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Sample records for architecture hla federation

  1. High Level Architecture (HLA) federation with Umbra and OPNET federates.

    Energy Technology Data Exchange (ETDEWEB)

    Oppel, Fred John III; Hart, Brian; Van Leeuwen, Brian P.

    2004-03-01

    Network-centric systems that depend on mobile wireless ad hoc networks for their information exchange require detailed analysis to support their development. In many cases, this critical analysis is best provided with high-fidelity system simulations that include the effects of network architectures and protocols. In this research, we developed a high-fidelity system simulation capability using an HLA federation. The HLA federation, consisting of the Umbra system simulator and OPNET Modeler network simulator, provides a means for the system simulator to both affect, and be affected by, events in the network simulator. Advances are also made in increasing the fidelity of the wireless communication channel and reducing simulation run-time with a dead reckoning capability. A simulation experiment is included to demonstrate the developed modeling and simulation capability.

  2. High level architecture evolved modular federation object model

    CERN Document Server

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

    2009-01-01

    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.

  3. High level architecture evolved modular federation object model

    Institute of Scientific and Technical Information of China (English)

    Wang Wenguang; Xu Yongping; Chen Xin; Li Qun; Wang Weiping

    2009-01-01

    To improve the agility, dynamics, composability, reusability, and development efficiency restricted by monolithic federation object model (FOM), a modular FOM is 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 compoable simulation both in academia and practice is presented and future directions are pointed out.

  4. Interoperability between Heterogeneous Federation Architectures: Illustration with SAML and WS-Federation

    CERN Document Server

    Ates, Mikaël; Lardon, Jérémy; Fayolle, Jacques; Sauviac, B; 10.1109/SITIS.2007.148

    2008-01-01

    Digital identity management intra and inter information systems, and, service oriented architectures, are the roots of identity federation. This kind of security architectures aims at enabling information system interoperability. Existing architectures, however, do not consider interoperability of heterogeneous federation architectures, which rely on different federation protocols.In this paper, we try to initiate an in-depth reflection on this issue, through the comparison of two main federation architecture specifications: SAML and WS-Federation. We firstly propose an overall outline of identity federation. We furthermore address the issue of interoperability for federation architectures using a different federation protocol. Afterwards, we compare SAML and WS-Federation. Eventually, we define the ways of convergence, and therefore, of interoperability.

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

    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.

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

    CERN Document Server

    Tolk, Andreas

    2010-01-01

    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...

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

    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.

  8. Service-oriented high level architecture

    CERN Document Server

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

    2009-01-01

    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.

  9. 潜艇综合训练仿真系统HLA联邦设计与开发研究%HLA Federation Design and Development Research of Submarine Synthetic Training Simulation System

    Institute of Scientific and Technical Information of China (English)

    吴金平; 陆铭华; 李践飞

    2011-01-01

    为了构造潜艇综合训练仿真系统更为合理的体系结构,增强联邦各仿真部位和控制部位的可重用性和互操作性,在技术手段上保证潜艇综合训练仿真系统的开发水平和训练质量,结合潜艇部队装备发展和作战训练实际,针对仿真驱动的潜艇实装作战训练仿真系统,基于高层体系结构(HLA)机制,结合HLA接口规范所提供的六类服务,重点研究潜艇综合训练仿真系统联邦的设计与开发过程等内容.%In order to form more reasonable configuration frame and enhance the reusability and interoperation of every simulation part and control part of submarine synthetic training simulation system federation, to achieve better development standard and training quality of submarine synthetic training simulation system at the aspect of technology, combined with the development of equipment and the reality of combat training of submarine force, according to analyzing submarine real-equipped combat simulation training system with the drive of simulation, based on the mechanism of HLA(High Level Architecture) and combined with six types of service provided by HLA Interface Specification, HLA federation design and development course research of submarine synthetic training simulation system was put emphasis on.

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

    Science.gov (United States)

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

    2012-01-01

    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

  11. A Study on Discrete Event Simulation (DES) in a High-Level Architecture (HLA) Networked Simulation

    Science.gov (United States)

    2010-12-01

    and syntactic interpretations of the data fields in the standardized Object Model Template ( OMT ) and customized the Federation Object Model (FOM...to the Object Model Template ( OMT ) defined in the IEEE 1516 standards [7]. The FOM is a consolidated list of types of objects and their attribute...Federation Object Model (FOM) to be used that is designed according to the Object Model Template ( OMT ). This would provide the common data structure template

  12. The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture

    Science.gov (United States)

    Garrido, Federico; Perea, Francisco; Bernal, Mónica; Sánchez-Palencia, Abel; Aptsiauri, Natalia; Ruiz-Cabello, Francisco

    2017-01-01

    Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I) expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/“soft” or irreversible/“hard” due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL). PMID:28264447

  13. The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture

    Directory of Open Access Journals (Sweden)

    Federico Garrido

    2017-02-01

    Full Text Available Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/“soft” or irreversible/“hard” due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL.

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

    Directory of Open Access Journals (Sweden)

    Rafael J. Martínez

    2011-04-01

    Full Text Available 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 have been considered in the design of the new architecture. Furthermore, coordination and cooperation among the different elements in the system is allowed in the proposed control system. By integrating a network oriented device server Player, Java Agent Development Framework (JADE and High Level Architecture (HLA, the previous concepts have been considered in the new architecture presented in this paper. HLA can be considered the most important part because it not only allows the data distribution and implicit communication among the parts of the system but also allows to simultaneously operate with simulated and real entities, thus allowing the use of hybrid systems in the development of applications.

  15. A new HLA-based distributed control architecture for agricultural teams of robots in hybrid applications with real and simulated devices or environments.

    Science.gov (United States)

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

    2011-01-01

    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 have been considered in the design of the new architecture. Furthermore, coordination and cooperation among the different elements in the system is allowed in the proposed control system. By integrating a network oriented device server Player, Java Agent Development Framework (JADE) and High Level Architecture (HLA), the previous concepts have been considered in the new architecture presented in this paper. HLA can be considered the most important part because it not only allows the data distribution and implicit communication among the parts of the system but also allows to simultaneously operate with simulated and real entities, thus allowing the use of hybrid systems in the development of applications.

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

    Science.gov (United States)

    Wilson, Jeffery A.

    2012-01-01

    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).…

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

    Science.gov (United States)

    2010-07-01

    ... Federal agencies meet in providing architectural and interior design services? 102-76.25 Section 102-76.25...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 76-DESIGN AND CONSTRUCTION Design and Construction § 102-76.25 What standards must Federal agencies meet in providing architectural and interior design...

  18. 41 CFR 102-77.25 - Do Federal agencies have responsibilities to provide national visibility for Art-in-Architecture?

    Science.gov (United States)

    2010-07-01

    ... 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,...

  19. Building Real-Time Collaborative Applications with a Federated Architecture

    Directory of Open Access Journals (Sweden)

    Pablo Ojanguren-Menendez

    2015-12-01

    Full Text Available Real-time collaboration is being offered by multiple libraries and APIs (Google Drive Real-time API, Microsoft Real-Time Communications API, TogetherJS, ShareJS, rapidly becoming a mainstream option for webservices developers. However, they are offered as centralised services running in a single server, regardless if they are free/open source or proprietary software. After re-engineering Apache Wave (former Google Wave, we can now provide the first decentralised and federated free/open source alternative. The new API allows to develop new real-time collaborative web applications in both JavaScript and Java environments.

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

    NARCIS (Netherlands)

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

    2006-01-01

    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

  1. A Software Architecture for Control of Value Production in Federated Systems

    Directory of Open Access Journals (Sweden)

    Jay S. Bayne

    2003-08-01

    Full Text Available Federated enterprises are defined as interactive commercial entities that produce products and consume resources through a network of open, free-market transactions. Value production in such entities is defined as the real-time computation of enterprise value propositions. These computations are increasingly taking place in a grid-connected space – a space that must provide for secure, real-time, reliable end-to-end transactions governed by formal trading protocols. We present the concept of a value production unit (VPU as a key element of federated trading systems, and a software architecture for automation and control of federations of such VPUs.

  2. Template Driven Code Generator for HLA Middleware

    NARCIS (Netherlands)

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

    2007-01-01

    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

  3. Improved D-IDS using the federated peer-to-peer architecture

    Institute of Scientific and Technical Information of China (English)

    Hoan Kyu Lee; In Joo Jang; Hyeong Seon Yoo

    2007-01-01

    A number of IDSs have been proposed for a networked or distributed environment. A modified D-IDS using federated peer-to-peer architecture, MCR (Multicast Reflector) and modified shaker protocol were proposed. The suggested scheme can be implemented easily and performs the information sharing between low-level IDS agents. As all users within a group monitor each other's, the common control server can perform detect intrusions with less cost and support the detection of the inside intruders.

  4. Local storage federation through XRootD architecture for interactive distributed analysis

    Science.gov (United States)

    Colamaria, F.; Colella, D.; Donvito, G.; Elia, D.; Franco, A.; Luparello, G.; Maggi, G.; Miniello, G.; Vallero, S.; Vino, G.

    2015-12-01

    A cloud-based Virtual Analysis Facility (VAF) for the ALICE experiment at the LHC has been deployed in Bari. Similar facilities are currently running in other Italian sites with the aim to create a federation of interoperating farms able to provide their computing resources for interactive distributed analysis. The use of cloud technology, along with elastic provisioning of computing resources as an alternative to the grid for running data intensive analyses, is the main challenge of these facilities. One of the crucial aspects of the user-driven analysis execution is the data access. A local storage facility has the disadvantage that the stored data can be accessed only locally, i.e. from within the single VAF. To overcome such a limitation a federated infrastructure, which provides full access to all the data belonging to the federation independently from the site where they are stored, has been set up. The federation architecture exploits both cloud computing and XRootD technologies, in order to provide a dynamic, easy-to-use and well performing solution for data handling. It should allow the users to store the files and efficiently retrieve the data, since it implements a dynamic distributed cache among many datacenters in Italy connected to one another through the high-bandwidth national network. Details on the preliminary architecture implementation and performance studies are discussed.

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

    Data.gov (United States)

    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...

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

    Data.gov (United States)

    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...

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

    Science.gov (United States)

    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

    2012-01-01

    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.

  8. 41 CFR 102-77.10 - What basic Art-in-Architecture policy governs Federal agencies?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What basic Art-in... Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL..., and artistic work in other media, must reflect the national cultural heritage and emphasize the...

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

    Science.gov (United States)

    Makiya, George K.

    2012-01-01

    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…

  10. Three Dimensional Computer Graphics Federates for the 2012 Smackdown Simulation

    Science.gov (United States)

    Fordyce, Crystal; Govindaiah, Swetha; Muratet, Sean; O'Neil, Daniel A.; Schricker, Bradley C.

    2012-01-01

    The Simulation Interoperability Standards Organization (SISO) Smackdown is a two-year old annual event held at the 2012 Spring Simulation Interoperability Workshop (SIW). A primary objective of the Smackdown event is to provide college students with hands-on experience in developing distributed simulations using High Level Architecture (HLA). Participating for the second time, the University of Alabama in Huntsville (UAHuntsville) deployed four federates, two federates simulated a communications server and a lunar communications satellite with a radio. The other two federates generated 3D computer graphics displays for the communication satellite constellation and for the surface based lunar resupply mission. Using the Light-Weight Java Graphics Library, the satellite display federate presented a lunar-texture mapped sphere of the moon and four Telemetry Data Relay Satellites (TDRS), which received object attributes from the lunar communications satellite federate to drive their motion. The surface mission display federate was an enhanced version of the federate developed by ForwardSim, Inc. for the 2011 Smackdown simulation. Enhancements included a dead-reckoning algorithm and a visual indication of which communication satellite was in line of sight of Hadley Rille. This paper concentrates on these two federates by describing the functions, algorithms, HLA object attributes received from other federates, development experiences and recommendations for future, participating Smackdown teams.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

    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.

  12. 面向广域网的高层体系结构设计%Design on WAN-Oriented High Level Architecture

    Institute of Scientific and Technical Information of China (English)

    范希辉; 刘萍; 杨艾军; 黎明曦

    2012-01-01

    To solve the deficiency of traditional high level architecture in solving large scale simulation, and achieve the expansion of the HLA to wide area network (WAN), put forward a new method of Run-Time Infrastructure (RTI) layered framework. Combine service oriented architecture (SOA) with HLA, the Web services provider RTI component and federate was designed. An instance was tested in lab environment, results show that the method can effectively support distributed simulation applications in WAN.%针对传统高层体系结构(high level architecture,HLA)在解决大规模仿真问题时存在的不足,为实现HLA 向广域网的扩展,提出了面向服务的运行支撑环境(run-time infrastructure,RTI)分层体系结构.将面向服务的体系结构(service oriented architecture,SOA)与HLA相结合,将Web服务技术应用于RTI,对涉及的Web服务提供组件、联邦成员设计等关键问题给出了设计方案,并通过实例在实验室环境下进行了仿真测试.测试结果表明,该设计能有效支撑广域网环境的分布式仿真应用.

  13. Improving the Federation Agreements definition ; New proposals out of the NATO MSG-052 Working Group Knowledge Network for Federation Architecture and Design

    NARCIS (Netherlands)

    Huiskamp, W.; Chaigneau, S.; Cutts, D.E.

    2008-01-01

    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

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

    NARCIS (Netherlands)

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

    2007-01-01

    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

  15. AMBIGUITY OF LOCI DURING HLA-TYPING ON SSO TECHNOLOGY AND ATTEMPT TO RESOLVE THEM

    Directory of Open Access Journals (Sweden)

    M. A. Loginova

    2010-01-01

    Full Text Available Sequence specific oligonucleotides typing was used to identify human leukocyte antigen (HLA-A, B, DRB1 alleles from 705 recruited volunteers with Volga Federal District for unrelated hematopoietic stem cell registry and 155 of their number at locus HLA-C. 48 samples cannot be entered into the database because of ambiguities in the identification of allelic loci on HLA-class I – HLA-A, HLA-B. To resolution of ambiguity use reagents kits AlleleSEQR HLA Sequencing, which allowed to reveal the ambiguity of the locus HLA-A, 44% of cases, the loci HLA-B and HLA-C – 40% of cases. Application software HARPs Finder showed the possibility of resolution of all identified allelic ambiguities (with the exception of types of ambiguity – A*03/A*32 or A*74:13/A*32:04 and A*01/A*11 or A*36:04/A*11 with the addition of basic kits AlleleSEQR HLA Sequencing reagents kit Al- leleSEQR HARPs. 

  16. HLA Multi Agent/Short-Lived Ontology Platform for Enterprise Interoperability

    OpenAIRE

    Zacharewicz, Gregory; Labarthe, Olivier; Chen, David; Vallespir, Bruno

    2010-01-01

    International audience; This paper aims at proposing an specification of the Federation oriented Enterprise Interoperability concept, using Multi Agent / HLA paradigm and the rising notion of Short-Lived Ontology. We give first, a review of Enterprise Interoperability. Then, we recall on Artificial Agent Concept and HLA Standard that appear to be adequate to support execution of the studied concept. Indeed, on the one hand Agent dialogue fits the concept of information exchange in a federated...

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

    Institute of Scientific and Technical Information of China (English)

    张展; 贾莉婷; 张琳琳

    2009-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    王利; 赵振南; 张亮

    2013-01-01

    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.

  19. Comparison of HLA allelic imputation programs

    Science.gov (United States)

    Shaffer, Christian M.; Bastarache, Lisa; Gaudieri, Silvana; Glazer, Andrew M.; Steiner, Heidi E.; Mosley, Jonathan D.; Mallal, Simon; Denny, Joshua C.; Phillips, Elizabeth J.; Roden, Dan M.

    2017-01-01

    Imputation of human leukocyte antigen (HLA) alleles from SNP-level data is attractive due to importance of HLA alleles in human disease, widespread availability of genome-wide association study (GWAS) data, and expertise required for HLA sequencing. However, comprehensive evaluations of HLA imputations programs are limited. We compared HLA imputation results of HIBAG, SNP2HLA, and HLA*IMP:02 to sequenced HLA alleles in 3,265 samples from BioVU, a de-identified electronic health record database coupled to a DNA biorepository. We performed four-digit HLA sequencing for HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1 using long-read 454 FLX sequencing. All samples were genotyped using both the Illumina HumanExome BeadChip platform and a GWAS platform. Call rates and concordance rates were compared by platform, frequency of allele, and race/ethnicity. Overall concordance rates were similar between programs in European Americans (EA) (0.975 [SNP2HLA]; 0.939 [HLA*IMP:02]; 0.976 [HIBAG]). SNP2HLA provided a significant advantage in terms of call rate and the number of alleles imputed. Concordance rates were lower overall for African Americans (AAs). These observations were consistent when accuracy was compared across HLA loci. All imputation programs performed similarly for low frequency HLA alleles. Higher concordance rates were observed when HLA alleles were imputed from GWAS platforms versus the HumanExome BeadChip, suggesting that high genomic coverage is preferred as input for HLA allelic imputation. These findings provide guidance on the best use of HLA imputation methods and elucidate their limitations. PMID:28207879

  20. Classification of human leukocyte antigen (HLA) supertypes

    DEFF Research Database (Denmark)

    Wang, Mingjun; Claesson, Mogens H

    2014-01-01

    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...... 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...

  1. An Overview of Research on Federated Architecture of Innovation Experimental Platform for Future Intemet%未来互联网联邦制创新试验平台研究

    Institute of Scientific and Technical Information of China (English)

    张健; 陈方岳

    2012-01-01

    创新试验平台的构建是未来互联网研究的重要组成部分。本文以未来互联网创新试验平台为研究对象,重点研究了联邦制的未来互联网创新试验平台,并总结了未来互联网联邦制创新试验平台的基本架构。%Construction of innovation experimental platform is important part of the research of future Intemet. Based on summarizing the state-of-the-art of future Intemet innovation experimental platform, the federated architecture for future lnternet innovation experimental platform is mainly analyzed. And a general federated architecture for future Intemet innovation experimental platform is given as a conclusion finally.

  2. HLA class I expression in bladder carcinomas.

    Science.gov (United States)

    Cabrera, T; Pedrajas, G; Cozar, J M; Garrido, A; Vicente, J; Tallada, M; Garrido, F

    2003-10-01

    HLA class I molecules are frequently lost in a large variety of human carcinomas, possibly because of T-cell immune selection of major histocompatibility complex class I deficient tumor variants. We report that this phenomenon is also a frequent event in bladder carcinomas. Of a total of 72 bladder carcinomas, 72% of the tumors had at least one alteration in HLA class I expression. These altered HLA class I phenotypes were classified as total HLA class I loss (25%; phenotype I); HLA-A or/and HLA-B locus-specific loss (12%; phenotype III); and HLA class I allelic loss (35%; phenotype II or IV). Comparison of histopathological parameters with HLA class I expression showed a statistically significant relationship with the degree of differentiation and tumor recurrence.

  3. Research about the disassociated cases between HLA-DRB1、HLA-DRB3、 HLA-DRB4、HLA-DRB5 locus and HLA-DQ locus%HLA-DRB1、HLA-DRB3、HLA-DRB4、HLA-DRB5与HLA-DQ位点不关联病例的研究

    Institute of Scientific and Technical Information of China (English)

    赵丹丹; 孙敬芬; 朱海燕; 韩晓苹; 金荔; 刘楠; 奚永志; 高春纪; 于力

    2008-01-01

    目的:完善目前已知的HLA-DR与HLA-DQ关联表.方法:从2000~2006年间到我们实验室配型的供患者中选出与关联表不相符的16例标本并对这些标本进行高分辨鉴定.结果:发现在中国汉族人中的五条HLA-DR与HLA-DQ位点连锁遗传的单倍体.结论:为目前所用的HLA-DR与HLA-DQ位点关联表在中国人群中增加五个新的单倍体,使关联表更适合于中国人群.

  4. HLA Immune Function Genes in Autism

    Directory of Open Access Journals (Sweden)

    Anthony R. Torres

    2012-01-01

    Full Text Available The human leukocyte antigen (HLA genes on chromosome 6 are instrumental in many innate and adaptive immune responses. The HLA genes/haplotypes can also be involved in immune dysfunction and autoimmune diseases. It is now becoming apparent that many of the non-antigen-presenting HLA genes make significant contributions to autoimmune diseases. Interestingly, it has been reported that autism subjects often have associations with HLA genes/haplotypes, suggesting an underlying dysregulation of the immune system mediated by HLA genes. Genetic studies have only succeeded in identifying autism-causing genes in a small number of subjects suggesting that the genome has not been adequately interrogated. Close examination of the HLA region in autism has been relatively ignored, largely due to extraordinary genetic complexity. It is our proposition that genetic polymorphisms in the HLA region, especially in the non-antigen-presenting regions, may be important in the etiology of autism in certain subjects.

  5. HLA dosage effect in narcolepsy with cataplexy.

    Science.gov (United States)

    van der Heide, Astrid; Verduijn, Willem; Haasnoot, Geert W; Drabbels, Jos J M; Lammers, Gert J; Claas, Frans H J

    2015-01-01

    Narcolepsy with cataplexy is a sleep disorder caused by the loss of hypocretin-producing neurons in the hypothalamus. It is tightly associated with a specific human leukocyte antigen (HLA)-allele: HLA-DQB1*06:02. Based on this, an autoimmune process has been hypothesized. A functional HLA-DQ molecule consists of a DQα and a DQβ chain. HLA-DQB1*06:02 (DQβ) has a strong preference for binding to HLA-DQA1*01:02 (DQα), and together they form the functional DQ0602 dimer. A dosage effect would be expected if the HLA-DQ0602 dimer itself is directly involved in the aetiology. An increased expression of the HLA-DQ0602 dimer is expected in individuals homozygous for HLA-DQB1*06:02-DQA1*01:02, but is also hypothesized in individuals heterozygous for HLA-DQB1*06:02 and homozygous for HLA-DQA1*01:02. To study the impact of the expression of the HLA-DQ0602 dimer on narcolepsy susceptibility, 248 Dutch narcolepsy patients and 1272 Dutch control subjects, all of them positive for DQB1*06:02 (heterozygous and homozygous), were HLA-genotyped with attention not only to DQB1 but also to DQA1*01:02. DQB1*06:02-DQA1*01:02 homozygosity was significantly more often seen in patients compared to controls (O.R. 2.29) confirming previous observations. More importantly, a significantly higher prevalence of homozygosity for DQA1*01:02 was found in HLA-DQB1*06:02 heterozygous patients compared to controls (O.R. 2.37, p < 0.001). The latter finding clearly supports a direct role of the HLA-DQ molecule in the development of disease.

  6. HLA-A, HLA-B, and HLA-DRB1 allele distribution in a large Armenian population sample.

    Science.gov (United States)

    Matevosyan, L; Chattopadhyay, S; Madelian, V; Avagyan, S; Nazaretyan, M; Hyussian, A; Vardapetyan, E; Arutunyan, R; Jordan, F

    2011-07-01

    Human leukocyte antigen (HLA)-A, HLA-B, and HLA-DRB1 gene frequencies were investigated in 4279 unrelated Armenian bone marrow donors. HLA alleles were defined by using PCR amplification with sequence specific primers (PCR-SSP) high- and low-resolution kits. The aim of this study was to examine the HLA diversity at the high-resolution level in a large Armenian population sample, and to compare HLA allele group distribution in Armenian subpopulations. The most frequently observed alleles in the HLA class I were HLA-A*0201, A*0101, A*2402, A*0301, HLA-B*5101, HLA-B*3501, and B*4901. Among DRB1 alleles, high frequencies of DRB1*1104 and DRB1*1501 were observed, followed by DRB1*1101 and DRB1*1401. The most common three-locus haplotype found in the Armenian population was A*33-B*14-DRB1*01, followed by A*03-B*35-DRB1*01. Our results show a similar distribution of alleles in Armenian subpopulations from different countries, and from different regions of the Republics of Armenia and Karabagh. The low level of genetic distances between subpopulations indicates a high level of population homogeneity, and the genetic distances between Armenians and other populations show Armenians as a distinct ethnic group relative to others, reflecting the fact that Armenians have been an 'isolated population' throughout centuries. This study is the first comprehensive investigation of HLA-allele group distribution in a subset of Armenian populations, and the first to provide HLA-allele and haplotype frequencies at a high-resolution level. It is a valuable reference for organ transplantation and for future studies of HLA-associated diseases in Armenian populations.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...

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

    Science.gov (United States)

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

    2011-12-01

    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.

  9. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    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...... 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 can...... 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 there can be a close...

  10. Dynamic Multicast Grouping Approach in HLA-Based Distributed Interactive Simulation

    Institute of Scientific and Technical Information of China (English)

    DAI Zhong-jian; HOU Chao-zhen

    2005-01-01

    In order to improve the efficiency of data distributed management service in distributed interactive simulation based on high level architecture (HLA) and to reduce the network traffic and save the system resource, the approaches of multicast grouping in HLA-based distributed interactive simulation are discussed. Then a new dynamic multicast grouping approach is proposed. This approach is based on the current publication and subscription region in the process of simulation. The results of simulation experiment show that this approach can significantly reduce the message overhead and use fewer multicast groups.

  11. Multi-population classical HLA type imputation.

    Directory of Open Access Journals (Sweden)

    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.

  12. DIFFERENTIAL IMPACT OF HLA-A, HLA-B AND HLA-DR COMPATIBILITY ON THE RENAL ALLOGRAFT SURVIVAL

    OpenAIRE

    V. Y. Abramov; Y. G. Moysyuk; N. N. Kaluzhina; N. B. Bogdanova; V. V. Morozova; N. V. Apanasenko

    2012-01-01

    We studied the long-term results of 532 deceased donor kidney transplantations to investigate the impact of HLA match on the survival of renal allograft. All transplants were performed in our center in 1996–2009 and moni- tored prospectively for 1–14 years. We found, the survival of 58 kidneys grafted with 0–2 mismatch for HLA- ABDR to be significantly better (Plogrank = 0,016) than the survival of the kidneys grafted with 3–6 HLA-ABDR mismatch. The full compatibility for HLA-A (n = 75) did n...

  13. HLA Typing for the Next Generation.

    Directory of Open Access Journals (Sweden)

    Neema P Mayor

    Full Text Available Allele-level resolution data at primary HLA typing is the ideal for most histocompatibility testing laboratories. Many high-throughput molecular HLA typing approaches are unable to determine the phase of observed DNA sequence polymorphisms, leading to ambiguous results. The use of higher resolution methods is often restricted due to cost and time limitations. Here we report on the feasibility of using Pacific Biosciences' Single Molecule Real-Time (SMRT DNA sequencing technology for high-resolution and high-throughput HLA typing. Seven DNA samples were typed for HLA-A, -B and -C. The results showed that SMRT DNA sequencing technology was able to generate sequences that spanned entire HLA Class I genes that allowed for accurate allele calling. Eight novel genomic HLA class I sequences were identified, four were novel alleles, three were confirmed as genomic sequence extensions and one corrected an existing genomic reference sequence. This method has the potential to revolutionize the field of HLA typing. The clinical impact of achieving this level of resolution HLA typing data is likely to considerable, particularly in applications such as organ and blood stem cell transplantation where matching donors and recipients for their HLA is of utmost importance.

  14. [The HLA system and habitual abortion].

    Science.gov (United States)

    Hajek-Rosenmayr, A

    1990-01-01

    HLA-antigens are extremely polymorphic. A calculation of the polymorphism shows a number of 398.476.343 possible HLA-phenotypes, if HLA-A, -B, -C and -DR antigens are taken into account. The compatibility of HLA-antigens of recipient and donor plays a crucial role in transplantation: HLA-antigens are the traits, which are recognized by the immune system of the recipient in the frame of a rejection of the transplant or by the donor in the frame of a graft-versus-host reaction. Large international statistics show that HLA-incompatibility between recipient and donor leads to short transplant function periods, while compatibility brings about good transplant function. Therefore, matching of HLA-antigens plays an important role in transplantation of solid organs, mainly kidneys (3, 4, 5), and is completely necessary in bone marrow transplantation. Also in pregnancy, HLA-antigens are important: If HLA compatibility between mother and child is high, the risk for habitual abortion is higher than in normal pregnancies (6, 7).

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    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...

  16. Amino acid residues 56 to 69 of HLA-A2 specify an antigenic determinant shared by HLA-A2 and HLA-B17.

    Science.gov (United States)

    Ways, J P; Rothbard, J B; Parham, P

    1986-07-01

    The mouse monoclonal antibody MA2.1 was previously used to define an epitope shared by native HLA-A2 and HLA-B17 molecules and amino acid sequence comparison of nine HLA-A,B,C molecules identified residues 62 to 65 as the region most likely to form this epitope. An unabsorbed rabbit antiserum raised against a peptide corresponding to residues 56 to 69 of HLA-A2 gives highly specific reactions with HLA-A2 and HLA-B17 heavy chains in Western blots. No interactions with native HLA-A2 and B17 molecules were detected in a variety of assays. Although the topographic relationship between the epitopes recognized by the rabbit antiserum and the monoclonal antibody could not be determined, the results show that residues 56 to 69 of HLA-A2 can form epitopes with specificity for HLA-A2 and HLA-B17.

  17. DIFFERENTIAL IMPACT OF HLA-A, HLA-B AND HLA-DR COMPATIBILITY ON THE RENAL ALLOGRAFT SURVIVAL

    Directory of Open Access Journals (Sweden)

    V. Y. Abramov

    2012-01-01

    Full Text Available We studied the long-term results of 532 deceased donor kidney transplantations to investigate the impact of HLA match on the survival of renal allograft. All transplants were performed in our center in 1996–2009 and moni- tored prospectively for 1–14 years. We found, the survival of 58 kidneys grafted with 0–2 mismatch for HLA- ABDR to be significantly better (Plogrank = 0,016 than the survival of the kidneys grafted with 3–6 HLA-ABDR mismatch. The full compatibility for HLA-A (n = 75 did not influence the long-term survival (Plogrank = 0,48. The absence of HLA-DR mismatch had a beneficial effect for survival of 68 kidneys (Plogrank = 0,07. Eighteen cases with the full HLA-B compatibility between graft and recipient demonstrated excellent long-term survival (Plogrank = 0,007. HLA-B compatibility influenced significantly (P = 0,042 the survival of transplanted kidney in the Cox regression model adjusted for donor and recipient age, panel-reactive antibody level, re-transplant, and immunosuppression protocol. The data obtained support the conclusion, that HLA compatibility should be one of the criteria of deceased donor kidney allocation. 

  18. HLA typing in acute optic neuritis

    DEFF Research Database (Denmark)

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

    1997-01-01

    OBJECTIVE: To study the association of brain magnetic resonance imaging (MRI) findings and HLA findings to clarify the relationship between monosymptomatic optic neuritis (ON) and ON as part of clinically definite multiple sclerosis (CDMS). DESIGN: Population-based cohort of patients with ON refe......OBJECTIVE: To study the association of brain magnetic resonance imaging (MRI) findings and HLA findings to clarify the relationship between monosymptomatic optic neuritis (ON) and ON as part of clinically definite multiple sclerosis (CDMS). DESIGN: Population-based cohort of patients......: The 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

  19. Monocytic HLA DR antigens in schizophrenic patients.

    Science.gov (United States)

    Krause, Daniela; Wagner, Jenny; Matz, Judith; Weidinger, Elif; Obermeier, Michael; Riedel, Michael; Gruber, Rudolf; Schwarz, Markus; Mueller, Norbert

    2012-01-01

    A genetic association of specific human leukocyte antigens (HLA) DR genes and schizophrenia has recently been shown. These HLA play a fundamental role in the control of immune responses. Furthermore infectious agents have been proposed to be involved in the pathogenesis of schizophrenia. In this study we investigated the rate of HLA DR positive monocytes in schizophrenic patients compared to controls with a special focus on the adaption to in vitro stimulation with toll-like receptor ligands. Patients with schizophrenia and matched controls were included. For each individual, we evaluated the rate of HLA DR positive monocytes (either incubated at 37 °C or after stimulation with lipopolysaccharide or Poly I:C). We found a significantly higher percentage of schizophrenic patients with elevated HLA DR positive cells (p=0.045) as compared to controls. The adjustment rate from baseline levels of monocytic HLA DR positive cells to stimulation with Poly I:C was significantly lower in schizophrenic patients (p=0.038). The increased monocytic HLA DR in schizophrenic patients and the maladjustment of their monocytic HLA DR levels to an infectious stimulus might be a sign for a disturbed monocytic immune balance in schizophrenic individuals.

  20. Soluble HLA-G expression and renal graft acceptance.

    Science.gov (United States)

    Qiu, J; Terasaki, P I; Miller, J; Mizutani, K; Cai, J; Carosella, E D

    2006-09-01

    HLA-G is a potentially interesting molecule associated with immunosuppressive function. We survey here the presence of soluble HLA-G (sHLA-G) in serial serum samples of renal transplants. A total of 330 sera of from 65 patients were tested for sHLA-G with ELISA. IgG/IgM antibodies to HLA, and MICA antibodies were also previously tested. After serial analysis of the 65 patients' 330 sera, 50% of 26 patients in functioning group had consistent sHLA-G expression or became positive, in comparison to 20.5% among 39 patients who rejected their transplants (p=0.013). Thus sHLA-G was associated with functioning transplants. Eighty percent (77 of 96) of the HLA IgG positive sera had no sHLA-G expression, while 81.4% (83 of 102) of the HLA-G(+) sera had no HLA IgG (p=0.005), which showed a negative association between sHLA-G and the presence of HLA IgG antibodies (which was previously been shown to be associated with failure). In this preliminary survey, sHLA-G was found in the serum of about 30% of renal transplant patients. sHLA-G had a negative association with allograft failure from chronic rejection, and a negative relationship with the production of HLA IgG antibodies. The significance of sHLA-G in renal transplants remains to be determined.

  1. Service orientation for the design of HLA federations

    NARCIS (Netherlands)

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

    2014-01-01

    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

  2. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    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 can...... 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...... be transformed and reapplied endlessly through its confrontation with shifting information from outside the realms of architecture. A selection of architects’ statements on their own work will be used to demonstrate how in quite diverse contemporary practices the re-use of existing architectures is applied...

  3. HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy

    Science.gov (United States)

    Ollila, Hanna M.; Ravel, Jean-Marie; Han, Fang; Faraco, Juliette; Lin, Ling; Zheng, Xiuwen; Plazzi, Giuseppe; Dauvilliers, Yves; Pizza, Fabio; Hong, Seung-Chul; Jennum, Poul; Knudsen, Stine; Kornum, Birgitte R.; Dong, Xiao Song; Yan, Han; Hong, Heeseung; Coquillard, Cristin; Mahlios, Joshua; Jolanki, Otto; Einen, Mali; Lavault, Sophie; Högl, Birgit; Frauscher, Birgit; Crowe, Catherine; Partinen, Markku; Huang, Yu Shu; Bourgin, Patrice; Vaarala, Outi; Désautels, Alex; Montplaisir, Jacques; Mack, Steven J.; Mindrinos, Michael; Fernandez-Vina, Marcelo; Mignot, Emmanuel

    2015-01-01

    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 predisposing effects of HLA-DPB1∗05:01 in Asians (OR = 1.76 [1.34–2.31], p = 4.71 × 10−05). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38–0.55] p = 8.99 × 10−17) and DP0501 (OR = 1.38 [1.18–1.61], p = 7.11 × 10−5). HLA-class-II-independent associations with HLA-A∗11:01 (OR = 1.32 [1.13–1.54], p = 4.92 × 10−4), HLA-B∗35:03 (OR = 1.96 [1.41–2.70], p = 5.14 × 10−5), and HLA-B∗51:01 (OR = 1.49 [1.25–1.78], p = 1.09 × 10−5) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza. PMID:25574827

  4. [HL-A antigens in dust allergy in children].

    Science.gov (United States)

    Seignalet, J; Levallois, C; Lapinski, H; Jean, R

    1976-12-01

    The distribution of 29 HLA antigens has been compared in 60 unrelated children presenting a dust allergy and in 300 healthy controls. We observed an increased frequency for HLA-Aw19 and HLA-B5 in patients. Yet, the differences are not very significant and there is probably no association between one HLA gene and the dust allergy.

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

    Science.gov (United States)

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

    2013-01-01

    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.

  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

    Directory of Open Access Journals (Sweden)

    Xiangyu eRao

    2013-11-01

    Full Text Available Different 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 favouring haplotypes having HLA molecules with distinct binding motifs, which would result the largest possible presented peptide repertoires in the context of infectious diseases.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  8. HLA diversity in the 1000 genomes dataset.

    Directory of Open Access Journals (Sweden)

    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. [Detection of common determinants of HLA antigens A2 and B17 by absorption using human HLA serum].

    Science.gov (United States)

    Májský, A; Korínková, P

    1983-01-01

    Attempts of cross absorption where sera of anti-HLA A2 + B17, anti-HLA A2 and anti-HLA B17 with thrombocytes were absorbed from donors of HLA A2 positive, B17 negative and HLA A2 negative, B17 positive, revealed that anti-HLA A2 and anti-HLA B17 could be eliminated from the sera of both HLA types on the platelets. Thus, the findings allow the existence of a common determinant of HLA A2 and B17-antigens to be assumed. This is the first case where the evidence of a cross reaction between antigens of two different HLA loci with human sera could be established.

  10. Architectural slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

    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.......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...

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

    Directory of Open Access Journals (Sweden)

    Spaans Vivian M

    2012-09-01

    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

  12. Statistical resolution of ambiguous HLA typing data.

    Directory of Open Access Journals (Sweden)

    Jennifer Listgarten

    2008-02-01

    Full Text Available High-resolution HLA typing plays a central role in many areas of immunology, such as in identifying immunogenetic risk factors for disease, in studying how the genomes of pathogens evolve in response to immune selection pressures, and also in vaccine design, where identification of HLA-restricted epitopes may be used to guide the selection of vaccine immunogens. Perhaps one of the most immediate applications is in direct medical decisions concerning the matching of stem cell transplant donors to unrelated recipients. However, high-resolution HLA typing is frequently unavailable due to its high cost or the inability to re-type historical data. In this paper, we introduce and evaluate a method for statistical, in silico refinement of ambiguous and/or low-resolution HLA data. Our method, which requires an independent, high-resolution training data set drawn from the same population as the data to be refined, uses linkage disequilibrium in HLA haplotypes as well as four-digit allele frequency data to probabilistically refine HLA typings. Central to our approach is the use of haplotype inference. We introduce new methodology to this area, improving upon the Expectation-Maximization (EM-based approaches currently used within the HLA community. Our improvements are achieved by using a parsimonious parameterization for haplotype distributions and by smoothing the maximum likelihood (ML solution. These improvements make it possible to scale the refinement to a larger number of alleles and loci in a more computationally efficient and stable manner. We also show how to augment our method in order to incorporate ethnicity information (as HLA allele distributions vary widely according to race/ethnicity as well as geographic area, and demonstrate the potential utility of this experimentally. A tool based on our approach is freely available for research purposes at http://microsoft.com/science.

  13. Future Network Architectures

    DEFF Research Database (Denmark)

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

    2015-01-01

    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 spec...

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

    Science.gov (United States)

    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

    2016-03-01

    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.

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

    OpenAIRE

    2013-01-01

    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 assoc...

  16. HLA-B27 subtypes among the Chukotka native groups

    Energy Technology Data Exchange (ETDEWEB)

    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

    1995-12-31

    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.

  17. HLA antigens and asthma in Greeks.

    Science.gov (United States)

    Apostolakis, J; Toumbis, M; Konstantopoulos, K; Kamaroulias, D; Anagnostakis, J; Georgoulias, V; Fessas, P; Zervas, J

    1996-04-01

    HLA-A and -B antigens were determined in a group of 76 Greek asthmatic patients: 35 children (1.5-15 years) and 41 adults (18-73 years). The results were compared to those of 400 healthy unrelated controls from the same population. The standard NIH lymphocytotoxicity test was applied. When all 76 patients were compared to the controls, a statistically significant lower frequency of HLA-B5 and -B35 antigens was noted. When adults were analysed alone, an increased frequency of HLA-B8 was found. On the other hand, in the asthmatic children sub-group, the HLA-A10 antigen was significantly higher and the HLA-B5 was significantly lower than in the controls. These data imply that different HLA antigens may be involved in the pathogenesis of several clinical forms of asthma and that, in order to study the role of immunogenetic factor(s) in the pathogenesis of this disease, more adequate grouping criteria are needed.

  18. Architectural Prototyping

    DEFF Research Database (Denmark)

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

    2004-01-01

    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...

  19. Architectural prototyping

    DEFF Research Database (Denmark)

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

    2004-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Yamín Rocío Arias-Murillo

    2011-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Yazmin Rocío Árias-Murillo

    2010-12-01

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  3. HLA-DQA1 and HLA-DQB1 alleles and haplotypes in two Brazilian Indian tribes: evidence of conservative evolution of HLA-DQ.

    Science.gov (United States)

    Sotomaior, V S; Faucz, F R; Schafhauser, C; Janzen-Dück, M; Boldt, A B; Petzl-Erler, M L

    1998-08-01

    Nucleotide sequence polymorphism of the HLA-DQA1 and HLA-DQB1 class II genes was analyzed in the Kaingang and Guarani Amerindians from southern Brazil using PCR sequence-specific oligonucleotide typing methods. Four different DQA1-DQB1 haplotypes were found: DQA1*0401-DQB1*0402 (associated with DRB1*0802, DRB1*08041, and DRB1*0807), DQA1*0501-DQB1*0301 (associated with DRB1*1602, DRB1*1413, and DRB1*1402), DQA1*03-DQB1*0302 (associated with DRB1*0404 and DRB1*0411), and DQA1*03-DQB1*03032 (associated with DRB1*09012). These HLA-DQA1 and HLA-DQB1 alleles and haplotypes are common in many other populations of all major ethnic groups. Alleles and haplotypes introduced into the populations by post-Columbian admixture were seen at low frequency both in the Kaingang (3.2%) and in the Guarani (3.8%). No novel HLA-DQA1 and HLA-DQB1 alleles have thus far been identified in Amerindians. This differs from previous results for HLA-DRB1, another class II locus presenting novel alleles (i.e., alleles not found in other ethnic groups and probably generated after migration of paleo-Indians to the Americas) in the Guarani and in other South American Indian populations. The distribution of the HLA-DQ alleles and haplotypes in Amerindians indicates a weaker diversifying selective pressure on the HLA-DQ genes compared with HLA-DRB1 and HLA-B. The more conservative evolution of HLA-DQA1 and HLA-DQB1 compared with HLA-DRB1 is strong evidence of (still not well-defined) functional differences of these class II genes.

  4. Low-cost, simultaneous, single-sequence genotyping of the HLA-A, HLA-B and HLA-C loci.

    Science.gov (United States)

    Abbott, W G H; Tukuitonga, C F; Ofanoa, M; Munn, S R; Gane, E J

    2006-07-01

    New automated DNA sequencing technology has enabled the development of an assay for genotyping the three major HLA class 1 loci from a single sequence of each gene containing exon 3, intron 2 and exon 2. The assay allows 31 subjects (with 3 negative controls) to be genotyped at all three loci simultaneously, using a 96-well plate format. Genotypes were assigned by comparing each sequence to a database of 307 HLA-A, 563 HLA-B and 166 HLA-C alleles. Unequivocal, 4-digit allele assignments were made for 40 of 130 HLA-A genes, 82 of 130 HLA-B genes and 97 of 130 HLA-C genes from 21 European, 20 Tongan and 24 Niuean subjects. Ambiguity in interpretation of the sequence contributed to 66 of the 170 equivocal allele assignments, and 105 equivocal assignments were due to polymorphisms outside exons 2 and 3. All known alternative interpretations of ambiguous genotypes were identified, and seven HLA-B and two HLA-C ambiguities were resolved by reading the out-of-phase exon 2 sequence that followed an indel in intron 2. The genotypes of a subgroup of 27 heterozygous subjects, whose genotypes contained all of the alleles identified in this study, were confirmed with commercial, generic PCR-SSP typing. In European subjects, the repertoire of HLA-B/HLA-C haplotypes was almost identical to previously published data. We identified five new HLA-B/HLA-C haplotypes in the Polynesian subjects, and the remaining haplotypes were of Asian origin. In summary, we are describing a low-cost, sequencing assay for the three major HLA class I loci that provides a level of resolution that is comparable with a commercial PCR-SSP assay.

  5. Robotic Architectures

    Directory of Open Access Journals (Sweden)

    Mbali Mtshali

    2010-01-01

    Full Text Available In the development of mobile robotic systems, a robotic architecture plays a crucial role in interconnecting all the sub-systems and controlling the system. The design of robotic architectures for mobile autonomous robots is a challenging and complex task. With a number of existing architectures and tools to choose from, a review of the existing robotic architecture is essential. This paper surveys the different paradigms in robotic architectures. A classification of the existing robotic architectures and comparison of different proposals attributes and properties have been carried out. The paper also provides a view on the current state of designing robot architectures. It also proposes a conceptual model of a generalised robotic architecture for mobile autonomous robots.Defence Science Journal, 2010, 60(1, pp.15-22, DOI:http://dx.doi.org/10.14429/dsj.60.96

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-01-01

    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.

  7. Architecture & Environment

    Science.gov (United States)

    Erickson, Mary; Delahunt, Michael

    2010-01-01

    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-A and HLA-B alleles associated in psoriasis patients from Mumbai, Western India

    Directory of Open Access Journals (Sweden)

    Shankarkumar Umapathy

    2011-01-01

    Full Text Available Background: Psoriasis, a common autoimmune disorder characterized by T cell-mediated keratinocyte hyperproliferation, is known to be associated with the presence of certain specific Human Leukocyte Antigen (HLA alleles. Aim: To evaluate distribution of HLA-A and HLA-B alleles and hence identify the susceptible allele of psoriasis from patients in Western India. Materials and Methods: The study design included 84 psoriasis patients and 291 normal individuals as controls from same geographical region. HLA-A and HLA-B typing was done using Serology typing. Standard statistical analysis was followed to identify the odds ratio (OR, allele frequencies, and significant P value using Graphpad software. Results: The study revealed significant increase in frequencies of HLA-A2 (OR-3.976, P<0.0001, B8 (OR-5.647, P<0.0001, B17 (OR-5.452, P<0.0001, and B44 (OR-50.460, P<0.0001, when compared with controls. Furthermore, the frequencies of HLA-A28 (OR-0.074, P=0.0024, B5 (OR-0.059, P<0.0001, B12 (OR-0.051, P=0.0002, and B15 (OR-0.237, P=0.0230 were significantly decreased in psoriasis patients. Conclusion: This study shows the strong association of HLA-A2, B8, and B17 antigens with psoriasis conferring susceptibility to psoriasis patients from Western India, while the antigens HLA-A28, B5, and B12 show strong negative association with the disease.

  9. Federal Holidays

    Data.gov (United States)

    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...

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

    Directory of Open Access Journals (Sweden)

    Amirzargar AA

    2010-11-01

    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

  11. [HLA antigens in juvenile rheumatoid arthritis].

    Science.gov (United States)

    Rumba, I V; Sochnev, A M; Kukaĭne, E M; Burshteĭn, A M; Benevolenskaia, L I

    1990-01-01

    Antigens of I class HLA system (locus A and B) were investigated in 67 patients of Latvian nationality suffering from juvenile rheumatoid arthritis (JRA). Associations of HLA antigens with juvenile rheumatoid arthritis partially coincided with the ones revealed earlier. Typing established an increased incidence of antigen B27 (p less than 0.01) and gaplotype A2, B40 (p less than 0.01). Antigen B15 possessed a protective action with respect to JRA. Interlocus combinations demonstrated a closer association with the disease than a single antigen. The authors also revealed markers of various clinico-anatomical variants of JRA.

  12. Expression of HLA Class I and HLA Class II by Tumor Cells in Chinese Classical Hodgkin Lymphoma Patients

    NARCIS (Netherlands)

    Huang, Xin; van den Berg, Anke; Gao, Zifen; Visser, Lydia; Nolte, Ilja; Vos, Hans; Hepkema, Bouke; Kooistra, Wierd; Poppema, Sibrand; Diepstra, Arjan

    2010-01-01

    Background: In Caucasian populations, the tumor cells of Epstein Barr virus (EBV)-positive classical Hodgkin Lymphomas (cHL) patients more frequently express HLA class I and HLA class II molecules compared to EBV-negative cHL patients. HLA expression (in relation to EBV) in Asian cHL patients has no

  13. Frequencies of allele groups HLA-A, HLA-B and HLA-DRB1 in a population from the northwestern region of São Paulo State, Brazil.

    Science.gov (United States)

    Ayo, C M; da Silveira Camargo, A V; Xavier, D H; Batista, M F; Carneiro, O A; Brandão de Mattos, C C; Ricci, O; de Mattos, L C

    2015-02-01

    The aim of this study was to estimate the HLA-A, HLA-B and HLA-DRB1 allele groups frequencies in a population of 1559 volunteer bone marrow donors from the northwestern region of São Paulo State grouped according to ethnicity. An additional objective was to compare the allele frequencies of the current study with data published for other Brazilian populations. The allele groups were characterized by the PCR-rSSO method using Luminex(®) technology. Twenty HLA-A, 32 HLA-B and 13 HLA-DRB1 allele groups were identified. The most common allele groups in European descent and mixed African and European descent samples were HLA-A*02, HLA-B*35 and HLA-DRB1*13, while HLA-A*02, HLA-B*35 and HLA-DRB1*11 were more common in African descent samples. The HLA-A*23, HLA-A*36, HLA-B*58 and HLA-B*81 allele groups were more common in sample from African descent than European descent, and the HLA-DRB1*08 was more common in mixed African and European descent than in European descent. Allele group frequencies were compared with samples from other Brazilian regions. The HLA-A*30 and HLA-A*23 were more common in this study than in the populations of Rio Grande do Sul and Paraná; and the HLA-A*01, HLA-B*18, HLA-B*57 and HLA-DRB1*11 were more common in this study than in the population of Piauí. The least frequent allele groups were HLA-A*31, HLA-B*15, HLA-B*40 and HLA-DRB1*08 for the population of Piauí, HLA-A*01 and HLA-A*11 for Parana, HLA-A*02 and -A*03 for Rio Grande do Sul and HLA-DRB1*04 for Paraná, Rio Grande do Sul and Piauí. These data provide an overview on the knowledge on HLA diversity in the population of the northwestern region of São Paulo State and show that the genes of this system are useful to distinguish different ethnic groups.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    HLA-G levels are significantly lower in fetal compared with maternal blood at term documents for the first time that sHLA-G is not freely transferred over the placental barrier. Soluble HLA-G levels in maternal and fetal blood were found to be correlated, which may be due to shared genetic factors...... of importance for production of sHLA-G in the mother and child, or it may support the theory that sHLA-G in the pregnant woman and the fetus is partly derived from a "shared organ", the placenta....

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

    DEFF Research Database (Denmark)

    Jørgensen, A; Röpke, C; Nielsen, M

    1996-01-01

    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-DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN-gamma treatment strongly upregulated the HLA-DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels...

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

    Science.gov (United States)

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

    2016-07-01

    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.

  17. Human lymphocyte antigens (HLA) and Graves' disease in Turkey.

    Science.gov (United States)

    Orhan, Y; Azezli, A; Carin, M; Aral, F; Sencer, E; Molvalilar, S

    1993-09-01

    To evaluate the association of HLA types with Turkish patients with Graves' disease, HLA typing, clinical findings, and thyroid antibodies were correlated. The HLA types, clinical findings (ophthalmopathy and age at onset), and thyroid stimulating hormone (TSH) receptor (TRAb) and antithyroid microsomal antibodies (MAb) were analyzed. Seventy Turkish patients with Graves' disease and 306 control subjects were assessed. Serological HLA typing was performed in HLA A, B, C, DR, and DQ loci. There was a significantly increased prevalence of HLA B8, B49, DR3, DR4, and DR10 in Graves' disease. The association of Graves' disease with HLA DR3 was found to be less strong than previously described. The HLA DR4 antigen may contribute to the predisposition of Graves' disease in Turkey. The results suggest that HLA B7, B13, DR7, DQw2, and DQw3 may confer a protective effect for Graves' disease in Turkey. Patients carrying HLA B12, B18, and B44 haplotypes had a tendency to develop the disease at a later age. The difference from the other studies may be the result of the selection of the controls; in part, of the variability in serological typing reagents; and, also, of the rather weak HLA associations with the disease.

  18. Architectural freedom and industrialised architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    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......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 inge.vestergaard@aarch.dk 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...

  19. Preimplantation HLA typing for stem cell transplantation treatment of hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Anver Kuliev

    2014-09-01

    Full Text Available Preimplantation genetic diagnosis (PGD for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world’s largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, resulting in birth of 132 unaffected children. A total of 146 cases were performed together with preimplantation HLA typing, resulting in detection and transfer of HLA matched unaffected embryos in 83 of them, yielding the birth of 16 HLA matched children, potential donors for their affected siblings. The presented experience of HLA matched stem cell transplantation for thalassemia, following PGD demonstrated a successful hematopoietic reconstitution both for younger and older patients. The data show that PGD is an efficient approach for HLA matched stem cell transplantation treatment for thalassemia.

  20. The structure of HLA-DR52c: Comparison to other HLA-DRB3 alleles

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Shaodong; Crawford, Frances; Marrack, Philippa; Kappler, John W. (HHMI)

    2008-09-05

    Class II major histocompatibility complex (MHCII) molecules present antigens to CD4{sup +} T cells. In addition to the most commonly studied human MHCII isotype, HLA-DR, whose {beta} chain is encoded by the HLA-DRB1 locus, several other isotypes that use the same {alpha} chain but have {beta} chains encoded by other genes. These other DR molecules also are expressed in antigen-presenting cells and are known to participate in peptide presentation to T cells and to be recognized as alloantigens by other T cells. Like some of the HLA-DRB1 alleles, several of these alternate DR molecules have been associated with specific autoimmune diseases and T cell hypersensitivity. Here we present the structure of an HLA-DR molecule (DR52c) containing one of these alternate {beta} chains (HLA-DRB3*0301) bound to a self-peptide derived from the Tu elongation factor. The molecule shares structurally conserved elements with other MHC class II molecules but has some unique features in the peptide-binding groove. Comparison of the three major HLA-DBR3 alleles (DR52a, b, and c) suggests that they were derived from one another by recombination events that scrambled the four major peptide-binding pockets at peptide positions 1, 4, 6, and 9 but left virtually no polymorphisms elsewhere in the molecules.

  1. 基于HLA/RTI的多无人机编队飞行仿真系统框架%Multi-UAVS Formation Flying Simulation System Based on HLA/RTI

    Institute of Scientific and Technical Information of China (English)

    王国丽; 王琪

    2012-01-01

    为实现多无人机编队的飞行仿真,提出了多无人机编队的飞行仿真系统设计方案.在对系统需求分析的基础上,设计了仿真系统的总体组成.以高层体系结构(High Level Architecture,HLA)作为框架,利用三维可视化建模工具Creator、视景仿真软件Vega Prime和HLA仿真支撑平台RTI,开发了基于HLA/RTI进行分布式仿真的多无人机编队飞行系统框架.RTI为通信支撑层,建立了多机实时通信的飞行仿真系统,由管理者发号施令,并将飞行结果实时存储,仿真人员可进行分析,改进飞行效果.%The design of the multi-UAVS and formation simulation system is proposed for realizing the flight simulation of multi-UAVS formation. Based on the research of system requirements, the overall system and structure frame are designed. Following the technique frame of HLA(high level architecture), Using visual modeling tool-Multigen Creator, visual simulation software-Multigen Vega Prime and HLA simulation support plat-RTI, A multi-UAVS formation flying simulation system based on HLA/RTI is designed. RTI is communications support layer, Establish a real-time communication of multi-machine flight simulation system, Receive orders form managers and store the flight results in real time, simulation people can be analyzed the results to improve the flight effect.

  2. Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance of HLA-F autoantibodies.

    Science.gov (United States)

    Jucaud, V; Ravindranath, M H; Terasaki, P I; Morales-Buenrostro, L E; Hiepe, F; Rose, T; Biesen, R

    2016-03-01

    T lymphocyte hyperactivity and progressive inflammation in systemic lupus erythematosus (SLE) patients results in over-expression of human leucocyte antigen (HLA)-Ib on the surface of lymphocytes. These are shed into the circulation upon inflammation, and may augment production of antibodies promoting pathogenicity of the disease. The objective was to evaluate the association of HLA-Ib (HLA-E, HLA-F and HLA-G) antibodies to the disease activity of SLE. The immunoglobulin (Ig)G/IgM reactivity to HLA-Ib and β2m in the sera of 69 German, 29 Mexican female SLE patients and 17 German female controls was measured by multiplex Luminex(®)-based flow cytometry. The values were expressed as mean flourescence intensity (MFI). Only the German SLE cohort was analysed in relation to the clinical disease activity. In the controls, anti-HLA-G IgG predominated over other HLA-Ib antibodies, whereas SLE patients had a preponderance of anti-HLA-F IgG over the other HLA-Ib antibodies. The disease activity index, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000, was reflected only in the levels of anti-HLA-F IgG. Anti-HLA-F IgG with MFI level of 500-1999 was associated with active SLE, whereas inactive SLE revealed higher MFI (>2000). When anti-HLA-F IgG were cross-reactive with other HLA-Ib alleles, their reactivity was reflected in the levels of anti-HLA-E and -G IgG. The prevalence of HLA-F-monospecific antibodies in SLE patients was also associated with the clinical disease activity. Anti-HLA-F IgG is possibly involved in the clearance of HLA-F shed from lymphocytes and inflamed tissues to lessen the disease's severity, and thus emerges as a beneficial immune biomarker. Therefore, anti-HLA-Ib IgG should be considered as a biomarker in standard SLE diagnostics.

  3. Imputing Variants in HLA-DR Beta Genes Reveals That HLA-DRB1 Is Solely Associated with Rheumatoid Arthritis and Systemic Lupus Erythematosus.

    Directory of Open Access Journals (Sweden)

    Kwangwoo Kim

    Full Text Available The genetic association of HLA-DRB1 with rheumatoid arthritis (RA and systemic lupus erythematosus (SLE is well documented, but association with other HLA-DR beta genes (HLA-DRB3, HLA-DRB4 and HLA-DRB5 has not been thoroughly studied, despite their similar functions and chromosomal positions. We examined variants in all functional HLA-DR beta genes in RA and SLE patients and controls, down to the amino-acid level, to better understand disease association with the HLA-DR locus. To this end, we improved an existing HLA reference panel to impute variants in all protein-coding HLA-DR beta genes. Using the reference panel, HLA variants were inferred from high-density SNP data of 9,271 RA-control subjects and 5,342 SLE-control subjects. Disease association tests were performed by logistic regression and log-likelihood ratio tests. After imputation using the newly constructed HLA reference panel and statistical analysis, we observed that HLA-DRB1 variants better accounted for the association between MHC and susceptibility to RA and SLE than did the other three HLA-DRB variants. Moreover, there were no secondary effects in HLA-DRB3, HLA-DRB4, or HLA-DRB5 in RA or SLE. Of all the HLA-DR beta chain paralogs, those encoded by HLA-DRB1 solely or dominantly influence susceptibility to RA and SLE.

  4. Imputing Variants in HLA-DR Beta Genes Reveals That HLA-DRB1 Is Solely Associated with Rheumatoid Arthritis and Systemic Lupus Erythematosus

    Science.gov (United States)

    Kim, Kwangwoo; Bang, So-Young; Yoo, Dae Hyun; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Kang, Young Mo; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Kim, Seong-Kyu; Choe, Jung-Yoon; Nath, Swapan K.; Lee, Hye-Soon; Bae, Sang-Cheol

    2016-01-01

    The genetic association of HLA-DRB1 with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is well documented, but association with other HLA-DR beta genes (HLA-DRB3, HLA-DRB4 and HLA-DRB5) has not been thoroughly studied, despite their similar functions and chromosomal positions. We examined variants in all functional HLA-DR beta genes in RA and SLE patients and controls, down to the amino-acid level, to better understand disease association with the HLA-DR locus. To this end, we improved an existing HLA reference panel to impute variants in all protein-coding HLA-DR beta genes. Using the reference panel, HLA variants were inferred from high-density SNP data of 9,271 RA-control subjects and 5,342 SLE-control subjects. Disease association tests were performed by logistic regression and log-likelihood ratio tests. After imputation using the newly constructed HLA reference panel and statistical analysis, we observed that HLA-DRB1 variants better accounted for the association between MHC and susceptibility to RA and SLE than did the other three HLA-DRB variants. Moreover, there were no secondary effects in HLA-DRB3, HLA-DRB4, or HLA-DRB5 in RA or SLE. Of all the HLA-DR beta chain paralogs, those encoded by HLA-DRB1 solely or dominantly influence susceptibility to RA and SLE. PMID:26919467

  5. ANALYZING HLA HAPLOTYPE OF THE LOCI HLA-A, -B, AND -DRB1 IN MONGOLIA ETHNIC GROUP

    Institute of Scientific and Technical Information of China (English)

    Zhang Hongbo; Li Shengbin

    2006-01-01

    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.

  6. HLA-G and classical HLA class I expression in primary colorectal cancer and associated liver metastases.

    Science.gov (United States)

    Swets, Marloes; König, Marion H; Zaalberg, Anniek; Dekker-Ensink, Neeltje G; Gelderblom, Hans; van de Velde, Cornelis J H; van den Elsen, Peter J; Kuppen, Peter J K

    2016-09-01

    De novo expression of HLA-G has been demonstrated in colorectal cancer. HLA-G, amongst others, inhibits natural killer cell function, contributing to host immune defense evasion. Another mechanism to escape anti-tumor immunity is loss of HLA class I. Therefore, we determined HLA-G and HLA class I expression on primary colorectal tumors and associated liver metastases, in order to get insight in the metastasizing process regarding escaping anti-tumor immunity. HLA-G expression was evaluated using three mAbs; 4H84, MEM-G/1 and MEM-G/2. In total 81 colorectal cancer patients were evaluated. Formalin-fixed paraffin-embedded tissue sections of primary tumors and associated liver metastases, were immunohistochemically stained. A concordance between expression or loss/downregulation in the primary tumor and associated liver metastasis regarding HLA class I expression was observed in 80% of the cases. In contrast with the hypothesis of escaping NK cell-killing, we demonstrated for each HLA-G detecting mAbs used in this study, that the majority of the primary tumors that positively stained for HLA-G did not express HLA-G in the associated liver metastasis. Furthermore, we revealed the existence of non-specific binding and in addition we found that the different epitopes of HLA-G detected by 4H84, MEM-G/1 and MEM-G/2 mAbs were expressed differentially in colorectal tumor tissues.

  7. Software architecture

    CERN Document Server

    Vogel, Oliver; Chughtai, Arif

    2011-01-01

    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

  8. Green Architecture

    Science.gov (United States)

    Lee, Seung-Ho

    Today, the environment has become a main subject in lots of science disciplines and the industrial development due to the global warming. This paper presents the analysis of the tendency of Green Architecture in France on the threes axes: Regulations and Approach for the Sustainable Architecture (Certificate and Standard), Renewable Materials (Green Materials) and Strategies (Equipments) of Sustainable Technology. The definition of 'Green Architecture' will be cited in the introduction and the question of the interdisciplinary for the technological development in 'Green Architecture' will be raised up in the conclusion.

  9. 41 CFR 102-77.15 - Who funds the Art-in-Architecture efforts?

    Science.gov (United States)

    2010-07-01

    ...-Architecture efforts? 102-77.15 Section 102-77.15 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 77-ART-IN-ARCHITECTURE Art-in-Architecture § 102-77.15 Who funds the Art-in-Architecture efforts? To the extent...

  10. DHLAS: A web-based information system for statistical genetic analysis of HLA population data.

    Science.gov (United States)

    Thriskos, P; Zintzaras, E; Germenis, A

    2007-03-01

    DHLAS (database HLA system) is a user-friendly, web-based information system for the analysis of human leukocyte antigens (HLA) data from population studies. DHLAS has been developed using JAVA and the R system, it runs on a Java Virtual Machine and its user-interface is web-based powered by the servlet engine TOMCAT. It utilizes STRUTS, a Model-View-Controller framework and uses several GNU packages to perform several of its tasks. The database engine it relies upon for fast access is MySQL, but others can be used a well. The system estimates metrics, performs statistical testing and produces graphs required for HLA population studies: (i) Hardy-Weinberg equilibrium (calculated using both asymptotic and exact tests), (ii) genetics distances (Euclidian or Nei), (iii) phylogenetic trees using the unweighted pair group method with averages and neigbor-joining method, (iv) linkage disequilibrium (pairwise and overall, including variance estimations), (v) haplotype frequencies (estimate using the expectation-maximization algorithm) and (vi) discriminant analysis. The main merit of DHLAS is the incorporation of a database, thus, the data can be stored and manipulated along with integrated genetic data analysis procedures. In addition, it has an open architecture allowing the inclusion of other functions and procedures.

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

    NARCIS (Netherlands)

    Reinders, Judith

    2006-01-01

    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. HLA class II genes: typing by DNA analysis.

    Science.gov (United States)

    Bidwell, J L; Bidwell, E A; Bradley, B A

    1990-04-01

    A detailed understanding of the structure and function of the human major histocompatibility complex (MHC) has ensued from studies by molecular biologist during the last decade. Virtually all of the HLA genes have now been cloned, and the nucleotide sequences of their different allelic forms have been determined. Typing for these HLA alleles is a fundamental prerequisite for tissue matching in allogeneic organ transplantation. Until very recently, typing procedures have been dominated by serological and cellular methods. The availability of cloned DNA from HLA genes has now permitted the technique of restriction fragment length polymorphism (RFLP) analysis to be applied, with remarkable success and advantage, to phenotyping of both HLA Class I and Class II determinants. For the HLA Class II genes DR and DQ, a simple two-stage RFLP analysis permits the accurate identification of all specificities defined by serology, and of many which are defined by cellular typing. At the present time, however, RFLP typing of HLA Class I genes is not as practicable or as informative as that for HLA Class II genes. The present clinical applications of HLA-DR and DQ RFLP typing are predominantly in phenotyping of living donors, including selection of HLA-matched volunteer bone marrow donors, in allograft survival studies, and in studies of HLA Class II-associated diseases. However, the time taken to perform RFLP analysis precludes its use for the typing of cadaveric kidney donors. Nucleotide sequence data for the alleles of HLA Class II genes have now permitted the development of allele-specific oligonucleotide (ASO) typing, a second category of DNA analysis. This has been greatly facilitated by the ability to amplify specific HLA Class II DNA 'target' sequences using the polymerase chain reaction (PCR) technique. The accuracy of DNA typing techniques should ensure that this methodology will eventually replace conventional HLA phenotyping.

  13. Local architecture

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Local architecture refers to structures built in the countryside,such as temples,memorial halls,residences, stores,pavilions, bridges,decorated archways, and wells. Because these structures were all built by focal craftsmen and villagers in the traditional local style, they are generally called local architecture.

  14. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    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 fir

  15. Architectural Contestation

    NARCIS (Netherlands)

    Merle, J.

    2012-01-01

    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, consequ

  16. Architectural geometry

    NARCIS (Netherlands)

    Pottmann, Helmut; Eigensatz, Michael; Vaxman, A.; Wallner, Johannes

    2015-01-01

    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

  17. Architectural Narratives

    DEFF Research Database (Denmark)

    Kiib, Hans

    2010-01-01

    and architectural heritage; another group tries to embed new performative technologies in expressive architectural representation. Finally, this essay provides a theoretical framework for the analysis of the political rationales of these projects and for the architectural representation bridges the gap between......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...

  18. Architectural Theatricality

    DEFF Research Database (Denmark)

    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...... 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...

  19. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    and well-being, as well as outline a set of basic design principles ‘predicting’ the future interior architectural qualities of patient eating environments. Methodologically the thesis is based on an explorative study employing an abductive approach and hermeneutic-interpretative strategy utilizing tactics......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...

  20. HLA class I-mediated control of HIV-1 in the Japanese population, in which the protective HLA-B*57 and HLA-B*27 alleles are absent.

    Science.gov (United States)

    Naruto, Takuya; Gatanaga, Hiroyuki; Nelson, George; Sakai, Keiko; Carrington, Mary; Oka, Shinichi; Takiguchi, Masafumi

    2012-10-01

    We investigated the effect of HLA class I alleles on clinical parameters for HIV-1 disease progression in the Japanese population, where two strongly protective alleles, HLA-B*57 and HLA-B*27, are virtually nonexistent. HLA-B alleles showed a dominant role, primarily through HLA-B*67:01 and the HLA-B*52:01-C*12:02 haplotype. Neither a rare-allele nor a heterozygote advantage was found, suggesting that the effect of HLA alleles in the Japanese population is either different from those observed in Africans and Caucasians or undetectable due to limited power.

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

    NARCIS (Netherlands)

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

    2003-01-01

    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

  2. Haplotypes of the HLA-G 3’ Untranslated Region Respond to Endogenous Factors of HLA-G+ and HLA-G- Cell Lines Differentially

    Science.gov (United States)

    Cagnin, Natalia F.; Sgorla de Almeida, Bibiana; Castelli, Erick C.; Carosella, Edgardo D.; Donadi, Eduardo A.; Moreau, Philippe

    2017-01-01

    The immune checkpoint HLA-G prevents maternal rejection of the fetus and contributes in cancer invasion and acceptance of allografts. The 5’ and 3’ regulatory regions of the HLA-G gene are polymorphic and balancing selection probably maintains this variability. It is proposed that nucleotide variations may affect the level of HLA-G expression. To investigate this issue we aimed to analyze how haplotypes of the 3’ untranslated region (3’UTR) with highest worldwide frequencies, namely UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-18 and UTR-7, impact the expression of a luciferase reporter gene in vitro. Experiments performed with the HLA-G positive cell lines JEG-3 (choricarcinoma) and FON (melanoma), and with the HLA-G negative cell lines M8 (melanoma) and U251MG (glioblastoma) showed that the HLA-G 3’UTR polymorphism influences the response to endogenous cellular factors and may vary according to the cell type. UTR-5 and UTR-7 impact the activity of luciferase the most whereas UTR-2, UTR-3, UTR-4, and UTR-18 have intermediate impact, and UTR-1 has the lowest impact. These results corroborate the previous associations between amounts of plasma sHLA-G levels and 3’UTR haplotypes in healthy individuals and reinforce that 3’UTR typing may be a predictor of the genetic predisposition of an individual to express different levels of HLA-G. PMID:28045999

  3. Role of HLA adaptation in HIV evolution

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  4. HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies of 10 918 Koreans from bone marrow donor registry in Korea.

    Science.gov (United States)

    Park, H; Lee, Y-J; Song, E Y; Park, M H

    2016-10-01

    The human leucocyte antigen (HLA) system is the most polymorphic genetic system in humans, and HLA matching is crucial in organ transplantation, especially in hematopoietic stem cell transplantation. We investigated HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies at allelic level in 10 918 Koreans from bone marrow donor registry in Korea. Intermediate resolution HLA typing was performed using Luminex technology (Wakunaga, Japan), and additional allelic level typing was performed using PCR-single-strand conformation polymorphism method and/or sequence-based typing (Abbott Molecular, USA). Allele and haplotype frequencies were calculated by direct counting and maximum likelihood methods, respectively. A total of 39 HLA-A, 66 HLA-B and 47 HLA-DRB1 alleles were identified. High-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, *02:06, *11:01, *24:02, *31:01 and *33:03), 6 HLA-B (B*15:01, *35:01, *44:03, *51:01, 54:01 and *58:01) and 8 HLA-DRB1 (DRB1*01:01, *04:05, *04:06, *07:01, *08:03, *09:01, *13:02 and *15:01) alleles. At each locus, A*02, B*15 and DRB1*14 generic groups were most diverse at allelic level, consisting of 9, 12 and 11 different alleles, respectively. A total of 366, 197 and 21 different HLA-A-B-DRB1 haplotypes were estimated with frequencies of ≥0.05%, ≥0.1% and ≥0.5%, respectively. The five most common haplotypes with frequencies of ≥2.0% were A*33:03-B*44:03-DRB1*13:02 (4.97%), A*33:03-B*58:01-DRB1*13:02, A*33:03-B*44:03-DRB1*07:01, A*24:02-B*07:02-DRB1*01:01 and A*24:02-B*52:01-DRB1*15:02. Among 34 serologic HLA-A-B-DR haplotypes with frequencies of ≥0.5%, 17 haplotypes revealed allele-level diversity and majority of the allelic variation was arising from A2, A26, B61, B62, DR4 and DR14 specificities. Haplotype diversity obtained in this study is the most comprehensive data thus far reported in Koreans, and the information will be useful for unrelated stem cell transplantation as well as for disease

  5. Identification of two new HLA-B alleles, HLA-B*0732 and HLA-B*5809, by sequence-based typing.

    Science.gov (United States)

    Longhi, E; Frison, S; Poli, F; Espadas de Arias, A; Zanuso, C; Guizzardi, E; Scalamogna, M

    2004-03-01

    Here, we have described the characterization of two novel human leukocyte antigen-B (HLA-B) alleles. The new alleles, HLA-B*0732 and HLA-B*5809, were identified in Italian Caucasian individuals. B*0732 differs from HLA-B*0708 by one nucleotidic change at position 412 (from G to A) in exon 3, leading to an amino acidic substitution from Asp (GAC) to Asn (AAC) at codon 114. The sequence of B*5809 is identical to that of HLA-B*5801, except for a point mutation at position 583 in exon 3, where a T is substituted by a C. This change leads to an amino acidic substitution from Tyr (TAC) to His (CAC) at codon 171.

  6. HLA: The Major Histocompatibility Complex of Man

    Science.gov (United States)

    1991-01-01

    pauciarticular, (la) C d males with onset over the age of eight, (I b) a form with iritis , and (2) conversion to polyarticular. The sound- ness of this clinical...relative risk (RR) is defined as B27. Early onset pauciarticular JRA and iritis are as- a X d sociated with HLA-DR5, DRw8, and in some patients RR = bXc

  7. HLA polymorphism in Sudanese renal donors

    Directory of Open Access Journals (Sweden)

    Ameer M Dafalla

    2011-01-01

    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.

  8. Architectural technology

    DEFF Research Database (Denmark)

    2005-01-01

    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...

  9. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    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...... 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....

  10. HLA-C Downmodulation by HIV-1 Vpu.

    Science.gov (United States)

    Barker, Edward; Evans, David T

    2016-05-11

    It is widely held that HIV-1 Nef downmodulates HLA-A and -B to protect infected cells from CD8(+) T cells but leaves HLA-C on the cell surface to inhibit NK cells. In this issue of Cell Host & Microbe, Apps et al. (2016) revise this model by showing that the Vpu protein of primary HIV-1 isolates downmodulate HLA-C.

  11. HLA DRB1* ASSOCIATION WITH REPRODUCTIVE DISORDERS IN WOMEN

    Directory of Open Access Journals (Sweden)

    L. A. Gordeeva

    2007-01-01

    Full Text Available Abstract. HLA DRB1* gene associations with idiopathic fetal losses and infertility were studied in women. It was shown that idiopathic fetal losses are associated with HLA DRB1*04 specificity, whereas infertility correlated with HLA DRB1*04/07 genotype. The associations revealed may indicate to a special role of autoimmune events in women during pregnancy. The authors suggest a hypothesis on existence of several immune modes of reproductive losses. HLA genotyping may be applied as a basic technique for their determination.

  12. HLA-B27 Determination by Polymerase Chain Reaction

    OpenAIRE

    Kilpatrick, D C

    1996-01-01

    A method for determining the presence or absence of HLA-827 by selective amplification of a region in the third exon of the HLA-B27 gene common to B*270 I to B*2705 inclusive, was evaluated. This polymerase chain reaction/sequence specific primer (PCR-SSP) method gave perfect correlation with serological typing on 40 individuals of previously determined HLA type and on 50 further clinical samples elaluated blind. It was concluded that HLA-B27 determination by PCR-SSP is simple, reliable. cost...

  13. HLA-B27 Determination by Polymerase Chain Reaction

    Directory of Open Access Journals (Sweden)

    D. C. Kilpatrick

    1996-01-01

    Full Text Available A method for determining the presence or absence of HLA-827 by selective amplification of a region in the third exon of the HLA-B27 gene common to B*270 I to B*2705 inclusive, was evaluated. This polymerase chain reaction/sequence specific primer (PCR-SSP method gave perfect correlation with serological typing on 40 individuals of previously determined HLA type and on 50 further clinical samples elaluated blind. It was concluded that HLA-B27 determination by PCR-SSP is simple, reliable. cost-effectile and convient for laboratory staff.

  14. Architectural Engineers

    DEFF Research Database (Denmark)

    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 design professions have always been an amorphous phenomena difficult to merge under one label. New constellations continually emerge, questioning, stretching, and reconfiguring the understanding of design and the professional practices linked to it. In this paper the idea of architectural....... 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...

  15. Architectural Mealscapes

    DEFF Research Database (Denmark)

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

    2012-01-01

    the 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. Systemic Architecture

    DEFF Research Database (Denmark)

    Poletto, Marco; Pasquero, Claudia

    2012-01-01

    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......-gardens and the coding of proto-interfaces. These prototypes of machinic architecture materialize as synthetic hybrids embedded with biological life (proto-gardens), computational power, behavioural responsiveness (cyber-gardens), spatial articulation (coMachines and fibrous structures), remote sensing (FUNclouds...

  17. A Doctrine-oriented MRM Method in HLA-based Simulation

    Institute of Scientific and Technical Information of China (English)

    HUSiquan; FANZhihua

    2003-01-01

    MRM (Multi-resolution modeling) is becoming more important as large complex distributed simulations are carried out inside and out of military simulation community. Most current distributed simulations are implemented in the framework of HLA (High level architecture), which was originally defined by US DOD (Department of defense) and has been accepted by IEEE and OMG as an industrial simulation standard. This paper analyzes the requirements of MRM in HLA (High level architecture)-based simulations. Traditional most adopted practical method "aggregation/disaggregation" has temporal inconsistency problem because it discard the other level as it's at one level. The mainstream theoretic method "MRE (Multiple representation entity)" conquers this problem by propagating changes at one resolution to others, but it has weakness in mapping consistence. This paper suggested a doctrine-oriented MRM method. This novel method has good operational easiness and keeps the consistency problem simpler than MRE by enforcing unidirectional map between entities in different resolutions. A case study is also provided to illustrate its advantage to aggregation/disaggregation method.

  18. Structural basis of cross-allele presentation by HLA-A*0301 and HLA-A*1101 revealed by two HIV-derived peptide complexes.

    Science.gov (United States)

    Zhang, Shihong; Liu, Jun; Cheng, Hao; Tan, Shuguang; Qi, Jianxun; Yan, Jinghua; Gao, George F

    2011-10-01

    Human leukocyte antigens (HLA) are initially classified by serotyping but recently can be re-grouped by their peptide-presentation characteristics into supertypes. Both HLA-A*0301 and HLA-A*1101 are grouped into A3 supertype. Although a number of cross-presented T cell epitopes of HLA-A*0301 and HLA-A*1101 have been identified, the molecular mechanisms of cross-presentation remain elusive. Herein, the structures of HLA-A*0301 with two HIV-derived immunodominant T cell epitopes were solved and their characteristics in comparison with HLA-A*1101 presenting the same peptides were analyzed. The comparable structures of HLA-A*0301 and HLA-A*1101 with subtle differences illustrate the common modes of cross-presented peptides and the strict HLA-restriction of T cell receptor (TCR)-recognition.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    haplotype in populations of African descent, has variously been assigned to the A1, A3, or A24 supertypes. Using a biochemical HLA-A*3001 binding assay, and a large panel of nonamer peptides and peptide libraries, we here demonstrate that the specificity of HLA-A*3001 most closely resembles that of the HLA-A......3 supertype. We discuss approaches to supertype assignment and underscore the importance of experimental verification....

  20. Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis

    Science.gov (United States)

    Nishida, Nao; Ohashi, Jun; Khor, Seik-Soon; Sugiyama, Masaya; Tsuchiura, Takayo; Sawai, Hiromi; Hino, Keisuke; Honda, Masao; Kaneko, Shuichi; Yatsuhashi, Hiroshi; Yokosuka, Osamu; Koike, Kazuhiko; Kurosaki, Masayuki; Izumi, Namiki; Korenaga, Masaaki; Kang, Jong-Hon; Tanaka, Eiji; Taketomi, Akinobu; Eguchi, Yuichiro; Sakamoto, Naoya; Yamamoto, Kazuhide; Tamori, Akihiro; Sakaida, Isao; Hige, Shuhei; Itoh, Yoshito; Mochida, Satoshi; Mita, Eiji; Takikawa, Yasuhiro; Ide, Tatsuya; Hiasa, Yoichi; Kojima, Hiroto; Yamamoto, Ken; Nakamura, Minoru; Saji, Hiroh; Sasazuki, Takehiko; Kanto, Tatsuya; Tokunaga, Katsushi; Mizokami, Masashi

    2016-01-01

    Associations of variants located in the HLA class II region with chronic hepatitis B (CHB) infection have been identified in Asian populations. Here, HLA imputation method was applied to determine HLA alleles using genome-wide SNP typing data of 1,975 Japanese individuals (1,033 HBV patients and 942 healthy controls). Together with data of an additional 1,481 Japanese healthy controls, association tests of six HLA loci including HLA-A, C, B, DRB1, DQB1, and DPB1, were performed. Although the strongest association was detected at a SNP located in the HLA-DP locus in a SNP-based GWAS using data from the 1,975 Japanese individuals, HLA genotyping-based analysis identified DQB1*06:01 as having the strongest association, showing a greater association with CHB susceptibility (OR = 1.76, P = 6.57 × 10−18) than any one of five HLA-DPB1 alleles that were previously reported as CHB susceptibility alleles. Moreover, HLA haplotype analysis showed that, among the five previously reported HLA-DPB1 susceptibility and protective alleles, the association of two DPB1 alleles (DPB1*09:01, and *04:01) had come from linkage disequilibrium with HLA-DR-DQ haplotypes, DRB1*15:02-DQB1*06:01 and DRB1*13:02-DQB1*06:04, respectively. The present study showed an example that SNP-based GWAS does not necessarily detect the primary susceptibility locus in the HLA region. PMID:27091392

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

    Directory of Open Access Journals (Sweden)

    Mohammadreza Bazrafshani

    2014-12-01

    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.

  2. Future Architectures for NREN infrastructures

    DEFF Research Database (Denmark)

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

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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......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......-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...

  4. Clinical features of sarcoidosis in relation to HLA distribution and HLA-DRB3 genotyping by PCR-RFLP.

    OpenAIRE

    Ishihara, M; Ishida, T.; Mizuki, N; Inoko, H.; Ando, H; Ohno, S

    1995-01-01

    BACKGROUND--Susceptibility to the development of sarcoidosis has been demonstrated to be associated with HLA-DR5, -DR6, and -DR8 encoded by the DRB1 gene. However, involvement of the DRB3 (HLA-DR52) gene in the development of sarcoidosis remains unclear. METHODS--HLA-DRB3 genotyping was performed using the PCR-RFLP method and the clinical features of the patients with and without the DR3, 5, 6, 8 group antigens were compared. RESULTS--HLA-DRB3 genotyping indicated an association between DRB3*...

  5. HLA II class antigens and susceptibility to coeliac disease

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2011-01-01

    Full Text Available Coeliac disease (CD is a systemic autoimmune, complex and multifactorial disorder, which is caused by interactions between genetic and environmental factors. The only established genetic risk factors so far are the human leucocyte antigens. The aim of this study was to assess the distribution of II class human leukocyte antigens (HLA in patients with coeliac disease and to investigate the susceptibility to coeliac disease in family members. We typed HLA DR and DQ antigens in 37 patients from Vojvodina with coeliac disease, 23 first-degree relatives, and 210 controls, serologically using standard lymphocytotoxicity technique. HLA DQ5(1, DQ6(1, DR11(5, DQ7(3, DQ2 and DR15(2 were the most common antigens in the control group. Frequency of HLA DQ2, DR3 and DR7 was higher in CD patients than in the control group. The relative risks for HLA DQ2, DR3 and DR7 were 4.846, 6.986 and 2.106, respectively, while positive association was found between HLA DQ2 and DR3 and CD. Frequency of HLA DQ2, DR3 and DR16(2 was higher in first-degree relatives than in the control group while a positive association was found between HLA DQ2 and DR3. A negative association was found between HLA DQ5(1 and DQ6(1 in coeliac patients from Vojvodina and their relatives, in addition to HLA DR11(5 in the group of relatives (RR=0.363,PF=0.232. These findings indicate the impact of the HLA testing for CD in clinical practice in order to rule out the possibility to CD in doubtful cases or in at-risk subjects.

  6. Human leukocyte antigen (HLA) pharmacogenomic tests: potential and pitfalls.

    Science.gov (United States)

    Daly, Ann K

    2014-02-01

    Adverse drug reactions involving a range of prescribed drugs and affecting the skin, liver and other organs show strong associations with particular HLA alleles. For some reactions, HLA typing prior to prescription, so that those positive for the risk allele are not given the drug associated with the reaction, shows high positive and negative predictive values. The best example of clinical implementation relates to the hypersensitivity reaction induced by the anti-HIV drug abacavir. When this reaction is phenotyped accurately, 100% of those who develop it are positive for HLA-B*57:01. Drug regulators worldwide now recommend genotyping for HLA-B*57:01 before abacavir is prescribed. Serious skin rashes including Stevens-Johnson syndrome and toxic epidermal necrosis can be induced by carbamazepine and other anticonvulsant drugs. In certain East Asians, these reactions are significantly associated with HLA-B*15:02, and typing for this allele is now recommended prior to carbamazepine prescription in these populations. Other HLA associations have been described for skin rash induced by carbamazepine, allopurinol and nevirapine and for liver injury induced by flucloxacillin, amoxicillin-clavulanate, lapatanib, lumiracoxib and ticlopidine. However, the predictive values for typing HLA alleles associated with these adverse reactions are lower. Clinical implementation therefore seems unlikely. Performing HLA typing is relatively complex compared with genotyping assays for single nucleotide polymorphisms. With emphasis on HLA-B*57:01, the approaches used commonly, including use of sequence-specific oligonucleotide PCR primers and DNA sequencing are considered, together with their successful implementation. Genotyping single nucleotide polymorphisms tagging HLA alleles is a simpler alternative to HLA typing but appears insufficiently accurate for clinical use.

  7. Molecular genetics (HLA) of Behçet's disease.

    Science.gov (United States)

    Mizuki, N; Inoko, H; Ohno, S

    1997-12-01

    Behçet's disease (BD) has been known to be strongly associated with the human leukocyte antigen (HLA) B51. This B51 association has been confirmed in many different ethnic groups between the Middle East and Japan, and it has been proposed that BD is prevalent in those ethnic groups along the old Silk Route. The hypothesis could be made that B51 molecules are primarily involved in BD development through specific antigen presentation. However, polymorphic analyses of the TNFB gene and Tau-a microsatellite between the HLA-B and TNF genes indicate that the pathogenic gene of BD is not the HLA-B51 gene itself but another gene located around the HLA-B gene. HLA-C genotyping by the PCR-SSP method also suggests that the BD pathogenic gene is not the HLA-C gene itself but other gene located near the HLA-B gene. Recently we sequenced a single contig of 236,822 bp from the MICA gene (58.2 kb centromeric of HLA-B) to 90.8 kb telomeric of HLA-C and identified 8 novel genes designated NOB1-8 (NOB: new organization associated with HLA-B). During the course of the genomic sequence analysis we clarified the genetic structure of the MICA (MHC class I chain-related gene A) gene and found a triplet repeat microsatellite polymorphism of (GCT/AGC)n in the transmebrane (TM) region. Furthermore, the microsatellite allele consisting of 6 repetitions of GCT/AGC (MICA A6 allele) was present at a significantly higher frequency in the BD patient group than in the control group and a significant fraction of B51-negative patients were positive for this MICA A6 allele. These results suggest the possibility of a primary association of BD with MICA rather than HLA-B.

  8. Structural analysis of the HLA-A/HLA-F subregion: Precise localization of two new multigene families closely associated with the HLA class I sequences

    Energy Technology Data Exchange (ETDEWEB)

    Pichon, L.; Carn, G.; Bouric, P. [CNRS, Rennes (France)] [and others

    1996-03-01

    Positional cloning strategies for the hemochromatosis gene have previously concentrated on a target area restricted to a maximum genomic expanse of 400 kb around the HLA-A and HLA-F loci. Recently, the candidate region has been extended to 2-3 Mb on the distal side of the MHC. In this study, 10 coding sequences [hemochromatosis candidate genes (HCG) I to X] were isolated by cDNA selection using YACs covering the HLA-A/HLA-F subregion. Two of these (HCG II and HCG IV) belong to multigene families, as well as other sequences already described in this region, i.e., P5, pMC 6.7, and HLA class I. Fingerprinting of the four YACSs overlapping the region was performed and allowed partial localization of the different multigene family sequences on each YAC without defining their exact positions. Fingerprinting on cosmids isolated from the ICRF chromosome 6-specific cosmid library allowed more precise localization of the redundant sequences in all of the multigene families and revealed their apparent organization in clusters. Further examination of these intertwined sequences demonstrated that this structural organization resulted from a succession of complex phenomena, including duplications and contractions. This study presents a precise description of the structural organization of the HLA-A/HLA-F region and a determination of the sequences involved in the megabase size polymorphism observed among the A3, A24, and A31 haplotypes. 29 refs., 2 figs., 2 tabs.

  9. A novel HLA-Cw*01 variant allele, HLA-Cw*0130.

    Science.gov (United States)

    Deng, Z-H; Wang, D-M

    2009-12-01

    The novel HLA-Cw*0130 variant allele differs from the closest allele Cw*010201 by single nucleotide change at genomic nt 959 T>C (CDS nt 583 T>C, codon 171 TAC>CAC) in exon 3, which causes an amino acid change Tyr171His.

  10. Korean BAC library construction and characterization of HLA-DRA, HLA-DRB3.

    Science.gov (United States)

    Park, Mi-Hyun; Lee, Hye-Ja; Bok, Jeong; Kim, Cheol-Hwan; Hong, Seong-Tshool; Park, Chan; Kimm, KuChan; Oh, Bermseok; Lee, Jong-Young

    2006-07-31

    A human bacterial artificial chromosome (BAC) library was constructed with high molecular weight DNA extracted from the blood of a male Korean. This Korean BAC library contains 100,224 clones of insert size ranging from 70 to 150 kb, with an average size of 86 kb, corresponding to a 2.9-fold redundancy of the genome. The average insert size was determined from 288 randomly selected BAC clones that were well distributed among all the chromosomes. We developed a pooling system and three-step PCR screen for the Korean BAC library to isolate desired BAC clones, and we confirmed its utility using primer pairs designed for one of the clones. The Korean BAC library and screening pools will allow PCR-based screening of the Korean genome for any gene of interest. We also determined the allele types of HLA-DRA and HLA-DRB3 of clone KB55453, located in the HLA class II region on chromosome 6p21.3. The HLA-DRA and DRB3 genes in this clone were identified as the DRA*010202 and DRB3*01010201 types, respectively. The haplotype found in this library will provide useful information in future human disease studies.

  11. Architectural geometry

    KAUST Repository

    Pottmann, Helmut

    2014-11-26

    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.

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

    Science.gov (United States)

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

    2015-01-01

    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 then classified according to ASAS criteria, the axial spondyloarthritis pattern (axSpA) being defined by ascertained sacroiliitis and the peripheral pattern (pSpA) by enthesitis and/or arthritis in extremities. A combined ax/p pattern was also considered. Results Only HLA-B27 and HLA-B15 alleles were associated with SpA. ASAS criteria for axSpA were met in 152 patients (12 with isolated axSpA and 140 with a combined ax/p patterns). When the ASAS peripheral criteria were applied, 161 patients met these criteria (13 with isolated pSpA and 148 with a combined ax/p pattern). HLA-B27 was found in 83% of patients with axSpA and 43% of ax/pSpA patients according to axASAS. HLA-B27 occurred in 7% controls but not in any patient with isolated pSpA. HLA-B15 was encountered in 31% of patients with isolated pSpA and 20% of ax/pSpA patients according to pASAS criteria. Moreover, 2 healthy controls, but none of our patients with isolated axSpA were positive for HLA-B15. Conclusions Our data suggest that the presence of HLA-B15 favours the development of isolated/combined peripheral rather than isolated axSpA, while HLA-B27 promotes an isolated/combined axial disease and excludes a peripheral pattern. HLA-B15 should be considered in addition to HLA-B27 when diagnosing patients with SpA according to ASAS criteria. PMID:26560062

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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 recurren...

  14. The role of HLA-E polymorphism in immunological response

    Directory of Open Access Journals (Sweden)

    Milena Iwaszko

    2011-09-01

    Full Text Available The HLA-E protein is one of the most extensively studied MHC class Ib antigens and the least polymorphic one compared to other MHC class I molecules. In the human population there have been reported just ten alleles encoding three different peptides. Only two of these alleles, namely HLA-E*0101 and HLA-E*0103, are widely distributed (around 50�0each. The proteins encoded by these alleles differ from each other in one amino acid at position 107. In HLA-E*0101 it is arginine and in HLA-E*0103 it is glycine. The difference between these proteins manifests itself in surface expression levels, affinities to leader peptides and thermal stabilities of their complexes.The HLA-E molecule is a ligand for CD94/NKG2 receptors on NK cells and TCR receptors on NK-CTL (NK-cytotoxic T lymphocyte cells, so it plays a double role in both innate and adaptive immunity. This paper reviews the knowledge on the role of the HLA-E molecule in the immunological response. Aspects related to polymorphism of the HLA-E gene and the course of several diseases including type I diabetes, ankylosing spondylitis, HCV and HIV infections, nasopharyngeal cancer and recurrent spontaneous abortions, as well as the outcome of hematopoietic stem cell transplantation, are presented and discussed in more detail.

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

    Science.gov (United States)

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

    2016-09-01

    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.

  16. Criteria to define HLA haplotype loss in human solid tumors

    NARCIS (Netherlands)

    Ramal, LM; van der Zwan, AW; Collado, A; Lopez-Nevot, MA; Tilanus, M; Garrido, F

    2000-01-01

    Short tandem repeat (STR) markers are currently used to define loss of heterozygosity (LOH) of genes and chromosomes in tumors. Chromosome 6 and chromosome 15 STR markers are applied to define loss of HLA and related genes (e.g. TAP and beta(2)m) The number of STR identified in the HLA region is sti

  17. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens

    Directory of Open Access Journals (Sweden)

    Shinji Amari

    2013-01-01

    Full Text Available The three-dimensional (3D structures of human leukocyte antigen (HLA molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  18. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens.

    Science.gov (United States)

    Amari, Shinji; Kataoka, Ryoichi; Ikegami, Takashi; Hirayama, Noriaki

    2013-01-01

    The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  19. HLA-DP antigens in patients with alopecia areata

    DEFF Research Database (Denmark)

    Ødum, Niels; Morling, N; Georgsen, J;

    1990-01-01

    The distribution of HLA-DP antigens were studied in 41 patients with alopecia areata (AA) and 188 ethnically matched controls. An increase of DR4 and possibly DR5 in 24 of these patients has previously been reported. HLA-DP typing for DPw1 through w6 and the local specificity, CDP HEI, was perfor...

  20. Polymorphisms of HLA genes in Western Javanese (Indonesia): close affinities to Southeast Asian populations.

    Science.gov (United States)

    Yuliwulandari, R; Kashiwase, K; Nakajima, H; Uddin, J; Susmiarsih, T P; Sofro, A S M; Tokunaga, K

    2009-01-01

    Identification of human leukocyte antigen (HLA) antigens that are known as the highest polymorphic genes has become a valuable tool for tissue transplantation, platelet transfusion, disease susceptibility or resistance, and forensic and anthropological studies. In the present study, the allele and haplotype frequencies of HLA-A, HLA-B, and HLA-DRB1 were studied in 237 unrelated healthy Western Javanese (Indonesia) by the high-resolution polymerase chain reaction-Luminex method. A total of 18 A, 40 B, and 20 DRB1 alleles were identified. The most frequent HLA-A, -B, and -DRB1 alleles were HLA-A*2407 (21.6%), HLA-B*1502 (11.6%) and HLA-B*1513 (11.2%), and DRB1*1202 (37.8%), respectively. The most frequent two-locus haplotypes were HLA-A*2407-B*3505 (7%) and HLA-B*1513-DRB1*1202 (9.2%), and three-locus haplotypes were HLA-A*3401-B*1521-DRB1*150201 (4.6%), HLA-A*2407-B*3505-DRB1*1202 (4.3%), and HLA-A*330301-B*440302-DRB1*070101 (4.2%). HLA allele and haplotype frequencies in addition to phylogenetic tree and principal component analyses based on the four-digit sequence-level allele frequencies for HLA-A, HLA-B, and HLA-DRB1 showed that Western Javanese (Indonesia) was closest to Southeast Asian populations.

  1. Architectural Anthropology

    DEFF Research Database (Denmark)

    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...

  2. Ultraspecific probes for high throughput HLA typing

    Directory of Open Access Journals (Sweden)

    Eggers Rick

    2009-02-01

    Full Text Available Abstract Background The variations within an individual's HLA (Human Leukocyte Antigen genes have been linked to many immunological events, e.g. susceptibility to disease, response to vaccines, and the success of blood, tissue, and organ transplants. Although the microarray format has the potential to achieve high-resolution typing, this has yet to be attained due to inefficiencies of current probe design strategies. Results We present a novel three-step approach for the design of high-throughput microarray assays for HLA typing. This approach first selects sequences containing the SNPs present in all alleles of the locus of interest and next calculates the number of base changes necessary to convert a candidate probe sequences to the closest subsequence within the set of sequences that are likely to be present in the sample including the remainder of the human genome in order to identify those candidate probes which are "ultraspecific" for the allele of interest. Due to the high specificity of these sequences, it is possible that preliminary steps such as PCR amplification are no longer necessary. Lastly, the minimum number of these ultraspecific probes is selected such that the highest resolution typing can be achieved for the minimal cost of production. As an example, an array was designed and in silico results were obtained for typing of the HLA-B locus. Conclusion The assay presented here provides a higher resolution than has previously been developed and includes more alleles than previously considered. Based upon the in silico and preliminary experimental results, we believe that the proposed approach can be readily applied to any highly polymorphic gene system.

  3. HLA-G expression in the peripheral blood of live kidney transplant recipients

    Institute of Scientific and Technical Information of China (English)

    XIAO Li; ZHOU Wen-qiang; SHI Bing-yi; FENG Kai; HE Xiu-yun; WEI Yu-xiang; GAO Yu

    2013-01-01

    Background The human leukocyte antigen-G (HLA-G) has been considered to be an important tolerogeneic molecule playing an essential role in maternal-fetal tolerance,upregulated in the context of transplantation,malignancy,and inflammation,and has been correlated with various clinical outcomes.The aim of this study was to investigate the clinical relevance of the expression of membrane HLA-G (mHLA-G),intracellular HLA-G (iHLA-G),and soluble HLA-G (sHLA-G) in the peripheral blood of live kidney transplant recipients.Methods We compared the expression of the three HLA-G isoforms in three groups,healthy donors (n=20),recipients with acute rejection (n=19),and functioning transplants (n=30).Flow cytometry was used to detect the expression of mHLA-G and iHLA-G in the T lymphocytes of peripheral blood from subjects in the three groups.Enzyme-linked immunosorbent assays were used to detect sHLA-G in the plasma from the three groups.Results There were no significant differences in mHLA-G and intracellular HLA-G among the three groups,but the sHLA-G plasma level was higher in the functioning group than in the acute rejection or healthy group.We found a subset of CD4+HLA-G+ and CD8+HLA-G+T lymphocytes with low rates of mHLA-G expression in the peripheral blood of kidney transplantation recipients.Intracellular expression of HLA-G was detected in T lymphocytes.However,there was no correlation between acute rejection and the mHLA-G or intracellular HLA-G expression.Conclusion sHLA-G was the major isoform in the peripheral blood of live kidney transplant recipients and high sHLA-G levels were associated with allograft acceptance.

  4. Expression of the Classical and Nonclassical HLA Molecules in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Gisela Bevilacqua Rolfsen Ferreira da Silva

    2013-01-01

    Full Text Available Considering that downregulation of HLA expression could represent a potential mechanism for breast carcinogenesis and metastasis, the aim of the present study was to use immunohistochemical methods to analyze the expression of HLA-Ia, HLA-DR, HLA-DQ, HLA-E, and HLA-G in invasive ductal carcinoma (IDC of the breast and to relate this HLA profile to anatomopathological parameters. Fifty-two IDC from breast biopsies were stratified according to histological differentiation (well, moderately, and poorly differentiated and to the presence of metastases in axillary lymph nodes. The expression of HLA molecules was assessed by immunohistochemistry, using a computer-assisted system. Overall, 31 (59.6% out of the 52 IDC breast biopsies exhibited high expression of HLA-G, but only 14 (26.9% showed high expression of HLA-E. A large number (41, 78.8% of the biopsies showed low expression of HLA-Ia, while 45 (86.5% showed high expression of HLA-DQ and 36 (69.2% underexpressed HLA-DR. Moreover, 24 (41.2% of 52 biopsies had both low HLA-Ia expression and high HLA-G expression, while 11 (21.2% had low HLA-Ia expression and high HLA-E expression. These results suggest that, by different mechanisms, the downregulation of HLA-Ia, HLA-E, and HLA-DR and the upregulation of HLA-G and HLA-DQ are associated with immune response evasion and breast cancer aggressiveness.

  5. Automatic Functionality Assignment to AUTOSAR Multicore Distributed Architectures

    DEFF Research Database (Denmark)

    Maticu, Florin; Pop, Paul; Axbrink, Christian

    2016-01-01

    The automotive electronic architectures have moved from federated architectures, where one function is implemented in one ECU (Electronic Control Unit), to distributed architectures, where several functions may share resources on an ECU. In addition, multicore ECUs are being adopted because of be...

  6. Role of HLA-A in Handedness

    OpenAIRE

    2015-01-01

    AbstractA relationship exists between cerebral dominance and right or left handedness. Left-hemisphere dominance occurs in 97% of right-handed people and in 70% of left-handed people. The other 30% of left-handed individuals have anomalous or right-hemisphere dominance. Both environmental and genetic factors have been proposed to explain the human handedness. Aim of this study was to determine the effect of genetic factor of human leukocytes antigens (HLA-A) on development of left handedness....

  7. Multithreading architecture

    CERN Document Server

    Nemirovsky, Mario

    2013-01-01

    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

  8. Architectural Anthropology

    DEFF Research Database (Denmark)

    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...

  9. Study of HLA-DR synthesis in cultured human keratinocytes.

    Science.gov (United States)

    Wikner, N E; Huff, J C; Norris, D A; Boyce, S T; Cary, M; Kissinger, M; Weston, W L

    1986-11-01

    Within the normal human epidermis only Langerhans and indeterminate cells express HLA-DR. Human keratinocytes (HK), however, may also express HLA-DR in certain disease states characterized by mononuclear cell infiltrates. Previous studies have shown that HK synthesize HLA-DR in response to stimulation by interferon gamma (INF-gamma). The purposes of this study were to define conditions under which cultured HK might express HLA-DR and to compare the HLA-DR synthesis of HK with that of monocytes. HLA-DR expression by HK as determined by indirect immunofluorescence of HK cultures was absent under standard low calcium conditions and remained absent with the addition of calcium, serum, mitogens, and supernatants from Pam-212 cells containing epidermal thymocyte-activating factor. HLA-DR expression in HK was induced by cocultivation with concanavalin A-stimulated peripheral blood mononuclear cells (PBMC), but not unstimulated PBMC. This effect was time-dependent and directly related to the number of PBMC. HLA-DR expression was also induced in a time- and dose-dependent manner by addition of supernatant from stimulated PBMC (SS) or by addition of recombinant INF-gamma but not by addition of interleukin (IL)-1 or IL-2. Induction by either SS or INF-gamma was blocked by an antiserum to INF-gamma. As determined by a semiquantitative immunoprecipitation technique, HLA-DR synthesis by HK was directly related to INF-gamma concentration. The pattern of HLA-DR peptides produced by HK was similar to that of monocytes, but the relative quantity synthesized was far less than that of monocytes.

  10. Crystal structures of two peptide-HLA-B*1501 complexes; structural characterization of the HLA-B62 supertype

    DEFF Research Database (Denmark)

    Roder, G; Blicher, Thomas; Justesen, Sune Frederik Lamdahl;

    2006-01-01

    of human immune responses, the structure of at least one member of each supertype should be determined. Here, the structures of two immunogenic peptide-HLA-B*1501 complexes are described. The structure of HLA-B*1501 in complex with a peptide (LEKARGSTY, corresponding to positions 274-282 in the Epstein-Barr...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...

  12. The Presence of Anti-HLA Antibodies before and after Allogeneic Hematopoietic Stem Cells Transplantation from HLA-Mismatched Unrelated Donors

    Directory of Open Access Journals (Sweden)

    Anna Koclega

    2012-01-01

    Full Text Available Although anti-human leukocyte antigen antibodies (anti-HLA Abs are important factors responsible for graft rejection in solid organ transplantation and play a role in post-transfusion complications, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT has not been finally defined. Enormous polymorphism of HLA-genes, their immunogenicity and heterogeneity of antibodies, as well as the growing number of allo-HSCTs from partially HLA-mismatched donors, increase the probability that anti-HLA antibodies could be important factors responsible for the treatment outcomes. We have examined the incidence of anti-HLA antibodies in a group of 30 allo-HSCT recipients from HLA-mismatched unrelated donors. Anti-HLA Abs were identified in sera collected before and after allo-HSCT. We have used automated DynaChip assay utilizing microchips bearing purified class I and II HLA antigens for detection of anti-HLA Abs. We have detected anit-HLA antibodies against HLA-A, B, C, DR, DQ and DP, but no donor or recipient-specific anti-HLA Abs were detected in the studied group. The preliminary results indicate that anti-HLA antibodies are present before and after allo-HSCT in HLA-mismatched recipients.

  13. Promoter methylation and mRNA expression of HLA-G in relation to HLA-G protein expression in colorectal cancer.

    Science.gov (United States)

    Swets, Marloes; Seneby, Lina; Boot, Arnoud; van Wezel, Tom; Gelderblom, Hans; van de Velde, Cornelis J H; van den Elsen, Peter J; Kuppen, Peter J K

    2016-09-01

    Expression of human leukocyte antigen-G (HLA-G) is a suggested mechanism used by tumor cells to escape from host immune recognition and destruction. Advances in the field have made it evident that HLA-G is expressed in different types of malignancies including colorectal cancer (CRC). We analyzed HLA-G expression in 21 low passage CRC cell lines. The level of DNA methylation of the HLA-G gene and the presence of mRNA encoding HLA-G was measured. Moreover, HLA-G protein expression was determined by flow cytometry and immunohistochemistry (IHC). IHC was performed with three different monoclonal antibodies (mAbs) (4H84, MEM-G/1 and MEM-G/2). In addition, HLA-G protein expression was measured in matching primary tumor tissues. RNA analysis using RT-PCR followed by sequencing in 6 samples indicated strong homology of the PCR product with HLA-G3 in 5 samples. In accordance, in none of the cell lines, HLA-G1 expression was detected by flow-cytometry. Furthermore, no association between HLA-G DNA methylation patterns and HLA-G mRNA expression was observed. In addition, different immunohistochemical staining profiles among various anti-HLA-G mAbs were observed. In conclusion, the results of this study show that the HLA-G3 isoform was expressed in some of the CRC cell lines irrespective of the level of DNA methylation of HLA-G.

  14. 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

    Institute of Scientific and Technical Information of China (English)

    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

    2012-01-01

    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

  15. Architectural Tops

    Science.gov (United States)

    Mahoney, Ellen

    2010-01-01

    The development of the skyscraper is an American story that combines architectural history, economic power, and technological achievement. Each city in the United States can be identified by the profile of its buildings. The design of the tops of skyscrapers was the inspiration for the students in the author's high-school ceramic class to develop…

  16. Religious Architecture

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    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.

  17. Architectural Illusion.

    Science.gov (United States)

    Doornek, Richard R.

    1990-01-01

    Presents a lesson plan developed around the work of architectural muralist Richard Haas. Discusses the significance of mural painting and gives key concepts for the lesson. Lists class activities for the elementary and secondary grades. Provides a photograph of the Haas mural on the Fountainbleau Hilton Hotel, 1986. (GG)

  18. Textile Architecture

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen

    2010-01-01

    Textiles can be used as building skins, adding new aesthetic and functional qualities to architecture. Just like we as humans can put on a coat, buildings can also get dressed. Depending on our mood, or on the weather, we can change coat, and so can the building. But the idea of using textiles...

  19. Federal Lands

    Data.gov (United States)

    Department of Homeland Security — This map layer consists of federally owned or administered lands of theUnited States, Puerto Rico, and the U.S. Virgin Islands. Only areas of 640 acres or more are...

  20. Impact on parents of hla-dq/dq8 genotyping in healthy children from coeliac families

    NARCIS (Netherlands)

    Wessels, M.M.S.; Vriezinga, S.L.; Koletzko, S.; Werkstetter, K.; Castillejo-De Villasante, G.; Shamir, R.; Hartman, C.; Putter, H.; Pal, S.M. van der; Wijmenga, C.; Bravi, E.; Mearin, M.L.

    2015-01-01

    Due to the association of coeliac disease and HLA-specificities DQ2 and DQ8, HLA-typing can be used for risk determination of the disease. This study was designed to evaluate the knowledge of parents from coeliac families regarding HLA-typing and the impact of HLA-typing on the perception of the hea

  1. HLA-DP related suppression of mixed lymphocyte reaction with alloactivated lymphocytes

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jakobsen, B K

    1986-01-01

    We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and DR...

  2. HLA-class II genes in Mexican Amerindian Mayas: relatedness with Guatemalan Mayans and other populations.

    Science.gov (United States)

    Vargas-Alarcón, Gilberto; Granados, Julio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Canto-Cetina, Thelma; Coral-Vázquez, Ramón Mauricio; Areces, Cristina; Gómez-Prieto, Pablo; Arnaiz-Villena, Antonio

    2011-01-01

    We analyzed the HLA class II allele frequencies in 50 healthy unrelated Mayan individuals. The relationship with other worldwide populations was studied by using HLA data from 71 different populations. The most frequent alleles were HLA-DRB1*04, HLA-DRB1*01, HLA-DQB1*0302 and HLA-DQB1*0501. When comparisons with other Mexican Amerindian groups were made, some differences were observed. Mayans showed an increased frequency of HLA-DRB1*01 when compared to Nahuas, Mayos, Teenek and Mazatecans (p Mayas showing that languages do not correlate with genes, particularly in Amerindians. The data corroborate the restricted polymorphism of HLA-DRB1 and DQB1 alleles and the high frequency of HLA-DRB1*04 and HLA-DQB1*0302 in Mayans from Mexico.

  3. Immunoregulatory Role of HLA-G in Allergic Diseases

    Directory of Open Access Journals (Sweden)

    Giuseppe Murdaca

    2016-01-01

    Full Text Available Allergic diseases are sustained by a T-helper 2 polarization leading to interleukin-4 secretion, IgE-dependent inflammation, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, play a central role in modulation of immune responses. Elevated levels of soluble HLA-G (sHLA-G molecules are detected in serum of patients with allergic rhinitis to seasonal and perennial allergens and correlate with allergen-specific IgE levels, clinical severity, drug consumption, and response to allergen-specific immunotherapy. sHLA-G molecules are also found in airway epithelium of patients with allergic asthma and high levels of sHLA-G molecules are detectable in plasma and bronchoalveolar lavage of asthmatic patients correlating with allergen-specific IgE levels. Finally, HLA-G molecules are expressed by T cells, monocytes-macrophages, and Langerhans cells infiltrating the dermis of atopic dermatitis patients. Collectively, although at present it is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

    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.

  5. Infection and HLA-G Molecules in Nasal Polyposis

    Directory of Open Access Journals (Sweden)

    Roberta Rizzo

    2014-01-01

    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.

  6. MUF architecture /art London

    DEFF Research Database (Denmark)

    Svenningsen Kajita, Heidi

    2009-01-01

    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...

  7. Kosmos = architecture

    Directory of Open Access Journals (Sweden)

    Tine Kurent

    1985-12-01

    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.

  8. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    putting an emphasis on architecture as unified scenery guided by the four motives hearth, enclosure, dressing and context. This theoretical framework draws on the Gastronomic Analogy put forth by James Fergusson in 1862 and an interpretation of the writings of the 19th century architect Gottfried Semper...... with the material appearance of objects, but also the imaginary world of dreams and memories which are concealed with the communicative significance of intentions when designing the future super hospitals....

  9. Architectural Theatricality

    DEFF Research Database (Denmark)

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

    2013-01-01

    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 used......’ is an overlooked element in hospital eating environments today, and further point at how Semper’s discourse on theatricality can be used to add a more nuanced perspective to future hospitality studies....

  10. HLA ANTIGENS AND VOGT-KOYANAGI- HARADA'S DISEASE

    Institute of Scientific and Technical Information of China (English)

    1991-01-01

    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.

  11. Plasma Levels of Soluble HLA-E and HLA-F at Diagnosis May Predict Overall Survival of Neuroblastoma Patients

    Directory of Open Access Journals (Sweden)

    Fabio Morandi

    2013-01-01

    Full Text Available The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS of neuroblastoma (NB patients. Concentration of soluble (s biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3 or serum (calprotectin samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient’s outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS, whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.

  12. Plasma levels of soluble HLA-E and HLA-F at diagnosis may predict overall survival of neuroblastoma patients.

    Science.gov (United States)

    Morandi, Fabio; Cangemi, Giuliana; Barco, Sebastiano; Amoroso, Loredana; Giuliano, Maria; Gigliotti, Anna Rita; Pistoia, Vito; Corrias, Maria Valeria

    2013-01-01

    The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS) of neuroblastoma (NB) patients. Concentration of soluble (s) biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3) or serum (calprotectin) samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient's outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS), whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.

  13. Clinical and immunological significance of HLA-E in stem cell transplantation and cancer.

    Science.gov (United States)

    Wieten, L; Mahaweni, N M; Voorter, C E M; Bos, G M J; Tilanus, M G J

    2014-12-01

    Human leukocyte antigen-E (HLA-E) is a nonclassical HLA class I molecule that canonically binds peptides derived from the leader sequence of classical HLA class I. HLA-E can also bind peptides from stress protein [e.g. heat shock protein 60 (Hsp60)] and pathogens, illustrating the importance of HLA-E for anti-viral and anti-tumor immunity. Like classical HLA class I molecules, HLA-E is ubiquitously expressed, however, it is characterized by only a very limited sequence variability and two dominant protein forms have been described (HLA-E*01:01 and HLA-E*01:03). HLA-E influences both the innate and the adaptive arms of the immune system by the engagement of inhibitory (e.g. NKG2A) and activating receptors [e.g. αβ T cell receptor (αβTCR) or NKG2C] on NK cells and CD8 T cells. The effects of HLA-E on the cellular immune response are therefore complex and not completely understood yet. Here, we aim to provide an overview of the immunological and clinical relevance of HLA-E and HLA-E polymorphism in stem cell transplantation and in cancer. We review novel insights in the mechanism via which HLA-E expression levels are controlled and how the cellular immune response in transplantation and cancer is influenced by HLA-E.

  14. Development of a high-resolution NGS-based HLA-typing and analysis pipeline.

    Science.gov (United States)

    Wittig, Michael; Anmarkrud, Jarl A; Kässens, Jan C; Koch, Simon; Forster, Michael; Ellinghaus, Eva; Hov, Johannes R; Sauer, Sascha; Schimmler, Manfred; Ziemann, Malte; Görg, Siegfried; Jacob, Frank; Karlsen, Tom H; Franke, Andre

    2015-06-23

    The human leukocyte antigen (HLA) complex contains the most polymorphic genes in the human genome. The classical HLA class I and II genes define the specificity of adaptive immune responses. Genetic variation at the HLA genes is associated with susceptibility to autoimmune and infectious diseases and plays a major role in transplantation medicine and immunology. Currently, the HLA genes are characterized using Sanger- or next-generation sequencing (NGS) of a limited amplicon repertoire or labeled oligonucleotides for allele-specific sequences. High-quality NGS-based methods are in proprietary use and not publicly available. Here, we introduce the first highly automated open-kit/open-source HLA-typing method for NGS. The method employs in-solution targeted capturing of the classical class I (HLA-A, HLA-B, HLA-C) and class II HLA genes (HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1). The calling algorithm allows for highly confident allele-calling to three-field resolution (cDNA nucleotide variants). The method was validated on 357 commercially available DNA samples with known HLA alleles obtained by classical typing. Our results showed on average an accurate allele call rate of 0.99 in a fully automated manner, identifying also errors in the reference data. Finally, our method provides the flexibility to add further enrichment target regions.

  15. Prospective HLA-DR matching in cadaveric renal transplants: a single center study.

    Science.gov (United States)

    Mendez, R; Iwaki, Y; Mendez, R; Bogaard, T; Self, B

    1983-03-01

    We reviewed 77 potential cadaveric allograft recipients who had undergone prospective HLA-A and B locus and HLA-DR antigen identification. Matching was accomplished, giving first priority to HLA-DR compatibility and relying on HLA-A and B antigen matching only in situations of total HLA-DR incompatibility. Complete HLA-DR identification occurred in 56 per cent of all patients. There were 15 patients (19.5 per cent) who received a 2/2 HLA-DR perfect match, with 86.7 plus or minus 8.8 per cent 1-year actuarial graft survival, and 41 (53 per cent) who received a 1/2 HLA-DR match, with 58.2 plus or minus 7.8 per cent 1-year actual allograft survival. Finally, 21 patients (27 per cent) received a 0/2 HLA-DR match, with 64.9 plus or minus 10.7 per cent actual survival. These results and their mirrored mismatching results showed statistically significant allograft success in only the HLA-DR 2/2 matches. Matching for HLA 2 DR donors proved a statistically significant success over the other HLA-DR allograft matches and the older controversial matching system based on HLA-A and B locus antigens. The restricted gene polymorphism of the HLA-DR systems allows for a relatively high percentage of perfect HLA-DR matches.

  16. ENDOGENOUS EXPRESSION AND HLA STABILIZATION ASSAY OF PLASMODIUM FALCIPARUM CTL EPITOPE MINIGENE IN HUMAN HLA-A2.1 AND HLA-B51 CELLS

    Institute of Scientific and Technical Information of China (English)

    唐玉阳; 王恒

    2001-01-01

    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.

  17. PingFederate

    Data.gov (United States)

    US Agency for International Development — PingFederate Server provides Identity Federation and Single Sign On Capabilities. Federated identity management (or identity federation) enables enterprises to...

  18. The Type 1 Diabetes - HLA Susceptibility Interactome - Identification of HLA Genotype-Specific Disease Genes for Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, C.; Hansen, Niclas Tue; Bergholdt, R.;

    2010-01-01

    Background: The individual contribution of genes in the HLA region to the risk of developing type 1 diabetes (T1D) is confounded by the high linkage disequilibrium (LD) in this region. Using a novel approach we have combined genetic association data with information on functional protein...... on HLA-DRB1 genotypes. The best SNP signal in each gene was mapped to proteins in a human protein interaction network and their significance of clustering in functional network modules was evaluated. The significant network modules identified through this approach differed between the six HLA risk groups...

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Soluble monomers, dimers and HLA-G-expressing extracellular vesicles: the three dimensions of structural complexity to use HLA-G as a clinical biomarker.

    Science.gov (United States)

    Nardi, F da Silva; König, L; Wagner, B; Giebel, B; Santos Manvailer, L F; Rebmann, V

    2016-09-01

    The HLA-G molecule belongs to the family of nonclassical human leukocyte antigen (HLA) class I. At variance to classical HLA class I, HLA-G displays (i) a low number of nucleotide variations within the coding region, (ii) a high structural diversity, (iii) a restricted peptide repertoire, (iv) a limited tissue distribution and (v) strong immune-suppressive properties. The physiological HLA-G surface expression is restricted to the maternal-fetal interface and to immune-privileged adult tissues. Soluble forms of HLA-G (sHLA-G) are detectable in various body fluids. Cellular activation and pathological processes are associated with an aberrant or a neo-expression of HLA-G/sHLA-G. Functionally, HLA-G and its secreted forms are considered to be key players in the induction of short- and long-term tolerance. Thus, its unique expression profile and tolerance-inducing functions render HLA-G/sHLA-G an attractive biomarker to monitor the systemic health/disease status and disease activity/progression for clinical approaches in disease management and treatments. Here, we place emphasis on (i) the current status of the tolerance-inducing functions by HLA-G/sHLA-G, (ii) the current complexity to implement this molecule as a meaningful clinical biomarker regarding the three dimensions of structural diversity (monomers, dimers and HLA-G-expressing extracellular vesicles) with its functional implications, and (iii) novel and future approaches to detect and quantify sHLA-G structures and functions.

  1. Object-oriented modeling and design of database federations

    NARCIS (Netherlands)

    Balsters, H.

    2003-01-01

    We describe a logical architecture and a general semantic framework for precise specification of so-called database federations. A database federation provides for tight coupling of a collection of heterogeneous component databases into a global integrated system. Our approach to database federation

  2. DNA polymorphism of HLA class II genes in alopecia areata

    DEFF Research Database (Denmark)

    Morling, N; Frentz, G; Fugger, L;

    1992-01-01

    of the serologically defined HLA-DQw7 specificity. Individuals who carried both DQA1*0501 and DQB1*0301 seemed to have a further increased risk of developing AA compared to individuals carrying only one of these HLA class II genes. Analysis of the combined presence of DQB1*0301 and DPA1*0103 in AA suggests......We investigated the DNA restriction polymorphism (RFLP) of the Major Histocompatibility Complex (MHC) class II genes: HLA-DQA, -DQB, -DPA, and -DPB in 20 Danish patients with alopecia areata (AA) and in healthy Danes. The frequency in AA of the DQB1*0301 and DQw7 associated DQB Bgl/II 4.2 kb...... that an additive risk effect (synergism or interaction) exists between the DQB1*0301 and DPA1*0103 alleles which are situated at different HLA class II loci....

  3. The difference of ELISA and LABScreen in detecting HLA antibodies

    Institute of Scientific and Technical Information of China (English)

    吴萍萍

    2013-01-01

    Objective To compare the difference of ELISA and LABScreen in detecting HLA antibodies and evaluate their effects on allograft rejection.Methods Consecutive patients undergoing kidney transplantion from November,2008 to December,2009 in the First Affiliated Hospital

  4. From green architecture to architectural green

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    they have overshadowed the architectural potential of green architecture. The paper questions how a green space should perform, look like and function. Two examples are chosen to demonstrate thorough integrations between green and space. The examples are public buildings categorized as pavilions. One....... Architectural green could signify green architecture with inclusive interrelations between green and space, built and unbuilt, inside and outside. The aim of the term is to reflect a new focus in green architecture – its architectural performance. Ecological issues are not underestimated or ignored, but so far......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...

  5. Cross-reactions in the HLA system revealed by red blood cells expressing HLA determinants, with particular reference to cross-reaction between HLA-A2 and B17.

    Science.gov (United States)

    Nordhagen, R

    1983-01-01

    Sera with cytotoxic and haemagglutinating activity towards HLA-A2/28 were also shown to react with red blood cells (RBC) expressing the HLA-B17 antigen determinant. Absorption procedures with white blood cells (WBC) indicated that this was due to an HLA-A2/B17 cross-reaction. Absorption experiments with some other sera which previously had shown cytotoxic and haemagglutinating activity towards different HLA specificities, revealed broad cross-reaction related to HLA-B locus antigens.

  6. The role of HLA antibodies in allogeneic SCT: is the 'type-and-screen' strategy necessary not only for blood type but also for HLA?

    Science.gov (United States)

    Yoshihara, S; Taniguchi, K; Ogawa, H; Saji, H

    2012-12-01

    The role of HLA antibodies in SCT has drawn increasing attention because of the significantly increased number of patients who receive HLA-mismatched SCT, including cord blood transplantation, haploidentical SCT and unrelated SCT. Technical advancements in the methods of HLA Ab testing have realized rapid, accurate and objective identification, as well as quantification of specific HLA antibodies. Recent clinical studies have suggested that the presence of donor-specific HLA antibodies (DSA) in patients is associated with graft failure in HLA-mismatched SCT when the above-listed stem cell sources are used and results in different impacts. Of note, most of the 'HLA-matched' unrelated SCT actually involve HLA mismatches in HLA-DP and the presence of antibodies against this locus has been reported to be associated with graft failure. Thus, HLA Ab should be examined as a work-up for all patients who undergo SCT from 'alternative donors.' The simplest route for preventing HLA Ab-mediated graft failure in Ab-positive patients is to avoid donors who possess the target Ag of HLA antibodies. If SCT from such donors must be performed, treatment for DSA before SCT may improve the chances of successful donor engraftment.

  7. Cutting Edge: Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B.

    Science.gov (United States)

    Thananchai, Hathairat; Gillespie, Geraldine; Martin, Maureen P; Bashirova, Arman; Yawata, Nobuyo; Yawata, Makoto; Easterbrook, Philippa; McVicar, Daniel W; Maenaka, Katsumi; Parham, Peter; Carrington, Mary; Dong, Tao; Rowland-Jones, Sarah

    2007-01-01

    Although it is clear that KIR3DL1 recognizes Bw4(+) HLA-B, the role of Bw4(+) HLA-A allotypes as KIR3DL1 ligands is controversial. We therefore examined the binding of tetrameric HLA-A and -B complexes, including HLA*2402, a common Bw4(+) HLA-A allotype, to KIR3DL1*001, *005, *007, and *1502 allotypes. Only Bw4(+) tetramers bound KIR3DL1. Three of four HLA-A*2402 tetramers bound one or more KIR3DL1 allotypes and all four KIR3DL1 allotypes bound to one or more HLA-A*2402 tetramers, but with different binding specificities. Only KIR3DL1*005 bound both HLA-A*2402 and HLA-B*5703 tetramers. HLA-A*2402-expressing target cells were resistant to lysis by NK cells expressing KIR3DL1*001 or *005. This study shows that HLA-A*2402 is a ligand for KIR3DL1 and demonstrates how the binding of KIR3DL1 to Bw4(+) ligands depends upon the bound peptide as well as HLA and KIR3DL1 polymorphism.

  8. Textile Architecture

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen

    2010-01-01

    Textiles can be used as building skins, adding new aesthetic and functional qualities to architecture. Just like we as humans can put on a coat, buildings can also get dressed. Depending on our mood, or on the weather, we can change coat, and so can the building. But the idea of using textiles...... to create human habitation is not new. As Diether S. Hope phrases it, referring to tents: The history of development of humanity would be barely conceivable without free spanning textile membrane structures....

  9. Catalyst Architecture

    DEFF Research Database (Denmark)

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

    2014-01-01

    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 development...... meaningful for everyone. The exhibited works are designed by SANAA, Diller Scofidio + Renfro, James Corner Field Operation, JBMC Arquitetura e Urbanismo, Atelier Bow-Wow, Ateliers Jean Nouvel, COBE, Transform, BIG, Topotek1, Superflex, and by visual artist Jane Maria Petersen....

  10. Architectural dreaming

    Institute of Scientific and Technical Information of China (English)

    Mark Godfrey

    2004-01-01

    <正> For the first 800 years of its existence, Beijing retained essentially the same character: a walled palace city at its centre, organised on a strict north-south axis and contained within a sea of courtyard houses along lanes too narrow forcars. Today Beijing’s basic unit of architectural scale has become the skyscraper, erected a dozen at a time and facing massive highways. Ancient buildings are so small and unloved by comparison that they threaten to disappear from view. Fuelled by an economic boom, and propelled by banks flushed with mortgage cash, Beijing has embarked on the largest building campaign the world has ever seen.

  11. 75 FR 5637 - Culturally Significant Objects Imported for Exhibition Determinations: “Architecture as Icon...

    Science.gov (United States)

    2010-02-03

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF STATE Culturally Significant Objects Imported for Exhibition Determinations: ``Architecture as Icon: Perception and... Icon: Perception and Representation of Architecture in Byzantine Art,'' imported from abroad...

  12. Activating KIR/HLA complexes in classic Kaposi's Sarcoma

    Directory of Open Access Journals (Sweden)

    Guerini Franca R

    2012-04-01

    Full Text Available Abstract Background Classic Kaposi's Sarcoma (cKS is a rare vascular tumor associated with Human Herpesvirus 8 (KSHV infection, nevertheless not all KSHV-infected individuals have cKS. Objective We investigated whether particular KIR/HLA receptor/ligand genotypes would be preferentially present in KSHV-infected and uninfected individuals who have or have not developed cKS. Methods KIR/HLA genotypes were analyzed by molecular genotyping in 50 KSHV-infected individuals who did or did not have cKS and in 33 age-and sex-matched KSHV seronegative individuals. Results There was no association of individual KIR, HLA or receptor ligand combinations with KSHV infection. However, activating KIR and KIR/HLA genotypes were significantly more frequent in cKS cases, specifically KIR3DS1, KIR2DS1, and KIR2DS1 with its HLA-C2 ligand. Conclusion A nonspecific inflammatory response triggered by activation of NK cells upon KIR-HLA interaction could be associated with the pathogenesis of KS.

  13. Types of HLA in the bladder transitional cell carcinoma (TCC).

    Science.gov (United States)

    Yılmaz, Erkan; Uğur Özalp, Ali; Cekmen, Arman; Eren, Bülent; Onal, Bülent; Akkuş, Emre; Erdoğan, Ergun

    2013-02-01

    HLA plays a complementary role in the interaction between tumor and body immunology. The aim of this study was to determine the existence of the association between the HLA system and transitional cell carcinoma (TCC). Using standard micro-lymphocytotoxic method of Terasaki, HLA-A, B, DR and DQ antigen types of 30 patients with TCC of the bladder were compared with the control group (30 healthy people). In the TCC patient group, HLA -DQ6(1) and HLA -DQ7(3) antigens were detected with a significantly higher frequency than in the control group (p=0.018 and p=0.038, respectively), whereas HLA-A10, B4, DR53 and DQ1 antigens were detected with significantly higher frequency in the control group (p less 0.05 in all). It suggests that patients who had the antigens detected were at higher risk of TCC, and the ones who had the antigens displaying protective features as were detected in the control group, were at lesser risk.

  14. HLA-A, HLA-B, HLA-DRB1 allele and haplotype frequencies in 6384 umbilical cord blood units and transplantation matching and engraftment statistics in the Zhejiang cord blood bank of China.

    Science.gov (United States)

    Wang, F; He, J; Chen, S; Qin, F; Dai, B; Zhang, W; Zhu, F M; Lv, H J

    2014-02-01

    Umbilical cord blood (UCB) is a widely accepted source of progenitor cells, and now, many cord blood banks were established. Here, we analysed the HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies, HLA matching possibilities for searching potential donors and outcome of UCB transplantations in Zhejiang cord blood bank of China. A total of 6384 UCB units were characterized for 17 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles at the first field resolution level. Additionally, B*14, B*15 and B*40 were typed to the second field level. A total of 1372 distinct A-B-DRB1 haplotypes were identified. The frequencies of 7 haplotypes were more than 1%, and 439 haplotypes were blood bank of Zhejiang province. These data can help to select potential UCB donors for transplantation and used to assess the scale of new cord blood banking endeavours.

  15. Constructing Multi-subject Design and Optimized Calculation Environment of Powered Support based on HLA%基于 HLA 构建液压支架多学科设计优化计算环境

    Institute of Scientific and Technical Information of China (English)

    孟晓军; 王国法; 王金华; 安里千; 任怀伟; 王建国

    2014-01-01

    In order to solve whole optimization problem of heavy machinery such as powered support, multi-subject design collaborative optimization calculation environment based on high-level architecture was developed. This calculation environment encapsulated analysis and optimization implement of related subjects and searched for whole optimization design on the basis of single subject. By constructing consistency constraint of multi-subject, the goal of minimum distance of subject-level variable and system-level distribution value was reached, which realized collaborative optimization of multi-subject. Based on the model, coupled state variables of subjects were reflec-ted as publishable and order attribute of corresponding federal member object classes, interaction of coupled variable between subjects was realized, applying the coupling effect of multi-subject, whole optimization design was realized. Finally, taking the procedure of multi-subject design and optimization for a type of powered support as an example, application method of the calculation environment was introduced and its effectiveness was proved.%为了解决液压支架等重型机械的整体优化问题,开发了基于高层体系架构(HLA)的多学科设计协同优化计算环境。该计算环境封装了相关学科领域的分析优化工具,在单学科优化的基础上寻求整体优化设计;通过构造多学科间一致性约束,实现了最小化学科级设计变量与系统级分配目标值之间差距的目的,实现了学科间的协同优化;基于高层体系架构建立优化模型,将学科间的耦合状态变量映射为相关联邦成员对象类的可发布和订购属性,实现了学科间耦合变量的交互,充分利用学科间的耦合效应,实现了整体优化设计。最后通过某型号液压支架的多学科设计优化过程为例,描述了该计算环境的使用方法并且验证了其有效性。

  16. The Genetic Profile from HLA and Non-HLA Loci Allows Identification of Atypical Type 2 Diabetes Patients

    OpenAIRE

    Matias Fabregat; Mariana Fernandez; Gerardo Javiel; Graciela Vitarella; Adriana Mimbacas

    2015-01-01

    The complex diagnosis and treatment of diabetes highlight the need for markers to define how to monitor patients correctly during the course of their disease. Different studies demonstrate the existence of patients who cannot be clearly classified. We have previously shown that it is possible to differentiate “atypical diabetic patients” based on genotyping the HLA. In this work we show that the analysis of non-HLA related to type 1 diabetes in the INS-VNTR, SNP rs689...

  17. The conundrum of HLA-DRB1*14:01/*14:54 and HLA-DRB3*02:01/*02:02 mismatches in unrelated hematopoietic SCT.

    Science.gov (United States)

    Pasi, A; Crocchiolo, R; Bontempelli, M; Carcassi, C; Carella, G; Crespiatico, L; Garbarino, L; Mascaretti, L; Mazzi, B; Mazzola, G; Miotti, V; Porfirio, B; Tagliaferri, C; Valentini, T; Vecchiato, C; Fleischhauer, K; Sacchi, N; Bosi, A; Martinetti, M

    2011-07-01

    Uncertainty still exists on the role of polymorphisms outside the HLA-DRB1 binding site or inside the HLA-DRB3 binding groove in unrelated hematopoietic SCT (HSCT). The ideal model to solve the conundrum consists of the transplants mismatched for HLA-DRB1*14:01/*14:54 and/or for HLA-DRB3*02:01/*02:02. A task force was set up in Italy to recruit transplanted pairs defined as HLA-DRB1*14:01 before 2006, the year crucial for the proper definition of the HLA-DRB1*14:54 allele in molecular biology. Out of 2723 unrelated pairs, 189 transplanted in Italy from 1995 to 2006 were HLA-DRB1*14:01 positive; 103/189 pairs with good historical DNA were retyped for HLA-DRB1*14 and HLA-DRB3 at-high resolution level; 31/103 pairs had HLA-DRB1*14 and/or HLA-DRB3 mismatched; 99/103, having complete clinical data, underwent statistical analysis for OS, TRM, disease-free survival and acute and chronic GvHD. No significant involvement of HLA-DRB1*14:01/*14:54 or HLA-DRB3*02:01/*02:02 mismatches was found, either alone or combined. Our findings suggest that disparities at exon 3 of the HLA-DRB1 gene seem unlikely to influence the outcome after HSCT. The same may be envisaged for HLA-DRB3(*)02:01 and (*)02:02 alleles which, although differing in the Ag binding site, seem unable to modulate an appreciable immune response in an HSCT setting.

  18. HLA and epidermolysis bullosa: evidence for independent assortment of Weber-Cockayne subtype of epidermolysis bullosa and HLA complex.

    Science.gov (United States)

    Vaidya, S; Tyring, S K; Feldkamp, M; Johnson, L B; Fine, J D

    1991-05-01

    The purpose of this study was to examine the genetic linkage (but not the association) between HLA complex and Weber-Cockayne Subtype of epidermolysis bullosa (EBS-WC). We HLA typed 44 members of three multi-generation families in which 24 members have the clinical evidence of EBS-WC. The patterns of inheritance of various HLA haplotypes and the disease were mathematically analyzed to estimate frequency of recombination (i.e. genetic distance) between HLA complex and the disease by calculating Lod Scores for each family separately as well as all for three families combined. Our results show that only one family had a positive Lod Score. The Lod Scores for the remaining two families as well as the combined Lod Score for all three families were negative. These data suggest that odds are against the genetic linkage between HLA complex and Weber-Cockayne Subtype of epidermolysis bullosa and in favor of independent assortment of the disease and HLA complex.

  19. HLA-A*01:03, HLA-A*24:02, HLA-B*08:01, HLA-B*27:05, HLA-B*35:01, HLA-B*44:02, and HLA-C*07:01 Monochain Transgenic/H-2 Class I Null Mice

    DEFF Research Database (Denmark)

    Boucherma, Rachid; Kridane-Miledi, Hédia; Bouziat, Romain;

    2013-01-01

    surface expression of several transgenes was markedly reduced in recipient mice that coexpressed endogenous H-2 class I molecules, substantial surface expression of all human transgenes was observed in mice lacking H-2 class I molecules. In these HLA monochain transgenic/H-2 class I null mice, we observed...

  20. HLA-DR-expressing cells and T-lymphocytes in sural nerve biopsies

    DEFF Research Database (Denmark)

    Schrøder, H D; Olsson, T; Solders, G;

    1988-01-01

    was confirmed. HLA-DR expression was found in all biopsies and thus was not restricted to any particular type of neuropathy. The HLA-DR expression appeared to correlate with severity and activity of the neuropathy. HLA-DR-expressing macrophages wrapping myelinated fibers were prominent in primary demyelinating......Thirty-five sural nerve biopsies were stained immunohistochemically for HLA-DR antigen. HLA-DR was expressed on nonmyelinating Schwann cells, macrophages, vascular endothelium, and perineurium. By means of double immunofluorescence staining the identity of the HLA-DR presenting structures...

  1. HLA types in patients with rheumatoid arthritis developing leucopenia after both gold and sulphasalazine treatment.

    OpenAIRE

    Bliddal, H; Eiberg, B; Helin, P; Svejgaard, A.

    1989-01-01

    HLA types, especially HLA-DR3, are associated with the development of toxic reactions in patients with rheumatoid arthritis after treatment with gold or D-penicillamine. In this study, after treatment with sulphasalazine, leucopenia was observed in three patients, who all had a history of leucopenia after previous gold treatment. The HLA types of these patients did not include HLA-DR3; the two patients developing mild leucopenia had HLA-DR2 and the one developing agranulocytosis had HLA-DR4.

  2. Investigation of Asynchronous Events in Non-Time-Managed Federations

    Science.gov (United States)

    2005-09-01

    des messages. Cette etude, menee dans Ie cadre d’un contrat avec COGS 1M, visait it determiner I’impact de ces erreurs, y compris Ie nombre des... contrat Mait Ie premier d’une serie visant it Mudier I’utilisation des regroupements HLA sur des WAN it temps d’ attente considerable. Des recherches...federations is the role played by the Run- Time Infrastructure (RTI) and the management services that it provides. In the past, federations deemed to be

  3. Lab architecture

    Science.gov (United States)

    Crease, Robert P.

    2008-04-01

    There are few more dramatic illustrations of the vicissitudes of laboratory architecturethan the contrast between Building 20 at the Massachusetts Institute of Technology (MIT) and its replacement, the Ray and Maria Stata Center. Building 20 was built hurriedly in 1943 as temporary housing for MIT's famous Rad Lab, the site of wartime radar research, and it remained a productive laboratory space for over half a century. A decade ago it was demolished to make way for the Stata Center, an architecturally striking building designed by Frank Gehry to house MIT's computer science and artificial intelligence labs (above). But in 2004 - just two years after the Stata Center officially opened - the building was criticized for being unsuitable for research and became the subject of still ongoing lawsuits alleging design and construction failures.

  4. Platelet transfusion refractoriness attributable to HLA antibodies produced by donor-derived cells after allogeneic bone marrow transplantation from one HLA-antigen-mismatched mother.

    Science.gov (United States)

    Hatakeyama, Naoki; Hori, Tsukasa; Yamamoto, Masaki; Inazawa, Natsuko; Iesato, Kotoe; Miyazaki, Toru; Ikeda, Hisami; Tsutsumi, Hiroyuki; Suzuki, Nobuhiro

    2011-12-01

    PTR is a serious problem in patients being treated for hematologic disorders. Two patients with acute leukemia developed PTR after allogeneic BMT from one HLA-antigen-mismatched mother attributable to HLA antibodies, which could not be detected in their serum before BMT. HLA antibodies, whose specificity resembled that of each patient, were detected in each donor's serum. Each donor had probably been immunized during pregnancy by their partner's HLA antigens expressed by the fetus, consequently, transplanted donor-derived cells provoked HLA antibodies in each recipient early after BMT, and those HLA antibodies induced PTR. If the mothers are selected as donors for their children, they should be tested for the presence of HLA antibodies.

  5. HLA-KIR Interactions and Immunity to Viral Infections

    Directory of Open Access Journals (Sweden)

    Masoud Sabouri Ghannad

    2014-02-01

    Full Text Available Host genetic factors play a central role in determining the clinical phenotype of human diseases. Association between two polymorphic loci in human genome, human leukocyte antigen (HLA and killer cell immunoglobulin-like receptors (KIRs, and genetically complex infectious disease, particularly those of viral etiology, have been historically elusive. Hence, defining the influence of genetic diversity in HLA and KIRs on the outcome of viral infections has been extensively started in clinically well-defined cohort studies. HLA genes encode molecules which present antigenic peptide fragments to T lymphocytes as central players in adaptive immunity against infectious diseases. KIRs are expressed on natural killer cells which perform a crucial role in innate immunity to pathogen infection. The effector functions of NK cells such as direct killing of infected cells, cytokine production, and cross-talk with adaptive immune system depend on activation of NK cells, which is determined by their surface receptors. Among these receptors, KIRs, which interact with HLA class I, are mainly inhibitory and exhibit substantial genetic diversity. An extensive body of association studies indicates a role for HLA–KIRs interactions in infectious diseases, autoimmune disorders, cancer, transplantation, and reproduction. Various compound HLA-KIR genotypes appear to affect outcome of viral infections that suggests a role for HLA class I diversity in innate immunity as well as adaptive immune responses. The aim of this review is focusing on the impact of HLA and KIR alleles and different combinations of these alleles on clinical outcome of viral diseases to validate this proof-of-concept with respect to the therapeutic interventions.

  6. Association between HLA-C*04 and American cutaneous leishmaniasis in endemic region of southern Brazil.

    Science.gov (United States)

    Ribas-Silva, R C; Ribas, A D; Ferreira, E C; Silveira, T G V; Borelli, S D

    2015-11-23

    Leishmaniasis is a parasitic infectious disease with global repercussions. American cutaneous leishmaniasis (ACL) is endemic in southern Brazil and its pathogenesis varies according to parasite species, immune response, and host genetics. In terms of immunogenetics, many host genes, including HLA (human leukocyte antigen), could be involved in susceptibility to and protection against ACL. Accordingly, the aim of this study was to investigate the association between HLA class I genes (HLA-A, -B, and -C) and ACL in an endemic region of southern Brazil. The allele frequencies of 186 patients diagnosed with ACL and 278 healthy individuals were compared. HLA class I (HLA-A, -B, and -C) typing was carried out by PCR-SSO using Luminex technology. The results revealed an association between the HLA-C*04 allele and the patient study group, in which it appeared more frequently than in the control group [21.5 vs 13.49% (P = 0.0016 and Pc = 0.0258; OR = 1.7560; 95%CI = 1.2227-2.5240)], thereby suggesting an increased susceptibility to ACL. Additional allelic groups such as HLA-A*02, HLA-B*35, HLA-B*45, HLA-C*01, and HLA-C*15 were also implicated; however, further investigation is necessary to confirm their association with ACL. Therefore, the results obtained in this study demonstrate the involvement of HLA class I genes in the susceptibility or resistance to ACL, with significant association between HLA-C*04 and ACL susceptibility.

  7. A simplified method for screening siblings for HLA identity using short tandem repeat (STR) polymorphisms.

    Science.gov (United States)

    Schiller, Jennifer J; Hopp, Kathleen A; Pietz, Bradley C; Bick, David P; Lau, Eduardo C; Ellis, Thomas M

    2013-05-01

    Identifying an HLA-matched sibling donor for hematopoietic stem cell transplantation (HSCT) is time-consuming and expensive, and often limited by reimbursement caps imposed by insurance providers. To improve the effectiveness and efficiency of screening for HLA-matched siblings, we developed an assay for determining HLA identity using a panel of nine informative short tandem repeat (STR) loci located throughout the HLA complex. The STR panel was assessed for accuracy in identifying HLA-matched siblings in 88 family workups comprising a total of 132 related donor and recipient typing comparisons. All sibling pairs with identical STR alleles were also HLA identical. Of the 48 pairs mismatched at one or more STR alleles, all were genotypically HLA non-identical at one or more loci. The sensitivity and specificity of STR analysis for identifying HLA-matched siblings were 91% and 100%, respectively. Three false negatives occurred due to an STR mutation or possible HLA-DPB1/DQB1 recombination. Additionally, STR genotyping provided additional information allowing determination of the extent of HLA identity in families where HLA haplotype inheritance was ambiguous, due to extensive homozygosity or shared parental haplotypes. The HLA STR assay is a reliable and rapid test that can be used to inexpensively screen potential sibling donors for HLA identity.

  8. Creeping Federalization

    DEFF Research Database (Denmark)

    Sweeney, Richard J.

    2003-01-01

    for the better. Competition alsogenerates information about the effectiveness and costs of different commercial codes.Because any country's initial code is likely to be sub-optimal, and is likely to become lessoptimal over time, information on how to improve codes is valuable. Likely it is easier tolearn...... that make taxharmonization difficult to impose. Other types of harmonization have a less clear-cut costbenefitanalysis. A federal commercial code that is uniform across member states reducestransaction and information costs, compared to leaving important code issues to memberstates; further, many states may...

  9. KIR/HLA Interactions and Pathogen Immunity

    Directory of Open Access Journals (Sweden)

    Khaleel M. Jamil

    2011-01-01

    Full Text Available The innate immune system is the first line of defence in response to pathogen infection. Natural killer (NK cells perform a vital role in this response with the ability to directly kill infected cells, produce cytokines, and cross-talk with the adaptive immune system. These effector functions are dependent on activation of NK cells which is determined by surface receptor interactions with ligands on target cells. Of these receptors, the polymorphic killer immunoglobulin-like receptors (KIRs, which interact with MHC class 1 (also highly polymorphic, are largely inhibitory, and exhibit substantial genetic diversity. The result is a significant variation of NK cell repertoire between individuals and also between populations, with a multitude of possible KIR:HLA combinations. As each KIR:ligand interaction may have differential effects on NK cell activation and inhibition, this diversity has important potential influences on the host response to infections. Genetic studies have demonstrated associations between specific KIR:ligand combinations and the outcome of viral (and other infections, in particular hepatitis C and HIV infection. Detailed functional studies are not required to define the mechanisms underpinning these disease associations.

  10. Decoding the architectural theory

    Institute of Scientific and Technical Information of China (English)

    Gu Mengchao

    2008-01-01

    Starting from the illustration of the definition and concept of the architectural theory, the author established his unique understanding about the framework of the architectural theory and the innovation of the architectural theory underlined by Chinese characteristics.

  11. SUSTAINABLE ARCHITECTURE : WHAT ARCHITECTURE STUDENTS THINK

    OpenAIRE

    SATWIKO, PRASASTO

    2013-01-01

    Sustainable architecture has become a hot issue lately as the impacts of climate change become more intense. Architecture educations have responded by integrating knowledge of sustainable design in their curriculum. However, in the real life, new buildings keep coming with designs that completely ignore sustainable principles. This paper discusses the results of two national competitions on sustainable architecture targeted for architecture students (conducted in 2012 and 2013). The results a...

  12. Marshall Application Realignment System (MARS) Architecture

    Science.gov (United States)

    Belshe, Andrea; Sutton, Mandy

    2010-01-01

    The Marshall Application Realignment System (MARS) Architecture project was established to meet the certification requirements of the Department of Defense Architecture Framework (DoDAF) V2.0 Federal Enterprise Architecture Certification (FEAC) Institute program and to provide added value to the Marshall Space Flight Center (MSFC) Application Portfolio Management process. The MARS Architecture aims to: (1) address the NASA MSFC Chief Information Officer (CIO) strategic initiative to improve Application Portfolio Management (APM) by optimizing investments and improving portfolio performance, and (2) develop a decision-aiding capability by which applications registered within the MSFC application portfolio can be analyzed and considered for retirement or decommission. The MARS Architecture describes a to-be target capability that supports application portfolio analysis against scoring measures (based on value) and overall portfolio performance objectives (based on enterprise needs and policies). This scoring and decision-aiding capability supports the process by which MSFC application investments are realigned or retired from the application portfolio. The MARS Architecture is a multi-phase effort to: (1) conduct strategic architecture planning and knowledge development based on the DoDAF V2.0 six-step methodology, (2) describe one architecture through multiple viewpoints, (3) conduct portfolio analyses based on a defined operational concept, and (4) enable a new capability to support the MSFC enterprise IT management mission, vision, and goals. This report documents Phase 1 (Strategy and Design), which includes discovery, planning, and development of initial architecture viewpoints. Phase 2 will move forward the process of building the architecture, widening the scope to include application realignment (in addition to application retirement), and validating the underlying architecture logic before moving into Phase 3. The MARS Architecture key stakeholders are most

  13. The incidence of HLA-SD antigens in recessive retinitis pigmentosa.

    Science.gov (United States)

    Chen, M C; Marak, G E; Pilkerton, A R

    1978-01-01

    Eighteen patients with recessive retinitis pigmentosa were tissue typed for HLA-SD antigens. There was no evidence that a particular HLA-SD antigen was associated with autosomal recessive retinitis pigmentosa. PMID:638110

  14. Modeling Architectural Patterns Using Architectural Primitives

    NARCIS (Netherlands)

    Zdun, Uwe; Avgeriou, Paris

    2005-01-01

    Architectural patterns are a key point in architectural documentation. Regrettably, there is poor support for modeling architectural patterns, because the pattern elements are not directly matched by elements in modeling languages, and, at the same time, patterns support an inherent variability that

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    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...... 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...... compared to the sequence of HLA-6.0 (G*01011); one of these has not been reported before. We also found a deletion of the first base of codon 130 or the third of codon 129 in a heterozygous individual. This study, together with previous results, suggests that the polymorphism of exon 3 of the HLA-G gene...

  16. HLA-DR-positive cells in large plaque (atrophic) parapsoriasis.

    Science.gov (United States)

    McMillan, E M; Wasik, R; Everett, M A

    1981-10-01

    The development of a monoclonal antibody directed against HLA DR (Ia-like) antigens of B cells and monocytes but not against normal peripheral human T cells suggested that this antibody might be used as a marker of B cells and monocytes in tissue sections. The T cell nature of large plaque (atrophic) parapsoriasis has recently been demonstrated by the immunoperoxidase technic. Immunoperoxidase examination of serial sections of tissues from two cases of large plaque parapsoriasis with one T cell antiserum, two monoclonal T cell antibodies, and one monoclonal reagent directed against HLA DR indicated that T cells in the cutaneous infiltrates were also HLA DR-positive. Evidence is accumulating that HLA DR positivity may be expressed by activated T cells. The findings here therefore suggest that many of the T lymphoid cells in two cases of large plaque (atrophic) parapsoriasis examined were activated in nature, and that HLA DR may not be a specific marker for B cells and monocytes in certain pathologic conditions. Caution should therefore presently be exercised in attempting to use this marker for the specific identification of B cells and monocytes in pathologic specimens, without simultaneous testing for T cell markers.

  17. Molecular analysis of HLA-B in the Malaysian aborigines.

    Science.gov (United States)

    Hirayama, K; Zaidi, A S; Lokman Hakim, S; Kimura, A; Ong, K J; Kikuchi, M; Nasuruddin, H A; Kojima, S; Mak, J W

    1996-12-01

    We have examined 56 unrelated individuals from Malaysian aborigines for their DNA polymorphism of the HLA-B gene by sequence specific oligonucleotide probe (SSO) method. Using the SSO hybridization, we found that one specific DNA allele with a B*1513 like pattern of epitope combination (ECB1513) was dominant among the Melayu Asli (Af = 41.9%) and the Senoi (Af = 24%). To determine the nucleotide sequences of ECB1513, a DNA fragment spanning from the beginning of exon 1 to the middle of exon 4 of the HLA-B gene was amplified by polymerase chain reaction (PCR) from two ECB1513 positive individuals, and the PCR products were cloned and sequenced. This sequencing analysis confirmed that ECB1513 was identical to HLA-B*1513 in exon 1, 2, 3, and 4. Amino acid sequence of this major allele, HLA-B*1513, in the aborigines especially around the peptide binding groove (B and F pockets), was compared with that of African B*5301 that had been suggested to confer resistance to malaria infection in Africa. The amino acid residues composing of the F pocket were completely identical in B*1513 and B*5301. These observations suggest that a common environmental factor, the malaria infection, might have independently enhanced the selection of functional change in the polymorphic portion of HLA-B gene in Africa and in South-East Asia.

  18. Cancer treatment and the KIR-HLA system: an overview.

    Science.gov (United States)

    Leone, Patrizia; De Re, Valli; Vacca, Angelo; Dammacco, Franco; Racanelli, Vito

    2017-02-10

    Accumulating evidence indicates that the success of cancer therapy depends not only on a combination of adequate procedures (surgery, chemotherapy and radiotherapy) that aim to eliminate all tumor cells, but also on the functional state of the host immune system. HLA and KIR molecules, in particular, are critical to the interactions between tumor cells and both innate and adaptive immune cells such as NK cells and T cells. Different KIR-HLA gene combinations as well as different HLA expression levels on tumor cells associate with variable tumor prognosis and response to treatment. On the other hand, different therapies have different effects on HLA molecules and immune cell functions regulated by these molecules. Here, we provide an overview of the KIR-HLA system, a description of its alterations with clinical relevance in diverse tumor types, and an analysis of the consequences that conventional cancer therapies may have on it. We also discuss how this knowledge can be exploited to identify potential immunological biomarkers that can help to select patients for tailored therapy.

  19. HLA genes in Lamas Peruvian-Amazonian Amerindians.

    Science.gov (United States)

    Moscoso, Juan; Seclen, Segundo; Serrano-Vela, Juan I; Villena, A; Martinez-Laso, Jorge; Zamora, Jorge; Moreno, Almudena; Ira-Cachafeiro, Juan; Arnaiz-Villena, Antonio

    2006-04-01

    The Lamas Amerindians are the Chancas descents who established before 1532 a.d. (Spanish conquest) at Lamas City, Wayku quarter in a Peruvian-Amazonian province (San Martin). The Lamas HLA profile shows significant differences with other Amerindians HLA profile, i.e.: (a) a higher number of newly found haplotypes compared to other studied Amerindian populations, particularly HLA-A*02-B*48-DRB1*0403-DQB1*0302, A*02-B*48-DRB1*0804-DQB1*0402 and A*02-B*40-DRB1*0407-DQB1*0302; (b) a relative high frequency of HLA-DRB1*0901 (a high frequency southern Asian allele) and HLA-B*48 (a Na-Dene, Siberian and Eskimo allele); both alleles are also found frequently in Quechuas and Aymaras, but not in many other (particularly Meso American) Amerindians and (c) correspondence and neighbor-joining dendrogram analyses show that Lamas (Chancas) may have an origin close to Amazonian Indians that later reached the Andean altiplano.

  20. HLA in anthropology: the enigma of Easter Island.

    Science.gov (United States)

    Sanchez-Mazas, Alicia; Thorsby, Erik

    2013-01-01

    In this article, we first present four significant cases where human leukocyte antigen (HLA) studies have been useful for the reconstruction of human peopling history on the worldwide scale; i.e., the spread of modern humans from East Africa, the colonization of East Asia along two geographic routes, the co-evolution of genes and languages in Africa, and the peopling of Europe through a main northward migration. These examples show that natural selection did not erase the genetic signatures of our past migrations in the HLA genetic diversity patterns observed today. In the second part, we summarize our studies on Easter Island. Using genomic HLA typing, we could trace an introduction of HLA alleles of native American (Amerindian) origin to Easter Island before the Peruvian slave trades; i.e., before the 1860s, and provide suggestive evidence that they may have already been introduced in prehistoric time. Our results give further support to an initial Polynesian population of the island, but also reveal an early contribution by Amerindians. Together, our data illustrate the usefulness of typing for HLA alleles to complement genetic analyses in anthropological investigations.

  1. Lightweight enterprise architectures

    CERN Document Server

    Theuerkorn, Fenix

    2004-01-01

    STATE OF ARCHITECTUREArchitectural ChaosRelation of Technology and Architecture The Many Faces of Architecture The Scope of Enterprise Architecture The Need for Enterprise ArchitectureThe History of Architecture The Current Environment Standardization Barriers The Need for Lightweight Architecture in the EnterpriseThe Cost of TechnologyThe Benefits of Enterprise Architecture The Domains of Architecture The Gap between Business and ITWhere Does LEA Fit? LEA's FrameworkFrameworks, Methodologies, and Approaches The Framework of LEATypes of Methodologies Types of ApproachesActual System Environmen

  2. Software architecture 2

    CERN Document Server

    Oussalah, Mourad Chabanne

    2014-01-01

    Over the past 20 years, software architectures have significantly contributed to the development of complex and distributed systems. Nowadays, it is recognized that one of the critical problems in the design and development of any complex software system is its architecture, i.e. the organization of its architectural elements. Software Architecture presents the software architecture paradigms based on objects, components, services and models, as well as the various architectural techniques and methods, the analysis of architectural qualities, models of representation of architectural templa

  3. Software architecture 1

    CERN Document Server

    Oussalah , Mourad Chabane

    2014-01-01

    Over the past 20 years, software architectures have significantly contributed to the development of complex and distributed systems. Nowadays, it is recognized that one of the critical problems in the design and development of any complex software system is its architecture, i.e. the organization of its architectural elements. Software Architecture presents the software architecture paradigms based on objects, components, services and models, as well as the various architectural techniques and methods, the analysis of architectural qualities, models of representation of architectural template

  4. Principal Challenges Facing Electronic Records Management in Federal Agencies Today.

    Science.gov (United States)

    Patterson, Giovanna; Sprehe, J. Timothy

    2002-01-01

    Discusses electronic records management in the federal government. Highlights include managing electronic mail; information technology planning, systems design, and architecture; updating conventional records management; integrating electronic records management with other information technology systems; challenges of end-user training; business…

  5. High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis

    Directory of Open Access Journals (Sweden)

    Monaco Elisa Lo

    2011-10-01

    Full Text Available Abstract Background Human Leukocyte Antigen (HLA-E is a non-classical class I HLA molecule that can be stabilized by ligands donated by other classical (HLA-A, -B, -C and non-classical (HLA-G family members. HLA-E engages a variety of immune receptors expressed by cytotoxic T lymphocytes (CTLs, Natural killer (NK cells and NK-CTLs. In view of the opposing outcomes (activation or inhibition of the different HLA-E receptors, the preferred role (if any of HLA-E expressed in vivo on tumor cells remains to be established. Methods Taking advantage of MEM-E/02, a recently characterized antibody to denatured HLA-E molecules, HLA-E expression was assessed by immunohistochemistry on an archival collection (formalin-fixed paraffin-embedded of 149 colorectal primary carcinoma lesions paired with their morphologically normal mucosae. Lymphoid infiltrates were assessed for the expression of the HLA-E-specific, inhibitory, non-rearranging receptor NKG2A. Results High HLA-E expression did not significantly correlate with the expression of classical HLA-B and HLA-C molecules, but it did correlate with high expression of its preferential ligand donor HLA-A. In addition, it correlated with lymphoid cell infiltrates expressing the inhibitory NKG2A receptor, and was an independent predictor of good prognosis, particularly in a subset of patients whose tumors express HLA-A levels resembling those of their paired normal counterparts (HLA-A. Thus, combination phenotypes (HLA-Elo-int/HLA-AE and HLA-Ehi/HLA-AE of classical and non-classical class I HLA molecules mark two graded levels of good prognosis. Conclusions These results suggest that HLA-E favors activating immune responses to colorectal carcinoma. They also provide evidence in humans that tumor cells entertain extensive negotiation with the immune system until a compromise between recognition and escape is reached. It is implied that this process occurs stepwise, as predicted by the widely accepted

  6. Linkage of GLO with HLA and Bf. Effect of population and sex on recombination frequency.

    Science.gov (United States)

    Weitkamp, L R

    1976-05-01

    Further data on the linkage relationships of red cell glyoxalase I(GLO) with HLA and Bf are reported. The most likely order of loci is GLO: Bf: HLA-B: HLA-A. No sex difference in the frequency of recombination between GLO and HLA was noted, but recombination was more frequent for both males and females in the American black population than in the white population.

  7. HLA-G coding region and 3'untranslated region (3'UTR) in two Chinese Han populations.

    Science.gov (United States)

    Wang, Wen Yi; Tian, Wei; Liu, Xue Xiang; Li, Li Xin

    2016-08-01

    In this study, exons 2-4 and 3'untranslated region (3'UTR) of human leukocyte antigen (HLA)-G gene were investigated for 201 and 104 healthy unrelated Han samples recruited from Hunan Province, southern China and central Inner Mongolia Autonomous Region, northern China, respectively, using sequence-based typing and cloning methods. Totally 12 HLA-G alleles in the coding region, 9 variable sites in 3'UTR, 8 3'UTR haplotypes and 15 HLA-G extended haplotypes (EHs) incorporating the coding region and 3'UTR were observed. Very strong linkage disequilibrium (LD) was observed between HLA-A and HLA-G, and between HLA-G coding region and 3'UTR in each population (all global P=0.0000). Seven HLA-A-G haplotypes showed significant LD in both populations. Three HLA-G alleles in the coding region, 4 polymorphic sites in the 3'UTR, 3 3'UTR haplotypes and 4 HLA-G EHs differed significantly in their distributions between the 2 Chinese Han populations (all P≤0.0001). There was evidence for balancing selection acting on HLA-G 3'UTR positions +3010, +3142 and +3187 in the two populations. The NJ dendrograms demonstrated the existence of two basic HLA-G lineages and indicated that, HLA-G*01:01:01, the most common HLA-G allele, formed a separate lineage from other alleles. Our results shed new lights into HLA-G genetics among Chinese Han populations. The findings reported here are of importance for future studies related to post-transcriptional regulation of HLA-G allelic expression and the potential role of HLA-G in disease association in populations of Chinese ancestry.

  8. Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.

    Science.gov (United States)

    Guberina, Hana; Rebmann, Vera; Wagner, Bettina; da Silva Nardi, Fabiola; Dziallas, Phillip; Dolff, Sebastian; Bienholz, Anja; Wohlschlaeger, Jeremias; Bankfalvi, Agnes; Heinemann, Falko M; Witzke, Oliver; Zoet, Yvonne M; Claas, Frans H J; Horn, Peter A; Kribben, Andreas; Doxiadis, Ilias I N

    2017-03-01

    Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+ infiltrating cells correlated with HLA-E expression (pE-mediated immune activation. Moreover, HLA-E expression correlated with deterioration in renal allograft function (pE along with high numbers of mismatched HLA-class I leader peptides might represent additional targets for immune-activating responses.

  9. HLA-B17 and the HLA-A1, B17 haplotype in acute myelogenous leukemia.

    Science.gov (United States)

    Heise, E; Parrish, E; Cooper, R

    1979-08-01

    Seventy-nine Caucasians with acute myelogenous leukemia (AML) were genotyped to determine whether AML, the induction of remission or patient survival were associated with particular HLA phenotypes or haplotypes. HLA-B17 and B27 were increased in AML patients over 40 years of age. Combined analysis of four independent studies indicates that HLA-B17 is significantly but weakly associated with AML, relative risk = 1.48 (.01 less than P less than .025). The A1, B17 and Aw24, Bw35 haplotypes occurred more frequently in the AML group as compared to racial and geographic controls (uncorrected P = 0.0068 and 0.0098, respectively Fisher's Exact Test). Induction of remission occurred less frequently in patients with the B17 phenotype as compared to patients lacking this antigen (P = 0.047). Patient survival was associated with remission status (P = 0.002) but was not significantly associated with particular HLA phenotypes or haplotypes. These results indicate that a gene or genes in the HLA-B region of the major histocompatibility complex can influence susceptibility to AML and also the response to chemotherapy.

  10. Peptide Binding to HLA Class I Molecules: Homogenous, High-Throughput Screening, and Affinity Assays

    DEFF Research Database (Denmark)

    Harndahl, Mikkel; Justesen, Sune Frederik Lamdahl; Lamberth, Kasper;

    2009-01-01

    present a homogenous, proximity-based assay for detection of peptide binding to HLA class I molecules. It uses a conformation-dependent anti-HLA class I antibody, W6/32, as one tag and a biotinylated recombinant HLA class I molecule as the other tag, and a proximity-based signal is generated through...

  11. Narcolepsy-Associated HLA Class I Alleles Implicate Cell-Mediated Cytotoxicity

    NARCIS (Netherlands)

    Tafti, M.; Lammers, G.J.; Dauvilliers, Y.; Overeem, S.; Mayer, G.; Nowak, J.; Pfister, C.; Dubois, V.; Eliaou, J.F.; Eberhard, H.P.; Liblau, R.; Wierzbicka, A.; Geisler, P.; Bassetti, C.L.; Mathis, J.; Lecendreux, M.; Khatami, R.; Heinzer, R.; Haba-Rubio, J.; Feketeova, E.; Baumann, C.R.; Kutalik, Z.; Tiercy, J.M.

    2016-01-01

    STUDY OBJECTIVES: Narcolepsy with cataplexy is tightly associated with the HLA class II allele DQB1*06:02. Evidence indicates a complex contribution of HLA class II genes to narcolepsy susceptibility with a recent independent association with HLA-DPB1. The cause of narcolepsy is supposed be an autoi

  12. Unique features of HLA-mediated HIV evolution in a Mexican cohort: a comparative study

    Directory of Open Access Journals (Sweden)

    Brumme Zabrina L

    2009-08-01

    Full Text Available Abstract Background Mounting evidence indicates that HLA-mediated HIV evolution follows highly stereotypic pathways that result in HLA-associated footprints in HIV at the population level. However, it is not known whether characteristic HLA frequency distributions in different populations have resulted in additional unique footprints. Methods The phylogenetic dependency network model was applied to assess HLA-mediated evolution in datasets of HIV pol sequences from free plasma viruses and peripheral blood mononuclear cell (PBMC-integrated proviruses in an immunogenetically unique cohort of Mexican individuals. Our data were compared with data from the IHAC cohort, a large multi-center cohort of individuals from Canada, Australia and the USA. Results Forty three different HLA-HIV codon associations representing 30 HLA-HIV codon pairs were observed in the Mexican cohort (q Conclusion Our data support universal HLA-mediated HIV evolution at the population level, resulting in detectable HLA-associated footprints in the circulating virus. However, it also strongly suggests that unique genetic backgrounds in different HIV-infected populations may influence HIV evolution in a particular direction as particular HLA-HIV codon associations are determined by specific HLA frequency distributions. Our analysis also suggests a dynamic HLA-associated evolution in HIV with fewer HLA-HIV codon associations observed in the proviral compartment, which is likely enriched in early archived HIV sequences, compared to the plasma virus compartment. These results highlight the importance of comparative HIV evolutionary studies in immunologically different populations worldwide.

  13. HLA-G, immunocompetent cells and pregnancy outcome : a case of modulation

    NARCIS (Netherlands)

    Emmer, Peter Martin

    2003-01-01

    In this thesis we address the immunomodulatory role of human leukocyte antigen G (HLA-G). The placental trophoblast cells express HLA-G as membrane bound and soluble form (due to alternative splicing) at the fetomaternal interface. HLA-G putatively interacts with the maternal endometrial (decidual)

  14. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  15. System of Systems (SoS) Architecture Centric Acquisition

    Science.gov (United States)

    2016-06-07

    operation of the Software Engineering Institute, a federally funded research and development center. The Government of the United States has a royalty- free ...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Carnegie Mellon University , Software Engineering Institute,Pittsburgh,PA...Architecture Evaluation, System and Software Architecture Evaluation, Acquisition Planning Workshop, etc. – Capture comments and suggestions

  16. Data Centric Integration and Analysis of Information Technology Architectures

    Science.gov (United States)

    2007-09-01

    Systems Engineering Analysis Process and DoDAF Architecture Development Process............... 133 5. Federate Architecture Databases and Tools...constructed as a product of this thesis, this step is not applicable. 6. Source Data Collection The NPS Library was used to query the EBSCOhost , BOSUN...

  17. 41 CFR 102-77.20 - With whom should Federal agencies collaborate with when commissioning and selecting art for...

    Science.gov (United States)

    2010-07-01

    ... agencies collaborate with when commissioning and selecting art for Federal buildings? 102-77.20 Section 102... (Continued) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 77-ART-IN-ARCHITECTURE Art-in-Architecture § 102-77.20 With whom should Federal agencies collaborate with when commissioning and selecting art...

  18. El complejo mayor de histocompatibilidad humano: sistema HLA

    Directory of Open Access Journals (Sweden)

    Luis Fernando García

    1989-02-01

    Full Text Available

    El complejo mayor de histocompatibilidad humano, o sistema HLA, está localizado en el brazo corto del cromosoma 6. Sus genes codifican tres tipos de moléculas. Los antígenos clase I (HLA-A, B, C y E están formados por una cadena pesada unida no covalentemente a la β2-microglobulina y se expresan en la superficie de la mayoría de las células nucleadas del organismo. Estos antígenos actúan como elementos de restricción en la activación de los linfocitos T CD8+. Los antígenos clase II son dímeros compuestos por cadenas α y β y su distribución tisular está limitada sólo a algunos tipos de células. Estas moléculas actúan restringiendo la presentación de antígenos a los linfocitos CD4+. Los antígenos de clase III son proteínas plasmáticas del sistema del complemento. Los diferentes loci del sistema HLA son muy polimórficos y sus productos se heredan en bloques conocidos como haplotipos. Debido a que los diferentes grupos étnicos presentan variaciones en la frecuencia de ale ios y haplotipos, el HLA ha sido muy útil en los estudios antropogenéticos. Algunos antígenos HLA están presentes en pacientes con determinadas enfermedades con una frecuencia significativamente diferente a la encontrada en la población general. Estos hallazgos han sido de gran importancia para comprender la patogénesis y los mecanismos genéticos de resistencia o susceptibilidad a dichas enfermedades. En el campo de los transplantes de órganos, la compatibilidad HLA donante-receptor correlaciona con la sobrevida del injerto. El sistema HLA también parece tener mucha importancia en los fenómenos inmunológicos que ocurren durante el

  19. Architecture as Design Study.

    Science.gov (United States)

    Kauppinen, Heta

    1989-01-01

    Explores the use of analogies in architectural design, the importance of Gestalt theory and aesthetic cannons in understanding and being sensitive to architecture. Emphasizes the variation between public and professional appreciation of architecture. Notes that an understanding of architectural process enables students to improve the aesthetic…

  20. Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities

    DEFF Research Database (Denmark)

    Southwood, Scott; Solomon, Christopher; Hoof, Ilka;

    2011-01-01

    -binding characteristics with the HLA-A2 and HLA-A3 supertypes, respectively, the next most frequent human supertypes after HLA-B7. These data suggest that Chinese rhesus macaques may indeed be a more representative model of HLA gene diversity and function as compared to the species of Indian origin and therefore a better...

  1. Fiscal Federalism

    Directory of Open Access Journals (Sweden)

    Tatiana Mosteanu

    2007-06-01

    Full Text Available The central budget of a country collects only a fraction of the total fiscal revenues and executes only o fraction of the national public expenditures, the rest of the revenues and expenditures becoming the responsability of subnational governments. The economist Charles Tiebout developed a theoretical model which although makes an imperfect description of the reality, shows that people’s mobility is being influenced by tax rates and the amount of state/local expenditures. Thus, he suggests that the degree of responsibility that can be appointed to the local budgets should subscribe to the tax – benefits ratio, the extend of the positive externalities and the scale economies of public goods. Also, the issue of revenues distribution among communities is being raised, being identified three kinds of grants used by the public authorities: matching grants, block grants and conditional block grants. In the concept of fiscal federalism there can be found a limited analogy between national public finance theory and international public finance theory, with the international taxation as the pivotal element.

  2. Can You Hear Architecture

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2016-01-01

    Taking an off set in the understanding of architectural quality being based on multisensory architecture, the paper aims to discuss the current acoustic discourse in inclusive design and its implications to the integration of inclusive design in architectural discourse and practice as well...... design and architectural quality for people with a hearing disability and a newly conducted qualitative evaluation research in Denmark as well as architectural theories on multisensory aspects of architectural experiences, the paper uses examples of existing Nordic building cases to discuss the role...... of acoustics in both inclusive design and multisensory architecture....

  3. Genetically engineered blood pharming: generation of HLA-universal platelets derived from CD34+ progenitor cells.

    Science.gov (United States)

    Figueiredo, Constança; Blaszczyk, Rainer

    2014-01-01

    Blood pharming is a recently designed concept to enable in vitro production of blood cells that are safe, effective and readily available. This approach represents an alternative to blood donation and may contribute to overcome the shortage of blood products. However, the high variability of the human leukocyte antigen (HLA) loci remains a major hurdle to the application of off-the-shelf blood products. Refractoriness to platelet (PLT) transfusion caused by alloimmunization against HLA class I antigens constitutes a relevant clinical problem. Thus, it would be desirable to generate PLT units devoid of HLA antigens. To reduce the immunogenicity of cell-based therapeutics, we have permanently reduced HLA class I expression using an RNA interference strategy. Furthermore, we demonstrated that the generation of HLA class I-silenced (HLA-universal) PLTs from CD34+ progenitor cells using an shRNA targeting β2-microglobulin transcripts is feasible. CD34+ progenitor cells derived from G-CSF mobilised donors were transduced with a lentiviral vector encoding for the β2-microglobulin-specific shRNA and differentiated into PLTs using a liquid culture system. The functionality of HLA-silenced PLTs and their ability to escape HLA antibody-mediated cytotoxicity were evaluated in vitro and in vivo. Platelet activation in response to ADP and thrombin were assessed in vitro. The immune-evasion capability of HLA-universal megakaryocytes (MKs) and PLTs was tested in lymphocytotoxicity assays using anti-HLA antibodies. To assess the functionality of HLA-universal PLTs in vivo, HLA-silenced MKs were infused into NOD/SCID/IL-2Rγc(-/-) mice with or without anti-HLA antibodies. PLT generation was evaluated by flow cytometry using anti-CD42a and CD61 antibodies. HLA-universal PLTs demonstrated to be functionally similar to blood-derived PLTs. Lymphocytotoxicity assays showed that HLA-silencing efficiently protects MKs against HLA antibody-mediated complement-dependent cytotoxicity. 80

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

    DEFF Research Database (Denmark)

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

    1987-01-01

    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...... preliminary findings with a limited number of enzymes, the RFLP appears to be quite extensive both with the DP beta (14 different DNA markers defined by individual fragments or clusters thereof) and the DP alpha (8 markers) probes, especially when enzymes recognizing only four base pairs were used. A few...

  5. Study of HLA Class I gene in Indian schizophrenic patients of Siliguri, West Bengal.

    Science.gov (United States)

    Singh, Bisu; Bera, Nirmal Kumar; De, Santanu; Nayak, Chittaranjan; Chaudhuri, Tapas Kumar

    2011-09-30

    The authors studied the prevalence of the human leukocyte antigen (HLA) Class I gene in 136 (85 male, 51 female) India-born schizophrenia patients residing in and around the Siliguri subdivision of West Bengal by the PCR-SSP method. The control group consisted of 150 age- and sex-matched healthy individuals from the same ethnic group as the patients. Increased frequency of HLA A*03 as well as decreased frequencies of HLA A*31 and HLA B*51, was noted. The study suggests the possible existence of a susceptibility locus for schizophrenia within the HLA region.

  6. Impact on parents of HLA-DQ2/DQ8 genotyping in healthy children from coeliac families

    NARCIS (Netherlands)

    Wessels, Margreet M. S.; Vriezinga, Sabine L.; Koletzko, Sybille; Werkstetter, Katharina; Castillejo-De Villasante, Gemma; Shamir, Raanan; Hartman, Corina; Putter, Hein; van der Pal, Sylvia M.; Wijmenga, Cisca; Bravi, Enzo; Mearin, M. Luisa

    2015-01-01

    Due to the association of coeliac disease and HLA-specificities DQ2 and DQ8, HLA-typing can be used for risk determination of the disease. This study was designed to evaluate the knowledge of parents from coeliac families regarding HLA-typing and the impact of HLA-typing on the perception of the hea

  7. Evaluation of a competitive enzyme-linked immunosorbent assay for measurements of soluble HLA-G protein

    DEFF Research Database (Denmark)

    Rasmussen, M; Dahl, M; Buus, S;

    2014-01-01

    . We report a novel method, a competitive immunoassay, for measuring HLA-G5/sHLA-G1 in biological fluids. The sHLA-G immunoassay is based upon a competitive enzyme-linked immunosorbent assay (ELISA) principle. It includes a recombinant sHLA-G1 protein in complex with β2-microglobulin and a peptide...

  8. Insights into alpha-hemolysin (Hla) evolution and expression among Staphylococcus aureus clones with hospital and community origin

    DEFF Research Database (Denmark)

    Tavares, Ana; Nielsen, Jesper B; Boye, Kit;

    2014-01-01

    in the RNAIII binding site were not associated to hla expression. Although expression rates of hla were in general strain-specific, we observed CA clones showed significantly higher hla expression (p = 0.003) when compared with HA clones. CONCLUSION: We propose that the hla gene has evolved together...

  9. The Next Generation of HLA Image Products

    Science.gov (United States)

    Gaffney, N. I.; Casertano, S.; Ferguson, B.

    2012-09-01

    We present the re-engineered pipeline based on existing and improved algorithms with the aim of improving processing quality, cross-instrument portability, data flow management, and software maintenance. The Hubble Legacy Archive (HLA) is a project to add value to the Hubble Space Telescope data archive by producing and delivering science-ready drizzled data products and source lists derived from these products. Initially, ACS, NICMOS, and WFCP2 data were combined using instrument-specific pipelines based on scripts developed to process the ACS GOODS data and a separate set of scripts to generate source extractor and DAOPhot source lists. The new pipeline, initially designed for WFC3 data, isolates instrument-specific processing and is easily extendable to other instruments and to generating wide-area mosaics. Significant improvements have been made in image combination using improved alignment, source detection, and background equalization routines. It integrates improved alignment procedures, better noise model, and source list generation within a single code base. Wherever practical, PyRAF based routines have been replaced with non-IRAF based python libraries (e.g. NumPy and PyFITS). The data formats have been modified to handle better and more consistent propagation of information from individual exposures to the combined products. A new exposure layer stores the effective exposure time for each pixel in the sky which is key in properly interpreting combined images from diverse data that were not initially planned to be mosaiced. We worked to improve the validity of the metadata within our FITS headers for these products relative to standard IRAF/PyRAF processing. Any keywords that pertain to individual exposures have been removed from the primary and extension headers and placed in a table extension for more direct and efficient perusal. This mechanism also allows for more detailed information on the processing of individual images to be stored and propagated

  10. Association of the HLA-DQA1 and HLA-DQB1 Alleles in Type 2 Diabetes Mellitus and Diabetic Nephropathy in the Han Ethnicity of China

    Directory of Open Access Journals (Sweden)

    Ze-Jun Ma

    2013-01-01

    Full Text Available HLA gene system is one of the most polymorphic regions of the human genome. The association of HLA class II genes in T1DM pathogenesis has been reported for several ethnicities. Associations of HLA class II genes with T2DM have revealed inconsistent results. Moreover, correlations between DN and HLA alleles remain unclear. We carried out DNA typing chip by specific medium resolution typing probes in 310 T2DM subjects (including 210 patients with DN and 100 patients without DN in addition to 100 healthy controls. Differences were found between patients with T2DM and the control group in the frequencies of the HLA-DQA1*0301 (15.5% versus 8.0%, P<0.01 and the HLA-DQA1*0501 alleles (16.6% versus 8.5%, P<0.01. Differences were found between patients with DN and without DN in the frequencies of the HLA-DQA1*0302 (6.9% versus 13.5%, P<0.01 and HLA-DQB1*0501 alleles (5.8% versus 14.5%, P<0.01. Diabetes duration and systolic blood pressure were independent risk factors associated with DN (OR=2.277 and 1.366, resp., P<0.05, whereas the HLA-DQB1*0501 llele had a protective effect on DN (OR=0.53, P<0.05. These data suggest the HLA-DQA1*0301 and HLA-DQA1*0501 alleles are markers of susceptibility for T2DM, and the HLA-DQB1*0501 allele is associated with a protective effect on DN in Han ethnicity of China.

  11. HLA-E: strong association with beta2-microglobulin and surface expression in the absence of HLA class I signal sequence-derived peptides.

    Science.gov (United States)

    Lo Monaco, Elisa; Sibilio, Leonardo; Melucci, Elisa; Tremante, Elisa; Suchànek, Miloslav; Horejsi, Vaclav; Martayan, Aline; Giacomini, Patrizio

    2008-10-15

    The nonclassical class I HLA-E molecule folds in the presence of peptide ligands donated by the signal sequences of permissive class I HLA alleles, with the aid of TAP and tapasin. To identify HLA-E-specific Abs, four monoclonals of the previously described MEM series were screened by isoelectric focusing (IEF) blot and immunoprecipitation/IEF on >30 single-allele class I transfectants and HLA-homozygous B lymphoid cells coexpressing HLA-E and HLA-A, -B, -C, -F, or -G. Despite their HLA-E-restricted reactivity patterns (MEM-E/02 in IEF blot; MEM-E/07 and MEM-E/08 in immunoprecipitation), all of the MEM Abs unexpectedly reacted with beta(2)-microglobulin (beta(2)m)-free and denatured (but not beta(2)m-associated and folded) HLA-E H chains. Remarkably, other HLA-E-restricted Abs were also reactive with free H chains. Immunodepletion, in vitro assembly, flow cytometry, and three distinct surface-labeling methods, including a modified (conformation-independent) biotin-labeling assay, revealed the coexistence of HLA-E conformers with unusual and drastically antithetic features. MEM-reactive conformers were thermally unstable and poorly surface expressed, as expected, whereas beta(2)m-associated conformers were either unstable and weakly reactive with the prototypic conformational Ab W6/32, or exceptionally stable and strongly reactive with Abs to beta(2)m even in cells lacking permissive alleles (721.221), TAP (T2), or tapasin (721.220). Noncanonical, immature (endoglycosidase H-sensitive) HLA-E glycoforms were surface expressed in these cells, whereas mature glycoforms were exclusively expressed (and at much lower levels) in cells carrying permissive alleles. Thus, HLA-E is a good, and not a poor, beta(2)m assembler, and TAP/tapasin-assisted ligand donation is only one, and possibly not even the major, pathway leading to its stabilization and surface expression.

  12. REPORT OF HLA DISTRIBUTION IN 2315 VOLUNTEER DONORS OF CHINESE BONE MARROW BANK FROM NORTHWEST CHINA

    Institute of Scientific and Technical Information of China (English)

    Jin Tianbo; Gao Ya; Zhang Hongbo; Zhao Junhai; Lai Jianghua; Lai Shuping; Li Shengbin

    2005-01-01

    Objective To report the HLA data of volunteer donors of Chinese bank from Northwest China and characterize the distribution of HLA genes in Northwest China. Methods HLA-A, B antigens of 2315 volunteer donors were examined by the method of microlymphocytetoxicity (MLT) test .The antigen frequencies(AF) were assessed by directly counting; and based on that gene frequencies(GF) were calculated. HLA data from other population were collected and distribution characteristics were compared. With the raw data, Hardy-Weinberg equilibrium, statistical parameters of forensic medicine interest for HLA were computed. Results A total of 18 specific antigens were detected in HLA-A and the most frequent antigen was A2 . AF and GF were 0.5136 and 0.3026, respectively. A total of 42 specific antigens were detected in HLA-B and the most frequent antigen was A13. Its AF and GF were 0.1978 and 0.1044, respectively. The heterozygosity(H), polymorphism information content(PIC), discrimination power(DP) and probability of paternity exclusion (PPE) of HLA-A were 0.8215, 0.8212, 0.9356 and 0.7798 accordingly; while H,PIC, DP and PPE of HLA-B were 0.9322, 0.9322, 0.9878 and 0.9528. Conclusion The polymorphism of HLA-A,B genes is characteristic in Chinese. In this research, the genetic trait of HLA in 2315 volunteers is consistent with Northern Han population.

  13. Genetic HLA Study of Kurds in Iraq, Iran and Tbilisi (Caucasus, Georgia): Relatedness and Medical Implications

    Science.gov (United States)

    Muñiz, Ester; Campos, Cristina; Alonso-Rubio, Javier; Gomez-Casado, Eduardo; Salih, Shadallah Fareq; Martin-Villa, Manuel; Al-Qadi, Rawand

    2017-01-01

    Kurds from Iraq (Dohuk and Erbil Area, North Iraq) have been analyzed for HLA genes. Their HLA genetic profile has been compared with that of other Kurd groups from Iran and Tbilisi (Georgia, Caucasus) and also Worldwide populations. A total of 7,746 HLA chromosomes have been used. Genetic distances, NJ dendrograms and correspondence analyses have been carried out. Haplotype HLA-B*52—DRB1*15 is present in all three analyzed Kurd populations. HLA-A*02-B*51-DRB1*11 is present in Iraq and Georgia Kurds. Haplotypes common to Iran and Iraq Kurds are HLA DRB1*11—DQB1*03, HLA DRB1*03—DQB1*02 and others in a lower frequency. Our HLA study conclusions are that Kurds most probably belong to an ancient Mediterranean / Middle East / Caucasian genetic substratum and that present results and those previously obtained by us in Kurds may be useful for Medicine in future Kurd transplantation programs, HLA Epidemiology (HLA linked diseases) and Pharmacogenomics (HLA-associated drug side effects) and also for Anthropology. It is discussed that one of the most ancient Kurd ancestor groups is in Hurrians (2,000 years BC). PMID:28114347

  14. Interaction of the LILRB1 inhibitory receptor with HLA class Ia dimers.

    Science.gov (United States)

    Baía, Diogo; Pou, Jordi; Jones, Des; Mandelboim, Ofer; Trowsdale, John; Muntasell, Aura; López-Botet, Miguel

    2016-07-01

    Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) has been reported to interact with a wide spectrum of HLA class I (HLA-I) molecules, albeit with different affinities determined by allelic polymorphisms and conformational features. HLA-G dimerization and the presence of intracellular Cys residues in HLA-B7 have been shown to be critical for their recognition by LILRB1. We hypothesized that dimerization of classical HLA class Ia molecules, previously detected in exosomes, might enhance their interaction with LILRB1. A soluble LILRB1-Fc fusion protein and a sensitive cellular reporter system expressing a LILRB1-ζ chimera were employed to assess receptor interaction with different HLA class Ia molecules transfected in the human lymphoblastoid 721.221 cell line. Under these conditions, intracellular Cys residues and HLA-I dimerization appeared associated with increased LILRB1 recognition. On the other hand, a marginal interaction of LILRB1 with primary monocytic cells, irrespective of their high HLA-I expression, was enhanced by type I interferon (IFN). This effect appeared disproportionate to the cytokine-induced increase of surface HLA-I expression and was accompanied by detection of HLA class Ia dimers. Altogether, the results support that a regulated assembly of these noncanonical HLA-I conformers during the immune response may enhance the avidity of their interaction with LILRB1.

  15. A PRIMARY STUDY OF THE CORRELASTIONS BETWEEN HUMAN LEUKOCYTE ANTIGEN (HLA)AND OSTEOSARCOMA

    Institute of Scientific and Technical Information of China (English)

    Zhang Weibin; Luo Jiong; Shen Caiwei; Cai Tidong; Yang Yuqin; Yao Fangjuan; Fan LiAn

    1998-01-01

    Objective: To study the correlations between human leukocyte antigen (HLA) and osteosarcoma in Chinese Han nationality. Methods: The frequencies of HLA-A, B,DR, DQ locus antigens were tested in a group of 25osteosarcoma patients in comparison with 250 healthy controls by using complement-dependent microlymphocytotoxity technique. Both of them are Chinese Han nationality. The results were compared statistically.Results: The frequency of HLA-B35 was 0.400 in patient group, and comparing with 0.048 in controls. The relative risk of suffering from osteosarcoma in persons carrying HLA-B35 was 13.220 times as high as that in those without this antigen (P<0.01). Patients with HLA-B13 had increased in the relative risk of poor prognosis with 12.048 fold comparing with those without this antigen (P<0.05). A tendency of the worst prognosis was presented in the patients who carry both HLA-B13 and HLA-B35.For those patients with HLA-B40, the relative safety was 7.057 times higher than the negative persons (P<0.05).Conclusion: HLA-B35 is in close linkage to osteosarcoma susceptibility genes in Chinese Han nationality. HLA-B13and HLA-B40 may be associated to the malignant and resistant genes of osteosarcoma respectively.

  16. Systems Architecture for a Nationwide Healthcare System.

    Science.gov (United States)

    Abin, Jorge; Nemeth, Horacio; Friedmann, Ignacio

    2015-01-01

    From a national level to give Internet technology support, the Nationwide Integrated Healthcare System in Uruguay requires a model of Information Systems Architecture. This system has multiple healthcare providers (public and private), and a strong component of supplementary services. Thus, the data processing system should have an architecture that considers this fact, while integrating the central services provided by the Ministry of Public Health. The national electronic health record, as well as other related data processing systems, should be based on this architecture. The architecture model described here conceptualizes a federated framework of electronic health record systems, according to the IHE affinity model, HL7 standards, local standards on interoperability and security, as well as technical advice provided by AGESIC. It is the outcome of the research done by AGESIC and Systems Integration Laboratory (LINS) on the development and use of the e-Government Platform since 2008, as well as the research done by the team Salud.uy since 2013.

  17. HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions.

    Science.gov (United States)

    Magaret, A; Dong, L; John, M; Mallal, S A; James, I; Warren, T; Gaudieri, S; Koelle, D M; Wald, A

    2016-12-01

    Variation at HLA and KIR loci is associated with the severity of viral infections. To assess associations of genital HSV-2 infection with human HLA and KIR genetic loci, we measured the frequencies of genital herpes simplex virus (HSV) DNA detection and of genital lesions in HSV-2 seropositive persons. We followed 267 HSV-2 seropositive persons who collected daily genital swabs and recorded lesions for ⩾30 days. All persons were laboratory-documented as HIV-seronegative, and all were Caucasian by self-report. HSV detection rate and lesion frequency were compared by genotype using Poisson regression. Overall, HSV was detected on 19.1% of days and lesions on 11.6% of days. The presence of HLA-A*01 was directly associated with HSV detection frequency, whereas the presence of HLA-C*12 was inversely associated with HSV detection frequency. The presence of HLA-A*01 was directly associated with lesion rate, while HLA-A*26, -C*01 and -DQB1*0106 were associated with decreased lesions. We observed an interaction between the absence of both 2DS4del and HLA-Bw4 and higher lesion rate. Heterozygosity of HLA was also associated with reduced lesion frequency. Immune control of genital HSV infection relies on multiple interacting immunogenetic elements, including epistatic interactions between HLA and KIR.

  18. Identification of immunogenic HLA-B7 "Achilles' heel" epitopes within highly conserved regions of HIV

    DEFF Research Database (Denmark)

    De Groot, Anne S; Rivera, Daniel S; McMurry, Julie A;

    2008-01-01

    previously described as restricted by B7. The HLA-B7 restricted epitopes discovered using this in silico screening approach are highly conserved across strains and clades of HIV as well as conserved in the HIV genome over the 20 years since HIV-1 isolates were first sequenced. This study demonstrates......Genetic polymorphisms in class I human leukocyte antigen molecules (HLA) have been shown to determine susceptibility to HIV infection as well as the rate of progression to AIDS. In particular, the HLA-B7 supertype has been shown to be associated with high viral loads and rapid progression...... to disease. Using a multiplatform in silico/in vitro approach, we have prospectively identified 45 highly conserved, putative HLA-B7 restricted HIV CTL epitopes and evaluated them in HLA binding and ELISpot assays. All 45 epitopes (100%) bound to HLA-B7 in cell-based HLA binding assays: 28 (62%) bound...

  19. HLA B27 as Predisposition Factor to Suffer Age Related Macular Degeneration

    Science.gov (United States)

    Becerril, Enrique Villegas; Fernández, Rafael González; Torres, Luis Pérula; Lacomba, Manuel Santos; Galera, José María Gallardo

    2009-01-01

    To research whether specific alleles HLA class I (HLA-A and HLA-B) and class II (HLA-DR) are risk factors for the development of exudative type of Age Related Macular Degeneration (ARMD), HLA antigens are expressed both in normal and affected eyes with ARMD. We designed a prospective case-controlled study. We recruited 75 patients with choroidal neovascularization predominantly classic or occult, secondary to ARMD, and treated with photodynamic therapy. Two hundred and fifty patients over 55 years old, without ophthalmologic pathology who went to hospital for an analytical routine check were used as control. The analysis of the data shows a significant difference between two groups. Allele HLA-B27 correlated positively with ARMD (p < 0.0113). However, we didn't find alleles negatively associated. Thus HLA-B27 is an allele predisposed to suffer ARMD. PMID:19728932

  20. High Level Architecture Distributed Space System Simulation for Simulation Interoperability Standards Organization Simulation Smackdown

    Science.gov (United States)

    Li, Zuqun

    2011-01-01

    Modeling and Simulation plays a very important role in mission design. It not only reduces design cost, but also prepares astronauts for their mission tasks. The SISO Smackdown is a simulation event that facilitates modeling and simulation in academia. The scenario of this year s Smackdown was to simulate a lunar base supply mission. The mission objective was to transfer Earth supply cargo to a lunar base supply depot and retrieve He-3 to take back to Earth. Federates for this scenario include the environment federate, Earth-Moon transfer vehicle, lunar shuttle, lunar rover, supply depot, mobile ISRU plant, exploratory hopper, and communication satellite. These federates were built by teams from all around the world, including teams from MIT, JSC, University of Alabama in Huntsville, University of Bordeaux from France, and University of Genoa from Italy. This paper focuses on the lunar shuttle federate, which was programmed by the USRP intern team from NASA JSC. The shuttle was responsible for provide transportation between lunar orbit and the lunar surface. The lunar shuttle federate was built using the NASA standard simulation package called Trick, and it was extended with HLA functions using TrickHLA. HLA functions of the lunar shuttle federate include sending and receiving interaction, publishing and subscribing attributes, and packing and unpacking fixed record data. The dynamics model of the lunar shuttle was modeled with three degrees of freedom, and the state propagation was obeying the law of two body dynamics. The descending trajectory of the lunar shuttle was designed by first defining a unique descending orbit in 2D space, and then defining a unique orbit in 3D space with the assumption of a non-rotating moon. Finally this assumption was taken away to define the initial position of the lunar shuttle so that it will start descending a second after it joins the execution. VPN software from SonicWall was used to connect federates with RTI during testing

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    -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...

  2. Describing the Peptide Binding Specificity of HLA-C

    DEFF Research Database (Denmark)

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

    . We find preference for hydrophobic residues at the peptide C-terminus for all HLA-C molecules. Most molecules were found to have an additional strong anchor at P2 or P3, with auxiliary anchor observed at P1, P2, P3, and P7. The binding affinity is measured for peptides fitting the specificity matrix...

  3. Extensive HLA class Ⅱ studies in Chinese narcoleptic patients.

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: Narcolepsy is a debilitating, lifelong sleep disorder. Its familial occurrence suggests that genetic factors may be of importance in the etiology. Narcolepsy is a very rare disease among Chinese, thus it was of interest to study the association of narcolepsy with the HLA system in Chinese narcoleptic patients.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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 ...

  5. HLA-DP antigens in HIV-infected individuals

    DEFF Research Database (Denmark)

    Ødum, Niels; Georgsen, J; Fugger, L;

    1991-01-01

    We studied the distribution of HLA-DP antigens in 74 HIV-infected Danish homosexual men and 188 ethnically matched healthy individuals, using the primed lymphocyte typing (PLT) technique. Forty of the patients developed AIDS within 3 years after diagnosis, whereas the remaining 34 were healthy...

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

    DEFF Research Database (Denmark)

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

    1986-01-01

    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...

  7. HLA antigens in Tlingit Indians with rheumatoid arthritis.

    Science.gov (United States)

    Nelson, J L; Boyer, G; Templin, D; Lanier, A; Barrington, R; Nisperos, B; Smith, A; Mickelson, E; Hansen, J A

    1992-08-01

    HLA-DR4 has been described in association with rheumatoid arthritis (RA) in multiple populations. We have studied HLA antigens in Alaskan Tlingit Indians. HLA-DR4 was decreased in the RA group (n = 32) compared with controls (n = 62) (6% vs 21% p = 0.07). The predominant DR4 allele observed was DRB1*0403 (Dw13.1). The most striking observation in these studies was a marked predominance of the DRB1*1402 allele encoding Dw16 (DRw14). This allele was present in 91% of RA cases, but was also highly prevalent in controls (80%, OR = 2.4 p = 0.20). DRB1*1402 only was observed in 47% of cases and 31% of controls. The DRB3*0101 (DRw52), and the DQA*0501 and DQB*0301 alleles encoding a subset of DQw3 were associated with DRB1*1402 in cases and in controls. HLA-Bw62 was increased in RA cases (28%) compared with controls (8%) (OR = 4.5, p = 0.01, corrected p = ns).

  8. Modulation of HLA Expression in Human Cytomegalovirus Immune Evasion

    Institute of Scientific and Technical Information of China (English)

    Aifen Lin; Huihui Xu; Weihua Yan

    2007-01-01

    Human cytomegalovirus (hCMV) has evolved multiple mechanisms to escape the host immune recognition and innate or adaptive immune responses. Among them, hCMV has developed strategies to modulate the expression and/or function of human leukocyte antigens (HLAs), including by encoding series of infection stage-dependent hCMV proteins to detain and destroy the expression of HLA molecules on the surface of infected cells. This disturbs the antigen presentation and processing, by encoding MHC class Ⅰ homologues or selective up-regulation of particular HLA class Ⅰ molecules binding to NK cell inhibitory receptors, and by encoding specific ligand antagonists to interfere with NK cell activating receptors. Here we discussed the molecular mechanisms utilized by the hCMV to alter the formation, transportation and expression of HLA antigens on the infected cell surface. The knowledge about hCMV modulating HLA expression could benefit us to further understand the pathogenesis of viral diseases and may eventually develop novel effective immunotherapies to counteract viral infections and viral associated diseases.

  9. The Perception of Human Resources Enterprise Architecture within the Department of Defense

    Science.gov (United States)

    Delaquis, Richard Serge

    2012-01-01

    The Clinger Cohen Act of 1996 requires that all major Federal Government Information Technology (IT) systems prepare an Enterprise Architecture prior to IT acquisitions. Enterprise Architecture, like house blueprints, represents the system build, capabilities, processes, and data across the enterprise of IT systems. Enterprise Architecture is used…

  10. The Protective Role of HLA-DRB113 in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Andreia Bettencourt

    2015-01-01

    Full Text Available Autoimmune diseases (AIDs are characterized by a multifactorial aetiology and a complex genetic background, with the MHC region playing a major role. We genotyped for HLA-DRB1 locus 1228 patients with AIDs-213 with Systemic Lupus Erythematosus (SLE, 166 with Psoriasis or Psoriatic Arthritis (Ps + PsA, 153 with Rheumatoid Arthritis (RA, 67 with Systemic Sclerosis (SSc, 536 with Multiple Sclerosis (MS, and 93 with Myasthenia Gravis (MG and 282 unrelated controls. We confirmed previously established associations of HLA-DRB115 (OR = 2.17 and HLA-DRB103 (OR = 1.81 alleles with MS, HLA-DRB103 with SLE (OR = 2.49, HLA-DRB101 (OR = 1.79 and HLA-DRB104 (OR = 2.81 with RA, HLA-DRB107 with Ps + PsA (OR = 1.79, HLA-DRB101 (OR = 2.28 and HLA-DRB108 (OR = 3.01 with SSc, and HLA-DRB103 with MG (OR = 2.98. We further observed a consistent negative association of HLA-DRB113 allele with SLE, Ps + PsA, RA, and SSc (18.3%, 19.3%, 16.3%, and 11.9%, resp., versus 29.8% in controls. HLA-DRB113 frequency in the AIDs group was 20.0% (OR = 0.58. Although different alleles were associated with particular AIDs, the same allele, HLA-DRB113, was underrepresented in all of the six diseases analysed. This observation suggests that this allele may confer protection for AIDs, particularly for systemic and rheumatic disease. The protective effect of HLA-DRB113 could be explained by a more proficient antigen presentation by these molecules, favouring efficient clonal deletion during thymic selection.

  11. HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.

    Directory of Open Access Journals (Sweden)

    Stéphane Buhler

    Full Text Available Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model. However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used

  12. Enhancing Science with the Hubble Legacy Archive (HLA)

    Science.gov (United States)

    Whitmore, Bradley C.

    2009-01-01

    The Space Telescope Science Institute (STScI), in collaboration with the Space Telescope - European Coordinating Facility (ST-ECF) and the Canadian Astronomy Data Centre (CADC), is developing an enhanced archive for the Hubble Space Telescope (HST). The goal of the HLA is to optimize the science coming from the Hubble Space Telescope by providing better browsing capabilities and easy access to both standard and enhanced Hubble products. Some of the primary enhancements include: 1) providing "real time" access to the data (i.e., having the data online), 2) adding a footprint service to make it easier to browse and download images, 3) providing more extensive "composite images" (e.g., stacked images, mosaics, color images etc.), 4) improving absolute astrometry (i.e., from 1-2" to 0.3"), 5) extracting spectra from slitless spectroscopic data (from ST-ECF), and 6) developing source lists for applicable datasets. The HLA entered its Data Release 2 (DR2) phase of operation in September, 2008. The highlight of DR2 is the inclusion of enhanced WFPC2 images produced by CADC. This more than triples the number of enhanced HLA images. In addition, the number of ACS source lists has more than tripled, with 70 % of the ACS images having both DAOphot and SExtractor lists. The HLA currently contains enhanced products for ACS, WFPC2, and NICMOS GRISM extractions (from ST-ECF), and provides access to standard products for NICMOS, STIS, FOS, and GHRS via MAST. Demonstrations will be provided at the Space Telescope Science Institute booth during the conference and people will have the opportunity to use the system interactively. The url is http://hla.stsci.edu .

  13. HLA class I expression in primary hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian Huang; Mei-Ying Cai; Da-Peng Wei

    2002-01-01

    AIM: To investigate whether CTL vaccine therapy issuitable for primary hepatocellular carcinoma (HCC)from the viewpoint of HLA class I antigens expression.METHODS: The immunocytochemistry, image analysis,flow cytometry, and labeled streptavidin biotin (LSAB)method of immunohistochemistry were appliedrespectively to study 4 HCC cell lines (e.g. Alexander,HepG2, SMMC-7721, and QGY-7703) cultured in vitroand 6 frozen tissue specimens of HCC. RESULTS: The positive control cell line Raji had verystrong positive staining. Most mitotic and nonmitoticcells of the 4 HCC cell lines had various intensity ofHLA class Ⅰ antigens expression. The negative controlcell K562 and the control slides of all the cell lines hadno positive staining. In the 6 HCC specimensimmunohistochemically studied, histological normalhepatocytes had no or very weak positive staining andthe liver sinus had very strong positive staining. MostHCC cells in the sections from the 6 HCC specimenshad strong positive HLA class Ⅰ antigens staining. Thepositive staining was located in the cytoplasm, theperinuclear area, and at the cell membrane of the livercancer cells. Flow cytometry also revealed that Raji andthose 4 HCC cell lines had strong HLA class Ⅰ antigensexpression, which was confirmed quantitatively by theimage analysis. Tt showed that the objective grayscalevalues of Raji and those 4 HCC cell lines weresignificantly different from that of K562 (Raji 124.04+10.94, Alexander 165.97+5.35, HepG2 167.02+12.60,QGY-7703 161.46+7.13, SMMC-7721 165.93+5.21,K562 244.89+4.60, P<0.01). Significant differenceswere also found between Raji and the 4 HCC cell lines.CONCLUSION: HCC cells express HLA class I antigensstrongly. From this point of view, the active specificimmunotherapy of CTL vaccine is suitable andpracticable for HCC.

  14. HLA class I supertypes: a revised and updated classification

    Directory of Open Access Journals (Sweden)

    Brander Christian

    2008-01-01

    Full Text Available Abstract Background Class I major histocompatibility complex (MHC molecules bind, and present to T cells, short peptides derived from intracellular processing of proteins. The peptide repertoire of a specific molecule is to a large extent determined by the molecular structure accommodating so-called main anchor positions of the presented peptide. These receptors are extremely polymorphic, and much of the polymorphism influences the peptide-binding repertoire. However, despite this polymorphism, class I molecules can be clustered into sets of molecules that bind largely overlapping peptide repertoires. Almost a decade ago we introduced this concept of clustering human leukocyte antigen (HLA alleles and defined nine different groups, denominated as supertypes, on the basis of their main anchor specificity. The utility of this original supertype classification, as well several other subsequent arrangements derived by others, has been demonstrated in a large number of epitope identification studies. Results Following our original approach, in the present report we provide an updated classification of HLA-A and -B class I alleles into supertypes. The present analysis incorporates the large amount of class I MHC binding data and sequence information that has become available in the last decade. As a result, over 80% of the 945 different HLA-A and -B alleles examined to date can be assigned to one of the original nine supertypes. A few alleles are expected to be associated with repertoires that overlap multiple supertypes. Interestingly, the current analysis did not identify any additional supertype specificities. Conclusion As a result of this updated analysis, HLA supertype associations have been defined for over 750 different HLA-A and -B alleles. This information is expected to facilitate epitope identification and vaccine design studies, as well as investigations into disease association and correlates of immunity. In addition, the approach

  15. HLA and trisomy 21. Confirmation of a trend of restricted HLA heterogeneity in parents of Down syndrome children.

    Science.gov (United States)

    Aymé, S; Mercier, P; Dallest, R; Mattei, J F

    1984-03-01

    As the HLA system could play a role in the in utero selection process against abnormal fetuses, HLA-A and -B antigens were evidenced in 30 children with trisomy 21 and in their parents, using a standard microlymphocytotoxicity test. The comparison group included 60 families among whom 39 had HLA typing for paternity exclusion and 21 had been previously selected for a segregation study. Both groups consisted of nonconsanguineous Caucasians from the same geographical area. The Down syndrome (DS) children did not show a significant association with a specific HLA antigen. However, six out of 30 couples having a DS child showed two antigens shared at the A and/or B locus, compared to seven out of 60 control couples. The shared parental antigens were not selectively inherited, and the proportion of homozygote children at one locus was lower for DS (5/30) than for controls (13/60). These findings demonstrate the same trend as previously published but need to be confirmed by other investigators. Perhaps a strong selective pressure in favor of heterozygotes contributes to a better survival rate, as suggested from histocompatibility studies in animals.

  16. The impact of human leukocyte antigen (HLA) micropolymorphism on ligand specificity within the HLA-B*41 allotypic family

    Energy Technology Data Exchange (ETDEWEB)

    Bade-Döding, Christina; Theodossis, Alex; Gras, Stephanie; Kjer-Nielsen, Lars; Eiz-Vesper, Britta; Seltsam, Axel; Huyton, Trevor; Rossjohn, Jamie; McCluskey, James; Blasczyk, Rainer (Springe); (Hannover-MED); (Monash); (Melbourne)

    2011-09-28

    Polymorphic differences between human leukocyte antigen (HLA) molecules affect the specificity and conformation of their bound peptides and lead to differential selection of the T-cell repertoire. Mismatching during allogeneic transplantation can, therefore, lead to immunological reactions. We investigated the structure-function relationships of six members of the HLA-B*41 allelic group that differ by six polymorphic amino acids, including positions 80, 95, 97 and 114 within the antigen-binding cleft. Peptide-binding motifs for B*41:01, *41:02, *41:03, *41:04, *41:05 and *41:06 were determined by sequencing self-peptides from recombinant B*41 molecules by electrospray ionization tandem mass spectrometry. The crystal structures of HLA-B*41:03 bound to a natural 16-mer self-ligand (AEMYGSVTEHPSPSPL) and HLA-B*41:04 bound to a natural 11-mer self-ligand (HEEAVSVDRVL) were solved. Peptide analysis revealed that all B*41 alleles have an identical anchor motif at peptide position 2 (glutamic acid), but differ in their choice of C-terminal p{Omega} anchor (proline, valine, leucine). Additionally, B*41:04 displayed a greater preference for long peptides (>10 residues) when compared to the other B*41 allomorphs, while the longest peptide to be eluted from the allelic group (a 16mer) was obtained from B*41:03. The crystal structures of HLA-B*41:03 and HLA-B*41:04 revealed that both alleles interact in a highly conserved manner with the terminal regions of their respective ligands, while micropolymorphism-induced changes in the steric and electrostatic properties of the antigen-binding cleft account for differences in peptide repertoire and auxiliary anchoring. Differences in peptide repertoire, and peptide length specificity reflect the significant functional evolution of these closely related allotypes and signal their importance in allogeneic transplantation, especially B*41:03 and B*41:04, which accommodate longer peptides, creating structurally distinct peptide-HLA

  17. Exporting Humanist Architecture

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2016-01-01

    values and ethical stands involved in the export of Danish Architecture. Abstract: Danish architecture has, in a sense, been driven by an unwritten contract between the architects and the democratic state and its institutions. This contract may be viewed as an ethos – an architectural tradition...... with inherent aesthetic and moral values. Today, however, Danish architecture is also an export commodity. That raises questions, which should be debated as openly as possible. What does it mean for architecture and architects to practice in cultures and under political systems that do not use architecture...... as a way of generating humanism, freedom or equality? The essay outlines the background story, identifies a number of positions in relation to architecture exports and discusses some of the dilemmas that arise when Danish architecture is seen in an export perspective....

  18. Religious architecture: anthropological perspectives

    NARCIS (Netherlands)

    O. Verkaaik

    2013-01-01

    Religious Architecture: Anthropological Perspectives develops an anthropological perspective on modern religious architecture, including mosques, churches and synagogues. Borrowing from a range of theoretical perspectives on space-making and material religion, this volume looks at how religious buil

  19. Rhein-Ruhr architecture

    DEFF Research Database (Denmark)

    2002-01-01

    katalog til udstillingen 'Rhein - Ruhr architecture' Meldahls smedie, 15. marts - 28. april 2002. 99 sider......katalog til udstillingen 'Rhein - Ruhr architecture' Meldahls smedie, 15. marts - 28. april 2002. 99 sider...

  20. MiRNA-mediated control of HLA-G expression and function.

    Directory of Open Access Journals (Sweden)

    Irit Manaster

    Full Text Available HLA-G is a non-classical HLA class-Ib molecule expressed mainly by the extravillous cytotrophoblasts (EVT of the placenta. The expression of HLA-G on these fetal cells protects the EVT cells from immune rejection and is therefore important for a healthy pregnancy. The mechanisms controlling HLA-G expression are largely unknown. Here we demonstrate that miR-148a and miR-152 down-regulate HLA-G expression by binding its 3'UTR and that this down-regulation of HLA-G affects LILRB1 recognition and consequently, abolishes the LILRB1-mediated inhibition of NK cell killing. We further demonstrate that the C/G polymorphism at position +3142 of HLA-G 3'UTR has no effect on the miRNA targeting of HLA-G. We show that in the placenta both miR-148a and miR-152 miRNAs are expressed at relatively low levels, compared to other healthy tissues, and that the mRNA levels of HLA-G are particularly high and we therefore suggest that this might enable the tissue specific expression of HLA-G.

  1. HLA-G Expression and Role in Advanced-Stage Classical Hodgkin Lymphoma

    Science.gov (United States)

    Caocci, G.; Greco, M.; Fanni, D.; Senes, G.; Littera, R.; Lai, S.; Risso, P.; Carcassi, C.; Faa, G.; La Nasa, G.

    2016-01-01

    Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2. PMID:27349312

  2. Charting improvements in US registry HLA typing ambiguity using a typing resolution score.

    Science.gov (United States)

    Paunić, Vanja; Gragert, Loren; Schneider, Joel; Müller, Carlheinz; Maiers, Martin

    2016-07-01

    Unrelated stem cell registries have been collecting HLA typing of volunteer bone marrow donors for over 25years. Donor selection for hematopoietic stem cell transplantation is based primarily on matching the alleles of donors and patients at five polymorphic HLA loci. As HLA typing technologies have continually advanced since the beginnings of stem cell transplantation, registries have accrued typings of varied HLA typing ambiguity. We present a new typing resolution score (TRS), based on the likelihood of self-match, that allows the systematic comparison of HLA typings across different methods, data sets and populations. We apply the TRS to chart improvement in HLA typing within the Be The Match Registry of the United States from the initiation of DNA-based HLA typing to the current state of high-resolution typing using next-generation sequencing technologies. In addition, we present a publicly available online tool for evaluation of any given HLA typing. This TRS objectively evaluates HLA typing methods and can help define standards for acceptable recruitment HLA typing.

  3. Establishment of optimized ELISA system specific for HLA-G in body fluids.

    Science.gov (United States)

    Ouji-Sageshima, N; Geraghty, D E; Ishitani, A; Hatake, K; Ito, T

    2016-12-01

    Recently, human leukocyte antigen-G (HLA-G) has been a focus in the field of reproductive immunology, tumor progression and transplantation, because of its inhibitory function as ligand to the inhibitory receptors leukocyte immunoglobulin-like receptors (LILR) B1 and LILRB2. The HLA-G is expressed in distinct mRNA isoforms, one of which encodes a soluble HLA-G (sHLA-G) protein, detectable by sandwich ELISA. Therefore, sHLA-G ELISAs have been used as a noninvasive diagnosis system. While a number of sHLA-G-specific ELISAs have been described, our prior studies showed that data obtained by the conventional ELISA system detecting sHLA-G in body fluids was not consistent with the data obtained from immunoprecipitation (IP)/immunoblotting (IB). Therefore, we established an optimized ELISA system described in this report, which yields results consistent with IP/IB analysis. Using this system, we determined sHLA-G protein in amniotic fluids, and found that sHLA-G levels at preterm (∼36 weeks) were clearly higher than those at term (37-41 weeks). These data and supporting experiments showed that the ELISA system we established can be an useful tools for the detection of sHLA-G protein in body fluids than the conventional ELISA system.

  4. HLA-G Dimers in the Prolongation of Kidney Allograft Survival

    Directory of Open Access Journals (Sweden)

    Maureen Ezeakile

    2014-01-01

    Full Text Available Human leukocyte antigen-G (HLA-G contributes to acceptance of allografts in solid organ/tissue transplantation. Most studies have determined that soluble HLA-G isoforms are systematically detected in serum/plasma of transplanted patients with significantly fewer episodes of acute and/or chronic rejection of allogeneic tissue/organ. Current models of the interactions of HLA-G and its specific receptors explain it as functioning in a monomeric form. However, in recent years, new data has revealed the ability of HLA-G to form disulfide-linked dimeric complexes with high preferential binding and functional activities. Limited data are available on the role of soluble HLA-G dimers in clinical pathological conditions. We describe here the presence of soluble HLA-G dimers in kidney transplant patients. Our study showed that a high level of HLA-G dimers in plasma and increased expression of the membrane-bound form of HLA-G on monocytes are associated with prolongation of kidney allograft survival. We also determined that the presence of soluble HLA-G dimers links to the lower levels of proinflammatory cytokines, suggesting a potential role of HLA-G dimers in controlling the accompanying inflammatory state.

  5. Study of Soluble HLA-G in Congenital Human Cytomegalovirus Infection

    Science.gov (United States)

    Gabrielli, Liliana; Bortolotti, Daria; Gentili, Valentina; Piccirilli, Giulia; Chiereghin, Angela; Pavia, Claudia; Bolzani, Silvia; Guerra, Brunella; Simonazzi, Giuliana; Cervi, Francesca; Capretti, Maria Grazia; Luca, Dario Di; Landini, Maria Paola; Lazzarotto, Tiziana

    2016-01-01

    Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that is expressed during pregnancy contributing to maternal-fetal tolerance. HLA-G can be expressed as membrane-bound and soluble forms. HLA-G expression increases strongly during viral infections such as congenital human cytomegalovirus (HCMV) infections, with functional consequences in immunoregulation. In this work we investigated the expression of soluble (s)HLA-G and beta-2 microglobulin (component of HLA) molecules in correlation with the risk of transmission and severity of congenital HCMV infection. We analyzed 182 blood samples from 130 pregnant women and 52 nonpregnant women and 56 amniotic fluid samples from women experiencing primary HCMV infection. The median levels of sHLA-G in maternal serum of women with primary HCMV infection were higher in comparison with nonprimary and uninfected pregnant women (p < 0.001). AF from HCMV symptomatic fetuses presented higher sHLA-G levels in comparison with infected asymptomatic fetuses (p < 0.001), presence of HLA-G free-heavy chain, and a concentration gradient from amniotic fluid to maternal blood. No significant statistical difference of beta-2 microglobulin median levels was observed between all different groups. Our results suggest the determination of sHLA-G molecules in both maternal blood and amniotic fluid as a promising biomarker of diagnosis of maternal HCMV primary infection and fetal HCMV disease. PMID:27699182

  6. Prediction of HLA class II alleles using SNPs in an African population.

    Directory of Open Access Journals (Sweden)

    Fasil Tekola Ayele

    Full Text Available Despite the importance of the human leukocyte antigen (HLA gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs. However, the utility of these methods in African populations has not been systematically evaluated.In the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1 alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia.We demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countries.

  7. PREDICTIVE SIGNIFICANCE OF ANTI-HLA AUTOANTIBODIES IN HEART TRANSPLANT RECIPIENTS

    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko

    2013-01-01

    Full Text Available Aim. The aim of this study was to define the role of preformed anti-HLA antibodies (anti-HLA in antibody-mediated rejection (AMR and cardiac allograft vasculopathy (CAV after heart transplantation. Materials and Methods. 140 heart transplant recipients were followed after heart transplantation performed for 106 dilated and 34 – ischemic cardiomyopathy. Anti-HLA was determined before transplantation by ELISA. Results. Recipients were divided into 2 groups: anti-HLA positive (n = 45, 32,1% and anti-HLA negative (n = 95, 67,9%. The incidence of AMR in anti-HLA positive group was 12 (26,67% and 11 (11,58% in anti-HLA negative group. Risk of AMR was significantly higher in anti-HLA positive recipients (RR 2,3: 95% CI 1,02–4,81, р = 0,03. During first three years after transplantation CAV was diagnosed in 9 (20% of anti-HLA positive recipients and in 7 (6,8% of patients without anti-HLA. (RR 2,7: 95% CI 1,08–6,82, р = 0,03. Survival in freedom from CAV in anti-HLA negative recipients was much higher than in anti-HLA positive recipients (0,89 ± 0,07, 0,72 ± 0,06, resp. (p = 0,02.Conclusions. The presence of preformed anti-HLA antibodies in candidates for heart transplantation increase the risk of AMR and CAV post transplantation in 2,3 and 2,7 times, respectively. 

  8. Gene Map of the HLA Region, Graves' Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Sasazuki, Takehiko; Inoko, Hidetoshi; Morishima, Satoko; Morishima, Yasuo

    2016-01-01

    The human leukocyte antigen (HLA) genomic region spanning about 4 Mb is the most gene dense and the polymorphic stretches in the human genome. A total of the 269 loci were identified, including 145 protein coding genes mostly important for immunity and 50 noncoding RNAs (ncRNAs). Biological function of these ncRNAs remains unknown, becoming hot spot in the studies of HLA-associated diseases. The genomic diversity analysis in the HLA region facilitated by next-generation sequencing will pave the way to molecular understanding of linkage disequilibrium structure, population diversity, histocompatibility in transplantation, and associations with autoimmune diseases. The 4-digit DNA genotyping of HLA for six HLA loci, HLA-A through DP, in the patients with Graves' disease (GD) and Hashimoto thyroiditis (HT) identified six susceptible and three resistant HLA alleles. Their epistatic interactions in controlling the development of these diseases are shown. Four susceptible and one resistant HLA alleles are shared by GD and HT. Two HLA alleles associated with GD or HT control the titers of autoantibodies to thyroid antigens. All these observations led us to propose a new model for the development of GD and HT. Hematopoietic stem cell transplantation from unrelated donor (UR-HSCT) provides a natural experiment to elucidate the role of allogenic HLA molecules in immune response. Large cohort studies using HLA allele and clinical outcome data have elucidated that (1) HLA locus, allele, and haplotype mismatches between donor and patient, (2) specific amino acid substitution at specific positions of HLA molecules, and (3) ethnic background are all responsible for the immunological events related to UR-HSCT including acute graft-versus-host disease (GVHD), chronic GVHD, graft-versus-leukemia (GvL) effect, and graft failure.

  9. HLA-B alleles of the Cayapa of Ecuador: New B39 and B15 alleles

    Energy Technology Data Exchange (ETDEWEB)

    Garber, T.L.; Butler, L.M.; Watkins, D.I. [Univ. of Wisconsin, Madison, WI (United States)] [and others

    1995-05-01

    Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one new variant of HLA-B15 were found in the Cayapa: HLA-B*3905, HLA-B*3906, HLA-B*3907, and HLA-B*1522. A total of thirteen new HLA-B alleles have now been found in the four South American tribes studied. Each of these four tribes studied, including the Cayapa, had novel alleles that were not found in any of the other tribes, suggesting that many of these new HLA-B alleles may have evolved since the Paleo-Indians originally populated South America. Each of these 13 new alleles contained predicted amino acid replacements that were located in the peptide binding site. These amino acid replacements may affect the sequence motif of the bound peptides, suggesting that these new alleles have been maintained by selection. New allelic variants have been found for all common HLA-B locus antigenic groups present in South American tribes with the exception of B48. In spite of its high frequency in South American tribes, no evidence for variants of B48 has been found in all the Amerindians studied, suggesting that B48 may have unique characteristics among the B locus alleles. 70 refs., 2 figs., 2 tabs.

  10. HLA-B alleles of the Cayapa of Ecuador: new B39 and B15 alleles.

    Science.gov (United States)

    Garber, T L; Butler, L M; Trachtenberg, E A; Erlich, H A; Rickards, O; De Stefano, G; Watkins, D I

    1995-01-01

    Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one new variant of HLA-B15 were found in the Cayapa: HLA-B*3905, HLA-B*3906, HLA-B*3907, and HLA-B*1522. A total of thirteen new HLA-B alleles have now been found in the four South American tribes studied. Each of these four tribes studied, including the Cayapa, had novel alleles that were not found in any of the other tribes, suggesting that many of these new HLA-B alleles may have evolved since the Paleo-Indians originally populated South America. Each of these 13 new alleles contained predicted amino acid replacements that were located in the peptide binding site. These amino acid replacements may affect the sequence motif of the bound peptides, suggesting that these new alleles have been maintained by selection. New allelic variants have been found for all common HLA-B locus antigenic groups present in South American tribes with the exception of B48. In spite of its high frequency in South American tribes, no evidence for variants of B48 has been found in all the Amerindians studied, suggesting that B48 may have unique characteristics among the B locus alleles.

  11. HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Jesionek-Kupnicka, Dorota; Bojo, Marcin; Prochorec-Sobieszek, Monika; Szumera-Ciećkiewicz, Anna; Jabłońska, Joanna; Kalinka-Warzocha, Ewa; Kordek, Radzisław; Młynarski, Wojciech; Robak, Tadeusz; Warzocha, Krzysztof; Lech-Maranda, Ewa

    2016-06-01

    The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed.

  12. HLA-DM Polymorphism and Risk of Trichloroethylene Induced Medicamentosa-like Dermatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To establish the association between genetic polymorphisms of HLA-DMA and HLA-DMB and risk of developing trichloroethylene-induced medicamentosa-like dermatitis (TIMLD). Methods Sixty-one cases were medically confirmed to have been affected with TIMLD and 60 controls were selected from exposed workers who were free from TIMLD.The TIMLD cases and controls were similar in terms of age, sex, and duration of exposure. DNA was extracted both from the TIMLD cases and controls, HLA-DMA and HLA-DMB loci were amplified by using Touchdown PCR, and the alleles and genotypes were confirmed by restriction fragment length polymorphism (RFLP) and direct sequencing. Finally, the frequencies of HLA-DMA and HLA-DMB variants were compared between the two groups. Results The results showed that the frequency of HLA-DMA*0101 and HLA-DMB*0103 alleles was significantly increased in TIMLD patients than in controls (71.3% vs. 55.0% for HLA-DMA*0101; P<0.05) (11.5% vs. 3.3% for HLA-DMB*0103; P<0.05). In addition, the frequency of HLA-DMA*0102-*0102 homozygous genotype was also significantly higher in the controls than in the patients (25.0% vs.8.2%, P<0.05), whereas the frequency of heterozygous HLA-DMB *0101-*0102 genotype was lower in the patients in comparison with the controls. Conclusion The polymorphisms of HLA-DM may be associated with the susceptibility to TIMLD.

  13. Association of HLA-A*02:06 and HLA-DRB1*04:05 with clinical subtypes of juvenile idiopathic arthritis.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Miyamae, Takako; Naruto, Takuya; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Kaneko, Tetsuji; Goto, Hiroaki; Morita, Satoshi; Mizuki, Nobuhisa; Kimura, Akinori; Yokota, Shumpei

    2011-03-01

    Juvenile idiopathic arthritis (JIA) is one of the most common forms of pediatric chronic arthritis. JIA is a clinically heterogeneous disease. Therefore, the genetic background of JIA may also be heterogeneous. The aim of this study was to investigate associations between human leukocyte antigen (HLA) and susceptibility to JIA and/or uveitis, which is one of the most devastating complications of JIA. A total of 106 Japanese articular JIA patients (67 with polyarthritis and 39 with oligoarthritis) and 678 healthy controls were genotyped for HLA-A, -B and -DRB1 by PCR-sequence-specific oligonucleotide probe methodology. HLA-A(*)02:06 was the risk factor for JIA accompanied by uveitis after adjustment for clinical factors (corrected P-value < 0.001, odds ratio (OR) 11.7, 95% confidence interval (CI) 3.2-43.0). On the other hand, HLA-DRB1(*)04:05 was associated with polyarticular JIA (corrected P-value < 0.001, OR 2.9, 95% CI 1.7-4.8). We found an association of HLA-A(*)02:06 with susceptibility to JIA accompanied by uveitis, which might be considered a separate clinical JIA entity. We also found an association between HLA-DRB1(*)04:05 and polyarticular JIA. Thus, clinical subtypes of JIA can be classified by the presence of the specific HLA alleles, HLA-A(*)02:06 and DRB1(*)04:05.

  14. Comparison of allele frequency for HLA-DR and HLA-DQ between patients with ECC and caries-free children

    Directory of Open Access Journals (Sweden)

    Bagherian A

    2008-03-01

    Full Text Available Background: Early childhood caries (ECC is one of the most common diseases of childhood. The etiology of ECC is multifactorial and both genetic and environmental factors play important roles in the pathogenesis of the disease. Genetic variations in the hosts may contribute to changes in the risk for dental caries. Genetic factors such as human leukocyte antigen (HLA have recently been suggested as a predisposing factor. Aim: The aim of this study was to look for an association between HLA-DRB1 and HLA-DQB1 with ECC for developing new strategies for the diagnosis as well as the prevention of the disease. Design: In this study, we extracted the genomic DNAs from whole blood samples of 44 patients with ECC and 35 caries-free children by the salting-out method. We amplified the genomic DNA by PCR-SSP and then HLA-typing was performed for all alleles. Results: The results revealed a significant increase in the frequency of HLA-DRB1FNx0104 in the patient group (P = 0.019. The odds ratio for this allele was detected to be 10. The frequency of HLA-DQB1 alleles was not significantly different between the two groups. Conclusion: The above results suggest that HLA-DRB1FNx0104 is associated with the susceptibility to ECC. Thus HLA-DRB1FNx0104 detection as a molecular marker for early diagnosis of ECC may be recommended.

  15. The HLA-G*0105N null allele induces cell surface expression of HLA-E molecule and promotes CD94/NKG2A-mediated recognition in JAR choriocarcinoma cell line.

    Science.gov (United States)

    Sala, Frédéric G; Del Moral, Pierre-Marie; Pizzato, Nathalie; Legrand-Abravanel, Florence; Le Bouteiller, Philippe; Lenfant, Françoise

    2004-12-01

    HLA-G is a non-classical HLA class Ib molecule primarily expressed in trophoblast cells, and is thought to play a key role in the induction of materno-fetal tolerance during pregnancy. In addition, the HLA-G gene provides a suitable leader sequence peptide capable of binding to HLA-E. However, the existence of placentas homozygous for the HLA-G*0105N null allele suggests that HLA-G1 might not be essential for fetal survival. To investigate whether expression of the HLA-G*0105N allele supports HLA-E cell surface expression, we transfected the HLA-G*0105N gene into JAR trophoblast cells. Flow cytometry analysis showed that HLA-G*0105N-transfected cells express surface HLA-E to a similar extent as the unmutated HLA-G gene, whereas HLA-G1 cell surface expression was undetectable. Using the NKL cell line in a standard (51)Cr release assay, the HLA-E molecules were found to inhibit natural killer lysis, through a mechanism partially dependent on CD94/NKG2A-mediated recognition.

  16. Architectural Knitted Surfaces

    DEFF Research Database (Denmark)

    Mossé, Aurélie

    2010-01-01

    WGSN reports from the Architectural Knitted Surfaces workshop recently held at ShenkarCollege of Engineering and Design, Tel Aviv, which offered a cutting-edge insight into interactive knitted surfaces. With the increasing role of smart textiles in architecture, the Architectural Knitted Surfaces...

  17. HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous Nephropathy.

    Science.gov (United States)

    Le, Wei-Bo; Shi, Jing-Song; Zhang, Tao; Liu, Lei; Qin, Hua-Zhang; Liang, ShaoShan; Zhang, Yuan-Wei; Zheng, Cun-Xia; Jiang, Song; Qin, Wei-Song; Zhang, Hai-Tao; Liu, Zhi-Hong

    2016-12-27

    Idiopathic membranous nephropathy (MN) is associated with HLA; however, the HLA allele involved remains unknown. To identify the HLA risk alleles associated with phospholipase A2 receptor (PLA2R)-related MN in the Chinese population, we sequenced the entire MHC region in DNA samples from 99 patients with PLA2R-related MN, 50 patients with PLA2R-unrelated MN, and 100 healthy subjects. Two HLA risk alleles, HLA-DRB1*15:01 and HLA-DRB3*02:02, independently and strongly associated with an increased risk of PLA2R-related MN. After adjusting for HLA-DRB1*15:01 and HLA-DRB3*02:02, no other alleles showed significant association with PLA2R-related MN. A replication study in an independent cohort of 293 participants with PLA2R-related MN and 285 healthy controls validated these findings. In a joint analysis, a multivariate logistic regression model confirmed that HLA-DRB1*15:01 (odds ratio [OR], 24.9; 95% confidence interval [95% CI], 15.3 to 42.6; P=2.3×10(-35)) and HLA-DRB3*02:02 (OR, 17.7; 95% CI, 11.0 to 30.3; P=8.0×10(-29)) independently and strongly associated with PLA2R-related MN. As many as 98.7% of patients with PLA2R-related MN, compared with 43.9% of control subjects, carried at least one HLA risk allele. Subjects with either risk allele had higher odds of developing PLA2R-related MN than those without a risk allele (OR, 98.9; 95% CI, 44.4 to 281.7; P=2.5×10(-23)). These HLA risk alleles also associated with the age at disease onset in patients with PLA2R-related MN. In conclusion, our findings provide clear evidence that the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles independently and strongly associate with PLA2R-related MN in the Chinese population.

  18. Unique features of HLA-mediated HIV evolution in a Mexican cohort: a comparative study

    Science.gov (United States)

    Avila-Rios, Santiago; Ormsby, Christopher E; Carlson, Jonathan M; Valenzuela-Ponce, Humberto; Blanco-Heredia, Juan; Garrido-Rodriguez, Daniela; Garcia-Morales, Claudia; Heckerman, David; Brumme, Zabrina L; Mallal, Simon; John, Mina; Espinosa, Enrique; Reyes-Teran, Gustavo

    2009-01-01

    Background Mounting evidence indicates that HLA-mediated HIV evolution follows highly stereotypic pathways that result in HLA-associated footprints in HIV at the population level. However, it is not known whether characteristic HLA frequency distributions in different populations have resulted in additional unique footprints. Methods The phylogenetic dependency network model was applied to assess HLA-mediated evolution in datasets of HIV pol sequences from free plasma viruses and peripheral blood mononuclear cell (PBMC)-integrated proviruses in an immunogenetically unique cohort of Mexican individuals. Our data were compared with data from the IHAC cohort, a large multi-center cohort of individuals from Canada, Australia and the USA. Results Forty three different HLA-HIV codon associations representing 30 HLA-HIV codon pairs were observed in the Mexican cohort (q < 0.2). Strikingly, 23 (53%) of these associations differed from those observed in the well-powered IHAC cohort, strongly suggesting the existence of unique characteristics in HLA-mediated HIV evolution in the Mexican cohort. Furthermore, 17 of the 23 novel associations involved HLA alleles whose frequencies were not significantly different from those in IHAC, suggesting that their detection was not due to increased statistical power but to differences in patterns of epitope targeting. Interestingly, the consensus differed in four positions between the two cohorts and three of these positions could be explained by HLA-associated selection. Additionally, different HLA-HIV codon associations were seen when comparing HLA-mediated selection in plasma viruses and PBMC archived proviruses at the population level, with a significantly lower number of associations in the proviral dataset. Conclusion Our data support universal HLA-mediated HIV evolution at the population level, resulting in detectable HLA-associated footprints in the circulating virus. However, it also strongly suggests that unique genetic

  19. Correlation between HLA-G and tumor immunity and its advances%HLA-G与肿瘤免疫的相关进展

    Institute of Scientific and Technical Information of China (English)

    陈黎; 董延生; 李敏; 张雯珂; 姚元庆

    2016-01-01

    HLA-G belongs to non-classical HLA-class Ⅰ genes.It is expressed in the fetal-maternal interface on the extravillous cytotrophoblast and in such immune privilege tissues as the cornea and pancreas.However, under pathological conditions, such as tumor, inflammatory diseases and post transplantation, HLA-G is expressed abnormally.HLA-G can interact with its acceptors or immune cells and suppress the function of immune cells, which facilitates the escape of the surveillance of the human immune system and the consequent damage.In clinical studies,HLA-G is related to some clinical parameters.This review will focus on the expression, function and regulatory mechanisms of HLA-G in cancer immunology.%HLA-G是非经典人类白细胞抗原Ⅰ类基因的一种,在绒毛外细胞滋养层的母-胎界面,以及角膜、胰腺等免疫豁免组织中表达,病理状态如肿瘤、炎症、移植后等也出现不同程度的表达。肿瘤细胞表达HLA-G后通过作用于相应受体或免疫细胞,抑制免疫细胞的功能,从而躲避人体免疫系统的监视和杀伤,且HLA-G的表达情况与肿瘤临床参数具有相关性。该文对HLA-G在肿瘤免疫中的表达、功能、调节机制等的新进展进行综述。

  20. HLA-associated susceptibility to HIV-1 infection.

    Science.gov (United States)

    Fabio, G; Scorza, R; Lazzarin, A; Marchini, M; Zarantonello, M; D'Arminio, A; Marchisio, P; Plebani, A; Luzzati, R; Costigliola, P

    1992-01-01

    We studied HLA antigen distribution of 50 heterosexual partners of HIV+ drug abusers with more than 1 year of sexual exposure to HIV, 36 children born to seropositive mothers and 61 haemophiliac patients exposed to presumably infectious clotting factor concentrates. B52 and B44 antigens were associated with HIV resistance while B51 was associated with HIV susceptibility. Forty-nine HIV+ drug abusers, spouses of heterosexual partners studied and 25 HIV+ mothers of the children were also typed. DR11 phenotype was associated with infectiousness of HIV+ subjects. Our data suggest that the HLA region controls susceptibility to infection with HIV and infectiousness of HIV+ subjects in different risk groups. PMID:1733633

  1. A simple and safe method for single HLA-antigen-typing by a solid phase assay.

    Science.gov (United States)

    Häcker-Shahin, B; Giannitsis, D J

    1991-01-01

    A rapid solid phase assay for detection of single HLA-antigens on platelets was developed. The platelets were attached to the surface of polystyrene microtitre plate wells by means of a sodium carbonate buffer and centrifugation. Uncovered areas were blocked by a gelatin blocking buffer. After incubation with commercially available anti-HLA-sera the bound anti-HLA-specific antibodies directed against HLA-antigens present on the platelets were made visible by anti-IgG-coated indicator red cells and a brief centrifugation. A positive result, meaning the presence of an HLA-antigen, was indicated by a slight red cell adherence over the reaction surface. In the absence of the HLA-antigen no binding occurred and the indicator red cells formed a small red disc-like pellet.

  2. HLA antibody detection with solid phase assays: great expectations or expectations too great?

    Science.gov (United States)

    Gebel, H M; Bray, R A

    2014-09-01

    Alloantibodies directed against HLA antigens, are a barrier to long-term solid organ allograft survival. The clinical impact of preformed, donor-directed HLA alloantibodies range from acceptable risk to unequivocal contraindication for organ transplantation. HLA antibodies are key factors that limit patient access to donor organs. Serological methods were once the only approach to identify HLA antigens and antibodies. Limitations in these technologies led to the development of solid phase approaches. In the early 1990s, the development of the polymerase chain reaction enabled DNA-based HLA antigen testing to be performed. By the mid-1990s, microparticle-based technology that utilized flow cytometry for analysis was developed to detect both classes I and II HLA antibodies. These methodologies revolutionized clinical histocompatibility testing. The strengths and weaknesses of these assays are described in detail in this review.

  3. Chimerism representing both paternal alleles detected by HLA typing before kidney transplantation

    DEFF Research Database (Denmark)

    Christiansen, Mette; Petersen, Mikkel Steen; Møller, Bjarne Kuno

    2014-01-01

    We select donors and recipients for solid organ transplantations by employing HLA serology and PCR with sequence-specific primers (PCR-SSP). Routinely, patients and donors are typed for HLA-A and B using serological techniques, while HLA-C, HLA-DRB1, and HLA-DQB1 are typed with PCR-SSP. In a 38......-year-old female kidney transplantation recipient, the PCR-SSP technique yielded very unusual results, whereas her parents were assigned routinely. The mother had the following HLA types: A3,33(19); B7,39(16); C*07; DQB1*06; DRB1*13; the father A2,11; B27,35; C*01,*04; DQB1*03,*05; DRB1...

  4. HLA Alleles Associated with Slow Progression to AIDS Truly Prefer to Present HIV-1 p24

    DEFF Research Database (Denmark)

    Borghans, J. A.; Molgaard, A.; Boer, R. J. de;

    2007-01-01

    BACKGROUND: The mechanism behind the association between human leukocyte antigen (HLA) molecules and the rate of HIV-1 disease progression is still poorly understood. Recent data suggest that "protective" HLA molecules, i.e. those associated with a low HIV-1 viral load and relatively slow disease...... and effect, we predicted HIV-1 epitopes from the whole genome of HIV-1, and found that protective HLA alleles have a true preference for the p24 Gag protein, while non-protective HLA alleles preferentially target HIV-1 Nef. In line with this, we found a significant negative correlation between the predicted...... affinity of the best-binding p24 epitopes and the relative hazard of HIV-1 disease progression for a large number of HLA molecules. When the epitopes targeted by protective HLA alleles were mapped to the known p24 structure, we found that mutations in these epitopes are likely to disturb the p24 dimer...

  5. Software architecture evolution

    DEFF Research Database (Denmark)

    Barais, Olivier; Le Meur, Anne-Francoise; Duchien, Laurence

    2008-01-01

    Software architectures must frequently evolve to cope with changing requirements, and this evolution often implies integrating new concerns. Unfortunately, when the new concerns are crosscutting, existing architecture description languages provide little or no support for this kind of evolution....... The software architect must modify multiple elements of the architecture manually, which risks introducing inconsistencies. This chapter provides an overview, comparison and detailed treatment of the various state-of-the-art approaches to describing and evolving software architectures. Furthermore, we discuss...... one particular framework named Tran SAT, which addresses the above problems of software architecture evolution. Tran SAT provides a new element in the software architecture descriptions language, called an architectural aspect, for describing new concerns and their integration into an existing...

  6. HLA and malaria in four colombian ethnic groups

    Directory of Open Access Journals (Sweden)

    Marcos Restrepo

    1988-10-01

    Full Text Available HLA antigens and their relationship with malaria infection were studied in four different ethnic groups in Colombia (South America: two groups of indians (Kunas and Katios, one of negroes and a group of mixed ancestry. A total of 965 persons were studied, 415 with malaria and 550 as controls. HLA-A,B, and C antigen frequencies in the four groups are reported. The association of each HLA antigen with malaria infection due to P. vivax and to P. falciparum was evaluated. Negroes, Kunas and Katios indians variously lack from 6 to 9 of the HLA antigens found in the mixed group. In the designated ethnic groups, antigens B5, B13, B15, Cw2 and Cw4 showed borderline association with malaria infection. However, in the mixed ethnic group, statistically significant associations were found with malaria infection and the presence of A9, Aw19, B17, B35, and Z98 (a B21-B45: crossreacting determinant with few differences when P. vivax infection and P. falciparum infection were considered individually. This finding may represent a lack of general resistance to malaria in the group that harbors antigens of Caucasian origin. These individuals have been in direct and permanent contact with malaria only in the past 65 years. In contrast, indians, both Kunas and Katios, and Negroes have lived for centuries in malaria endemic areas, and it is possible that a natural selection system has developed through which only those individuals able to initiate an acute immune response to malaria have survived.

  7. Characterization of recombination in the HLA class II region

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, M.; Carrington, M. [National Cancer Institute, Frederick, MD (United States); Noble, J. [Roche Molecular Systems, Almeda, CA (United States)] [and others

    1997-02-01

    Studies of linkage disequilibrium across the HLA class II region have been useful in predicting where recombination is most likely to occur. The strong associations between genes within the 85-kb region from DQB1 to DRB1 are consistent with low frequency of recombination in this segment of DNA. Conversely, a lack of association between alleles of TAP1 and TAP2 ({approximately}15 kb) has been observed, suggesting that recombination occurs here with relatively high frequency. Much of the HLA class II region has now been sequenced, providing the tools to undertake detailed analysis of recombination. Twenty-seven families containing one or two recombinant chromosomes within the 500-kb interval between the DPB1 and DRB1 genes were used to determine patterns of recombination across this region. SSCP analysis and microsatellite typing yielded identification of 127 novel polymorphic markers distributed throughout the class II region, allowing refinement of the site of crossover in 30 class II recombinant chromosomes. The three regions where recombination was observed most frequently are as follows: the 45-kb interval between HLA-DNA and RING3 (11 cases), the 50-kb interval between DQB3 and DQB1 (6 cases), and an 8.8-kb segment of the TAP2 gene (3 cases). Six of the 10 remaining recombinants await further characterization, pending identification of additional informative markers, while four recombinants were localized to other intervals (outliers). Analysis of association between markers flanking HLA-DNA to RING3 (45 kb), as well as TAP1 to TAP2 (15 kb), by use of independent CEPH haplotypes indicated little or no linkage disequilibrium, supporting the familial recombination data. A notable sequence motif located within a region associated with increased rates of recombination consisted of a (TGGA){sub 12} tandem repeat within the TAP2 gene. 74 refs., 3 figs., 2 tabs.

  8. Proteome sampling by the HLA class I antigen processing pathway.

    Directory of Open Access Journals (Sweden)

    Ilka Hoof

    Full Text Available The peptide repertoire that is presented by the set of HLA class I molecules of an individual is formed by the different players of the antigen processing pathway and the stringent binding environment of the HLA class I molecules. Peptide elution studies have shown that only a subset of the human proteome is sampled by the antigen processing machinery and represented on the cell surface. In our study, we quantified the role of each factor relevant in shaping the HLA class I peptide repertoire by combining peptide elution data, in silico predictions of antigen processing and presentation, and data on gene expression and protein abundance. Our results indicate that gene expression level, protein abundance, and rate of potential binding peptides per protein have a clear impact on sampling probability. Furthermore, once a protein is available for the antigen processing machinery in sufficient amounts, C-terminal processing efficiency and binding affinity to the HLA class I molecule determine the identity of the presented peptides. Having studied the impact of each of these factors separately, we subsequently combined all factors in a logistic regression model in order to quantify their relative impact. This model demonstrated the superiority of protein abundance over gene expression level in predicting sampling probability. Being able to discriminate between sampled and non-sampled proteins to a significant degree, our approach can potentially be used to predict the sampling probability of self proteins and of pathogen-derived proteins, which is of importance for the identification of autoimmune antigens and vaccination targets.

  9. [Routine application of HLA class II oligotyping. Value of automatization].

    Science.gov (United States)

    Caillat-Zucman, S; Bach, J F

    1992-12-02

    HLA class II typing by DNA amplification and hybridization with allele-specific oligonucleotides has led to an improvement of the overall typing accuracy. In an attempt to apply this procedure to a large-scale analysis, we sought to implement an automation system using the Biomek 1,000 robotic work-station. This system allows a rapid preparation of many consecutive samples and avoids the risk of human errors. It is now routinely used in several laboratories.

  10. El HLA y su implicación en Odontología HLA and his implication in dentistry

    Directory of Open Access Journals (Sweden)

    M Rioboo Crespo

    2005-04-01

    Full Text Available El sistema HLA constituye uno de los sistemas genéticos más fascinantes del hombre, capaz de codificar una serie de moléculas (moléculas del HLA tipo I y tipo II presentes en las membranas de la mayoría de las células nucleadas del organismo implicadas en procesos vitales básicos, tales como la respuesta inmunológica , con el fin de mantener la integridad del individuo y de la especie. Considerado inicialmente como un simple marcador genético, los esfuerzos en la búsqueda de su aplicación clínica están a la orden del día asociándose a diversas enfermedades sobretodo autoinmunes o con disfunciones inmunológicas. En nuestro campo, está cobrando cada vez más importancia la posibilidad de que el estudio del HLA nos permita explicar la susceptibilidad, la etiología y la patogénesis de determinadas enfermedades muy frecuentes en la consulta odontológica como la caries, los trastornos temporomandibulares y la enfermedad periodontal, entre otras. Así, los estudios experimentales más actuales se centran en el estudio del HLA para determinar el rol de la respuesta inmune de la pulpa ante determinadas situaciones, investigar una posible vacuna para la caries e incluso averiguar si realmente existe una predisposición genética para el acúmulo de microorganismos orales. En cuanto al estudio del HLA dentro del campo de los trastornos temporomandibulares, se observa que no solo se ha empleado en la investigación de enfermedades multisistémicas como la Espondilitis Anquilosante o la Artritis Juvenil, sino que se ha demostrado que puede tener utilidad en el campo de la etiopatogénesis de diversas alteraciones temporomandibulares. Por último, su asociación con las enfermedades periodontales están cobrando cada vez más importancia, aunque se afirme que la susceptibilidad y resistencia de las periodontitis estén influenciadas por determinadas combinaciones de antígenos de HLA, es necesario llevar a cabo un estudio más exaustivo

  11. The Mycobacterium tuberculosis phagosome is a HLA-I processing competent organelle.

    Directory of Open Access Journals (Sweden)

    Jeff E Grotzke

    2009-04-01

    Full Text Available Mycobacterium tuberculosis (Mtb resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-gamma release by CD8(+ T cell clones, we examined the processing and presentation pathway for two Mtb-derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib. Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER-golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER-golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I:peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E:peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER-localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb-derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens.

  12. Association of HLA-A, -B, and -DRB1 with pulmonary tuberculosis in western Javanese Indonesia.

    Science.gov (United States)

    Yuliwulandari, Rika; Sachrowardi, Qomariyah; Nakajima, Humiaki; Kashiwase, Koichi; Hirayasu, Kouyuki; Mabuchi, Akihiko; Sofro, Abdul Salam Mudzakir; Tokunaga, Katsushi

    2010-07-01

    Genetic studies of pulmonary tuberculosis (PTB), including those of human leukocyte antigen (HLA) genes, have been reported in several populations. Some studies also have reported these genes to have a stronger role in severe tuberculosis. We investigated HLA class I and II alleles and haplotypes to ascertain their role in susceptibility and resistance to new and recurrent PTB in 257 PTB patients (216 new and 41 recurrent PTB patients) and 236 healthy controls in Western Javanese (Indonesia). HLA-B*4006 was associated with new PTB (p = 0.044, p(adj) = ns), whereas HLA-B*1802, HLA-B*4001 and HLA-DRB1*1101 were associated with recurrent PTB (p = 0.013, p(adj) = 0.016; p = 0.015, p(adj) = 0.028; and p = 0.008, p(adj) = 0.027 for new PTB vs recurrent PTB, respectively). Except for HLA-B*4006, those associations remained significant after adjustment for age and gender by logistic regression analysis, although they disappeared after correction for multiple testing. Haplotype HLA-B*1802-DRB1*1202 was associated with susceptibility to recurrent PTB (p = 0.014, odds ratio = 3.8, 95% confidence interval = 1.18-12.27). In contrast, HLA-DRB1*1202 in the absence of HLA-B*1802 showed a significant association with resistance to recurrent PTB (p = 8.2 x 10(-4), odds ratio = 0.32, 95% confidence interval = 0.16-0.64), suggesting that stronger susceptibility effect of HLA-B*1802 masked the protective effect of HLA-DRB1*1202. Further studies using larger number of patients with recurrent PTB will be needed to confirm our findings.

  13. HLA-G expression levels influence the tolerogenic activity of human DC-10

    Science.gov (United States)

    Amodio, Giada; Comi, Michela; Tomasoni, Daniela; Gianolini, Monica Emma; Rizzo, Roberta; LeMaoult, Joël; Roncarolo, Maria-Grazia; Gregori, Silvia

    2015-01-01

    Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with known immune-modulatory functions. Our group identified a subset of human dendritic cells, named DC-10, that induce adaptive interleukin-10-producing T regulatory type 1 (Tr1) cells via the interleukin-10-dependent HLA-G/ILT4 pathway. In this study we aimed at defining the role of HLA-G in DC-10-mediated Tr1 cell differentiation. We analyzed phenotype, functions, and genetic variations in the 3′ untranslated region of the HLA-G locus of in vitro-differentiated DC-10 from 67 healthy donors. We showed that HLA-G expression on DC-10 is donor-dependent. Functional studies demonstrated that DC-10, independently of HLA-G expression, secrete interleukin-10 and negligible levels of interleukin-12. Interestingly, DC-10 with high HLA-G promote allo-specific anergic T cells that contain a significantly higher frequency of Tr1 cells, defined as interleukin-10-producing (P=0.0121) or CD49b+LAG-3+ (P=0.0031) T cells, compared to DC-10 with low HLA-G. We found that the HLA-G expression on DC-10 is genetically imprinted, being associated with specific variations in the 3′ untranslated region of the gene, and it may be finely tuned by microRNA-mediated post-transcriptional regulation. These data highlight the important role of HLA-G in boosting DC-10 tolerogenic activity and confirm that interleukin-10 production by DC-10 is necessary but not sufficient to promote Tr1 cells at high frequency. These new insights into the role of HLA-G in DC-10-mediated induction of Tr1 cells provide additional information for clinical use in Tr1- or DC-10-based cell therapy approaches. PMID:25661445

  14. HLA-G expression and role in advanced-stage classical Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    G. Caocci

    2016-04-01

    Full Text Available Non-classical human leucocyte antigen (HLA-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL, in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp deletion-insertion (del-ins polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy patients with a 2-year progression-free survival rate (PFS of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.

  15. Preformed donor HLA-DP-specific antibodies mediate acute and chronic antibody-mediated rejection following renal transplantation.

    Science.gov (United States)

    Jolly, E C; Key, T; Rasheed, H; Morgan, H; Butler, A; Pritchard, N; Taylor, C J; Clatworthy, M R

    2012-10-01

    Donor-specific HLA alloantibodies may cause acute and chronic antibody-mediated rejection (AMR) and significantly compromise allograft survival. The clinical relevance of antibodies directed against some HLA class II antigens, particularly HLA-DP, is less clear with conflicting reports on their pathogenicity. We report two patients with high levels of pretransplant donor-specific HLA-DP antibodies who subsequently developed recurrent acute AMR and graft failure. In both cases, there were no other donor-specific HLA alloantibodies, suggesting that the HLA-DP-specific antibodies may be directly pathogenic.

  16. Prevalence of HLA DQB1*0602 allele in patients with migraine Prevalência do alelo HLA DQB1*0602 em pacientes com enxaqueca

    Directory of Open Access Journals (Sweden)

    Fernando Morgadinho Santos Coelho

    2007-12-01

    Full Text Available BACKGROUND: Studies have shown a high prevalence of migraine among narcoleptic patients. HLA-DQB1*0602 and HLA DRB1 alleles are closely associated with narcolepsy. An increase in the HLA-DRB1 allele frequency in patients with visual aura has raised greater awareness of the genetic background in migraine. PURPOSE: Since the regions DR and DQ of the HLA are in tightly linkage desiquilibrium we hypothesize that HLA-DQB1*0602 might be associated to the pathophysiology of migraine. METHOD: We analyzed the presence of HLA DQB1*0602 allele in 50 healthy subjects with no history of migraine, 53 patients with migraine without aura and 52 patients with migraine with aura. RESULTS: There was no difference in the frequency of HLA DQB1*0602 allele when control subjects and all patients were compared. We failed to note any difference in frequencies when comparing migraine patients with and without aura. CONCLUSION: Further studies with different patient populations, with other hypothalamic markers (melatonin, hypocretin in migraine patients may shed light on to its pathophysiology.CONTEXTO: Estudos têm demonstrado o aumento da prevalência de enxaqueca em pacientes com narcolepsia, um distúrbio de sono associado a um gene do sistema HLA, o alelo HLA-DQB1*0602. As regiões DQ e DR do HLA estão em alto desequilíbrio de ligação e já foi descrito um aumento da freqüência do alelo HLA DRB1 em pacientes com enxaqueca com aura visual, o que fortalece uma hipótese de herança genética para a enxaqueca. OBJETIVO: Nossa hipótese é que o alelo HLA-DQB1*0602 pode estar relacionado com a fisiopatologia da enxaqueca destes pacientes. MÉTODO: Nós analisamos a presença do alelo HLA-DQB1*0602 em 50 voluntários sadios sem história de enxaqueca, 53 pacientes com enxaqueca sem aura e 52 pacientes com aura. RESULTADOS: Não houve diferença entre os controles sadios e os pacientes com enxaqueca. Não houve diferença entre os pacientes com enxaqueca com e sem

  17. Recognition of HLA-A3 and HLA-A11 by KIR3DL2 is peptide-specific.

    Science.gov (United States)

    Hansasuta, Pokrath; Dong, Tao; Thananchai, Hathairat; Weekes, Michael; Willberg, Christian; Aldemir, Hatice; Rowland-Jones, Sarah; Braud, Veronique M

    2004-06-01

    The recognition of MHC class I molecules by killer cell immunoglobulin-like receptors (KIR) is central to the control of NK cell function and can also modulate the CTL activation threshold. Among KIR receptors, KIR3DL2 is thought to interact with HLA-A3 and -A11, although direct evidence has been lacking. In this study, we show that HLA-A3 and -A11 tetramers specifically bind to KIR3DL2*001 transfectants and that this recognition is peptide-specific. Single amino acid substitutions in the nonamer peptide underline a critical role for residue 8 in recognition of KIR3DL2. However, the role of this interaction in vivo still remains to be established.

  18. EXPRESSION OF HLA-CLASS Ⅱ GENESOF IDDM PATIENTS ON THE SURFACE OF THE LTK- CELLS

    Institute of Scientific and Technical Information of China (English)

    王姮; 孙琦

    1994-01-01

    To investigate the function of HLA-class Ⅱ genes in the autoimmune response of insulin dependent diabetes mellitus(DDM),the HLA-class Ⅱ gene of IDDM patients was introd uced into Ltk-cells with pSV2-neo plas-mid,using the calcium phosphate precipitation technique.We obtained a stable cell line expressing the HLA-class Ⅱ gene from lymphocytes of IDDM patients.Expression was identified by direct ox erythocyte-CrCl3-HLA DR monoclonal antibody rosetting.

  19. Associations of HLA DR and DQ molecules with Lyme borreliosis in Latvian patients

    Directory of Open Access Journals (Sweden)

    Kovalchuka Lilija

    2012-08-01

    Full Text Available Abstract Background Many autoimmune diseases are associated with variants of HLA genes such as those encoding the MHC complex. This correlation is not absolute, but may help in understanding of the molecular mechanism of disease. The purpose of this study was to determine HLA-DR,-DQ alleles in Latvian patients with Lyme borreliosis and control (healthy persons. Case patients and control subjects were similar in age, gender and ethnic heritage and differed only as regards the presence of Borrelia burgdorferi infection. The study included 25 patients with clinical stage – erythema migrans and 30 control (healthy persons. HLA genotyping was performed by PCR with sequence-specific primers. Results The results show difference in HLA-DRB1 alleles distribution between patients and control subjects. The frequencies of HLA-DRB1 *04 (OR 11.24; p  Conclusions HLA predisposition to Lyme borreliosis appears not to be limited to HLA molecules, but some HLA-DR alleles also have a significant influence, and, may have implications in our understanding of pathogenesis of this disease. In particular, HLA-DRB1*04 and DRB1 *17 (03 may contribute to the Lyme borreliosis development in Latvian population

  20. HIV subtype influences HLA-B*07:02-associated HIV disease outcome

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N; Adland, Emily; Koyanagi, Madoka

    2014-01-01

    Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA......% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8(+) T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed....

  1. HLA-G expression in melanoma: A way for tumor cells to escape from immunosurveillance

    Science.gov (United States)

    Paul, Pascale; Rouas-Freiss, Nathalie; Khalil-Daher, Iman; Moreau, Philippe; Riteau, Beatrice; Le Gal, Frederique Anne; Avril, Marie Francoise; Dausset, Jean; Guillet, Jean Gerard; Carosella, Edgardo D.

    1998-01-01

    Considering the well established role of nonclassical HLA-G class I molecules in inhibiting natural killer (NK) cell function, the consequence of abnormal HLA-G expression in malignant cells should be the escape of tumors from immunosurveillance. To examine this hypothesis, we analyzed HLA-G expression and NK sensitivity in human malignant melanoma cells. Our analysis of three melanoma cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma cell lines exhibit a high level of HLA-G transcription with differential HLA-G isoform transcription and protein expression patterns, (ii) a higher level of HLA-G transcription ex vivo is detected in a skin melanoma metastasis biopsy compared with a healthy skin fragment from the same individual, and (iii) HLA-G protein isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus appears of critical importance to consider the specific role of HLA-G expression in tumors in the design of future cancer immunotherapies. PMID:9539768

  2. The role of antigens and HLA class I haplotypes in indigenous women in Tashkent with hysteromyoma

    Directory of Open Access Journals (Sweden)

    Landish Isanbaeva

    2011-05-01

    Full Text Available Immunogenetic analysis on HLA I class in 177 indigenous women with uterine myoma showed the positive association in the risk of uterine fibroids with antigens HLA-B8/B22 and haplotype A28/B22; antigens HLA-A28, Cw5 and haplotype B17-Sw5 played role of auxiliary markers. HLA-antigens A2, B35, Cw4 and haplotypes A2-B35, B5-Cw4 showed the negative association. Carrying immunogenetic studies may be useful to search for individual genes involved in the determination of the disease - uterine fibroids, especially among patients with hereditary anamnesis.

  3. Identification of the core regulators of the HLA I-peptide binding process

    Science.gov (United States)

    Zhang, Yu-Hang; Xing, Zhihao; Liu, Chenglin; Wang, ShaoPeng; Huang, Tao; Cai, Yu-Dong; Kong, Xiangyin

    2017-01-01

    During the display of peptide/human leukocyte antigen (HLA) -I complex for further immune recognition, the cleaved and transported antigenic peptides have to bind to HLA-I protein and the binding affinity between peptide epitopes and HLA proteins directly influences the immune recognition ability in human beings. Key factors affecting the binding affinity during the generation, selection and presentation processes of HLA-I complex have not yet been fully discovered. In this study, a new method describing the HLA class I-peptide interactions was proposed. Three hundred and forty features of HLA I proteins and peptide sequences were utilized for analysis by four candidate algorithms, screening the optimal classifier. Features derived from the optimal classifier were further selected and systematically analyzed, revealing the core regulators. The results validated the hypothesis that features of HLA I proteins and related peptides simultaneously affect the binding process, though with discrepant redundancy. Besides, the high relative ratio (16/20) of the amino acid composition features suggests the unique role of sequence signatures for the binding processes. Integrating biological, evolutionary and chemical features of both HLA I molecules and peptides, this study may provide a new perspective of the underlying mechanisms of HLA I-mediated immune reactions. PMID:28211542

  4. A common minimal motif for the ligands of HLA-B*27 class I molecules.

    Directory of Open Access Journals (Sweden)

    Alejandro Barriga

    Full Text Available CD8(+ T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.

  5. Matrix metalloproteinase-2 (MMP-2) generates soluble HLA-G1 by cell surface proteolytic shedding.

    Science.gov (United States)

    Rizzo, Roberta; Trentini, Alessandro; Bortolotti, Daria; Manfrinato, Maria C; Rotola, Antonella; Castellazzi, Massimiliano; Melchiorri, Loredana; Di Luca, Dario; Dallocchio, Franco; Fainardi, Enrico; Bellini, Tiziana

    2013-09-01

    Human leukocyte antigen-G (HLA-G) molecules are non-classical HLA class I antigens with an important role in pregnancy immune regulation and inflammation control. Soluble HLA-G proteins can be generated through two mechanisms: alternative splicing and proteolytic release, which is known to be metalloprotease mediated. Among this class of enzymes, matrix metalloproteinases (MMPs) might be involved in the HLA-G1 membrane cleavage. Of particular interest are MMP-2 and MMP-9, which regulate the inflammatory process by cytokine and chemokine modulation. We evaluated the effect of MMP-9 and MMP-2 on HLA-G1 membrane shedding. In particular, we analyzed the in vitro effect of these two gelatinases on the secretion of HLA-G1 via proteolytic cleavage in 221-G1-transfected cell line, in JEG3 cell line, and in peripheral blood mononuclear cells. The results obtained by both cell lines showed the role of MMP-2 in HLA-G1 shedding. On the contrary, MMP-9 was not involved in this process. In addition, we identified three possible highly specific cleavage sites for MMP-2, whereas none were detected for MMP-9. This study suggests an effective link between MMP-2 and HLA-G1 shedding, increasing our knowledge on the regulatory machinery beyond HLA-G regulation in physiological and pathological conditions.

  6. ABPS-INDUCED HLA-DR EXPRESSION IN MONOCYTES%ABPS诱导单核细胞HLA-DR表达

    Institute of Scientific and Technical Information of China (English)

    王宇学; 彭颖; 吕建新; 金丽琴

    2004-01-01

    目的研究牛膝多糖(ABPS)在体外激活单核细胞的效应.方法采集健康成人抗凝血,用贴壁法分离单核细胞,调节细胞数接种到24孔板.在370 C,5%CO2条件下,以同一时间不同ABPS浓度或同一ABPS浓度不同时间培养,用流式细胞术和电镜检测单核细胞的激活.结果 ABPS诱导单核细胞超微结构和HLA-DR的改变.结论 ABPS上调HLA-DR表达并能激活单核细胞.%Objective To investigate the activating effect of Achyrathes bidentata polysaccharides (ABPS) on mononuclear cells in vitro.Method Heparinized blood was collected from adults. The monocytes were separated by the anchoring technique. Freshly isolated in 24-well flat-bottom plates, the cells were cultured with serially diluted ABPS-RPMI1640 for identical time or with the same ABPS-RPMI1640 for different periods at 37℃ in 5% CO2. The activation of the cells was assayed by electron microscopy and flow cytometry. Result Monocytes cultured with ABPS underwent substaintial changes in the cell ultrastructure, and the expression of HLA-DR was up-regulated in these cells in significant dose- and time-dependent manner. Conclusion ABPS can induce the expression of HLA-DR in the monocytes, and thereby activate them.

  7. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations.

    Science.gov (United States)

    González-Galarza, Faviel F; Takeshita, Louise Y C; Santos, Eduardo J M; Kempson, Felicity; Maia, Maria Helena Thomaz; da Silva, Andrea Luciana Soares; Teles e Silva, André Luiz; Ghattaoraya, Gurpreet S; Alfirevic, Ana; Jones, Andrew R; Middleton, Derek

    2015-01-01

    It has been 12 years since the Allele Frequency Net Database (AFND; http://www.allelefrequencies.net) was first launched, providing the scientific community with an online repository for the storage of immune gene frequencies in different populations across the world. There have been a significant number of improvements from the first version, making AFND a primary resource for many clinical and scientific areas including histocompatibility, immunogenetics, pharmacogenetics and anthropology studies, among many others. The most widely used part of AFND stores population frequency data (alleles, genes or haplotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex class I chain-related genes (MIC) and a number of cytokine gene polymorphisms. AFND now contains >1400 populations from more than 10 million healthy individuals. Here, we report how the main features of AFND have been updated to include a new section on 'HLA epitope' frequencies in populations, a new section capturing the results of studies identifying HLA associations with adverse drug reactions (ADRs) and one for the examination of infectious and autoimmune diseases associated with KIR polymorphisms-thus extending AFND to serve a new user base in these growing areas of research. New criteria on data quality have also been included.

  8. Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

    Science.gov (United States)

    Gagne, K; Loiseau, P; Dubois, V; Dufossé, F; Perrier, P; Dormoy, A; Jollet, I; Renac, V; Masson, D; Picard, C; Lafarge, X; Hanau, D; Quainon, F; Delbos, F; Coeffic, B; Absi, Léna; Eliaou, J-F; Moalic, V; Fort, M; de Matteis, M; Theodorou, I; Hau, F; Batho, A; Pedron, B; Caillat-Zucman, S; Marry, E; Raus, N; Yakoub-Agha, I; Cesbron, A

    2015-02-01

    We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

  9. The impact of HLA-G 3' UTR variants and sHLA-G on risk and clinical correlates of schizophrenia.

    Science.gov (United States)

    Rajasekaran, Ashwini; Shivakumar, Venkataram; Kalmady, Sunil V; Narayanaswamy, Janardhanan C; Subbana, Manjula; Venugopal, Deepthi; Amaresha, Anekal C; Venkatasubramanian, Ganesan; Berk, Michael; Debnath, Monojit

    2016-12-01

    The Major Histocompatibility Complex (MHC)/Human Leukocyte Antigen (HLA) is known to influence the pathogenesis of several complex human diseases resulting from gene-environmental interactions. Recently, it has emerged as one of the risk determinants of schizophrenia. The HLA-G protein (a non-classical MHC class I molecule), encoded by the HLA-G gene, is shown to play important role in embryonic development. Importantly, its genetic variations and aberrant expression have been implicated in pregnancy complications like preeclampsia, inflammation, and autoimmunity. Converging evidence implicates these phenomena as risk mechanisms of schizophrenia. However, the functional implications of HLA-G in schizophrenia are yet to be empirically examined. The impact of two functional polymorphisms [14bp Insertion/Deletion (INDEL) and +3187 A>G] and soluble HLA-G (sHLA-G) levels on schizophrenia risk was evaluated. In this exploratory study, the Ins/Ins genotype of 14bp INDEL was found to confer a strong risk for schizophrenia. Further, low levels of sHLA-G were shown to have a significant impact on Clinical Global Impression (CGI) severity in people with schizophrenia.

  10. Association between HLA-DRB1, HLA-DRQB1 alleles, and CD4(+)CD28(null) T cells in a Chinese population with coronary heart disease.

    Science.gov (United States)

    Sun, Wenjie; Cui, Ying; Zhen, Lihui; Huang, Lijuan

    2011-03-01

    CD4(+)CD28(null) T cells are present in increased numbers in the peripheral blood of patients with acute coronary syndrome. However, the triggers of expansion of these cells are unclear. Susceptibility to coronary heart disease (CHD) is strongly associated with alleles of human leukocyte antigen (HLA), but it is not equally strong in different human populations. The objective of the study was to investigate association between CD4(+)CD28(null) T cells and HLA-DRB1 alleles. The HLA alleles were determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) method, in a group of CHD patients and control subjects from the same area. The number of CD4(+)CD28(null) T cells was measured using the flow cytometry technique. The HLA-DRB1*01 (RR = 4.705, P Chinese population, and increased numbers of CD4(+)CD28(null) T cells were found in association with HLA-DRB1*04 (17.1%) and DRB*01 (12.9%), while decreased numbers of CD4(+)CD28(null) T cells were present in subjects with DRB1*15 (0.8%). CHD in Chinese population is strongly associated with HLA-DRB1*01 and DRB1*04 haplotypes, and formation of CD4(+)CD28(null) T cells was related to HLA-DRB1*01, DRB1*04, and DRB1*15 alleles.

  11. HLA class I and class II alleles and haplotypes in Mexican mestizos established from serological typing of 50 families.

    Science.gov (United States)

    De Leo, C; Castelan, N; Lopez, M; Gonzalez, N; Weckmann, A L; Melin-Aldana, H; Vargas-Alarcon, G; Bordes, J; Alarcon-Segovia, D; Granados, J; Ramirez, E; Lisker, R

    1997-12-01

    We describe new information on the frequency and association of class II antigens (HLA-DR and HLA-DQ) of the major histocompatibility complex (MHC) in Mexicans. The study includes HLA-B typing and its association with the HLA-DR antigens determined in 50 families, which included 100 individuals. This family study allowed the establishment of the precise composition of the 200 HLA haplotypes, which cannot be obtained from unrelated individuals. The predominant antigens in decreasing order of frequency were B35, B39, and B61 at the B locus; DR4, DR5, and DR8 at the DR locus; and DQ3 at the DQ locus. The most common HLA-B,HLA-DR haplotype (considering broad specificities) was B16,DR4, with a frequency of 8.0%. Five HLA-B,HLA-DR haplotypes showed significant delta values (observed vs. expected frequencies) after correcting for the number of comparisons. On the other hand, the most common HLA-DR,HLA-DQ haplotypes were DR4,DQ3 and DR5,DQ3 with a frequency higher than 10%. Ten of the 17 HLA-DR,HLA-DQ haplotypes had significant postcorrection delta values.

  12. The HLA-net GENE[RATE] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas.

    Science.gov (United States)

    Nunes, J M; Buhler, S; Roessli, D; Sanchez-Mazas, A

    2014-05-01

    In this review, we present for the first time an integrated version of the Gene[rate] computer tools which have been developed during the last 5 years to analyse human leukocyte antigen (HLA) data in human populations, as well as the results of their application to a large dataset of 145 HLA-typed population samples from Europe and its two neighbouring areas, North Africa and West Asia, now forming part of the Gene[va] database. All these computer tools and genetic data are, from now, publicly available through a newly designed bioinformatics platform, HLA-net, here presented as a main achievement of the HLA-NET scientific programme. The Gene[rate] pipeline offers user-friendly computer tools to estimate allele and haplotype frequencies, to test Hardy-Weinberg equilibrium (HWE), selective neutrality and linkage disequilibrium, to recode HLA data, to convert file formats, to display population frequencies of chosen alleles and haplotypes in selected geographic regions, and to perform genetic comparisons among chosen sets of population samples, including new data provided by the user. Both numerical and graphical outputs are generated, the latter being highly explicit and of publication quality. All these analyses can be performed on the pipeline after scrupulous validation of the population sample's characterisation and HLA typing reporting according to HLA-NET recommendations. The Gene[va] database offers direct access to the HLA-A, -B, -C, -DQA1, -DQB1, -DRB1 and -DPB1 frequencies and summary statistics of 145 population samples having successfully passed these HLA-NET 'filters', and representing three European subregions (South-East, North-East and Central-West Europe) and two neighbouring areas (North Africa, as far as Sudan, and West Asia, as far as South India). The analysis of these data, summarized in this review, shows a substantial genetic variation at the regional level in this continental area. These results have main implications for population genetics

  13. HLA-DRB1 alleles and HLA-DRB1 shared epitopes are markers for juvenile rheumatoid arthritis subgroups in Colombian mestizos.

    Science.gov (United States)

    Garavito, Gloria; Yunis, Edmond J; Egea, Eduardo; Ramirez, Luis A; Malagón, Clara; Iglesias, Antonio; De La Cruz, Oscar F; Uribe, Oscar; Navarro, Edgar; Martinez, Paz; Jaraquemada, Dolores

    2004-04-01

    We studied the association of human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 alleles and HLA haplotypes with juvenile rheumatoid arthritis (JRA) in 65 patients and 65 controls from Colombia. The JRA subsets were distinguished on the basis of criteria established by the American College of Rheumatology. Two alleles were associated with protection, HLA-DRB1*1501 (p = 0.002) and HLA-DRB1*1402 (p = 0.01). HLA-DRB1*1602 (p = 0.0000002) was associated with susceptibility for systemic JRA and HLA-DRB1*1104 (p = 0.0002) for pauciarticular JRA. Amino acid sequences at residues 70-74 of DRB1 chain shared by HLA-DRB1 alleles (shared epitomes) were also informative. The polyarticular JRA subset revealed association with (70)QRRAA(74), which includes HLA-DRB1*04, 01, and (70)DRRAA(74), which includes DRB1*1601, 1602, 1101, and 1104. Two new findings of interest were the association of the haplotypes DRB1*1104, DQB1*0301(p = 0.0002) with pauciarticular JRA and DRB1*1602, DQB1*0301 (p = 0.0000002) association with systemic JRA. The DRB1 alleles of these two haplotypes share the epitope (70)DRRAA(74)and were associated with both the pauciarticular and the systemic subset of JRA. Our results suggest that studies of disease susceptibility in populations of admixed genetic background should take into account the contribution of different ethnic groups or nationalities in the recruitment of controls and patients studied in order to rule out genetic stratification.

  14. HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats.

    Directory of Open Access Journals (Sweden)

    Osiris Marroquin Belaunzaran

    Full Text Available HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA. HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272 and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS patients and HLA-B27 transgenic rats. We characterized a novel B272-specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders.The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry.HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM. HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules.HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

  15. The production and crystallization of the human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 complexed with deamidated gliadin peptides implicated in coeliac disease

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Kate N.; Reid, Hugh H.; Borg, Natalie A.; Broughton, Sophie E.; Huyton, Trevor [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia); Anderson, Robert P. [Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3050 (Australia); Department of Gastroenterology, The Royal Melbourne Hospital, Grattan Street, Parkville, Victoria 3050 (Australia); McCluskey, James [Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010 (Australia); Rossjohn, Jamie, E-mail: jamie.rossjohn@med.monash.edu.au [The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800 (Australia)

    2007-12-01

    The production and crystallization of human leukocyte antigen class II molecules HLA-DQ2 and HLA-DQ8 in complex with deamidated gliadin peptides is reported. Crystals of HLA-DQ2{sup PQPELPYPQ} diffracted to 3.9 Å, while the HLA-DQ8{sup EGSFQPSQE} crystals diffracted to 2.1 Å, allowing structure determination by molecular replacement. The major histocompatibility complex (MHC) class II molecules HLA-DQ2 and HLA-DQ8 are key risk factors in coeliac disease, as they bind deamidated gluten peptides that are subsequently recognized by CD4{sup +} T cells. Here, the production and crystallization of both HLA-DQ2 and HLA-DQ8 in complex with the deamidated gliadin peptides DQ2 α-I (PQPELPYPQ) and DQ8 α-I (EGSFQPSQE), respectively, are reported.

  16. Software architecture and engineering for patient records: current and future.

    Science.gov (United States)

    Weng, Chunhua; Levine, Betty A; Mun, Seong K

    2009-05-01

    During the "The National Forum on the Future of the Defense Health Information System," a track focusing on "Systems Architecture and Software Engineering" included eight presenters. These presenters identified three key areas of interest in this field, which include the need for open enterprise architecture and a federated database design, net centrality based on service-oriented architecture, and the need for focus on software usability and reusability. The eight panelists provided recommendations related to the suitability of service-oriented architecture and the enabling technologies of grid computing and Web 2.0 for building health services research centers and federated data warehouses to facilitate large-scale collaborative health care and research. Finally, they discussed the need to leverage industry best practices for software engineering to facilitate rapid software development, testing, and deployment.

  17. Architecture humanitarian emergencies

    DEFF Research Database (Denmark)

    Gomez-Guillamon, Maria; Eskemose Andersen, Jørgen; Contreras, Jorge Lobos

    2013-01-01

    Introduced by scientific articles conserning architecture and human rights in light of cultures, emergencies, social equality and sustainability, democracy, economy, artistic development and science into architecture. Concluding in definition of needs for new roles, processes and education of arc......, Architettura di Alghero in Italy, Architecture and Design of Kocaeli University in Turkey, University of Aguascalientes in Mexico, Architectura y Urbanismo of University of Chile and Escuela de Architectura of Universidad Austral in Chile....

  18. Identification of HLA-G*01:17, a new allele possibly generated by an interloci gene conversion event involving exon 3 of HLA-B.

    Science.gov (United States)

    Czarnecki, Chris; Van Domselaar, Gary; Embreé, Joanne; Brunham, Robert; Plummer, Francis A; Luo, Ma

    2011-03-01

    HLA-G*01:17 was discovered in a woman of Kenyan descent who was enrolled in a mother-to-child HIV-1 transmission cohort. The new allele was identical to HLA-G*01:06 at exons 2, 3, and 4 with the exception of a base pair substitution at codon 169 (CAC → CGC) resulting in a coding change from histidine to arginine and codon 171 (TAC → CAC), resulting in turn in a coding change from tyrosine to histidine. The World Health Organization (WHO) Nomenclature Committee has named this allele HLA-G*01:17.

  19. A cis-eQTL of HLA-DRB1 and a frameshift mutation of MICA contribute to the pattern of association of HLA alleles with cervical cancer.

    Science.gov (United States)

    Chen, Dan; Gyllensten, Ulf

    2014-04-01

    The association of classic human leukocyte antigen (HLA) alleles with risk of cervical cancer has been extensively studied, and a protective effect has consistently been found for DRB1*1301, DQA1*0103, and/or DQB1*0603 (these three alleles are in perfect linkage disequilibrium [LD] and often occur on the same haplotype in Europeans), while reports have differed widely with respect to the effect of HLA-B*07, DRB1*1501, and/or DQB1*0602 (the last two alleles are also in perfect LD in Europeans). It is not clear whether the reported HLA alleles are responsible for the differences in cervical cancer susceptibility, or if functional variants at other locations within the major histocompatibility complex (MHC) region may explain the effect. In order to assess the relative contribution of both classic HLA alleles and single-nucleotide polymorphisms (SNPs) within the MHC region to cervical cancer susceptibility, we have imputed classic HLA alleles in 1034 cervical cancer patients and 3948 controls in a Swedish population for an integrated analysis. We found that the protective haplotype DRB1*1301-DQA1*0103-DQB1*0603 has a direct effect on cervical cancer and always occurs together with the C allele of a HLA-DRB1 cis-eQTL (rs9272143), which increases the expression of HLA-DRB1. The haplotype rs9272143C-DRB1*1301-DQA1*0103-DQB1*0603 conferred the strongest protection against cervical cancer (odds ratio [OR] = 0.41, 95% confidence interval [CI] = 0.32-0.52, P = 6.2 × 10(-13)). On the other hand, the associations with HLA-B*0702 and DRB1*1501-DQB1*0602 are attributable to the joint effects of both the HLA-DRB1 cis-eQTL (rs9272143) and a frameshift mutation (G inserion of rs67841474, also known as A5.1) of the MHC class I polypeptide-related sequence A gene (MICA). Variation in LD between the classic HLA loci, rs9272143 and rs67841474 between populations may explain the different associations of HLA-B*07 and DRB1*1501-DQB1*0602 with cervical cancer between studies. The

  20. Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: Unique clinical and HLA associations

    Science.gov (United States)

    Bowlus, Christopher L.; Li, Chin-Shang; Karlsen, Tom H.; Lie, Benedicte A.; Selmi, Carlo

    2010-01-01

    Primary sclerosing cholangitis (PSC) is well characterized in European populations. We aimed to characterize clinical characteristics and human leukocyte antigen (HLA) associations in a population of European American, Hispanic and African-American PSC patients listed for liver transplantation. Demographic, clinical, and HLA data stratified by population from 6,767 liver transplant (LT) registrants of the United Network for Organ Sharing (UNOS) with a diagnosis of PSC (4.7% of registrants) were compared to registrants with other diagnoses. Compared to European Americans and Hispanics, African American cases were significantly younger (46.6 ± 13.7, 42.3 ± 15.9, and 39.7 ± 13.1, respectively; p = 0.002), listed with a higher Model of End Stage Liver Disease (MELD) score (15.2 ± 7.5, 14.9 ± 7.6, and 18.1 ± 9.3, respectively; p = 0.001), and less frequently noted to have inflammatory bowel disease (71.4% versus 60.5%, p < 0.01) compared to European Americans. In multivariate analysis, African origin was a significant factor associated with listing for LT with PSC (OR relative to European Americans 1.33, 95% C.I. 1.27 – 1.41). HLA associations in European Americans, Hispanics and African Americans with PSC compared to alcoholic liver disease were detected for HLA-B8, HLA-DR13 and the protective HLA-DR4. However, HLA-DR3, which is in linkage disequilibrium with HLA-B8, only showed associations in European Americans and Hispanics. African Americans with PSC listed for LT differ clinically from European Americans and Hispanics. The association with HLA-B8 but not HLA-DR3 in African Americans should make possible the refinement of the HLA associations in PSC. PMID:21031548

  1. HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations

    Directory of Open Access Journals (Sweden)

    B.L. Liphaus

    2007-04-01

    Full Text Available Human leukocyte antigens (HLA DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.

  2. Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Feng, E-mail: jiangfeng1161@163.com [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Zhao, Hongxi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Wang, Li [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China); Guo, Xinyu [Assisted Reproductive Center, General Hospital of Guangzhou Military Command, Guangzhou 510010 (China); Wang, Xiaohong; Yin, Guowu [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Hu, Yunsheng [Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Li, Yi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Yao, Yuanqing, E-mail: yuanqingyaoxa@163.com [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China)

    2015-02-27

    Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions.

  3. Association of HLA-G 3' untranslated region variants with type 1 diabetes mellitus.

    Science.gov (United States)

    de Albuquerque, Rafael S; Mendes-Junior, Celso Teixeira; Lucena-Silva, Norma; da Silva, Camila Leal Lopes; Rassi, Diane Meire; Veiga-Castelli, Luciana C; Foss-Freitas, Maria Cristina; Foss, Milton César; Deghaide, Neifi Hassan Saloum; Moreau, Philippe; Gregori, Silvia; Castelli, Erick C; Donadi, Eduardo Antônio

    2016-04-01

    Besides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA-G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3' untranslated region (3'UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3'UTR-17 (14bpINS/+3001T/+3003T/+3010C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bpDEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA-G.

  4. IT Architecture For Dummies

    CERN Document Server

    Hausman, Kalani Kirk

    2010-01-01

    A solid introduction to the practices, plans, and skills required for developing a smart system architecture. Information architecture combines IT skills with business skills in order to align the IT structure of an organization with the mission, goals, and objectives of its business. This friendly introduction to IT architecture walks you through the myriad issues and complex decisions that many organizations face when setting up IT systems to work in sync with business procedures. Veteran IT professional and author Kirk Hausman explains the business value behind IT architecture and provides

  5. Towards a Media Architecture

    DEFF Research Database (Denmark)

    Ebsen, Tobias

    2010-01-01

    This text explores the concept of media architecture as a phenomenon of visual culture that describes the use of screen-technology in new spatial configurations in practices of architecture and art. I shall argue that this phenomenon is not necessarily a revolutionary new approach, but rather...... a result of conceptual changes in both modes visual representation and in expressions of architecture. These are changes the may be described as an evolution of ideas and consequent experiments that can be traced back to changes in the history of art and the various styles and ideologies of architecture....

  6. Grid Architecture 2

    Energy Technology Data Exchange (ETDEWEB)

    Taft, Jeffrey D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-01-01

    The report describes work done on Grid Architecture under the auspices of the Department of Electricity Office of Electricity Delivery and Reliability in 2015. As described in the first Grid Architecture report, the primary purpose of this work is to provide stakeholder insight about grid issues so as to enable superior decision making on their part. Doing this requires the creation of various work products, including oft-times complex diagrams, analyses, and explanations. This report provides architectural insights into several important grid topics and also describes work done to advance the science of Grid Architecture as well.

  7. Elements of Architecture

    DEFF Research Database (Denmark)

    Elements of Architecture explores new ways of engaging architecture in archaeology. It conceives of architecture both as the physical evidence of past societies and as existing beyond the physical environment, considering how people in the past have not just dwelled in buildings but have existed...... and affective impacts, of these material remains. The contributions in this volume investigate the way time, performance and movement, both physically and emotionally, are central aspects of understanding architectural assemblages. It is a book about the constellations of people, places and things that emerge...

  8. Analysis of the HLA-DPB1 Allelic Polymorphism in Neuromyelitis Optica Patients%视神经脊髓炎患者HLA-DPB1等位基因多态性的研究

    Institute of Scientific and Technical Information of China (English)

    单岩东; 张昆南; 王朝东; 高幼奇; 熊英琼; 谢旭芳; 吴晓牧

    2008-01-01

    目的 探讨视神经脊髓炎(neuromyelitis optica,NMO)患者人类白细胞抗原(HLA)-DPB1等位基因的多态性.方法 采用基于测序的分型方法(sequence-based typing,SBT)分析13例NMO患者的HLA-DPB1等位基因的多态性.结果 13例NMO患者中共检测到6种HLA-DPB1等位基因片段.HLA-DPB1*0501的频率显著高于HLA-DPB1*0201、HLA-DPB1*0202、HLA-DPB1*0301、HLA-DPB1*1301、HLA-DPB1*2101(P<0.05).结论 在NMO患者的HLA-DPB1等位基因多态性的研究中,HLA-DPB1*0501的频率显著高于其他,推测HLA-DPB1*0501可能与NMO的易患性有关.

  9. The diversity of the HLA-E-restricted peptide repertoire explains the immunological impact of the Arg107Gly mismatch.

    Science.gov (United States)

    Celik, Alexander A; Kraemer, Thomas; Huyton, Trevor; Blasczyk, Rainer; Bade-Döding, Christina

    2016-01-01

    Human leukocyte antigen (HLA)-E molecules are potent inhibitors of NK cell-mediated killing. Low in polymorphisms, two alleles are widely expressed among diverse populations: HLA-E*01:01 and HLA-E*01:03. Both alleles are distinguished by one SNP resulting in the substitution Arg107Gly. Both alleles present a limited set of peptides derived from class I leader sequences physiologically; however, HLA-E*01:01 presents non-canonical peptides in the absence of HLA class I molecules. To further assess the functional differences between both alleles, we analyzed the peptide repertoire of HLA-E*01:03 by applying soluble HLA technology followed by mass-spectrometric peptide sequencing. HLA-E*01:03 restricted peptides showed a length of 9-17 amino acids and differed in their biophysical properties, no overlap in the peptide repertoire of both allelic variants could be observed; however, both alleles shared marginal peptides from the same proteomic content. Artificial APCs expressing empty HLA-E*01:01 or E*01:03 molecules were generated and stabilized using cognate HLA class I-derived peptide ligands to analyze the impact of residue 107 within the HLA-E heavy chain on the NKG2/CD94 receptor engagement. Differences in peptide stabilization could be translated to the density and half-life time of peptide-HLA-E molecules on the cell surface that subsequently impacted NK cell inhibition as verified by cytotoxicity assays. Taken together, these data illustrate functional differences of HLA-E allelic variants induced by a single amino acid. Furthermore, the function of HLA-E in pathophysiologic situations when the HLA processing machinery is interrupted seems to be more emphasized than previously described, implying a crucial role for HLA-E in tumor or viral immune episodes.

  10. Results of kidney transplantation in relation to HLA-A, B, DR matching and quality of donor organ.

    Science.gov (United States)

    Lenhard, V; Dreikorn, K; Röhl, L

    1980-01-01

    The influence of HLA compatibility as well as immediate postoperative function on survival rates was investigated in 203 cadaver kidney transplants. HLA compatibility, especially DR compatibility, improved transplant survival significantly. A direct correlation was found between primary transplant function and long-term results. HLA compatibility and quality of the donor organ had a cumulative effect on kidney transplant survival. Our results are a further indication that besides HLA compatibility, optimal quality of donor organs has crucial significance for the results of transplantation.

  11. Residues Met76 and Gln79 in HLA-G α1 domain involved in KIR2DL4 recognition

    Institute of Scientific and Technical Information of China (English)

    Wei Hua YAN; Li An FAN

    2005-01-01

    Human leukocyte antigen-G (HLA-G) has long been speculated as a beneficial factor for a successful pregnancy for its restricted expression on fetal-maternal extravillous cytotrophoblasts and its capability of modulating uterine natural killer cell (uNK) function such as cytotoxicity and cytokine production through NK cell receptors. HLA class I α1domain is an important killer cell Ig-like receptor (KIR) recognition site and the Met76 and Gln79 are unique to HLA-G in this region. NK cell receptor KIR2DL4 is a specific receptor for HLA-G, yet the recognition site on HLA-G remains unknown. In this study, retroviral transduction was applied to express the wild type HLA-G (HLA-wtG), mutant HLA-G (HLA-mG) on the chronic myelogenous leukemia cell line K562 cells and KIR2DL4 molecule on NK-92 cells,respectively. KIR2DL4-IgG Fc fusion protein was generated to determine the binding specificity between KIR2DL4and HLA-G. Our results showed that residue Met76, Gln79 mutated to Ala76,79 in the α1 domain of HLA-G protein could affect the binding affinity between KIR2DL4 and HLA-G, meanwhile, the KIR2DL4 transfected NK-92 cells (NK-92-2DL4) showed a considerably different cytolysis ability against the HLA-wtG and HLA-mG transfected K562 targets.Taken together, our data indicated that residue Met76 and Gln79 in HLA-G α1 domain plays a critical role in the recognition of KIR2DL4, which could be an explanation for the isoforms of HLA-G, all containing the α1 domain, with the potential to regulate NK functions.

  12. Preformed Donor HLA-DP-Specific Antibodies Mediate Acute and Chronic Antibody-Mediated Rejection Following Renal Transplantation

    OpenAIRE

    Jolly, E. C.; Key, T; H. Rasheed; Morgan, H; Butler, A; Pritchard, N.; Taylor, C J; Clatworthy, M. R.

    2012-01-01

    Donor-specific HLA alloantibodies may cause acute and chronic antibody-mediated rejection (AMR) and significantly compromise allograft survival. The clinical relevance of antibodies directed against some HLA class II antigens, particularly HLA-DP, is less clear with conflicting reports on their pathogenicity. We report two patients with high levels of pretransplant donor-specific HLA-DP antibodies who subsequently developed recurrent acute AMR and graft failure. In both cases, there were no o...

  13. On Detailing in Contemporary Architecture

    DEFF Research Database (Denmark)

    Kristensen, Claus; Kirkegaard, Poul Henning

    2010-01-01

    / tactility can blur the meaning of the architecture and turn it into an empty statement. The present paper will outline detailing in contemporary architecture and discuss the issue with respect to architectural quality. Architectural cases considered as sublime piece of architecture will be presented...

  14. HLA analysis in patients with degenerative diseases of the temporomandibular joint.

    Science.gov (United States)

    Learreta, Jorge A; Bono, Andrea E; Durst, Andreas C

    2011-01-01

    The aim of this study was to determine the presence of HLA alleles, specifically HLA-DR alleles, and to correlate them with clinical and radiological features of patients with degenerative processes (DP) of the temporomandibular joint (TMJ). The final goal was to determine which allele can be used to identify patients having more aggressive forms of the articular pathologies. Thirty-two (32) Caucasian patients with DP of the TMJ were included in the study. The SSOP (Luminex Corp., Austin, TX) method was used to determine class II HLA alleles. The presence of HLA-II DR in patients with DP of the TMJ was 98%. The presence of HLA was significantly higher in patients with DP of the TMJ than in healthy subjects (66%) (p=0.003). HLA DR52 was significantly more frequent in patients than in healthy individuals (40.62% vs. 13.79%, p = 0.041). While the percentage of DR11 positive individuals was also higher among patients than among healthy control subjects, the association with DP of the TMJ was not significant (p=0.220). Patients having the DR52 allele had higher deformation or DP. It was concluded that HLA-DR54 and DR11 alleles are associated with a higher susceptibility to DP of the TMJ, and HLA-DR54 and DR52 are associated with a higher severity of DP.

  15. Identification of multiple independent susceptibility loci in the HLA region in Behcet's disease

    NARCIS (Netherlands)

    Hughes, Travis; Coit, Patrick; Adler, Adam; Yilmaz, Vuslat; Aksu, Kenan; Duzgun, Nursen; Keser, Gokhan; Cefle, Ayse; Yazici, Ayten; Ergen, Andac; Alpsoy, Erkan; Salvarani, Carlo; Casali, Bruno; Koetter, Ina; Gutierrez-Achury, Javier; Wijmenga, Cisca; Direskeneli, Haner; Saruhan-Direskeneli, Guher; Sawalha, Amr H.

    2013-01-01

    Behcet's disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B*51 and Behcet's disease and exploring additional susceptibility loci in the human leukocyte antigen (HLA) region are comp

  16. A statistical framework for modeling HLA-dependent T cell response data.

    Directory of Open Access Journals (Sweden)

    Jennifer Listgarten

    2007-10-01

    Full Text Available The identification of T cell epitopes and their HLA (human leukocyte antigen restrictions is important for applications such as the design of cellular vaccines for HIV. Traditional methods for such identification are costly and time-consuming. Recently, a more expeditious laboratory technique using ELISpot assays has been developed that allows for rapid screening of specific responses. However, this assay does not directly provide information concerning the HLA restriction of a response, a critical piece of information for vaccine design. Thus, we introduce, apply, and validate a statistical model for identifying HLA-restricted epitopes from ELISpot data. By looking at patterns across a broad range of donors, in conjunction with our statistical model, we can determine (probabilistically which of the HLA alleles are likely to be responsible for the observed reactivities. Additionally, we can provide a good estimate of the number of false positives generated by our analysis (i.e., the false discovery rate. This model allows us to learn about new HLA-restricted epitopes from ELISpot data in an efficient, cost-effective, and high-throughput manner. We applied our approach to data from donors infected with HIV and identified many potential new HLA restrictions. Among 134 such predictions, six were confirmed in the lab and the remainder could not be ruled as invalid. These results shed light on the extent of HLA class I promiscuity, which has significant implications for the understanding of HLA class I antigen presentation and vaccine development.

  17. Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides

    DEFF Research Database (Denmark)

    Pedersen, Sara Ram; Christensen, Jan Pravsgaard; Buus, Søren;

    2016-01-01

    The aim of the present study was to identify influenza A-derived peptides which bind to both HLA class I and -II molecules and by immunization lead to both HLA class I and class II restricted immune responses. Eight influenza A-derived 9-11mer peptides with simultaneous binding to both HLA-A*02......:01 and HLA-DRB1*01:01 molecules were identified by bioinformatics and biochemical technology. Immunization of transgenic HLA-A*02:01/HLA-DRB1*01:01 mice with four of these double binding peptides gave rise to both HLA class I and class II restricted responses by CD8 and CD4 T cells, respectively, whereas...... with this, peptide vaccination did not decrease virus titres in the lungs of intranasally influenza challenged mice. Our data show that HLA class I and class II double binding peptides can be identified by bioinformatics and biochemical technology. By immunization, double binding peptides can give rise...

  18. Stimulation of HIV-specific T cell clonotypes using allogeneic HLA.

    Science.gov (United States)

    Almeida, Coral-Ann; van Miert, Paula; O'Driscoll, Kane; Zoet, Yvonne M; Chopra, Abha; Watson, Mark; de Santis, Dianne; Witt, Campbell; John, Mina; Claas, Frans H J; D'Orsogna, Lloyd J

    2017-03-28

    We hypothesized that HIV-specific CD8 T cell clonotypes can be stimulated by allogeneic HLA molecules. Multiple HIV-specific CD8 T cell clones were derived from 12 individuals with chronic HIV infection, specific for 13 different HIV Gag antigens and restricted to 7 different HLA molecules. The generated T cell clones were assayed for alloreactivity against a panel of single HLA class I expressing cell lines (SALs). HIV-specific T cells recognising at least one allogeneic HLA molecule could be identified from 7 of 12 patients tested. Allorecognition was associated with IFNγ cytokine production, CD137 upregulation and cytotoxicity, suggesting high avidity allo-stimulation. Allo-HLA recognition by HIV-specific T cells was specific to the HIV target peptide/HLA restriction and TCR TRBV usage of the T cells. HIV-specific T cells do crossreact against allogeneic HLA molecules in an epitope and TRBV specific manner. Therefore allo-HLA stimulation could be exploited to induce or augment HIV-specific T cell responses.

  19. Mapping of HLA- DQ haplotypes in a group of Danish patients with celiac disease

    DEFF Research Database (Denmark)

    Lund, Flemming; Hermansen, Mette N; Pedersen, Merete F

    2015-01-01

    BACKGROUND: A cost-effective identification of HLA- DQ risk haplotypes using the single nucleotide polymorphism (SNP) technique has recently been applied in the diagnosis of celiac disease (CD) in four European populations. The objective of the study was to map risk HLA- DQ haplotypes in a group...

  20. A major non-HLA locus in celiac disease maps to chromosome 19.

    NARCIS (Netherlands)

    Belzen, van MJ; Meijer, JW; Sandkuijl, L.A.; Bardoel, A.F.; Mulder, C.J.J.; Pearson, PL; Houwen, RH; Wijmenga, C.

    2003-01-01

    BACKGROUND AND AIMS: The pathogenesis of celiac disease is still unknown despite its well-known association with human leukocyte antigen (HLA)-DQ2 and DQ8. It is clear that non-HLA genes contribute to celiac disease development as well, but none of the previous genome-wide screens in celiac disease

  1. Associations of HLA-A, -B and -DRB1 types with oral diseases in Swiss adults.

    Directory of Open Access Journals (Sweden)

    Matti Mauramo

    Full Text Available Human leukocyte antigens (HLA are crucial components of host defense against microbial challenge but the associations of HLA types with oral infectious diseases have not been studied in detail. This prospective cross-sectional study examined associations of HLA-A, -B and -DRB1 types with common oral diseases in a healthy Swiss adult population. 257 subjects (107 m, 150 f, mean age: 43.5 yr; range: 21-58 yr with known HLA-A, -B and -DRB1 profiles and comprehensive medical records were included. A thorough anamnesis was followed by oral examinations including saliva flow measurements, the DMFT score for cariological status, complete periodontal status with plaque and bleeding indexes as well as assessment of mucosal alterations and temporomandibular dysfunction (TMD. Student's t-test and Pearson chi-square test were utilized to compare the oral diseases between HLA positive and negative subjects. Bonferroni correction for multiple comparisons was used and PBonf<0.05 was considered statistically significant. HLA types -B15 (PBonf = 0.002, -B51 (PBonf = 0.02 and -DRB1*12 (PBonf = 0.02 were associated with less periodontal disease manifestations. HLA-A32 had a positive association with TMD dysfunction (PBonf = 0.012. No other statistically significant associations were observed. In conclusion, HLA types may contribute to the development of oral diseases in generally healthy Caucasian adults.

  2. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study.

    Science.gov (United States)

    Ovsyannikova, Inna G; Pankratz, V Shane; Salk, Hannah M; Kennedy, Richard B; Poland, Gregory A

    2014-09-01

    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.

  3. Shift in expression of HLA-G mRNA spliceforms in pregnancies complicated by preeclampsia.

    NARCIS (Netherlands)

    Emmer, P.M.; Joosten, I.; Schut, M.H.; Zusterzeel, P.L.M.; Hendriks, J.C.M.; Steegers, E.A.P.

    2004-01-01

    OBJECTIVE: Despite emerging data on the in vitro modulatory effects of trophoblast-associated human leukocyte antigen G (HLA-G), its in vivo function needs to be determined. Immunohistochemical studies show a decrease in protein expression of trophoblast HLA-G in preeclampsia. Such a decrease in pro

  4. HLA-G5 and G7 Isoforms in Pregnant Women.

    Directory of Open Access Journals (Sweden)

    Saeid Abediankenari

    2015-04-01

    Full Text Available Human leukocyte antigen-G which is an immune tolerance effecter molecule has an important role in the maintenance of fetus during pregnancy. Abortion is one of the complications of pregnancy period.  In this research, we have studied levels of HLA-G 5, HLA-G7 isoforms in the abortion-threatened pregnant women in comparison with controls. In a case-control study, 101 abortion-threatened women and 101 healthy pregnant women (healthy controls with age range 21-32 years were studied. Gene expression of HLA-5 and HLA-7 isoforms was analyzed by real-time polymerase chain reaction after mRNA extraction and cDNA synthesis. The results indicated that HLA-G5 was significantly lower in abortion-threatened women in comparison with the control group whereas HLA-G7 was not significantly differentbetween the 2 groups. HLA-G is a vital molecule during pregnancy that can be a key factor in prevention of abortion. It is concluded that determination of HLA-G5 can be of value in pregnancy.

  5. Signal transduction by HLA class II antigens expressed on activated T cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Martin, P J; Schieven, G L;

    1991-01-01

    Human T cells express HLA class II antigens upon activation. Although activated, class II+ T cells can present alloantigens under certain circumstances, the functional role of class II antigens on activated T cells remains largely unknown. Here, we report that cross-linking of HLA-DR molecules ex...

  6. A monoclonal antibody that recognizes an antigenic determinant shared by HLA A2 and B17.

    Science.gov (United States)

    McMichael, A J; Parham, P; Rust, N; Brodsky, F

    1980-09-01

    A hybridoma monoclonal anti-HLA antibody has been produced by the technique of Kohler and Milstein [1]. This antibody recognizes a new specificity common to HLA A2 and B17. It was shown to be a single antibody by isoelectric focusing and absorption experiments.

  7. HLA-DRB1 alleles genotyping in patients with rheumatoid arthritis in Chinese.

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    Objective: To explore the role of HLA-DRB1 genes in the development of rheumatoid arthritis (RA) and the correlations between HLA-DR alleles and clinical manifestations of patients with RA. Methods: 86 patients and 106 race matched controls in whom HLADR typing was performed by the method of DNA amplification with sequence-specific primers (PCR-SSP)

  8. HLA-DRB1 ALLELES GENOTYPING IN PATIENTS WITH RHEUMATOID ARTHRITIS IN CHINESE

    Institute of Scientific and Technical Information of China (English)

    赵岩; 董怡; 朱席林; 邱长春

    1996-01-01

    Objective. To explore the role of HLA-DRB1 genes in the development of rheumatoid arthritis(RA) and the correlations between HLA-DR alleles and clinical manifestations of patients with RA.Methods. 86 patients with rheumatoid arthritis and 106 race matched controls were studied in whom HLA-DR typing was perfomed by the method of DNA amplification with sequence-specific primers(PCR-SSP). The subtypes of HLA-DR4 were determined by the method of hybridization of PCR products with sequence-specific oligonucletides(PCR SSO). The absence or presence of the patients.Results.Compared with controls,an increased gene frequency of HLA-DR4(48.8% vs 17.9%,P<0.001) and a decreased frequency of HLA-DR7(16.3% vs 27.4%,P=0.06) were found.The DRB1 0405 account for 61.9% of DR4+RA patients with respect to age,sex,duration of disease,rheumatoid factor(RF),extra-articular manifestations including secondary Sjogren's syndrome.According to the wrisr X-ray stage,the patlents of DR4+were more severe than that of DR4-P(P<0.05).Conclusion.HLA-DR4 and DR4 subtype of DRB1 0405 are related to the development of RA in Chinese.HLA-DR4 can be a useful prognosric marker in the patients with RA.

  9. Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases

    NARCIS (Netherlands)

    Lenz, Tobias L; Deutsch, Aaron J; Han, Buhm; Hu, Xinli; Okada, Yukinori; Eyre, Stephen; Knapp, Michael; Zhernakova, Alexandra; Huizinga, Tom W J; Abecasis, Gonçalo; Becker, Jessica; Boeckxstaens, Guy E; Chen, Wei-Min; Franke, Andre; Gladman, Dafna D; Gockel, Ines; Gutierrez-Achury, Javier; Martin, Javier; Nair, Rajan P; Nöthen, Markus M; Onengut-Gumuscu, Suna; Rahman, Proton; Rantapää-Dahlqvist, Solbritt; Stuart, Philip E; Tsoi, Lam C; van Heel, David A; Worthington, Jane; Wouters, Mira M; Klareskog, Lars; Elder, James T; Gregersen, Peter K; Schumacher, Johannes; Rich, Stephen S; Wijmenga, Cisca; Sunyaev, Shamil R; de Bakker, Paul I W; Raychaudhuri, Soumya

    2015-01-01

    Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the

  10. IMPORTANCE OF RESEARCH HLA ANTIBODIES CLASS I AND II, AND MICA ANTIBODIES IN KIDNEY TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutia

    2011-01-01

    Full Text Available The purpose of this study was to investigate the occurrence of HLA and MICA antibodies in patients from the waiting list for kidney transplantation and their influence on the course of post-transplant period. Determination of HLA antibodies class I and II, and MICA antibodies was performed on a platform of Luminex (xMAP-tech- nology using sets LABScreen ONE LAMBDA (U.S.. A total of 156 patients from the waiting list for kidney transplantation. Revealed the presence of HLA and MICA antibodies in the serum of 31.4% of patients. Regraf- ted patients increased the content of antibodies to the antigens of HLA system was noted in 88.2% of cases, 47% met the combination of antibodies to the I, II classes and MICA. In patients awaiting first kidney transplantation, HLA and MICA antibodies were determined in 23.7% of cases. The presence of pretransplant HLA and MICA antibodies had a significant influence on the course of post-transplant period. Patients with the presence of HLA and MICA in 50% of cases delayed graft function. Sessions of plasmapheresis can reduce the concentration of HLA and MICA antibodies on average by 61.1%. 

  11. The outcome of thirteen patients with nonmalignant hematologic diseases treated with HLA haploidentical stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    陶媛

    2014-01-01

    Objective To evaluate the clinical efficacy and safety of human leukocyte antigen(HLA)haploidentical stem cell transplantation in nonmalignant hematologic diseases.Methods To analyze the outcome of 13 patients with nonmalignant hematologic diseases who underwent HLA haploidentical stem cell transplantation from September

  12. HLA-A gene polymorphisms contribute to osteoporosis susceptibility in postmenopausal Han Chinese women.

    Science.gov (United States)

    Li, S M; Guo, H; Yang, H J; Lv, M Q; Zhou, D X

    2015-08-28

    Osteoporosis is a common disease characterized by low bone mineral density, deterioration in bone microarchitecture, and increased fracture risk and is more prevalent in postmenopausal women. HLA is a complex gene family; previous studies have shown that it plays an important role in the pathogenesis of osteoporosis among Japanese and Greek populations. Prompted by these findings, this study was designed to explore the associations between HLA-A gene polymorphisms and postmenopausal osteoporosis in the Han Chinese population. The polymerase chain reaction-sequence-based typing method was used for DNA genotyping at the HLA-A locus in 70 patients with postmenopausal osteoporosis and 73 healthy controls. We identified 17 HLA-A alleles in patients with postmenopausal osteoporosis and 20 HLA-A alleles in control subjects. Furthermore, we found that the frequency of the HLA-A* 02:07 allele was significantly higher in patients with postmenopausal osteoporosis than in control subjects (P = 0.023), and the relative risk was 4.065 (95% confidence interval = 1.109-14.893). Our study provides supportive evidence for the contribution of HLA-A gene polymorphisms to the susceptibility to postmenopausal osteoporosis and suggests that HLA-A* 02:07 is likely an important genetic risk factor for postmenopausal osteoporosis in the Han Chinese population.

  13. HLA class I homologous transcripts in the human embryonal carcinoma cell line Tera-2.

    Science.gov (United States)

    Rinke de Wit, T F; Struyk, L; Vloemans, S; Glazebrook, J; Boyle, J M; Stern, P L; van den Elsen, P J

    1990-01-01

    We have used the human teratocarcinoma-derived embryonal carcinoma cell line Tera-2 cl. 13 to explore the putative expression of novel HLA class I(-like) genes. Serological analyses revealed that Tera-2 cells do not express polymorphic HLA class I (-A, -B, -C) specificities, but do express HLA class I-like antigens. These phenotypic properties parallel those of certain mouse embryonal carcinoma cells. To study the expression of HLA class I(-like) genes in the Tera-2 cells two different approaches were used. Screening of a Tera-2 cDNA library with a full-length HLA class I cDNA probe under conditions that would allow for the identification of relatively distinct HLA class I-like sequences yielded 27 positive clones, all of which were of the regular HLA-A, -B, -C type. Reverse northern hybridizations of the restriction enzyme-digested Tlab region comprising cosmids with Tera-2 cDNA as the probe resulted in the identification of several putative human genes whose equivalents map within the mouse Tla region. However, none of these genes appeared to be structurally related to HLA class I. A putative H3.3 histone gene was identified in the proximal Tla region of the C57BL/10 mouse. It is concluded that no structural homologues of mouse Qa/Tla genes are expressed in the human developmental cell line Tera-2.

  14. Human monoclonal HLA antibodies reveal interspecies crossreactive swine MHC class I epitopes relevant for xenotransplantation.

    NARCIS (Netherlands)

    Mulder, A.; Kardol, M.J.; Arn, J.S.; Eijsink, C.; Franke, M.E.; Schreuder, G.M.; Haasnoot, G.W.; Doxiadis, I.I.; Sachs, D.H.; Smith, D.M.; Claas, F.H.

    2010-01-01

    Crossreactivity of anti-HLA antibodies with SLA alleles may limit the use of pig xenografts in some highly sensitized patients. An understanding of the molecular basis for this crossreactivity may allow better selection of xenograft donors. We have tested 68 human monoclonal HLA class I antibodies (

  15. HLA-DP antigens are involved in the susceptibility to multiple sclerosis

    DEFF Research Database (Denmark)

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

    1988-01-01

    Forty-five unrelated patients with multiple sclerosis (MS) from Sweden and 166 Danish controls were typed for HLA-DP using Primed Lymphocyte Typing. Thirty-nine MS-patients and 63 controls were also DNA-typed with the Restriction Fragment Length Polymorphism (RFLP) technique for HLA-DP and -DR ge...

  16. Increased frequency of HLA-DPw2 in pauciarticular onset juvenile chronic arthritis

    DEFF Research Database (Denmark)

    Ødum, Niels; Morling, Niels; Friis, J;

    1986-01-01

    Thirty-six unrelated Danish patients with pauciarticular Juvenile Chronic Arthritis (PJCA) and 120 controls were typed for HLA-DPw1-w6 and the local specificity CDPHEI with bulk-expanded Primed Lymphocyte Typing (PLT) cells. The frequency of HLA-DPw2 was 52.8% in PJCA patients and 16.7% in contro...

  17. Genome-wide association study identifies new HLA class II haplotypes strongly protective against narcolepsy

    DEFF Research Database (Denmark)

    Hor, Hyun; Kutalik, Zoltán; Dauvilliers, Yves;

    2010-01-01

    Narcolepsy is a rare sleep disorder with the strongest human leukocyte antigen (HLA) association ever reported. Since the associated HLA-DRB1*1501-DQB1*0602 haplotype is common in the general population (15-25%), it has been suggested that it is almost necessary but not sufficient for developing ...

  18. Adult onset spinocerebellar ataxia linked to HLA in a South African kindred of mixed ancestry.

    Science.gov (United States)

    Bryer, A; Martell, R W; du Toit, E D; Beighton, P

    1992-09-01

    Hereditary spinocerebellar ataxia (SCA) is a relatively common disorder in the Western Cape region of South Africa. At present there are no genetic markers available for prenatal or presymptomatic diagnosis. A large kindred of mixed ancestry with late onset SCA was studied in which the disorder segregated in an autosomal dominant fashion. HLA typing was undertaken on 44 family members, and the HLA haplotypes were assigned on the basis of segregation. The LIPED computer program, with a correction factor allowing for the age of onset, was used to analyze the pedigree for linkage to HLA. Of 22 individuals in whom disease status could be definitely assessed, only one recombinant between HLA and the SCA locus occurred. The lod score reached a maximum of 4.13 at a recombination fraction of 0.05, indicating the odds to be approximately 13,500 to 1 in favor of linkage between HLA and the putative disease allele for SCA. A possible recombination within the HLA region suggested that the disease allele lies telomeric of the HLA region. In view of the recent demonstration of tight linkage between SCA1 and D6S89, however, HLA should not be used for presymptomatic diagnosis or genetic counselling.

  19. HLA class I and class II associations with ESRD in Saudi Arabian population.

    Directory of Open Access Journals (Sweden)

    Nuha Mahmoud Hamdi

    Full Text Available BACKGROUND: Chronic renal failure (CRF leads in the majority of instances to end stage renal disease (ESRD requiring renal replacement therapy. Our interest was to evaluate the possible associations of HLA class I and class II antigens with ESRD independent of other factors, in Saudi Arabia population. METHODOLOGY: A retrospective study to determine the HLA class I and class II polymorphisms and their association with ESRD, was performed on 350 patients with ESRD, and 105 healthy unrelated control. Patients and control groups were typed by SSOP lumenix techniques. The alleles positively associated to the ESRD were: HLA-B*15, B*18, B*49 - DRB1*03, negatively associated alleles were A*26, HLA-B*39, B*50. The haplotypes positively associated with ESRD were: HLA-A*01-DRB1*13 and HLA-A*30-DRBI*03. The negatively associated haplotypes were: HLA-A*02-B*39, A*02-B*50, A*24-B*35, A*24-B*58, A*24-DRB1*16, A*68-DRB1*04, A*02-DQB1*03, A*29-DQB1*02, A*29-DOB1*05 and B*27-DRB1*07 and the last one is the most significant protective haplotypes. CONCLUSION: The high Relative Risk (RR observed and its statistical correlation reflect the strength of the described association between HLA antigens and ESRD.

  20. Role of microRNAs on HLA-G expression in human tumors.

    Science.gov (United States)

    Seliger, Barbara

    2016-09-01

    The non-classical human leukocyte antigen G (HLA-G) known to protect the embryo from immune cell destruction leading to fetal maternal tolerance is often overexpressed in human tumors of distinct origin thereby leading to an escape from T and NK cell-mediated immune response. The molecular mechanisms controlling HLA-G expression are complex and involve deregulation at the transcriptional, epigenetic and posttranscriptional level. Using bioinformatics and high through put analyses a number of microRNAs (miRs) have been identified, which were able to bind to the 3' UTR of HLA-G with distinct efficacy. This caused by a downregulation of HLA-G surface expression, which was associated with an increased immune response thereby overcoming the HLA-G-mediated immune tolerance. Reduced expression of HLA-G-specific miRs was associated with tumor progression and metastases and appear to affect directly or indirectly tumor characteristics, such as cell proliferation, apoptosis and resistance to chemotherapy. Recently, an interaction between long non-coding RNAs, such as HOTAIR, and HLA-G-specific miRs has also been demonstrated. This review summarizes the control of HLA-G expression and function by microRNAs as well as its clinical significance.

  1. HLA-DP antigens in patients with chronic autoimmune thrombocytopenia (AITP)

    DEFF Research Database (Denmark)

    Mueller-Eckhardt, G; Pawelec, G; Haas, R;

    1989-01-01

    AITP, a disease with well-defined autoimmune character, has been previously studied for a possible HLA association. However, no such association with antigens of the A, B, C or DR loci was found. As this does not exclude a possible association with HLA-DP antigens, we have investigated 36 patients...

  2. Association of HLA-DRB1, DQB1 Alleles with Chronic Urticaria

    Institute of Scientific and Technical Information of China (English)

    CHEN Jing; TAN Zhijian; LI Jiawen; XIONG Ping

    2005-01-01

    Summary: In order to investigate the association of genotypes of HLA-DRB1 and HLA-DQB1 alleles with the genetic susceptibility of chronic urticaria (CU), genotypes of HLA-DRB1 and HLA-DQB1 genes were detected by polymerase chain reactions with sequence-specific primers (PCR-SSP) in 42 patients with CU (19 men and 23 women, mean age 30.67±12.45 y old as well as 193 racially matched healthy persons in ethnic Han from Hubei provinece. Gene frequencies of HLA-DRB1*12, *0901 (RR=3.11, χ2=7.579, P=0.006; RR=2.47, χ2=5.684, P=0.017) were significantly increased in CU patients as compared with that in healthy people. Gene frequencies of HLA-DQB1*05 (RR=0.26, χ2=6.683, P=0.01) were significantly decreased in CU patients. It was suggested that CU was found strongly associated with HLA-DRB1*12, *0901 and HLA-DQB1*05, the former might be the genetic markers for susceptibility to CU, but the latter might play a resistive role.

  3. A Group Training System of Command and Drive Simulators of Certain Type Airplane Based on HLA%基于HLA的某型飞机指挥驾驶模拟器组训系统

    Institute of Scientific and Technical Information of China (English)

    林亚军; 王述运; 周晓光; 谷树山

    2012-01-01

    为解决多飞行训练模拟器与飞行训练指挥模拟器互联的复杂仿真任务问题,设计一种基于高层体系结构(high level architecture,HLA)的模拟器组训系统.以某型飞机飞行训练模拟器、飞行指挥训练模拟器为基础,提出多飞行训练模拟器与飞行训练指挥模拟器组训系统的结构,在原有平台的基础上,采用HLA/RTI作为其体系结构和支撑平台,对飞行指挥训练模拟器进行升级改造,实现了4种气象条件下各个飞行科目的模拟飞行日训练.仿真结果表明:该系统能减少实装损耗,保障飞行安全,具有较高的军事经济价值.%In order to solve the complex simulation mission of netting many fight simulators with command simulator, the paper studied and designed a new group training system of simulator based on high level architecture (HLA). Based on certain type airplane simulator and flight command simulator, the system structure of group training system by netting many current fight simulators with a current command simulator is presented. By adopting HLA/RTI as system structure and support platform, and upgrading the command and training simulator, the group training system can carry out each flight subject in four kinds of weather conditions. The simulation result shows that the system can reduce the wastage of actual equipment and ensure the flight security, has important military training value.

  4. Association between HLA-B51 alleles and Behcet's disease in Chinese Han nationality%HLA-B51与白塞病相关性研究

    Institute of Scientific and Technical Information of China (English)

    李晓建; 陈明华; 郑志忠

    2009-01-01

    Objective To investigate the possible association between HLA-B51 alleles and Behcet's disease (BD). Methods Totally, 61 Chinese patients of Han nationality, who were diagnosed with BD according to the International Study Group (ISG) criteria, were recruited. The control cohort consisted of 100 healthy individuals. Blood samples were obtained from all the subjects. PCR-sequenee specific primers (SSPs) were used to for the genotyping of HLA-B51 alleles (HLA-B5101-HLA-B5109). Results Com- pared with the control group (11 positive, 11% ), the frequency of HLA-B51 (18 positive, 29.5% ) was sig- nificantly increased in BD patients (χ2=8.79, P<0.01, RR=3.39). The HLA-B51-positive patients and controls consistently carried HLA-B5101 allele with no other alleles observed. There were 15 males and 3 females in HLA-B51 positive patients, 22 males and 21 females in HLA-B51-negative patients, and signifi- cant differences in gender distribution was observed between HLA-B51-positive and negative patients (P<0.05 ). Moreover, the average age of onset in HLA-B51-positive patients significantly differed from that in HLA-B51-negative patients (28.4±10 years vs 37.3±12 years, P<0.05). However, no significant differ- ences were noticed in the clinical types, course, skin lesions, prevalence of genital ulcer, eye damage, joint involvement, or pathergy reaction between HLA-B51-positive and -negative patients (P0.05). Conclu- sions This study supports that HLA-B5101 allele is associated not only with the development of BD, but also with the gender and onset age of patients with BD of Chinese Han nationality.%目的 探讨HLA-B51等位基因和白塞病的相关性.方法 应用PCR-SSP(序列特异性引物)技术对61例中国汉族白塞病患者及100例正常人对照的HLA-B5101~HLA-B5109等位基因进行检测.结果 与对照组(11例阳性,11%)相比,白塞病组HLA-B51频率(18例阳性,29.5%)明显增高(χ2=8.79,P<0.01,RR=3.39),且白塞病组与对照组中HLA-B51阳性者均为HLA

  5. HLA-A and HLA-B allele frequencies in a mestizo population from Guadalajara, Mexico, determined by sequence-based typing.

    Science.gov (United States)

    Leal, C A; Mendoza-Carrera, F; Rivas, F; Rodriguez-Reynoso, S; Portilla-de Buen, E

    2005-12-01

    HLA-A and HLA-B genes were typed by DNA sequencing in a mestizo population from Guadalajara, Jalisco, Mexico. Thirty-seven HLA-A and 51 HLA-B alleles were observed in 103 samples. The common typical Amerindian alleles (>5%) and haplotypes (>or=2.0%) found were A*02010101, *24020101, *310102, B*350101, and *4002, and A*310102-B*4002, A*240201-B*350101, and the typical European alleles were A*010101, *29010101, B*1402, B*180101, and A*020101-B*1402, A*020101-B*510101, and A*3002-B*180101. This reflects the blending of the two main parental populations of mestizos: Amerindian and Iberian. Mexicans were found to be relatively closer to the Portuguese than to Spaniards. This proximity may indicate a larger Portuguese influence in Mexicans than previously considered. Present data contribute to the understanding of the genetic structure in Mexico.

  6. Two novel HLA-DRB TaqI RFLPs distinguish HLA-Bw57-DR7-DRB4-null from DRB4-positive haplotypes

    Energy Technology Data Exchange (ETDEWEB)

    Segurado, O.G.; Iglesias-Casarrubios, P.; Martinez-Laso, J.; Vicario, J.L.; Corell, A.; Arnaiz-Villena, A. (Hospital 12 de Octubre, Madrid (Spain))

    1990-02-25

    A 517 bp PstI fragment of an HLA-DRB clone, pRTV1 probe, was used. Genomic DNA TaqI digests hybridized with the DRB probe show two novel RFLPs of 3.8 and 3.1 kb. The allele frequency was analyzed in unrelated individuals, n=194; positive for the 3.8 kb band, n=81 (42%); positive for the 3.1 kb band, n=6 (3%). The 3.8 kb RFLP is only present in all haplotypes bearing HLA-DR4, 9,7.1 and 7.2a{sup *} (DQs2); the 3.1 kb RFLP is only present in all haplotypes bearing HLA-DR7.2k{sup *} (DQw9). The RFLPs were localized to the HLA region on chromosome 6.

  7. Expression of HLA-G in patients with B-cell chronic lymphocytic leukemia (B-CLL.

    Directory of Open Access Journals (Sweden)

    M Schmitt

    2009-01-01

    Full Text Available The expression of HLA-G was reported in certain malignancies and its role in escaping from immunosurveillance in cancers was proposed since HLA-G is a nonconventional HLA class I molecule that protects fetus from immunorecognition during pregnancy. Recent studies proposed HLA-G as novel prognostic marker for patients with B-CLL. HLA-G was showed to bear even better prognostic information compared to Zeta-chain associated protein of 70kDa (ZAP-70 and CD38 although some other authors did not find HLA-G expression in CLL. Therefore in this study we characterized the expression of HLA-G on both RNA and protein level. In most of 20 B-CLL patients we were able to detect signal from HLA-G using flow cytometry analysis. The expression of HLA-G was confirmed on messenger level by real-time RT-PCR experiments. No correlation between HLA-G expression and expression of well established prognostic factors such as ZAP-70 and CD38 was detected. These results confirm that HLA-G is expressed on CLL leukemic cells. Furthermore the expression of HLA-G on CLL cells suggests that this molecule might be involved in escaping of CLL cells from immunosurveillance.

  8. 76 FR 5787 - Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant...

    Science.gov (United States)

    2011-02-02

    ... Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant Programs... Perkins Loan, Federal Work-Study (FWS), and Federal Supplemental Educational Opportunity Grant (FSEOG... Federal Perkins Loan Program, Federal Work-Study Program, and Federal Supplemental Educational...

  9. Workflow automation architecture standard

    Energy Technology Data Exchange (ETDEWEB)

    Moshofsky, R.P.; Rohen, W.T. [Boeing Computer Services Co., Richland, WA (United States)

    1994-11-14

    This document presents an architectural standard for application of workflow automation technology. The standard includes a functional architecture, process for developing an automated workflow system for a work group, functional and collateral specifications for workflow automation, and results of a proof of concept prototype.

  10. Architecture and Stages

    DEFF Research Database (Denmark)

    Kiib, Hans

    2009-01-01

    as "experiencescape" - a space between tourism, culture, learning and economy. Strategies related to these challenges involve new architectural concepts and art as ‘engines' for a change. New expressive architecture and old industrial buildings are often combined into hybrid narratives, linking the past...

  11. Aesthetics of sustainable architecture

    NARCIS (Netherlands)

    Lee, S.

    2011-01-01

    The purpose of this book is to reveal, explore and further the debate on the aesthetic potentials of sustainable architecture and its practice. This book opens a new area of scholarship and discourse in the design and production of sustainable architecture, one that is based in aesthetics. The chapt

  12. SMRF architecture concepts

    NARCIS (Netherlands)

    Rossum, W.L. van; Wit, J.J.M. de; Otten, M.P.G.; Huizing, A.G.

    2011-01-01

    This presents three valuable applications of scalable multifunction RF (SMRF) systems. These systems allow radar, ESM, and communication functionality using a single front-end architecture. With the use of a novel system design tool, concepts for SMRF architectures for airborne, ground-based and nav

  13. Architecture and energy

    DEFF Research Database (Denmark)

    Marsh, Rob; Lauring, Michael

    2011-01-01

    Traditional low-energy architecture has not necessarily led to reduced energy consumption. A paradigm shift is proposed promoting pluralistic energy-saving strategies.......Traditional low-energy architecture has not necessarily led to reduced energy consumption. A paradigm shift is proposed promoting pluralistic energy-saving strategies....

  14. Digitally-Driven Architecture

    Directory of Open Access Journals (Sweden)

    Henriette Bier

    2014-07-01

    Full Text Available The shift from mechanical to digital forces architects to reposition themselves: Architects generate digital information, which can be used not only in designing and fabricating building components but also in embedding behaviours into buildings. This implies that, similar to the way that industrial design and fabrication with its concepts of standardisation and serial production influenced modernist architecture, digital design and fabrication influences contemporary architecture. While standardisation focused on processes of rationalisation of form, mass-customisation as a new paradigm that replaces mass-production, addresses non-standard, complex, and flexible designs. Furthermore, knowledge about the designed object can be encoded in digital data pertaining not just to the geometry of a design but also to its physical or other behaviours within an environment. Digitally-driven architecture implies, therefore, not only digitally-designed and fabricated architecture, it also implies architecture – built form – that can be controlled, actuated, and animated by digital means.In this context, this sixth Footprint issue examines the influence of digital means as pragmatic and conceptual instruments for actuating architecture. The focus is not so much on computer-based systems for the development of architectural designs, but on architecture incorporating digital control, sens­ing, actuating, or other mechanisms that enable buildings to inter­act with their users and surroundings in real time in the real world through physical or sensory change and variation.

  15. Teaching American Indian Architecture.

    Science.gov (United States)

    Winchell, Dick

    1991-01-01

    Reviews "Native American Architecture," by Nabokov and Easton, an encyclopedic work that examines technology, climate, social structure, economics, religion, and history in relation to house design and the "meaning" of space among tribes of nine regions. Describes this book's use in a college course on Native American architecture. (SV)

  16. Software Architecture Evolution

    Science.gov (United States)

    Barnes, Jeffrey M.

    2013-01-01

    Many software systems eventually undergo changes to their basic architectural structure. Such changes may be prompted by new feature requests, new quality attribute requirements, changing technology, or other reasons. Whatever the causes, architecture evolution is commonplace in real-world software projects. Today's software architects, however,…

  17. Applying neuroscience to architecture.

    Science.gov (United States)

    Eberhard, John P

    2009-06-25

    Architectural practice and neuroscience research use our brains and minds in much the same way. However, the link between neuroscience knowledge and architectural design--with rare exceptions--has yet to be made. The concept of linking these two fields is a challenge worth considering.

  18. TAP Service Federation Factory

    Science.gov (United States)

    Hume, A. C.; Krause, A.; Holliman, M.; Mann, R. G.; Noddle, K.; Voutsinas, S.

    2012-09-01

    This paper describes a prototype federation service for multiple TAP endpoints. Users can create a new TAP resource that allows them to query the federation as if all tables were in a single database.

  19. Federal Fleet Report

    Data.gov (United States)

    General Services Administration — Annual report of Federal agencies' motor vehicle fleet data collected in the Federal Automotive Statistical Tool (FAST), a web-based reporting tool cosponsored by...

  20. HLA-C increases HIV-1 infectivity and is associated with gp120

    Directory of Open Access Journals (Sweden)

    Beretta Alberto

    2008-08-01

    Full Text Available Abstract Background A recently identified genetic polymorphism located in the 5' region of the HLA-C gene is associated with individual variations in HIV-1 viral load and with differences in HLA-C expression levels. HLA-C has the potential to restrict HIV-1 by presenting epitopes to cytotoxic T cells but it is also a potent inhibitor of NK cells. In addition, HLA-C molecules incorporated within the HIV-1 envelope have been shown to bind to the envelope glycoprotein gp120 and enhance viral infectivity. We investigated this last property in cell fusion assays where the expression of HLA-C was silenced by small interfering RNA sequences. Syncytia formation was analyzed by co-cultivating cell lines expressing HIV-1 gp120/gp41 from different laboratory and primary isolates with target cells expressing different HIV-1 co-receptors. Virus infectivity was analyzed using pseudoviruses. Molecular complexes generated during cell fusion (fusion complexes were purified and analyzed for their HLA-C content. Results HLA-C positive cells co-expressing HIV-1 gp120/gp41 fused more rapidly and produced larger syncytia than HLA-C negative cells. Transient transfection of gp120/gp41 from different primary isolates in HLA-C positive cells resulted in a significant cell fusion increase. Fusion efficiency was reduced in HLA-C silenced cells compared to non-silenced cells when co-cultivated with different target cell lines expressing HIV-1 co-receptors. Similarly, pseudoviruses produced from HLA-C silenced cells were significantly less infectious. HLA-C was co-purified with gp120 from cells before and after fusion and was associated with the fusion complex. Conclusion Virionic HLA-C molecules associate to Env and increase the infectivity of both R5 and X4 viruses. Genetic polymorphisms associated to variations in HLA-C expression levels may therefore influence the individual viral set point not only by means of a regulation of the virus-specific immune response but also

  1. Collaborative Simulation Run-time Management Environment Based on HLA

    Institute of Scientific and Technical Information of China (English)

    王江云; 柴旭东; 王行仁

    2002-01-01

    The Collaborative Simulation Run-time Management Environment based on HLA (CSRME) mainly focuses on simulation problems for the system design of the complex distributed simulation. CSRME can integrate all the simulation tools and simulation applications that comply with the well-documented interface standards defined by CSRME. CSRME supports both the interoperability of different simulations and the integration of simulation tools, as well as provides simulation run-time management, simulation time management and simulation data management. Finally, the distributed command training system is analyzed and realized to validate the theories of CSRME.

  2. HLA-B27 and ankylosing spondylitis: tales from China.

    Science.gov (United States)

    de Castro, J A López

    2010-01-01

    The two most frequent HLA-B27 subtypes worldwide are B*2704 and B*2705. In the Han population of China B*2704 and, to a lower extent, B*2705 are found with significant frequency, and both are associated to ankylosing spondylitis (AS). Two articles in this issue report that the association to AS in this ethnic group is stronger for B*2704 than for B*2705. Thus, at least among the Han, B*2704 would be the strongest known susceptibility factor for AS.

  3. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

    Science.gov (United States)

    Pereyra, Florencia; Jia, Xiaoming; McLaren, Paul J; Telenti, Amalio; de Bakker, Paul I W; Walker, Bruce D; Ripke, Stephan; Brumme, Chanson J; Pulit, Sara L; Carrington, Mary; Kadie, Carl M; Carlson, Jonathan M; Heckerman, David; Graham, Robert R; Plenge, Robert M; Deeks, Steven G; Gianniny, Lauren; Crawford, Gabriel; Sullivan, Jordan; Gonzalez, Elena; Davies, Leela; Camargo, Amy; Moore, Jamie M; Beattie, Nicole; Gupta, Supriya; Crenshaw, Andrew; Burtt, Noël P; Guiducci, Candace; Gupta, Namrata; Gao, Xiaojiang; Qi, Ying; Yuki, Yuko; Piechocka-Trocha, Alicja; Cutrell, Emily; Rosenberg, Rachel; Moss, Kristin L; Lemay, Paul; O'Leary, Jessica; Schaefer, Todd; Verma, Pranshu; Toth, Ildiko; Block, Brian; Baker, Brett; Rothchild, Alissa; Lian, Jeffrey; Proudfoot, Jacqueline; Alvino, Donna Marie L; Vine, Seanna; Addo, Marylyn M; Allen, Todd M; Altfeld, Marcus; Henn, Matthew R; Le Gall, Sylvie; Streeck, Hendrik; Haas, David W; Kuritzkes, Daniel R; Robbins, Gregory K; Shafer, Robert W; Gulick, Roy M; Shikuma, Cecilia M; Haubrich, Richard; Riddler, Sharon; Sax, Paul E; Daar, Eric S; Ribaudo, Heather J; Agan, Brian; Agarwal, Shanu; Ahern, Richard L; Allen, Brady L; Altidor, Sherly; Altschuler, Eric L; Ambardar, Sujata; Anastos, Kathryn; Anderson, Ben; Anderson, Val; Andrady, Ushan; Antoniskis, Diana; Bangsberg, David; Barbaro, Daniel; Barrie, William; Bartczak, J; Barton, Simon; Basden, Patricia; Basgoz, Nesli; Bazner, Suzane; Bellos, Nicholaos C; Benson, Anne M; Berger, Judith; Bernard, Nicole F; Bernard, Annette M; Birch, Christopher; Bodner, Stanley J; Bolan, Robert K; Boudreaux, Emilie T; Bradley, Meg; Braun, James F; Brndjar, Jon E; Brown, Stephen J; Brown, Katherine; Brown, Sheldon T; Burack, Jedidiah; Bush, Larry M; Cafaro, Virginia; Campbell, Omobolaji; Campbell, John; Carlson, Robert H; Carmichael, J Kevin; Casey, Kathleen K; Cavacuiti, Chris; Celestin, Gregory; Chambers, Steven T; Chez, Nancy; Chirch, Lisa M; Cimoch, Paul J; Cohen, Daniel; Cohn, Lillian E; Conway, Brian; Cooper, David A; Cornelson, Brian; Cox, David T; Cristofano, Michael V; Cuchural, George; Czartoski, Julie L; Dahman, Joseph M; Daly, Jennifer S; Davis, Benjamin T; Davis, Kristine; Davod, Sheila M; DeJesus, Edwin; Dietz, Craig A; Dunham, Eleanor; Dunn, Michael E; Ellerin, Todd B; Eron, Joseph J; Fangman, John J W; Farel, Claire E; Ferlazzo, Helen; Fidler, Sarah; Fleenor-Ford, Anita; Frankel, Renee; Freedberg, Kenneth A; French, Neel K; Fuchs, Jonathan D; Fuller, Jon D; Gaberman, Jonna; Gallant, Joel E; Gandhi, Rajesh T; Garcia, Efrain; Garmon, Donald; Gathe, Joseph C; Gaultier, Cyril R; Gebre, Wondwoosen; Gilman, Frank D; Gilson, Ian; Goepfert, Paul A; Gottlieb, Michael S; Goulston, Claudia; Groger, Richard K; Gurley, T Douglas; Haber, Stuart; Hardwicke, Robin; Hardy, W David; Harrigan, P Richard; Hawkins, Trevor N; Heath, Sonya; Hecht, Frederick M; Henry, W Keith; Hladek, Melissa; Hoffman, Robert P; Horton, James M; Hsu, Ricky K; Huhn, Gregory D; Hunt, Peter; Hupert, Mark J; Illeman, Mark L; Jaeger, Hans; Jellinger, Robert M; John, Mina; Johnson, Jennifer A; Johnson, Kristin L; Johnson, Heather; Johnson, Kay; Joly, Jennifer; Jordan, Wilbert C; Kauffman, Carol A; Khanlou, Homayoon; Killian, Robert K; Kim, Arthur Y; Kim, David D; Kinder, Clifford A; Kirchner, Jeffrey T; Kogelman, Laura; Kojic, Erna Milunka; Korthuis, P Todd; Kurisu, Wayne; Kwon, Douglas S; LaMar, Melissa; Lampiris, Harry; Lanzafame, Massimiliano; Lederman, Michael M; Lee, David M; Lee, Jean M L; Lee, Marah J; Lee, Edward T Y; Lemoine, Janice; Levy, Jay A; Llibre, Josep M; Liguori, Michael A; Little, Susan J; Liu, Anne Y; Lopez, Alvaro J; Loutfy, Mono R; Loy, Dawn; Mohammed, Debbie Y; Man, Alan; Mansour, Michael K; Marconi, Vincent C; Markowitz, Martin; Marques, Rui; Martin, Jeffrey N; Martin, Harold L; Mayer, Kenneth Hugh; McElrath, M Juliana; McGhee, Theresa A; McGovern, Barbara H; McGowan, Katherine; McIntyre, Dawn; Mcleod, Gavin X; Menezes, Prema; Mesa, Greg; Metroka, Craig E; Meyer-Olson, Dirk; Miller, Andy O; Montgomery, Kate; Mounzer, Karam C; Nagami, Ellen H; Nagin, Iris; Nahass, Ronald G; Nelson, Margret O; Nielsen, Craig; Norene, David L; O'Connor, David H; Ojikutu, Bisola O; Okulicz, Jason; Oladehin, Olakunle O; Oldfield, Edward C; Olender, Susan A; Ostrowski, Mario; Owen, William F; Pae, Eunice; Parsonnet, Jeffrey; Pavlatos, Andrew M; Perlmutter, Aaron M; Pierce, Michael N; Pincus, Jonathan M; Pisani, Leandro; Price, Lawrence Jay; Proia, Laurie; Prokesch, Richard C; Pujet, Heather Calderon; Ramgopal, Moti; Rathod, Almas; Rausch, Michael; Ravishankar, J; Rhame, Frank S; Richards, Constance Shamuyarira; Richman, Douglas D; Rodes, Berta; Rodriguez, Milagros; Rose, Richard C; Rosenberg, Eric S; Rosenthal, Daniel; Ross, Polly E; Rubin, David S; Rumbaugh, Elease; Saenz, Luis; Salvaggio, Michelle R; Sanchez, William C; Sanjana, Veeraf M; Santiago, Steven; Schmidt, Wolfgang; Schuitemaker, Hanneke; Sestak, Philip M; Shalit, Peter; Shay, William; Shirvani, Vivian N; Silebi, Vanessa I; Sizemore, James M; Skolnik, Paul R; Sokol-Anderson, Marcia; Sosman, James M; Stabile, Paul; Stapleton, Jack T; Starrett, Sheree; Stein, Francine; Stellbrink, Hans-Jurgen; Sterman, F Lisa; Stone, Valerie E; Stone, David R; Tambussi, Giuseppe; Taplitz, Randy A; Tedaldi, Ellen M; Telenti, Amalio; Theisen, William; Torres, Richard; Tosiello, Lorraine; Tremblay, Cecile; Tribble, Marc A; Trinh, Phuong D; Tsao, Alice; Ueda, Peggy; Vaccaro, Anthony; Valadas, Emilia; Vanig, Thanes J; Vecino, Isabel; Vega, Vilma M; Veikley, Wenoah; Wade, Barbara H; Walworth, Charles; Wanidworanun, Chingchai; Ward, Douglas J; Warner, Daniel A; Weber, Robert D; Webster, Duncan; Weis, Steve; Wheeler, David A; White, David J; Wilkins, Ed; Winston, Alan; Wlodaver, Clifford G; van't Wout, Angelique; Wright, David P; Yang, Otto O; Yurdin, David L; Zabukovic, Brandon W; Zachary, Kimon C; Zeeman, Beth; Zhao, Meng

    2010-12-10

    Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

  4. Intra HLA-D/DR region recombinant detected by primed lymphocyte typing (PLT)

    DEFF Research Database (Denmark)

    Jakobsen, B K; Kristensen, T; Lamm, L U

    1983-01-01

    lymphocyte typing (PLT) for HLA-D/DR region associated DP antigens. None of these studies gave evidence that the recombinations had occurred within the HLA region. Mixed leucocyte culture (MLC) tests within the families showed no detectable stimulation between the HLA identical siblings in two...... to reactive reagents. One of these (GHx), reacted with a determinant which segregated within the GG family as if child G was a paternal recombinant between the HLA-D, DR, DP, and C4 loci, on the one hand, and on the other hand one or more loci governing other HLA-D/DR region controlled lymphocyte activating...... it reacted with a determinant significantly associated with D/DR/DP2. Other PLT reagents could be generated within the family against lymphocyte activating determinants controlled by genes in the two paternal haplotypes telomeric to the assumed recombinational site. These reagents gave stronger reactions...

  5. Implication of HLA-C and KIR alleles in human papillomavirus infection and associated cervical lesions.

    Science.gov (United States)

    Rizzo, Roberta; Gentili, Valentina; Rotola, Antonella; Bortolotti, Daria; Cassai, Enzo; Di Luca, Dario

    2014-11-01

    Human papillomavirus (HPV) regulation of host immune response leads to cervical lesions. In particular, natural killer (NK) cells are crucial for HPV control. Since specific HLA-I/KIR interactions modify NK cell activation, we analyzed HLA-C and KIR alleles in HPV infection and lesion development in 150 controls, 33 condyloma acuminatum, and 111 invasive cervical cancer (ICC) patients. We showed an increase in HLA-C1/KIR2DL2 and HLA-C1/KIR2DL3 pairs in HPV high-risk infected patients (OR 3.05, 3.24) with ICC (OR 1.33, 3.68). These data suggest HLA-C and KIR typing as risk marker for HPV infection and lesion evolution.

  6. Clinical validation of NGS technology for HLA: An early adopter's perspective.

    Science.gov (United States)

    Weimer, Eric T

    2016-10-01

    Clinical validation of NGS for HLA typing has been a topic of interest with many laboratories investigating the merits. NGS has proven effective at reducing ambiguities and costs while providing more detailed information on HLA genes not previously sequenced. The ability of NGS to multiplex many patients within a single run presents unique challenges and sequencing new regions of HLA genes requires application of our knowledge of genetics to accurately determine HLA typing. This review represents my laboratory's experience in validation of NGS for HLA typing. It describes the obstacles faced with validation of NGS and is broken down into pre-analytic, analytic, and post-analytic challenges. Each section includes solutions to address them.

  7. New evidence for balancing selection at the HLA-G locus in South Amerindians

    Directory of Open Access Journals (Sweden)

    Tiago Degani Veit

    2012-01-01

    Full Text Available HLA-G is a non-classical HLA (Human Leukocyte Antigen molecule characterized by limited tissue distribution under normal physiological conditions and low variability at both DNA and protein levels. Several studies suggest that HLA-G could play a role, as an immunoregulatory molecule, in situations as diverse as transplantation, cancer, viral infections and inflammatory diseases. A total of 237 individuals from 21 South American tribes speaking nine different linguistic families were studied in relation to the 14 bp insertion/deletion polymorphism at the HLA-G gene. A consistent (seven in nine excess of heterozygosity in samples classified by language was obtained. Our data supply evidences for balancing selection acting at the HLA-G 14 bp INDEL region. Enhanced fetal survival in a pathogen-rich environment may account for these findings.

  8. Impact of rheumatoid arthritis-associated HLA-DRβ1 subtypes on protein kinase A signaling

    Institute of Scientific and Technical Information of China (English)

    栗占国; 韩蕾; 贾汝琳; 李晶

    2003-01-01

    Objective To investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRβ1*0401, *0402, *0403, *0404 and *0101 subtypes on the protein kinase A (PKA) signaling pathway. Methods Adenylate cyclase (AC), cAMP and PKA activity in transfectants expressing RA-associated HLA-DRβ1 subtypes and their mutants were detected. Results Compared to HLA-DRβ1*0402 transfectants, the RA-associated HLA-DRβ1*0401, *0404 and *0101 transfectants produced significantly lower levels of AC, cAMP and PKA. Conclusion RA-associated HLA-DRβ1 molecules are involved in the pathogenesis of RA through down-regulation of the PKA signaling pathway.

  9. HLA-DR4 and career prospects in rheumatology: is there a link?

    Science.gov (United States)

    Gough, A.; Faint, J.; Salmon, M.; Bacon, P.; Emery, P.

    1995-01-01

    OBJECTIVE--To determine whether HLA type is associated with career progress in rheumatology. DESIGN--Comparison of HLA type after HLA analysis of samples of venous blood. SETTING--Department of Rheumatology Research, University of Birmingham. SUBJECTS--All (37) staff in the department. RESULTS--All the senior academics and most staff with a PhD expressed HLA-DR4. The prevalence of expression in each of these groups was significantly greater than that found in the controls. None of the junior doctors or secretaries expressed DR4. CONCLUSION--The junior doctors in the department have poor career prospects as HLA-DR4 seems to be associated with academic achievement. Images p1666-a PMID:8541751

  10. [Nucleotide sequence of HLA-DQA1 promoter region (QAP) in a lung cancer patient].

    Science.gov (United States)

    Qiu, C; Zhou, W; Song, C

    1996-06-01

    The HLA-DQA1 allele and nucleotide sequence of HLA-DQA1 promoter region (QAP) in a patient with IDDM complicated lung cancer have been identified by PCR/SSCP, PCR/SSCP and PCR/sequencing. The results showed that: (1) All of the lung cancer patient and his family members carried HLA-DQA1* 0301/0501 alleles. (2) a single base substitution G-->A at position -155 and deletion CAA at position -161 to -163 occurred in the patient. These results suggest that the mutation of HLA-DQA1 promoter region may modulate HLA-DQA1 gene expression by trans-acting factors binding to variant cis-acting elements and may be responsible for pathogenesis of lung cancer.

  11. Architecture as liminal Space

    Directory of Open Access Journals (Sweden)

    Nilly Harag

    2015-11-01

    Full Text Available The point of departure of the architectural project has to stem from the combination of inner and outer journeys in between the real or imagined limits. The pressing challenge is to destabilize the neat division of architecture into separate bodies of knowledge and pose the architect’s mode of action on the threshold between the concrete and the universal. Architecture is a lens, an instrument one looks through to bring new perspectives into focus, enabling the transformation of experience from a magnified self-concentrated space to a wide horizon. Architecture narrates relations between spaces and examines its validity through signifying practices of design. Design for itself becomes the language of the current, of the immediate fashion. Architecture can fulfill peoples’ dreams and miraculously can provide them tools to invent new ones: Curiosity is the first motive to act.

  12. Can architecture be barbaric?

    Science.gov (United States)

    Hürol, Yonca

    2009-06-01

    The title of this article is adapted from Theodor W. Adorno's famous dictum: 'To write poetry after Auschwitz is barbaric.' After the catastrophic earthquake in Kocaeli, Turkey on the 17th of August 1999, in which more than 40,000 people died or were lost, Necdet Teymur, who was then the dean of the Faculty of Architecture of the Middle East Technical University, referred to Adorno in one of his 'earthquake poems' and asked: 'Is architecture possible after 17th of August?' The main objective of this article is to interpret Teymur's question in respect of its connection to Adorno's philosophy with a view to make a contribution to the politics and ethics of architecture in Turkey. Teymur's question helps in providing a new interpretation of a critical approach to architecture and architectural technology through Adorno's philosophy. The paper also presents a discussion of Adorno's dictum, which serves for a better understanding of its universality/particularity.

  13. Product Architecture Modularity Strategies

    DEFF Research Database (Denmark)

    Mikkola, Juliana Hsuan

    2003-01-01

    The focus of this paper is to integrate various perspectives on product architecture modularity into a general framework, and also to propose a way to measure the degree of modularization embedded in product architectures. Various trade-offs between modular and integral product architectures...... and how components and interfaces influence the degree of modularization are considered. In order to gain a better understanding of product architecture modularity as a strategy, a theoretical framework and propositions are drawn from various academic literature sources. Based on the literature review......, the following key elements of product architecture are identified: components (standard and new-to-the-firm), interfaces (standardization and specification), degree of coupling, and substitutability. A mathematical function, termed modularization function, is introduced to measure the degree of modularization...

  14. Architecture as Ars Combinatoria

    Directory of Open Access Journals (Sweden)

    Francesco Cacciatore

    2015-11-01

    Full Text Available Architecture today, no longer reflects the limits of experimentation and innovation. An extremely low-tech art whose field of possibilities consists of choosing and using that which has already been done in the past. It is because of this that the key skill a designer should have is the ability to recognize the complexity in forms around them: cities have the widest programming opportunities for architecture, in the two-way relationship that is established from the city that takes form in architecture and an architecture that finds its place in the contemporary city. Thus, architecture has its foundation in hospitality, an element that differentiates it significantly from the design.

  15. 一种基于HLA Evovled的云仿真技术研究%Cloud Simulation Technology Based on HLA Evolved

    Institute of Scientific and Technical Information of China (English)

    高武奇; 康凤举; 钟联炯; 傅妍芳

    2011-01-01

    In order to realize the sharing of HLA simulation resources on Internet,the infrastructure and realizing framework of a cloud simulation based on HLA Evolved were put forward on the reference of cloud computing and the technical improvement of HLA Evolved.RTI component,modular FOM/SOM object model and WSDL API for the Web services were studied.The key techniques were settled,such as the technique of semantic service registration,discovery and composition,the technique of monitoring and prediction and the technique of distributed simulating and storage based on Hadoop.Then,the research was tested by the designed simulation supposition.The result shows that cloud simulation based on HLA Evolved design approach is feasible and effective.%针对现有HLA仿真资源难以与Internet共享使用的问题,借鉴云计算的思想,采用HLA Evolved相关的技术改进,提出了一种基于HLA Evolved的云仿真的体系结构和框架实现方案;研究了用于Web服务的RTI组件、模块化FOM/SOM对象模型和WSDL API函数等HLA Evolved技术,解决了基于多层语义的服务注册、发现、组合和平台的监控、预测及基于Hadoop的分布式存储、仿真技术;完成了一种战术通信网系统的云仿真测试实验,证明了基于HLA Evolved的云仿真设计方法的可行、有效。

  16. Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, Róisín M. [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Friis, Lone [University of Oxford, Oxford OX3 9DS (United Kingdom); Siebold, Christian [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Friese, Manuel A. [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Oxford OX3 9DU (United Kingdom); Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg (Germany); Fugger, Lars, E-mail: lars.fugger@imm.ox.ac.uk [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Oxford OX3 9DU (United Kingdom); Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej 100, 8200 N Aarhus (Denmark); Jones, E. Yvonne, E-mail: lars.fugger@imm.ox.ac.uk [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); University of Oxford, Oxford OX3 9DS (United Kingdom)

    2011-05-01

    The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. HLA-A3 is a predisposing allele for multiple sclerosis (MS), an autoimmune disease of the central nervous system. The KLIETYFSK peptide is a naturally processed epitope of proteolipid protein, a myelin protein and candidate target for immune-mediated myelin destruction in MS. Comparison of the structure of HLA-A3 with that of HLA-A2, an MHC class I molecule which is protective against MS, indicates that both MHC class I molecules present very similar faces for T-cell receptor recognition whilst differing in the specificity of their peptide-binding grooves. These characteristics may underlie the opposing (predisposing versus protective) associations that they exhibit both in humans and in mouse models of MS-like disease. Furthermore, subtle alterations within the peptide-binding groove of HLA-A3 and other A3-like MHC class I molecules, members of the so-called A3 superfamily, may be sufficient to alter their presentation of autoantigen peptides such as KLIETYFSK. This in turn may modulate their contribution to the associated risk of autoimmune disease.

  17. MHC class II super-enhancer increases surface expression of HLA-DR and HLA-DQ and affects cytokine production in autoimmune vitiligo.

    Science.gov (United States)

    Cavalli, Giulio; Hayashi, Masahiro; Jin, Ying; Yorgov, Daniel; Santorico, Stephanie A; Holcomb, Cherie; Rastrou, Melinda; Erlich, Henry; Tengesdal, Isak W; Dagna, Lorenzo; Neff, C Preston; Palmer, Brent E; Spritz, Richard A; Dinarello, Charles A

    2016-02-02

    Genetic risk for autoimmunity in HLA genes is most often attributed to structural specificity resulting in presentation of self-antigens. Autoimmune vitiligo is strongly associated with the MHC class II region. Here, we fine-map vitiligo MHC class II genetic risk to three SNPs only 47 bp apart, located within a predicted super-enhancer in an intergenic region between HLA-DRB1 and HLA-DQA1, localized by a genome-wide association study of 2,853 Caucasian vitiligo patients. The super-enhancer corresponds to an expression quantitative trait locus for expression of HLA-DR and HLA-DQ RNA; we observed elevated surface expression of HLA-DR (P = 0.008) and HLA-DQ (P = 0.02) on monocytes from healthy subjects homozygous for the high-risk SNP haplotype. Unexpectedly, pathogen-stimulated peripheral blood mononuclear cells from subjects homozygous for the high-risk super-enhancer haplotype exhibited greater increase in production of IFN-γ and IL-1β than cells from subjects homozygous for the low-risk haplotype. Specifically, production of IFN-γ on stimulation of dectin-1, mannose, and Toll-like receptors with Candida albicans and Staphylococcus epidermidis was 2.5- and 2.9-fold higher in high-risk subjects than in low-risk subjects, respectively (P = 0.007 and P = 0.01). Similarly, production of IL-1β was fivefold higher in high-risk subjects than in low-risk subjects (P = 0.02). Increased production of immunostimulatory cytokines in subjects carrying the high-risk haplotype may act as an "adjuvant" during the presentation of autoantigens, tying together genetic variation in the MHC with the development of autoimmunity. This study demonstrates that for risk of autoimmune vitiligo, expression level of HLA class II molecules is as or more important than antigen specificity.

  18. A Simplified PCR-SSP Method for HLA-A2 Subtype in a Population of Wuhan, China

    Institute of Scientific and Technical Information of China (English)

    Bing Liang; Lijun Zhu; Zhihui Liang; Xiufang Weng; Xiaoling Lu; Cai'e Zhang; Hui Li; Xiongwen Wu

    2006-01-01

    HLA-A2 is the most frequent HLA-A allele in all ethnic populations, and an important restriction element for peptide presentation to T cells in infectious disease and cancer. However, the HLA-A2 supertype consisting of up to 75 subtypes, mutation studies and analyses using cytotoxic T lymphocytes suggest the functional relevance of subtype-specific differences in HLA-A2 molecules for peptide binding and T-cell recognition. Therefore, it is necessary for T-cell response study to discriminate the HLA-A2 subtypes and to understand the profile of HLA-A2 allelic distribution in a given population. In this study, we developed a simple, robust approach based on the nested polymerase chain reaction using sequence-specific primers (PCR-SSP) to discriminate 17 HLA-A2 subtypes which cover the most HLA-A2 alleles (> 99% allele frequency) reported in Chinese, using 15 combinations of 19 allelic specific primers. In the first round of PCR, 3 combinations of 5 primers were used to determine whether the tested sample was HLA-A2 positive, meanwhile the subtypes of HLA-A*0209 and HLA-A*0215N were determined for the variant position of these two subtypes is in exon 4 instead of exon 2, 3. Samples of HLA-A2 positive were subtyped in the second round of PCR, using PCR products of the first round as templates. This strategy was applied to test the samples of 78 random HLA-A2 positive individuals for their HLA-A2 subtypes. Those samples were screened for HLA-A2 positive by the first round PCR-SSP from 154 healthy blood donors in Wuhan, China. The subtyping results were verified by using flow cytometric analysis (FCM) with HLA-A2 specific monoclonal antibody BB7.2 and DNA sequencing. The typing results of the samples show 50.7% random individuals in the population carry HLA-A2, HLA-A*0201 ranks the first (allele frequency = 15.5%), followed by A*0207 (5.8%),A*0206 (4.7%), A*0203 (2.6%), A*0210 (0.7%), and these 5 alleles account for 99.0% HLA-A2 subtypes of allele frequency. Our study

  19. Minimalism in architecture: Abstract conceptualization of architecture

    Directory of Open Access Journals (Sweden)

    Vasilski Dragana

    2015-01-01

    Full Text Available Minimalism in architecture contains the idea of the minimum as a leading creative tend to be considered and interpreted in working through phenomena of empathy and abstraction. In the Western culture, the root of this idea is found in empathy of Wilhelm Worringer and abstraction of Kasimir Malevich. In his dissertation, 'Abstraction and Empathy' Worringer presented his thesis on the psychology of style through which he explained the two opposing basic forms: abstraction and empathy. His conclusion on empathy as a psychological basis of observation expression is significant due to the verbal congruence with contemporary minimalist expression. His intuition was enhenced furthermore by figure of Malevich. Abstraction, as an expression of inner unfettered inspiration, has played a crucial role in the development of modern art and architecture of the twentieth century. Abstraction, which is one of the basic methods of learning in psychology (separating relevant from irrelevant features, Carl Jung is used to discover ideas. Minimalism in architecture emphasizes the level of abstraction to which the individual functions are reduced. Different types of abstraction are present: in the form as well as function of the basic elements: walls and windows. The case study is an example of Sou Fujimoto who is unequivocal in its commitment to the autonomy of abstract conceptualization of architecture.

  20. Distribution of HLA-G extended haplotypes and one HLA-E polymorphism in a large-scale study of mother-child dyads with and without severe preeclampsia and eclampsia.

    Science.gov (United States)

    Nilsson, L L; Djurisic, S; Andersen, A-M N; Melbye, M; Bjerre, D; Ferrero-Miliani, L; Hackmon, R; Geraghty, D E; Hviid, T V F

    2016-10-01

    The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants. Most nucleotide variations are clustered in the 5'-upstream regulatory region (5'URR) and 3'-untranslated regulatory region (3'UTR) of HLA-G and reflect a stringent expressional control. Based on genotyping and full gene sequencing of HLA-G in a large number of cases and controls (n > 900), the present study, which to our knowledge is the largest and most comprehensive performed, investigated the association between the HLA-G 14-bp ins/del (rs66554220) and HLA-E polymorphisms in mother and newborn dyads from pregnancies complicated by severe preeclampsia/eclampsia and from uncomplicated pregnancies. Furthermore, results from extended HLA-G haplotyping in the newborns are presented in order to assess whether a combined contribution of nucleotide variations spanning the 5'URR, coding region, and 3'UTR of HLA-G describes the genetic association with severe preeclampsia more closely. In contrast to earlier findings, the HLA-G 14-bp ins/del polymorphism was not associated with severe preeclampsia. Furthermore, the polymorphism (rs1264457) defining the two nonsynonymous HLA-E alleles, HLA-E*01:01:xx:xx and HLA-E*01:03:xx:xx, were not associated with severe preeclampsia. Finally, no specific HLA-G haplotypes were significantly associated with increased risk of developing severe preeclampsia/eclampsia.

  1. A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Judith Field

    Full Text Available We conducted an association study across the human leukocyte antigen (HLA complex to identify loci associated with multiple sclerosis (MS. Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each P ≤ 4 x 10(-6. All associations were significant in an independent replication cohort of 2212 cases and 2251 controls (P ≤ 0.001 and were highly significant in the combined dataset (P ≤ 6 x 10(-8. The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set P = 9 x 10(-9, replication set P = 7 x 10(-4, combined P = 2 x 10(-10. HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.

  2. Heme Oxygenase-1 Inhibits HLA Class I Antibody-Dependent Endothelial Cell Activation.

    Directory of Open Access Journals (Sweden)

    Eva Zilian

    Full Text Available Antibody-mediated rejection (AMR is a key limiting factor for long-term graft survival in solid organ transplantation. Human leukocyte antigen (HLA class I (HLA I antibodies (Abs play a major role in the pathogenesis of AMR via their interactions with HLA molecules on vascular endothelial cells (ECs. The antioxidant enzyme heme oxygenase (HO-1 has anti-inflammatory functions in the endothelium. As complement-independent effects of HLA I Abs can activate ECs, it was the goal of the current study to investigate the role of HO-1 on activation of human ECs by HLA I Abs. In cell cultures of various primary human macro- and microvascular ECs treatment with monoclonal pan- and allele-specific HLA I Abs up-regulated the expression of inducible proinflammatory adhesion molecules and chemokines (vascular cell adhesion molecule-1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1], interleukin-8 [IL-8] and monocyte chemotactic protein 1 [MCP-1]. Pharmacological induction of HO-1 with cobalt-protoporphyrin IX reduced, whereas inhibition of HO-1 with either zinc-protoporphyrin IX or siRNA-mediated knockdown increased HLA I Ab-dependent up-regulation of VCAM-1. Treatment with two carbon monoxide (CO-releasing molecules, which liberate the gaseous HO product CO, blocked HLA I Ab-dependent EC activation. Finally, in an in vitro adhesion assay exposure of ECs to HLA I Abs led to increased monocyte binding, which was counteracted by up-regulation of HO-1. In conclusion, HLA I Ab-dependent EC activation is modulated by endothelial HO-1 and targeted induction of this enzyme may be a novel therapeutic approach for the treatment of AMR in solid organ transplantation.

  3. HLA-B7-restricted islet epitopes are differentially recognized in type 1 diabetic children and adults and form weak peptide-HLA complexes

    DEFF Research Database (Denmark)

    Scotto, Matthieu; Afonso, Georgia; Østerbye, Thomas;

    2012-01-01

    The cartography of β-cell epitopes targeted by CD8(+) T cells in type 1 diabetic (T1D) patients remains largely confined to the common HLA-A2 restriction. We aimed to identify β-cell epitopes restricted by the HLA-B7 (B*07:02) molecule, which is associated with mild T1D protection. Using DNA...... immunization on HLA-B7-transgenic mice and prediction algorithms, we identified GAD and preproinsulin candidate epitopes. Interferon-γ (IFN-γ) enzyme-linked immunospot assays on peripheral blood mononuclear cells showed that most candidates were recognized by new-onset T1D patients, but not by type 2 diabetic...... and healthy subjects. Some epitopes were highly immunodominant and specific to either T1D children (GAD(530-538); 44% T cell-positive patients) or adults (GAD(311-320); 38%). All epitopes displayed weak binding affinity and stability for HLA-B7 compared with HLA-A2-restricted ones, a general feature of HLA-B7...

  4. HLA and Celiac Disease Susceptibility: New Genetic Factors Bring Open Questions about the HLA Influence and Gene-Dosage Effects

    Science.gov (United States)

    Medrano, Luz María; Dema, Bárbara; López-Larios, Arturo; Maluenda, Carlos; Bodas, Andrés; López-Palacios, Natalia; Figueredo, M. Ángeles; Fernández-Arquero, Miguel; Núñez, Concepción

    2012-01-01

    Celiac disease (CD) is a chronic inflammatory disorder triggered after gluten ingestion in genetically susceptible individuals. The major genetic determinants are HLA-DQA1*05 and HLA-DQB1*02, which encode the DQ2 heterodimer. These alleles are commonly inherited in cis with DRB1*03∶01, which is associated with numerous immune-related disorders, in some cases contributing with a different amount of risk depending on the haplotype context. We aimed at investigating those possible differences involving DRB1*03∶01-carrying haplotypes in CD susceptibility. A family (274 trios) and a case-control sample (369 CD cases/461 controls) were analyzed. DRB1*03∶01-carrying individuals were classified according to the haplotype present (ancestral haplotype (AH) 8.1, AH 18.2 or non-conserved haplotype) after genotyping of HLA-DRB1, -DQA1, -DQB1, -B8, TNF -308, TNF -376 and the TNFa and TNFb microsatellites. We observe that the AH 8.1 confers higher risk than the remaining DRB1*03∶01-carrying haplotypes, and this effect only involves individuals possessing a single copy of DQB1*02. CD risk for these individuals is similar to the one conferred by inherit DQA1*05 and DQB1*02 in trans. It seems that an additional CD susceptibility factor is present in the AH 8.1 but not in other DRB1*03∶01-carrying haplotypes. This factor could be shared with individuals possessing DQ2.5 trans, according to the similar risk observed in those two groups of individuals. PMID:23119005

  5. HLA genes in Uros from Titikaka Lake, Peru: origin and relationship with other Amerindians and worldwide populations.

    Science.gov (United States)

    Arnaiz-Villena, A; Gonzalez-Alcos, V; Serrano-Vela, J I; Reguera, R; Barbolla, L; Parga-Lozano, C; Gómez-Prieto, P; Abd-El-Fatah-Khalil, S; Moscoso, J

    2009-06-01

    Uros population from the Titikaka Lake live in about 42 floating reed ('totora') islands in front of Puno City (Peru) at a 4000 m high altiplano. They present both an mtDNA and a human leucocyte antigen (HLA) profile different from the surrounding populations: mtDNA A2 haplogroup is common to Uros and Amazon forest lowland Amerindians. HLA genetic distances between populations have been calculated and neighbour-joining dendrograms and correspondence analyses were carried out. Approximately 15 006 HLA chromosomes from worldwide populations have been used for comparisons. Only eight HLA-A alleles have been found, three of them accounting for most of the frequencies. The same phenomenon is seen for HLA-B, HLA-DRB1 and HLA-DQB1 alleles: a few alleles (3, 4 and 3, respectively) are present in most individuals. The presence of HLA-B*4801 and HLA-DRB1*0901 alleles in a relatively high frequency (although not the most frequent alleles found) is a characteristic shared with Asians and some populations from the Andean altiplano. Three specific Uros haplotypes have been found among the most frequent ones: HLA-A*680102-B*3505-DRB1*0403-DQB1*0302; HLA-A*2402-B*1504-DRB1*1402-DQB1*0301; and HLA-A*2402-B*4801-DRB1*0403-DQB1*0302. The present study suggests that Uros may have been one of the first populations from the shores of the Titikaka Lake coming from the Amazonian forest, which might have given rise to other later differentiated ethnic group (i.e. Aymaras). Uros HLA profile is also useful to study genetic epidemiology of diseases linked to HLA and to construct a future transplant waiting list by adding up regional lists in order to get a bigger pool for transplanting with better HLA matching.

  6. Data-Centric Enterprise Architecture

    OpenAIRE

    Zeinab Rajabi; Maryam Nooraei Abade

    2012-01-01

    Enterprises choose Enterprise Architecture (EA) solution, in order to overcome dynamic business challenges and in coordinate various enterprise elements. In this article, a solution is suggested for the Enterprise Architecture development. The solution focuses on architecture data in the Enterprise Architecture development process. Data-centric architecture approach is preferred product-centric architecture approach. We suggest using Enterprise Ontology (EO) as context for collecting architec...

  7. Hybrid architecture: object, landscape, infrastructure

    OpenAIRE

    Pinto de Freitas, Rita

    2011-01-01

    The concept of "hybrid architecture" developed in this study considers hybrid all architecture that is at once object, landscape and infrastructure. Hybrid architecture, pushed by the fact that it concentrates in a single architectural intervention a triple object-, landscape- and infrastructure-related nature, generates architectural answers with very specific features, and its study achieves following goals: 1: Clarify the term hybrid related to architectural intervention; 2: Tran...

  8. ANALYZING HLA HAPLOTYPE OF THE LOCI HLA-A,-B, AND-DRB1 IN MONGOLIA ETHNIC GROUP

    Institute of Scientific and Technical Information of China (English)

    张洪波; 李生斌

    2006-01-01

    Mongolian is a main ethnic group in China.The Mongol people have a well-established andglorious culture.Their clai mto the reputation of"horseback people"rests ontheir special affection forthe grasslands and horses,which is derived fromtheir thousands of years nomadic history[1-2].Thehuman leukocyte antigen(HLA)are located on theshort ar m of human chromosome6encoding t wodistinct classes of highly polymorphic cell surfacemolecules that bind and present processed antigens inthe for mof peptides to Tlymphocy...

  9. Fractal Geometry of Architecture

    Science.gov (United States)

    Lorenz, Wolfgang E.

    In Fractals smaller parts and the whole are linked together. Fractals are self-similar, as those parts are, at least approximately, scaled-down copies of the rough whole. In architecture, such a concept has also been known for a long time. Not only architects of the twentieth century called for an overall idea that is mirrored in every single detail, but also Gothic cathedrals and Indian temples offer self-similarity. This study mainly focuses upon the question whether this concept of self-similarity makes architecture with fractal properties more diverse and interesting than Euclidean Modern architecture. The first part gives an introduction and explains Fractal properties in various natural and architectural objects, presenting the underlying structure by computer programmed renderings. In this connection, differences between the fractal, architectural concept and true, mathematical Fractals are worked out to become aware of limits. This is the basis for dealing with the problem whether fractal-like architecture, particularly facades, can be measured so that different designs can be compared with each other under the aspect of fractal properties. Finally the usability of the Box-Counting Method, an easy-to-use measurement method of Fractal Dimension is analyzed with regard to architecture.

  10. Avionics Architecture for Exploration Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Avionics Architectures for Exploration Project team will develop a system level environment and architecture that will accommodate equipment from multiple...

  11. Integrated Data Assimilation Architecture Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Integrated Data Assimilation Architecture (IDAA) is a middleware architecture that facilitates the incorporation of heterogeneous sensing and control devices...

  12. [Extending preimplantation genetic diagnosis to HLA typing: the French exception].

    Science.gov (United States)

    Steffann, Julie; Frydman, Nelly; Burlet, Philippe; Gigarel, Nadine; Hesters, Laetitia; Kerbrat, Violaine; Lamazou, Frédéric; Munnich, Arnold; Frydman, René

    2011-01-01

    Umut-Talha, a "sibling savior", was born on 26 January 2011 at Beclère Hospital after embryo selection at the Paris preimplantation genetic diagnosis (PGD) center. His birth revived the controversy over "double PGD". This procedure, authorized in France since 2006, allows couples who already have a child with a serious, incurable genetic disease, to opt for PGD in order to select a healthy embryo that is HLA-matched to the affected sibling and who may thus serve as an ombilical cord blood donor. The procedure is particularly complex and the baby take-home rate is still very low. Double PGD is strictly regulated in France, and candidate couples must first receive individual authorization from the Biomedicine Agency. In our experience, these couples have a strong desire to have children, as reflected by the large number of prior spontaneous pregnancies (25% of couples). Likewise, most of these couples request embryo transfer even when there is no HLA-matched embryo, which accounts for more than half of embryo transfers. The controversy surrounding this practice has flared up again in recent weeks, over the concepts of "designer babies" and "double savior siblings" (the baby is selected to be free of the hereditary disease, and may also serve as a stem cell donor for the affected sibling).

  13. Identifying coevolutionary patterns in human leukocyte antigen (HLA) molecules.

    Science.gov (United States)

    Jiang, Xiaowei; Fares, Mario A

    2010-05-01

    The antigenic peptide, major histocompatibility complex molecule (MHC; also called human leukocyte antigen, HLA), coreceptor CD8, or CD4 and T-cell receptor (TCR) function as a complex to initiate effectors' mechanisms of the immune system. The tight functional and physical interaction among these molecules may have involved strong coevolution links among domains within and between proteins. Despite the importance of unraveling such dependencies to understand the arms race of host-pathogen interaction, no previous studies have aimed at achieving such an objective. Here, we perform an exhaustive coevolution analysis and show that indeed such dependencies are strongly shaping the evolution and probably the function of these molecules. We identify intramolecular coevolution in HLA class I and II at domains important for their immune activity. Most of the amino acid sites identified to be coevolving in HLAI have been also detected to undergo positive Darwinian selection highlighting therefore their adaptive value. We also identify coevolution among antigen-binding pockets (P1-P9) and among these and TCR-binding sites. Conversely to HLAI, coevolution is weaker in HLAII. Our results support that such coevolutionary patterns are due to selective pressures of host-pathogen coevolution and cooperative binding of TCRs, antigenic peptides, and CD8/CD4 to HLAI and HLAII.

  14. Polymorphism of the HLA-DQA1 and -DQB1 genes of Han population in Jiangsu Province, China

    Institute of Scientific and Technical Information of China (English)

    YU Rong-bin; HONG Xin; DING Wei-liang; TAN Yong-fei; WU Guan-ling

    2006-01-01

    @@ The HLA genes, located on the short arm of human chromosome 6, encode peptides involved in host immune response, are important in tissue transplantation and are associated with a variety of infectious, autoimmune, and inflammatory diseases. Moreover, the HLA loci display an unprecedented degree of diversity and the distribution of HLA alleles and haplotypes among different populations is considerably variable.1 The expression of particular HLA alleles may be associated with the susceptibility or resistance to some diseases.2 In this study, the genetic polymorphism of HLA-DQA1 and -DQB1 in Jiangsu Han population was analyzed by polymerase chain reaction-sequence-based typing (PCR-SBT).

  15. Distribution of HLA-G extended haplotypes and one HLA-E polymorphism in a large-scale study of mother-child dyads with and without severe preeclampsia and eclampsia

    DEFF Research Database (Denmark)

    Nilsson, L. L.; Djurisic, S.; Andersen, A.-M. N.;

    2016-01-01

    The etiological pathways and pathogenesis of preeclampsia have rendered difficult to disentangle. Accumulating evidence points toward a maladapted maternal immune system, which may involve aberrant placental expression of immunomodulatory human leukocyte antigen (HLA) class Ib molecules during...... pregnancy. Several studies have shown aberrant or reduced expression of HLA-G in the placenta and in maternal blood in cases of preeclampsia compared with controls. Unlike classical HLA class Ia loci, the nonclassical HLA-G has limited polymorphic variants. Most nucleotide variations are clustered in the 5...... comprehensive performed, investigated the association between the HLA-G 14-bp ins/del (rs66554220) and HLA-E polymorphisms in mother and newborn dyads from pregnancies complicated by severe preeclampsia/eclampsia and from uncomplicated pregnancies. Furthermore, results from extended HLA-G haplotyping...

  16. Role of HLA antigens in Rh (D) alloimmunized pregnant women from Mumbai, Maharashtra, India

    Indian Academy of Sciences (India)

    U Shankar Kumar; K Ghosh; S S Gupte; S C Gupte; D Mohanty

    2002-03-01

    Immunogenetic studies in various diseases provide potential genetic markers. We have studied the incidence of HLA A, B, C, DR and DQ loci antigen in Rh (D) antigen isoimmunized mothers compared to those nonimmunized isoimmunized Rh negative mothers. Seventy six mothers who were immunized to Rh (D) antigen due to pregnancy (responders) and fifty four mothers who did not develop Rh (D) isoimmunization despite positive pregnancies (nonresponders) were selected for the study. Standard methods of serological HLA typing, ABO and Rh (D) groups, and screening for Rh D antibodies were used. 392 unrelated individuals from the population were compared as controls. In addition 45 unrelated individuals from the same population were typed for HLA DRB and DQB gene using PCR-SSP kits. The genotype frequencies of HLA A2, A3, A28, B13, B17, B35, B52, B60, Cw2, Cw6, DR4, and DQ3 were significantly increased, while the frequencies of the HLA A11, A29, A31, B7, B37, B51, Cw1 and DR9 were decreased in the responder women when compared to the non-responder women. HLA A30 (19) split antigen was not identified in immunized women while HLA A23 (9) split antigen was not identified in non immunized women. HLA A3, B17, Cw2 and DR4 showed a significant relative risk among the immunized responder women. When compared with Rh immunized women (responders) reported from USA, England and Hungary the phenotype frequencies of HLA A11, A24, A28, B5, B17, B40, DR2 and DR5 were increased while HLA A23, B8, B18, and DR6 were decreased in the Indian Rh immunized women. Two locus haplotype frequency analysis observed among the responders women revealed that among the significant haplotypes expressed A2–B5, B7–Cw1, DR2–DQ1 were highly significant haplotypes in positive linkage, while A1–B5, and A1–B7 were in significant negative linkage disequilibrium. The haplotype frequencies were ≤ one when these common hapoltypes were compared with control population. Thus in the present study it is evident

  17. High-Accuracy HLA Type Inference from Whole-Genome Sequencing Data Using Population Reference Graphs.

    Science.gov (United States)

    Dilthey, Alexander T; Gourraud, Pierre-Antoine; Mentzer, Alexander J; Cereb, Nezih; Iqbal, Zamin; McVean, Gil

    2016-10-01

    Genetic variation at the Human Leucocyte Antigen (HLA) genes is associated with many autoimmune and infectious disease phenotypes, is an important element of the immunological distinction between self and non-self, and shapes immune epitope repertoires. Determining the allelic state of the HLA genes (HLA typing) as a by-product of standard whole-genome sequencing data would therefore be highly desirable and enable the immunogenetic characterization of samples in currently ongoing population sequencing projects. Extensive hyperpolymorphism and sequence similarity between the HLA genes, however, pose problems for accurate read mapping and make HLA type inference from whole-genome sequencing data a challenging problem. We describe how to address these challenges in a Population Reference Graph (PRG) framework. First, we construct a PRG for 46 (mostly HLA) genes and pseudogenes, their genomic context and their characterized sequence variants, integrating a database of over 10,000 known allele sequences. Second, we present a sequence-to-PRG paired-end read mapping algorithm that enables accurate read mapping for the HLA genes. Third, we infer the most likely pair of underlying alleles at G group resolution from the IMGT/HLA database at each locus, employing a simple likelihood framework. We show that HLA*PRG, our algorithm, outperforms existing methods by a wide margin. We evaluate HLA*PRG on six classical class I and class II HLA genes (HLA-A, -B, -C, -DQA1, -DQB1, -DRB1) and on a set of 14 samples (3 samples with 2 x 100bp, 11 samples with 2 x 250bp Illumina HiSeq data). Of 158 alleles tested, we correctly infer 157 alleles (99.4%). We also identify and re-type two erroneous alleles in the original validation data. We conclude that HLA*PRG for the first time achieves accuracies comparable to gold-standard reference methods from standard whole-genome sequencing data, though high computational demands (currently ~30-250 CPU hours per sample) remain a significant

  18. HLA-A*68:02-restricted Gag-specific cytotoxic T lymphocyte responses can drive selection pressure on HIV but are subdominant and ineffective

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N; Buus, Anette Stryhn; Harndahl, Mikkel

    2013-01-01

    Human leukocyte allele (HLA) class I polymorphism has the greatest impact of human genetic variation on viral load set point. A substantial part of this effect is due to the action of HLA-B and HLA-C alleles. With few exceptions the role of HLA-A molecules in immune control of HIV is unclear....

  19. RECONSTRUCTING DECONSTRUCTION IN ARCHITECTURE

    Directory of Open Access Journals (Sweden)

    IDHAM Noor Cholis

    2013-12-01

    Full Text Available This paper examines deconstruction in architecture and forms used, which triggered by dispute of form and its scientification claimed by deconstructivists. Deconstruction terminologyis studied in the first part related to architecture field as a base knowledge. Some sample works of known deconstructionist architects are assessed in order to understand how their building is deconstructed and what forms they used. Discussion about form and its relation to other fields is then pursued by discussing the involvement of terminology of science, aesthetic pattern, and human life. The results of this discussion give clear understanding how form related to deconstruction in architecture are used.

  20. ARCHITECTURE INFORMS HISTORY

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Clusters of ancient architecture in central China have recently been entered on the world heritage list A group of ancient architecture in Dengfeng,central China’s Henan Province,was added to the world heritage list at the 34th session of the World Heritage Committee in Brazil on August 1 this year.The architectural collection is China’s 39th property inscribed on the list,and the third world heritage site in the province after the Longmen Grottoes and Yinxu in Anyang,site of the capital of the late Shang Dynasty(1600-1046 B.C.).

  1. Adaptive Architectural Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Kirkegaard, Poul Henning

    2010-01-01

    . The general scopes of this paper are to develop a new adaptive kinetic architectural structure, particularly a reconfigurable architectural structure which can transform body shape from planar geometries to hyper-surfaces using different control strategies, i.e. a transformation into more than one or two...... different shape alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock- up concept...

  2. Towards Adaptive Evolutionary Architecture

    DEFF Research Database (Denmark)

    Bak, Sebastian HOlt; Rask, Nina; Risi, Sebastian

    2016-01-01

    This paper presents first results from an interdisciplinary project, in which the fields of architecture, philosophy and artificial life are combined to explore possible futures of architecture. Through an interactive evolutionary installation, called EvoCurtain, we investigate aspects of how...... to the development of designs tailored to the individual preferences of inhabitants, changing the roles of architects and designers entirely. Architecture-as-it-could-be is a philosophical approach conducted through artistic methods to anticipate the technological futures of human-centered development within...

  3. Computer architecture technology trends

    CERN Document Server

    1991-01-01

    Please note this is a Short Discount publication. This year's edition of Computer Architecture Technology Trends analyses the trends which are taking place in the architecture of computing systems today. Due to the sheer number of different applications to which computers are being applied, there seems no end to the different adoptions which proliferate. There are, however, some underlying trends which appear. Decision makers should be aware of these trends when specifying architectures, particularly for future applications. This report is fully revised and updated and provides insight in

  4. HLA-DRB1 and HLA-DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

    Science.gov (United States)

    Muro, Manuel; Mondejar-López, Pedro; Moya-Quiles, María Rosa; Salgado, Gema; Pastor-Vivero, María Dolores; Lopez-Hernandez, Ruth; Boix, Francisco; Campillo, José Antonio; Minguela, Alfredo; Garcia-Alonso, Ana; Sánchez-Solís, Manuel; Álvarez-López, María Rocío

    2013-03-01

    Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA-DRB1 alleles have previously been associated with ABPA-CF susceptibility; however, HLA-DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA-CF and determine their roles in susceptibility or protection. Patients with ABPA-CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA-DRB1 and -DQB1 genotyping was performed by the Luminex PCR-SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR-SSP was also performed by high-resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA-DRB1*5:01 and -DRB1*11:04 alleles occurred with greater frequency in patients with ABPA-CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA-CF lacking DRB1*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA-DQB1 region, the HLA-DQB1*06:02 allele occurred more frequently in patients with ABPA-CF than in those with AST and CF and healthy controls, whereas HLA-DQB1*02:01 occurred less frequently in patients with ABPA-CF. These data confirm that there is a correlation between HLA-DRB1*15:01, -DRB1*11:04, DRB1*11:01, -DRB1*04 and -DRB1*07:01 alleles and ABPA-CF susceptibility and suggest that HLA-DQB1*02:01 is an ABPA-CF resistance allele.

  5. A new human leukocyte antigen class Ⅰ allele, HLA- B * 52:11*%HLA-Ⅰ类基因新等位基因HLA-B*52:11的序列分析及确认

    Institute of Scientific and Technical Information of China (English)

    李晓丰; 章旭; 张坤莲; 陈阳; 刘显智; 李剑平

    2011-01-01

    目的 序列分析及确定1个HLA新等位基因.方法 应用基于Luminex平台的聚合酶链式反应-序列特异性寡核苷酸探针(polymerase chain reaction- sequence specific oligonucleotide probes,PCR-SSOP)基因分型方法、PCR产物测序和基因克隆测序方法,通过软件分析该基因序列及与最相近等位基因的序列差异.结果 PCR-SSOP结果显示,该样品HLA-Ⅰ类基因B位点反应格局出现异常提示;测序结果最终表明其B位点第3外显子序列与所有已知HLA-B等位基因序列均不一致,在所检测的外显子第2、3、4区域中,与序列最相近的等位基因HLA-B* 52:01:01的差异只是在第3外显子产生了nt 583 C→T一个核苷酸替代,并导致相应的195位密码子由CAC(H)→TAC(Y),氨基酸组成由组氨酸变为酪氨酸.结论 经序列分析1个HLA-Ⅰ类基因的新等位基因被确认,已被世界卫生组织HLA因子命名委员会正式命名为HLA-B* 52:11.%Objective To identify and confirm a novel HLA allele.Methods A new human leukocyte antigen class Ⅰ allele was found during routine HLA genotyping by polymerase chain reaction-sequence specific oligonucleotide probes(PCR-SSOP) and sequencing-based typing (SBT).Results The novel HLA-B * 52 allele was identical to B * 52:01:01 with an exception of one base substitution at position 583 of exon 3 where a ‘C' was changed to ‘T' resulting in codon 195 changed from CAC(H) to TAC(Y).Conclusion A new HLA class Ⅰ allele,B * 52:11,is identified,and is named officially by the WHO Nomenclature Committee.

  6. Rapid DNA typing for HLA-C using sequence-specific primers (PCR-SSP): identification of serological and non-serologically defined HLA-C alleles including several new alleles.

    Science.gov (United States)

    Bunce, M; Welsh, K I

    1994-01-01

    Detection of HLA-C antigens by complement mediated cytotoxicity using human alloantisera is often difficult. Between 20 to 40% of individuals in every race have undetectable HLA-C locus antigens and 9 out of the 29 sequenced HLA-C alleles so far published encode serologically undetected antigens. In addition, HLA-C molecules are expressed at the cell surface at about 10% of the levels of HLA-A and HLA-B. Recently, amplification of DNA using sequence-specific primers (PCR-SSP) has proved a reliable and rapid method for typing HLA-DR, HLA-DQA and HLA-DQB genes. PCR-SSP takes two hours to perform and is therefore suitable for the genotyping of cadaveric donors. We have designed a set of primers which will positively identify the HLA-C alleles corresponding to the serologically defined series HLA-Cw1, Cw2, Cw3, Cw4, Cw5, Cw6, Cw7 and Cw8. The serologically undetectable alleles have also been detected in groups according to sequence homology. In addition, three new unsequenced variants have been identified. DNA samples from 56 International Histocompatibility Workshop reference cell lines and 103 control individuals have been typed by the HLA-C PCR-SSP technique. 4/56 cell line types and 11/103 normal control individuals types were discrepant with the reported serological types. All combinations of serologically detectable and most of the serologically blank HLA-C antigens can be readily identified. DNA typing for HLA-Cw by PCR-SSP can take as little as 130 minutes from start to finish, including DNA preparation.

  7. Architectures of prototypes and architectural prototyping

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Christensen, Michael; Sandvad, Elmer;

    1998-01-01

    together as a team, but developed a prototype that more than fulfilled the expectations of the shipping company. The prototype should: - complete the first major phase within 10 weeks, - be highly vertical illustrating future work practice, - continuously live up to new requirements from prototyping...... sessions with users, - evolve over a long period of time to contain more functionality - allow for 6-7 developers working intensively in parallel. Explicit focus on the software architecture and letting the architecture evolve with the prototype played a major role in resolving these conflicting......This paper reports from experience obtained through development of a prototype of a global customer service system in a project involving a large shipping company and a university research group. The research group had no previous knowledge of the complex business of shipping and had never worked...

  8. HLA-F coding and regulatory segments variability determined by massively parallel sequencing procedures in a Brazilian population sample.

    Science.gov (United States)

    Lima, Thálitta Hetamaro Ayala; Buttura, Renato Vidal; Donadi, Eduardo Antônio; Veiga-Castelli, Luciana Caricati; Mendes-Junior, Celso Teixeira; Castelli, Erick C

    2016-10-01

    Human Leucocyte Antigen F (HLA-F) is a non-classical HLA class I gene distinguished from its classical counterparts by low allelic polymorphism and distinctive expression patterns. Its exact function remains unknown. It is believed that HLA-F has tolerogenic and immune modulatory properties. Currently, there is little information regarding the HLA-F allelic variation among human populations and the available studies have evaluated only a fraction of the HLA-F gene segment and/or have searched for known alleles only. Here we present a strategy to evaluate the complete HLA-F variability including its 5' upstream, coding and 3' downstream segments by using massively parallel sequencing procedures. HLA-F variability was surveyed on 196 individuals from the Brazilian Southeast. The results indicate that the HLA-F gene is indeed conserved at the protein level, where thirty coding haplotypes or coding alleles were detected, encoding only four different HLA-F full-length protein molecules. Moreover, a same protein molecule is encoded by 82.45% of all coding alleles detected in this Brazilian population sample. However, the HLA-F nucleotide and haplotype variability is much higher than our current knowledge both in Brazilians and considering the 1000 Genomes Project data. This protein conservation is probably a consequence of the key role of HLA-F in the immune system physiology.

  9. Preparation and Identification of HLA-A*1101 Tetramer Loading with Human Cytomegalovirus pp65 Antigen Peptide

    Institute of Scientific and Technical Information of China (English)

    Fengyao Li; Lihui Xu; Qingbing Zha; Xiaoyun Chi; Qiantao Jia; Xianhui He

    2007-01-01

    MHC/peptide tetramer technology has been widely used to study antigen-specific T cells, especially for identifying virus-specific CD8+ T cells in humans. The tetramer molecule is composed of HLA heavy chain, β2-microglobulin (β2m), an antigenic peptide, and fluorescent-labeled streptavidin. To further investigate the HLA-A*1101-restricted CD8+ T cell responses against human cytomegalovirus (HCMV), we established an approach to prepare HLA-A*1101 tetramer complexed with a peptide from HCMV. The cDNA encoding HLA-A*1101 heavy chain was cloned and the prokaryotic expression vector for the ectodomain of HLA-A*1101 fused with a BirA substrate peptide (HLA-A*1101-BSP) at its carboxyl terminus was constructed. The fusion protein was highly expressed as inclusion bodies under optimized conditions in Escherichia coli. Moreover, HLA-A*1101-BSP protein was refolded in the presence of β2m and an HCMV peptide pp6516-24 (GPISGHVLK, GPI). Soluble HLA-A*1101-GPI monomer was biotinylated and purified to a purity of 95%, which was subsequently combined with streptavidin to form tetramers at a yield of > 80%. The HLA-A*1101-GPI tetramers could bind to virus-specific CD8+ T cells,suggesting soluble HLA-A*1101-GPI tetramers were biologically functional. This study provides the basis for further evaluation of HLA-A*1101-restricted CD8+ T cell responses against HCMV infection.

  10. Occurrence of Fatal and Nonfatal Adverse Outcomes after Heart Transplantation in Patients with Pretransplant Noncytotoxic HLA Antibodies

    Directory of Open Access Journals (Sweden)

    Luciano Potena

    2013-01-01

    Full Text Available HLA antibodies (HLA ab in transplant candidates have been associated with poor outcome. However, clinical relevance of noncytotoxic antibodies after heart transplant (HT is controversial. By using a Luminex-based HLA screening, we retested pretransplant sera from HT recipients testing negative for cytotoxic HLA ab and for prospective crossmatch. Out of the 173 consecutive patients assayed (52±13y; 16% females; 47% ischemic etiology, 32 (18% showed pretransplant HLA ab, and 12 (7% tested positive against both class I and class II HLA. Recipients with any HLA ab had poorer survival than those without (65±9 versus 82±3%; P=0.02, accounting for a doubled independent mortality risk (P=0.04. In addition, HLA-ab detection was associated with increased prevalence of early graft failure (35 versus 15%; P=0.05 and late cellular rejection (29 versus 11%; P=0.03. Of the subgroup of 37 patients suspected for antibody mediated rejection (AMR, the 9 with pretransplant HLA ab were more likely to display pathological AMR grade 2 (P=0.04. By an inexpensive, luminex-based, HLA-screening assay, we were able to detect non-cytotoxic HLA ab predicting fatal and nonfatal adverse outcomes after heart transplant. Allocation strategies and desensitization protocols need to be developed and prospectively tested in these patients.

  11. 75 FR 12217 - Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant...

    Science.gov (United States)

    2010-03-15

    ... Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant programs... Perkins Loan, Federal Work-Study (FWS), and Federal Supplemental Educational Opportunity Grant (FSEOG.... (2) General Provisions for the Federal Perkins Loan Program, Federal Work-Study Program, and...

  12. 77 FR 4547 - Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant...

    Science.gov (United States)

    2012-01-30

    ... Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant Programs... requests and documents from postsecondary institutions for the Federal Perkins Loan, Federal Work-Study.... (2) General Provisions for the Federal Perkins Loan Program, Federal Work-Study Program, and...

  13. 78 FR 14776 - Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant...

    Science.gov (United States)

    2013-03-07

    ... Federal Perkins Loan, Federal Work-Study, and Federal Supplemental Educational Opportunity Grant Programs... requests and documents from postsecondary institutions for the Federal Perkins Loan, Federal Work-Study..., Federal Work-Study Program, and Federal Supplemental Educational Opportunity Grant Program, 34 CFR...

  14. Association of HLA-BFNx011502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians

    Directory of Open Access Journals (Sweden)

    Mehta Timir

    2009-01-01

    Full Text Available Background: Stevens-Johnson Syndrome (SJS and toxic epidermal necrolysis are severe cutaneous reactions caused by certain drugs, including antiepileptic carbamazepine. A strong association has been reported between human leucocyte antigen (HLA-BFNx011502 and carbamazepine-induced SJS in Han Chinese patients. European studies suggested that HLA-BFNx011502 is not a universal marker but is ethnicity-specific for Asians. Aim: To study the association between HLA-BFNx011502 and carbamazepine-induced SJS in Indian patients. Methods: Eight individuals who fulfilled the diagnostic criteria of SJS induced by carbamazepine were identified and HLA-B molecular typing was performed. HLA-B genotyping was carried out by polymerase chain reaction using sequence-specific primers. Results: Out of eight patients studied for genotype, six patients were found to have the HLA-BFNx011502 allele. Conclusion: This study suggests an association between HLA-BFNx011502 and carbamazepine-induced SJS in Indian patients.

  15. Everolimus but not mycophenolate mofetil therapy is associated with soluble HLA-G expression in heart transplant patients

    DEFF Research Database (Denmark)

    Sheshgiri, Rohit; Gustafsson, Finn; Sheedy, Jill

    2009-01-01

    mechanisms remain unclear, immunosuppressive therapy has been reported to influence this expression. METHODS: We compared sHLA-G expression in heart transplant recipients receiving two different anti-proliferative agents: mycophenolate mofetil (MMF) and everolimus (RAD). Twelve-hour pharmacokinetic (PK......) studies were conducted in patients after cyclosporine (CsA) administration in conjunction with RAD or MMF, during which plasma HLA-G concentrations were measured by enzyme-linked immunoassay (ELISA). RESULTS: Among patients receiving RAD, 78% expressed detectable levels of plasma HLA-G (1,002 +/- 511 ng....../ml) compared with 25% of patients receiving MMF (612 +/- 438 ng/ml, p = 0.03). In all sHLA-G(+) patients, expression remained constant, with no significant changes in HLA-G levels throughout the 12-hour PK study period. CsA did not appear to influence sHLA-G expression, as there was no correlation between HLA...

  16. Analysis of Architecture Pattern Usage in Legacy System Architecture Documentation

    NARCIS (Netherlands)

    Harrison, Neil B.; Avgeriou, Paris

    2008-01-01

    Architecture patterns are an important tool in architectural design. However, while many architecture patterns have been identified, there is little in-depth understanding of their actual use in software architectures. For instance, there is no overview of how many patterns are used per system or wh

  17. Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance

    Directory of Open Access Journals (Sweden)

    Lisa K. Denzin

    2013-12-01

    Full Text Available Major histocompatibility class II (MHCII molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs. This process is mediated by interaction of MHCII with the conserved, nonpolymorphic MHCII-like molecule HLA-DM (DM. DM activity is directly opposed by HLA-DO (DO, another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, thereby inhibiting peptide loading. Inhibition of DM function enables low stability MHC complexes to survive and populate the surface of APCS. As a consequence, DO promotes the display of a broader pool of low abundance self-peptides. Broadening the peptide repertoire theoretically reduces the likelihood of inadvertently acquiring a density of self-ligands that is sufficient to activate self-reactive T cells. One function of DO, therefore, is to promote T cell tolerance by shaping the visible image of self. Recent data also shows that DO influences the adaptive immune response by controlling B cell entry into the germinal center reaction. This review explores the data supporting these concepts.

  18. Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies

    DEFF Research Database (Denmark)

    Odum, Niels; Ledbetter, J A; Martin, P

    1991-01-01

    adhesion between T and B cells by activating the CD18/CD11a (LFA-1) adhesion pathway. Here we report that monoclonal antibodies (mAb) against HLA-DR (L243, p4.1, HB10a, VI15) and certain broad class II reacting mAb (TU35, TU39), but not anti-DQ (TU22, Leu-10) mAb, induced homotypic aggregation of human......, but not the class I-negative parental line, 221, showed homotypic aggregation in response to an HLA-G specific mAb (87G) and a broad reacting class I-specific mAb (IOT2). Both cell lines responded with aggregation to anti-class II mAb (TU35). The anti-class I mAb, W6/32, had no effect on all cell lines tested...... and two anti-beta 2-microglobulin mAb had variable, weak effects. The aggregation response was an active, temperature-sensitive process which was almost totally abrogated by azide and by cytochalasins B and E, but unaffected by colchicine, EDTA, aphidicolin, actinomycin D and protein tyrosine kinase...

  19. Association of Alport's syndrome with HLA-DR2 antigen in a group of unrelated patients

    Directory of Open Access Journals (Sweden)

    E.A. Donadi

    1998-04-01

    Full Text Available A few family studies have evaluated HLA antigens in Alport's syndrome; however, there are no large population studies. In the present report, we studied 40 unrelated white patients with Alport's syndrome seen at the Unit of Renal Transplantation, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil. HLA-A, -B, -DR and -DQ antigens were typed using a complement-dependent microlymphocytotoxicity assay. A control white population (N = 403 from the same geographical area was also typed for HLA antigens. Although the frequencies of HLA-A and -B antigens of patients were not statistically different from controls, the frequency of HLA-DR2 antigen observed in patients (65% was significantly increased in relation to controls (26%; P<0.001. The relative risk and etiologic fraction for HLA-DR2 antigen were 5.2 and 0.525, respectively. Although few immunological abnormalities have been shown in Alport's syndrome, in this report we emphasize the association of HLA molecules and Alport's syndrome. Besides the well-known inherited molecular defects encoded by type IV collagen genes in Alport's syndrome, the major histocompatibility alleles may be in linkage disequilibrium with these defective collagen genes

  20. Maternal KIR in combination with paternal HLA-C2 regulate human birth weight.

    Science.gov (United States)

    Hiby, Susan E; Apps, Richard; Chazara, Olympe; Farrell, Lydia E; Magnus, Per; Trogstad, Lill; Gjessing, Håkon K; Carrington, Mary; Moffett, Ashley

    2014-06-01

    Human birth weight is subject to stabilizing selection; babies born too small or too large are less likely to survive. Particular combinations of maternal/fetal immune system genes are associated with pregnancies where the babies are ≤ 5th birth weight centile, specifically an inhibitory maternal KIR AA genotype with a paternally derived fetal HLA-C2 ligand. We have now analyzed maternal KIR and fetal HLA-C combinations at the opposite end of the birth weight spectrum. Mother/baby pairs (n = 1316) were genotyped for maternal KIR as well as fetal and maternal HLA-C. Presence of a maternal-activating KIR2DS1 gene was associated with increased birth weight in linear or logistic regression analyses of all pregnancies >5th centile (p = 0.005, n = 1316). Effect of KIR2DS1 was most significant in pregnancies where its ligand, HLA-C2, was paternally but not maternally inherited by a fetus (p = 0.005, odds ratio = 2.65). Thus, maternal KIR are more frequently inhibitory with small babies but activating with big babies. At both extremes of birth weight, the KIR associations occur when their HLA-C2 ligand is paternally inherited by a fetus. We conclude that the two polymorphic immune gene systems, KIR and HLA-C, contribute to successful reproduction by maintaining birth weight between two extremes with a clear role for paternal HLA.

  1. Repression of hla by rot is dependent on sae in Staphylococcus aureus.

    Science.gov (United States)

    Li, Dongmei; Cheung, Ambrose

    2008-03-01

    The regulatory locus sae is a two-component system in Staphylococcus aureus that regulates many important virulence factors, including alpha-toxin (encoded by hla) at the transcriptional level. The SarA homologs Rot and SarT were previously shown to be repressors of hla in selected S. aureus backgrounds. To delineate the interaction of rot and sae and the contribution of sarT to hla expression, an assortment of rot and sae isogenic single mutants, a rot sae double mutant, and a rot sae sarT markerless triple mutant were constructed from wild-type strain COL. Using Northern blot analysis and transcriptional reporter gene green fluorescent protein, fusion, and phenotypic assays, we found that the repression of hla by rot is dependent on sae. A rot sae sarT triple mutant was not able to rescue the hla defect of the rot sae double mutant. Among the three sae promoters, the distal sae P3 promoter is the strongest in vitro. Interestingly, the sae P3 promoter activities correlate with hla expression in rot, rot sae, and rot sae sarT mutants of COL. Transcriptional study has also shown that rot repressed sae, especially at the sae P3 promoter. Collectively, our data implicated the importance of sae in the rot-mediated repression of hla in S. aureus.

  2. A serological study of the HLA-B17 cross-reactive group.

    Science.gov (United States)

    Darke, C

    1984-03-01

    The HLA-B17 cross-reactive group and the participation of the subdivisions of B17 ( Bw57 and Bw58 ) in cross-reactivity were investigated by the serological analysis of 81 cytotoxic HLA antisera (produced by pregnancy alone), the HLA typing of the antiserum donors and the identification of their immunizing antigens. The sera, all of which contained B17 activity, were produced in response to one of 10 HLA antigens (A2, Bw44, Bw49, Bw51, Bw55 , Bw56 , Bw57 , Bw58 , Bw62 and Bw63 ). Antisera stimulated by Bw57 and Bw58 cross-reacted with Bw49 and both subdivisions of B5 and B15, with bidirectional cross-reactivity occurring in many instances. Bidirectional cross-reactivity was also observed between Bw57 and A2 (an A2 stimulated antiserum also reacted with Bw58 ), and Bw57 and Bw55 . Immunization by Bw62 produced some antisera which showed strong cross-reactivity with Bw57 but no reactivity with Bw58 . Significant HLA-B antigen frequency disturbances were found in the responders to the B17 cross-reactive group antigens. Twenty-five HLA antigens were found to comprise the B17 cross-reactive group and its related cross-reactions. The multideterminant nature of the HLA antigens is again emphasized by these findings.

  3. HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats.

    Directory of Open Access Journals (Sweden)

    Phoebe Lin

    Full Text Available The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human β2-microglobulin (hβ2m, compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hβ2m and hβ2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.

  4. Pregnancy and breastfeeding: a new theory for sHLA-G in breast cancer patients?

    Science.gov (United States)

    Zidi, Inès; Kharrat, Najla; Sebai, Refaat; Zidi, Nour; Ben Yahia, Hamza; Bouaziz, Aicha; Rifi, Hela; Mezlini, Amel; Rizzo, Roberta

    2016-04-01

    It is now widely recognized that HLA-G molecule is implicated in immune tolerance and particularly in immune subversion of tumor cells. In this study, we explored levels of soluble HLA-G (sHLA-G) in plasma samples obtained from women with breast cancer (BC). Additionally, we correlated sHLA-G concentration with pregnancy and breastfeeding history. We reported in this preliminary work significant differences in sHLA-G levels between BC patients with/without breastfeeding experience (p = 0.04). Interestingly, among women with BC, only those without previous pregnancy experience present significant increase in sHLA-G (p = 0.02). Of relevance, we demonstrated that patients without both pregnancy and breastfeeding history have advanced SBR III grade, associated with significant enhancement in tumor size compared with patients who had both experiences (p = 0.028). Taken together, our results indicate the potential implication of previous pregnancy and breastfeeding experience in sHLA-G expression during BC. We theorized that having pregnancy and breastfeeding history may protect against advanced BC stages.

  5. Associations between polymorphisms of HLA-B gene and postmenopausal osteoporosis in Chinese Han population.

    Science.gov (United States)

    Li, S-M; Zhou, D-X; Liu, M-Y

    2014-08-01

    Osteoporosis is a systemic skeletal disease, which is more prevalent in postmenopausal women. Osteoporosis likely develops beginning with genetic risk. This study explored the relationships between polymorphisms of HLA-B gene and postmenopausal osteoporosis in a Chinese Han population. Polymerase chain reaction sequence-based typing (PCR-SBT) method was used for DNA typing at HLA-B locus in 70 patients with postmenopausal osteoporosis and 73 healthy controls in female Han population of Shaanxi Province, situated in north-western China. We found that 40 HLA-B alleles in postmenopausal osteoporosis patients and control subjects, respectively. Furthermore, the frequency of HLA-B* 3501 allele was significantly higher in postmenopausal osteoporosis patients than in the control group (P = 0.033), and the relative risk was 7.632 (95% CI: 0.927-62.850). Our results suggest that HLA-B* 3501 was likely an important risk factor for postmenopausal osteoporosis. As different populations have different HLA polymorphisms, further investigation of the relationship of various HLA genes and osteoporosis with larger sample size is still necessary in the future.

  6. HLA DRB1 alleles and hepatitis C virus infection in chronic kidney disease patients.

    Science.gov (United States)

    Shaheen, Noha Mohamed Hosni; Soliman, Amin Roshdy; El-Khashab, Sahier Omar; Hanna, Mariam Onsy Farag

    2013-01-01

    T cell responses against HCV are regulated by the host's human leukocyte antigen (HLA) alleles, which thus are ideal candidate genes to investigate for associations with HCV susceptibility. We aimed to identify associations of HLA DRB1* alleles with HCV infection in a high risk of exposure population, chronic kidney disease (CKD) patients on dialysis, and to study any possible relationships with allele zygosity. The study population comprised 110 HCV infected and 143 HCV uninfected CKD patients undergoing regular hemodialysis. HLA DRB1* alleles were determined using polymerase chain reaction followed by hybridization with sequence-specific oligonucleotide probes. We found a significant negative association between HLA DRB1*03 and HCV infection, but the association did not retain significance after adjustment for multiple comparisons. HLA DRB1*03 was found at reduced frequency in HCV antibody positive compared to HCV antibody negative CKD patients on regular dialysis (corrected p was not significant). No significant association between HCV infection and HLA DRB1* zygosity was observed. Our results suggest that there is minimal evidence for a significant role of a particular HLA DRB1* allele or allele zygosity in the susceptibility or protection to HCV in high-risk hemodialysis patients with similar exposure to infection.

  7. HLA class I donor-specific triplet antibodies detected after renal transplantation.

    Science.gov (United States)

    Varnavidou-Nicolaidou, A; Doxiadis, I I N; Iniotaki-Theodoraki, A; Patargias, T; Stavropoulos-Giokas, C; Kyriakides, G K

    2004-01-01

    The purpose of this study was to investigate whether IgG, non-donor-specific anti-HLA class I antibodies (HLAabI) detected after renal transplantation recognize immunogenic amino acid triplets expressed on the foreign graft. In addition, we sought to evaluate the effect of these antibodies as well as other posttransplant HLAabI on graft outcome. Posttransplant sera from 264 renal recipients were tested for the presence of IgG HLAabI and HLA class II-specific alloantibodies (HLAabII) by ELISA. The HLAMatchmaker computer algorithm was used to define the HLA class I non-donor-specific antibodies, which seem to recognize immunogenic amino acid triplets. Donor-specific triplet antibodies (DSTRab) were detected in 16 of 22 (72.7%) recipients based on at least one HLA-A or -B mismatched antigen with the donor. DSTRab were found either without (n = 7) or with (n = 9) HLA donor-specific antibodies (HLA-DSA). The presence of DSTRab alone in the periphery was associated with acute rejection, whereas the presence of both DSTRab and HLA-DSA was associated with chronic rejection and graft failure.

  8. HLA-G profile of infertile couples who underwent assisted reproduction treatment.

    Science.gov (United States)

    Costa, Cynthia Hernandes; Gelmini, Georgia Fernanda; Nardi, Fabiola Silva; Roxo, Valéria Maria Munhoz Sperandio; Schuffner, Alessandro; da Graça Bicalho, Maria

    2016-12-01

    HLA-G codes for a non-classical class I (Ib) protein which is mainly expressed in trophoblast cells. Many pieces of evidence pointed out its essential role conferring immunological tolerance to the fetus. Some HLA-G alleles have been linked to enhanced or reduced HLA-G protein levels expression, which have been associated with reproductive failure. In this study 33 couples undergoing ART (assisted reproduction treatment; n=66) and 120 couples who conceived naturally (controls; n=240) were enrolled in the study. Genotyping was performed by SBT and tagged an 1837bp at 5'URR as well as exons 2, 3 and4 of HLA-G. Alleles, genotypes and haplotypes were compared between infertile and control groups using Fisher Exact Test. The haplotype HLA-G(∗)010101b/HLA-G(∗)01:01:01 showed statistically significant higher frequency in control groups. The immunogenetics of infertility is complex and might be dependent on different genes involved in the establishment of a successful pregnancy. A better understanding of HLA-G alleles and haplotypes structure and how the genetic diversity at their regulatory sites could impact on their level of expression and build up the susceptibility or protection conditions may shed light on the comprehension of immunogenetics mechanisms acting at the fetus-maternal interface.

  9. Robot Electronics Architecture

    Science.gov (United States)

    Garrett, Michael; Magnone, Lee; Aghazarian, Hrand; Baumgartner, Eric; Kennedy, Brett

    2008-01-01

    An electronics architecture has been developed to enable the rapid construction and testing of prototypes of robotic systems. This architecture is designed to be a research vehicle of great stability, reliability, and versatility. A system according to this architecture can easily be reconfigured (including expanded or contracted) to satisfy a variety of needs with respect to input, output, processing of data, sensing, actuation, and power. The architecture affords a variety of expandable input/output options that enable ready integration of instruments, actuators, sensors, and other devices as independent modular units. The separation of different electrical functions onto independent circuit boards facilitates the development of corresponding simple and modular software interfaces. As a result, both hardware and software can be made to expand or contract in modular fashion while expending a minimum of time and effort.

  10. Architecture for the senses

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2009-01-01

    findings from the PhD thesis 'A House for the Senses' by the author, a study of architectural requirements in housing design implied by a sensory impairment. The empirical research project is based on qualitative interviews and 1:1 testing in existing housing with participants who were either blind, deaf......Accommodating sensory disabilities in architectural design requires specific design considerations. These are different from the ones included by the existing design concept 'accessibility', which primarily accommodates physical disabilites. Hence a new design concept 'sensory accessbility......' is presented as a parallel and complementary concept to the existing one. Sensory accessiblity accommodates sensory disabilities and describes architectural design requirements needed to ensure access to to the sensory experiences and architectural quality of a given space. The article is based on research...

  11. DSP Architecture Design Essentials

    CERN Document Server

    Marković, Dejan

    2012-01-01

    In DSP Architecture Design Essentials, authors Dejan Marković and Robert W. Brodersen cover a key subject for the successful realization of DSP algorithms for communications, multimedia, and healthcare applications. The book addresses the need for DSP architecture design that maps advanced DSP algorithms to hardware in the most power- and area-efficient way. The key feature of this text is a design methodology based on a high-level design model that leads to hardware implementation with minimum power and area. The methodology includes algorithm-level considerations such as automated word-length reduction and intrinsic data properties that can be leveraged to reduce hardware complexity. From a high-level data-flow graph model, an architecture exploration methodology based on linear programming is used to create an array of architectural solutions tailored to the underlying hardware technology. The book is supplemented with online material: bibliography, design examples, CAD tutorials and custom software.

  12. Analyzing architecture articles

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In the present study, we express the quality, function, and characteristics of architecture to help people comprehensively understand what architecture is. We also reveal the problems and conflict found in population, land, water resources, pollution, energy, and the organization systems in construction. China’s economy is transforming. We should focus on the cities, architectural environment, energy conservation, emission-reduction, and low-carbon output that will result in successful green development. We should macroscopically and microscopically analyze the development, from the natural environment to the artificial environment; from the relationship between human beings and nature to the combination of social ecology in cities, and farmlands. We must learn to develop and control them harmoniously and scientifically to provide a foundation for the methods used in architecture research.

  13. Ancient Chinese Architecture

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    CHINESE people have accu-mulated a great deal ofexperience in architecture,constantly improving building ma-terials and thus creating uniquebuilding styles.The history of ancient Chinesearchitechtural development can be

  14. ARCHITECTURE INFORMS HISTORY

    Institute of Scientific and Technical Information of China (English)

    ZAN JIFANG

    2010-01-01

    @@ Agroup of ancient architecture in Dengfeng, central China's Henan Province, was added to the world heritage list at the 34th session of the World Heritage Committee in Brazil on August 1 this year. The architectural col-lection is China's 39th property inscribed on the list, and the third world heritage site in the province after the Longmen Grottoes and Yinxu in Anyang, site of the capital of the late Shang Dynasty (1600-1046 B.C.).

  15. BioArchitecture

    OpenAIRE

    Gunning, Peter

    2012-01-01

    Volume 1 has defined the scope of BioArchitecture. From the outset we have strived to ensure that BioArchitecture is not limited to the three major polymer systems of the cytoplasm. I am happy to say that a cursory glance at the contents of volume 1 makes it clear that we are interested in all aspects of bioarchitecture from molecules to polymers to cells to tissue to the organism.

  16. Essential software architecture

    CERN Document Server

    Gorton, Ian

    2011-01-01

    Job titles like ""Technical Architect"" and ""Chief Architect"" nowadays abound in software industry, yet many people suspect that ""architecture"" is one of the most overused and least understood terms in professional software development. Gorton's book tries to resolve this dilemma. It concisely describes the essential elements of knowledge and key skills required to be a software architect. The explanations encompass the essentials of architecture thinking, practices, and supporting technologies. They range from a general understanding of structure and quality attributes through technical i

  17. Artificial cognition architectures

    CERN Document Server

    Crowder, James A; Friess, Shelli A

    2013-01-01

    The goal of this book is to establish the foundation, principles, theory, and concepts that are the backbone of real, autonomous Artificial Intelligence. Presented here are some basic human intelligence concepts framed for Artificial Intelligence systems. These include concepts like Metacognition and Metamemory, along with architectural constructs for Artificial Intelligence versions of human brain functions like the prefrontal cortex. Also presented are possible hardware and software architectures that lend themselves to learning, reasoning, and self-evolution

  18. Climate and architecture

    DEFF Research Database (Denmark)

    Tind Kristensen, Eva; Friis Møller, Winnie; Rotne, Georg

    2010-01-01

    Climate and Architecture analyserer klimaets rolle i arkitekturen. Intentionen med bogen er at pege på nogle af de mange muligheder for bygningers klimaregulering, som et mere detaljeret studie af de lokale klimatiske forhold og den stedlige byggeskik tilbyder.......Climate and Architecture analyserer klimaets rolle i arkitekturen. Intentionen med bogen er at pege på nogle af de mange muligheder for bygningers klimaregulering, som et mere detaljeret studie af de lokale klimatiske forhold og den stedlige byggeskik tilbyder....

  19. Greek architecture now

    DEFF Research Database (Denmark)

    Skousbøll, Karin Merete

    2006-01-01

    With the author's Scandinavian viewpoint the aim of this book has been an investigation into contemporary Greek architecture and at the same time providing an understanding for its essential characteristics based on the historic, cultural heritage of Hellas.......With the author's Scandinavian viewpoint the aim of this book has been an investigation into contemporary Greek architecture and at the same time providing an understanding for its essential characteristics based on the historic, cultural heritage of Hellas....

  20. The HLA-A*31:01 allele: influence on carbamazepine treatment

    Science.gov (United States)

    Yip, Vincent Lai Ming; Pirmohamed, Munir

    2017-01-01

    Carbamazepine (CBZ) is an effective anticonvulsant that can sometimes cause hypersensitivity reactions that vary in frequency and severity. Strong associations have been reported between specific human leukocyte antigen (HLA) alleles and susceptibility to CBZ hypersensitivity reactions. Screening for HLA-B*15:02 is mandated in patients from South East Asia because of a strong association with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). HLA-A*31:01 predisposes to multiple phenotypes of CBZ hypersensitivity including maculopapular exanthema, hypersensitivity syndrome, and SJS/TEN in a range of populations including Europeans, Japanese, South Koreans and Han Chinese, although the effect size varies between the different phenotypes and populations. Between 47 Caucasians and 67 Japanese patients would need to be tested for HLA-A*31:01 in order to avoid a single case of CBZ hypersensitivity. A cost-effectiveness study has demonstrated that HLA-A*31:01 screening would be cost-effective. Patient preference assessment has also revealed that patients prefer pharmacogenetic screening and prescription of alternative anticonvulsants compared to current standard of practice without pharmacogenetic testing. For patients who test positive for HLA-A*31:01, alternative treatments are available. When alternatives have failed or are unavailable, HLA-A*31:01 testing can alert clinicians to 1) patients who are at increased risk of CBZ hypersensitivity who can then be targeted for more intensive monitoring and 2) increase diagnostic certainty in cases where hypersensitivity has already occurred, so patients can be advised to avoid structurally related drugs in the future. On the basis of the current evidence, we would favor screening all patients for HLA-A*31:01 and HLA-B*15:02 prior to starting CBZ therapy. PMID:28203102