of HLA-G +14/+14 bp and a decreased frequency of HLA-G -14/-14 bp were observed in SLE patients. There median concentration of sHLA-G was significantly lower in the plasma of SLE patients compared with that in the plasma of healthy controls (P < 0.0001). Furthermore, the results...... antigen (HLA)-G molecule in innate and adaptive cellular responses has been reported, suggesting a role in inflammatory diseases. A 14 bp sequence insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene has been associated to the stability of HLA-G messenger RNA. The...... insertion of the 14 bp sequence seems to be associated with lower levels of soluble HLA-G (sHLA-G). The aim of this study was to evaluate the possible association of the presence of the 14 bp sequence (+14 bp) with SLE. We have HLA-G genotyped 200 SLE patients and 451 healthy control subjects (HS; Italian...


    Zhang Hongbo; Li Shengbin


    Objective To investigate HLA-A,-B and -DRB1 allele and HLA-A-B-DRB1 haplotype frequencies in Mongolia ethnic group. Methods HLA-A, -B, -DRB1 allele and haplotype in the Mongolia ethnic group were investigated based on 93 individuals by PCR- sequence-based typing (SBT) method. Results Twenty-one alleles were detected for HLA-A, 44 for HLA-B, and 26 for HLA-DRB1. The most frequent alleles were HLA-A*2402(0.2097), HLA-B*1302(0.0699), and HLA-DRB1*0701(0.1237). The most common HLA-A-B-DRB1 haplotype were A*3001-B*1302-DRB1*0701, A*0101-B*3701-DRB1*1001, followed by the A*0201-B*4601-DRB1*0901, A*2402-B*4801-DRB1*1101, A*2402-B*5201-DRB1*1501, A*3201-B*3503-DRB1*1301, and A*3303-B*5801-DRB1*0301, which were also presented in Chinese populations. Conclusion The data can be used in forensic and paternity tests to estimate the frequency of a DNA profile or anthropologic research. The characteristics of the distribution of HLA alleles revealed that Mongolia ethnic group is characterized by northern Mongolian Chinese.

  2. Human Leukocyte Antigen (HLA) Class I Restricted Epitope Discovery in Yellow Fewer and Dengue Viruses: Importance of HLA Binding Strength

    Lund, Ole; Nascimento, Eduardo J. M.; Maciel, Milton, Jr;


    Epitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV...... epitopes were selected using the EpiSelect algorithm to allow for optimal coverage of viral strains. The selected predicted epitopes were synthesized and approximately 75% were found to bind the predicted restricting HLA molecule with an affinity, K(D), stronger than 500 nM. The immunogenicity of 25 HLA......-A*02:01, 28 HLA-A*24:02 and 28 HLA-B*07:02 binding peptides was tested in three HLA-transgenic mice models and led to the identification of 17 HLA-A*02:01, 4 HLA-A*2402 and 4 HLA-B*07:02 immunogenic peptides. The immunogenic peptides bound HLA significantly stronger than the non-immunogenic peptides...

  3. Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules

    Cytotoxic T lymphocyte (CTL) clones specific for human minor histocompatibility antigens (hmHAs) were produced from a patient who had been grafted with the kidneys from his mother and two HLA-identical sisters. Of eight CTL clones generated, four recognized an hmHA (hmHA-1) expressed on cells from the mother and sister 3 (second donor); two recognized another antigen (hmHA-2) on cells from the father, sister (third donor), and sister 3; and the remaining two clones recognized still another antigen (hmHA-3) on cells from the father and sister 3. Panel studies revealed that CTL recognition of hmHA-1 was restricted by HLA-B35 and that of hmHA-2 and hmHA-3 was restricted by HLA-B38. The HLA-B35 restriction of the hmHA-1 -specific CTL clones was substantiated by the fact that they killed HLA-A null/HLA-B null Hmy2CIR targets transfected with HLA-B35 but not HLA-B51, -Bw52, or -Bw53 transfected Hmy2CIR targets. These data demonstrated that the five amino acids substitutions on the α1 domain between HLA-B35 and -Bw53, which are associated with Bw4/Bw6 epitopes, play a critical role in the relationship of hmHA-1 to HLA-B35 molecules. The fact that the hmHA-1-specific CTLs failed to kill Hmy2CIR cells expressing HLA-B35/51 chimeric molecules composed of the α1 domain of HLA-B35 and other domains of HLA-B51 indicated that eight residues on the α2 domain also affect the interaction of hmHA-1 and the HLA-B35 molecules

  4. The Potential of HLA-G-Bearing Extracellular Vesicles as a Future Element in HLA-G Immune Biology.

    Rebmann, Vera; König, Lisa; Nardi, Fabiola da Silva; Wagner, Bettina; Manvailer, Luis Felipe Santos; Horn, Peter A


    The HLA-G molecule is a member of the non-classical HLA class I family. Its surface expression is physiologically restricted to the maternal-fetal interface and to immune privileged adult tissues. Despite the restricted tissue expression, HLA-G is detectable in body fluids as secreted soluble molecules. A unique feature of HLA-G is the structural diversity as surface expressed and as secreted molecules. Secreted HLA-G can be found in various body fluids either as free soluble HLA-G or as part of extracellular vesicles (EVs), which are composed of various antigens/ligands/receptors, bioactive lipids, cytokines, growth factors, and genetic information, such as mRNA and microRNA. Functionally, HLA-G and its secreted forms are considered to play a crucial role in the network of immune-regulatory tolerance mechanisms, preferentially interacting with the cognate inhibitory receptors LILRB1 and LILRB2. The HLA-G mediated tolerance is described in processes of pregnancy, inflammation, and cancer. However, almost all functional and clinical implications of HLA-G in vivo and in vitro have been established based on simple single ligand/receptor interactions at the cell surface, whereas HLA-G-bearing EVs were in minor research focus. Indeed, cytotrophoblast cells, mesenchymal stem cells, and cancer cells were recently described to secrete HLA-G-bearing EVs, displaying immunosuppressive effects and modulating the tumor microenvironment. However, numerous functional and clinical open questions persist. Here, we (i) introduce basic aspects of EVs biology, (ii) summarize the functional knowledge, clinical implications and open questions of HLA-G-bearing EVs, and (iii) discuss HLA-G-bearing EVs as a future element in HLA-G biology. PMID:27199995

  5. Architecture Sustainability

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich


    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The first Web extra at is an audio interview in which Davide Falessi speaks with guest editors Paris Avgeriou and Rich Hilliard about the importance of architecture sustainabil...

  6. Software architecture

    Vogel, Oliver; Chughtai, Arif


    As a software architect you work in a wide-ranging and dynamic environment. You have to understand the needs of your customer, design architectures that satisfy both functional and non-functional requirements, and lead development teams in implementing the architecture. And it is an environment that is constantly changing: trends such as cloud computing, service orientation, and model-driven procedures open up new architectural possibilities. This book will help you to develop a holistic architectural awareness and knowledge base that extends beyond concrete methods, techniques, and technologi

  7. Catalyst Architecture

    Kiib, Hans; Marling, Gitte; Hansen, Peter Mandal


    How can architecture promote the enriching experiences of the tolerant, the democratic, and the learning city - a city worth living in, worth supporting and worth investing in? Catalyst Architecture comprises architectural projects, which, by virtue of their location, context and their combination...... of programs, have a role in mediating positive social and/or cultural development. In this sense, we talk about architecture as a catalyst for: sustainable adaptation of the city’s infrastructure appropriate renovation of dilapidated urban districts strengthening of social cohesiveness in the city...

  8. The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma.

    Yang, Huimin; Yu, Kaihui; Zhang, Ruoheng; Li, Jiatong; Wei, Xiaomou; Zhang, Yuening; Zhang, Chengdong; Xiao, Feifan; Zhao, Dong; Lin, Xuandong; Wu, Huayu; Yang, Xiaoli


    Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual's susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities. PMID:27059731

  9. HLA-DRB1和HLA-DQB1基因与肿瘤的关联性研究%A relevance between tumor and HLA-DRB1 and HLA-DQB1 gene polymorphism

    周秀英; 于雅宁; 刘辉


    Objective To study the relevance between tumor and HLA-DRB1 and HLA-DQB1 gene polymorphism via analyzing 18 alleles of HLA-H gene locus of some tumor patients.Methods 18 alleles ofHLA-Ⅱ gene locus of 42 tumor patients were analyzed and compared.with those of 100 healthy people using PCR-SSP (polymerase chain reaction-sequence specific primers) technology.Results The HLA-DQB1 * 03 frequency of the tumor group was 65.5%,it was significantly higher than the 42.0% of the control group,RR =2.62,P <0.0001; the HLA-DQB1 * 06 frequency of tumor group was 10.7%,it was significantly lower than 24.0% of the control group,RR =0.38,P value was of 0.010.Condusion It is suggested that HLA-DQB1 * 03 may be the susceptibility gene of tumor,HLA-DQB1 * 06 may be the resistance genes of tumor.%目的 通过对42例肿瘤患者HLA-DRB1和HLA-DQB1座位的18个等位基因位点的检测,探讨HLA-DRB1和HLA-DQB1基因多态性与肿瘤的关联性.方法 采用PCR-SSP技术,检测42例肿瘤患者的HLA-DRB1和HLA-DQBI基因位点18个,并以100例健康人作为对照.结果 肿瘤HLA-DQB1* 03型频率的65.5%,高于对照组的42.0%,RR =2.62,P<0.0001;肿瘤组HLA-DQB1* 06型频率为10.7%,明显低于对照组的24.0%,RR =0.38,P=0.010.结论 HLA-DQB1* 03可能是肿瘤的易感基因,HLA-DQB1* 06可能是肿瘤的抗性基因.




    The frequency of HLA types in a selected group of 40 patients with myasthenia gravis in relation to the effect of thymectomy and also to gender, and thymus histology was studied. As generally described we found a significant increase in the frequency of HLA-A1, HLA-B8, HLA-DR3 and HLA-DQ2 in the tot

  11. Head and neck squamous cell carcinoma susceptibility genes in the HLA region

    Reinders, Judith


    The Human Leukocyte Antigen (HLA) region on the short arm of chromosome 6 includes the classical HLA genes and in addition HLA-related and non-HLA related genes. The majority of the genes located in this region are directly or indirectly involved in the immune response. The polymorphic HLA molecules

  12. Human leukocyte antigen (HLA)-G during pregnancy part I

    Klitkou, Louise; Dahl, Mette; Hviid, Thomas Vauvert F;


    Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on trophoblast cells and has been proposed to have immunomodulatory functions during pregnancy. Soluble HLA-G1 (sHLA-G1) can be generated by the shedding of membrane-bound HLA-G molecules; however......, three soluble isoforms also exist (HLA-G5 to -G6). During pregnancy, it is unknown whether there is a correlation between sHLA-G levels in maternal and fetal blood. In 246 pregnancies, we have measured the levels of sHLA-G1/-G5 in maternal blood plasma samples from gestational week 20 (GW20) and at term......, as well as in umbilical cord blood samples. Soluble HLA-G levels declined by 38.4% in maternal blood from GW20 to term, and sHLA-G levels were significantly lower in maternal blood at term than in GW20 (P<0.001). At term, the sHLA-G levels were significantly higher in maternal blood than in umbilical...

  13. Systemic Architecture

    Poletto, Marco; Pasquero, Claudia


    This is a manual investigating the subject of urban ecology and systemic development from the perspective of architectural design. It sets out to explore two main goals: to discuss the contemporary relevance of a systemic practice to architectural design, and to share a toolbox of informational...... design protocols developed to describe the city as a territory of self-organization. Collecting together nearly a decade of design experiments by the authors and their practice, ecoLogicStudio, the book discusses key disciplinary definitions such as ecologic urbanism, algorithmic architecture, bottom......-up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto...

  14. Mutations in the HLA class II genes leading to loss of expression of HLA-DR and HLA-DQ in diffuse large B-cell lymphoma

    Jordanova, ES; Philippo, K; Giphart, MJ; Schuuring, E; Kluin, PM


    Loss of expression of human leukocyte antigen (HLA) class II molecules on tumor cells affects the onset and modulation of the immune response through lack of activation of CD4(+) T lymphocytes. Previously, we showed that the frequent loss of expression of HLA class II in diffuse large B-cell lymphom

  15. HLA-G Molecules in Autoimmune Diseases and Infections

    Rizzo, Roberta; Bortolotti, Daria; Bolzani, Silvia; Fainardi, Enrico


    Human leukocyte antigen (HLA)-G molecule, a non-classical HLA-Ib molecule, is less polymorphic when compared to classical HLA class I molecules. Human leukocyte antigen-G (HLA-G) was first detected on cytotrophoblast cells at the feto-maternal interface but its expression is prevalent during viral infections and several autoimmune diseases. HLA-G gene is characterized by polymorphisms at the 3′ un-translated region and 5′ upstream regulatory region that regulate its expression and are associated with autoimmune diseases and viral infection susceptibility, creating an unbalanced and pathologic environment. This review focuses on the role of HLA-G genetic polymorphisms, mRNA, and protein expression in autoimmune conditions and viral infections. PMID:25477881

  16. Association of HLA-DRB1 and HLA-DQB1 gene polymorphisms with pemphigus%HLA-DRB1和HLA-DQB1基因多态性与天疱疮的相关性

    吴桂菊; 张勇; 朱海琴; 王颖; 潘萌


    Objective To explore the genetic association of human leucocyte antigen ( HLA) -DRB1 and HLA-DQB1 allele polymorphisms with pemphigus. Methods Fifty-eight patients with pemphigus ( case group) and 89 normal controls (control group) were selected in Shanghai as study objectives. HLA-DRB1 and HLA-DQB1 alleles in two groups were typed by polymerase chain reaction-sequence specific primers (PCR-SSP). Direct count method was adopted to calculate allele frequencies, and comparison was performed between groups. Odds ratios (OR) of allele frequencies were used to evaluate the association of gene with disease. Results A total of 13 HLA-DRB1 alleles and 5 HLA-DQB1 alleles were detected in case group and control group. The frequencies of HLA-DRB1 * 14 allele and HLA- DQB1 * 05 allele in case group were significantly higher than those in control group (17. 24% vs 1. 69% , P = 0. 000, Pc < 0. 05, OR = 12. 150; 18. 97% vs 6.74%, P = 0.001, Pc < 0.05, OR = 3. 238). The frequency of HLA-DQB1 * 06 allele in case group was significantly lower than that in control group (15.52% vs 30.90%, P=0.003, Pe<0.05, OR =0.411). Conclusion HLA-DRB1 * 14 and HLA-DQB1 * 05 may be predisposing genes, while HLA-DQB1 * 06 may be protective gene of pemphigus in Shanghai.%目的 探讨人白细胞抗原(HLA)-DRB1和HLA-DQB1等位基因多态性与天疱疮的遗传相关性.方法 以上海地区的58例天疱疮患者(病例组)和89名正常对照者(对照组)作为研究对象.采用聚合酶链反应-序列特异性引物分型技术(PCR-SSP)对两组HLA-DRB1和HLA-DQB1等位基因进行分型,直接计数法计算等位基因频率并进行组间比较,以等位基因频率的比值比(OR)评价基因与疾病的关联性.结果 病例组和对照组共检测到13种HLA-DRB1等位基因和5种HLA-DQB1等位基因.统计学分析结果表明:病例组HLA-DRB1*14和HLA-DQB1*05等位基因频率分别为17.24%和18.97%,显著高于对照组的1.69%(P=0.000,P值的校正值Pc<0.05,OR=12

  17. [The HLA system in the Moroccan population: General review].

    Brick, C; Atouf, O; Essakalli, M


    The Moroccan population is an interesting study model of Human Leukocyte Antigen (HLA) polymorphism given its ethnic and genetic diversity. Through an analysis of the literature, this work proposes to establish a balance of knowledge for this population in the field of histocompatibility: HLA diversity, anthropology, transplantation and HLA associations and diseases. This analysis shows that the HLA system has not been fully explored within the Moroccan population. However, the results obtained allowed us to initiate a database reflecting the specific healthy Moroccan population HLA polymorphism to identify immigration flows and relationships with different people of the world and to reveal the association of certain HLA alleles with frequent pathologies. We also propose to analyze the reasons hindering the development of this activity in Morocco and we will try to identify some perspectives. PMID:26597780

  18. HLA-G polymorphisms in couples with recurrent spontaneous abortions

    Hviid, T V; Hylenius, S; Hoegh, A M;


    The etiology of a fraction of recurrent spontaneous abortions (RSA) may involve immunological mechanisms. Aberrant profiles of Th1 and Th2 cytokines have been observed which are not present in uncomplicated pregnancies. Studies of classical HLA class I and II antigens in relation to RSA have not...... been conclusive. Furthermore, these antigens are not expressed in the placenta with the exception of HLA-C. However, HLA-G is expressed on especially invasive cytotrophoblasts and exists in both membrane and soluble forms. HLA-G may be involved in materno-fetal tolerance. Therefore, 61 RSA couples...... (with three or more spontaneous abortions) and 47 fertile control couples were HLA-G genotyped by direct DNA sequencing and analyzed for specific polymorphisms. No statistically significant differences were observed in the distribution of HLA-G alleles between controls and RSA couples, however, 15% of...

  19. HLA polymorphism in Sudanese renal donors

    Ameer M Dafalla


    Full Text Available The main objective of this study is to provide a database for renal transplantation in Sudan and to determine the HLA antigens and haplotype frequencies (HFs in the study subjects. HLA typing was performed using the complement-dependant lymphocytotoxicity test in 250 unrelated healthy individuals selected as donors in the Sudanese Renal Transplantation Program. Considerable polymorphism was observed at each locus; A2 (0.28, A30 (0.12, A3 (0.09, A24 (0.09, A1 (0.09, and A68 (0.06 were the most frequent antigens in the A locus, while B51 (0.092, B41 (0.081, B39 (0.078, B57 (0.060, B35 (0.068, B 50 (0.053 and B 52 (0.051 were the most common B locus antigens. DR13 (0.444 and DR15 (0.160 showed the highest antigen frequencies (AFs in the DR locus. In the DQ locus, DQ1 showed the highest gene frequency (0.498, while DQ2 and DQ3 AFs were (0.185 and (0.238, respectively. The most common HLA-A and -B haplotypes in positive linkage disequilibrium were A24, B38; A1, B7; and A3, B52. The common HLA-A and -B HFs in positive linkage disequilibrium in the main three tribe-stocks of the study subjects (Gaalia, Nile Nubian and Johyna were A24, B38 for Gaalia; A24, B38 and A2, B7 for Johyna; and A2, B64 and A3, B53 for Nile Nubian. These results suggest that both class I and class II polymorphisms of the study subjects depict considerable heterogeneity, which reflects recent admixture of this group with neighboring Arabs and African populations.

  20. Class II HLA antigens in multiple sclerosis.

    Miller, D H; Hornabrook, R W; Dagger, J; Fong, R


    HLA typing in Wellington revealed a stronger association of multiple sclerosis with DR2 than with DQw1. The association with DQw1 appeared to be due to linkage disequilibrium of this antigen with DR2. These results, when considered in conjunction with other studies, are most easily explained by the hypothesis that susceptibility to multiple sclerosis is influenced by multiple risk factors, with DR2 being an important risk factor in Caucasoid populations. PMID:2732726

  1. HLA Genotyping and Antibody Characterization Using the Luminex™ Multiplex Technology

    Heinemann, Falko Markus


    The Luminex-based human leukocyte antigen (HLA) antibody screening technology is widespread used in laboratories affiliated to kidney transplantation programs and enables both screening (i.e. the definition of positive or negative antibody status) and antibody identification with high sensitivity and specificity. HLA typing at different levels of resolution with Luminex technology uses sequence-specific oligonucleotide probes bound to color-coded microbeads in order to identify HLA alleles en...

  2. Associations of HLA alleles with specific language impairment

    Nudel, Ron; Simpson, Nuala H; Baird, Gillian; O’Hare, Anne; Conti-Ramsden, Gina; Bolton, Patrick F.; Hennessy, Elizabeth R; Monaco, Anthony P; Knight, Julian C.; Winney, Bruce; Fisher, Simon E.; Newbury, Dianne F


    Background Human leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected. However, to date, no studies have investigated the possible involvement of HLA loci in specific language impairment (SLI), a disorder that is defined primarily upon unexpected language impairment. We report association analyses of single-nucleotide polymorphisms (SNPs) and HLA types in a cohort of individuals affected by language impairment. Methods We perf...

  3. Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules

    Antoniou, Antony N.; Izabela Lenart; Guiliano, David B.


    The association between HLA-B27 and the group of autoimmune inflammatory arthritic diseases, the spondyloarthropathies (SpAs) which include ankylosing spondylitis (AS) and Reactive Arthritis (ReA), has been well established and remains the strongest association between any HLA molecule and autoimmune disease. The mechanism behind this striking association remains elusive; however animal model and biochemical data suggest that HLA-B27 misfolding may be key to understanding its association with...

  4. HLA-B27 Misfolding and Ankylosing Spondylitis

    Colbert, Robert A.; Tran, Tri M.; Layh-Schmitt, Gerlinde


    Understanding how HLA-B27 contributes to the pathogenesis of spondyloarthritis continues to be an important goal. Current efforts are aimed largely on three areas of investigation; peptide presentation to CD8 T cells, abnormal forms of the HLA-B27 heavy chain and their recognition by leukocyte immunoglobulin-like receptors on immune effector cells, and HLA-B27 heavy chain misfolding and intrinsic biological effects on affected cells. In this chapter we review our current understanding of the ...

  5. The IMGT/HLA and IPD databases.

    Robinson, James; Waller, Matthew J; Fail, Sylvie C; Marsh, Steven G E


    The IMGT/HLA database ( has provided a centralized repository for the sequences of the alleles named by the WHO Nomenclature Committee for Factors of the HLA System since 1998. Since its initial release, the database has rapidly grown in size and is recognized as the primary source of information for the study of sequences of the human major histocompatibility complex. The Immuno Polymorphism Database (IPD; is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD currently consists of four databases: IPD-KIR contains the allelic sequences of killer-cell immunoglobulin-like receptors; IPD-MHC is a database of sequences of the major histocompatibility complex of different species; IPD-HPA contains alloantigens expressed only on platelets (human platelet antigens or HPA); and IPD-ESTDAB provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. PMID:16944494

  6. Association and frequency of HLA-A, B and HLA-DR genes in south Tunisian patients with spondyloarthritis (SpA)

    N. Mahfoudh; M. Siala; M. Rihl; A. Kammoun; F. Frikha; H. Fourati; M. Younes; R. Gdoura; L. Gaddour; F. Hakim; Z. Bahloul; S. Baklouti; N. Bargaoui; S. Sellami; A. Hammami; H. Makni


    The aim of this study is to investigate the association of HLA-A, B and HLA-DR gene expression and to assess an association of additional HLA antigens besides HLA-B27 in south Tunisian patients with spondyloarthritis (SpA). Eighty-five patients diagnosed with ankylosing spondylitis (AS, n = 68) and

  7. Autoinflammation and HLA-B27: Beyond Antigen Presentation.

    Sibley, Cailin H


    HLA-B27 associated disorders comprise a group of inflammatory conditions which have in common an association with the HLA class I molecule, HLA-B27. Given this association, these diseases are classically considered disorders of adaptive immunity. However, mounting data are challenging this assumption and confirming that innate immunity plays a more prominent role in pathogenesis than previously suspected. In this review, the concept of autoinflammation is discussed and evidence is presented from human and animal models to support a key role for innate immunity in HLA-B27 associated disorders. PMID:27229619

  8. HLA-B27 Positivity: associated health implications

    Cox, C. L.; Gibbons, H.; Evans, P; Withers, T.; Titmus, K.


    HLA-B27 positivity makes the onset of autoimmune diseases such as uveitis, ankylosing spondylitis and Crohn's disease more likely to occur. Ankylosing spondylitis and Crohn's disease are two types of HLA-B27 positive diseases that demonstrate a direct association with uveitis. Although the possession of HLA-B27 positivity is not mandatory for autoimmune diseases such as uveitis to occur, HLA-B27 positivity not only makes it more likely but may modify the clinical picture in which a patient pr...

  9. Bartonella henselae associated uveitis and HLA-B27

    Kerkhoff, F.T.; Rothova, A


    AIM—To investigate the frequency of HLA-B27 in patients with presumed Bartonella henselae associated uveitis and to describe the clinical characteristics of HLA-B27 positive patients with uveitis and presumed ocular bartonellosis (POB).
METHODS—The diagnosis of POB was considered in 19 patients with unexplained uveitis (except for the HLA-B27 association) and high positive IgG (titre ⩾1:900) and/or IgM (titre ⩾1:250) antibodies against B henselae. In addition to B henselae serology and HLA-B2...

  10. HLA-DP specific responses in allogeneic stem cell transplantation

    Rutten, Caroline Elisabeth


    Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, whereas a significant decreased risk of disease relapse was still observed. In this thesis we showed that HLA-DPB1 mismatched allo-SCT followed by donor lymp...

  11. Humanizing Architecture

    Toft, Tanya Søndergaard


    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles to...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  12. Architectural technology


    The booklet offers an overall introduction to the Institute of Architectural Technology and its projects and activities, and an invitation to the reader to contact the institute or the individual researcher for further information. The research, which takes place at the Institute of Architectural...... Technology at the Roayl Danish Academy of Fine Arts, School of Architecture, reflects a spread between strategic, goal-oriented pilot projects, commissioned by a ministry, a fund or a private company, and on the other hand projects which originate from strong personal interests and enthusiasm of individual...

  13. Frequency determination of HLA-DRB1 and HLA-DQB1 alleles in children with primary vesicoureteral reflux

    Mohammadreza Bazrafshani


    Conclusion: The HLA cluster might affect on susceptibility to vesicoureteral reflux es-pecially by locus which located close to HLA-DRB1 and HLA-DQB1 genes. This study demonstrates for the first time in Iran. However, further extensive researches with a large number of samples from different populations and ethnicities are required to val-idate the results obtained in this study.

  14. HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom.

    M A Brown; Pile, K D; Kennedy, L G; Calin, A.; Darke, C; Bell, J.; Wordsworth, B P; Cornélis, F


    OBJECTIVE: To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. METHODS: HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically mat...

  15. Architectural Mealscapes

    Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning


    German architect Gottfried Semper developed a theory on the “four elements of Architecture” tracing the origin of architecture back to the rise of the early human settlement and the creation of fire. With the notion ‘hearth’ as the first motive in architecture and the definition of three enclosing...... motives; mounding, enclosure and roof, Semper linked the cultural and social values of the primordial fireplace with the order and shape of architecture. He claimed that any building ever made was nothing but a variation of the first primitive shelters erected around the fireplace, and that the three...... enclosing motives existed only as defenders of the “sacred flame”. In that way Semper developed the idea that any architectural scenery can be described, analyzed and explained by understanding the contextual, symbolic and social values of how the four basic motives of hearth, mounding, enclosure, and roof...

  16. HLA-B*57 Micropolymorphism shapes HLA allele-specific epitope immunogenicity, selection pressure, and HIV immune control

    Kløverpris, Henrik Nyhus; Buus, Anette Stryhn; van der Stok, Mary;


    The genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B*57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B*57 alleles and the closely related HLA-B*5801 are often grouped together...... because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B*57 alleles, termed HLA-B*57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C......-clade-infected subjects from southern Africa, HLA-B*5703 is associated with a lower viral-load set point than HLA-B*5702 and HLA-B*5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma; P = 0.24 and P = 0.0005). In order to better understand these observed differences in HLA-B*57/5801-mediated immune control of...

  17. HLA-B27 typing in the categorisation of uveitis in a HLA-B27 rich population

    Huhtinen, M; Karma, A


    AIMS—To determine whether HLA-B27 typing helps the clinician in the diagnostic examination of uveitis in a HLA-B27 rich population and also whether the clinical picture of HLA-B27 positive unilateral acute or recurrent anterior uveitis (AAU) is distinguishable from the idiopathic negative form.
METHODS—During a 3 year period 220 consecutive patients with undetermined uveitis at onset were examined in the Helsinki University Eye Clinic. HLA-B27 antigen was tested for 85% of the patients. Other...

  18. Framing Architecture

    Shirey, David E.


    The following thesis is comprised of a pair of projects focused on the making of architecture through the concept of framing. The work was conducted at the Academia dà ­Architettura in Mendrisio, Switzerland, under the direction of Peter Zumthor, Miguel Kreisler and Myriam Sterling, emphasizing the relationship between ordered structures and contextual propriety. The making of architecture is inherently most pure when approached as the subtraction of unnecessary elements and a distillation ...

  19. Textile Architecture

    Maurin, Bernard; Motro, René


    The basic idea for a textile architecture project originates during early meetings between the architect and the engineer. The morphologic richness of such projects is provided by the varying curvatures of shapes, in contradiction with a classical straight line and orthogonal architecture. However the rules of construction are quite different in terms of realisation and of mechanical behaviour: textile membranes are subjected to a pre-stress conferring them their rigidity, and a major objecti...

  20. Fractal Architecture

    Rumież, Agnieszka


    Research focuses on the recognition of the disposition of natural environment, which serves as an inspiration for cultural creation as it has always been in the history of architecture. Modern mathematical model of fractal geometry has been used to understand patterns occurring in the surrounding. The comparative analysis has been conducted between the abstract mathematical model and architectural composition in the view of contemporary cognitive paradigms. In conclusion, a hypothesis of a ne...

  1. IAIMS Architecture

    Hripcsak, George


    An information system architecture defines the components of a system and the interfaces among the components. A good architecture is essential for creating an Integrated Advanced Information Management System (IAIMS) that works as an integrated whole yet is flexible enough to accommodate many users and roles, multiple applications, changing vendors, evolving user needs, and advancing technology. Modularity and layering promote flexibility by reducing the complexity of...

  2. HLA and skin cancer HLA e câncer de pele

    Renan Rangel Bonamigo


    Full Text Available Skin cancer - melanoma and non melanoma - are common neoplasm with rising incidence over the last decades. It is an important public health problem. Its pathogenesis is not completely understood and the same happens with the genetic factors involved. The genes that encode the HLA are associated with some tumors and they may be responsible for one of the mechanisms that take part in the development of the before mentioned cancers. We have reviewed the literature on the subject of HLA antigens, melanoma and non melanoma skin cancer.Os cânceres da pele - melanoma e não-melanoma - são neoplasias comuns e com incidência crescente ao longo de décadas. Representam um importante problema de saúde pública. A patogênese destas neoplasias não é completamente compreendida, assim como não o são os fatores genéticos envolvidos. Os genes HLA estão associados a alguns tumores e podem representar um dos mecanismos implicados no desenvolvimento do câncer de pele. Apresenta-se uma revisão atualizada sobre a relação entre antígenos HLA, câncer da pele não-melanoma e melanoma.

  3. Polymorphism of exon 3 of the HLA-G gene

    Hviid, T V; Meldgaard, M; Sørensen, Steen; Morling, N


    rate of embryos. HLA-G seems to play an important role in the feto-maternal relationship. The polymorphism of the HLA-G locus is not fully clarified. One study has shown extensive nucleotide sequence variation in the exon 3 (alpha-2 domain) in healthy African Americans. A few studies in other...

  4. New Developments in HLA-G in Cardiac Transplantation.

    Lazarte, Julieta; Tumiati, Laura C; Rao, Vivek; Delgado, Diego H


    Human Leukocyte Antigen-G (HLA-G) is a non-classical class 1b protein, whose gene is located on chromosome 6 (6p21.31). HLA-G inhibits the immune cells' cytotoxic activity by interacting with specific receptors on their membranes. Since it is a naturally occurring immune modulator, HLA-G has been investigated in transplantation. Indeed, a number of investigations reveal that HLA-G expression is influenced by genetic polymorphisms and in turn, those polymorphisms are associated with detrimental or beneficial outcomes in various pathological situations. The present review introduces the HLA-G molecule, the gene and its polymorphisms. It focuses on the expression of HLA-G and the role of polymorphisms primarily in heart transplant outcomes, secondarily in other transplant organs, as well as the role of the allograft and effect of medical therapy. We discuss the limitations in HLA-G transplant investigations and future directions. The immune inhibiting activity of HLA-G has a great deal of potential for its utilization in enhancing diagnostic, preventive and therapeutic strategies against rejection in the setting of transplantation. PMID:26707934

  5. Isolated HLA-B27 associated Achilles tendinitis.

    I. Olivieri; Gemignani, G; Gherardi, S; Grassi, L.; M.L. Ciompi


    The case of a 37 year old man with a longstanding HLA-B27 associated bilateral Achilles tendinitis without seronegative spondyloarthropathy is reported. This case suggests that heel enthesopathy may for a long time be the only clinical manifestation of the HLA-B27 associated disease process.

  6. Federal Holidays

    Office of Personnel Management — Federal law (5 U.S.C. 6103) establishes the following public holidays for Federal employees. Please note that most Federal employees work on a Monday through Friday...

  7. Architectural geometry

    Pottmann, Helmut


    Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural geometry, meanwhile contains a great wealth of individual contributions which are relevant in various fields. For mathematicians, the relation to discrete differential geometry is significant, in particular the integrable system viewpoint. Besides, new application contexts have become available for quite some old-established concepts. Regarding graphics and geometry processing, architectural geometry yields interesting new questions but also new objects, e.g. replacing meshes by other combinatorial arrangements. Numerical optimization plays a major role but in itself would be powerless without geometric understanding. Summing up, architectural geometry has become a rewarding field of study. We here survey the main directions which have been pursued, we show real projects where geometric considerations have played a role, and we outline open problems which we think are significant for the future development of both theory and practice of architectural geometry.

  8. HLA-B27, but not HLA-B7, immunodominance to influenza is ERAP dependent.

    Akram, Ali; Lin, Aifeng; Gracey, Eric; Streutker, Catherine J; Inman, Robert D


    Endoplasmic reticulum-associated aminopeptidase-1 (ERAP1) plays a critical role in the processing of peptides prior to binding to MHC class I molecules. In this article, we show for the first time, to our knowledge, that the HLA-B27 immunodominant influenza nucleoprotein (NP) 383-391 epitope is made as an N-terminally extended 14-mer before it is trimmed by ERAP. In the absence of ERAP, there is a significant reduction in the CTL response to the B27/NP383-391 epitope in influenza A (flu)-infected B27/ERAP(-/-) mice. With the use of tetramer staining, the number of naive CD8(+) T cells expressing TCR Vβ8.1 in B27/ERAP(-/-) transgenic mice is significantly lower than that seen in B27/ERAP(+/+) mice. HLA-B27 surface expression in naive and flu-infected B27/ERAP(-/-) mice is also lower than the expression seen for the same allele in naive and flu-infected B27/ERAP(+/+) mice. In contrast, surface expression of HLA-B7 was unaffected by the absence of ERAP in B7/ERAP(-/-) transgenic mice. The B7-restricted NP418-426 CTL response in flu-infected B7/ERAP(-/-) and B7/ERAP(+/+) mice was also similar. These results provide, to our knowledge, the first in vivo demonstration of ERAP functionally influencing host immune response in an HLA allele-specific manner. This principle has relevance to diseases such as ankylosing spondylitis, in which HLA-B27 and ERAP jointly contribute to disease predisposition. PMID:24835397

  9. Polymorphism of exon 3 of the HLA-G gene

    Hviid, T V; Meldgaard, Michael; Sørensen, S;


    HLA-G is a non-classical MHC class I gene with a limited tissue distribution. The most pronounced expression is detected in the cytotrophoblast of first trimester placenta. It is possible to detect mRNA for HLA-G in preimplantation blastocysts where expression is correlated with a high cleavage...... rate of embryos. HLA-G seems to play an important role in the feto-maternal relationship. The polymorphism of the HLA-G locus is not fully clarified. One study has shown extensive nucleotide sequence variation in the exon 3 (alpha-2 domain) in healthy African Americans. A few studies in other...... populations have only revealed a limited polymorphism. We investigated the polymorphism of the exon 3 of HLA-G by means of Polymerase Chain Reaction (PCR)-Single Strand Conformation Polymorphism (SSCP)- and DNA sequencing analysis in a Danish population. We detected four single-base substitutions in exon 3...

  10. Peptide binding predictions for HLA DR, DP and DQ molecules

    Wang, P.; Sidney, J.; Kim, Y.;


    BACKGROUND: MHC class II binding predictions are widely used to identify epitope candidates in infectious agents, allergens, cancer and autoantigens. The vast majority of prediction algorithms for human MHC class II to date have targeted HLA molecules encoded in the DR locus. This reflects a...... significant gap in knowledge as HLA DP and DQ molecules are presumably equally important, and have only been studied less because they are more difficult to handle experimentally. RESULTS: In this study, we aimed to narrow this gap by providing a large scale dataset of over 17,000 HLA-peptide binding...... affinities for a set of 11 HLA DP and DQ alleles. We also expanded our dataset for HLA DR alleles resulting in a total of 40,000 MHC class II binding affinities covering 26 allelic variants. Utilizing this dataset, we generated prediction tools utilizing several machine learning algorithms and evaluated...

  11. HLA antigens in psoriasis and psoriatic arthritis.

    Woodrow, J. C.; Ilchysyn, A


    HLA phenotypes were determined in 50 patients with psoriasis alone and in 50 patients with psoriasis and psoriatic arthritis. Positive associations were found in both groups with B13, B17, B37, Cw6, and DR7, and in addition with C4A6. Higher relative risks were found in respect to the patients with psoriasis alone compared with those with arthritis, and this suggests the involvement of additional genetic factors predisposing to peripheral arthritis. In patients with psoriasis only, the presen...

  12. IAIMS architecture.

    Hripcsak, G


    An information system architecture defines the components of a system and the interfaces among the components. A good architecture is essential for creating an Integrated Advanced Information Management System (IAIMS) that works as an integrated whole yet is flexible enough to accommodate many users and roles, multiple applications, changing vendors, evolving user needs, and advancing technology. Modularity and layering promote flexibility by reducing the complexity of a system and by restricting the ways in which components may interact. Enterprise-wide mediation promotes integration by providing message routing, support for standards, dictionary-based code translation, a centralized conceptual data schema, business rule implementation, and consistent access to databases. Several IAIMS sites have adopted a client-server architecture, and some have adopted a three-tiered approach, separating user interface functions, application logic, and repositories. PMID:9067884

  13. Architectural Anthropology

    Stender, Marie

    Architecture and anthropology have always had a common focus on dwelling, housing, urban life and spatial organisation. Current developments in both disciplines make it even more relevant to explore their boundaries and overlaps. Architects are inspired by anthropological insights and methods......, while recent material and spatial turns in anthropology have also brought an increasing interest in design, architecture and the built environment. Understanding the relationship between the social and the physical is at the heart of both disciplines, and they can obviously benefit from further...... collaboration: How can qualitative anthropological approaches contribute to contemporary architecture? And just as importantly: What can anthropologists learn from architects’ understanding of spatial and material surroundings? Recent theoretical developments in anthropology stress the role of materials and...

  14. Architectural Narratives

    Kiib, Hans


    In this essay, I focus on the combination of programs and the architecture of cultural projects that have emerged within the last few years. These projects are characterized as “hybrid cultural projects,” because they intend to combine experience with entertainment, play, and learning. This essay...... identifies new rationales related to this development, and it argues that “cultural planning” has increasingly shifted its focus from a cultural institutional approach to a more market-oriented strategy that integrates art and business. The role of architecture has changed, too. It not only provides a...... functional framework for these concepts, but tries increasingly to endow the main idea of the cultural project with a spatially aesthetic expression - a shift towards “experience architecture.” A great number of these projects typically recycle and reinterpret narratives related to historical buildings and...

  15. Architectural Engineers

    Petersen, Rikke Premer

    engineering is addresses from two perspectives – as an educational response and an occupational constellation. Architecture and engineering are two of the traditional design professions and they frequently meet in the occupational setting, but at educational institutions they remain largely estranged. The...... paper builds on a multi-sited study of an architectural engineering program at the Technical University of Denmark and an architectural engineering team within an international engineering consultancy based on Denmark. They are both responding to new tendencies within the building industry where the...... role of engineers and architects increasingly overlap during the design process, but their approaches reflect different perceptions of the consequences. The paper discusses some of the challenges that design education, not only within engineering, is facing today: young designers must be equipped with...

  16. Architectural Theatricality

    Tvedebrink, Tenna Doktor Olsen

    initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture...... environments and a knowledge gap therefore exists in present hospital designs. Consequently, the purpose of this thesis has been to investigate if any research-based knowledge exist supporting the hypothesis that the interior architectural qualities of eating environments influence patient food intake, health...... such as a literature review, timeline and historical outline to create a “knowledge map”, which in an eclectic manner merges the positive, normative and polemical knowledge rooted in research, objects and writings. The results of these investigations show that sparse researchbased knowledge exist directly taking...

  17. Restriction fragment length polymorphism of the HLA-DP subregion and correlations to HLA-DP phenotypes

    Hyldig-Nielsen, J J; Morling, Niels; Ødum, Niels;


    The restriction fragment length polymorphism (RFLP) of the class II HLA-DP subregion of the major histocompatibility complex (MHC) of humans has been unraveled by Southern blotting using DP alpha and DP beta probes in a study of 46 unrelated individuals with known HLA-DP types. Contrary to earlier...

  18. Architectural Anthropology

    Stender, Marie

    and other spaces that architects are preoccupied with. On the other hand, the distinction between architecture and design is not merely one of scale. Design and architecture represent – at least in Denmark – also quite different disciplinary traditions and methods. Where designers develop prototypes......, architects tend to work with models and plans that are not easily understood by lay people. Further, many architects are themselves sceptical towards notions of user-involvement and collaborative design. They fear that the imagination of citizens and users is restricted to what they are already familiar with...

  19. Reframing Architecture

    Riis, Søren


    I would like to thank Prof. Stephen Read (2011) and Prof. Andrew Benjamin (2011) for both giving inspiring and elaborate comments on my article “Dwelling in-between walls: the architectural surround”. As I will try to demonstrate below, their two different responses not only supplement my article...... focuses on how the absence of an initial distinction might threaten the endeavour of my paper. In my reply to Read and Benjamin, I will discuss their suggestions and arguments, while at the same time hopefully clarifying the postphenomenological approach to architecture....

  20. Multithreading architecture

    Nemirovsky, Mario


    Multithreaded architectures now appear across the entire range of computing devices, from the highest-performing general purpose devices to low-end embedded processors. Multithreading enables a processor core to more effectively utilize its computational resources, as a stall in one thread need not cause execution resources to be idle. This enables the computer architect to maximize performance within area constraints, power constraints, or energy constraints. However, the architectural options for the processor designer or architect looking to implement multithreading are quite extensive and

  1. Analysis of allele frequencies of HLA-DRB1 * 12 : 01 : 01G and HLA-DRB1 * 14 : 01 : 01G groups%HLA-DRB1*12:01:01G和HLA-DRB1*14:01:01G组内等位基因频率的统计分析

    何俊俊; 章伟; 和艳敏; 王炜; 韩浙东; 陈男英; 朱发明; 吕杭军; 严力行


    目的 区分并计算人类白细胞抗原(human leukocyte antigen,HLA) HLA-DRB1* 12:01:01G(HLA-DRB1* 12:01:01/12:06/12:10/12:17)和HLA-DRB1* 14:01:01G(DRB1* 14:01:01/14:54)组内等位基因及其相对频率,并分析其与HLA-DRB3和HLA-DQB1的连锁情况.方法 收集115例HLA-DRB1*12:01:01G组和108例HLA-DRB1*14:01:01G组标本,采用单核苷酸序列分析(polymerase chain reaction-sequence based typing,PCR-SBT)方法检测HLA-DRB1* 12:01:01G组等位基因的第1~3外显子序列和HLA-DRB1* 14:01:01G组的第2、3外显子序列.HLA-DRB3和HLA-DQB1基因分型采用PCR-SBT方法.结果 115例HLA-DRB1* 12:01:01G组标本中,101例(87.8%)为HLA-DRB1* 12:01:01,14例(12.2%)为HLA-DRB1* 12:10,未发现HLA-DRB1* 12:06和HLA-DRB1* 12:17. 108例HLA-DRB1*14:01:01G组标本全部为HLA-DRB1*14:54. HLA-DRB1*12:01:01与HLA-DRB3* 01:01:02和HLA-DQB1* 03:01连锁,HLA-DRB1* 12:10则与HLA-DRB3* 02:02:01和HLA-DQB1* 03:01连锁.HLA-DRB1* 14:54与HLA-DRB3* 02:02:01和HLA-DQB1* 05:02、*05:03连锁.结论 HLA-DRB1* 12:01:01G组中HLA-DRB1* 12:01:01频率最高,而HLA-DRB1* 14:01:01G组则以HLA-DRB1* 14:54频率最高.%Objective To discriminate and analyze the relative frequencies of alleles in HLA-DRB1 * 12:01:01G(HLA-DRB1 * 12:01:01 /12:06/12:10/12:17) and HLA-DRB1 * 14:01:01G (DRB1 * 14:01:01/14:54) groups and assess their associations with HLA-DRB3 and HLA-DQB1 loci.Methods A total of 115 DNA samples previously typed as HLA-DRB1 * 12:01:01G and 108 samples from HLA-DRB1 * 14:01:01G were selected.DNA sequences for exons 1 to 3 of the HLA-DRB1 locus were analyzed for HLA-DRB1 * 12:01:01G,and exons 2 to 3 were analyzed for HLA-DRB1 * 14:01:01G by polymerase chain reaction sequence-based typing (PCR-SBT).Genotyping of HLA-DRB3 and HLA-DQB1 were achieved by PCRSBT.Results Among 115 samples previously typed as HLA-DRB1 * 12:01:01G,101 (87.8%) were confirmed as HLA-DRB1 * 12:01:01 and 14 (12.2%) were HLA-DRB1 * 12:10,but HLA-DRB1 * 12:06 and HLA-DRB1 * 12

  2. 肝细胞癌组织中HLA-DR,-DQ的表达及其意义%Expression of HLA-DR and HLA-DQ in Hepatocellular Carcinoma and its Significance.

    李宏涛; 肖文华; 李秋文; 郝怡鑫; 朱建华; 王如良; 叶明


    Objective To study the expression of HLA - DR and HLA - DQ antigens in hepatocellular carcinoma ( HCC ) and its significance. Methods The expression of HLA - DR and HLA - DQ antigens in human 38 HCCs cases were detected with immunohistochemistry, then the relations between the expression of genes with clinical and pathology parameters ( such as cancerous differentiation and metastasis and others) were analyzed by Chi square test. Results The immunoreactivity of HLA - DR and - DQ proteins were mainly distributed in cytoplasm of cancerous cells, the positive rate of HLA - DR and DQ expression were 5. 3% (2/35 ) and 92. 1% ( 35/38) respectively. HLA - DR was related with gender of HCC patients, HLA - DQ was positive relation with non - lymphatic metastasis of HCC (P <0.0001 ). Conclusion HLA - DQ expression is very common in HCCs; The absence of HLA - DQ expression may contribute to lymphnodes metastasis in HCC.%目的 探讨人白细胞抗原(HLA)-DR和-DQ分子在肝细胞癌的表达及其意义.方法 采用免疫组化法分别检测HLA-DR和HLA-DQ抗原在38例人肝癌组织芯片中的表达情况,并和临床病理资料进行相关性分析.结果 肝癌组织中HLA-DR和HLA-DQ抗原信号主要定位于细胞浆.HLA-DR的阳性率为5.3%(2/38),HLA-DQ的阳性率为92.1%(35/38),但在4例伴淋巴结转移的肝癌中,3例无HLA-DQ的表达,HLA-DQ表达与肝癌的淋巴结转移负相关(P<0.0001).HLA-DR和HLA-DQ表达与年龄和肝癌的组织分化无相关性(P>0.05).结论 HLA-DQ的表达在肝癌组织中很常见,无HLA-DQ的表达可能提示与淋巴结转移有关.

  3. Future Architectures for NREN infrastructures

    Wessing, Henrik; Bozorgebrahimi, Kurosh; Belter, Bartosz; Tzanakaki, Anna; Naegele-Jackson, Susanne; Olifer, Victor; Metz, Andreas; Vojtech, Josef; Skoda, Pavel

    resources. In this work, the key findings from related projects are integrated to provide the building blocks forefficient use and sharing of spectrum. A new network architecture is derived to support exactly the service orchestration and the federated useof resources. It comprises four layers from the...... heterogeneous multi-technology physical layer up to the service provisioning and orchestration....

  4. From green architecture to architectural green

    Earon, Ofri


    The paper investigates the topic of green architecture from an architectural point of view and not an energy point of view. The purpose of the paper is to establish a debate about the architectural language and spatial characteristics of green architecture. In this light, green becomes an adjective...... that describes the architectural exclusivity of this particular architecture genre. The adjective green expresses architectural qualities differentiating green architecture from none-green architecture. Currently, adding trees and vegetation to the building’s facade is the main architectural characteristics...... of green architecture. The paper argues that this greenification of facades is insufficient. The green is only a skin cladding the exterior envelope without having a spatial significance. Through the paper it is proposed to flip the order of words from green architecture to architectural green...

  5. Donor-reactive cytokine profiles after HLA-identical living-related kidney transplantation

    J.H. Gerrits (Jeroen); J. van de Wetering (Jacqueline); J.J. Drabbels (Jos); F.H.J. Claas (Frans); W. Weimar (Willem); N.M. van Besouw (Nicole)


    textabstractBackground. After HLA-identical living-related (LR) kidney transplantation, only non-HLA antigen mismatches between donor and recipient may exist. We questioned whether donor-reactive responses against non-HLA antigens could be found after HLA-identical LR kidney transplantation, and won

  6. Role of HLA Adaptation in HIV Evolution

    Kløverpris, Henrik N.; Leslie, Alasdair; Goulder, Philip


    Killing of HIV-infected cells by CD8+ T-cells imposes strong selection pressure on the virus toward escape. The HLA class I molecules that are successful in mediating some degree of control over the virus are those that tend to present epitopes in conserved regions of the proteome, such as in p24 Gag, in which escape also comes at a significant cost to viral replicative capacity (VRC). In some instances, compensatory mutations can fully correct for the fitness cost of such an escape variant; in others, correction is only partial. The consequences of these events within the HIV-infected host, and at the population level following transmission of escape variants, are discussed. The accumulation of escape mutants in populations over the course of the epidemic already shows instances of protective HLA molecules losing their impact, and in certain cases, a modest decline in HIV virulence in association with population-level increase in mutants that reduce VRC. PMID:26834742

  7. Distribution of HLA antigens in families of patients with leukaemias

    Vojvodić Svetlana


    Full Text Available Introduction. Since the discovery of major histocompatihility complex influence on manse leukaemia in 1964, an HLA association with leukaemia in humans has been considered as a possible genetic risk factor that contributes to development of leukaemia. In addition to associations of several IILA antigens with leukaemias, it has been observed that patients with leukaemia have an increase in the frequency of HLA identical siblings, higher degree of HLA compatibility with their parents as well as higher parental HLA sharing rate in comparison to the families without patients suffering from leukaemia. Material and methods. To test hypothesis that susceptibility to leukaemia can be caused bv influence of a recessive genes associated with the major histocompatibilily complex in man, we analyzed the distribution of I class HLA antigens in 77 families of patients suffering from different types of leukaemia. In the affected families and in 72 families of healthy controls, we investigated HLA identical sibling frequency, parental sharing of one, two or three HLA antigens and degree of compatibility of parents and off springs: existence of haploidentity, compatibility in l' and 4/4 HLA antigens of A and B loci. Results We have found that in families with affected persons there is a statistically significant difference in number of HLA identical siblings in comparison to the group of healthy controls (t=2,63. Also the results have shown that among the parents of affected persons there is a statistically significant difference in mutual compatibility in one (t=3,012 and two ft= 2,4 HLA antigens. In addition, we observed an increase in the frequency of higher rate of compatibility between patients and their parents (t=3,88 in l' HLA antigens, to their mothers (t=2,83 and to their fathers (t=2,55, respectively, in comparison to the healthy control group. Conclusion The results of this study show that in families with persons suffering from leukaemia there are

  8. HLA polymorphism of the Zhuang population reflects the common HLA characteristics among Zhuang-Dong language-speaking populations

    Li SHI; Katsushi TOKUNAGA; Jia-you CHU; Xiao-qin HUANG; Lei SHI; Yu-fen TAO; Yu-feng YAO; Liang YU; Ke-qin LIN; Wen YI; Hao SUN


    A study of the human leukocyte antigen (HLA) genetic characteristics in the Zhuang, the largest ethnic population in China, would provide insight into Zhuang history and give a useful tool for disease associations, transplantation, and anthropology. In the present study, we report the comprehensive HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles and haplotypes in the Zhuang population of southern China for the first time. A total of 13 HLA-A, 24 HLA-B, 22 HLA-C, and 18 HLA-DRB1 were identified in 104 Zhuang individuals. The frequencies of HLA-A*11:01, A*02:07, A*24:02, A*02:03, and A*33:03 on A loci, B*15:02, B*58:01, B*46:01, and B*13:01 on B loci, C*03:04, C*08:01, C*01:02, C*03:02, and C*07:02 on C loci, and DRB1*15:01, DRB1*16:02, DRB1*14:01, DRB1*15:02, and DRB1*03:01 on the DRB1 loci were >10%. The A*33:03-C*03:02-B*58:01-DRB1*03:01 and A*02:07-C*01:02-B*46:01-DRB1*14:01 haplotypes were predominant in the Zhuang. The phylogenetic tree, as well as the analysis of haplotypes, suggested that the Zhuang are genetically similar to southern Chinese populations, especially the Zhuang-Dong language-speaking populations, such as the Bouyei, Dai, and Maonan. Even though the Zhuang and southern Chinese populations shared common alleles and haplotypes, the Zhuang has maintained its unique genetic characteristics.

  9. Fiscal Federalism

    Feng, Xingyuan; Ljungwall, Christer; Guo, Sujian; Wu, Alfred M.


    critical review of the theories on fiscal federalism, we develop a refined prototype of fiscal federalism. The model shows that quasi-traditional fiscal federalism is a much closer reality in China, while we argue that the refined fiscal federalism should be the direction of future reform in China....

  10. An HLA-C amino-acid variant in addition to HLA-B*27 confers risk for ankylosing spondylitis in the Korean population

    Kim, Kwangwoo; Bang, So-Young; Lee, Seunghun; Lee, Hye-Soon; Shim, Seung-Cheol; Kang, Young Mo; Suh, Chang-Hee; Sun, Celi; Nath, Swapan K; Bae, Sang-Cheol; Kim, Tae-Hwan


    Introduction The presence of the HLA-B*27 allele is a major risk factor for the development of ankylosing spondylitis (AS), which causes chronic inflammation of the spine and other sites. We investigated residual effects outside HLA-B within the major histocompatibility complex (MHC) region in the Korean population. Methods Using the Korean HLA reference panel, we inferred the classic HLA alleles and amino-acid residues of the six HLA genes (HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1) and MHC sin...

  11. Religious Architecture


    The main religions of ancient China were Buddhism,Taoism and Islam, of which Buddhism was the most widespread. As a result, Buddhist temples and towers are found all over China, and have become important components of the country's ancient architecture.

  12. 原发性肾病综合征与HLA-A、HLA-B、HLA-DRB1基因相关性的研究%The correlation study of alleles of HLA-A, HLA-B and HLA-DRB1 in patients with idiopathic nephrotic syndrome

    樊晓光; 杨菲; 张德梅; 阎冰


    目的 探讨HLA-A、HLA-B、HLA-DRB1位点基因与山西汉族激素抵抗肾病综合征(SRNS)的相关性.方法 用聚合酶链反应序列特异性引物法,对30例SRNS患者(成人22例,儿童8例)和45例正常对照者进行了HLA-A、HLA-B、HLA-DRB1等位基因分型,并分析了A、B、DRB1基因在各组的分布.结果 SRNS患者组HLA-B*15、B*44基因频率较正常对照组增高(P<0.05);成人SRNS患者组HLA-DRB1*07、B*44基因频率较正常对照组增高(P<0.05),成人SRNS患者组HLA-DRB1*15基因频率较正常对照组降低(P<0.05);儿童SRNS患者组HLA-DRB1*10基因频率较正常对照组增高(P<0.05).结论 SRNS发病可能与HLA-B*15、B*44基因有关,成人SRNS发病可能与HLA-DRB1*07、B*44基因有关,HLA-DRB1*15对成人SRNS发病可能有保护作用,儿童SRNS发病可能与HLA-DRB1*10基因有关;HLA与SRNS的相关性不仅与人种、国家和地区有关,还可能与发病年龄有关.

  13. Study on polymorphisms of HLA-A, HLA-B and HLA-DRB1 loci among HIV long-term nonprogressors in Lishui%丽水市HIV感染长期不进展者HLA-A、HLA-B和HLA-DRB1基因多态性的研究

    叶灵; 雷永良; 陈沙彬; 叶碧峰; 陈秀英


    目的 从基因水平了解丽水市艾滋病病毒(HIV)感染长期不进展者(LTNPs)与典型进展者(TPs)的人类白细胞抗原(HLA)-A、HLA-B和HLA-DRB1位点等位基因频率,比较两类人群的差异,初步探索保护性基因和易感基因.方法 应用聚合酶链反应-序列特异性引物技术(PCR-SSP),对丽水市42例LTNPs和48例TPs进行HLA-A、HLA-B和HLA-DRB1等位基因分型.结果 共鉴定出9个HLA-A等位基因,16个HLA-B等位基因,12个HLA-DRB1等位基因.HLA-A* 02频率LTNPs组(44.05%)高于TPs组(20.83%)(P<0.01),而A*11频率则是LINPs组(20.24%)低于TPs组(42.71%) (P<0.01);HLA-B* 40频率LTNPs组(17.86%)低于TPs组(28.13%) (P>0.05);HLA-DRB* 15频率LTNPs组(5.95%)低于TPs组(29.17%) (P<0.01);LTNPs组HLA基因座纯合子频率(15.87%)低于TPs组(33.33%)(P<0.01).结论 在该人群中,HLA-A* 02等位基因可能与延缓艾滋病疾病进程相关,而HLA-A* 11、B* 40、DRB1* 15可能加速艾滋病疾病进程.含HLA基因杂合子者对疾病显示出更好的抵御能力.

  14. HIV control through a single nucleotide on the HLA-B locus

    Kløverpris, Henrik N; Harndahl, Mikkel; Leslie, Alasdair J;


    Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells, and...... strong linkage disequilibrium between HLA class I alleles complicates the discrimination of individual HLA allelic effects from those of other HLA and non-HLA alleles on the same haplotype. Here, we exploit an experiment of nature involving two recently diverged HLA alleles, HLA-B*42:01 and HLA-B*42......:02, which differ by only a single amino acid. Crucially, they occur primarily on identical HLA class I haplotypes and, as Bw6 alleles, do not act as NK cell ligands and are therefore largely unconfounded by other genetic factors. We show that in an outbred cohort (n = 2,093) of HIV C...

  15. HLA region excluded by linkage analyses of early onset periodontitis

    Sun, C.; Wang, S.; Lopez, N.


    Previous studies suggested that HLA genes may influence susceptibility to early-onset periodontitis (EOP). Segregation analyses indicate that EOP may be due to a single major gene. We conducted linkage analyses to assess possible HLA effects on EOP. Fifty families with two or more close relatives affected by EOP were ascertained in Virginia and Chile. A microsatellite polymorphism within the HLA region (at the tumor necrosis factor beta locus) was typed using PCR. Linkage analyses used a donimant model most strongly supported by previous studies. Assuming locus homogeneity, our results exclude a susceptibility gene within 10 cM on either side of our marker locus. This encompasses all of the HLA region. Analyses assuming alternative models gave qualitatively similar results. Allowing for locus heterogeneity, our data still provide no support for HLA-region involvement. However, our data do not statistically exclude (LOD <-2.0) hypotheses of disease-locus heterogeneity, including models where up to half of our families could contain an EOP disease gene located in the HLA region. This is due to the limited power of even our relatively large collection of families and the inherent difficulties of mapping genes for disorders that have complex and heterogeneous etiologies. Additional statistical analyses, recruitment of families, and typing of flanking DNA markers are planned to more conclusively address these issues with respect to the HLA region and other candidate locations in the human genome. Additional results for markers covering most of the human genome will also be presented.

  16. Relationship between Ankylosing Spondylitis and HLA-B27,HLA-Cw and KIRs%HLA-B27、HLA-Cw、KIRs与强直性脊柱炎



    强直性脊柱炎(AS)是一种慢性进行性炎症性关节炎,具有明显的家族倾向.虽然,人类白细胞抗原B27(HLA-B27)被认为与AS的发病密切相关,但是由于AS发病机制复杂,HLA-B27仅为导致AS易感的主要基因之一.近年来研究发现,自然杀伤细胞免疫球蛋白样受体(KIRs)和HLA-Cw基因与AS的发生发展也有一定的相关性,且HLA-Cw与活化性/抑制性KIRs之间的失衡可能是影响AS发病机制的关键因素.%Ankylosing spondylitis( AS )is a kind of chronic progressive arthritis which presents clear familial predisposition. Although it has been confirmed that the expression of human leukocyte an-tigen-B27( HLA-B27 )closely related to AS,it is not the only susceptibility genes on AS. Recent studies found that killer immunoglobulin-like receptors( KIR )and HLA-Cw also participated the generation and development of AS. The imbalance between HLA-Cw and activation/inhibition of KIRs might play an important role in the pathogenes is of AS.

  17. HLA-A29-Positive Uveitis: Birdshot Chorioretinopathy, What Else

    Ilaria Zucchiatti


    Full Text Available Birdshot chorioretinopathy (BSCR is a relatively rare form of uveitis, which is strongly correlated with the histocompatibility leukocyte antigen (HLA-A29 class I type. Nevertheless, HLA typing is not diagnostic. The purpose of the present study was to retrospectively evaluate the ocular manifestations associated with the presence of HLA-A29 other than typical BSCR. Charts of consecutive patients with a diagnosis of intraocular inflammation and who were found to be positive for the presence of HLA-A29 were retrospectively reviewed. Only 7 patients met the criteria for a definite diagnosis of BSCR. Among the other 11 patients, the disease was bilateral in 7 patients and unilateral in 4 patients. A definite diagnosis of the following conditions were found: intraocular and CNS lymphoma in 1 patient, posterior tubercular uveitis with occlusive vasculitis in 1 patient, latent ocular tuberculosis in 1 patient, Fuchs' uveitis in 1 patient, herpetic panuveitis in 1 patient and HLA-B27 anterior uveitis in another patient. Although BSCR is strongly related to the HLA-A29 phenotype, and its presence confers a relative risk of disease, the definite diagnosis requires specific ocular characteristics. HLA-A29 typing alone is not a diagnostic requirement for the definite diagnosis of BSCR and should only be considered as a supportive finding.

  18. Competition-based cellular peptide binding assays for 13 prevalent HLA class I alleles using fluorescein-labeled synthetic peptides.

    Kessler, Jan H; Mommaas, Bregje; Mutis, Tuna; Huijbers, Ivo; Vissers, Debby; Benckhuijsen, Willemien E; Schreuder, Geziena M Th; Offringa, Rienk; Goulmy, Els; Melief, Cornelis J M; van der Burg, Sjoerd H; Drijfhout, Jan W


    We report the development, validation, and application of competition-based peptide binding assays for 13 prevalent human leukocyte antigen (HLA) class I alleles. The assays are based on peptide binding to HLA molecules on living cells carrying the particular allele. Competition for binding between the test peptide of interest and a fluorescein-labeled HLA class I binding peptide is used as read out. The use of cell membrane-bound HLA class I molecules circumvents the need for laborious biochemical purification of these molecules in soluble form. Previously, we have applied this principle for HLA-A2 and HLA-A3. We now describe the assays for HLA-A1, HLA-A11, HLA-A24, HLA-A68, HLA-B7, HLA-B8, HLA-B14, HLA-B35, HLA-B60, HLA-B61, and HLA-B62. Together with HLA-A2 and HLA-A3, these alleles cover more than 95% of the Caucasian population. Several allele-specific parameters were determined for each assay. Using these assays, we identified novel HLA class I high-affinity binding peptides from HIVpol, p53, PRAME, and minor histocompatibility antigen HA-1. Thus these convenient and accurate peptide-binding assays will be useful for the identification of putative cytotoxic T lymphocyte epitopes presented on a diverse array of HLA class I molecules. PMID:12559627

  19. Distribution of HLA-A, -B, and -C Alleles and HLA/KIR Combinations in Han Population in China

    Yunsong Shen


    Full Text Available We investigated polymorphisms of the human leukocyte antigen (HLA class I (A, B, and C loci of a Han population (n, 239 from the Yunnan province, Southwest China, using high-resolution polymerase chain reaction-Luminex (PCR-Luminex typing. We combined the HLA data from this study with the KIR genotypes from a previous study of this Han population to analyze the combination of KIR/HLA ligands. A total of 27 HLA-A, 54 HLA-B, and 31 HLA-C alleles were found in this population. The frequencies of A*11:01, A*24:02, B*40:01, B*46:01, C*01:02, C*03:04, and C*07:02 were all > 10%. The following haplotypes were common, with frequencies > 5%: 1 A-B (A*02:07-B*46:01, 2 A-C (A*02:07-C*01:02, and A*11:01-C*07:02, 4 C-B (B*13:01-C*03:04, B*40:01-C*07:02, B*46:01-C*01:02 and B*58:01-C*03:02, and 1 A-C-B (A*02:07-C*01:02-B*46:01. Analysis of KIR3D and their ligands HLA-A3/A11 and HLA-Bw4 showed that the frequencies of 3DL2+-A3/A11+ and 3DL2+-A3/A11− were 0.527 and 0.473, and the frequencies of 3DL1+-Bw4+, 3DL1+-Bw4−, 3DL1−-Bw4+, and 3DL1−-Bw4− were 0.552, 0.397, 0.038, and 0.013, respectively. The results of KIR/HLA-C combination analysis showed that all individuals had at least one inhibitory or activating KIR/HLA-C pair, and one KIR/HLA-C pair was the most frequent (157/239, followed by two pairs (46/239, three pairs (33/239, and no pairs (3/239. Comparison of KIR gene and HLA gene and their pair frequency between Yunnan Han and the isolated Han (FYDH who also lived in Yunnan province showed no significant difference (P>0.05 in KIR frequencies, but significant differences (P0.05 between the two populations for KIR/HLA pairs.

  20. Infection and HLA-G Molecules in Nasal Polyposis

    Rizzo, Roberta; Malagutti, Nicola; Bortolotti, Daria; Gentili, Valentina; Rotola, Antonella; Fainardi, Enrico; Pezzolo, Teresa; Aimoni, Claudia; Pelucchi, Stefano; Di Luca, Dario; Pastore, Antonio


    Sinonasal polyposis (SNP) is a chronic inflammatory pathology with an unclear aetiopathogenesis. Human papillomavirus (HPV) infection is one candidate for the development of SNP for its epithelial cell trophism, hyperproliferative effect, and the induction of immune-modulatory molecules as HLA-G. We enrolled 10 patients with SNP without concomitant allergic diseases (SNP-WoAD), 10 patients with SNP and suffering from allergic diseases (SNP-WAD), and 10 control subjects who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA and the expression of membrane HLA-G (mHLA-G) and IL-10 receptor (IL-10R) and of soluble HLA-G (sHLA-G) and IL-10 by polyp epithelial cells. The results showed the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5), all characterized by a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV-11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was observed in HPV negative polyps. These data highlight new aspects of polyposis aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic markers in the follow-up of SNP-WoAD. PMID:24741599

  1. Infection and HLA-G Molecules in Nasal Polyposis

    Roberta Rizzo


    Full Text Available Sinonasal polyposis (SNP is a chronic inflammatory pathology with an unclear aetiopathogenesis. Human papillomavirus (HPV infection is one candidate for the development of SNP for its epithelial cell trophism, hyperproliferative effect, and the induction of immune-modulatory molecules as HLA-G. We enrolled 10 patients with SNP without concomitant allergic diseases (SNP-WoAD, 10 patients with SNP and suffering from allergic diseases (SNP-WAD, and 10 control subjects who underwent rhinoplasty. We analyzed the presence of high- and low-risk HPV DNA and the expression of membrane HLA-G (mHLA-G and IL-10 receptor (IL-10R and of soluble HLA-G (sHLA-G and IL-10 by polyp epithelial cells. The results showed the presence of HPV-11 in 50% of SNP-WoAD patients (OR:5.5, all characterized by a relapsing disease. HPV-11 infection was absent in nonrelapsing SNP-WoAD patients, in SNP-WAD patients and in controls, supporting the hypothesis that HPV-11 increases risk of relapsing disease. HPV-11 positive SNP-WoAD patients presented with mHLA-G and IL-10R on epithelial cells from nasal polyps and showed secretion of sHLA-G and IL-10 in culture supernatants. No HLA-G expression was observed in HPV negative polyps. These data highlight new aspects of polyposis aetiopathogenesis and suggest HPV-11 and HLA-G/IL-10 presence as prognostic markers in the follow-up of SNP-WoAD.

  2. HLA typing in patients with recurrent aphthous stomatitis

    Taghavi Zenouz A


    Full Text Available Recurrent aphthous stomatitis (RAS is a common oral disorder that despite extensive"nresearches, the etiology of this phenomenon is still unknown. Because this phenomenon has been observed"nmore often in families than in individual cases, genetic influence has been investigated in most researches."nPurpose: The aim of the present study was to evaluate the association between Human Leukocyte Antigen"n(HLA and aphthous stomatitis more precisely."nMaterials and Methods: in this study, 60 patients with RAS were examined for HLA-A and HLA- B types"nand 37 of them were examined for HLA- DR and HLA-DQ types. The results were compared through Fisher"ntest with those of 25 healthy control subjects, aged more than 30 years."nResults: A significant decrease in the frequency of some antigens such as HLA-DQW 3 and HLA-A 26 in"nsubjects with RAS was observed. Therefore, according to the results of this study, these antigens were"nconsidered as resistant antigens to recurrent aphthous stomatitis. In contrast, there was no significant increase"nin the frequency of any HLA antigens in the test group, compared to the control group. This finding is in"ncontrast with the multiple reports about Behcet's disease. (Because a high frequency of HLA-B 51 has been"nfound in Behcet's syndrome."nConclusion: According to the findings of this study, it is suggested that the pathogenicity of aphthous"nulcerations in Behcet's disease and recurrent aphthous stomatitis is not the same. However, further studies are"nnecessary to prove this theory.

  3. Molecular basis for HLA-DQ associations with IDDM.

    Nepom, G T; Kwok, W W


    Autoimmune diabetes is the clinical end point for a sequential cascade of immunologic events that occur in a genetically susceptible individual. Structural and functional analysis of the HLA class II susceptibility genes in IDDM suggests likely molecular mechanisms for several of the key steps in this cascade of autoimmune events. We outline a pathway in which the HLA-DQ genes associated with IDDM bias the immunologic repertoire toward autoimmune specificities, creating an autoimmune-prone individual, followed by amplification and triggering events that promote subsequent immune activation. There are several direct links between genetics and autoimmune disease in this pathway: the developmental maturation of T-cells in a genetically susceptible individual occurs through molecular interactions between the T-cell receptor and the HLA-peptide complex. Selection of T-cells with receptors likely to contribute to autoreactivity may preferentially occur in the context of specific HLA-DQ alleles that are diabetes prone, because of inefficiencies in the peptide-MHC structural interactions of these molecules. Subsequent activation of these T-cells in the context of recognizing islet-associated antigens can trigger a poorly regulated immune response that results in progressive islet destruction. These subsequent diabetes-specific events are also directed by specific HLA genes, most prominently by the binding of specific antigenic peptides by the disease-associated HLA molecules. In this sequential cascade, opportunities for environmental influences and modulation by non-HLA genes are identified that likely act in concert with the predominant genetic susceptibility contributed by the HLA molecules themselves. Clarification of the steps in this pathway extends our understanding of the prevailing role of HLA genes in IDDM pathogenesis and suggests opportunities to intervene at discrete initiating, disease-promoting, or regulatory steps in IDDM development. PMID:9703314

  4. Invasion and persistence of Salmonella in human fibroblasts positive or negative for endogenous HLA B27

    Huppertz, H; Heesemann, J


    OBJECTIVE—Analysis of the interaction of enteropathogenic bacteria with HLA B27 transfected murine fibroblasts showed a specific influence of HLA B27 on microbial invasiveness. This possible novel mechanism for the action of HLA B27 should be verified by using endogenous HLA B27 positive and negative human fibroblasts as a model for the direct interaction of arthritogenic bacteria and host cells.
METHODS—Fibroblasts were obtained from healthy donors positive or negative for HLA B27; cultivate...

  5. The role of HLA-B27 in inflammatory arthritis

    Lynch, Sarah Janice


    Electronic version excludes material for which permission has not been granted by the rights holder The MHC class I allele, HLA-B27, is strongly associated with a group of inflammatory arthritic conditions collectively known as spondyloarthropathies (SpA). Ankylosing spondylitis (AS) shows the strongest association with 90-95 % of patients being HLA-B27 positive. The relationship between HLA-B27 and SpA has been known for over 30 years, however despite ongoing research, the reason for thi...

  6. Enhanced neutrophil migration in vivo HLA B27 positive subjects.

    Koivuranta-Vaara, P; Repo, H; Leirisalo, M; Kiistala, U; Osterman, T; Vapaatalo, H


    Chemotaxis of polymorphonuclear leucocytes in vivo was studied in patients with previous yersinia arthritis and in healthy subjects with or without HLA B27 by means of a skin chamber technique. Irrespective of previous arthritis the number of neutrophils in the chamber media was significantly higher in HLA B27 positive subjects than in those without HLA B27. The amounts of prostaglandins E2, F2 alpha, and 6-keto-F1 alpha in the chamber media correlated positively with the corresponding cell c...



    Thirty patients with Vogt-Koyanagi-Haradas disease were typed for HLA-A and HLA-B antigenic determinants by a microlymphocytotoxicity technique. HLA-B22 antigen showed an increased frequency of 43.3% in the patient group(relative risk=8.69; exact P<0.0001; corrected P<0.0025) compared with normal control group(frequency=7.69%). This association suggests that immunogenetic factor may play an important role in the pathogenesis of Vogt-Koyanagi-Harada's disease.

  8. Presence of HLA-DR molecules and HLA-DRB1 mRNA in circulating CD4+ T cells

    Revenfeld, Anne Louise Schacht; Steffensen, Rudi; Pugholm, Lotte Hatting;


    The human major histocompatibility complex class II (MHCII) isotype HLA-DR is currently used as an activation marker for T cells. However, whether an endogenous protein expression or a molecular acquisition accounts for the presence of HLA-DR on T cells remains undetermined and still controversial....... In order to further characterize this phenomenon, we compared several aspects of the presence of the HLA-DR protein to the presence of associated mRNA (HLA-DRB1), focusing on human T cells from peripheral blood of healthy individuals. Using a flow cytometric approach, we determined that the HLA......-DR observed on CD4+ T cells was almost exclusively cell surface-associated, while for autologous CD19+ B cells, the protein could be located in the plasma membrane as well as in the cytoplasm. Moreover, negligible expression levels of HLA-DRB1 were found in CD4+ T cells, using an HLA-DRB1 allele-specific q...

  9. Kosmos = architecture

    Tine Kurent


    Full Text Available The old Greek word "kosmos" means not only "cosmos", but also "the beautiful order", "the way of building", "building", "scenography", "mankind", and, in the time of the New Testament, also "pagans". The word "arhitekton", meaning first the "master of theatrical scenography", acquired the meaning of "builder", when the words "kosmos" and ~kosmetes" became pejorative. The fear that architecture was not considered one of the arts before Renaissance, since none of the Muses supervised the art of building, results from the misunderstanding of the word "kosmos". Urania was the Goddes of the activity implied in the verb "kosmein", meaning "to put in the beautiful order" - everything, from the universe to the man-made space, i. e. the architecture.

  10. 新等位基因HLA-B*13:01:06的核苷酸序列分析%Nucleotide sequence analysis for a new HLA-B allele HLA-B * 13 : 01 : 06

    熊白玉; 谭茵; 黄颖烽; 杨劭宇; 罗宏图; 沈樑; 周泰成; 肖灿军


    Objective To confirm a new allele HLA-B * 13:01:06 and analyze its nucleotide sequence.Methods Genomic DNA was extracted using a Qiagen DNA extraction kit.Nucleotide sequences of HLA-A,HLA-B,HLA-C and HLA-DRB1 were analyzed by polymerase chain reaction-sequence based typing (PCR-SBT).HLA high-resolution results were assigned,and the nucleotide sequences of HLA-B locus was compared with that of HLA-B * 13:01:01.Results The nucleotide sequence of the new allele shows a strong similarity to that of HLA-B * 13:01:01.One nucleotide in exon 2 has changed from G→A at position 219 (codon 49 GCG→GCA),which however did not result in amino acid change.Conclusion The novel allele verified by sequencing has been submitted to GenBank and officially named as HLA-B * 13:01:06 by the World Health Organization HLA Nomenclature Committee.%目的 对1例HLA新等位基因进行确认并分析其核苷酸序列.方法 采用Qiagen试剂盒提取样本DNA,PCR-测序分型技术获得HLA-A、HLA-B、HLA-C、HLA-DRB1的核苷酸序列及HLA高分辨率分型结果,并分析HLA-B位点与HLA-B* 13:01:01等位基因序列的异同.结果 HLA-B位点中发现1个与HLA-B* 13:01:01核苷酸序列高度相似的新等位基因,与HLA-B* 13:01:01相比,该等位基因第2外显子的219位碱基出现G→A点突变,49位密码子由GCG→GCA,两者编码的氨基酸相同.结论 该基因序列为新的HLA等位基因,并被世界卫生组织HLA因子命名委员会正式命名为HLA-B* 13:01:06.


    唐玉阳; 王恒


    Objective. To evaluate the Plasmodium falciparum CTL epitope vaccines in HLA class I allele specific human cell lines that have high frequency among Chinese population. Methods. Synthesized oligonucleotides encoding for P.f. CTL epitope genes, constructed eukaryotic expression plasmids, transfected the minigenes into HLA class I allele specific human cell lines and identified endogenous expressing of the minigenes by RT-PCR and HLA stabilization assay. Results. Two mini-genes encoding Plasmodium falciparum CTL epitopes were designed and cloned, respectively, into an eukaryotic expressing vector to form TR26 which was restricted to HLA-B51, SH6 which was restricted to HLA-A2.1, and TS, which had the two aforementioned mini-genes fused in tandem. All of these CTL epitope genes were transfected and endogenously expressed in respective cell lines containing appropriate HLA molecules. The obviously increased expressions of HLA class I molecules were detected in the transfected cell lines. It was demonstrated that the two discrete Plasmodium falciparum epitope genes were effectively processed and presented, and the close proximity of the two epitope genes in one chain as in mini-gene TS did not interfere with the processing and presenting of each epitope gene in corresponding cell line. Conclusion. A successful expression and presentation of multiple CTL epitope mini-gene in MHC class I allele specific human cell lines were demonstrated by an in vitro assay, which could be corresponding to the vaccination of CTL vaccines in people with different MHC I molecules. This work also suggested the possibility of constructing a multiple CTL epitope plasmodium falciparum DNA vaccine that could cover most of Chinese population.

  12. MUF architecture /art London

    Svenningsen Kajita, Heidi


    Om MUF architecture samt interview med Liza Fior og Katherine Clarke, partnere i muf architecture/art......Om MUF architecture samt interview med Liza Fior og Katherine Clarke, partnere i muf architecture/art...

  13. Two Cases of Transfusion-related Acute Lung Injury Triggered by HLA and Anti-HLA Antibody Reaction

    Lee, Ji Hyun; Kang, Eun-Suk; Kim, Dae-Won


    Transfusion-related acute lung injury (TRALI) is a serious adverse transfusion reaction that is presented as acute hypoxemia and non-cardiogenic pulmonary edema, which develops during or within 6 hr of transfusion. Major pathogenesis of TRALI is known to be related with anti-HLA class I, anti-HLA class II, or anti-HNA in donor's plasma. However, anti-HLA or anti-HNA in recipient against transfused donor's leukocyte antigens also cause TRALI in minor pathogenesis and which comprises about 10% ...

  14. HLA-B27和强直性脊柱炎%HLA-B27 antigen and ankylosing spondylitis

    陶赞英; 郑明慈



  15. Identification of a novel HLA-A allele, HLA-A*01:195, in a UAE national.

    Abdrabou, Wael; Witzel, Ini-Isabée; Paduch, Agnieszka; Tay, Guan; Alsafar, Habiba


    A novel human leucocyte antigen (HLA)-A allele, HLA-A*01:195, was identified by sequence-based typing (SBT) in a UAE national subject. The novel allele is identical to its closest known allele, HLA-A*01:01:01:01, in exon 2, 3 and 4, except for a single nucleotide mutation of A to G at position 442 in exon 3 (codon 124 in the α2 domain of the α chain of the mature protein). This A to G mutation results in an amino acid change of isoleucine #124 to valine. PMID:27184862

  16. Interaction between HLA-B60 and HLA-B27 as a Better Predictor of Ankylosing Spondylitis in a Taiwanese Population.

    James Cheng-Chung Wei

    Full Text Available Ankylosing spondylitis (AS is a form of chronic inflammatory spondyloarthritis (SpA that causes pain and stiffness in spines or joints. Human leukocyte antigen B27 (HLA-B27 and B60 (HLA-B60 have been reported as major genetic risk factors of AS. In addition, rs13202464, located on major histocompatibility complex (MHC region, showed high sensitivity (98.7% and specificity (98.0% for HLA-B27.The aim of our study is to test whether the interaction between HLA-B60 and HLA-B27 (rs13202464 can serve as a better predictor of AS. We have genotyped HLA-B60 and rs13202464 among 471 patients with AS and 557 healthy subjects. Combined risk factors were investigated to test the biological interaction.Our results indicated that the relative risk (RR for HLA-B27+/HLA-B60- was 152 (95% CI 91 to 255 and it increased to 201 (95% CI 85 to 475 in HLA-B27+/HLA-B60+ patients (with HLA-B27-/HLA-B60- as reference. Combinational analysis of two risk factors (HLA-B27+/HLA-B60+ showed a relative excess risk due to interaction (RERI of 46.79 (95% CI: -117.58 to 211.16, attributable proportion (AP of 0.23 (95% CI: -0.41 to 0.88 and a synergy index (S of 1.31 (95% CI: 0.56 to 3.04.In conclusion, genetic interaction analysis revealed that the interaction between HLA-B60 and HLA-B27 is a better marker for the risk of AS susceptibility in a Taiwanese population.

  17. Federation views as a basis for querying and updating database federations

    Balsters, H.; Brock, E.O. de


    This paper addresses the problem of how to query and update so-called database federations. A database federation provides for tight coupling of a collection of heterogeneous component databases into a global integrated system. This problem of querying and updating a database federation is tackled by describing a logical architecture and a general semantic framework for precise specification of such database federations, with the aim to provide a basis for implementing a federation by means o...

  18. Pathogenicity of Misfolded and Dimeric HLA-B27 Molecules

    Antony N. Antoniou


    Full Text Available The association between HLA-B27 and the group of autoimmune inflammatory arthritic diseases, the spondyloarthropathies (SpAs which include ankylosing spondylitis (AS and Reactive Arthritis (ReA, has been well established and remains the strongest association between any HLA molecule and autoimmune disease. The mechanism behind this striking association remains elusive; however animal model and biochemical data suggest that HLA-B27 misfolding may be key to understanding its association with the SpAs. Recent investigations have focused on the unusual biochemical structures of HLA-B27 and their potential role in SpA pathogenesis. Here we discuss how these unusual biochemical structures may participate in cellular events leading to chronic inflammation and thus disease progression.

  19. Hlađenje mlijeka u bazenu kapaciteta 1000 litara

    Jovanović, Velimir


    U cilju izdavanja javne isprave (atesta) o tehničkim karakteristikama i tehnološkim svojstvima bazena za hlađenje mlijeka kapaciteta 1000 litara izvršena su ispitivanja koja su dala podatke o brzini hlađenja održavanju temperature (izolacija), osjetljivosti termostata, radu miješalice, o točnosti utvrđivanja količina mlijeka pomoću mjernog štapa, utrošku električne energije i općoj podobnosti za sanitaciju. Ispitivani bazen za hlađenje mlijeka ispunjava tehnološke zahtjeve za pravilno hlađenj...

  20. Advances in DNA sequencing technologies for high resolution HLA typing.

    Cereb, Nezih; Kim, Hwa Ran; Ryu, Jaejun; Yang, Soo Young


    This communication describes our experience in large-scale G group-level high resolution HLA typing using three different DNA sequencing platforms - ABI 3730 xl, Illumina MiSeq and PacBio RS II. Recent advances in DNA sequencing technologies, so-called next generation sequencing (NGS), have brought breakthroughs in deciphering the genetic information in all living species at a large scale and at an affordable level. The NGS DNA indexing system allows sequencing multiple genes for large number of individuals in a single run. Our laboratory has adopted and used these technologies for HLA molecular testing services. We found that each sequencing technology has its own strengths and weaknesses, and their sequencing performances complement each other. HLA genes are highly complex and genotyping them is quite challenging. Using these three sequencing platforms, we were able to meet all requirements for G group-level high resolution and high volume HLA typing. PMID:26423536

  1. Multiple joint tuberculosis presenting as HLA-B27 disease

    Hopkins, G. O.


    A case of multifocal osteoarticular tuberculosis in a young Caucasian male is presented. The diagnostic difficulty, compounded by slow progression of the disorder and the presence of the tissue antigen HLA-B27, is discussed.

  2. Coexisting HLA-B27 positive spondyloarthritis and polyarteritis nodosa.

    Sattar, M A


    A 38 year old woman presented with widespread polyarteritis nodosa a few years after the onset of HLA-B27 positive spondyloarthritis. The concomitant coexistence of these two disorders suggests a possible association in this genetically susceptible subject.

  3. PCR-SBT检测HLA-C座位1-7外显子序列鉴别HLA-C*07:01:01G和C*07:02:01G组等位基因%Discrimination of Alleles in HLA-C * 07:01 :O1G and HLA-C * 07:02 :O1G Groups through Detection Sequences in Exons 1 to 7 of HLA-C Locus by Using Polymerase Chain Reaction Sequence-Based Typing

    吕杭军; 章伟; 可俊俊; 和艳敏; 王炜; 韩浙东; 陈男英; 朱发明; 严力行


    This study was aimed to discriminate the alleles in the HLA-C * 07-.01-01G and HLA-C * 07-.02-01G groups and analyze their associations with HLA-B locus. Samples previously typed as HLA-C * 07 -.01 ;01G and HLA-C * 07-.02 -01G were collected. The nucleotide sequences in exons 1 to 7 of the HLA-C locus were sequenced by ploymerase chain reaction sequence-based typing ( PCR-SBT) and HLA-B genotyping was also preformed by PCR-SBT in these samples. The results showed that 4 samples(30. 8% ) were confirmed as HLA-C * 07-.01 -.01 and 9 samples (69. 2% ) were HLA-C* 07-.06 among 13 samples previously typed as HLA-C * 07-.01:01G. Linkage disequilibrium (LD) analysis showed that HLA-C * 07-.06 allele was strongly related with HLA-B * 44 -.03. All samples were typed as C*07'; 02 -.01 among 102 individuals previously typed as C * 07-.02-.01G. LD analysis showed that C * 07-.02 -.01 was strongly related with HLA-B *51:01, B *46:01, B * 39-.01, B *40:01, B * 38-.02, B * 15-.02 alleles. It is concluded that HLA-C * 07-.01:01 and HLA-C * 07-.06 alleles are confirmed in the HLA-C * 07-.01:01G group and HLA-C *07:02:01 is a preferred allele in the HLA-C * 07-.02-.01G.%本研究旨在探讨区分人类白细胞抗原(HLA)-C* 07:01:01G和HLA-C* 07:02:01G组内等位基因,并分析其与HLA-B的连锁情况.通过收集HLA-C* 07:01:01G组和HLA-C* 07:02:01G组标本,采用聚合酶链反应测序分析方法(PCR-SBT)检测HLA-C座位第1-7外显子编码序列,并采用PCR-SBT方法对标本进行HLA-B基因分型.结果表明,13例HLA-C* 07:01:01G组标本中,4例(30.8%)标本为HLA-C* 07:01:01,9例(69.2%)标本为HLA-C* 07:06;连锁分析显示,HLA-C* 07:06与HLA-B* 44:03高度连锁.102例HLA-C* 07:02:01G组标本全部为HLA-C* 07:02:01;连锁分析显示,HLA-C* 07:02:01与HLA-B* 51:01、B*46:01、B*39:01、B*40:01、B* 38:02、B*15:02高度连锁.结论:HLA-C* 07:01:01G组中发现存在HLA-C* 07:01:01和HLA-C* 07:06,而HLA-C* 07:02:01G组中以HLA-C* 07:02:01为主导.

  4. HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBVI Hodgkin lymphoma

    Niens, Marijke; Jarreft, Ruth F.; Hepkema, Bouke; Nolte, Ilja M.; Diepstra, Arjan; Platteel, Mathieu; Kouprie, Niels; Delury, Craig P.; Gallagher, Alice; Visser, Lydia; Poppema, Sibrand; te Meerman, Gerard J.; Van den Berg, Anke


    Previous studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV)-positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the

  5. Haptic architecture becomes architectural hap

    Herssens, Jasmien; Heylighen, Ann


    Universal Design is a recent design paradigm which aims at handicap elimination in the physical environment and strives for a more humanized architecture. After pointing out the value of Universal Design, the paper advances human centred design as a possible methodology to make this paradigm operational. Key to this methodology is the explicit attention for cognitive human factors in experiencing space and—the focus of this paper—for the role played by the sense of tou...

  6. Role for HLA in susceptibility to infectious mononucleosis

    Farrell, Paul J


    Factors involved in determining whether infectious mononucleosis occurs after primary EBV infection may include age, dose of virus received, and various genetic markers. A study by McAulay and colleagues reported in this issue of the JCI shows that the presence of certain HLA class I alleles correlates with the incidence and severity of infectious mononucleosis (see the related article beginning on page 3042). These same HLA alleles are also risk factors for EBV-associated Hodgkin lymphoma (H...

  7. HLA-B*5701 testing to predict abacavir hypersensitivity

    Ma, Joseph D.; Lee, Kelly C.; Kuo, Grace M


    Abacavir is a nucleoside reverse transcriptase inhibitor used for combination antiretroviral therapy for treating human immunodeficiency virus (HIV) infection. An adverse effect from abacavir is a treatment-limiting hypersensitivity reaction, which can be severe and potentially life-threatening. Abacavir-induced hypersensitivity reaction has been associated with the presence of the major histocompatibility complex class I allele HLA-B*5701. A screening test for the HLA-B*5701 allele can assis...

  8. Implications of HLA sequence-based typing in transplantation

    Shankarkumar U


    Full Text Available Serology-based conventional microlymphocytotoxicity HLA typing method, which has been regarded as the gold standard in organ and hematopoietic stem cell transplantation, has been replaced now by DNA-based typing. Many laboratories all over the world have already switched over to molecular methods. Microlymphocytotoxicity-based tissue typing was done using commercial sera, while the molecular typing by genomic DNA based. DNA quality and its quantity obtained using various DNA extraction protocols was found to be an important factor in the molecular method of tissue typing in transplant outcome. Many polymerase chain reaction-based molecular techniques have been adopted with far reaching clinical outcome. The sequence-based typing (SBT has been the ultimate technique, which has been of the highest reliability in defining the HLA alleles. The nonavailability of specific HLA antisera from native populations, large number of blank alleles yet to be defined and comparable low resolution of HLA alleles in SSP or SSOP technique, suggests that highly refined DNA-based methods like SBT should be used as an adjunct to HLA serology and/or low/intermediate/high resolution HLA typing in order to achieve a better transplant outcome.

  9. IMGT/HLA and the Immuno Polymorphism Database.

    Robinson, James; Halliwell, Jason A; Marsh, Steven G E


    The IMGT/HLA Database ( was first released over 15 years ago, providing the HLA community with a searchable repository of highly curated HLA sequences. The HLA complex is located within the 6p21.3 region of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and are highly polymorphic, with some genes currently having over 3,000 known allelic variants. The Immuno Polymorphism Database (IPD) ( expands on this model, with a further set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. IPD currently consists of four databases: IPD-KIR contains the allelic sequences of killer-cell immunoglobulin-like receptors; IPD-MHC is a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute we are able to provide public access to this data through the website PMID:25048120

  10. HLA- DR Alleles in Pakistani Patients of Pemphigus Vulgaris

    Objective: To determine frequency of HLA-DR alleles in Pakistani patients of pemphigus vulgaris in comparison with local healthy controls. Study Design: Cross-sectional, comparative study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January 2011 to January 2014. Methodology: Twenty eight patients with biopsy proven diagnosis of pemphigus vulgaris referred from Department of Dermatology, Military Hospital, Rawalpindi were included. Patients were compared with a group of 150 unrelated local healthy subjects. DNA was extracted from peripheral blood collected in Tri-potassium EDTA. HLA-DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using SSP (sequence specific primers). HLA type was determined by agarose gel electrophoresis and results recorded. Phenotype frequency of various alleles among patient group and control group was calculated by direct counting and significance of their association was determined by Fisher's exact test/ Chi square test. Results: A total of 12 male and 16 female patients, with age ranging from 21 to 34 (mean 23.4 years) were genotype for HLA-DRB1 loci. A statistically significant association of the disease with HLA-DRB1*04 was observed (50% versus 20.7% in controls, p < 0.05). Conclusion: There is a strong association of HLA-DRB1*04 with pemphigus vulgaris in Pakistani population. (author)