WorldWideScience

Sample records for markup language aml

  1. A Leaner, Meaner Markup Language.

    Science.gov (United States)

    Online & CD-ROM Review, 1997

    1997-01-01

    In 1996 a working group of the World Wide Web Consortium developed and released a simpler form of markup language, Extensible Markup Language (XML), combining the flexibility of standard Generalized Markup Language (SGML) and the Web suitability of HyperText Markup Language (HTML). Reviews SGML and discusses XML's suitability for journal…

  2. The Accelerator Markup Language and the Universal Accelerator Parser

    International Nuclear Information System (INIS)

    Sagan, D.; Forster, M.; Cornell U., LNS; Bates, D.A.; LBL, Berkeley; Wolski, A.; Liverpool U.; Cockcroft Inst. Accel. Sci. Tech.; Schmidt, F.; CERN; Walker, N.J.; DESY; Larrieu, T.; Roblin, Y.; Jefferson Lab; Pelaia, T.; Oak Ridge; Tenenbaum, P.; Woodley, M.; SLAC; Reiche, S.; UCLA

    2006-01-01

    A major obstacle to collaboration on accelerator projects has been the sharing of lattice description files between modeling codes. To address this problem, a lattice description format called Accelerator Markup Language (AML) has been created. AML is based upon the standard eXtensible Markup Language (XML) format; this provides the flexibility for AML to be easily extended to satisfy changing requirements. In conjunction with AML, a software library, called the Universal Accelerator Parser (UAP), is being developed to speed the integration of AML into any program. The UAP is structured to make it relatively straightforward (by giving appropriate specifications) to read and write lattice files in any format. This will allow programs that use the UAP code to read a variety of different file formats. Additionally, this will greatly simplify conversion of files from one format to another. Currently, besides AML, the UAP supports the MAD lattice format

  3. Astronomical Instrumentation System Markup Language

    Science.gov (United States)

    Goldbaum, Jesse M.

    2016-05-01

    The Astronomical Instrumentation System Markup Language (AISML) is an Extensible Markup Language (XML) based file format for maintaining and exchanging information about astronomical instrumentation. The factors behind the need for an AISML are first discussed followed by the reasons why XML was chosen as the format. Next it's shown how XML also provides the framework for a more precise definition of an astronomical instrument and how these instruments can be combined to form an Astronomical Instrumentation System (AIS). AISML files for several instruments as well as one for a sample AIS are provided. The files demonstrate how AISML can be utilized for various tasks from web page generation and programming interface to instrument maintenance and quality management. The advantages of widespread adoption of AISML are discussed.

  4. The geometry description markup language

    International Nuclear Information System (INIS)

    Chytracek, R.

    2001-01-01

    Currently, a lot of effort is being put on designing complex detectors. A number of simulation and reconstruction frameworks and applications have been developed with the aim to make this job easier. A very important role in this activity is played by the geometry description of the detector apparatus layout and its working environment. However, no real common approach to represent geometry data is available and such data can be found in various forms starting from custom semi-structured text files, source code (C/C++/FORTRAN), to XML and database solutions. The XML (Extensible Markup Language) has proven to provide an interesting approach for describing detector geometries, with several different but incompatible XML-based solutions existing. Therefore, interoperability and geometry data exchange among different frameworks is not possible at present. The author introduces a markup language for geometry descriptions. Its aim is to define a common approach for sharing and exchanging of geometry description data. Its requirements and design have been driven by experience and user feedback from existing projects which have their geometry description in XML

  5. Answer Markup Algorithms for Southeast Asian Languages.

    Science.gov (United States)

    Henry, George M.

    1991-01-01

    Typical markup methods for providing feedback to foreign language learners are not applicable to languages not written in a strictly linear fashion. A modification of Hart's edit markup software is described, along with a second variation based on a simple edit distance algorithm adapted to a general Southeast Asian font system. (10 references)…

  6. An Introduction to the Extensible Markup Language (XML).

    Science.gov (United States)

    Bryan, Martin

    1998-01-01

    Describes Extensible Markup Language (XML), a subset of the Standard Generalized Markup Language (SGML) that is designed to make it easy to interchange structured documents over the Internet. Topics include Document Type Definition (DTD), components of XML, the use of XML, text and non-text elements, and uses for XML-coded files. (LRW)

  7. Genomic Sequence Variation Markup Language (GSVML).

    Science.gov (United States)

    Nakaya, Jun; Kimura, Michio; Hiroi, Kaei; Ido, Keisuke; Yang, Woosung; Tanaka, Hiroshi

    2010-02-01

    With the aim of making good use of internationally accumulated genomic sequence variation data, which is increasing rapidly due to the explosive amount of genomic research at present, the development of an interoperable data exchange format and its international standardization are necessary. Genomic Sequence Variation Markup Language (GSVML) will focus on genomic sequence variation data and human health applications, such as gene based medicine or pharmacogenomics. We developed GSVML through eight steps, based on case analysis and domain investigations. By focusing on the design scope to human health applications and genomic sequence variation, we attempted to eliminate ambiguity and to ensure practicability. We intended to satisfy the requirements derived from the use case analysis of human-based clinical genomic applications. Based on database investigations, we attempted to minimize the redundancy of the data format, while maximizing the data covering range. We also attempted to ensure communication and interface ability with other Markup Languages, for exchange of omics data among various omics researchers or facilities. The interface ability with developing clinical standards, such as the Health Level Seven Genotype Information model, was analyzed. We developed the human health-oriented GSVML comprising variation data, direct annotation, and indirect annotation categories; the variation data category is required, while the direct and indirect annotation categories are optional. The annotation categories contain omics and clinical information, and have internal relationships. For designing, we examined 6 cases for three criteria as human health application and 15 data elements for three criteria as data formats for genomic sequence variation data exchange. The data format of five international SNP databases and six Markup Languages and the interface ability to the Health Level Seven Genotype Model in terms of 317 items were investigated. GSVML was developed as

  8. STMML. A markup language for scientific, technical and medical publishing

    Directory of Open Access Journals (Sweden)

    Peter Murray-Rust

    2006-01-01

    Full Text Available STMML is an XML-based markup language covering many generic aspects of scientific information. It has been developed as a re-usable core for more specific markup languages. It supports data structures, data types, metadata, scientific units and some basic components of scientific narrative. The central means of adding semantic information is through dictionaries. The specification is through an XML Schema which can be used to validate STMML documents or fragments. Many examples of the language are given.

  9. Descriptive markup languages and the development of digital humanities

    Directory of Open Access Journals (Sweden)

    Boris Bosančić

    2012-11-01

    Full Text Available The paper discusses the role of descriptive markup languages in the development of digital humanities, a new research discipline that is part of social sciences and humanities, which focuses on the use of computers in research. A chronological review of the development of digital humanities, and then descriptive markup languages is exposed, through several developmental stages. It is shown that the development of digital humanities since the mid-1980s and the appearance of SGML, markup language that was the foundation of TEI, a key standard for the encoding and exchange of humanities texts in the digital environment, is inseparable from the development of markup languages. Special attention is dedicated to the presentation of the Text Encoding Initiative – TEI development, a key organization that developed the titled standard, both from organizational and markup perspectives. By this time, TEI standard is published in five versions, and during 2000s SGML is replaced by XML markup language. Key words: markup languages, digital humanities, text encoding, TEI, SGML, XML

  10. Chemical Markup, XML and the World-Wide Web. 8. Polymer Markup Language.

    Science.gov (United States)

    Adams, Nico; Winter, Jerry; Murray-Rust, Peter; Rzepa, Henry S

    2008-11-01

    Polymers are among the most important classes of materials but are only inadequately supported by modern informatics. The paper discusses the reasons why polymer informatics is considerably more challenging than small molecule informatics and develops a vision for the computer-aided design of polymers, based on modern semantic web technologies. The paper then discusses the development of Polymer Markup Language (PML). PML is an extensible language, designed to support the (structural) representation of polymers and polymer-related information. PML closely interoperates with Chemical Markup Language (CML) and overcomes a number of the previously identified challenges.

  11. On the Power of Fuzzy Markup Language

    CERN Document Server

    Loia, Vincenzo; Lee, Chang-Shing; Wang, Mei-Hui

    2013-01-01

    One of the most successful methodology that arose from the worldwide diffusion of Fuzzy Logic is Fuzzy Control. After the first attempts dated in the seventies, this methodology has been widely exploited for controlling many industrial components and systems. At the same time, and very independently from Fuzzy Logic or Fuzzy Control, the birth of the Web has impacted upon almost all aspects of computing discipline. Evolution of Web, Web 2.0 and Web 3.0 has been making scenarios of ubiquitous computing much more feasible;  consequently information technology has been thoroughly integrated into everyday objects and activities. What happens when Fuzzy Logic meets Web technology? Interesting results might come out, as you will discover in this book. Fuzzy Mark-up Language is a son of this synergistic view, where some technological issues of Web are re-interpreted taking into account the transparent notion of Fuzzy Control, as discussed here.  The concept of a Fuzzy Control that is conceived and modeled in terms...

  12. AllerML: markup language for allergens.

    Science.gov (United States)

    Ivanciuc, Ovidiu; Gendel, Steven M; Power, Trevor D; Schein, Catherine H; Braun, Werner

    2011-06-01

    Many concerns have been raised about the potential allergenicity of novel, recombinant proteins into food crops. Guidelines, proposed by WHO/FAO and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity or cross-reactivities of all proteins introduced, for example, to improve nutritional value or promote crop resistance. However, there are no universally accepted standards that can be used to encode data on the biology of allergens to facilitate using data from multiple databases in this screening. Therefore, we developed AllerML a markup language for allergens to assist in the automated exchange of information between databases and in the integration of the bioinformatics tools that are used to investigate allergenicity and cross-reactivity. As proof of concept, AllerML was implemented using the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/) database. General implementation of AllerML will promote automatic flow of validated data that will aid in allergy research and regulatory analysis. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. PIML: the Pathogen Information Markup Language.

    Science.gov (United States)

    He, Yongqun; Vines, Richard R; Wattam, Alice R; Abramochkin, Georgiy V; Dickerman, Allan W; Eckart, J Dana; Sobral, Bruno W S

    2005-01-01

    A vast amount of information about human, animal and plant pathogens has been acquired, stored and displayed in varied formats through different resources, both electronically and otherwise. However, there is no community standard format for organizing this information or agreement on machine-readable format(s) for data exchange, thereby hampering interoperation efforts across information systems harboring such infectious disease data. The Pathogen Information Markup Language (PIML) is a free, open, XML-based format for representing pathogen information. XSLT-based visual presentations of valid PIML documents were developed and can be accessed through the PathInfo website or as part of the interoperable web services federation known as ToolBus/PathPort. Currently, detailed PIML documents are available for 21 pathogens deemed of high priority with regard to public health and national biological defense. A dynamic query system allows simple queries as well as comparisons among these pathogens. Continuing efforts are being taken to include other groups' supporting PIML and to develop more PIML documents. All the PIML-related information is accessible from http://www.vbi.vt.edu/pathport/pathinfo/

  14. Definition of an XML markup language for clinical laboratory procedures and comparison with generic XML markup.

    Science.gov (United States)

    Saadawi, Gilan M; Harrison, James H

    2006-10-01

    Clinical laboratory procedure manuals are typically maintained as word processor files and are inefficient to store and search, require substantial effort for review and updating, and integrate poorly with other laboratory information. Electronic document management systems could improve procedure management and utility. As a first step toward building such systems, we have developed a prototype electronic format for laboratory procedures using Extensible Markup Language (XML). Representative laboratory procedures were analyzed to identify document structure and data elements. This information was used to create a markup vocabulary, CLP-ML, expressed as an XML Document Type Definition (DTD). To determine whether this markup provided advantages over generic markup, we compared procedures structured with CLP-ML or with the vocabulary of the Health Level Seven, Inc. (HL7) Clinical Document Architecture (CDA) narrative block. CLP-ML includes 124 XML tags and supports a variety of procedure types across different laboratory sections. When compared with a general-purpose markup vocabulary (CDA narrative block), CLP-ML documents were easier to edit and read, less complex structurally, and simpler to traverse for searching and retrieval. In combination with appropriate software, CLP-ML is designed to support electronic authoring, reviewing, distributing, and searching of clinical laboratory procedures from a central repository, decreasing procedure maintenance effort and increasing the utility of procedure information. A standard electronic procedure format could also allow laboratories and vendors to share procedures and procedure layouts, minimizing duplicative word processor editing. Our results suggest that laboratory-specific markup such as CLP-ML will provide greater benefit for such systems than generic markup.

  15. Improving Interoperability by Incorporating UnitsML Into Markup Languages.

    Science.gov (United States)

    Celebi, Ismet; Dragoset, Robert A; Olsen, Karen J; Schaefer, Reinhold; Kramer, Gary W

    2010-01-01

    Maintaining the integrity of analytical data over time is a challenge. Years ago, data were recorded on paper that was pasted directly into a laboratory notebook. The digital age has made maintaining the integrity of data harder. Nowadays, digitized analytical data are often separated from information about how the sample was collected and prepared for analysis and how the data were acquired. The data are stored on digital media, while the related information about the data may be written in a paper notebook or stored separately in other digital files. Sometimes the connection between this "scientific meta-data" and the analytical data is lost, rendering the spectrum or chromatogram useless. We have been working with ASTM Subcommittee E13.15 on Analytical Data to create the Analytical Information Markup Language or AnIML-a new way to interchange and store spectroscopy and chromatography data based on XML (Extensible Markup Language). XML is a language for describing what data are by enclosing them in computer-useable tags. Recording the units associated with the analytical data and metadata is an essential issue for any data representation scheme that must be addressed by all domain-specific markup languages. As scientific markup languages proliferate, it is very desirable to have a single scheme for handling units to facilitate moving information between different data domains. At NIST, we have been developing a general markup language just for units that we call UnitsML. This presentation will describe how UnitsML is used and how it is being incorporated into AnIML.

  16. The Behavior Markup Language: Recent Developments and Challenges

    NARCIS (Netherlands)

    Vilhjalmsson, Hannes; Cantelmo, Nathan; Cassell, Justine; Chafai, Nicholas E.; Kipp, Michael; Kopp, Stefan; Mancini, Maurizio; Marsella, Stacy; Marshall, Andrew N.; Pelachaud, Catherine; Ruttkay, Z.M.; Thorisson, Kristinn R.; van Welbergen, H.; van der Werf, Rick J.; Pelachaud, Catherine; Martin, Jean-Claude; Andre, Elisabeth; Collet, Gerard; Karpouzis, Kostas; Pele, Danielle

    2007-01-01

    Since the beginning of the SAIBA effort to unify key interfaces in the multi-modal behavior generation process, the Behavior Markup Language (BML) has both gained ground as an important component in many projects worldwide, and continues to undergo further refinement. This paper reports on the

  17. The Petri Net Markup Language : concepts, technology, and tools

    NARCIS (Netherlands)

    Billington, J.; Christensen, S.; Hee, van K.M.; Kindler, E.; Kummer, O.; Petrucci, L.; Post, R.D.J.; Stehno, C.; Weber, M.; Aalst, van der W.M.P.; Best, E.

    2003-01-01

    The Petri Net Markup Language (PNML) is an XML-based interchange format for Petri nets. In order to support different versions of Petri nets and, in particular, future versions of Petri nets, PNML allows the definition of Petri net types.Due to this flexibility, PNML is a starting point for a

  18. Wanda ML - a markup language for digital annotation

    NARCIS (Netherlands)

    Franke, K.Y.; Guyon, I.; Schomaker, L.R.B.; Vuurpijl, L.G.

    2004-01-01

    WANDAML is an XML-based markup language for the annotation and filter journaling of digital documents. It addresses in particular the needs of forensic handwriting data examination, by allowing experts to enter information about writer, material (pen, paper), script and content, and to record chains

  19. The WANDAML Markup Language for Digital Document Annotation

    NARCIS (Netherlands)

    Franke, K.; Guyon, I.; Schomaker, L.; Vuurpijl, L.

    2004-01-01

    WANDAML is an XML-based markup language for the annotation and filter journaling of digital documents. It addresses in particular the needs of forensic handwriting data examination, by allowing experts to enter information about writer, material (pen, paper), script and content, and to record chains

  20. Field Data and the Gas Hydrate Markup Language

    Directory of Open Access Journals (Sweden)

    Ralf Löwner

    2007-06-01

    Full Text Available Data and information exchange are crucial for any kind of scientific research activities and are becoming more and more important. The comparison between different data sets and different disciplines creates new data, adds value, and finally accumulates knowledge. Also the distribution and accessibility of research results is an important factor for international work. The gas hydrate research community is dispersed across the globe and therefore, a common technical communication language or format is strongly demanded. The CODATA Gas Hydrate Data Task Group is creating the Gas Hydrate Markup Language (GHML, a standard based on the Extensible Markup Language (XML to enable the transport, modeling, and storage of all manner of objects related to gas hydrate research. GHML initially offers an easily deducible content because of the text-based encoding of information, which does not use binary data. The result of these investigations is a custom-designed application schema, which describes the features, elements, and their properties, defining all aspects of Gas Hydrates. One of the components of GHML is the "Field Data" module, which is used for all data and information coming from the field. It considers international standards, particularly the standards defined by the W3C (World Wide Web Consortium and the OGC (Open Geospatial Consortium. Various related standards were analyzed and compared with our requirements (in particular the Geographic Markup Language (ISO19136, GML and the whole ISO19000 series. However, the requirements demanded a quick solution and an XML application schema readable for any scientist without a background in information technology. Therefore, ideas, concepts and definitions have been used to build up the modules of GHML without importing any of these Markup languages. This enables a comprehensive schema and simple use.

  1. Instrument Remote Control via the Astronomical Instrument Markup Language

    Science.gov (United States)

    Sall, Ken; Ames, Troy; Warsaw, Craig; Koons, Lisa; Shafer, Richard

    1998-01-01

    The Instrument Remote Control (IRC) project ongoing at NASA's Goddard Space Flight Center's (GSFC) Information Systems Center (ISC) supports NASA's mission by defining an adaptive intranet-based framework that provides robust interactive and distributed control and monitoring of remote instruments. An astronomical IRC architecture that combines the platform-independent processing capabilities of Java with the power of Extensible Markup Language (XML) to express hierarchical data in an equally platform-independent, as well as human readable manner, has been developed. This architecture is implemented using a variety of XML support tools and Application Programming Interfaces (API) written in Java. IRC will enable trusted astronomers from around the world to easily access infrared instruments (e.g., telescopes, cameras, and spectrometers) located in remote, inhospitable environments, such as the South Pole, a high Chilean mountaintop, or an airborne observatory aboard a Boeing 747. Using IRC's frameworks, an astronomer or other scientist can easily define the type of onboard instrument, control the instrument remotely, and return monitoring data all through the intranet. The Astronomical Instrument Markup Language (AIML) is the first implementation of the more general Instrument Markup Language (IML). The key aspects of our approach to instrument description and control applies to many domains, from medical instruments to machine assembly lines. The concepts behind AIML apply equally well to the description and control of instruments in general. IRC enables us to apply our techniques to several instruments, preferably from different observatories.

  2. Experimental Applications of Automatic Test Markup Language (ATML)

    Science.gov (United States)

    Lansdowne, Chatwin A.; McCartney, Patrick; Gorringe, Chris

    2012-01-01

    The authors describe challenging use-cases for Automatic Test Markup Language (ATML), and evaluate solutions. The first case uses ATML Test Results to deliver active features to support test procedure development and test flow, and bridging mixed software development environments. The second case examines adding attributes to Systems Modelling Language (SysML) to create a linkage for deriving information from a model to fill in an ATML document set. Both cases are outside the original concept of operations for ATML but are typical when integrating large heterogeneous systems with modular contributions from multiple disciplines.

  3. Nassi-Schneiderman Diagram in HTML Based on AML

    Science.gov (United States)

    Menyhárt, László

    2013-01-01

    In an earlier work I defined an extension of XML called Algorithm Markup Language (AML) for easy and understandable coding in an IDE which supports XML editing (e.g. NetBeans). The AML extension contains annotations and native language (English or Hungarian) tag names used when coding our algorithm. This paper presents a drawing tool with which…

  4. Field Markup Language: biological field representation in XML.

    Science.gov (United States)

    Chang, David; Lovell, Nigel H; Dokos, Socrates

    2007-01-01

    With an ever increasing number of biological models available on the internet, a standardized modeling framework is required to allow information to be accessed or visualized. Based on the Physiome Modeling Framework, the Field Markup Language (FML) is being developed to describe and exchange field information for biological models. In this paper, we describe the basic features of FML, its supporting application framework and its ability to incorporate CellML models to construct tissue-scale biological models. As a typical application example, we present a spatially-heterogeneous cardiac pacemaker model which utilizes both FML and CellML to describe and solve the underlying equations of electrical activation and propagation.

  5. Geospatial Visualization of Scientific Data Through Keyhole Markup Language

    Science.gov (United States)

    Wernecke, J.; Bailey, J. E.

    2008-12-01

    The development of virtual globes has provided a fun and innovative tool for exploring the surface of the Earth. However, it has been the paralleling maturation of Keyhole Markup Language (KML) that has created a new medium and perspective through which to visualize scientific datasets. Originally created by Keyhole Inc., and then acquired by Google in 2004, in 2007 KML was given over to the Open Geospatial Consortium (OGC). It became an OGC international standard on 14 April 2008, and has subsequently been adopted by all major geobrowser developers (e.g., Google, Microsoft, ESRI, NASA) and many smaller ones (e.g., Earthbrowser). By making KML a standard at a relatively young stage in its evolution, developers of the language are seeking to avoid the issues that plagued the early World Wide Web and development of Hypertext Markup Language (HTML). The popularity and utility of Google Earth, in particular, has been enhanced by KML features such as the Smithsonian volcano layer and the dynamic weather layers. Through KML, users can view real-time earthquake locations (USGS), view animations of polar sea-ice coverage (NSIDC), or read about the daily activities of chimpanzees (Jane Goodall Institute). Perhaps even more powerful is the fact that any users can create, edit, and share their own KML, with no or relatively little knowledge of manipulating computer code. We present an overview of the best current scientific uses of KML and a guide to how scientists can learn to use KML themselves.

  6. Development of Markup Language for Medical Record Charting: A Charting Language.

    Science.gov (United States)

    Jung, Won-Mo; Chae, Younbyoung; Jang, Bo-Hyoung

    2015-01-01

    Nowadays a lot of trials for collecting electronic medical records (EMRs) exist. However, structuring data format for EMR is an especially labour-intensive task for practitioners. Here we propose a new mark-up language for medical record charting (called Charting Language), which borrows useful properties from programming languages. Thus, with Charting Language, the text data described in dynamic situation can be easily used to extract information.

  7. Earth Science Markup Language: Transitioning From Design to Application

    Science.gov (United States)

    Moe, Karen; Graves, Sara; Ramachandran, Rahul

    2002-01-01

    The primary objective of the proposed Earth Science Markup Language (ESML) research is to transition from design to application. The resulting schema and prototype software will foster community acceptance for the "define once, use anywhere" concept central to ESML. Supporting goals include: 1. Refinement of the ESML schema and software libraries in cooperation with the user community. 2. Application of the ESML schema and software libraries to a variety of Earth science data sets and analysis tools. 3. Development of supporting prototype software for enhanced ease of use. 4. Cooperation with standards bodies in order to assure ESML is aligned with related metadata standards as appropriate. 5. Widespread publication of the ESML approach, schema, and software.

  8. Pathology data integration with eXtensible Markup Language.

    Science.gov (United States)

    Berman, Jules J

    2005-02-01

    It is impossible to overstate the importance of XML (eXtensible Markup Language) as a data organization tool. With XML, pathologists can annotate all of their data (clinical and anatomic) in a format that can transform every pathology report into a database, without compromising narrative structure. The purpose of this manuscript is to provide an overview of XML for pathologists. Examples will demonstrate how pathologists can use XML to annotate individual data elements and to structure reports in a common format that can be merged with other XML files or queried using standard XML tools. This manuscript gives pathologists a glimpse into how XML allows pathology data to be linked to other types of biomedical data and reduces our dependence on centralized proprietary databases.

  9. Computerization of guidelines: towards a "guideline markup language".

    Science.gov (United States)

    Dart, T; Xu, Y; Chatellier, G; Degoulet, P

    2001-01-01

    Medical decision making is one of the most difficult daily tasks for physicians. Guidelines have been designed to reduce variance between physicians in daily practice, to improve patient outcomes and to control costs. In fact, few physicians use guidelines in daily practice. A way to ease the use of guidelines is to implement computerised guidelines (computer reminders). We present in this paper a method of computerising guidelines. Our objectives were: 1) to propose a generic model that can be instantiated for any specific guidelines; 2) to use eXtensible Markup Language (XML) as a guideline representation language to instantiate the generic model for a specific guideline. Our model is an object representation of a clinical algorithm, it has been validated by running two different guidelines issued by a French official Agency. In spite of some limitations, we found that this model is expressive enough to represent complex guidelines devoted to diabetes and hypertension management. We conclude that XML can be used as a description format to structure guidelines and as an interface between paper-based guidelines and computer applications.

  10. Extensions to the Dynamic Aerospace Vehicle Exchange Markup Language

    Science.gov (United States)

    Brian, Geoffrey J.; Jackson, E. Bruce

    2011-01-01

    The Dynamic Aerospace Vehicle Exchange Markup Language (DAVE-ML) is a syntactical language for exchanging flight vehicle dynamic model data. It provides a framework for encoding entire flight vehicle dynamic model data packages for exchange and/or long-term archiving. Version 2.0.1 of DAVE-ML provides much of the functionality envisioned for exchanging aerospace vehicle data; however, it is limited in only supporting scalar time-independent data. Additional functionality is required to support vector and matrix data, abstracting sub-system models, detailing dynamics system models (both discrete and continuous), and defining a dynamic data format (such as time sequenced data) for validation of dynamics system models and vehicle simulation packages. Extensions to DAVE-ML have been proposed to manage data as vectors and n-dimensional matrices, and record dynamic data in a compatible form. These capabilities will improve the clarity of data being exchanged, simplify the naming of parameters, and permit static and dynamic data to be stored using a common syntax within a single file; thereby enhancing the framework provided by DAVE-ML for exchanging entire flight vehicle dynamic simulation models.

  11. QUESTION ANSWERING SYSTEM BERBASIS ARTIFICIAL INTELLIGENCE MARKUP LANGUAGE SEBAGAI MEDIA INFORMASI

    Directory of Open Access Journals (Sweden)

    Fajrin Azwary

    2016-04-01

    Full Text Available Artificial intelligence technology nowadays, can be processed with a variety of forms, such as chatbot, and the various methods, one of them using Artificial Intelligence Markup Language (AIML. AIML using template matching, by comparing the specific patterns in the database. AIML template design process begins with determining the necessary information, then formed into questions, these questions adapted to AIML pattern. From the results of the study, can be known that the Question-Answering System in the chatbot using Artificial Intelligence Markup Language are able to communicate and deliver information. Keywords: Artificial Intelligence, Template Matching, Artificial Intelligence Markup Language, AIML Teknologi kecerdasan buatan saat ini dapat diolah dengan berbagai macam bentuk, seperti ChatBot, dan berbagai macam metode, salah satunya menggunakan Artificial Intelligence Markup Language (AIML. AIML menggunakan metode template matching yaitu dengan membandingkan pola-pola tertentu pada database. Proses perancangan template AIML diawali dengan menentukan informasi yang diperlukan, kemudian dibentuk menjadi pertanyaan, pertanyaan tersebut disesuaikan dengan bentuk pattern AIML. Hasil penelitian dapat diperoleh bahwa Question-Answering System dalam bentuk ChatBot menggunakan Artificial Intelligence Markup Language dapat berkomunikasi dan menyampaikan informasi. Kata kunci : Kecerdasan Buatan, Pencocokan Pola, Artificial Intelligence Markup Language, AIML

  12. CytometryML: a markup language for analytical cytology

    Science.gov (United States)

    Leif, Robert C.; Leif, Stephanie H.; Leif, Suzanne B.

    2003-06-01

    Cytometry Markup Language, CytometryML, is a proposed new analytical cytology data standard. CytometryML is a set of XML schemas for encoding both flow cytometry and digital microscopy text based data types. CytometryML schemas reference both DICOM (Digital Imaging and Communications in Medicine) codes and FCS keywords. These schemas provide representations for the keywords in FCS 3.0 and will soon include DICOM microscopic image data. Flow Cytometry Standard (FCS) list-mode has been mapped to the DICOM Waveform Information Object. A preliminary version of a list mode binary data type, which does not presently exist in DICOM, has been designed. This binary type is required to enhance the storage and transmission of flow cytometry and digital microscopy data. Index files based on Waveform indices will be used to rapidly locate the cells present in individual subsets. DICOM has the advantage of employing standard file types, TIF and JPEG, for Digital Microscopy. Using an XML schema based representation means that standard commercial software packages such as Excel and MathCad can be used to analyze, display, and store analytical cytometry data. Furthermore, by providing one standard for both DICOM data and analytical cytology data, it eliminates the need to create and maintain special purpose interfaces for analytical cytology data thereby integrating the data into the larger DICOM and other clinical communities. A draft version of CytometryML is available at www.newportinstruments.com.

  13. The basics of CrossRef extensible markup language

    Directory of Open Access Journals (Sweden)

    Rachael Lammey

    2014-08-01

    Full Text Available CrossRef is an association of scholarly publishers that develops shared infrastructure to support more effective scholarly communications. Launched in 2000, CrossRef’s citation-linking network today covers over 68 million journal articles and other content items (books chapters, data, theses, and technical reports from thousands of scholarly and professional publishers around the globe. CrossRef has over 4,000 member publishers who join as members in order to avail of a number of CrossRef services, reference linking via the Digital Object Identifier (DOI being the core service. To deposit CrossRef DOIs, publishers and editors need to become familiar with the basics of extensible markup language (XML. This article will give an introduction to CrossRef XML and what publishers need to do in order to start to deposit DOIs with CrossRef and thus ensure their publications are discoverable and can be linked to consistently in an online environment.

  14. TumorML: Concept and requirements of an in silico cancer modelling markup language.

    Science.gov (United States)

    Johnson, David; Cooper, Jonathan; McKeever, Steve

    2011-01-01

    This paper describes the initial groundwork carried out as part of the European Commission funded Transatlantic Tumor Model Repositories project, to develop a new markup language for computational cancer modelling, TumorML. In this paper we describe the motivations for such a language, arguing that current state-of-the-art biomodelling languages are not suited to the cancer modelling domain. We go on to describe the work that needs to be done to develop TumorML, the conceptual design, and a description of what existing markup languages will be used to compose the language specification.

  15. Systematic reconstruction of TRANSPATH data into cell system markup language.

    Science.gov (United States)

    Nagasaki, Masao; Saito, Ayumu; Li, Chen; Jeong, Euna; Miyano, Satoru

    2008-06-23

    Many biological repositories store information based on experimental study of the biological processes within a cell, such as protein-protein interactions, metabolic pathways, signal transduction pathways, or regulations of transcription factors and miRNA. Unfortunately, it is difficult to directly use such information when generating simulation-based models. Thus, modeling rules for encoding biological knowledge into system-dynamics-oriented standardized formats would be very useful for fully understanding cellular dynamics at the system level. We selected the TRANSPATH database, a manually curated high-quality pathway database, which provides a plentiful source of cellular events in humans, mice, and rats, collected from over 31,500 publications. In this work, we have developed 16 modeling rules based on hybrid functional Petri net with extension (HFPNe), which is suitable for graphical representing and simulating biological processes. In the modeling rules, each Petri net element is incorporated with Cell System Ontology to enable semantic interoperability of models. As a formal ontology for biological pathway modeling with dynamics, CSO also defines biological terminology and corresponding icons. By combining HFPNe with the CSO features, it is possible to make TRANSPATH data to simulation-based and semantically valid models. The results are encoded into a biological pathway format, Cell System Markup Language (CSML), which eases the exchange and integration of biological data and models. By using the 16 modeling rules, 97% of the reactions in TRANSPATH are converted into simulation-based models represented in CSML. This reconstruction demonstrates that it is possible to use our rules to generate quantitative models from static pathway descriptions.

  16. A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

    Science.gov (United States)

    Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

    2016-06-17

    Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function.

  17. Generating Systems Biology Markup Language Models from the Synthetic Biology Open Language.

    Science.gov (United States)

    Roehner, Nicholas; Zhang, Zhen; Nguyen, Tramy; Myers, Chris J

    2015-08-21

    In the context of synthetic biology, model generation is the automated process of constructing biochemical models based on genetic designs. This paper discusses the use cases for model generation in genetic design automation (GDA) software tools and introduces the foundational concepts of standards and model annotation that make this process useful. Finally, this paper presents an implementation of model generation in the GDA software tool iBioSim and provides an example of generating a Systems Biology Markup Language (SBML) model from a design of a 4-input AND sensor written in the Synthetic Biology Open Language (SBOL).

  18. An object-oriented approach for harmonization of multimedia markup languages

    Science.gov (United States)

    Chen, Yih-Feng; Kuo, May-Chen; Sun, Xiaoming; Kuo, C.-C. Jay

    2003-12-01

    An object-oriented methodology is proposed to harmonize several different markup languages in this research. First, we adopt the Unified Modelling Language (UML) as the data model to formalize the concept and the process of the harmonization process between the eXtensible Markup Language (XML) applications. Then, we design the Harmonization eXtensible Markup Language (HXML) based on the data model and formalize the transformation between the Document Type Definitions (DTDs) of the original XML applications and HXML. The transformation between instances is also discussed. We use the harmonization of SMIL and X3D as an example to demonstrate the proposed methodology. This methodology can be generalized to various application domains.

  19. Development of clinical contents model markup language for electronic health records.

    Science.gov (United States)

    Yun, Ji-Hyun; Ahn, Sun-Ju; Kim, Yoon

    2012-09-01

    To develop dedicated markup language for clinical contents models (CCM) to facilitate the active use of CCM in electronic health record systems. Based on analysis of the structure and characteristics of CCM in the clinical domain, we designed extensible markup language (XML) based CCM markup language (CCML) schema manually. CCML faithfully reflects CCM in both the syntactic and semantic aspects. As this language is based on XML, it can be expressed and processed in computer systems and can be used in a technology-neutral way. CCML HAS THE FOLLOWING STRENGTHS: it is machine-readable and highly human-readable, it does not require a dedicated parser, and it can be applied for existing electronic health record systems.

  20. SuML: A Survey Markup Language for Generalized Survey Encoding

    Science.gov (United States)

    Barclay, MW; Lober, WB; Karras, BT

    2002-01-01

    There is a need in clinical and research settings for a sophisticated, generalized, web based survey tool that supports complex logic, separation of content and presentation, and computable guidelines. There are many commercial and open source survey packages available that provide simple logic; few provide sophistication beyond “goto” statements; none support the use of guidelines. These tools are driven by databases, static web pages, and structured documents using markup languages such as eXtensible Markup Language (XML). We propose a generalized, guideline aware language and an implementation architecture using open source standards.

  1. Development of the atomic and molecular data markup language for internet data exchange

    International Nuclear Information System (INIS)

    Ralchenko, Yuri; Clark Robert E.H.; Humbert, Denis; Schultz, David R.; Kato, Takako; Rhee, Yong Joo

    2006-01-01

    Accelerated development of the Internet technologies, including those relevant to the atomic and molecular physics, poses new requirements for the proper communication between computers, users and applications. To this end, a new standard for atomic and molecular data exchange that would reflect the recent achievements in this field becomes a necessity. We report here on development of the Atomic and Molecular Data Markup Language (AMDML) that is based on eXtensible Markup Language (XML). The present version of the AMDML Schema covers atomic spectroscopic data as well as the electron-impact collisions. (author)

  2. The Systems Biology Markup Language (SBML: Language Specification for Level 3 Version 2 Core

    Directory of Open Access Journals (Sweden)

    Hucka Michael

    2018-03-01

    Full Text Available Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language, validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/.

  3. The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 2 Core.

    Science.gov (United States)

    Hucka, Michael; Bergmann, Frank T; Dräger, Andreas; Hoops, Stefan; Keating, Sarah M; Le Novère, Nicolas; Myers, Chris J; Olivier, Brett G; Sahle, Sven; Schaff, James C; Smith, Lucian P; Waltemath, Dagmar; Wilkinson, Darren J

    2018-03-09

    Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 2 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language), validation rules that determine the validity of an SBML document, and examples of models in SBML form. The design of Version 2 differs from Version 1 principally in allowing new MathML constructs, making more child elements optional, and adding identifiers to all SBML elements instead of only selected elements. Other materials and software are available from the SBML project website at http://sbml.org/.

  4. The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core.

    Science.gov (United States)

    Hucka, Michael; Bergmann, Frank T; Hoops, Stefan; Keating, Sarah M; Sahle, Sven; Schaff, James C; Smith, Lucian P; Wilkinson, Darren J

    2015-09-04

    Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/.

  5. The Systems Biology Markup Language (SBML: Language Specification for Level 3 Version 1 Core

    Directory of Open Access Journals (Sweden)

    Hucka Michael

    2018-04-01

    Full Text Available Computational models can help researchers to interpret data, understand biological functions, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that different software systems can exchange. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Release 2 of Version 1 of SBML Level 3 Core. The specification defines the data structures prescribed by SBML, their encoding in XML (the eXtensible Markup Language, validation rules that determine the validity of an SBML document, and examples of models in SBML form. No design changes have been made to the description of models between Release 1 and Release 2; changes are restricted to the format of annotations, the correction of errata and the addition of clarifications. Other materials and software are available from the SBML project website at http://sbml.org/.

  6. A primer on the Petri Net Markup Language and ISO/IEC 15909-2

    DEFF Research Database (Denmark)

    Hillah, L. M.; Kindler, Ekkart; Kordon, F.

    2009-01-01

    Standard, defines a transfer format for high-level nets. The transfer format defined in Part 2 of ISO/IEC 15909 is (or is based on) the \\emph{Petri Net Markup Language} (PNML), which was originally introduced as an interchange format for different kinds of Petri nets. In ISO/IEC 15909-2, however...

  7. Developing a Markup Language for Encoding Graphic Content in Plan Documents

    Science.gov (United States)

    Li, Jinghuan

    2009-01-01

    While deliberating and making decisions, participants in urban development processes need easy access to the pertinent content scattered among different plans. A Planning Markup Language (PML) has been proposed to represent the underlying structure of plans in an XML-compliant way. However, PML currently covers only textual information and lacks…

  8. Representing Information in Patient Reports Using Natural Language Processing and the Extensible Markup Language

    Science.gov (United States)

    Friedman, Carol; Hripcsak, George; Shagina, Lyuda; Liu, Hongfang

    1999-01-01

    Objective: To design a document model that provides reliable and efficient access to clinical information in patient reports for a broad range of clinical applications, and to implement an automated method using natural language processing that maps textual reports to a form consistent with the model. Methods: A document model that encodes structured clinical information in patient reports while retaining the original contents was designed using the extensible markup language (XML), and a document type definition (DTD) was created. An existing natural language processor (NLP) was modified to generate output consistent with the model. Two hundred reports were processed using the modified NLP system, and the XML output that was generated was validated using an XML validating parser. Results: The modified NLP system successfully processed all 200 reports. The output of one report was invalid, and 199 reports were valid XML forms consistent with the DTD. Conclusions: Natural language processing can be used to automatically create an enriched document that contains a structured component whose elements are linked to portions of the original textual report. This integrated document model provides a representation where documents containing specific information can be accurately and efficiently retrieved by querying the structured components. If manual review of the documents is desired, the salient information in the original reports can also be identified and highlighted. Using an XML model of tagging provides an additional benefit in that software tools that manipulate XML documents are readily available. PMID:9925230

  9. The carbohydrate sequence markup language (CabosML): an XML description of carbohydrate structures.

    Science.gov (United States)

    Kikuchi, Norihiro; Kameyama, Akihiko; Nakaya, Shuuichi; Ito, Hiromi; Sato, Takashi; Shikanai, Toshihide; Takahashi, Yoriko; Narimatsu, Hisashi

    2005-04-15

    Bioinformatics resources for glycomics are very poor as compared with those for genomics and proteomics. The complexity of carbohydrate sequences makes it difficult to define a common language to represent them, and the development of bioinformatics tools for glycomics has not progressed. In this study, we developed a carbohydrate sequence markup language (CabosML), an XML description of carbohydrate structures. The language definition (XML Schema) and an experimental database of carbohydrate structures using an XML database management system are available at http://www.phoenix.hydra.mki.co.jp/CabosDemo.html kikuchi@hydra.mki.co.jp.

  10. Semantic Web Services with Web Ontology Language (OWL-S) - Specification of Agent-Services for DARPA Agent Markup Language (DAML)

    National Research Council Canada - National Science Library

    Sycara, Katia P

    2006-01-01

    CMU did research and development on semantic web services using OWL-S, the semantic web service language under the Defense Advanced Research Projects Agency- DARPA Agent Markup Language (DARPA-DAML) program...

  11. ArdenML: The Arden Syntax Markup Language (or Arden Syntax: It's Not Just Text Any More!)

    Science.gov (United States)

    Sailors, R. Matthew

    2001-01-01

    It is no longer necessary to think of Arden Syntax as simply a text-based knowledge base format. The development of ArdenML (Arden Syntax Markup Language), an XML-based markup language allows structured access to most of the maintenance and library categories without the need to write or buy a compiler may lead to the development of simple commercial and freeware tools for processing Arden Syntax Medical Logic Modules (MLMs)

  12. QUESTION ANSWERING SYSTEM BERBASIS ARTIFICIAL INTELLIGENCE MARKUP LANGUAGE SEBAGAI MEDIA INFORMASI

    OpenAIRE

    Fajrin Azwary; Fatma Indriani; Dodon T. Nugrahadi

    2016-01-01

    Artificial intelligence technology nowadays, can be processed with a variety of forms, such as chatbot, and the various methods, one of them using Artificial Intelligence Markup Language (AIML). AIML using template matching, by comparing the specific patterns in the database. AIML template design process begins with determining the necessary information, then formed into questions, these questions adapted to AIML pattern. From the results of the study, can be known that the Question-Answering...

  13. Standard generalized markup language: A guide for transmitting encoded bibliographic records

    International Nuclear Information System (INIS)

    1994-09-01

    This document provides the guidance necessary to transmit to DOE's Office of Scientific and Technical Information (OSTI) an encoded bibliographic record that conforms to International Standard ISO 8879, Information Processing -- Text and office systems -- Standard Generalized Markup Language (SGML). Included in this document are element and attribute tag definitions, sample bibliographic records, the bibliographic document type definition, and instructions on how to transmit a bibliographic record electronically to OSTI

  14. Standard generalized markup language: A guide for transmitting encoded bibliographic records

    Energy Technology Data Exchange (ETDEWEB)

    1994-09-01

    This document provides the guidance necessary to transmit to DOE`s Office of Scientific and Technical Information (OSTI) an encoded bibliographic record that conforms to International Standard ISO 8879, Information Processing -- Text and office systems -- Standard Generalized Markup Language (SGML). Included in this document are element and attribute tag definitions, sample bibliographic records, the bibliographic document type definition, and instructions on how to transmit a bibliographic record electronically to OSTI.

  15. Root system markup language: toward a unified root architecture description language.

    Science.gov (United States)

    Lobet, Guillaume; Pound, Michael P; Diener, Julien; Pradal, Christophe; Draye, Xavier; Godin, Christophe; Javaux, Mathieu; Leitner, Daniel; Meunier, Félicien; Nacry, Philippe; Pridmore, Tony P; Schnepf, Andrea

    2015-03-01

    The number of image analysis tools supporting the extraction of architectural features of root systems has increased in recent years. These tools offer a handy set of complementary facilities, yet it is widely accepted that none of these software tools is able to extract in an efficient way the growing array of static and dynamic features for different types of images and species. We describe the Root System Markup Language (RSML), which has been designed to overcome two major challenges: (1) to enable portability of root architecture data between different software tools in an easy and interoperable manner, allowing seamless collaborative work; and (2) to provide a standard format upon which to base central repositories that will soon arise following the expanding worldwide root phenotyping effort. RSML follows the XML standard to store two- or three-dimensional image metadata, plant and root properties and geometries, continuous functions along individual root paths, and a suite of annotations at the image, plant, or root scale at one or several time points. Plant ontologies are used to describe botanical entities that are relevant at the scale of root system architecture. An XML schema describes the features and constraints of RSML, and open-source packages have been developed in several languages (R, Excel, Java, Python, and C#) to enable researchers to integrate RSML files into popular research workflow. © 2015 American Society of Plant Biologists. All Rights Reserved.

  16. Fuzzy Markup language : a new solution for transparent intelligent agents

    NARCIS (Netherlands)

    Acampora, G.; Loia, V.

    2011-01-01

    From an industrial and technological point of view, fuzzy control theory deals with the development of a particular system controller on a specific hardware by means of an open or legacy programming language that is useful to address, in a high-level fashion, the hardware constraints. Independently

  17. A methodology to annotate systems biology markup language models with the synthetic biology open language.

    Science.gov (United States)

    Roehner, Nicholas; Myers, Chris J

    2014-02-21

    Recently, we have begun to witness the potential of synthetic biology, noted here in the form of bacteria and yeast that have been genetically engineered to produce biofuels, manufacture drug precursors, and even invade tumor cells. The success of these projects, however, has often failed in translation and application to new projects, a problem exacerbated by a lack of engineering standards that combine descriptions of the structure and function of DNA. To address this need, this paper describes a methodology to connect the systems biology markup language (SBML) to the synthetic biology open language (SBOL), existing standards that describe biochemical models and DNA components, respectively. Our methodology involves first annotating SBML model elements such as species and reactions with SBOL DNA components. A graph is then constructed from the model, with vertices corresponding to elements within the model and edges corresponding to the cause-and-effect relationships between these elements. Lastly, the graph is traversed to assemble the annotating DNA components into a composite DNA component, which is used to annotate the model itself and can be referenced by other composite models and DNA components. In this way, our methodology can be used to build up a hierarchical library of models annotated with DNA components. Such a library is a useful input to any future genetic technology mapping algorithm that would automate the process of composing DNA components to satisfy a behavioral specification. Our methodology for SBML-to-SBOL annotation is implemented in the latest version of our genetic design automation (GDA) software tool, iBioSim.

  18. The medical simulation markup language - simplifying the biomechanical modeling workflow.

    Science.gov (United States)

    Suwelack, Stefan; Stoll, Markus; Schalck, Sebastian; Schoch, Nicolai; Dillmann, Rüdiger; Bendl, Rolf; Heuveline, Vincent; Speidel, Stefanie

    2014-01-01

    Modeling and simulation of the human body by means of continuum mechanics has become an important tool in diagnostics, computer-assisted interventions and training. This modeling approach seeks to construct patient-specific biomechanical models from tomographic data. Usually many different tools such as segmentation and meshing algorithms are involved in this workflow. In this paper we present a generalized and flexible description for biomechanical models. The unique feature of the new modeling language is that it not only describes the final biomechanical simulation, but also the workflow how the biomechanical model is constructed from tomographic data. In this way, the MSML can act as a middleware between all tools used in the modeling pipeline. The MSML thus greatly facilitates the prototyping of medical simulation workflows for clinical and research purposes. In this paper, we not only detail the XML-based modeling scheme, but also present a concrete implementation. Different examples highlight the flexibility, robustness and ease-of-use of the approach.

  19. Automatically Generating a Distributed 3D Battlespace Using USMTF and XML-MTF Air Tasking Order, Extensible Markup Language (XML) and Virtual Reality Modeling Language (VRML)

    National Research Council Canada - National Science Library

    Murray, Mark

    2000-01-01

    .... To more effectively exchange and share data, the Defense Information Systems Agency (DISA), the lead agency for the USMTF, is actively engaged in extending the USMTF standard with a new data sharing technology called Extensible Markup Language (XML...

  20. Automatically Generating a Distributed 3D Virtual Battlespace Using USMTF and XML-MTF Air Tasking Orders, Extensible Markup Language (XML) and Virtual Reality Modeling Language (VRML)

    National Research Council Canada - National Science Library

    Murray, Mark

    2000-01-01

    .... To more effectively exchange and share data, the Defense Information Systems Agency (DISA), the lead agency for the USMTF, is actively engaged in extending the USMTF standard with a new data sharing technology called Extensible Markup Language (XML...

  1. Pharmacometrics Markup Language (PharmML): Opening New Perspectives for Model Exchange in Drug Development

    Science.gov (United States)

    Swat, MJ; Moodie, S; Wimalaratne, SM; Kristensen, NR; Lavielle, M; Mari, A; Magni, P; Smith, MK; Bizzotto, R; Pasotti, L; Mezzalana, E; Comets, E; Sarr, C; Terranova, N; Blaudez, E; Chan, P; Chard, J; Chatel, K; Chenel, M; Edwards, D; Franklin, C; Giorgino, T; Glont, M; Girard, P; Grenon, P; Harling, K; Hooker, AC; Kaye, R; Keizer, R; Kloft, C; Kok, JN; Kokash, N; Laibe, C; Laveille, C; Lestini, G; Mentré, F; Munafo, A; Nordgren, R; Nyberg, HB; Parra-Guillen, ZP; Plan, E; Ribba, B; Smith, G; Trocóniz, IF; Yvon, F; Milligan, PA; Harnisch, L; Karlsson, M; Hermjakob, H; Le Novère, N

    2015-01-01

    The lack of a common exchange format for mathematical models in pharmacometrics has been a long-standing problem. Such a format has the potential to increase productivity and analysis quality, simplify the handling of complex workflows, ensure reproducibility of research, and facilitate the reuse of existing model resources. Pharmacometrics Markup Language (PharmML), currently under development by the Drug Disease Model Resources (DDMoRe) consortium, is intended to become an exchange standard in pharmacometrics by providing means to encode models, trial designs, and modeling steps. PMID:26225259

  2. Pharmacometrics Markup Language (PharmML): Opening New Perspectives for Model Exchange in Drug Development.

    Science.gov (United States)

    Swat, M J; Moodie, S; Wimalaratne, S M; Kristensen, N R; Lavielle, M; Mari, A; Magni, P; Smith, M K; Bizzotto, R; Pasotti, L; Mezzalana, E; Comets, E; Sarr, C; Terranova, N; Blaudez, E; Chan, P; Chard, J; Chatel, K; Chenel, M; Edwards, D; Franklin, C; Giorgino, T; Glont, M; Girard, P; Grenon, P; Harling, K; Hooker, A C; Kaye, R; Keizer, R; Kloft, C; Kok, J N; Kokash, N; Laibe, C; Laveille, C; Lestini, G; Mentré, F; Munafo, A; Nordgren, R; Nyberg, H B; Parra-Guillen, Z P; Plan, E; Ribba, B; Smith, G; Trocóniz, I F; Yvon, F; Milligan, P A; Harnisch, L; Karlsson, M; Hermjakob, H; Le Novère, N

    2015-06-01

    The lack of a common exchange format for mathematical models in pharmacometrics has been a long-standing problem. Such a format has the potential to increase productivity and analysis quality, simplify the handling of complex workflows, ensure reproducibility of research, and facilitate the reuse of existing model resources. Pharmacometrics Markup Language (PharmML), currently under development by the Drug Disease Model Resources (DDMoRe) consortium, is intended to become an exchange standard in pharmacometrics by providing means to encode models, trial designs, and modeling steps.

  3. cluML: A markup language for clustering and cluster validity assessment of microarray data.

    Science.gov (United States)

    Bolshakova, Nadia; Cunningham, Pádraig

    2005-01-01

    cluML is a new markup language for microarray data clustering and cluster validity assessment. The XML-based format has been designed to address some of the limitations observed in traditional formats, such as inability to store multiple clustering (including biclustering) and validation results within a dataset. cluML is an effective tool to support biomedical knowledge representation in gene expression data analysis. Although cluML was developed for DNA microarray analysis applications, it can be effectively used for the representation of clustering and for the validation of other biomedical and physical data that has no limitations.

  4. Semantic markup of nouns and adjectives for the Electronic corpus of texts in Tuvan language

    Directory of Open Access Journals (Sweden)

    Bajlak Ch. Oorzhak

    2016-12-01

    Full Text Available The article examines the progress of semantic markup of the Electronic corpus of texts in Tuvan language (ECTTL, which is another stage of adding Tuvan texts to the database and marking up the corpus. ECTTL is a collaborative project by researchers from Tuvan State University (Research and Education Center of Turkic Studies and Department of Information Technologies. Semantic markup of Tuvan lexis will come as a search engine and reference system which will help users find text snippets containing words with desired meanings in ECTTL. The first stage of this process is setting up databases of basic lexemes of Tuvan language. All meaningful lexemes were classified into the following semantic groups: humans, animals, objects, natural objects and phenomena, and abstract concepts. All Tuvan object nouns, as well as both descriptive and relative adjectives, were assigned to one of these lexico-semantic classes. Each class, sub-class and descriptor is tagged in Tuvan, Russian and English; these tags, in turn, will help automatize searching. The databases of meaningful lexemes of Tuvan language will also outline their lexical combinations. The automatized system will contain information on semantic combinations of adjectives with nouns, adverbs with verbs, nouns with verbs, as well as on the combinations which are semantically incompatible.

  5. Gaussian Process Regression (GPR) Representation in Predictive Model Markup Language (PMML).

    Science.gov (United States)

    Park, J; Lechevalier, D; Ak, R; Ferguson, M; Law, K H; Lee, Y-T T; Rachuri, S

    2017-01-01

    This paper describes Gaussian process regression (GPR) models presented in predictive model markup language (PMML). PMML is an extensible-markup-language (XML) -based standard language used to represent data-mining and predictive analytic models, as well as pre- and post-processed data. The previous PMML version, PMML 4.2, did not provide capabilities for representing probabilistic (stochastic) machine-learning algorithms that are widely used for constructing predictive models taking the associated uncertainties into consideration. The newly released PMML version 4.3, which includes the GPR model, provides new features: confidence bounds and distribution for the predictive estimations. Both features are needed to establish the foundation for uncertainty quantification analysis. Among various probabilistic machine-learning algorithms, GPR has been widely used for approximating a target function because of its capability of representing complex input and output relationships without predefining a set of basis functions, and predicting a target output with uncertainty quantification. GPR is being employed to various manufacturing data-analytics applications, which necessitates representing this model in a standardized form for easy and rapid employment. In this paper, we present a GPR model and its representation in PMML. Furthermore, we demonstrate a prototype using a real data set in the manufacturing domain.

  6. SBRML: a markup language for associating systems biology data with models.

    Science.gov (United States)

    Dada, Joseph O; Spasić, Irena; Paton, Norman W; Mendes, Pedro

    2010-04-01

    Research in systems biology is carried out through a combination of experiments and models. Several data standards have been adopted for representing models (Systems Biology Markup Language) and various types of relevant experimental data (such as FuGE and those of the Proteomics Standards Initiative). However, until now, there has been no standard way to associate a model and its entities to the corresponding datasets, or vice versa. Such a standard would provide a means to represent computational simulation results as well as to frame experimental data in the context of a particular model. Target applications include model-driven data analysis, parameter estimation, and sharing and archiving model simulations. We propose the Systems Biology Results Markup Language (SBRML), an XML-based language that associates a model with several datasets. Each dataset is represented as a series of values associated with model variables, and their corresponding parameter values. SBRML provides a flexible way of indexing the results to model parameter values, which supports both spreadsheet-like data and multidimensional data cubes. We present and discuss several examples of SBRML usage in applications such as enzyme kinetics, microarray gene expression and various types of simulation results. The XML Schema file for SBRML is available at http://www.comp-sys-bio.org/SBRML under the Academic Free License (AFL) v3.0.

  7. Simulation Experiment Description Markup Language (SED-ML Level 1 Version 3 (L1V3

    Directory of Open Access Journals (Sweden)

    Bergmann Frank T.

    2018-03-01

    Full Text Available The creation of computational simulation experiments to inform modern biological research poses challenges to reproduce, annotate, archive, and share such experiments. Efforts such as SBML or CellML standardize the formal representation of computational models in various areas of biology. The Simulation Experiment Description Markup Language (SED-ML describes what procedures the models are subjected to, and the details of those procedures. These standards, together with further COMBINE standards, describe models sufficiently well for the reproduction of simulation studies among users and software tools. The Simulation Experiment Description Markup Language (SED-ML is an XML-based format that encodes, for a given simulation experiment, (i which models to use; (ii which modifications to apply to models before simulation; (iii which simulation procedures to run on each model; (iv how to post-process the data; and (v how these results should be plotted and reported. SED-ML Level 1 Version 1 (L1V1 implemented support for the encoding of basic time course simulations. SED-ML L1V2 added support for more complex types of simulations, specifically repeated tasks and chained simulation procedures. SED-ML L1V3 extends L1V2 by means to describe which datasets and subsets thereof to use within a simulation experiment.

  8. Systems Biology Markup Language (SBML Level 2 Version 5: Structures and Facilities for Model Definitions

    Directory of Open Access Journals (Sweden)

    Hucka Michael

    2015-06-01

    Full Text Available Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 5 of SBML Level 2. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org/.

  9. Systems Biology Markup Language (SBML) Level 2 Version 5: Structures and Facilities for Model Definitions.

    Science.gov (United States)

    Hucka, Michael; Bergmann, Frank T; Dräger, Andreas; Hoops, Stefan; Keating, Sarah M; Le Novère, Nicolas; Myers, Chris J; Olivier, Brett G; Sahle, Sven; Schaff, James C; Smith, Lucian P; Waltemath, Dagmar; Wilkinson, Darren J

    2015-09-04

    Computational models can help researchers to interpret data, understand biological function, and make quantitative predictions. The Systems Biology Markup Language (SBML) is a file format for representing computational models in a declarative form that can be exchanged between different software systems. SBML is oriented towards describing biological processes of the sort common in research on a number of topics, including metabolic pathways, cell signaling pathways, and many others. By supporting SBML as an input/output format, different tools can all operate on an identical representation of a model, removing opportunities for translation errors and assuring a common starting point for analyses and simulations. This document provides the specification for Version 5 of SBML Level 2. The specification defines the data structures prescribed by SBML as well as their encoding in XML, the eXtensible Markup Language. This specification also defines validation rules that determine the validity of an SBML document, and provides many examples of models in SBML form. Other materials and software are available from the SBML project web site, http://sbml.org.

  10. Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 2.

    Science.gov (United States)

    Bergmann, Frank T; Cooper, Jonathan; Le Novère, Nicolas; Nickerson, David; Waltemath, Dagmar

    2015-09-04

    The number, size and complexity of computational models of biological systems are growing at an ever increasing pace. It is imperative to build on existing studies by reusing and adapting existing models and parts thereof. The description of the structure of models is not sufficient to enable the reproduction of simulation results. One also needs to describe the procedures the models are subjected to, as recommended by the Minimum Information About a Simulation Experiment (MIASE) guidelines. This document presents Level 1 Version 2 of the Simulation Experiment Description Markup Language (SED-ML), a computer-readable format for encoding simulation and analysis experiments to apply to computational models. SED-ML files are encoded in the Extensible Markup Language (XML) and can be used in conjunction with any XML-based model encoding format, such as CellML or SBML. A SED-ML file includes details of which models to use, how to modify them prior to executing a simulation, which simulation and analysis procedures to apply, which results to extract and how to present them. Level 1 Version 2 extends the format by allowing the encoding of repeated and chained procedures.

  11. Biological Dynamics Markup Language (BDML): an open format for representing quantitative biological dynamics data.

    Science.gov (United States)

    Kyoda, Koji; Tohsato, Yukako; Ho, Kenneth H L; Onami, Shuichi

    2015-04-01

    Recent progress in live-cell imaging and modeling techniques has resulted in generation of a large amount of quantitative data (from experimental measurements and computer simulations) on spatiotemporal dynamics of biological objects such as molecules, cells and organisms. Although many research groups have independently dedicated their efforts to developing software tools for visualizing and analyzing these data, these tools are often not compatible with each other because of different data formats. We developed an open unified format, Biological Dynamics Markup Language (BDML; current version: 0.2), which provides a basic framework for representing quantitative biological dynamics data for objects ranging from molecules to cells to organisms. BDML is based on Extensible Markup Language (XML). Its advantages are machine and human readability and extensibility. BDML will improve the efficiency of development and evaluation of software tools for data visualization and analysis. A specification and a schema file for BDML are freely available online at http://ssbd.qbic.riken.jp/bdml/. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

  12. Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 3 (L1V3).

    Science.gov (United States)

    Bergmann, Frank T; Cooper, Jonathan; König, Matthias; Moraru, Ion; Nickerson, David; Le Novère, Nicolas; Olivier, Brett G; Sahle, Sven; Smith, Lucian; Waltemath, Dagmar

    2018-03-19

    The creation of computational simulation experiments to inform modern biological research poses challenges to reproduce, annotate, archive, and share such experiments. Efforts such as SBML or CellML standardize the formal representation of computational models in various areas of biology. The Simulation Experiment Description Markup Language (SED-ML) describes what procedures the models are subjected to, and the details of those procedures. These standards, together with further COMBINE standards, describe models sufficiently well for the reproduction of simulation studies among users and software tools. The Simulation Experiment Description Markup Language (SED-ML) is an XML-based format that encodes, for a given simulation experiment, (i) which models to use; (ii) which modifications to apply to models before simulation; (iii) which simulation procedures to run on each model; (iv) how to post-process the data; and (v) how these results should be plotted and reported. SED-ML Level 1 Version 1 (L1V1) implemented support for the encoding of basic time course simulations. SED-ML L1V2 added support for more complex types of simulations, specifically repeated tasks and chained simulation procedures. SED-ML L1V3 extends L1V2 by means to describe which datasets and subsets thereof to use within a simulation experiment.

  13. Extensible Markup Language: How Might It Alter the Software Documentation Process and the Role of the Technical Communicator?

    Science.gov (United States)

    Battalio, John T.

    2002-01-01

    Describes the influence that Extensible Markup Language (XML) will have on the software documentation process and subsequently on the curricula of advanced undergraduate and master's programs in technical communication. Recommends how curricula of advanced undergraduate and master's programs in technical communication ought to change in order to…

  14. Using Extensible Markup Language (XML) for the Single Source Delivery of Educational Resources by Print and Online: A Case Study

    Science.gov (United States)

    Walsh, Lucas

    2007-01-01

    This article seeks to provide an introduction to Extensible Markup Language (XML) by looking at its use in a single source publishing approach to the provision of teaching resources in both hardcopy and online. Using the development of the International Baccalaureate Organisation's online Economics Subject Guide as a practical example, this…

  15. The semantics of Chemical Markup Language (CML for computational chemistry : CompChem

    Directory of Open Access Journals (Sweden)

    Phadungsukanan Weerapong

    2012-08-01

    Full Text Available Abstract This paper introduces a subdomain chemistry format for storing computational chemistry data called CompChem. It has been developed based on the design, concepts and methodologies of Chemical Markup Language (CML by adding computational chemistry semantics on top of the CML Schema. The format allows a wide range of ab initio quantum chemistry calculations of individual molecules to be stored. These calculations include, for example, single point energy calculation, molecular geometry optimization, and vibrational frequency analysis. The paper also describes the supporting infrastructure, such as processing software, dictionaries, validation tools and database repositories. In addition, some of the challenges and difficulties in developing common computational chemistry dictionaries are discussed. The uses of CompChem are illustrated by two practical applications.

  16. The semantics of Chemical Markup Language (CML) for computational chemistry : CompChem.

    Science.gov (United States)

    Phadungsukanan, Weerapong; Kraft, Markus; Townsend, Joe A; Murray-Rust, Peter

    2012-08-07

    : This paper introduces a subdomain chemistry format for storing computational chemistry data called CompChem. It has been developed based on the design, concepts and methodologies of Chemical Markup Language (CML) by adding computational chemistry semantics on top of the CML Schema. The format allows a wide range of ab initio quantum chemistry calculations of individual molecules to be stored. These calculations include, for example, single point energy calculation, molecular geometry optimization, and vibrational frequency analysis. The paper also describes the supporting infrastructure, such as processing software, dictionaries, validation tools and database repositories. In addition, some of the challenges and difficulties in developing common computational chemistry dictionaries are discussed. The uses of CompChem are illustrated by two practical applications.

  17. SBML-PET-MPI: a parallel parameter estimation tool for Systems Biology Markup Language based models.

    Science.gov (United States)

    Zi, Zhike

    2011-04-01

    Parameter estimation is crucial for the modeling and dynamic analysis of biological systems. However, implementing parameter estimation is time consuming and computationally demanding. Here, we introduced a parallel parameter estimation tool for Systems Biology Markup Language (SBML)-based models (SBML-PET-MPI). SBML-PET-MPI allows the user to perform parameter estimation and parameter uncertainty analysis by collectively fitting multiple experimental datasets. The tool is developed and parallelized using the message passing interface (MPI) protocol, which provides good scalability with the number of processors. SBML-PET-MPI is freely available for non-commercial use at http://www.bioss.uni-freiburg.de/cms/sbml-pet-mpi.html or http://sites.google.com/site/sbmlpetmpi/.

  18. The gel electrophoresis markup language (GelML) from the Proteomics Standards Initiative.

    Science.gov (United States)

    Gibson, Frank; Hoogland, Christine; Martinez-Bartolomé, Salvador; Medina-Aunon, J Alberto; Albar, Juan Pablo; Babnigg, Gyorgy; Wipat, Anil; Hermjakob, Henning; Almeida, Jonas S; Stanislaus, Romesh; Paton, Norman W; Jones, Andrew R

    2010-09-01

    The Human Proteome Organisation's Proteomics Standards Initiative has developed the GelML (gel electrophoresis markup language) data exchange format for representing gel electrophoresis experiments performed in proteomics investigations. The format closely follows the reporting guidelines for gel electrophoresis, which are part of the Minimum Information About a Proteomics Experiment (MIAPE) set of modules. GelML supports the capture of metadata (such as experimental protocols) and data (such as gel images) resulting from gel electrophoresis so that laboratories can be compliant with the MIAPE Gel Electrophoresis guidelines, while allowing such data sets to be exchanged or downloaded from public repositories. The format is sufficiently flexible to capture data from a broad range of experimental processes, and complements other PSI formats for MS data and the results of protein and peptide identifications to capture entire gel-based proteome workflows. GelML has resulted from the open standardisation process of PSI consisting of both public consultation and anonymous review of the specifications.

  19. SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool.

    Science.gov (United States)

    Zi, Zhike; Zheng, Yanan; Rundell, Ann E; Klipp, Edda

    2008-08-15

    It has long been recognized that sensitivity analysis plays a key role in modeling and analyzing cellular and biochemical processes. Systems biology markup language (SBML) has become a well-known platform for coding and sharing mathematical models of such processes. However, current SBML compatible software tools are limited in their ability to perform global sensitivity analyses of these models. This work introduces a freely downloadable, software package, SBML-SAT, which implements algorithms for simulation, steady state analysis, robustness analysis and local and global sensitivity analysis for SBML models. This software tool extends current capabilities through its execution of global sensitivity analyses using multi-parametric sensitivity analysis, partial rank correlation coefficient, SOBOL's method, and weighted average of local sensitivity analyses in addition to its ability to handle systems with discontinuous events and intuitive graphical user interface. SBML-SAT provides the community of systems biologists a new tool for the analysis of their SBML models of biochemical and cellular processes.

  20. Light at Night Markup Language (LANML): XML Technology for Light at Night Monitoring Data

    Science.gov (United States)

    Craine, B. L.; Craine, E. R.; Craine, E. M.; Crawford, D. L.

    2013-05-01

    Light at Night Markup Language (LANML) is a standard, based upon XML, useful in acquiring, validating, transporting, archiving and analyzing multi-dimensional light at night (LAN) datasets of any size. The LANML standard can accommodate a variety of measurement scenarios including single spot measures, static time-series, web based monitoring networks, mobile measurements, and airborne measurements. LANML is human-readable, machine-readable, and does not require a dedicated parser. In addition LANML is flexible; ensuring future extensions of the format will remain backward compatible with analysis software. The XML technology is at the heart of communicating over the internet and can be equally useful at the desktop level, making this standard particularly attractive for web based applications, educational outreach and efficient collaboration between research groups.

  1. Gene Fusion Markup Language: a prototype for exchanging gene fusion data.

    Science.gov (United States)

    Kalyana-Sundaram, Shanker; Shanmugam, Achiraman; Chinnaiyan, Arul M

    2012-10-16

    An avalanche of next generation sequencing (NGS) studies has generated an unprecedented amount of genomic structural variation data. These studies have also identified many novel gene fusion candidates with more detailed resolution than previously achieved. However, in the excitement and necessity of publishing the observations from this recently developed cutting-edge technology, no community standardization approach has arisen to organize and represent the data with the essential attributes in an interchangeable manner. As transcriptome studies have been widely used for gene fusion discoveries, the current non-standard mode of data representation could potentially impede data accessibility, critical analyses, and further discoveries in the near future. Here we propose a prototype, Gene Fusion Markup Language (GFML) as an initiative to provide a standard format for organizing and representing the significant features of gene fusion data. GFML will offer the advantage of representing the data in a machine-readable format to enable data exchange, automated analysis interpretation, and independent verification. As this database-independent exchange initiative evolves it will further facilitate the formation of related databases, repositories, and analysis tools. The GFML prototype is made available at http://code.google.com/p/gfml-prototype/. The Gene Fusion Markup Language (GFML) presented here could facilitate the development of a standard format for organizing, integrating and representing the significant features of gene fusion data in an inter-operable and query-able fashion that will enable biologically intuitive access to gene fusion findings and expedite functional characterization. A similar model is envisaged for other NGS data analyses.

  2. Coding practice of the Journal Article Tag Suite extensible markup language

    Directory of Open Access Journals (Sweden)

    Sun Huh

    2014-08-01

    Full Text Available In general, the Journal Article Tag Suite (JATS extensible markup language (XML coding is processed automatically by an XML filtering program. In this article, the basic tagging in JATS is explained in terms of coding practice. A text editor that supports UTF-8 encoding is necessary to input JATS XML data that works in every language. Any character representable in Unicode can be used in JATS XML, and commonly available web browsers can be used to view JATS XML files. JATS XML files can refer to document type definitions, extensible stylesheet language files, and cascading style sheets, but they must specify the locations of those files. Tools for validating JATS XML files are available via the web sites of PubMed Central and ScienceCentral. Once these files are uploaded to a web server, they can be accessed from all over the world by anyone with a browser. Encoding an example article in JATS XML may help editors in deciding on the adoption of JATS XML.

  3. FuGEFlow: data model and markup language for flow cytometry

    Directory of Open Access Journals (Sweden)

    Manion Frank J

    2009-06-01

    Full Text Available Abstract Background Flow cytometry technology is widely used in both health care and research. The rapid expansion of flow cytometry applications has outpaced the development of data storage and analysis tools. Collaborative efforts being taken to eliminate this gap include building common vocabularies and ontologies, designing generic data models, and defining data exchange formats. The Minimum Information about a Flow Cytometry Experiment (MIFlowCyt standard was recently adopted by the International Society for Advancement of Cytometry. This standard guides researchers on the information that should be included in peer reviewed publications, but it is insufficient for data exchange and integration between computational systems. The Functional Genomics Experiment (FuGE formalizes common aspects of comprehensive and high throughput experiments across different biological technologies. We have extended FuGE object model to accommodate flow cytometry data and metadata. Methods We used the MagicDraw modelling tool to design a UML model (Flow-OM according to the FuGE extension guidelines and the AndroMDA toolkit to transform the model to a markup language (Flow-ML. We mapped each MIFlowCyt term to either an existing FuGE class or to a new FuGEFlow class. The development environment was validated by comparing the official FuGE XSD to the schema we generated from the FuGE object model using our configuration. After the Flow-OM model was completed, the final version of the Flow-ML was generated and validated against an example MIFlowCyt compliant experiment description. Results The extension of FuGE for flow cytometry has resulted in a generic FuGE-compliant data model (FuGEFlow, which accommodates and links together all information required by MIFlowCyt. The FuGEFlow model can be used to build software and databases using FuGE software toolkits to facilitate automated exchange and manipulation of potentially large flow cytometry experimental data sets

  4. FuGEFlow: data model and markup language for flow cytometry.

    Science.gov (United States)

    Qian, Yu; Tchuvatkina, Olga; Spidlen, Josef; Wilkinson, Peter; Gasparetto, Maura; Jones, Andrew R; Manion, Frank J; Scheuermann, Richard H; Sekaly, Rafick-Pierre; Brinkman, Ryan R

    2009-06-16

    Flow cytometry technology is widely used in both health care and research. The rapid expansion of flow cytometry applications has outpaced the development of data storage and analysis tools. Collaborative efforts being taken to eliminate this gap include building common vocabularies and ontologies, designing generic data models, and defining data exchange formats. The Minimum Information about a Flow Cytometry Experiment (MIFlowCyt) standard was recently adopted by the International Society for Advancement of Cytometry. This standard guides researchers on the information that should be included in peer reviewed publications, but it is insufficient for data exchange and integration between computational systems. The Functional Genomics Experiment (FuGE) formalizes common aspects of comprehensive and high throughput experiments across different biological technologies. We have extended FuGE object model to accommodate flow cytometry data and metadata. We used the MagicDraw modelling tool to design a UML model (Flow-OM) according to the FuGE extension guidelines and the AndroMDA toolkit to transform the model to a markup language (Flow-ML). We mapped each MIFlowCyt term to either an existing FuGE class or to a new FuGEFlow class. The development environment was validated by comparing the official FuGE XSD to the schema we generated from the FuGE object model using our configuration. After the Flow-OM model was completed, the final version of the Flow-ML was generated and validated against an example MIFlowCyt compliant experiment description. The extension of FuGE for flow cytometry has resulted in a generic FuGE-compliant data model (FuGEFlow), which accommodates and links together all information required by MIFlowCyt. The FuGEFlow model can be used to build software and databases using FuGE software toolkits to facilitate automated exchange and manipulation of potentially large flow cytometry experimental data sets. Additional project documentation, including

  5. The Systems Biology Markup Language (SBML) Level 3 Package: Layout, Version 1 Core.

    Science.gov (United States)

    Gauges, Ralph; Rost, Ursula; Sahle, Sven; Wengler, Katja; Bergmann, Frank Thomas

    2015-09-04

    Many software tools provide facilities for depicting reaction network diagrams in a visual form. Two aspects of such a visual diagram can be distinguished: the layout (i.e.: the positioning and connections) of the elements in the diagram, and the graphical form of the elements (for example, the glyphs used for symbols, the properties of the lines connecting them, and so on). For software tools that also read and write models in SBML (Systems Biology Markup Language) format, a common need is to store the network diagram together with the SBML representation of the model. This in turn raises the question of how to encode the layout and the rendering of these diagrams. The SBML Level 3 Version 1 Core specification does not provide a mechanism for explicitly encoding diagrams, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The Layout package for SBML Level 3 adds the necessary features to SBML so that diagram layouts can be encoded in SBML files, and a companion package called SBML Rendering specifies how the graphical rendering of elements can be encoded. The SBML Layout package is based on the principle that reaction network diagrams should be described as representations of entities such as species and reactions (with direct links to the underlying SBML elements), and not as arbitrary drawings or graphs; for this reason, existing languages for the description of vector drawings (such as SVG) or general graphs (such as GraphML) cannot be used.

  6. SBMLeditor: effective creation of models in the Systems Biology Markup language (SBML).

    Science.gov (United States)

    Rodriguez, Nicolas; Donizelli, Marco; Le Novère, Nicolas

    2007-03-06

    The need to build a tool to facilitate the quick creation and editing of models encoded in the Systems Biology Markup language (SBML) has been growing with the number of users and the increased complexity of the language. SBMLeditor tries to answer this need by providing a very simple, low level editor of SBML files. Users can create and remove all the necessary bits and pieces of SBML in a controlled way, that maintains the validity of the final SBML file. SBMLeditor is written in JAVA using JCompneur, a library providing interfaces to easily display an XML document as a tree. This decreases dramatically the development time for a new XML editor. The possibility to include custom dialogs for different tags allows a lot of freedom for the editing and validation of the document. In addition to Xerces, SBMLeditor uses libSBML to check the validity and consistency of SBML files. A graphical equation editor allows an easy manipulation of MathML. SBMLeditor can be used as a module of the Systems Biology Workbench. SBMLeditor contains many improvements compared to a generic XML editor, and allow users to create an SBML model quickly and without syntactic errors.

  7. Reproducible computational biology experiments with SED-ML--the Simulation Experiment Description Markup Language.

    Science.gov (United States)

    Waltemath, Dagmar; Adams, Richard; Bergmann, Frank T; Hucka, Michael; Kolpakov, Fedor; Miller, Andrew K; Moraru, Ion I; Nickerson, David; Sahle, Sven; Snoep, Jacky L; Le Novère, Nicolas

    2011-12-15

    The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools. In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions. With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from different fields of research

  8. Reproducible computational biology experiments with SED-ML - The Simulation Experiment Description Markup Language

    Science.gov (United States)

    2011-01-01

    Background The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools. Results In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions. Conclusions With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from

  9. Histoimmunogenetics Markup Language 1.0: Reporting next generation sequencing-based HLA and KIR genotyping.

    Science.gov (United States)

    Milius, Robert P; Heuer, Michael; Valiga, Daniel; Doroschak, Kathryn J; Kennedy, Caleb J; Bolon, Yung-Tsi; Schneider, Joel; Pollack, Jane; Kim, Hwa Ran; Cereb, Nezih; Hollenbach, Jill A; Mack, Steven J; Maiers, Martin

    2015-12-01

    We present an electronic format for exchanging data for HLA and KIR genotyping with extensions for next-generation sequencing (NGS). This format addresses NGS data exchange by refining the Histoimmunogenetics Markup Language (HML) to conform to the proposed Minimum Information for Reporting Immunogenomic NGS Genotyping (MIRING) reporting guidelines (miring.immunogenomics.org). Our refinements of HML include two major additions. First, NGS is supported by new XML structures to capture additional NGS data and metadata required to produce a genotyping result, including analysis-dependent (dynamic) and method-dependent (static) components. A full genotype, consensus sequence, and the surrounding metadata are included directly, while the raw sequence reads and platform documentation are externally referenced. Second, genotype ambiguity is fully represented by integrating Genotype List Strings, which use a hierarchical set of delimiters to represent allele and genotype ambiguity in a complete and accurate fashion. HML also continues to enable the transmission of legacy methods (e.g. site-specific oligonucleotide, sequence-specific priming, and Sequence Based Typing (SBT)), adding features such as allowing multiple group-specific sequencing primers, and fully leveraging techniques that combine multiple methods to obtain a single result, such as SBT integrated with NGS. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Efficient Analysis of Systems Biology Markup Language Models of Cellular Populations Using Arrays.

    Science.gov (United States)

    Watanabe, Leandro; Myers, Chris J

    2016-08-19

    The Systems Biology Markup Language (SBML) has been widely used for modeling biological systems. Although SBML has been successful in representing a wide variety of biochemical models, the core standard lacks the structure for representing large complex regular systems in a standard way, such as whole-cell and cellular population models. These models require a large number of variables to represent certain aspects of these types of models, such as the chromosome in the whole-cell model and the many identical cell models in a cellular population. While SBML core is not designed to handle these types of models efficiently, the proposed SBML arrays package can represent such regular structures more easily. However, in order to take full advantage of the package, analysis needs to be aware of the arrays structure. When expanding the array constructs within a model, some of the advantages of using arrays are lost. This paper describes a more efficient way to simulate arrayed models. To illustrate the proposed method, this paper uses a population of repressilator and genetic toggle switch circuits as examples. Results show that there are memory benefits using this approach with a modest cost in runtime.

  11. A two-way interface between limited Systems Biology Markup Language and R

    Directory of Open Access Journals (Sweden)

    Radivoyevitch Tomas

    2004-12-01

    Full Text Available Abstract Background Systems Biology Markup Language (SBML is gaining broad usage as a standard for representing dynamical systems as data structures. The open source statistical programming environment R is widely used by biostatisticians involved in microarray analyses. An interface between SBML and R does not exist, though one might be useful to R users interested in SBML, and SBML users interested in R. Results A model structure that parallels SBML to a limited degree is defined in R. An interface between this structure and SBML is provided through two function definitions: write.SBML( which maps this R model structure to SBML level 2, and read.SBML( which maps a limited range of SBML level 2 files back to R. A published model of purine metabolism is provided in this SBML-like format and used to test the interface. The model reproduces published time course responses before and after its mapping through SBML. Conclusions List infrastructure preexisting in R makes it well-suited for manipulating SBML models. Further developments of this SBML-R interface seem to be warranted.

  12. The Systems Biology Markup Language (SBML Level 3 Package: Layout, Version 1 Core

    Directory of Open Access Journals (Sweden)

    Gauges Ralph

    2015-06-01

    Full Text Available Many software tools provide facilities for depicting reaction network diagrams in a visual form. Two aspects of such a visual diagram can be distinguished: the layout (i.e.: the positioning and connections of the elements in the diagram, and the graphical form of the elements (for example, the glyphs used for symbols, the properties of the lines connecting them, and so on. For software tools that also read and write models in SBML (Systems Biology Markup Language format, a common need is to store the network diagram together with the SBML representation of the model. This in turn raises the question of how to encode the layout and the rendering of these diagrams. The SBML Level 3 Version 1 Core specification does not provide a mechanism for explicitly encoding diagrams, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The Layout package for SBML Level 3 adds the necessary features to SBML so that diagram layouts can be encoded in SBML files, and a companion package called SBML Rendering specifies how the graphical rendering of elements can be encoded.

  13. A two-way interface between limited Systems Biology Markup Language and R.

    Science.gov (United States)

    Radivoyevitch, Tomas

    2004-12-07

    Systems Biology Markup Language (SBML) is gaining broad usage as a standard for representing dynamical systems as data structures. The open source statistical programming environment R is widely used by biostatisticians involved in microarray analyses. An interface between SBML and R does not exist, though one might be useful to R users interested in SBML, and SBML users interested in R. A model structure that parallels SBML to a limited degree is defined in R. An interface between this structure and SBML is provided through two function definitions: write.SBML() which maps this R model structure to SBML level 2, and read.SBML() which maps a limited range of SBML level 2 files back to R. A published model of purine metabolism is provided in this SBML-like format and used to test the interface. The model reproduces published time course responses before and after its mapping through SBML. List infrastructure preexisting in R makes it well-suited for manipulating SBML models. Further developments of this SBML-R interface seem to be warranted.

  14. Transparent ICD and DRG coding using information technology: linking and associating information sources with the eXtensible Markup Language.

    Science.gov (United States)

    Hoelzer, Simon; Schweiger, Ralf K; Dudeck, Joachim

    2003-01-01

    With the introduction of ICD-10 as the standard for diagnostics, it becomes necessary to develop an electronic representation of its complete content, inherent semantics, and coding rules. The authors' design relates to the current efforts by the CEN/TC 251 to establish a European standard for hierarchical classification systems in health care. The authors have developed an electronic representation of ICD-10 with the eXtensible Markup Language (XML) that facilitates integration into current information systems and coding software, taking different languages and versions into account. In this context, XML provides a complete processing framework of related technologies and standard tools that helps develop interoperable applications. XML provides semantic markup. It allows domain-specific definition of tags and hierarchical document structure. The idea of linking and thus combining information from different sources is a valuable feature of XML. In addition, XML topic maps are used to describe relationships between different sources, or "semantically associated" parts of these sources. The issue of achieving a standardized medical vocabulary becomes more and more important with the stepwise implementation of diagnostically related groups, for example. The aim of the authors' work is to provide a transparent and open infrastructure that can be used to support clinical coding and to develop further software applications. The authors are assuming that a comprehensive representation of the content, structure, inherent semantics, and layout of medical classification systems can be achieved through a document-oriented approach.

  15. From data to analysis: linking NWChem and Avogadro with the syntax and semantics of Chemical Markup Language

    Energy Technology Data Exchange (ETDEWEB)

    De Jong, Wibe A.; Walker, Andrew M.; Hanwell, Marcus D.

    2013-05-24

    Background Multidisciplinary integrated research requires the ability to couple the diverse sets of data obtained from a range of complex experiments and computer simulations. Integrating data requires semantically rich information. In this paper the generation of semantically rich data from the NWChem computational chemistry software is discussed within the Chemical Markup Language (CML) framework. Results The NWChem computational chemistry software has been modified and coupled to the FoX library to write CML compliant XML data files. The FoX library was expanded to represent the lexical input files used by the computational chemistry software. Conclusions The production of CML compliant XML files for the computational chemistry software NWChem can be relatively easily accomplished using the FoX library. A unified computational chemistry or CompChem convention and dictionary needs to be developed through a community-based effort. The long-term goal is to enable a researcher to do Google-style chemistry and physics searches.

  16. The Biological Connection Markup Language: a SBGN-compliant format for visualization, filtering and analysis of biological pathways.

    Science.gov (United States)

    Beltrame, Luca; Calura, Enrica; Popovici, Razvan R; Rizzetto, Lisa; Guedez, Damariz Rivero; Donato, Michele; Romualdi, Chiara; Draghici, Sorin; Cavalieri, Duccio

    2011-08-01

    Many models and analysis of signaling pathways have been proposed. However, neither of them takes into account that a biological pathway is not a fixed system, but instead it depends on the organism, tissue and cell type as well as on physiological, pathological and experimental conditions. The Biological Connection Markup Language (BCML) is a format to describe, annotate and visualize pathways. BCML is able to store multiple information, permitting a selective view of the pathway as it exists and/or behave in specific organisms, tissues and cells. Furthermore, BCML can be automatically converted into data formats suitable for analysis and into a fully SBGN-compliant graphical representation, making it an important tool that can be used by both computational biologists and 'wet lab' scientists. The XML schema and the BCML software suite are freely available under the LGPL for download at http://bcml.dc-atlas.net. They are implemented in Java and supported on MS Windows, Linux and OS X.

  17. Restructuring an EHR system and the Medical Markup Language (MML) standard to improve interoperability by archetype technology.

    Science.gov (United States)

    Kobayashi, Shinji; Kume, Naoto; Yoshihara, Hiroyuki

    2015-01-01

    In 2001, we developed an EHR system for regional healthcare information inter-exchange and to provide individual patient data to patients. This system was adopted in three regions in Japan. We also developed a Medical Markup Language (MML) standard for inter- and intra-hospital communications. The system was built on a legacy platform, however, and had not been appropriately maintained or updated to meet clinical requirements. To improve future maintenance costs, we reconstructed the EHR system using archetype technology on the Ruby on Rails platform, and generated MML equivalent forms from archetypes. The system was deployed as a cloud-based system for preliminary use as a regional EHR. The system now has the capability to catch up with new requirements, maintaining semantic interoperability with archetype technology. It is also more flexible than the legacy EHR system.

  18. Evolving a lingua franca and associated software infrastructure for computational systems biology: the Systems Biology Markup Language (SBML) project.

    Science.gov (United States)

    Hucka, M; Finney, A; Bornstein, B J; Keating, S M; Shapiro, B E; Matthews, J; Kovitz, B L; Schilstra, M J; Funahashi, A; Doyle, J C; Kitano, H

    2004-06-01

    Biologists are increasingly recognising that computational modelling is crucial for making sense of the vast quantities of complex experimental data that are now being collected. The systems biology field needs agreed-upon information standards if models are to be shared, evaluated and developed cooperatively. Over the last four years, our team has been developing the Systems Biology Markup Language (SBML) in collaboration with an international community of modellers and software developers. SBML has become a de facto standard format for representing formal, quantitative and qualitative models at the level of biochemical reactions and regulatory networks. In this article, we summarise the current and upcoming versions of SBML and our efforts at developing software infrastructure for supporting and broadening its use. We also provide a brief overview of the many SBML-compatible software tools available today.

  19. A standard MIGS/MIMS compliant XML Schema: toward the development of the Genomic Contextual Data Markup Language (GCDML).

    Science.gov (United States)

    Kottmann, Renzo; Gray, Tanya; Murphy, Sean; Kagan, Leonid; Kravitz, Saul; Lombardot, Thierry; Field, Dawn; Glöckner, Frank Oliver

    2008-06-01

    The Genomic Contextual Data Markup Language (GCDML) is a core project of the Genomic Standards Consortium (GSC) that implements the "Minimum Information about a Genome Sequence" (MIGS) specification and its extension, the "Minimum Information about a Metagenome Sequence" (MIMS). GCDML is an XML Schema for generating MIGS/MIMS compliant reports for data entry, exchange, and storage. When mature, this sample-centric, strongly-typed schema will provide a diverse set of descriptors for describing the exact origin and processing of a biological sample, from sampling to sequencing, and subsequent analysis. Here we describe the need for such a project, outline design principles required to support the project, and make an open call for participation in defining the future content of GCDML. GCDML is freely available, and can be downloaded, along with documentation, from the GSC Web site (http://gensc.org).

  20. The evolution of the CUAHSI Water Markup Language (WaterML)

    Science.gov (United States)

    Zaslavsky, I.; Valentine, D.; Maidment, D.; Tarboton, D. G.; Whiteaker, T.; Hooper, R.; Kirschtel, D.; Rodriguez, M.

    2009-04-01

    The CUAHSI Hydrologic Information System (HIS, his.cuahsi.org) uses web services as the core data exchange mechanism which provides programmatic connection between many heterogeneous sources of hydrologic data and a variety of online and desktop client applications. The service message schema follows the CUAHSI Water Markup Language (WaterML) 1.x specification (see OGC Discussion Paper 07-041r1). Data sources that can be queried via WaterML-compliant water data services include national and international repositories such as USGS NWIS (National Water Information System), USEPA STORET (Storage & Retrieval), USDA SNOTEL (Snowpack Telemetry), NCDC ISH and ISD(Integrated Surface Hourly and Daily Data), MODIS (Moderate Resolution Imaging Spectroradiometer), and DAYMET (Daily Surface Weather Data and Climatological Summaries). Besides government data sources, CUAHSI HIS provides access to a growing number of academic hydrologic observation networks. These networks are registered by researchers associated with 11 hydrologic observatory testbeds around the US, and other research, government and commercial groups wishing to join the emerging CUAHSI Water Data Federation. The Hydrologic Information Server (HIS Server) software stack deployed at NSF-supported hydrologic observatory sites and other universities around the country, supports a hydrologic data publication workflow which includes the following steps: (1) observational data are loaded from static files or streamed from sensors into a local instance of an Observations Data Model (ODM) database; (2) a generic web service template is configured for the new ODM instance to expose the data as a WaterML-compliant water data service, and (3) the new water data service is registered at the HISCentral registry (hiscentral.cuahsi.org), its metadata are harvested and semantically tagged using concepts from a hydrologic ontology. As a result, the new service is indexed in the CUAHSI central metadata catalog, and becomes

  1. ART-ML: a new markup language for modelling and representation of biological processes in cardiovascular diseases.

    Science.gov (United States)

    Karvounis, E C; Exarchos, T P; Fotiou, E; Sakellarios, A I; Iliopoulou, D; Koutsouris, D; Fotiadis, D I

    2013-01-01

    With an ever increasing number of biological models available on the internet, a standardized modelling framework is required to allow information to be accessed and visualized. In this paper we propose a novel Extensible Markup Language (XML) based format called ART-ML that aims at supporting the interoperability and the reuse of models of geometry, blood flow, plaque progression and stent modelling, exported by any cardiovascular disease modelling software. ART-ML has been developed and tested using ARTool. ARTool is a platform for the automatic processing of various image modalities of coronary and carotid arteries. The images and their content are fused to develop morphological models of the arteries in 3D representations. All the above described procedures integrate disparate data formats, protocols and tools. ART-ML proposes a representation way, expanding ARTool, for interpretability of the individual resources, creating a standard unified model for the description of data and, consequently, a format for their exchange and representation that is machine independent. More specifically, ARTool platform incorporates efficient algorithms which are able to perform blood flow simulations and atherosclerotic plaque evolution modelling. Integration of data layers between different modules within ARTool are based upon the interchange of information included in the ART-ML model repository. ART-ML provides a markup representation that enables the representation and management of embedded models within the cardiovascular disease modelling platform, the storage and interchange of well-defined information. The corresponding ART-ML model incorporates all relevant information regarding geometry, blood flow, plaque progression and stent modelling procedures. All created models are stored in a model repository database which is accessible to the research community using efficient web interfaces, enabling the interoperability of any cardiovascular disease modelling software

  2. A program code generator for multiphysics biological simulation using markup languages.

    Science.gov (United States)

    Amano, Akira; Kawabata, Masanari; Yamashita, Yoshiharu; Rusty Punzalan, Florencio; Shimayoshi, Takao; Kuwabara, Hiroaki; Kunieda, Yoshitoshi

    2012-01-01

    To cope with the complexity of the biological function simulation models, model representation with description language is becoming popular. However, simulation software itself becomes complex in these environment, thus, it is difficult to modify the simulation conditions, target computation resources or calculation methods. In the complex biological function simulation software, there are 1) model equations, 2) boundary conditions and 3) calculation schemes. Use of description model file is useful for first point and partly second point, however, third point is difficult to handle for various calculation schemes which is required for simulation models constructed from two or more elementary models. We introduce a simulation software generation system which use description language based description of coupling calculation scheme together with cell model description file. By using this software, we can easily generate biological simulation code with variety of coupling calculation schemes. To show the efficiency of our system, example of coupling calculation scheme with three elementary models are shown.

  3. From data to analysis: linking NWChem and Avogadro with the syntax and semantics of Chemical Markup Language.

    Science.gov (United States)

    de Jong, Wibe A; Walker, Andrew M; Hanwell, Marcus D

    2013-05-24

    Multidisciplinary integrated research requires the ability to couple the diverse sets of data obtained from a range of complex experiments and computer simulations. Integrating data requires semantically rich information. In this paper an end-to-end use of semantically rich data in computational chemistry is demonstrated utilizing the Chemical Markup Language (CML) framework. Semantically rich data is generated by the NWChem computational chemistry software with the FoX library and utilized by the Avogadro molecular editor for analysis and visualization. The NWChem computational chemistry software has been modified and coupled to the FoX library to write CML compliant XML data files. The FoX library was expanded to represent the lexical input files and molecular orbitals used by the computational chemistry software. Draft dictionary entries and a format for molecular orbitals within CML CompChem were developed. The Avogadro application was extended to read in CML data, and display molecular geometry and electronic structure in the GUI allowing for an end-to-end solution where Avogadro can create input structures, generate input files, NWChem can run the calculation and Avogadro can then read in and analyse the CML output produced. The developments outlined in this paper will be made available in future releases of NWChem, FoX, and Avogadro. The production of CML compliant XML files for computational chemistry software such as NWChem can be accomplished relatively easily using the FoX library. The CML data can be read in by a newly developed reader in Avogadro and analysed or visualized in various ways. A community-based effort is needed to further develop the CML CompChem convention and dictionary. This will enable the long-term goal of allowing a researcher to run simple "Google-style" searches of chemistry and physics and have the results of computational calculations returned in a comprehensible form alongside articles from the published literature.

  4. TME2/342: The Role of the EXtensible Markup Language (XML) for Future Healthcare Application Development

    Science.gov (United States)

    Noelle, G; Dudeck, J

    1999-01-01

    Two years, since the World Wide Web Consortium (W3C) has published the first specification of the eXtensible Markup Language (XML) there exist some concrete tools and applications to work with XML-based data. In particular, new generation Web browsers offer great opportunities to develop new kinds of medical, web-based applications. There are several data-exchange formats in medicine, which have been established in the last years: HL-7, DICOM, EDIFACT and, in the case of Germany, xDT. Whereas communication and information exchange becomes increasingly important, the development of appropriate and necessary interfaces causes problems, rising costs and effort. It has been also recognised that it is difficult to define a standardised interchange format, for one of the major future developments in medical telematics: the electronic patient record (EPR) and its availability on the Internet. Whereas XML, especially in an industrial environment, is celebrated as a generic standard and a solution for all problems concerning e-commerce, in a medical context there are only few applications developed. Nevertheless, the medical environment is an appropriate area for building XML applications: as the information and communication management becomes increasingly important in medical businesses, the role of the Internet changes quickly from an information to a communication medium. The first XML based applications in healthcare show us the advantage for a future engagement of the healthcare industry in XML: such applications are open, easy to extend and cost-effective. Additionally, XML is much more than a simple new data interchange format: many proposals for data query (XQL), data presentation (XSL) and other extensions have been proposed to the W3C and partly realised in medical applications.

  5. Hyper Text Mark-up Language and Dublin Core metadata element set usage in websites of Iranian State Universities’ libraries

    Science.gov (United States)

    Zare-Farashbandi, Firoozeh; Ramezan-Shirazi, Mahtab; Ashrafi-Rizi, Hasan; Nouri, Rasool

    2014-01-01

    Introduction: Recent progress in providing innovative solutions in the organization of electronic resources and research in this area shows a global trend in the use of new strategies such as metadata to facilitate description, place for, organization and retrieval of resources in the web environment. In this context, library metadata standards have a special place; therefore, the purpose of the present study has been a comparative study on the Central Libraries’ Websites of Iran State Universities for Hyper Text Mark-up Language (HTML) and Dublin Core metadata elements usage in 2011. Materials and Methods: The method of this study is applied-descriptive and data collection tool is the check lists created by the researchers. Statistical community includes 98 websites of the Iranian State Universities of the Ministry of Health and Medical Education and Ministry of Science, Research and Technology and method of sampling is the census. Information was collected through observation and direct visits to websites and data analysis was prepared by Microsoft Excel software, 2011. Results: The results of this study indicate that none of the websites use Dublin Core (DC) metadata and that only a few of them have used overlaps elements between HTML meta tags and Dublin Core (DC) elements. The percentage of overlaps of DC elements centralization in the Ministry of Health were 56% for both description and keywords and, in the Ministry of Science, were 45% for the keywords and 39% for the description. But, HTML meta tags have moderate presence in both Ministries, as the most-used elements were keywords and description (56%) and the least-used elements were date and formatter (0%). Conclusion: It was observed that the Ministry of Health and Ministry of Science follows the same path for using Dublin Core standard on their websites in the future. Because Central Library Websites are an example of scientific web pages, special attention in designing them can help the researchers

  6. Hyper Text Mark-up Language and Dublin Core metadata element set usage in websites of Iranian State Universities' libraries.

    Science.gov (United States)

    Zare-Farashbandi, Firoozeh; Ramezan-Shirazi, Mahtab; Ashrafi-Rizi, Hasan; Nouri, Rasool

    2014-01-01

    Recent progress in providing innovative solutions in the organization of electronic resources and research in this area shows a global trend in the use of new strategies such as metadata to facilitate description, place for, organization and retrieval of resources in the web environment. In this context, library metadata standards have a special place; therefore, the purpose of the present study has been a comparative study on the Central Libraries' Websites of Iran State Universities for Hyper Text Mark-up Language (HTML) and Dublin Core metadata elements usage in 2011. The method of this study is applied-descriptive and data collection tool is the check lists created by the researchers. Statistical community includes 98 websites of the Iranian State Universities of the Ministry of Health and Medical Education and Ministry of Science, Research and Technology and method of sampling is the census. Information was collected through observation and direct visits to websites and data analysis was prepared by Microsoft Excel software, 2011. The results of this study indicate that none of the websites use Dublin Core (DC) metadata and that only a few of them have used overlaps elements between HTML meta tags and Dublin Core (DC) elements. The percentage of overlaps of DC elements centralization in the Ministry of Health were 56% for both description and keywords and, in the Ministry of Science, were 45% for the keywords and 39% for the description. But, HTML meta tags have moderate presence in both Ministries, as the most-used elements were keywords and description (56%) and the least-used elements were date and formatter (0%). It was observed that the Ministry of Health and Ministry of Science follows the same path for using Dublin Core standard on their websites in the future. Because Central Library Websites are an example of scientific web pages, special attention in designing them can help the researchers to achieve faster and more accurate information resources

  7. Markups and Exporting Behavior

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic Michel Patrick

    2012-01-01

    In this paper, we develop a method to estimate markups using plant-level production data. Our approach relies on cost minimizing producers and the existence of at least one variable input of production. The suggested empirical framework relies on the estimation of a production function and provides...... estimates of plant- level markups without specifying how firms compete in the product market. We rely on our method to explore the relationship be- tween markups and export behavior. We find that markups are estimated significantly higher when controlling for unobserved productivity; that exporters charge......, on average, higher markups and that markups increase upon export entry....

  8. An Attempt to Construct a Database of Photographic Data of Radiolarian Fossils with the Hypertext Markup Language

    OpenAIRE

    磯貝, 芳徳; 水谷, 伸治郎; Yoshinori, Isogai; Shinjiro, Mizutani

    1998-01-01

    放散虫化石の走査型電子顕微鏡写真のコレクションを,Hypertext Markup Languageを用いてデータベース化した.このデータベースは約千枚の放散虫化石の写真を現時点でもっており,化石名,地質学的年代,発掘地名など多様な視点から検索することができる.このデータベースの構築によって,計算機やデータベースについて特別な技術を持っていない通常の研究者が,自身のデータベースを自らの手で構築しようとするとき,Hypertext Markup Languageが有効であることを示した.さらにインターネットを経由して,誰でもこのデータベースを利用できる点は,Hypertext Markup Languageを用いたデータベースの特筆するき特徴である.データベース構築の過程を記述し,現況を報告する.さらに当データベース構築の背景にある考えや問題点について議論する....

  9. Atmospheric Measurements Laboratory (AML)

    Data.gov (United States)

    Federal Laboratory Consortium — The Atmospheric Measurements Laboratory (AML) is one of the nation's leading research facilities for understanding aerosols, clouds, and their interactions. The AML...

  10. The development of MML (Medical Markup Language) version 3.0 as a medical document exchange format for HL7 messages.

    Science.gov (United States)

    Guo, Jinqiu; Takada, Akira; Tanaka, Koji; Sato, Junzo; Suzuki, Muneou; Suzuki, Toshiaki; Nakashima, Yusei; Araki, Kenji; Yoshihara, Hiroyuki

    2004-12-01

    Medical Markup Language (MML), as a set of standards, has been developed over the last 8 years to allow the exchange of medical data between different medical information providers. MML Version 2.21 used XML as a metalanguage and was announced in 1999. In 2001, MML was updated to Version 2.3, which contained 12 modules. The latest version--Version 3.0--is based on the HL7 Clinical Document Architecture (CDA). During the development of this new version, the structure of MML Version 2.3 was analyzed, subdivided into several categories, and redefined so the information defined in MML could be described in HL7 CDA Level One. As a result of this development, it has become possible to exchange MML Version 3.0 medical documents via HL7 messages.

  11. PENGUKURAN KINERJA BEBERAPA SISTEM BASIS DATA RELASIONAL DENGAN KEMAMPUAN MENYIMPAN DATA BERFORMAT GML (GEOGRAPHY MARKUP LANGUAGE YANG DAPAT DIGUNAKAN UNTUK MENDASARI APLIKASI-APLIKASI SISTEM INFORMASI GEOGRAFIS

    Directory of Open Access Journals (Sweden)

    Adi Nugroho

    2009-01-01

    Full Text Available If we want to represent spatial data to user using GIS (Geographical Information System applications, we have 2 choices about the underlying database, that is general RDBMS (Relational Database Management System for saving general spatial data (number, char, varchar, etc., or saving spatial data in GML (Geography Markup Language format. (GML is an another XML’s special vocabulary for spatial data. If we choose GML for saving spatial data, we also have 2 choices, that is saving spatial data in XML Enabled Database (relational databases that can be use for saving XML data or we can use Native XML Database (NXD, that is special databases that can be use for saving XML data. In this paper, we try to make performance comparison for several XML Enabled Database when we do GML’s CRUD (Create-Read-Update-Delete operations to these databases. On the other side, we also want to see flexibility of XML Enabled Database from programmers view.

  12. SGML-Based Markup for Literary Texts: Two Problems and Some Solutions.

    Science.gov (United States)

    Barnard, David; And Others

    1988-01-01

    Identifies the Standard Generalized Markup Language (SGML) as the best basis for a markup standard for encoding literary texts. Outlines solutions to problems using SGML and discusses the problem of maintaining multiple views of a document. Examines several ways of reducing the burden of markups. (GEA)

  13. GIBS Keyhole Markup Language (KML)

    Data.gov (United States)

    National Aeronautics and Space Administration — The KML documentation standard provides a solution for imagery integration into mapping tools that utilize support the KML standard, specifically Google Earth. Using...

  14. Access/AML -

    Data.gov (United States)

    Department of Transportation — The AccessAML is a web-based internet single application designed to reduce the vulnerability associated with several accounts assinged to a single users. This is a...

  15. Treatment of Markup in Statistical Machine Translation

    OpenAIRE

    Müller, Mathias

    2017-01-01

    We present work on handling XML markup in Statistical Machine Translation (SMT). The methods we propose can be used to effectively preserve markup (for instance inline formatting or structure) and to place markup correctly in a machine-translated segment. We evaluate our approaches with parallel data that naturally contains markup or where markup was inserted to create synthetic examples. In our experiments, hybrid reinsertion has proven the most accurate method to handle markup, while alignm...

  16. Acute myeloid leukemia (AML) - children

    Science.gov (United States)

    Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

  17. Managing and Querying Image Annotation and Markup in XML

    Science.gov (United States)

    Wang, Fusheng; Pan, Tony; Sharma, Ashish; Saltz, Joel

    2010-01-01

    Proprietary approaches for representing annotations and image markup are serious barriers for researchers to share image data and knowledge. The Annotation and Image Markup (AIM) project is developing a standard based information model for image annotation and markup in health care and clinical trial environments. The complex hierarchical structures of AIM data model pose new challenges for managing such data in terms of performance and support of complex queries. In this paper, we present our work on managing AIM data through a native XML approach, and supporting complex image and annotation queries through native extension of XQuery language. Through integration with xService, AIM databases can now be conveniently shared through caGrid. PMID:21218167

  18. Managing and Querying Image Annotation and Markup in XML.

    Science.gov (United States)

    Wang, Fusheng; Pan, Tony; Sharma, Ashish; Saltz, Joel

    2010-01-01

    Proprietary approaches for representing annotations and image markup are serious barriers for researchers to share image data and knowledge. The Annotation and Image Markup (AIM) project is developing a standard based information model for image annotation and markup in health care and clinical trial environments. The complex hierarchical structures of AIM data model pose new challenges for managing such data in terms of performance and support of complex queries. In this paper, we present our work on managing AIM data through a native XML approach, and supporting complex image and annotation queries through native extension of XQuery language. Through integration with xService, AIM databases can now be conveniently shared through caGrid.

  19. Percentage Retail Mark-Ups

    OpenAIRE

    Thomas von Ungern-Sternberg

    1999-01-01

    A common assumption in the literature on the double marginalization problem is that the retailer can set his mark-up only in the second stage of the game after the producer has moved. To the extent that the sequence of moves is designed to reflect the relative bargaining power of the two parties it is just as plausible to let the retailer move first. Furthermore, retailers frequently calculate their selling prices by adding a percentage mark-up to their wholesale prices. This allows a retaile...

  20. TEI Standoff Markup - A work in progress

    NARCIS (Netherlands)

    Spadini, E.; Turska, Magdalena; Broughton, Misha

    2015-01-01

    Markup is said to be standoff, or external, when the markup data is placed outside of the text it is meant to tag” (). One of the most widely recognized limitations of inline XML markup is its inability to cope with element overlap; standoff has been considered as a possible solution to

  1. Endogenous Markups, Firm Productivity and International Trade:

    DEFF Research Database (Denmark)

    Bellone, Flora; Musso, Patrick; Nesta, Lionel

    ) markups are positively related to firm productivity; 3) markups are negatively related to import penetration; 4) markups are positively related to firm export intensity and markups are higher on the export market than on the domestic ones in the presence of trade barriers and/or if competitors...... on the export market are less efficient than competitors on the domestic market. We estimate micro-level price cost margins (PCMs) using firm-level data extending the techniques developed by Hall (1986, 1988) and extended by Domowitz et al. (1988) and Roeger (1995) for the French manufacturing industry from......In this paper, we test key micro-level theoretical predictions ofMelitz and Ottaviano (MO) (2008), a model of international trade with heterogenous firms and endogenous mark-ups. At the firm-level, the MO model predicts that: 1) firm markups are negatively related to domestic market size; 2...

  2. Markups and Firm-Level Export Status

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic

    We derive an estimating equation to estimate markups using the insight of Hall (1986) and the control function approach of Olley and Pakes (1996). We rely on our method to explore the relationship between markups and export behavior using plant-level data. We find significantly higher markups when...... we control for unobserved productivity shocks. Furthermore, we find significant higher markups for exporting firms and present new evidence on markup-export status dynamics. More specifically, we find that firms' markups significantly increase (decrease) after entering (exiting) export markets. We...... see these results as a first step in opening up the productivity-export black box, and provide a potential explanation for the big measured productivity premia for firms entering export markets....

  3. Wine Price Markup in California Restaurants

    OpenAIRE

    Amspacher, William

    2011-01-01

    The study quantifies the relationship between retail wine price and restaurant mark-up. Ordinary Least Squares regressions were run to estimate how restaurant mark-up responded to retail price. Separate regressions were run for white wine, red wine, and both red and white combined. Both slope and intercept coefficients for each of these regressions were highly significant and indicated the expected inverse relationship between retail price and mark-up.

  4. Markups and Firm-Level Export Status

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic

    and export behavior using plant-level data. We find that i) markups are estimated significantly higher when controlling for unobserved productivity, ii) exporters charge on average higher markups and iii) firms' markups increase (decrease) upon export entry (exit).We see these findings as a first step...... in opening up the productivity-export black box, and provide a potential explanation for the big measured productivity premia for firms entering export markets....

  5. LOG2MARKUP: State module to transform a Stata text log into a markup document

    DEFF Research Database (Denmark)

    2016-01-01

    log2markup extract parts of the text version from the Stata log command and transform the logfile into a markup based document with the same name, but with extension markup (or otherwise specified in option extension) instead of log. The author usually uses markdown for writing documents. However...

  6. AML (Logistics Center) Local Area Network -

    Data.gov (United States)

    Department of Transportation — The AML LAN is designed to facilitate the services and resources needed to support the operations of the FAA Logistics Center users. The AML LAN provides support for...

  7. Data Display Markup Language (DDML) Handbook

    Science.gov (United States)

    2017-01-31

    purpose of this handbook is to improve the use of DDML as a standard by presenting clear guidelines and thereby eliminating any misinterpretations ...code is slightly different for internal translators than for external translators. Like external translators, special considerations must be accounted

  8. Fuzzy markup language for malware behavioral analysis

    NARCIS (Netherlands)

    Huang, H.-D.; Acampora, G.; Loia, V.; Lee, C.-S.; Hagras, H.; Wang, M.-H.; Kao, H.-Y.; Chang, J.-G.; Acampora, G.; Loia, V.; Lee, Ch.-Sh.; Wang, M.-H.

    2013-01-01

    In recent years, antimalware applications represented one of the most important research topics in the area of network security threat. In addition, malware have become a growing important problem for governments and commercial organizations. The key point of the research on the network security is

  9. Markup cyclicality, employment adjustment, and financial constraints

    OpenAIRE

    Askildsen, Jan Erik; Nilsen, Øivind Anti

    2001-01-01

    We investigate the existence of markups and their cyclical behaviour. Markup is not directly observed. Instead, it is given as a price-cost relation that is estimated from a dynamic model of the firm. The model incorporates potential costly employment adjustments and takes into consideration that firms may be financially constrained. When considering size of the future labour stock, financially constrained firms may behave as if they have a higher discount factor, which may affect the realise...

  10. Chemical Markup, XML, and the World Wide Web. 7. CMLSpect, an XML vocabulary for spectral data.

    Science.gov (United States)

    Kuhn, Stefan; Helmus, Tobias; Lancashire, Robert J; Murray-Rust, Peter; Rzepa, Henry S; Steinbeck, Christoph; Willighagen, Egon L

    2007-01-01

    CMLSpect is an extension of Chemical Markup Language (CML) for managing spectral and other analytical data. It is designed to be flexible enough to contain a wide variety of spectral data. The paper describes the CMLElements used and gives practical examples for common types of spectra. In addition it demonstrates how different views of the data can be expressed and what problems still exist.

  11. XML/TEI Stand-off Markup. One step beyond.

    NARCIS (Netherlands)

    Spadini, E.; Turska, Magdalena

    2018-01-01

    Stand-off markup is widely considered as a possible solution for overcoming the limitation of inline XML markup, primarily dealing with multiple overlapping hierarchies. Considering previous contributions on the subject and implementations of stand-off markup, we propose a new TEI-based model for

  12. Socioeconomic Status (SES) and Childhood Acute Myeloid Leukemia (AML) Mortality

    Science.gov (United States)

    Knoble, Naomi B.; Alderfer, Melissa A.; Hossain, Md Jobayer

    2016-01-01

    Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3,651 pediatric AML patients, aged 0–19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02–1.12) and 1.05(1.00–1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1: (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3: (high economic/educational disadvantage, high-mobility) and Cluster 6: (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI) = 1.19(1.0–1.4) and 1.23 (1.1–1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features. PMID:27543948

  13. Monopoly, Pareto and Ramsey mark-ups

    NARCIS (Netherlands)

    Ten Raa, T.

    2009-01-01

    Monopoly prices are too high. It is a price level problem, in the sense that the relative mark-ups have Ramsey optimal proportions, at least for independent constant elasticity demands. I show that this feature of monopoly prices breaks down the moment one demand is replaced by the textbook linear

  14. Hospital markup and operation outcomes in the United States.

    Science.gov (United States)

    Gani, Faiz; Ejaz, Aslam; Makary, Martin A; Pawlik, Timothy M

    2016-07-01

    Although the price hospitals charge for operations has broad financial implications, hospital pricing is not subject to regulation. We sought to characterize national variation in hospital price markup for major cardiothoracic and gastrointestinal operations and to evaluate perioperative outcomes of hospitals relative to hospital price markup. All hospitals in which a patient underwent a cardiothoracic or gastrointestinal procedure were identified using the Nationwide Inpatient Sample for 2012. Markup ratios (ratio of charges to costs) for the total cost of hospitalization were compared across hospitals. Risk-adjusted morbidity, failure-to-rescue, and mortality were calculated using multivariable, hierarchical logistic regression. Among the 3,498 hospitals identified, markup ratios ranged from 0.5-12.2, with a median markup ratio of 2.8 (interquartile range 2.7-3.9). For the 888 hospitals with extreme markup (greatest markup ratio quartile: markup ratio >3.9), the median markup ratio was 4.9 (interquartile range 4.3-6.0), with 10% of these hospitals billing more than 7 times the Medicare-allowable costs (markup ratio ≥7.25). Extreme markup hospitals were more often large (46.3% vs 33.8%, P markup ratio compared with 19.3% (n = 452) and 6.8% (n = 35) of nonprofit and government hospitals, respectively. Perioperative morbidity (32.7% vs 26.4%, P markup hospitals. There is wide variation in hospital markup for cardiothoracic and gastrointestinal procedures, with approximately a quarter of hospital charges being 4 times greater than the actual cost of hospitalization. Hospitals with an extreme markup had greater perioperative morbidity. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Osteolytic Bone Lesions - A Rare Presentation of AML M6.

    Science.gov (United States)

    Geetha, N; Sreelesh, K P; Priya, M J; Lali, V S; Rekha, N

    2015-01-01

    Acute myeloid leukemia (AML) M6 is a rare form of AML accounting for M6 before. We discuss the case of a 17 year old boy with AML M6, who presented with osteolytic lesion of right humerus. He was treated with induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  16. Monopoly, Pareto and Ramsey mark-ups

    OpenAIRE

    Ten Raa, T.

    2009-01-01

    Monopoly prices are too high. It is a price level problem, in the sense that the relative mark-ups have Ramsey optimal proportions, at least for independent constant elasticity demands. I show that this feature of monopoly prices breaks down the moment one demand is replaced by the textbook linear demand or, even within the constant elasticity framework, dependence is introduced. The analysis provides a single Generalized Inverse Elasticity Rule for the problems of monopoly, Pareto and Ramsey.

  17. Domain-specific markup languages and descriptive metadata: their functions in scientific resource discoveryLinguagens de marcação específicas por domínio e metadados descritivos: funções para a descoberta de recursos científicos

    Directory of Open Access Journals (Sweden)

    Marcia Lei Zeng

    2010-01-01

    Full Text Available While metadata has been a strong focus within information professionals‟ publications, projects, and initiatives during the last two decades, a significant number of domain-specific markup languages have also been developing on a parallel path at the same rate as metadata standards; yet, they do not receive comparable attention. This essay discusses the functions of these two kinds of approaches in scientific resource discovery and points out their potential complementary roles through appropriate interoperability approaches.Enquanto os metadados tiveram grande foco em publicações, projetos e iniciativas dos profissionais da informação durante as últimas duas décadas, um número significativo de linguagens de marcação específicas por domínio também se desenvolveram paralelamente a uma taxa equivalente aos padrões de metadados; mas ainda não recebem atenção comparável. Esse artigo discute as funções desses dois tipos de abordagens na descoberta de recursos científicos e aponta papéis potenciais e complementares por meio de abordagens de interoperabilidade apropriadas.

  18. WHO HAS THERAPY-RELATED AML?

    Directory of Open Access Journals (Sweden)

    Robert Gale

    2017-03-01

    Full Text Available Therapy-related leukemia or therapy-related myeloid neoplasm are widely-used terms to designate leukemia developing in persons who previously received anti-cancer therapy (for example, see references 1, 2, especially if the prior anti-cancer therapy included drugs such as alkylators, DNA-intercalators, topoisomerase-2-inhibitors, purines and/or ionizing radiations.   Sometimes specific genes such as AML1, EVI1, NRAS or MLL are mutated by therapy or gene variants are produced which activate mutagens or interfere with DNA repair, such FANC, NQ01 or AML2. 3-5   But how can we know if AML in someone is a therapy-related? Keywords: Therapy-related leukemia; alkylators; ionizing radiations; Topoisomerase Inhibitors; DNA Repair

  19. The National Cancer Informatics Program (NCIP) Annotation and Image Markup (AIM) Foundation model.

    Science.gov (United States)

    Mongkolwat, Pattanasak; Kleper, Vladimir; Talbot, Skip; Rubin, Daniel

    2014-12-01

    Knowledge contained within in vivo imaging annotated by human experts or computer programs is typically stored as unstructured text and separated from other associated information. The National Cancer Informatics Program (NCIP) Annotation and Image Markup (AIM) Foundation information model is an evolution of the National Institute of Health's (NIH) National Cancer Institute's (NCI) Cancer Bioinformatics Grid (caBIG®) AIM model. The model applies to various image types created by various techniques and disciplines. It has evolved in response to the feedback and changing demands from the imaging community at NCI. The foundation model serves as a base for other imaging disciplines that want to extend the type of information the model collects. The model captures physical entities and their characteristics, imaging observation entities and their characteristics, markups (two- and three-dimensional), AIM statements, calculations, image source, inferences, annotation role, task context or workflow, audit trail, AIM creator details, equipment used to create AIM instances, subject demographics, and adjudication observations. An AIM instance can be stored as a Digital Imaging and Communications in Medicine (DICOM) structured reporting (SR) object or Extensible Markup Language (XML) document for further processing and analysis. An AIM instance consists of one or more annotations and associated markups of a single finding along with other ancillary information in the AIM model. An annotation describes information about the meaning of pixel data in an image. A markup is a graphical drawing placed on the image that depicts a region of interest. This paper describes fundamental AIM concepts and how to use and extend AIM for various imaging disciplines.

  20. Markup heterogeneity, export status ans the establishment of the euro

    OpenAIRE

    Guillou , Sarah; Nesta , Lionel

    2015-01-01

    We investigate the effects of the establishment of the euro on the markups of French manufacturing firms. Merging firm-level census data with customs data, we estimate time-varying firm-specific markups and distinguish between eurozone exporters from other firms between 1995 and 2007. We find that the establishment of the euro has had a pronounced pro-competitive impact by reducing firm markups by 14 percentage points. By reducing export costs, the euro represented an opp...

  1. Semantic Markup for Literary Scholars: How Descriptive Markup Affects the Study and Teaching of Literature.

    Science.gov (United States)

    Campbell, D. Grant

    2002-01-01

    Describes a qualitative study which investigated the attitudes of literary scholars towards the features of semantic markup for primary texts in XML format. Suggests that layout is a vital part of the reading process which implies that the standardization of DTDs (Document Type Definitions) should extend to styling as well. (Author/LRW)

  2. PENDEKATAN MODEL MATEMATIS UNTUK MENENTUKAN PERSENTASE MARKUP HARGA JUAL PRODUK

    Directory of Open Access Journals (Sweden)

    Oviliani Yenty Yuliana

    2002-01-01

    Full Text Available The purpose of this research is to design Mathematical models that can determine the selling volume as an alternative to improve the markup percentage. Mathematical models was designed with double regression statistic. Selling volume is a function of markup, market condition, and substitute condition variables. The designed Mathematical model has fulfilled by the test of: error upon assumption, accurate model, validation model, and multi collinear problem. The Mathematical model has applied in application program with expectation that the application program can give: (1 alternative to decide percentage markup for user, (2 Illustration of gross profit estimation that will be achieve for selected percentage markup, (3 Illustration of estimation percentage of the units sold that will be achieve for selected percentage markup, and (4 Illustration of total net income before tax will get for specific period. Abstract in Bahasa Indonesia : Penelitian ini bertujuan untuk merancang model Matematis guna menetapkan volume penjualan, sebagai alternatif untuk menentukan persentase markup harga jual produk. Model Matematis dirancang menggunakan Statistik Regresi Berganda. Volume penjualan merupakan fungsi dari variabel markup, kondisi pasar, dan kondisi pengganti. Model Matematis yang dirancang sudah memenuhi uji: asumsi atas error, akurasi model, validasi model, dan masalah multikolinearitas. Rancangan model Matematis tersebut diterapkan dalam program aplikasi dengan harapan dapat memberi: (1 alternatif bagi pengguna mengenai berapa besar markup yang sebaiknya ditetapkan, (2 gambaran perkiraan laba kotor yang akan diperoleh setiap pemilihan markup, (3 gambaran perkiraan persentase unit yang terjual setiap pemilihan markup, dan (4 gambaran total laba kotor sebelum pajak yang dapat diperoleh pada periode yang bersangkutan. Kata kunci: model Matematis, aplikasi program, volume penjualan, markup, laba kotor.

  3. AML (Advanced Mud Logging: First Among Equals

    Directory of Open Access Journals (Sweden)

    T. Loermans

    2017-09-01

    Full Text Available During the past ten years an enormous development in mud logging technology has been made. Traditional mud logging was only qualitative in nature, and mudlogs could not be used for the petrophysical well evaluations which form the basis for all subsequent activities on wells and fields. AML however can provide quantitative information, logs with a reliability, trueness and precision like LWD and WLL. Hence for well evaluation programmes there are now three different logging methods available, each with its own pros and cons on specific aspects: AML, LWD and WLL. The largest improvements have been made in mud gas analysis and elemental analysis of cuttings. Mud gas analysis can yield hydrocarbon fluid composition for some components with a quality like PVT analysis, hence not only revolutionising the sampling programme so far done with only LWD/WLL, but also making it possible to geosteer on fluid properties. Elemental analysis of cuttings, e.g. with XRF, with an ability well beyond the capabilities of the spectroscopy measurements possible earlier with LWD/WLL tools, is opening up improved ways to evaluate formations, especially of course where the traditional methods are falling short of requirements, such as in unconventional reservoirs. An overview and specific examples of these AML logs is given, from which it may be concluded that AML now ought to be considered as “first among its equals”.

  4. A quality assessment tool for markup-based clinical guidelines.

    Science.gov (United States)

    Shalom, Erez; Shahar, Yuval; Taieb-Maimon, Meirav; Lunenfeld, Eitan

    2008-11-06

    We introduce a tool for quality assessment of procedural and declarative knowledge. We developed this tool for evaluating the specification of mark-up-based clinical GLs. Using this graphical tool, the expert physician and knowledge engineer collaborate to perform scoring, using pre-defined scoring scale, each of the knowledge roles of the mark-ups, comparing it to a gold standard. The tool enables scoring the mark-ups simultaneously at different sites by different users at different locations.

  5. PENDEKATAN MODEL MATEMATIS UNTUK MENENTUKAN PERSENTASE MARKUP HARGA JUAL PRODUK

    OpenAIRE

    Oviliani Yenty Yuliana; Yohan Wahyudi; Siana Halim

    2002-01-01

    The purpose of this research is to design Mathematical models that can determine the selling volume as an alternative to improve the markup percentage. Mathematical models was designed with double regression statistic. Selling volume is a function of markup, market condition, and substitute condition variables. The designed Mathematical model has fulfilled by the test of: error upon assumption, accurate model, validation model, and multi collinear problem. The Mathematical model has applied i...

  6. The caBIG annotation and image Markup project.

    Science.gov (United States)

    Channin, David S; Mongkolwat, Pattanasak; Kleper, Vladimir; Sepukar, Kastubh; Rubin, Daniel L

    2010-04-01

    Image annotation and markup are at the core of medical interpretation in both the clinical and the research setting. Digital medical images are managed with the DICOM standard format. While DICOM contains a large amount of meta-data about whom, where, and how the image was acquired, DICOM says little about the content or meaning of the pixel data. An image annotation is the explanatory or descriptive information about the pixel data of an image that is generated by a human or machine observer. An image markup is the graphical symbols placed over the image to depict an annotation. While DICOM is the standard for medical image acquisition, manipulation, transmission, storage, and display, there are no standards for image annotation and markup. Many systems expect annotation to be reported verbally, while markups are stored in graphical overlays or proprietary formats. This makes it difficult to extract and compute with both of them. The goal of the Annotation and Image Markup (AIM) project is to develop a mechanism, for modeling, capturing, and serializing image annotation and markup data that can be adopted as a standard by the medical imaging community. The AIM project produces both human- and machine-readable artifacts. This paper describes the AIM information model, schemas, software libraries, and tools so as to prepare researchers and developers for their use of AIM.

  7. Osteoblasts Protect AML Cells from SDF-1-Induced Apoptosis

    Science.gov (United States)

    Kremer, Kimberly N.; Dudakovic, Amel; McGee-Lawrence, Meghan E.; Philips, Rachael L.; Hess, Allan D.; Smith, B. Douglas; van Wijnen, Andre J.; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; Hedin, Karen E.

    2014-01-01

    The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment. PMID:24851270

  8. The semantics of Chemical Markup Language (CML): dictionaries and conventions

    Science.gov (United States)

    2011-01-01

    The semantic architecture of CML consists of conventions, dictionaries and units. The conventions conform to a top-level specification and each convention can constrain compliant documents through machine-processing (validation). Dictionaries conform to a dictionary specification which also imposes machine validation on the dictionaries. Each dictionary can also be used to validate data in a CML document, and provide human-readable descriptions. An additional set of conventions and dictionaries are used to support scientific units. All conventions, dictionaries and dictionary elements are identifiable and addressable through unique URIs. PMID:21999509

  9. PML:PAGE-OM Markup Language: About PAGE-OM [

    Lifescience Database Archive (English)

    Full Text Available he Object Management Group (OMG) standardization organization, and this was approved in 2006. The latest meeting... to continue this model development was held in Tokyo in September 2007. The meeting discussed extension...ation as well as modeling experimental results for associations between genotype and phenotype. The outcome of that meeting

  10. The semantics of Chemical Markup Language (CML): dictionaries and conventions.

    Science.gov (United States)

    Murray-Rust, Peter; Townsend, Joe A; Adams, Sam E; Phadungsukanan, Weerapong; Thomas, Jens

    2011-10-14

    The semantic architecture of CML consists of conventions, dictionaries and units. The conventions conform to a top-level specification and each convention can constrain compliant documents through machine-processing (validation). Dictionaries conform to a dictionary specification which also imposes machine validation on the dictionaries. Each dictionary can also be used to validate data in a CML document, and provide human-readable descriptions. An additional set of conventions and dictionaries are used to support scientific units. All conventions, dictionaries and dictionary elements are identifiable and addressable through unique URIs.

  11. Changes in latent fingerprint examiners' markup between analysis and comparison.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2015-02-01

    After the initial analysis of a latent print, an examiner will sometimes revise the assessment during comparison with an exemplar. Changes between analysis and comparison may indicate that the initial analysis of the latent was inadequate, or that confirmation bias may have affected the comparison. 170 volunteer latent print examiners, each randomly assigned 22 pairs of prints from a pool of 320 total pairs, provided detailed markup documenting their interpretations of the prints and the bases for their comparison conclusions. We describe changes in value assessments and markup of features and clarity. When examiners individualized, they almost always added or deleted minutiae (90.3% of individualizations); every examiner revised at least some markups. For inconclusive and exclusion determinations, changes were less common, and features were added more frequently when the image pair was mated (same source). Even when individualizations were based on eight or fewer corresponding minutiae, in most cases some of those minutiae had been added during comparison. One erroneous individualization was observed: the markup changes were notably extreme, and almost all of the corresponding minutiae had been added during comparison. Latents assessed to be of value for exclusion only (VEO) during analysis were often individualized when compared to a mated exemplar (26%); in our previous work, where examiners were not required to provide markup of features, VEO individualizations were much less common (1.8%). Published by Elsevier Ireland Ltd.

  12. Standardized Semantic Markup for Reference Terminologies, Thesauri and Coding Systems: Benefits for distributed E-Health Applications.

    Science.gov (United States)

    Hoelzer, Simon; Schweiger, Ralf K; Liu, Raymond; Rudolf, Dirk; Rieger, Joerg; Dudeck, Joachim

    2005-01-01

    With the introduction of the ICD-10 as the standard for diagnosis, the development of an electronic representation of its complete content, inherent semantics and coding rules is necessary. Our concept refers to current efforts of the CEN/TC 251 to establish a European standard for hierarchical classification systems in healthcare. We have developed an electronic representation of the ICD-10 with the extensible Markup Language (XML) that facilitates the integration in current information systems or coding software taking into account different languages and versions. In this context, XML offers a complete framework of related technologies and standard tools for processing that helps to develop interoperable applications.

  13. XML schemas and mark-up practices of taxonomic literature.

    Science.gov (United States)

    Penev, Lyubomir; Lyal, Christopher Hc; Weitzman, Anna; Morse, David R; King, David; Sautter, Guido; Georgiev, Teodor; Morris, Robert A; Catapano, Terry; Agosti, Donat

    2011-01-01

    We review the three most widely used XML schemas used to mark-up taxonomic texts, TaxonX, TaxPub and taXMLit. These are described from the viewpoint of their development history, current status, implementation, and use cases. The concept of "taxon treatment" from the viewpoint of taxonomy mark-up into XML is discussed. TaxonX and taXMLit are primarily designed for legacy literature, the former being more lightweight and with a focus on recovery of taxon treatments, the latter providing a much more detailed set of tags to facilitate data extraction and analysis. TaxPub is an extension of the National Library of Medicine Document Type Definition (NLM DTD) for taxonomy focussed on layout and recovery and, as such, is best suited for mark-up of new publications and their archiving in PubMedCentral. All three schemas have their advantages and shortcomings and can be used for different purposes.

  14. Interexaminer variation of minutia markup on latent fingerprints.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2016-07-01

    Latent print examiners often differ in the number of minutiae they mark during analysis of a latent, and also during comparison of a latent with an exemplar. Differences in minutia counts understate interexaminer variability: examiners' markups may have similar minutia counts but differ greatly in which specific minutiae were marked. We assessed variability in minutia markup among 170 volunteer latent print examiners. Each provided detailed markup documenting their examinations of 22 latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. An average of 12 examiners marked each latent. The primary factors associated with minutia reproducibility were clarity, which regions of the prints examiners chose to mark, and agreement on value or comparison determinations. In clear areas (where the examiner was "certain of the location, presence, and absence of all minutiae"), median reproducibility was 82%; in unclear areas, median reproducibility was 46%. Differing interpretations regarding which regions should be marked (e.g., when there is ambiguity in the continuity of a print) contributed to variability in minutia markup: especially in unclear areas, marked minutiae were often far from the nearest minutia marked by a majority of examiners. Low reproducibility was also associated with differences in value or comparison determinations. Lack of standardization in minutia markup and unfamiliarity with test procedures presumably contribute to the variability we observed. We have identified factors accounting for interexaminer variability; implementing standards for detailed markup as part of documentation and focusing future training efforts on these factors may help to facilitate transparency and reduce subjectivity in the examination process. Published by Elsevier Ireland Ltd.

  15. Trade reforms, mark-ups and bargaining power of workers: the case ...

    African Journals Online (AJOL)

    Ethiopian Journal of Economics ... workers between 1996 and 2007, a model of mark-up with labor bargaining power was estimated using random effects and LDPDM. ... Keywords: Trade reform, mark-up, bargaining power, rent, trade unions ...

  16. Socioeconomic status (SES) and childhood acute myeloid leukemia (AML) mortality risk: Analysis of SEER data.

    Science.gov (United States)

    Knoble, Naomi B; Alderfer, Melissa A; Hossain, Md Jobayer

    2016-10-01

    Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3651 pediatric AML patients, aged 0-19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility; F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02-1.12) and 1.05(1.00-1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1 (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3 (high economic/educational disadvantage, high-mobility) and Cluster 6 (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI)=1.19(1.0-1.4) and 1.23 (1.1-1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features. Copyright © 2016 Elsevier Ltd. All

  17. Ontology aided modeling of organic reaction mechanisms with flexible and fragment based XML markup procedures.

    Science.gov (United States)

    Sankar, Punnaivanam; Aghila, Gnanasekaran

    2007-01-01

    The mechanism models for primary organic reactions encoding the structural fragments undergoing substitution, addition, elimination, and rearrangements are developed. In the proposed models, each and every structural component of mechanistic pathways is represented with flexible and fragment based markup technique in XML syntax. A significant feature of the system is the encoding of the electron movements along with the other components like charges, partial charges, half bonded species, lone pair electrons, free radicals, reaction arrows, etc. needed for a complete representation of reaction mechanism. The rendering of reaction schemes described with the proposed methodology is achieved with a concise XML extension language interoperating with the structure markup. The reaction scheme is visualized as 2D graphics in a browser by converting them into SVG documents enabling the desired layouts normally perceived by the chemists conventionally. An automatic representation of the complex patterns of the reaction mechanism is achieved by reusing the knowledge in chemical ontologies and developing artificial intelligence components in terms of axioms.

  18. XML Schema Languages: Beyond DTD.

    Science.gov (United States)

    Ioannides, Demetrios

    2000-01-01

    Discussion of XML (extensible markup language) and the traditional DTD (document type definition) format focuses on efforts of the World Wide Web Consortium's XML schema working group to develop a schema language to replace DTD that will be capable of defining the set of constraints of any possible data resource. (Contains 14 references.) (LRW)

  19. The applicability of the WHO classification in paediatric AML. A NOPHO-AML study

    DEFF Research Database (Denmark)

    Sandahl, Julie D; Kjeldsen, Eigil; Abrahamsson, Jonas

    2015-01-01

    The World Health Organization (WHO) classification of myeloid leukaemia was revised in 2008. It incorporates newly recognized entities and emphasizes the pivotal role of cytogenetic abnormalities. The aim of this study was to evaluate the usability of the WHO classification when applied to a large......(7q) into one group. We found that -7 (n = 14) had significantly poorer outcome than del(7q) (n = 11); 5-year event-free survival 26% vs. 67%, (P = 0·02), and 5-year overall survival 51% vs. 90%, (P = 0·04). The largest group was the highly heterogeneous AML not otherwise specified (NOS) (n = 280...

  20. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Directory of Open Access Journals (Sweden)

    Diamantina Vasilatou

    2014-01-01

    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  1. Trisomy 8 in Pediatric Acute Myeloid Leukemia. A NOPHO-AML Study

    DEFF Research Database (Denmark)

    Laursen, Anne Cathrine Lund; Sandahl, Julie Damgaard; Kjeldsen, Eigil

    2016-01-01

    Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML...

  2. The Long-Run Relationship Between Inflation and the Markup in the U.S.

    OpenAIRE

    Sandeep Mazumder

    2011-01-01

    This paper examines the long-run relationship between inflation and a new measure of the price-marginal cost markup. This new markup index is derived while accounting for labor adjustment costs, which a large number of the papers that estimate the markup have ignored. We then examine the long-run relationship between this markup measure, which is estimated using U.S. manufacturing data, and inflation. We find that decreases in the markup that are associated with a percentage point increase in...

  3. The markup is the model: reasoning about systems biology models in the Semantic Web era.

    Science.gov (United States)

    Kell, Douglas B; Mendes, Pedro

    2008-06-07

    Metabolic control analysis, co-invented by Reinhart Heinrich, is a formalism for the analysis of biochemical networks, and is a highly important intellectual forerunner of modern systems biology. Exchanging ideas and exchanging models are part of the international activities of science and scientists, and the Systems Biology Markup Language (SBML) allows one to perform the latter with great facility. Encoding such models in SBML allows their distributed analysis using loosely coupled workflows, and with the advent of the Internet the various software modules that one might use to analyze biochemical models can reside on entirely different computers and even on different continents. Optimization is at the core of many scientific and biotechnological activities, and Reinhart made many major contributions in this area, stimulating our own activities in the use of the methods of evolutionary computing for optimization.

  4. The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs

    NARCIS (Netherlands)

    Mandoli, Amit; Singh, Abhishek A.; Prange, Koen H. M.; Tijchon, Esther; Oerlemans, Marjolein; Dirks, Rene; Ter Huurne, Menno; Wierenga, Albertus T. J.; Janssen-Megens, Eva M.; Berentsen, Kim; Sharifi, Nilofar; Kim, Bowon; Matarese, Filomena; Nguyen, Luan N.; Hubner, Nina C.; Rao, Nagesha A.; van den Akker, Emile; Altucci, Lucia; Vellenga, Edo; Stunnenberg, Hendrik G.; Martens, Joost H. A.

    2016-01-01

    The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels

  5. Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML

    DEFF Research Database (Denmark)

    Preiss, Birgitte S; Bergman, Olav J; Friis, Lone S

    2010-01-01

    During a 15-year period, 161 adult patients were diagnosed with secondary acute myeloid leukemia (s-AML) in the region of Southern Denmark. In 73 patients, the AML diagnosis was preceded by myelodysplastic syndrome (MDS-AML), in 31 patients by an antecedent hematologic disease, and in 57 patients...

  6. Language

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum

    2016-01-01

    Purpose: – The purpose of this paper is to analyse the consequences of globalisation in the area of corporate communication, and investigate how language may be managed as a strategic resource. Design/methodology/approach: – A review of previous studies on the effects of globalisation on corporate...... communication and the implications of language management initiatives in international business. Findings: – Efficient language management can turn language into a strategic resource. Language needs analyses, i.e. linguistic auditing/language check-ups, can be used to determine the language situation...... of a company. Language policies and/or strategies can be used to regulate a company’s internal modes of communication. Language management tools can be deployed to address existing and expected language needs. Continuous feedback from the front line ensures strategic learning and reduces the risk of suboptimal...

  7. PD-1 signaling and inhibition in AML and MDS.

    Science.gov (United States)

    Haroun, Faysal; Solola, Sade A; Nassereddine, Samah; Tabbara, Imad

    2017-09-01

    Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.

  8. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas

    2013-01-01

    ) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. RESULTS: Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13......BACKGROUND: Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients...... treated with SCT. MATERIAL AND METHODS: Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17...

  9. SIMILARITIES OF ELDERLY AND THERAPY-RELATED AML

    Directory of Open Access Journals (Sweden)

    Francesco D'Alò

    2011-11-01

    Full Text Available Acute myeloid leukemia (AML is a clonal disorder of the hematopoietic stem cell, typical of the elderly, with a median age of over 60 years at diagnosis. In AML, older age is one of the strongest independent adverse prognostic factor, associated with decreased complete response rate, worse disease-free and overall survival, with highest rates of treatment related mortality, resistant disease and relapse, compared to younger patients. While clinical risk factors do not significantly differ between older and younger patients, outcomes are compromised in elderly patients not only by increased comorbidities and susceptibility to toxicity from therapy, but it is now recognized that elderly AML represents a biologically distinct disease, that is itself more aggressive and less responsive to therapy. In elderly individuals prolonged exposure to environmental carcinogens may be the basis for the aggressive biology of the disease. This may also be the basis for similarities between elderly AML and therapy-related myeloid malignancies, mimicking toxic effects of previous cytotoxic treatments on hematopoietic stem cells. Age is itself a risk factor for t-MN, which are more frequent in elderly patients, where also a shorter latency between treatment of primary tumor and t-MN has been reported. Similarities between therapy-related malignancies and elderly AML include morphological aspects, as the presence of multilineage dysplasia preceding and/or concomitant to the development of leukemia, and adverse cytogenetics, including poor karyotype and chromosome 5 and/or 7 abnormalities. Looking at molecular prognosticators in elderly AML, similar to t-MN,  reduced frequency of favorable factors, as reduced number of NPM1 and CEBPA mutated cases has been observed, together with increased incidence of negative factors, as increased MDR1 expression, accelerated telomere shortening  and frequency of methylation changes. Given the unfavorable prognosis of elderly and

  10. Are the determinants of markup size industry-specific? The case of Slovenian manufacturing firms

    Directory of Open Access Journals (Sweden)

    Ponikvar Nina

    2011-01-01

    Full Text Available The aim of this paper is to identify factors that affect the pricing policy in Slovenian manufacturing firms in terms of the markup size and, most of all, to explicitly account for the possibility of differences in pricing procedures among manufacturing industries. Accordingly, the analysis of the dynamic panel is carried out on an industry-by-industry basis, allowing the coefficients on the markup determinants to vary across industries. We find that the oligopoly theory of markup determination for the most part holds for the manufacturing sector as a whole, although large variability in markup determinants exists across industries within the Slovenian manufacturing. Our main conclusion is that each industry should be investigated separately in detail in order to assess the precise role of markup factors in the markup-determination process.

  11. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.

    2015-01-01

    chromosomal structural rearrangements and single nucleotide variants (SNVs). Conventional AML diagnostics and recent seminal next-generation sequencing (NGS) studies have identified more than 200 recurrent genetic aberrations presenting in various combinations in individual patients. Significantly, many...... of these aberrations occur in normal hematopoietic stem and progenitor cells (HSCs/HPCs) before definitive leukemic transformation through additional acquisition of a few (that is, mostly 1 or 2) leukemia-promoting driver aberrations. NGS studies on sorted bone marrow (BM) populations of AML patients with a normal...

  12. The Commercial Office Market and the Markup for Full Service Leases

    OpenAIRE

    Jonathan A. Wiley; Yu Liu; Dongshin Kim; Tom Springer

    2014-01-01

    Because landlords assume all of the operating expense risk, rents for gross leases exceed those for net leases. The markup, or spread, for gross leases varies between properties and across markets. Specifically, the markup is expected to increase with the cost of real estate services at the property, and to be influenced by market conditions. A matching procedure is applied to measure the services markup as the percentage difference between the actual rent on a gross lease relative to the act...

  13. The Price-Marginal Cost Markup and its Determinants in U.S. Manufacturing

    OpenAIRE

    Mazumder, Sandeep

    2009-01-01

    This paper estimates the price-marginal cost markup for US manufacturing using a new methodology. Most existing techniques of estimating the markup are a variant on Hall's (1988) framework involving the manipulation of the Solow Residual. However this paper argues that this notion is based on the unreasonable assumption that labor can be costlessly adjusted at a fixed wage rate. By relaxing this assumption, we are able to derive a generalized markup index, which when estimated using manufactu...

  14. Outcome of poor response paediatric AML using early SCT.

    Science.gov (United States)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas; Forestier, Erik; Gustafsson, Britt; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Hasle, Henrik

    2013-03-01

    Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients treated with SCT. Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13, matched sibling donors in 6, cord blood donor in 4, and haploidentical donor in two. The median follow-up for the 31 poor responding patients was 2.6 years (range 0.4 - 8.1 years) and 3-year probability of survival 70% (95% CI 59-77%). The poor responders in the NOPHO-AML 2004 protocol had a favourable prognosis treated with time-intensive induction followed by SCT. © 2012 John Wiley & Sons A/S.

  15. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy

    DEFF Research Database (Denmark)

    Bruedigam, Claudia; Bagger, Frederik Otzen; Heidel, Florian H.

    2014-01-01

    (-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia...... progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs....

  16. Planned growth as a determinant of the markup: the case of Slovenian manufacturing

    Directory of Open Access Journals (Sweden)

    Maks Tajnikar

    2009-11-01

    Full Text Available The paper follows the idea of heterodox economists that a cost-plus price is above all a reproductive price and growth price. The authors apply a firm-level model of markup determination which, in line with theory and empirical evidence, contains proposed firm-specific determinants of the markup, including the firm’s planned growth. The positive firm-level relationship between growth and markup that is found in data for Slovenian manufacturing firms implies that retained profits gathered via the markup are an important source of growth financing and that the investment decisions of Slovenian manufacturing firms affect their pricing policy and decisions on the markup size as proposed by Post-Keynesian theory. The authors thus conclude that at least a partial trade-off between a firm’s growth and competitive outcome exists in Slovenian manufacturing.

  17. Osteolytic bone lesions – A rare presentation of AML M6.

    Directory of Open Access Journals (Sweden)

    Geetha N.

    2015-02-01

    Full Text Available Acute myeloid leukemia (AML M6 is a rare form of AML  accounting  for < 5 % of all AML.  Extramedullary involvement  is very rarely seen in this entity.  Skeletal lesion has not been described in AML M6 before. We discuss the case of  a 17 year old boy with AML M6 who presented with  osteolytic lesion of right humerus.  He was treated with  induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  18. Successful treatment of congenital acute myeloid leukemia (AML-M6) in a premature infant.

    Science.gov (United States)

    van Dongen, Joyce C A; Dalinghaus, Michiel; Kroon, Andre A; de Vries, Andrica C H; van den Heuvel-Eibrink, Marry M

    2009-11-01

    Congenital acute myeloid leukemia (AML), and especially AML-M6 is a rare disease with a poor prognosis. Moreover, reports of treatment outcome of congenital AML-M6 in premature infants are not available. We report the first treated case of congenital AML-M6 in a premature girl, who received a full AML protocol. She presented with blueberry-muffin spots, anemia, high white blood cell count, and serious cardiopulmonary distress. Peripheral blood smears showed AML-M6 blasts. After treatment with a sequential low-dose cytarabine after birth and full-dose AML treatment according to the MRC-12 protocol at the age of 2 months, she now is in continuous complete remission for 4 years.

  19. Physical properties of Kentucky's AML landslides: Case studies analyzed

    International Nuclear Information System (INIS)

    Iannacchione, A.T.; Vallejo, L.E.

    1994-01-01

    Once an abandoned mined land (AML) landslide occurs and is identified as an emergency, engineers must rapidly implement a slope stabilization design. Correct slope remediation solutions are generally derived from well-executed geotechnical examinations. This paper summarizes a large body of geotechnical data compiled by the US office of Surface Mining Reclamation and Enforcement (OSM) from AML landslides in eastern Kentucky. Special attention is placed on the examination of subsurface failures, phreatic water levels, soil profiles, and soil composition information from numerous borehole exploration programs. Strength properties calculated from laboratory procedures and stability analysis techniques were also reviewed. Laboratory-determined soil shear strength values were found to be higher than those inferred from stability analysis. This suggests that postfailure determinations of the phreatic surface may be largely inappropriate when used in stability analysis or that laboratory-measured shear strengths are ineffective in replicating in situ colluvium/spoil slope properties

  20. A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML

    DEFF Research Database (Denmark)

    Knapper, Steven; Russell, Nigel; Gilkes, Amanda

    2017-01-01

    The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activ...

  1. Transcriptome Profiling of Pediatric Core Binding Factor AML.

    Directory of Open Access Journals (Sweden)

    Chih-Hao Hsu

    Full Text Available The t(8;21 and Inv(16 translocations disrupt the normal function of core binding factors alpha (CBFA and beta (CBFB, respectively. These translocations represent two of the most common genomic abnormalities in acute myeloid leukemia (AML patients, occurring in approximately 25% pediatric and 15% of adult with this malignancy. Both translocations are associated with favorable clinical outcomes after intensive chemotherapy, and given the perceived mechanistic similarities, patients with these translocations are frequently referred to as having CBF-AML. It remains uncertain as to whether, collectively, these translocations are mechanistically the same or impact different pathways in subtle ways that have both biological and clinical significance. Therefore, we used transcriptome sequencing (RNA-seq to investigate the similarities and differences in genes and pathways between these subtypes of pediatric AMLs. Diagnostic RNA from patients with t(8;21 (N = 17, Inv(16 (N = 14, and normal karyotype (NK, N = 33 were subjected to RNA-seq. Analyses compared the transcriptomes across these three cytogenetic subtypes, using the NK cohort as the control. A total of 1291 genes in t(8;21 and 474 genes in Inv(16 were differentially expressed relative to the NK controls, with 198 genes differentially expressed in both subtypes. The majority of these genes (175/198; binomial test p-value < 10(-30 are consistent in expression changes among the two subtypes suggesting the expression profiles are more similar between the CBF cohorts than in the NK cohort. Our analysis also revealed alternative splicing events (ASEs differentially expressed across subtypes, with 337 t(8;21-specific and 407 Inv(16-specific ASEs detected, the majority of which were acetylated proteins (p = 1.5 x 10(-51 and p = 1.8 x 10(-54 for the two subsets. In addition to known fusions, we identified and verified 16 de novo fusions in 43 patients, including three fusions involving NUP98 in six

  2. Intended and unintended consequences of China's zero markup drug policy.

    Science.gov (United States)

    Yi, Hongmei; Miller, Grant; Zhang, Linxiu; Li, Shaoping; Rozelle, Scott

    2015-08-01

    Since economic liberalization in the late 1970s, China's health care providers have grown heavily reliant on revenue from drugs, which they both prescribe and sell. To curb abuse and to promote the availability, safety, and appropriate use of essential drugs, China introduced its national essential drug list in 2009 and implemented a zero markup policy designed to decouple provider compensation from drug prescription and sales. We collected and analyzed representative data from China's township health centers and their catchment-area populations both before and after the reform. We found large reductions in drug revenue, as intended by policy makers. However, we also found a doubling of inpatient care that appeared to be driven by supply, instead of demand. Thus, the reform had an important unintended consequence: China's health care providers have sought new, potentially inappropriate, forms of revenue. Project HOPE—The People-to-People Health Foundation, Inc.

  3. Variation in markup of general surgical procedures by hospital market concentration.

    Science.gov (United States)

    Cerullo, Marcelo; Chen, Sophia Y; Dillhoff, Mary; Schmidt, Carl R; Canner, Joseph K; Pawlik, Timothy M

    2018-04-01

    Increasing hospital market concentration (with concomitantly decreasing hospital market competition) may be associated with rising hospital prices. Hospital markup - the relative increase in price over costs - has been associated with greater hospital market concentration. Patients undergoing a cardiothoracic or gastrointestinal procedure in the 2008-2011 Nationwide Inpatient Sample (NIS) were identified and linked to Hospital Market Structure Files. The association between market concentration, hospital markup and hospital for-profit status was assessed using mixed-effects log-linear models. A weighted total of 1,181,936 patients were identified. In highly concentrated markets, private for-profit status was associated with an 80.8% higher markup compared to public/private not-for-profit status (95%CI: +69.5% - +96.9%; p markup compared to public/private not-for-profit status in unconcentrated markets (95%CI: +45.4% - +81.1%; p markup. Government and private not-for-profit hospitals employed lower markups in more concentrated markets, whereas private for-profit hospitals employed higher markups in more concentrated markets. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Data on the interexaminer variation of minutia markup on latent fingerprints.

    Science.gov (United States)

    Ulery, Bradford T; Hicklin, R Austin; Roberts, Maria Antonia; Buscaglia, JoAnn

    2016-09-01

    The data in this article supports the research paper entitled "Interexaminer variation of minutia markup on latent fingerprints" [1]. The data in this article describes the variability in minutia markup during both analysis of the latents and comparison between latents and exemplars. The data was collected in the "White Box Latent Print Examiner Study," in which each of 170 volunteer latent print examiners provided detailed markup documenting their examinations of latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. Each examiner examined 22 latent-exemplar pairs; an average of 12 examiners marked each latent.

  5. The role of therapeutic leukapheresis in hyperleukocytotic AML.

    Directory of Open Access Journals (Sweden)

    Friederike Pastore

    Full Text Available Hyperleukocytosis in AML with leukostasis is a serious life-threatening condition leading to a high early mortality which requires immediate cytoreductive therapy. Therapeutic leukapheresis is currently recommended by the American Society of Apheresis in patients with a WBC>100 G/l with signs of leukostasis, but the role of prophylactic leukapheresis before clinical signs of leukostasis occur is unclear.We retrospectively analyzed the role of leukapheresis in 52 patients (median age 60 years with hyperleukocytotic AML with and without clinical signs of leukostasis. Since leukapheresis was performed more frequently in patients with signs of leukostasis due to the therapeutic policy in our hospital, we developed a risk score for early death within seven days after start of therapy (EDd7 to account for this selection bias and to independently measure the effect of leukapheresis on EDd7.20 patients received leukapheresis in combination to chemotherapy compared to 32 patients who received chemotherapy only. In a multivariate logistic regression model for the estimation of the probability of EDd7 thromboplastin time and creatinine remained as independent significant parameters and were combined to create an EDd7 risk score. The effect of leukapheresis on EDd7 was evaluated in a bivariate logistic regression together with the risk score. Leukapheresis did not significantly change early mortality in all patients with a WBC≥100 G/l.Prophylactic leukapheresis in hyperleukocytotic patients with and without leukostasis did not improve early mortality in our retrospective study. Larger and prospective clinical trials are needed to validate the risk score and to further explore the role of leukapheresis in AML with hyperleukocytosis.

  6. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia.

    Science.gov (United States)

    Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G

    2016-11-03

    Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL hi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. © 2016 by The American Society of Hematology.

  7. HTEL: a HyperText Expression Language

    DEFF Research Database (Denmark)

    Steensgaard-Madsen, Jørgen

    1999-01-01

    been submitted.A special tool has been used to build the HTEL-interpreter, as an example belonging a family of interpreters for domain specific languages. Members of that family have characteristics that are closely related to structural patterns found in the mark-ups of HTML. HTEL should also be seen...

  8. AML with t(7;12)(q36;p13) is associated with infancy and trisomy 19. Data from NOPHO-AML and review of the literature

    DEFF Research Database (Denmark)

    Espersen, Anne Dorte Lerche; Noren-Nyström, Ulrika; Abrahamsson, Jonas

    2018-01-01

    The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children ...). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation...

  9. SELECTION OF ONTOLOGY FOR WEB SERVICE DESCRIPTION LANGUAGE TO ONTOLOGY WEB LANGUAGE CONVERSION

    OpenAIRE

    J. Mannar Mannan; M. Sundarambal; S. Raghul

    2014-01-01

    Semantic web is to extend the current human readable web to encoding some of the semantic of resources in a machine processing form. As a Semantic web component, Semantic Web Services (SWS) uses a mark-up that makes the data into detailed and sophisticated machine readable way. One such language is Ontology Web Language (OWL). Existing conventional web service annotation can be changed to semantic web service by mapping Web Service Description Language (WSDL) with the semantic annotation of O...

  10. Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

    Directory of Open Access Journals (Sweden)

    Shinobu Tsuzuki

    2007-05-01

    Full Text Available AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo.The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo.These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood

  11. Asymptotically Matched Layer (AML) for transient wave propagation in a moving frame of reference

    DEFF Research Database (Denmark)

    Madsen, Stine Skov; Krenk, Steen

    2017-01-01

    The paper presents an Asymptotically Matched Layer (AML) formulation in a moving frame of reference for transient dynamic response of a multi-layer 2D half-space. A displacement based finite element formulation of the convected domain problem is presented together with the AML formulation in whic...

  12. Initiation of MLL-rearranged AML is dependent on C/EBPα

    DEFF Research Database (Denmark)

    Ohlsson, Ewa; Hasemann, Marie Sigurd; Willer, Anton

    2014-01-01

    have compared gene expression profiles from human MLL-rearranged AML to normal progenitors and identified the myeloid tumor suppressor C/EBPα as a putative collaborator in MLL-rearranged AML. Interestingly, we find that deletion of Cebpa rendered murine hematopoietic progenitors completely resistant...

  13. IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells.

    Science.gov (United States)

    Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit

    2015-05-14

    Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

  14. [Initial subretinal localization of acute myeloblastic leukemia (AML5) recurrence].

    Science.gov (United States)

    Le Gall, S; François, S; Urier, N; Genevieve, F; d'Hermies, F; Rachieru, P; Ifrah, N

    2001-10-13

    Reduced visual acuity in patients with acute leucemia can result from many causes including an ocular localization. A patient previously treated for acute myeloblastic leucemia-5 (AML5) developed bilateral vision impairment related to a subretinal localization of the leucemia. Meningeal and bone marrow relapse followed. The subretinal localization responded only to massive systemic steroid treatment. Although asymptomatic, ocular localizations are frequent in leucemia. Their prognostic impact depends on the ocular structure involved and on the chronology of onset--early or late in the leucemia course. The underlying pathophysiological mechanism of ocular involvement remains unexplained but hyperleucocytosis at presentation may be a risk factor and would justify at least systematic specialized examinations and discussion of prophylactic treatment.

  15. American experience in the implementation of AML / CFT system

    Directory of Open Access Journals (Sweden)

    Larin Dmitry

    2016-01-01

    Full Text Available This article presents a research into very specific matters and issues of creating and further improvement of Anti-Money Laundering and Combating the Financing of Terrorism system (abbreviated as AML/CFT in the USA. In contains a precise analysis of key elements of this system, as well as a deep look into the nature and purposes of financial intelligence “FinCEN”. Strong emphasis is laid on The US Foreign Account Tax Compliance Act (FATCA for the reason that, according to this Act, any foreign financial institution is legitimately forced to sign a special agreement with The US Internal Revenue Service (IRS, giving the Service power to maintain control over any American asset within its equity. The latter is understood as a legal right to investigate not only the accounts and property of American taxpayers, but to investigate any account or capital of any foreign institution having American shares or stocks.

  16. Prenatal origin of childhood AML occurs less frequently than in childhood ALL

    International Nuclear Information System (INIS)

    Burjanivova, Tatiana; Zuna, Jan; Madzo, Jozef; Muzikova, Katerina; Meyer, Claus; Schneider, Bjoern; Votava, Felix; Marschalek, Rolf; Stary, Jan; Trka, Jan

    2006-01-01

    While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

  17. Application of whole slide image markup and annotation for pathologist knowledge capture.

    Science.gov (United States)

    Campbell, Walter S; Foster, Kirk W; Hinrichs, Steven H

    2013-01-01

    The ability to transfer image markup and annotation data from one scanned image of a slide to a newly acquired image of the same slide within a single vendor platform was investigated. The goal was to study the ability to use image markup and annotation data files as a mechanism to capture and retain pathologist knowledge without retaining the entire whole slide image (WSI) file. Accepted mathematical principles were investigated as a method to overcome variations in scans of the same glass slide and to accurately associate image markup and annotation data across different WSI of the same glass slide. Trilateration was used to link fixed points within the image and slide to the placement of markups and annotations of the image in a metadata file. Variation in markup and annotation placement between WSI of the same glass slide was reduced from over 80 μ to less than 4 μ in the x-axis and from 17 μ to 6 μ in the y-axis (P < 0.025). This methodology allows for the creation of a highly reproducible image library of histopathology images and interpretations for educational and research use.

  18. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML.

    Science.gov (United States)

    Wong, Terrence N; Miller, Christopher A; Klco, Jeffery M; Petti, Allegra; Demeter, Ryan; Helton, Nichole M; Li, Tiandao; Fulton, Robert S; Heath, Sharon E; Mardis, Elaine R; Westervelt, Peter; DiPersio, John F; Walter, Matthew J; Welch, John S; Graubert, Timothy A; Wilson, Richard K; Ley, Timothy J; Link, Daniel C

    2016-02-18

    There is interest in using leukemia-gene panels and next-generation sequencing to assess acute myelogenous leukemia (AML) response to induction chemotherapy. Studies have shown that patients with AML in morphologic remission may continue to have clonal hematopoiesis with populations closely related to the founding AML clone and that this confers an increased risk of relapse. However, it remains unknown how induction chemotherapy influences the clonal evolution of a patient's nonleukemic hematopoietic population. Here, we report that 5 of 15 patients with genetic clearance of their founding AML clone after induction chemotherapy had a concomitant expansion of a hematopoietic population unrelated to the initial AML. These populations frequently harbored somatic mutations in genes recurrently mutated in AML or myelodysplastic syndromes and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that nonleukemic hematopoietic stem and progenitor cells, harboring specific aging-acquired mutations, may have a competitive fitness advantage after induction chemotherapy, expand, and persist long after the completion of chemotherapy. Although the clinical importance of these "rising" clones remains to be determined, it will be important to distinguish them from leukemia-related populations when assessing for molecular responses to induction chemotherapy. © 2016 by The American Society of Hematology.

  19. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Marianne van; Murphy, Eoin [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); Morrell, Ruth [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Knapper, Steven [Department of Haematology, School of Medicine, Cardiff University, Heath Park, CF14 4XN Cardiff (United Kingdom); O' Dwyer, Michael [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Samali, Afshin; Szegezdi, Eva, E-mail: eva.szegezdi@nuigalway.ie [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)

    2011-03-15

    Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  20. [Application of Next Generation Sequencing for AML/MDS Diagnosis and Treatment].

    Science.gov (United States)

    Cheng, Huan-Chen; Liu, Sheng-Wei; Liu, Yu; Zhao, Xue-Fei; Li, Wei; Qiu, Lin; Ma, Jun

    2017-12-01

    To detect the mutations of AML/MDS- related genes by using next generation sequencing (NGS), to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS, and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases. The specimens were collected from primary AML (68 cases) and MDS (57 cases) patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips. TET2 gene showed the highest mutation rate in AML (55.9%) and MDS (56.1%). The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3, C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack, but the mutation rate of TET2 gene was not obviously changed, whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression, but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission. Both AML and MDS have their own specific mutated genes and sites. Some gene mutations, such as CEBPA, can be used as an effective indicator to monitoring MRD in AML patients, but those only used for the evaluation of the disease progression and prognosis in MDS patients.

  1. High Frequency of AML1/RUNX1 Point Mutations in Radiation-Associated Myelodysplastic Syndrome Around Semipalatinsk Nuclear Test Site

    OpenAIRE

    Dinara, ZHARLYGANOVA; Hironori, HARADA; Yuka, HARADA; Sergey, SHINKAREV; Zhaxybay, ZHUMADILOV; Aigul, ZHUNUSOVA; Naylya J., TCHAIZHUNUSOVA; Kazbek N., APSALIKOV; Vadim, KEMAIKIN; Kassym, ZHUMADILOV; Noriyuki, KAWANO; Akiro, KIMURA; Masaharu, HOSHI; Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University; Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University

    2008-01-01

    It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients wi...

  2. The emerging role of immune checkpoint based approaches in AML and MDS.

    Science.gov (United States)

    Boddu, Prajwal; Kantarjian, Hagop; Garcia-Manero, Guillermo; Allison, James; Sharma, Padmanee; Daver, Naval

    2018-04-01

    The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases. CTLA-4 inhibition may be especially effective in treating late post-allogeneic stem cell transplant relapse of AML in patients with limited or no graft versus host disease. Immune checkpoint inhibition, specifically PD-1 inhibition, demonstrated limited single agent efficacy in patients with relapsed AML and with MDS post-hypomethylating therapy. Rationally designed combinations of PD-1 inhibitors with standard anti-leukemic therapy are needed. Hypomethylating agents such as azacitidine, up-regulate PD-1, PD-L1, and PD-L2 in patients with AML/MDS and up-regulation of these genes was associated with the emergence of resistance. The combination of azacitidine and PD-1/PD-L1 inhibition may be a potential mechanism to prevent or overcome resistance to 5-azacitidine. A number of such combinations are being evaluated in clinical trials with early encouraging results. Immune checkpoint inhibition is also an attractive option to improve relapse-free survival or eliminate minimal residual disease post induction and consolidation by enhancing T-cell surveillance in patients with high-risk AML. The ongoing clinical trials with checkpoint inhibitors in AML/MDS will improve our understanding of the immunobiology of these diseases and guide us to the most appropriate application of these agents in the therapy of AML/MDS.

  3. Focal Adhesion Kinase as a Potential Target in AML and MDS.

    Science.gov (United States)

    Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng; Yang, Hui; Garcia-Manero, Guillermo; Mak, Duncan H; Mu, Hong; Ruvolo, Vivian R; Qiu, Yihua; Coombes, Kevin; Zhang, Nianxiang; Ragon, Brittany; Weaver, David T; Pachter, Jonathan A; Kornblau, Steven; Andreeff, Michael

    2017-06-01

    Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics ( P = 2 × 10 -4 ) and relapse ( P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3 -ITD ( P = 0.0024) or RAS ( P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34 + ( P = 5.42 × 10 -20 ) and CD34 + CD38 - MDS ( P = 7.62 × 10 -9 ) cells compared with normal CD34 + cells. MDS patients with higher FAK in CD34 + cells tended to have better overall survival ( P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133-44. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. The DSD Schema Language

    DEFF Research Database (Denmark)

    Klarlund, Nils; Møller, Anders; Schwartzbach, Michael Ignatieff

    2002-01-01

    be specified as a set of trees. For example, XHTML is a user domain corresponding to a set of XML documents that make sense as hypertext. A notation for defining such a set of XML trees is called a schema language. We believe that a useful schema notation must identify most of the syntactic requirements......XML (Extensible Markup Language), a linear syntax for trees, has gathered a remarkable amount of interest in industry. The acceptance of XML opens new venues for the application of formal methods such as specification of abstract syntax tree sets and tree transformations. A user domain may...... on tree nodes depend on their context. We also support a general, declarative mechanism for inserting default elements and attributes. Also, we include a simple technique for reusing and evolving DSDs through selective redefinitions. The expressiveness of DSD is comparable to that of the schema language...

  5. Resolving Controlled Vocabulary in DITA Markup: A Case Example in Agroforestry

    Science.gov (United States)

    Zschocke, Thomas

    2012-01-01

    Purpose: This paper aims to address the issue of matching controlled vocabulary on agroforestry from knowledge organization systems (KOS) and incorporating these terms in DITA markup. The paper has been selected for an extended version from MTSR'11. Design/methodology/approach: After a general description of the steps taken to harmonize controlled…

  6. Modularization and Structured Markup for Learning Content in an Academic Environment

    Science.gov (United States)

    Schluep, Samuel; Bettoni, Marco; Schar, Sissel Guttormsen

    2006-01-01

    This article aims to present a flexible component model for modular, web-based learning content, and a simple structured markup schema for the separation of content and presentation. The article will also contain an overview of the dynamic Learning Content Management System (dLCMS) project, which implements these concepts. Content authors are a…

  7. A methodology for evaluation of a markup-based specification of clinical guidelines.

    Science.gov (United States)

    Shalom, Erez; Shahar, Yuval; Taieb-Maimon, Meirav; Lunenfeld, Eitan

    2008-11-06

    We introduce a three-phase, nine-step methodology for specification of clinical guidelines (GLs) by expert physicians, clinical editors, and knowledge engineers, and for quantitative evaluation of the specification's quality. We applied this methodology to a particular framework for incremental GL structuring (mark-up) and to GLs in three clinical domains with encouraging results.

  8. Patient-derived acute myeloid leukemia (AML) bone marrow cells display distinct intracellular kinase phosphorylation patterns

    International Nuclear Information System (INIS)

    Shults, Keith; Flye, Leanne; Green, Lisa; Daly, Thomas; Manro, Jason R; Lahn, Michael

    2009-01-01

    Multiparametric analyses of phospho-protein activation in patients with acute myeloid leukemia (AML) offers a quantitative measure to monitor the activity of novel intracellular kinase (IK) inhibitors. As recent clinical investigation with FMS-like tyrosine-3 inhibitors demonstrated, targeting IK with selective inhibitors can have a modest clinical benefit. Because multiple IKs are active in patients with AML, multikinase inhibitors may provide the necessary inhibition profile to achieve a more sustained clinical benefit. We here describe a method of assessing the activation of several IKs by flow cytometry. In 40 different samples of patients with AML we observed hyper-activated phospho-proteins at baseline, which is modestly increased by adding stem cell factor to AML cells. Finally, AML cells had a significantly different phospho-protein profile compared with cells of the lymphocyte gate. In conclusion, our method offers a way to determine the activation status of multiple kinases in AML and hence is a reliable assay to evaluate the pharmacodynamic activity of novel multikinase inhibitors

  9. Therapy-related AML/MDS after treatment of low-grade B-cell lymphoma

    International Nuclear Information System (INIS)

    Yanada, Masamitsu

    2008-01-01

    Described is the therapy-related AML (acute myelogenetic leukemia)/MDS (myelo-dysplasia syndrome), which is manifested after various treatments of low-grade B-cell lymphoma and has strongly attracted attention because of the markedly improved prognosis due to recent advantages of the therapy for the disease. AML/MDS occurs several years after chemotherapy and/or radiation therapy which cause DNA damage in hematopoietic cells, and the AML/MDS risk is known increased in patients undergone especially with autologous transplantation of those cells. AML/MDS has the feature similar to that caused either by alkylating agent or by topoisomerase-2 inhibitor, and the disease by radiation belong to the former. Yet unclear is the problem whether malignant cells causing the disease after therapy are derived from the remaining cells in the graft or in the body. Although irradiations of total body and total lymphaden as well as chemotherapy are said to be related to AML/MDS and local irradiation does not contribute to its risk, the most important factor for the disease is considered to be the autotransplantation as the recurrence occurs in 50% after it. Thus the treatment history should be taken into consideration for suppressing AML/MDS, for which follow up with consideration for the disease is required particularly after autotransplantation. (R.T.)

  10. Automation and integration of components for generalized semantic markup of electronic medical texts.

    Science.gov (United States)

    Dugan, J M; Berrios, D C; Liu, X; Kim, D K; Kaizer, H; Fagan, L M

    1999-01-01

    Our group has built an information retrieval system based on a complex semantic markup of medical textbooks. We describe the construction of a set of web-based knowledge-acquisition tools that expedites the collection and maintenance of the concepts required for text markup and the search interface required for information retrieval from the marked text. In the text markup system, domain experts (DEs) identify sections of text that contain one or more elements from a finite set of concepts. End users can then query the text using a predefined set of questions, each of which identifies a subset of complementary concepts. The search process matches that subset of concepts to relevant points in the text. The current process requires that the DE invest significant time to generate the required concepts and questions. We propose a new system--called ACQUIRE (Acquisition of Concepts and Queries in an Integrated Retrieval Environment)--that assists a DE in two essential tasks in the text-markup process. First, it helps her to develop, edit, and maintain the concept model: the set of concepts with which she marks the text. Second, ACQUIRE helps her to develop a query model: the set of specific questions that end users can later use to search the marked text. The DE incorporates concepts from the concept model when she creates the questions in the query model. The major benefit of the ACQUIRE system is a reduction in the time and effort required for the text-markup process. We compared the process of concept- and query-model creation using ACQUIRE to the process used in previous work by rebuilding two existing models that we previously constructed manually. We observed a significant decrease in the time required to build and maintain the concept and query models.

  11. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients.

    Directory of Open Access Journals (Sweden)

    Virginie Marcel

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML.

  12. c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

    International Nuclear Information System (INIS)

    Gao Fenghou; Wang Qiong; Wu Yingli; Li Xi; Zhao Kewen; Chen Guoqiang

    2007-01-01

    AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

  13. Simulation Experiment Description Markup Language (SED-ML Level 1 Version 2

    Directory of Open Access Journals (Sweden)

    Bergmann Frank T.

    2015-06-01

    Full Text Available The number, size and complexity of computational models of biological systems are growing at an ever increasing pace. It is imperative to build on existing studies by reusing and adapting existing models and parts thereof. The description of the structure of models is not sufficient to enable the reproduction of simulation results. One also needs to describe the procedures the models are subjected to, as recommended by the Minimum Information About a Simulation Experiment (MIASE guidelines.

  14. The Systems Biology Markup Language (SBML) Level 3 Package: Flux Balance Constraints.

    NARCIS (Netherlands)

    Olivier, B.G.; Bergmann, F.T.

    2015-01-01

    Constraint-based modeling is a well established modelling methodology used to analyze and study biological networks on both a medium and genome scale. Due to their large size, genome scale models are typically analysed using constraint-based optimization techniques. One widely used method is Flux

  15. Defense Advanced Research Projects Agency (DARPA) Agent Markup Language Computer Aided Knowledge Acquisition

    Science.gov (United States)

    2005-06-01

    thesaurus ontology and the GEDCOM genealogy ontology. The CALL thesaurus ontology was developed for monolingual thesauri. The Center for Army...corresponding relationships. The ontology design was based on the Guidelines for the Construction, Format and Management of Monolingual Thesauri...rdfs:comment>Terminilogical list of short dictionary containing the terminology of a specific subject field or of related fields</rdfs:comment

  16. KML (Keyhole Markup Language) : a key tool in the education of geo-resources.

    Science.gov (United States)

    Veltz, Isabelle

    2015-04-01

    Although going on the ground with pupils remains the best way to understand the geologic structure of a deposit, it is very difficult to bring them in a mining extraction site and it is impossible to explore whole regions in search of these resources. For those reasons the KML (with the Google earth interface) is a very complete tool for teaching geosciences. Simple and intuitive, its handling is quickly mastered by the pupils, it also allows the teachers to validate skills for IT certificates. It allows the use of KML files stemming from online banks, from personal productions of the teacher or from pupils' works. These tools offer a global approach in 3D as well as a geolocation-based access to any type of geological data. The resource on which I built this KML is taught in the curriculum of the 3 years of French high school, it is methane hydrate. This non conventional hydrocarbon molecule enters in this vague border between mineral an organic matter (as phosphate deposits). It has become for over ten year the subject of the race for the exploitation of the gas hydrates fields in order to try to supply to the world demand. The methane hydrate fields are very useful and interesting to study the 3 majors themes of geological resource: the exploration, the exploitation and the risks especially for environments and populations. The KML which I propose allows the pupils to put itself in the skin of a geologist in search of deposits or on the technician who is going to extract the resource. It also allows them to evaluate the risks connected to the effect of tectonics activity or climatic changes on the natural or catastrophic releasing of methane and its role in the increase of the greenhouse effect. This KML associated to plenty of pedagogic activities is directly downloadable for teachers at http://eduterre.ens-lyon.fr/eduterre-usages/actualites/methane/.

  17. The Systems Biology Markup Language (SBML) Level 3 Package: Qualitative Models, Version 1, Release 1.

    Science.gov (United States)

    Chaouiya, Claudine; Keating, Sarah M; Berenguier, Duncan; Naldi, Aurélien; Thieffry, Denis; van Iersel, Martijn P; Le Novère, Nicolas; Helikar, Tomáš

    2015-09-04

    Quantitative methods for modelling biological networks require an in-depth knowledge of the biochemical reactions and their stoichiometric and kinetic parameters. In many practical cases, this knowledge is missing. This has led to the development of several qualitative modelling methods using information such as, for example, gene expression data coming from functional genomic experiments. The SBML Level 3 Version 1 Core specification does not provide a mechanism for explicitly encoding qualitative models, but it does provide a mechanism for SBML packages to extend the Core specification and add additional syntactical constructs. The SBML Qualitative Models package for SBML Level 3 adds features so that qualitative models can be directly and explicitly encoded. The approach taken in this package is essentially based on the definition of regulatory or influence graphs. The SBML Qualitative Models package defines the structure and syntax necessary to describe qualitative models that associate discrete levels of activities with entity pools and the transitions between states that describe the processes involved. This is particularly suited to logical models (Boolean or multi-valued) and some classes of Petri net models can be encoded with the approach.

  18. The Systems Biology Markup Language (SBML) Level 3 Package: Flux Balance Constraints.

    Science.gov (United States)

    Olivier, Brett G; Bergmann, Frank T

    2015-09-04

    Constraint-based modeling is a well established modelling methodology used to analyze and study biological networks on both a medium and genome scale. Due to their large size, genome scale models are typically analysed using constraint-based optimization techniques. One widely used method is Flux Balance Analysis (FBA) which, for example, requires a modelling description to include: the definition of a stoichiometric matrix, an objective function and bounds on the values that fluxes can obtain at steady state. The Flux Balance Constraints (FBC) Package extends SBML Level 3 and provides a standardized format for the encoding, exchange and annotation of constraint-based models. It includes support for modelling concepts such as objective functions, flux bounds and model component annotation that facilitates reaction balancing. The FBC package establishes a base level for the unambiguous exchange of genome-scale, constraint-based models, that can be built upon by the community to meet future needs (e. g. by extending it to cover dynamic FBC models).

  19. Electronic Government: Challenges to Effective Adoption of the Extensible Markup Language

    National Research Council Canada - National Science Library

    2002-01-01

    ...) technology and the challenges the federal government faces in implementing it. XML is a flexible, nonproprietary set of standards designed to facilitate the exchange of information among disparate computer systems, using the Internet's protocols...

  20. Diet assessment based on type-2 fuzzy ontology and fuzzy markup language

    NARCIS (Netherlands)

    Acampora, G.; Lee, C.-S.; Wang, M.-H.; Hsu, C.-Y.; Hagras, H.

    2010-01-01

    Nowadays most people can get enough energy to maintain one-day activity, while few people know whether they eat healthily or not. It is quite important to analyze nutritional facts for foods eaten for those who are losing weight or suffering chronic diseases such as diabetes. This paper proposes a

  1. Electrocardiogram application based on heart rate variability ontology and fuzzy markup language

    NARCIS (Netherlands)

    Wang, M.-H.; Lee, C.-S.; Acampora, G.; Loia, V.; Gacek, A.; Pedrycz, W.

    2011-01-01

    The electrocardiogram (ECG) signal is adopted extensively as a low-cost diagnostic procedure to provide information concerning the healthy status of the heart. Heart rate variability (HRV) is a physiological phenomenon where the time interval between heart beats varies. It is measured by the

  2. imzML: Imaging Mass Spectrometry Markup Language: A common data format for mass spectrometry imaging.

    Science.gov (United States)

    Römpp, Andreas; Schramm, Thorsten; Hester, Alfons; Klinkert, Ivo; Both, Jean-Pierre; Heeren, Ron M A; Stöckli, Markus; Spengler, Bernhard

    2011-01-01

    Imaging mass spectrometry is the method of scanning a sample of interest and generating an "image" of the intensity distribution of a specific analyte. The data sets consist of a large number of mass spectra which are usually acquired with identical settings. Existing data formats are not sufficient to describe an MS imaging experiment completely. The data format imzML was developed to allow the flexible and efficient exchange of MS imaging data between different instruments and data analysis software.For this purpose, the MS imaging data is divided in two separate files. The mass spectral data is stored in a binary file to ensure efficient storage. All metadata (e.g., instrumental parameters, sample details) are stored in an XML file which is based on the standard data format mzML developed by HUPO-PSI. The original mzML controlled vocabulary was extended to include specific parameters of imaging mass spectrometry (such as x/y position and spatial resolution). The two files (XML and binary) are connected by offset values in the XML file and are unambiguously linked by a universally unique identifier. The resulting datasets are comparable in size to the raw data and the separate metadata file allows flexible handling of large datasets.Several imaging MS software tools already support imzML. This allows choosing from a (growing) number of processing tools. One is no longer limited to proprietary software, but is able to use the processing software which is best suited for a specific question or application. On the other hand, measurements from different instruments can be compared within one software application using identical settings for data processing. All necessary information for evaluating and implementing imzML can be found at http://www.imzML.org .

  3. Non-Stationary Inflation and the Markup: an Overview of the Research and some Implications for Policy

    OpenAIRE

    Bill Russell

    2006-01-01

    This paper reports on research into the negative relationship between inflation and the markup. It is argued that this relationship can be thought of as ‘long-run’ in nature which suggests that inflation has a persistent effect on the markup and, therefore, the real wage. A ‘rule of thumb’ from the estimates indicate that a 10 percentage point increase in inflation (as occurred worldwide in the 1970s) is associated with around a 7 per cent fall in the markup accompanied by a similar increase ...

  4. Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial.

    Science.gov (United States)

    Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, Maria C; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco

    2015-11-01

    Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies. © 2015 John Wiley & Sons Ltd.

  5. Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group.

    Science.gov (United States)

    Barnard, Dorothy R; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly; Woods, William G

    2007-07-01

    Myelodysplastic syndromes (MDS), acute erythroleukemia (FAB M6), and acute megakaryocytic leukemia (FAB M7) have overlapping features. Children without Down syndrome or acute promyelocytic leukemia who were newly diagnosed with primary myelodysplastic syndrome or acute myeloid leukemia (AML) M6 or M7 were compared to children with de novo AML M0-M5. All children were entered on the Children's Cancer Group therapeutic research study CCG 2891. The presentation and outcomes of the 132 children diagnosed with MDS (60 children), AML FAB M6 (19 children), or AML FAB M7 (53 children) were similar. Children with AML FAB M7 were diagnosed at a significantly younger age (P = 0.001). Children with MDS, M6, or M7 had significantly lower white blood cell (WBC) counts (P = 0.001), lower peripheral blast counts (P M6 and AML M7 resemble MDS in presentation, poor induction success rates, and outcomes.

  6. Age-related epigenetic drift in the pathogenesis of MDS and AML.

    Science.gov (United States)

    Maegawa, Shinji; Gough, Sheryl M; Watanabe-Okochi, Naoko; Lu, Yue; Zhang, Nianxiang; Castoro, Ryan J; Estecio, Marcos R H; Jelinek, Jaroslav; Liang, Shoudan; Kitamura, Toshio; Aplan, Peter D; Issa, Jean-Pierre J

    2014-04-01

    The myelodysplastic syndrome (MDS) is a clonal hematologic disorder that frequently evolves to acute myeloid leukemia (AML). Its pathogenesis remains unclear, but mutations in epigenetic modifiers are common and the disease often responds to DNA methylation inhibitors. We analyzed DNA methylation in the bone marrow and spleen in two mouse models of MDS/AML, the NUP98-HOXD13 (NHD13) mouse and the RUNX1 mutant mouse model. Methylation array analysis showed an average of 512/3445 (14.9%) genes hypermethylated in NHD13 MDS, and 331 (9.6%) genes hypermethylated in RUNX1 MDS. Thirty-two percent of genes in common between the two models (2/3 NHD13 mice and 2/3 RUNX1 mice) were also hypermethylated in at least two of 19 human MDS samples. Detailed analysis of 41 genes in mice showed progressive drift in DNA methylation from young to old normal bone marrow and spleen; to MDS, where we detected accelerated age-related methylation; and finally to AML, which markedly extends DNA methylation abnormalities. Most of these genes showed similar patterns in human MDS and AML. Repeat element hypomethylation was rare in MDS but marked the transition to AML in some cases. Our data show consistency in patterns of aberrant DNA methylation in human and mouse MDS and suggest that epigenetically, MDS displays an accelerated aging phenotype.

  7. The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients.

    Science.gov (United States)

    Dong-Feng, Zeng; Ting, Liu; Yong, Zhang; Cheng, Chang; Xi, Zhang; Pei-Yan, Kong

    2014-04-01

    Accumulating evidence indicates that the interaction of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle-dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML (acute myelogenous leukemia) chemotherapy resistance hasn't been fully understood. The c-MPL and TPO levels in different AML samples were measured by flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML cell line that had been co-cultured with different BMSC-derived osteoblasts was measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR). The levels of TPO/c-MPL in the initial and relapse AML patients were significantly higher than that in the control (P MPL expression was found in the bone marrow mononuclear cells of the relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived osteoblasts was the highest among all co-culture systems. High level of TPO/c-MPL signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and on their downstream effector molecules that direct the interactions between patient-derived blasts and leukemia repopulating cells need to be further studied.

  8. Firm Dynamics and Markup Variations: Implications for Sunspot Equilibria and Endogenous Economic Fluctuation

    OpenAIRE

    Nir Jaimovich

    2007-01-01

    This paper analyzes how the interaction between firms’ entry-and-exit decisions and variations in competition gives rise to self-fulfilling, expectation-driven fluctuations in aggregate economic activity and in measured total factor productivity (TFP). The analysis is based on a dynamic general equilibrium model in which net business formation is endogenously procyclical and leads to endogenous countercyclical variations in markups. This interaction leads to indeterminacy in which economic fl...

  9. Semi-automated XML markup of biosystematic legacy literature with the GoldenGATE editor.

    Science.gov (United States)

    Sautter, Guido; Böhm, Klemens; Agosti, Donat

    2007-01-01

    Today, digitization of legacy literature is a big issue. This also applies to the domain of biosystematics, where this process has just started. Digitized biosystematics literature requires a very precise and fine grained markup in order to be useful for detailed search, data linkage and mining. However, manual markup on sentence level and below is cumbersome and time consuming. In this paper, we present and evaluate the GoldenGATE editor, which is designed for the special needs of marking up OCR output with XML. It is built in order to support the user in this process as far as possible: Its functionality ranges from easy, intuitive tagging through markup conversion to dynamic binding of configurable plug-ins provided by third parties. Our evaluation shows that marking up an OCR document using GoldenGATE is three to four times faster than with an off-the-shelf XML editor like XML-Spy. Using domain-specific NLP-based plug-ins, these numbers are even higher.

  10. Automated Text Markup for Information Retrieval from an Electronic Textbook of Infectious Disease

    Science.gov (United States)

    Berrios, Daniel C.; Kehler, Andrew; Kim, David K.; Yu, Victor L.; Fagan, Lawrence M.

    1998-01-01

    The information needs of practicing clinicians frequently require textbook or journal searches. Making these sources available in electronic form improves the speed of these searches, but precision (i.e., the fraction of relevant to total documents retrieved) remains low. Improving the traditional keyword search by transforming search terms into canonical concepts does not improve search precision greatly. Kim et al. have designed and built a prototype system (MYCIN II) for computer-based information retrieval from a forthcoming electronic textbook of infectious disease. The system requires manual indexing by experts in the form of complex text markup. However, this mark-up process is time consuming (about 3 person-hours to generate, review, and transcribe the index for each of 218 chapters). We have designed and implemented a system to semiautomate the markup process. The system, information extraction for semiautomated indexing of documents (ISAID), uses query models and existing information-extraction tools to provide support for any user, including the author of the source material, to mark up tertiary information sources quickly and accurately.

  11. Myeloid Sarcoma Predicts Superior Outcome in Pediatric AML; Can Cytogenetics Solve the Puzzle?

    Science.gov (United States)

    Pramanik, Raja; Tyagi, Anudishi; Chopra, Anita; Kumar, Akash; Vishnubhatla, Sreenivas; Bakhshi, Sameer

    2018-06-01

    The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and survival outcomes in patients with acute myeloid leukemia (AML) with myeloid sarcoma (MS) and compare them with patients with AML without MS. This was a retrospective analysis of de novo pediatric AML patients with or without MS diagnosed at our cancer center between June 2003 and June 2016. MS was present in 121 of 570 (21.2%), the most frequent site being the orbit. Patients with MS had a younger median age (6 years vs. 10 years) and presented with higher hemoglobin and platelet but lower white blood cell count compared with patients without MS. Further, t (8; 21) (P < .01), loss of Y chromosome (P < .01), and deletion 9q (P = .03) were significantly higher in patients with AML with MS. Event-free survival (EFS; P = .003) and overall survival (OS; P = .001) were better among patients with AML with MS (median EFS 21.0 months and median OS 37.1 months) compared with those with AML without MS (median EFS 11.2 months and median OS 16.2 months). The t (8; 21) was significantly associated with MS (odds ratio, 3.92). In a comparison of the 4 groups divided according to the presence or absence of MS and t (8; 21), the subgroup of patients having MS without concomitant t (8; 21) was the only group to have a significantly better OS (hazard ratio, 0.53; 95% confidence interval, 0.34-0.82; P = .005). Although t (8; 21) was more frequently associated with MS, it did not appear to be the reason for better outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

    Science.gov (United States)

    Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia

    2018-04-01

    The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

  13. Disease evolution and outcomes in familial AML with germline CEBPA mutations

    DEFF Research Database (Denmark)

    Tawana, Kiran; Wang, Jun; Renneville, Aline

    2015-01-01

    collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant......, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course...

  14. Gene expression profiling in MDS and AML: potential and future avenues

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, K; Boultwood, J; Ferrari, S

    2011-01-01

    Today, the classification systems for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) already incorporate cytogenetic and molecular genetic aberrations in an attempt to better reflect disease biology. However, in many MDS/AML patients no genetic aberrations have been identified yet...... with regard to diagnosis, prediction of clinical outcome, discovery of novel subclasses and identification of novel therapeutic targets and novel drugs. As many challenges remain ahead, we discuss the pitfalls of this technology and its potential including future integrative studies with other genomics...

  15. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML

    Science.gov (United States)

    2018-03-05

    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  16. KRAS (G12D Cooperates with AML1/ETO to Initiate a Mouse Model Mimicking Human Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-01-01

    Full Text Available Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML, suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d. Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-. Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

  17. The TAK1-NF-κB axis as therapeutic target for AML

    NARCIS (Netherlands)

    Bosman, Matthieu Cornelis Johannes; Schepers, Hein; Jaques, Jennifer; Vos, Annet; Quax, Wim Johannes; Schuringa, Jan Jacob; Vellenga, Edo

    2014-01-01

    Development and maintenance of leukemia can partially be attributed to alterations in (anti) apoptotic gene expression. Genome-wide transcriptome analyses revealed that 89 apoptosis-associated genes were differentially expressed between patient acute myeloid leukemia (AML) CD34(+) cells and normal

  18. Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6.

    Science.gov (United States)

    Hasserjian, R P; Howard, J; Wood, A; Henry, K; Bain, B

    2001-03-01

    Classic erythroleukaemia (acute myeloid leukaemia M6, or M6 AML) is defined as an excess of myeloblasts in an erythroid predominant background. Leukaemia variants in which the primitive blast cells are demonstrably erythroid are extremely rare and poorly characterised. Variably referred to as "true erythroleukaemia" or "acute erythremic myelosis", they are often included within the M6 AML category even though they do not meet strict criteria for this type of AML. Two cases of acute erythroid neoplasia are presented with clinical, morphological, immunophenotypic, and cytogenetic analysis. Both patients presented with profound anaemia, one in a setting of long standing myelodysplasia. Bone marrow examination revealed a predominant population of highly dysplastic erythroid cells in both cases. In one case, the liver was infiltrated by neoplastic erythroid cells. Both patients died within four months of diagnosis. This report illustrates that cases of acute leukaemia occur in which the dominant neoplastic cell is a primitive erythroid cell without an accompanying increase in myeloblasts. This does not preclude the neoplastic clone originating in a multipotent haemopoietic stem cell, as suggested by cases arising in patients with myelodysplasia. Acute erythremic myelosis should be recognised as a distinct variant of M6 AML.

  19. Genetic and epigenetic similarities and differences between childhood and adult AML

    DEFF Research Database (Denmark)

    Juhl-Christensen, Caroline; Ommen, Hans Beier; Aggerholm, Anni

    2012-01-01

    The biology of acute myeloid leukemia (AML) is complex and includes both genetic and epigenetic aberrations. We addressed the combined consequences of promoter hypermethylation of p15, CDH1, ER, MDR1, and RARB2 and mutation of NPM1, CEBPA, FLT3, and WT1 in a Danish cohort of 70 pediatric and 383...

  20. Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AML)

    International Nuclear Information System (INIS)

    Tang, Ruoping; Faussat, Anne-Marie; Perrot, Jean-Yves; Marjanovic, Zora; Cohen, Simy; Storme, Thomas; Morjani, Hamid; Legrand, Ollivier; Marie, Jean-Pierre

    2008-01-01

    Chemotherapeutic drug efflux via the P-glycoprotein (P-gp) transporter encoded by the MDR1/ABCB1 gene is a significant cause of drug resistance in numerous malignancies, including acute leukemias, especially in older patients with acute myeloid leukemia (AML). Therefore, the P-gp modulators that block P-gp-mediated drug efflux have been developed, and used in combination with standard chemotherapy. In this paper, the capacity of zosuquidar, a specific P-gp modulator, to reverse chemoresistance was examined in both leukemia cell lines and primary AML blasts. The transporter protein expressions were analyzed by flow cytometry using their specific antibodies. The protein functionalities were assessed by the uptake of their fluorescence substrates in presence or absence their specific modulators. The drug cytotoxicity was evaluated by MTT test. Zosuquidar completely or partially restored drug sensitivity in all P-gp-expressing leukemia cell lines tested and enhanced the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AML blasts with active P-gp. In addition, P-gp inhibition by zosuquidar was found to be more potent than cyclosporine A in cells with highly active P-gp. These in vitro studies suggest that zosuquidar may be an effective adjunct to cytotoxic chemotherapy for AML patients whose blasts express P-gp, especially for older patients

  1. Prognostic Value of RUNX1 Mutations in AML: A Meta-Analysis

    Science.gov (United States)

    Jalili, Mahdi; Yaghmaie, Marjan; Ahmadvand, Mohammad; Alimoghaddam, Kamran; Mousavi, Seyed Asadollah; Vaezi, Mohammad; Ghavamzadeh, Ardeshir

    2018-02-26

    The RUNX1 (AML1) gene is a relatively infrequent mutational target in cases of acute myeloid leukemia (AML). Previous work indicated that RUNX1 mutations can have pathological and prognostic implications. To evaluate prognostic value, we conducted a meta-analysis of 4 previous published works with data for survival according to RUNX1 mutation status. Pooled hazard ratios for overall survival and disease-free survival were 1.55 (95% confidence interval (CI) = 1.11–2.15; p-value = 0.01) and 1.76 (95% CI = 1.24–2.52; p-value = 0.002), respectively, for cases positive for RUNX1 mutations. This evidence supports clinical implications of RUNX1 mutations in the development and progression of AML cases and points to the possibility of a distinct category within the newer WHO classification. Though it must be kept in mind that the present work was based on data extracted from observational studies, the findings suggest that the RUNX1 status can contribute to risk-stratification and decision-making in management of AML. Creative Commons Attribution License

  2. Defining Linkages between the GSC and NSF's LTER Program: How the Ecological Metadata Language (EML) Relates to GCDML and Other Outcomes

    Science.gov (United States)

    Inigo San Gil; Wade Sheldon; Tom Schmidt; Mark Servilla; Raul Aguilar; Corinna Gries; Tanya Gray; Dawn Field; James Cole; Jerry Yun Pan; Giri Palanisamy; Donald Henshaw; Margaret O' Brien; Linda Kinkel; Kathrine McMahon; Renzo Kottmann; Linda Amaral-Zettler; John Hobbie; Philip Goldstein; Robert P. Guralnick; James Brunt; William K. Michener

    2008-01-01

    The Genomic Standards Consortium (GSC) invited a representative of the Long-Term Ecological Research (LTER) to its fifth workshop to present the Ecological Metadata Language (EML) metadata standard and its relationship to the Minimum Information about a Genome/Metagenome Sequence (MIGS/MIMS) and its implementation, the Genomic Contextual Data Markup Language (GCDML)....

  3. Impact of the zero-markup drug policy on hospitalisation expenditure in western rural China: an interrupted time series analysis.

    Science.gov (United States)

    Yang, Caijun; Shen, Qian; Cai, Wenfang; Zhu, Wenwen; Li, Zongjie; Wu, Lina; Fang, Yu

    2017-02-01

    To assess the long-term effects of the introduction of China's zero-markup drug policy on hospitalisation expenditure and hospitalisation expenditures after reimbursement. An interrupted time series was used to evaluate the impact of the zero-markup drug policy on hospitalisation expenditure and hospitalisation expenditure after reimbursement at primary health institutions in Fufeng County of Shaanxi Province, western China. Two regression models were developed. Monthly average hospitalisation expenditure and monthly average hospitalisation expenditure after reimbursement in primary health institutions were analysed covering the period 2009 through to 2013. For the monthly average hospitalisation expenditure, the increasing trend was slowed down after the introduction of the zero-markup drug policy (coefficient = -16.49, P = 0.009). For the monthly average hospitalisation expenditure after reimbursement, the increasing trend was slowed down after the introduction of the zero-markup drug policy (coefficient = -10.84, P = 0.064), and a significant decrease in the intercept was noted after the second intervention of changes in reimbursement schemes of the new rural cooperative medical insurance (coefficient = -220.64, P markup drug policy in western China. However, hospitalisation expenditure and hospitalisation expenditure after reimbursement were still increasing. More effective policies are needed to prevent these costs from continuing to rise. © 2016 John Wiley & Sons Ltd.

  4. Peptide microarray profiling identifies phospholipase C gamma 1 (PLC-γ1) as a potential target for t(8;21) AML

    NARCIS (Netherlands)

    Mahmud, Hasan; Scherpen, Frank J. G.; Meeuwsen de Boer, Tiny; Lourens, Harm-Jan; Schoenherr, Caroline; Eder, Matthias; Scherr, Michaela; Guryev, Victor; de Bont, Eveline S.

    2017-01-01

    The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) which has a need for improved therapeutic strategies. We found PLC-γ1 as one of the highest phosphorylated peptides in t(8;21) AML samples compared to NBM or CN-AML in our

  5. Free Trade Agreements and Firm-Product Markups in Chilean Manufacturing

    DEFF Research Database (Denmark)

    Lamorgese, A.R.; Linarello, A.; Warzynski, Frederic Michel Patrick

    In this paper, we use detailed information about firms' product portfolio to study how trade liberalization affects prices, markups and productivity. We document these effects using firm product level data in Chilean manufacturing following two major trade agreements with the EU and the US....... The dataset provides information about the value and quantity of each good produced by the firm, as well as the amount of exports. One additional and unique characteristic of our dataset is that it provides a firm-product level measure of the unit average cost. We use this information to compute a firm...

  6. Proliferative status of primitive hematopoietic progenitors from patients with acute myelogenous leukemia (AML).

    Science.gov (United States)

    Guan, Y; Hogge, D E

    2000-12-01

    One possible explanation for the competitive advantage that malignant cells in patients with acute myelogenous leukemia (AML) appear to have over normal hematopoietic elements is that leukemic progenitors proliferate more rapidly than their normal progenitor cell counterparts. To test this hypothesis, an overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in both colony-forming cell (CFC) and long-term culture initiating cell (LTC-IC) assays from the peripheral blood of nine patients with newly diagnosed AML. Culture of AML cells in serum-free medium with 100 ng/ml Steel factor (SF), 20 ng/ml interleukin 3 (IL-3) and 20 ng/ml granulocyte colony-stimulating factor (G-CSF) for 16-24 h maintained the number of AML-CFC and LTC-IC at near input values (mean % input +/- s.d. for CFC and LTC-IC were 78 +/- 33 and 126 +/- 53, respectively). The addition of 20 muCi/ml high specific activity 3H-Tdr to these cultures reduced the numbers of both progenitor cell types from most of the patient samples substantially: mean % kill +/- s.d. for AML-CFC and LTC-IC were 64 +/- 27 and 82 +/- 16, respectively, indicating that a large proportion of both progenitor populations were actively cycling. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC were actively cycling (mean % kill +/- s.d.: 68 +/- 26 and 85 +/- 13, respectively). Interestingly, in six patient samples where a significant number of cytogenetically normal LTC-ICs were detected, the % kill of these cells (74 +/- 20) was similar to that of the abnormal progenitors. These data contrast with the predominantly quiescent cell cycle status of CFC and LTC-IC previously observed in steady-state peripheral blood from normal individuals but also provide evidence that a significant proportion of primitive malignant progenitors from AML patients are quiescent and therefore may be resistant to standard

  7. [Detection of heterogeneity and evolution of subclones in t(8;21) AML by QM-FISH].

    Science.gov (United States)

    Wang, Ying-chan; Hu, Lin-ping; Lin, Dong; Li, Cheng-wen; Yuan, Tian; Jia, Yu-jiao; Tian, Zheng; Tang, Ke-jing; Wang, Min; Wang, Jian-xiang

    2013-10-01

    To explore the heterogeneous subclones in acute myeloid leukemia (AML) with t(8;21) by quantitative multicolor- fluorescence in situ hybridization (QM-FISH), and to figure out whether there is putative ancestral relationship among different subclones. Bacterial artificial chromosomes (BAC) clones that contain the targeted genes including AML1, ETO, WT1, p27 and c-kit were searched in the data base UCSC Genome Bioinformatics. Multicolor FISH probes were prepared by linking fluorescein labeled dUTP or dCTP to targeted genes by nick translation. Bone marrow mononuclear cells from t (8;21) AML patients are dropped on to the wet surface of glass slides after hypotonic treatment and fixation. After hybridization, the fluorescence signals were captured by Zeiss fluorescence microscope. The copy number of AML1, ETO, WT1, p27, c- kit and the AML1-ETO fusion gene in AML1-ETO positive cells was counted. The cells with same signals were defined as a subclone. Various subclones were recorded and their proportions were calculated, and their evolutionary relationship was deduced. The subclones in matched primary and relapsed samples were compared, the evolution of dominant clones were figured out and the genomic abnormality that is associated with relapse and drug resistance were speculated. In this study, 36 primary AML with t(8;21) cases and 1 relapsed case paired with the primary case were detected. In these 36 primary cases, 4 cases (11.1%) acquired additional AML1-ETO fusion signal, 3(8.3%) had additional AML1 signal, 4(11.1%) had additional ETO signal, 20(55.6%) had additional WT1 signal, 15(41.7%) had additional p27 signal and 14(38.9%) had additional c-kit signal. In addition, 10(27.8%) displayed AML1 signal deletion, and such an aberration represents statistic significance in male patients. It seems that male patients usually accompany AML1 signal deletion. Of 36 cases, 28(77.8 %) harbored at least 2 subclones (ranged from 2 to 10). According to the genetic signature of

  8. DEMAND FOR AND SUPPLY OF MARK-UP AND PLS FUNDS IN ISLAMIC BANKING: SOME ALTERNATIVE EXPLANATIONS

    OpenAIRE

    KHAN, TARIQULLAH

    1995-01-01

    Profit and loss-sharing (PLS) and bai’ al murabahah lil amir bil shira (mark-up) are the two parent principles of Islamic financing. The use of PLS is limited and that of mark-up overwhelming in the operations of the Islamic banks. Several studies provide different explanations for this phenomenon. The dominant among these is the moral hazard hypothesis. Some alternative explanations are given in the present paper. The discussion is based on both demand (user of funds) and supply (bank) side ...

  9. Extreme Markup: The Fifty US Hospitals With The Highest Charge-To-Cost Ratios.

    Science.gov (United States)

    Bai, Ge; Anderson, Gerard F

    2015-06-01

    Using Medicare cost reports, we examined the fifty US hospitals with the highest charge-to-cost ratios in 2012. These hospitals have markups (ratios of charges over Medicare-allowable costs) approximately ten times their Medicare-allowable costs compared to a national average of 3.4 and a mode of 2.4. Analysis of the fifty hospitals showed that forty-nine are for profit (98 percent), forty-six are owned by for-profit hospital systems (92 percent), and twenty (40 percent) operate in Florida. One for-profit hospital system owns half of these fifty hospitals. While most public and private health insurers do not use hospital charges to set their payment rates, uninsured patients are commonly asked to pay the full charges, and out-of-network patients and casualty and workers' compensation insurers are often expected to pay a large portion of the full charges. Because it is difficult for patients to compare prices, market forces fail to constrain hospital charges. Federal and state governments may want to consider limitations on the charge-to-cost ratio, some form of all-payer rate setting, or mandated price disclosure to regulate hospital markups. Project HOPE—The People-to-People Health Foundation, Inc.

  10. Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene

    DEFF Research Database (Denmark)

    Agrawal-Singh, Shuchi; Isken, Fabienne; Agelopoulos, Konstantin

    2012-01-01

    to have lower H3Ac levels in AML compared with progenitor cells, which suggested that a large number of genes are epigenetically silenced in AML. Intriguingly, we identified peroxiredoxin 2 (PRDX2) as a novel potential tumor suppressor gene in AML. H3Ac was decreased at the PRDX2 gene promoter in AML......With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34+ progenitor cells. Importantly, core promoter regions tended......, which correlated with low mRNA and protein expression. We also observed DNA hypermethylation at the PRDX2 promoter in AML. Low protein expression of the antioxidant PRDX2 gene was clinically associated with poor prognosis in patients with AML. Functionally, PRDX2 acted as inhibitor of myeloid cell...

  11. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

    Science.gov (United States)

    Döhner, Hartmut; Estey, Elihu; Grimwade, David; Amadori, Sergio; Appelbaum, Frederick R; Büchner, Thomas; Dombret, Hervé; Ebert, Benjamin L; Fenaux, Pierre; Larson, Richard A; Levine, Ross L; Lo-Coco, Francesco; Naoe, Tomoki; Niederwieser, Dietger; Ossenkoppele, Gert J; Sanz, Miguel; Sierra, Jorge; Tallman, Martin S; Tien, Hwei-Fang; Wei, Andrew H; Löwenberg, Bob; Bloomfield, Clara D

    2017-01-26

    The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease. © 2017 by The American Society of Hematology.

  12. High frequency of streptococcal bacteraemia during childhood AML therapy irrespective of dose of cytarabine

    DEFF Research Database (Denmark)

    Johannsen, Katrine Helle; Handrup, Mette Møller; Lausen, Birgitte Frederiksen

    2013-01-01

    of cytarabine and more chemotherapy series (n = 6) than other protocols with the potential increased risk of severe VGS infections. PROCEDURE: Medical records of all Danish children enrolled on the NOPHO-AML-2004 protocol between January 2004 and September 2011 (n = 45) were retrospectively reviewed and all...... rate of VGS seemed independent of high-dose cytarabine but was more likely caused by the intensive chemotherapy treatment leading to severe mucositis and neutropenia....

  13. Problems getting from the laboratory to the field: Reclamation of an AML site

    International Nuclear Information System (INIS)

    Dick, W.A.; Stehouwer, R.C.

    1994-01-01

    Acid and toxic abandoned mineland sites provide an opportunity whereby flue gas desulfurization (FGD) by-product can be beneficially used as a reclamation amendment material. Studies are needed to compare the effectiveness of FGD by-product, as compared with resoil, for reclamation purposes. Initial studies provided information about the chemical and physical properties of the FGD by-product and how to transport and blend the FGD by-product with yard waste compost. Greenhouse studies indicated that rates of 125 dry tons/acre of FGD and 50 dry tons/acre of yard waste compost would provide optimum results for reclamation of acid and toxic spoil contained at the Fleming abandoned mineland (AML) site. Their results showed that heavy metal loading rates were much lower using the FGD/compost mixture than using resoil material. Dioxin in the mixture was also less than the 5 ppt level considered as normal background. The technical problems of using FGD by-product for reclamation of an AML site were solved. However, considerable efforts to educate the public about the merits of reclaiming the Fleming AML site using this FGD/compost mixture were required before initiating field reclamation activities. Education efforts must continue if FGD by-products are to achieve general acceptance as a reclamation alternative to resoil in cases where resoil is of scarce supply

  14. A multigene array for measurable residual disease detection in AML patients undergoing SCT

    Science.gov (United States)

    Goswami, M; McGowan, K S; Lu, K; Jain, N; Candia, J; Hensel, N F; Tang, J; Calvo, K R; Battiwalla, M; Barrett, A J; Hourigan, C S

    2015-01-01

    AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ–PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994–2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ–PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection. PMID:25665046

  15. Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner.

    Science.gov (United States)

    Man, Na; Tan, Yurong; Sun, Xiao-Jian; Liu, Fan; Cheng, Guoyan; Greenblatt, Sarah M; Martinez, Camilo; Karl, Daniel L; Ando, Koji; Sun, Ming; Hou, Dan; Chen, Bingyi; Xu, Mingjiang; Yang, Feng-Chun; Chen, Zhu; Chen, Saijuan; Nimer, Stephen D; Wang, Lan

    2017-05-18

    AML1-ETO (AE), a fusion oncoprotein generated by t(8;21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3-compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML. We report here that loss of Caspase-3 triggers a conserved, adaptive mechanism, namely autophagy (or macroautophagy), which acts to limit AE9a-driven leukemia. Furthermore, we identify ULK1 as a novel substrate of Caspase-3 and show that upregulation of ULK1 drives autophagy initiation in leukemia cells and that inhibition of ULK1 can rescue the phenotype induced by Caspase-3 deletion in vitro and in vivo. Collectively, these data highlight Caspase-3 as an important regulator of autophagy in AML and demonstrate that the balance and selectivity between its substrates can dictate the pace of disease. © 2017 by The American Society of Hematology.

  16. Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest in AML in vitro and prolongs survival in vivo.

    Science.gov (United States)

    Schnerch, Dominik; Schüler, Julia; Follo, Marie; Felthaus, Julia; Wider, Dagmar; Klingner, Kathrin; Greil, Christine; Duyster, Justus; Engelhardt, Monika; Wäsch, Ralph

    2017-03-28

    Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B. Therefore, we tested whether interfering with mitotic slippage through proteasome inhibition arrests and kills AML cells more efficiently during mitosis. We show that therapeutic doses of bortezomib block the slow degradation of cyclin B during a volasertib-induced mitotic arrest in AML cell lines and patient-derived primary AML cells. In a xenotransplant mouse model of human AML, mice receiving volasertib in combination with bortezomib showed superior disease control compared to mice receiving volasertib alone, highlighting the potential therapeutic impact of this drug combination.

  17. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    LENUS (Irish Health Repository)

    Rishi, Loveena

    2014-04-10

    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C\\/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C\\/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C\\/EBPα-p42, and in normal granulocyte\\/macrophage progenitor cells, we detect C\\/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C\\/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis.

  18. Integrating deep and shallow natural language processing components : representations and hybrid architectures

    OpenAIRE

    Schäfer, Ulrich

    2006-01-01

    We describe basic concepts and software architectures for the integration of shallow and deep (linguistics-based, semantics-oriented) natural language processing (NLP) components. The main goal of this novel, hybrid integration paradigm is improving robustness of deep processing. After an introduction to constraint-based natural language parsing, we give an overview of typical shallow processing tasks. We introduce XML standoff markup as an additional abstraction layer that eases integration ...

  19. Modeling Languages Refine Vehicle Design

    Science.gov (United States)

    2009-01-01

    Cincinnati, Ohio s TechnoSoft Inc. is a leading provider of object-oriented modeling and simulation technology used for commercial and defense applications. With funding from Small Business Innovation Research (SBIR) contracts issued by Langley Research Center, the company continued development on its adaptive modeling language, or AML, originally created for the U.S. Air Force. TechnoSoft then created what is now known as its Integrated Design and Engineering Analysis Environment, or IDEA, which can be used to design a variety of vehicles and machinery. IDEA's customers include clients in green industries, such as designers for power plant exhaust filtration systems and wind turbines.

  20. Treating metadata as annotations: separating the content markup from the content

    Directory of Open Access Journals (Sweden)

    Fredrik Paulsson

    2007-11-01

    Full Text Available The use of digital learning resources creates an increasing need for semantic metadata, describing the whole resource, as well as parts of resources. Traditionally, schemas such as Text Encoding Initiative (TEI have been used to add semantic markup for parts of resources. This is not sufficient for use in a ”metadata ecology”, where metadata is distributed, coherent to different Application Profiles, and added by different actors. A new methodology, where metadata is “pointed in” as annotations, using XPointers, and RDF is proposed. A suggestion for how such infrastructure can be implemented, using existing open standards for metadata, and for the web is presented. We argue that such methodology and infrastructure is necessary to realize the decentralized metadata infrastructure needed for a “metadata ecology".

  1. Modeling of the positioning system and visual mark-up of historical cadastral maps

    Directory of Open Access Journals (Sweden)

    Tomislav Jakopec

    2013-03-01

    Full Text Available The aim of the paper is to present of the possibilities of positioning and visual markup of historical cadastral maps onto Google maps using open source software. The corpus is stored in the Croatian State Archives in Zagreb, in the Maps Archive for Croatia and Slavonia. It is part of cadastral documentation that consists of cadastral material from the period of first cadastral survey conducted in the Kingdom of Croatia and Slavonia from 1847 to 1877, and which is used extensively according to the data provided by the customer service of the Croatian State Archives. User needs on the one side and the possibilities of innovative implementation of ICT on the other have motivated the development of the system which would use digital copies of original cadastral maps and connect them with systems like Google maps, and thus both protect the original materials and open up new avenues of research related to the use of originals. With this aim in mind, two cadastral map presentation models have been created. Firstly, there is a detailed display of the original, which enables its viewing using dynamic zooming. Secondly, the interactive display is facilitated through blending the cadastral maps with Google maps, which resulted in establishing links between the coordinates of the digital and original plans through transformation. The transparency of the original can be changed, and the user can intensify the visibility of the underlying layer (Google map or the top layer (cadastral map, which enables direct insight into parcel dynamics over a longer time-span. The system also allows for the mark-up of cadastral maps, which can lead to the development of the cumulative index of all terms found on cadastral maps. The paper is an example of the implementation of ICT for providing new services, strengthening cooperation with the interested public and related institutions, familiarizing the public with the archival material, and offering new possibilities for

  2. Balancing medicine prices and business sustainability: analyses of pharmacy costs, revenues and profit shed light on retail medicine mark-ups in rural Kyrgyzstan

    Directory of Open Access Journals (Sweden)

    Maddix Jason

    2010-07-01

    Full Text Available Abstract Background Numerous not-for-profit pharmacies have been created to improve access to medicines for the poor, but many have failed due to insufficient financial planning and management. These pharmacies are not well described in health services literature despite strong demand from policy makers, implementers, and researchers. Surveys reporting unaffordable medicine prices and high mark-ups have spurred efforts to reduce medicine prices, but price reduction goals are arbitrary in the absence of information on pharmacy costs, revenues, and profit structures. Health services research is needed to develop sustainable and "reasonable" medicine price goals and strategic initiatives to reach them. Methods We utilized cost accounting methods on inventory and financial information obtained from a not-for-profit rural pharmacy network in mountainous Kyrgyzstan to quantify costs, revenues, profits and medicine mark-ups during establishment and maintenance periods (October 2004-December 2007. Results Twelve pharmacies and one warehouse were established in remote Kyrgyzstan with 100%, respectively. Annual mark-ups increased dramatically each year to cover increasing recurrent costs, and by 2007, only 19% and 46% of products revealed mark-ups of 100%. 2007 medicine mark-ups varied substantially across these products, ranging from 32% to 244%. Mark-ups needed to sustain private pharmacies would be even higher in the absence of government subsidies. Conclusion Pharmacy networks can be established in hard-to-reach regions with little funding using public-private partnership, resource-sharing models. Medicine prices and mark-ups must be interpreted with consideration for regional costs of business. Mark-ups vary dramatically across medicines. Some mark-ups appear "excessive" but are likely necessary for pharmacy viability. Pharmacy financial data is available in remote settings and can be used towards determination of "reasonable" medicine price goals

  3. Balancing medicine prices and business sustainability: analyses of pharmacy costs, revenues and profit shed light on retail medicine mark-ups in rural Kyrgyzstan.

    Science.gov (United States)

    Waning, Brenda; Maddix, Jason; Soucy, Lyne

    2010-07-13

    Numerous not-for-profit pharmacies have been created to improve access to medicines for the poor, but many have failed due to insufficient financial planning and management. These pharmacies are not well described in health services literature despite strong demand from policy makers, implementers, and researchers. Surveys reporting unaffordable medicine prices and high mark-ups have spurred efforts to reduce medicine prices, but price reduction goals are arbitrary in the absence of information on pharmacy costs, revenues, and profit structures. Health services research is needed to develop sustainable and "reasonable" medicine price goals and strategic initiatives to reach them. We utilized cost accounting methods on inventory and financial information obtained from a not-for-profit rural pharmacy network in mountainous Kyrgyzstan to quantify costs, revenues, profits and medicine mark-ups during establishment and maintenance periods (October 2004-December 2007). Twelve pharmacies and one warehouse were established in remote Kyrgyzstan with 100%, respectively. Annual mark-ups increased dramatically each year to cover increasing recurrent costs, and by 2007, only 19% and 46% of products revealed mark-ups of 100%. 2007 medicine mark-ups varied substantially across these products, ranging from 32% to 244%. Mark-ups needed to sustain private pharmacies would be even higher in the absence of government subsidies. Pharmacy networks can be established in hard-to-reach regions with little funding using public-private partnership, resource-sharing models. Medicine prices and mark-ups must be interpreted with consideration for regional costs of business. Mark-ups vary dramatically across medicines. Some mark-ups appear "excessive" but are likely necessary for pharmacy viability. Pharmacy financial data is available in remote settings and can be used towards determination of "reasonable" medicine price goals. Health systems researchers must document the positive and negative

  4. Role of the Phosphorylation of mTOR in the Differentiation of AML Cells Triggered with CD44 Antigen

    KAUST Repository

    Darwish, Manar M

    2013-05-01

    Acute myeloid leukemia (AML) is a hematological disorder characterized by blockage of differentiation of myeloblasts. To date, the main therapy for AML is chemotherapy. Yet, studies are seeking a better treatment to enhance the survival rate of patients and minimize the relapsing of the disease. Since the major problem in these cells is that they are arrested in cellular differentiation, drugs that could induce their differentiation have proven to be efficient and of major interest for AML therapy. CD44 triggering appeared as a promising target for AML therapy as it has been shown that specific monoclonal antibodies, such as A3D8 and H90, reversed the blockage of differentiation, inhibited the proliferation of all AML subtypes, and in some cases, induced cell apoptosis. Studies conducted in our laboratory have added strength to these antibodies as potential treatment for AML. Indeed, our laboratory found that treating HL60 cells with A3D8 shows a decrease in the phosphorylation of the mammalian target of Rapamycin (mTOR) kinase correlated with the inhibition of proliferation/induction of differentiation of AML cells.The relationship between the induction of differentiation and the inhibition of proliferation and the decrease of mTOR phosphorylation remains to be clarified. To study the importance of the de-phosphorylation of mTOR and the observed effect of CD44 triggering on differentiation and/or proliferation, we sought to prepare phospho-mimic mutants of the mTOR kinase that will code for a constitutively phosphorylated form of mTOR and used two main methods to express this mutant in HL60 cells: lentiviral and simple transfection (cationic-liposomal transfection).

  5. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study.

    Science.gov (United States)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders; Glosli, Heidi; Jahnukainen, Kirsi; Jarfelt, Marianne; Jónmundsson, Guðmundur K; Malmros, Johan; Nysom, Karsten; Hasle, Henrik

    2013-12-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings. We included 137 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, who were alive by June 2007. Patients with relapse or treated with HSCT were excluded. AML survivors participated in a physical and biochemical examination (n = 102) and completed a questionnaire (n = 101). One of their siblings completed an identical questionnaire (n = 84). At a median follow-up of 11 years (range 5-25) after diagnosis of AML the survivors (median age 16 years, range 5-36) were either prepubertal or had entered puberty normally. Serum levels of FSH, LH, testosterone, estradiol, sex hormone binding globulin (SHBG), inhibin A and B, and testicular volumes were within normal ranges. Anti-Müllerian hormone (AMH) levels were decreased in 5 of 40 postpubertal females. Mean reported age at menarche was 13.1 (range 11-17) years. Among survivors 15 years of age or older 31% of females reported pregnancies and 9% of males reported pregnancies in their partners, rates comparable with the frequency reported by their siblings. Most AML survivors treated with chemotherapy had normal pubertal development and fertility, however, AMH levels were decreased in 13% of postpubertal females. Longer follow-up is necessary to evaluate possible risk of premature ovarian failure. © 2013 Wiley Periodicals, Inc.

  6. Therapy Related AML/MDS Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India.

    Science.gov (United States)

    Vyas, Chintan; Jain, Sandeep; Kapoor, Gauri

    2018-01-01

    Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating late effect of cancer treatment. There is limited data on incidence of t-AML/MDS from India. We retrospectively studied pediatric t AML/MDS at our institute between January 1996 and December 2015. Among 1285 children, 8 patients developed t-AML with a median age of 15.5 years. Overall incidence of t-AML/MDS was 0.62% [0.99% (4/402) in solid tumours and 0.45% (4/883) in leukemia/lymphoma, P  = 0.26] with 6390 patient years of follow up. Primary malignancy included sarcoma [bone (2), soft tissue (2)], B-non-Hodgkin lymphoma (2) and acute lymphoblastic leukemia (2). The median cumulative equivalent doses of cyclophosphamide, doxorubicin and etoposide were 6.8, 270 and 2.5 gm/m 2 respectively. Two patients received radiotherapy [rhabdomyosarcoma (50 Gy), synovial sarcoma (45 Gy)]. The median latency period to develop t-AML/MDS was 24 months (range 16.5-62 months). Most common FAB morphology was M4/M5 (7/8) and cytogenetic abnormality was MLL rearrangement (4/8). Five patients opted for treatment, 4 achieved remission out of which 2 patients are alive and disease free. Short latency periods, absence of pre-leukemic phase and 11q23 translocations were characteristic in the patients with t-AML/MDS. In view of poor outcome with conventional therapy, novel strategies and prevention need to be considered.

  7. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia.

    Science.gov (United States)

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop

    2016-02-01

    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

  8. Pressurized grout remote backfilling at AML sites near Beulah and Zap, North Dakota

    International Nuclear Information System (INIS)

    Weiner, E.J.; Dodd, W.E.

    1999-01-01

    The Abandoned Mine Lands (AML) Division of the North Dakota Public Service Commission (PSC) is charged with the reclamation of hazardous abandoned mine sites in North Dakota. Several underground lignite coalmines were operated near the cities of Beulah and Zap, North Dakota, from the early 1900's until about 1955. Coal seams in this area were relatively thick and the overburden generally shallow. As these mines have deteriorated with time, deep collapse features, or sinkholes, have surfaced in many areas. These features are very dangerous, especially when they occur at or near residential and commercial areas and public roads. In the past five years, sinkholes have surfaced beneath a commercial building (boat dealership, lounge, and gas station) and beneath a nearby occupied mobile home north of Beulah. sinkholes have also surfaced near KHOL Radio Station in Beulah and in the right of way of a public road south of Zap. The AML Division has conducted several emergency sinkhole-filling projects in these areas. In 1995--97, the AML Division conducted exploratory drilling which confirmed the presence of collapsing underground mines at these sites. The remediation of these sites around Beulah/Zap will take place over several years and involve three or more separate contracts due to budget considerations. In 1997, the AML Division began reclamation at these sties utilizing pressurized grout remote backfilling. In this technique, a cementitious grout is pumped through cased drill holes directly into the mine cavities to fill them and thereby stabilize the surface from collapse. The successful contractor for Phase One of the project was The Concrete Doctor, Inc. (TCDI). This paper will concentrate on Phase One of this work performed from June through September 1997. This project is especially interesting because grout was pumped through holes drilled inside the occupied commercial building. Grout was also pumped through angled holes that intercepted mined workings directly

  9. Pressurized grout remote backfilling at AML sites near Beulah and Zap, North Dakota

    Energy Technology Data Exchange (ETDEWEB)

    Weiner, E.J.; Dodd, W.E.

    1999-07-01

    The Abandoned Mine Lands (AML) Division of the North Dakota Public Service Commission (PSC) is charged with the reclamation of hazardous abandoned mine sites in North Dakota. Several underground lignite coalmines were operated near the cities of Beulah and Zap, North Dakota, from the early 1900's until about 1955. Coal seams in this area were relatively thick and the overburden generally shallow. As these mines have deteriorated with time, deep collapse features, or sinkholes, have surfaced in many areas. These features are very dangerous, especially when they occur at or near residential and commercial areas and public roads. In the past five years, sinkholes have surfaced beneath a commercial building (boat dealership, lounge, and gas station) and beneath a nearby occupied mobile home north of Beulah. sinkholes have also surfaced near KHOL Radio Station in Beulah and in the right of way of a public road south of Zap. The AML Division has conducted several emergency sinkhole-filling projects in these areas. In 1995--97, the AML Division conducted exploratory drilling which confirmed the presence of collapsing underground mines at these sites. The remediation of these sites around Beulah/Zap will take place over several years and involve three or more separate contracts due to budget considerations. In 1997, the AML Division began reclamation at these sties utilizing pressurized grout remote backfilling. In this technique, a cementitious grout is pumped through cased drill holes directly into the mine cavities to fill them and thereby stabilize the surface from collapse. The successful contractor for Phase One of the project was The Concrete Doctor, Inc. (TCDI). This paper will concentrate on Phase One of this work performed from June through September 1997. This project is especially interesting because grout was pumped through holes drilled inside the occupied commercial building. Grout was also pumped through angled holes that intercepted mined workings

  10. Tumor Lysis Syndrome (TLS following intrathecal chemotherapy in a child with acute myelogenous leukemia (AML

    Directory of Open Access Journals (Sweden)

    Chana L. Glasser, MD

    2017-01-01

    Full Text Available Tumor Lysis Syndrome (TLS is a well-known complication of induction therapy for hematologic malignancies. It is characterized by rapid breakdown of malignant white blood cells (WBCs leading to metabolic derangements and serious morbidity if left untreated. Most commonly, TLS is triggered by systemic chemotherapy, however, there have been case reports of TLS following intrathecal (IT chemotherapy, all in patients with acute lymphoblastic leukemia (ALL/lymphoma. Here, we report the first case of a patient with acute myelogenous leukemia (AML who developed TLS following a single dose of IT cytosine arabinoside (Ara-C.

  11. Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    KAUST Repository

    Aldehaiman, Mansour M.

    2018-04-01

    Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature nonfunctional highly proliferative hematopoietic cells in the blood, due to a blockage in myeloid differentiation at various stages. Since the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell (LSC). CD44 is a cell surface receptor that is over-expressed on AML cells. When bound to anti-CD44 monoclonal antibodies (mAbs), this differentiation block is relieved in AML cells and their proliferation is reduced. The molecular mechanisms that AML cells undergo to achieve this reversal of their apparent phenotype is not fully understood. To this end, we designed a study using quantitative phosphoproteomics approaches aimed at identifying differences in phosphorylation found on proteins involved in signaling pathways post-treatment with CD44-mAbs. The Rho family of GTPases emerged as one of the most transformed pathways following the treatment with CD44-mAbs. The P21 activated kinase 2(PAK2), a target of the Rho family of GTPases, was found to be differentially phosphorylated in AML cells post-treatment with CD44-mAbs. This protein has been found to possess a role similar to that of a switch that determines whether the cell survives or undergoes apoptosis. Beyond confirming these results by various biochemical approaches, our study aimed to determine the effect of knock down of PAK2 on AML cell proliferation and differentiation. In addition, over-expression of PAK2 mutants using plasmid cloning was also explored to fully understand how levels of PAK2 as well as the alteration of specific phospohorylation sites could alter AML cell responses to CD44-mAbs. Results from this study will be important in determining whether PAK2 could be used as a potential therapeutic target

  12. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study.

    Science.gov (United States)

    Steensma, David P; Abedi, Medrdad; Bejar, Rafael; Cogle, Christopher R; Foucar, Kathryn; Garcia-Manero, Guillermo; George, Tracy I; Grinblatt, David; Komrokji, Rami; Ma, Xiaomei; Maciejewski, Jaroslaw; Pollyea, Daniel A; Savona, Michael R; Scott, Bart; Sekeres, Mikkael A; Thompson, Michael A; Swern, Arlene S; Nifenecker, Melissa; Sugrue, Mary M; Erba, Harry

    2016-08-19

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting. Consequently, our understanding of the patterns of diagnostic evaluation, management, and outcomes of these patients is limited. Furthermore, there are few natural history studies of ICUS. To better understand how patients who have MDS, ICUS, or AML are managed in the routine clinical setting, the Connect MDS/AML Disease Registry, a multicenter, prospective, observational cohort study of patients newly diagnosed with these conditions has been initiated. The Connect MDS/AML Disease Registry will capture diagnosis, risk assessment, treatment, and outcomes data for approximately 1500 newly diagnosed patients from approximately 150 community and academic sites in the United States in 4 cohorts: (1) lower-risk MDS (International Prognostic Scoring System [IPSS] low and intermediate-1 risk), with and without del(5q); (2) higher-risk MDS (IPSS intermediate-2 and high risk); (3) ICUS; and (4) AML in patients aged ≥ 55 years (excluding acute promyelocytic leukemia). Diagnosis will be confirmed by central review. Baseline patient characteristics, diagnostic patterns, treatment patterns, clinical outcomes, health economics outcomes, and patient-reported health-related quality of life will be entered into an electronic data capture system at enrollment and quarterly for 8 years. A tissue substudy to explore the relationship between karyotypes, molecular markers, and clinical outcomes will be conducted, and is optional for patients. The Connect MDS/AML Disease

  13. RUNX1/AML1 point mutations take part in the pathogenesis of radiation-and therapy-related myeloid neoplasms

    International Nuclear Information System (INIS)

    Harada, Yuka; Kimura, Akiro; Harada, Hironori

    2012-01-01

    High frequency of myelodysplastic syndrome (MDS) has been reported in Hiroshima A-bomb exposed survivors, in resident around Semipalatinsk Nuclear Laboratory and in exposed people by Chernobyl Nuclear Power Station Accident. MDS/acute myeloid leukemia (AML) is thought to be caused by mutation of runt-related transcription factor 1 (RUNX1) gene after a long time post exposure to relatively low dose radiation. In this study, participation of RUNX1/AML1 point mutations was examined in pathogenesis of the title neoplasms experienced in authors' facility. Subjects were 18/417 cases in whom myeloproliferative neoplasms (MPN) had switched to MDS or AML in the follow-up period of 1-25 years, and 11/124 cases in whom t-MN (therapy-related myeloid neoplasms) had developed during the remission of acute promyelocytic leukemia (APL) in the 1-9.7 years follow up. Point mutations were analyzed by PCR-single strand conformation polymorphism (PCR-SSCP) followed by base sequencing. In the former cases above, RUNX1 point mutation was found in 5/18 cases and in the latter, 4/11. When patients with persistent decrease of blood cells post therapy of APL were followed up for mutation, their RUNX1 point mutation was detected before they were diagnosed to be morbid of MDS/AML. The point mutation was thus a biomarker of myelo-hematogenic cancer, and was thought useful for early diagnosis of MDS and AML. (T.T.)

  14. Design and kinetic analysis of hammerhead ribozyme and DNAzyme that specifically cleave TEL-AML1 chimeric mRNA

    International Nuclear Information System (INIS)

    Choi, Woo-Hyung; Choi, Bo-Ra; Kim, Jae Hyun; Yeo, Woon-Seok; Oh, Sangtaek; Kim, Dong-Eun

    2008-01-01

    In order to develop the oligonucleotides to abolish an expression of TEL-AML1 chimeric RNA, which is a genetic aberration that causes the acute lymphoblastic leukemia (ALL), hammerhead ribozymes and deoxyoligoribozymes that can specifically cleave TEL-AML1 fusion RNA were designed. Constructs of the deoxyribozyme with an asymmetric substrate binding arm (Dz26) and the hammerhead ribozyme with a 4 nt-bulged substrate binding arm in the stem III (buRz28) were able to cleave TEL-AML1 chimeric RNA specifically at sites close to the junction in vitro, without cleaving the normal TEL and AML1 RNA. Single-turnover kinetic analysis under enzyme-excess condition revealed that the buRz28 is superior to the Dz26 in terms of substrate binding and RNA-cleavage. In conjunction with current progress in a gene-delivery technology, the designed oligonucleotides that specifically cleave the TEL-AML1 chimeric mRNA are hoped to be applicable for the treatment of ALL in vivo

  15. Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission

    Directory of Open Access Journals (Sweden)

    Merk Martina

    2011-09-01

    Full Text Available Abstract Background Active dendritic cell (DC immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML. Here we present for the first time a GMP-compliant 3-day protocol for generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR agonists in intensively pretreated patients with AML. Methods Four different maturation cocktails were compared for their impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation in 20 AML patients and 25 healthy controls. Results Maturation cocktails containing the TLR7/8 agonists R848 or CL075, with and without the addition of the TLR3 agonist poly(I:C, induced DCs that had a positive costimulatory profile, secreted high levels of IL-12(p70, showed chemotaxis to CCR7 ligands, had the ability to activate NK cells, and efficiently stimulated antigen-specific CD8+ T cells. Conclusions Our results demonstrate that this approach translates into biologically improved DCs, not only in healthy controls but also in AML patients. This data supports the clinical application of TLR-matured DCs in patients with AML for activation of innate and adaptive immune responses.

  16. Paclitaxel Induced MDS and AML: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Udit Bhaskar Bhatnagar

    2016-01-01

    Full Text Available Therapy related acute myelogenous leukemia (AML and myelodysplastic syndromes (MDS have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies.

  17. Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate.

    Science.gov (United States)

    Pompetti, Franca; Spadano, Antonio; Sau, Antonella; Mennucci, Antonio; Russo, Rosa; Catinella, Virginia; Franchi, Paolo Guanciali; Calabrese, Giuseppe; Palka, Giandomenico; Fioritoni, Giuseppe; Iacone, Antonio

    2007-04-01

    BCR/ABL-positive acute myeloid leukemia (AML) is a rare disease, characterized by a poor prognosis, with resistance to induction chemotherapy and frequent relapses in responsive patients. Here we report a case of BCR/ABL-positive AML-M6 who, after relapse, was treated with Imatinib Mesylate (600 mg/die) and within 4 months achieved a cytogenetic and molecular complete response. After more than 4 years of continuous Imatinib therapy, nested RT-PCR for BCR/ABL is persistently negative. The case reported shows that the response obtained with Imatinib Mesylate in BCR/ABL-positive AML may be long lasting, offering a chance of successful treatment for this poor prognosis group of patients.

  18. Cellular intrinsic mechanism affecting the outcome of AML treated with Ara-C in a syngeneic mouse model.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhao

    Full Text Available The mechanisms underlying acute myeloid leukemia (AML treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C.

  19. An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells.

    Science.gov (United States)

    Zaidi, Sayyed K; Perez, Andrew W; White, Elizabeth S; Lian, Jane B; Stein, Janet L; Stein, Gary S

    2017-06-20

    Acute myeloid leukemia (AML) is characterized by an aggressive clinical course and frequent cytogenetic abnormalities that include specific chromosomal translocations. The 8;21 chromosomal rearrangement disrupts the key hematopoietic RUNX1 transcription factor, and contributes to leukemia through recruitment of co-repressor complexes to RUNX1 target genes, altered subnuclear localization, and deregulation of the myeloid gene regulatory program. However, a role of non-coding microRNAs (miRs) in t(8;21)-mediated leukemogenesis is minimally understood. We present evidence of an interplay between the tumor suppressor miR-29b-1 and the AML1-ETO (also designated RUNX1-RUNX1T1) oncogene that is encoded by the t(8;21). We find that AML1-ETO and corepressor NCoR co-occupy the miR-29a/b-1 locus and downregulate its expression in leukemia cells. Conversely, re-introduction of miR-29b-1 in leukemia cells expressing AML1-ETO causes significant downregulation at the protein level through direct targeting of the 3' untranslated region of the chimeric transcript. Restoration of miR-29b-1 expression in leukemia cells results in decreased cell growth and increased apoptosis. The AML1-ETO-dependent differentiation block and transcriptional program are partially reversed by miR-29b-1. Our findings establish a novel regulatory circuit between the tumor-suppressive miR-29b-1 and the oncogenic AML1-ETO that controls the leukemic phenotype in t(8;21)-carrying acute myeloid leukemia.

  20. Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance.

    Science.gov (United States)

    Vukovic, Milica; Guitart, Amelie V; Sepulveda, Catarina; Villacreces, Arnaud; O'Duibhir, Eoghan; Panagopoulou, Theano I; Ivens, Alasdair; Menendez-Gonzalez, Juan; Iglesias, Juan Manuel; Allen, Lewis; Glykofrydis, Fokion; Subramani, Chithra; Armesilla-Diaz, Alejandro; Post, Annemarie E M; Schaak, Katrin; Gezer, Deniz; So, Chi Wai Eric; Holyoake, Tessa L; Wood, Andrew; O'Carroll, Dónal; Ratcliffe, Peter J; Kranc, Kamil R

    2015-12-14

    Leukemogenesis occurs under hypoxic conditions within the bone marrow (BM). Knockdown of key mediators of cellular responses to hypoxia with shRNA, namely hypoxia-inducible factor-1α (HIF-1α) or HIF-2α, in human acute myeloid leukemia (AML) samples results in their apoptosis and inability to engraft, implicating HIF-1α or HIF-2α as therapeutic targets. However, genetic deletion of Hif-1α has no effect on mouse AML maintenance and may accelerate disease development. Here, we report the impact of conditional genetic deletion of Hif-2α or both Hif-1α and Hif-2α at different stages of leukemogenesis in mice. Deletion of Hif-2α accelerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9. Notably, the accelerated initiation of AML caused by Hif-2α deletion is further potentiated by Hif-1α codeletion. However, established LSCs lacking Hif-2α or both Hif-1α and Hif-2α propagate AML with the same latency as wild-type LSCs. Furthermore, pharmacological inhibition of the HIF pathway or HIF-2α knockout using the lentiviral CRISPR-Cas9 system in human established leukemic cells with MLL-AF9 translocation have no impact on their functions. We therefore conclude that although Hif-1α and Hif-2α synergize to suppress the development of AML, they are not required for LSC maintenance. © 2015 Vukovic et al.

  1. A new instrument to assess physician skill at thoracic ultrasound, including pleural effusion markup.

    Science.gov (United States)

    Salamonsen, Matthew; McGrath, David; Steiler, Geoff; Ware, Robert; Colt, Henri; Fielding, David

    2013-09-01

    To reduce complications and increase success, thoracic ultrasound is recommended to guide all chest drainage procedures. Despite this, no tools currently exist to assess proceduralist training or competence. This study aims to validate an instrument to assess physician skill at performing thoracic ultrasound, including effusion markup, and examine its validity. We developed an 11-domain, 100-point assessment sheet in line with British Thoracic Society guidelines: the Ultrasound-Guided Thoracentesis Skills and Tasks Assessment Test (UGSTAT). The test was used to assess 22 participants (eight novices, seven intermediates, seven advanced) on two occasions while performing thoracic ultrasound on a pleural effusion phantom. Each test was scored by two blinded expert examiners. Validity was examined by assessing the ability of the test to stratify participants according to expected skill level (analysis of variance) and demonstrating test-retest and intertester reproducibility by comparison of repeated scores (mean difference [95% CI] and paired t test) and the intraclass correlation coefficient. Mean scores for the novice, intermediate, and advanced groups were 49.3, 73.0, and 91.5 respectively, which were all significantly different (P < .0001). There were no significant differences between repeated scores. Procedural training on mannequins prior to unsupervised performance on patients is rapidly becoming the standard in medical education. This study has validated the UGSTAT, which can now be used to determine the adequacy of thoracic ultrasound training prior to clinical practice. It is likely that its role could be extended to live patients, providing a way to document ongoing procedural competence.

  2. Computerized tomographic simulation compared with clinical mark-up in palliative radiotherapy: A prospective study

    International Nuclear Information System (INIS)

    Haddad, Peiman; Cheung, Fred; Pond, Gregory; Easton, Debbie; Cops, Frederick; Bezjak, Andrea; McLean, Michael; Levin, Wilfred; Billingsley, Susan; Williams, Diane; Wong, Rebecca

    2006-01-01

    Purpose To evaluate the impact of computed tomographic (CT) planning in comparison to clinical mark-up (CM) for palliative radiation of chest wall metastases. Methods and Materials In patients treated with CM for chest wall bone metastases (without conventional simulation/fluoroscopy), two consecutive planning CT scans were acquired with and without an external marker to delineate the CM treatment field. The two sets of scans were fused for evaluation of clinical tumor volume (CTV) coverage by the CM technique. Under-coverage was defined as the proportion of CTV not covered by the CM 80% isodose. Results Twenty-one treatments (ribs 17, sternum 2, and scapula 2) formed the basis of our study. Due to technical reasons, comparable data between CM and CT plans were available for 19 treatments only. CM resulted in a mean CTV under-coverage of 36%. Eleven sites (58%) had an under-coverage of >20%. Mean volume of normal tissues receiving ≥80% of the dose was 5.4% in CM and 9.3% in CT plans (p = 0.017). Based on dose-volume histogram comparisons, CT planning resulted in a change of treatment technique from direct apposition to a tangential pair in 7 of 19 cases. Conclusions CT planning demonstrated a 36% under-coverage of CTV with CM of ribs and chest wall metastases

  3. Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Glosli, Heidi; Jahnukainen, Kirsi

    2014-01-01

    BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society...

  4. Functionally deregulated AML1/RUNX1 cooperates with BCR-ABL to induce a blastic phase-like phenotype of chronic myelogenous leukemia in mice.

    Directory of Open Access Journals (Sweden)

    Kiyoko Yamamoto

    Full Text Available Patients in the chronic phase (CP of chronic myelogenous leukemia (CML have been treated successfully following the advent of ABL kinase inhibitors, but once they progress to the blast crisis (BC phase the prognosis becomes dismal. Although mechanisms underlying the progression are largely unknown, recent studies revealed the presence of alterations of key molecules for hematopoiesis, such as AML1/RUNX1. Our analysis of 13 BC cases revealed that three cases had AML1 mutations and the transcript levels of wild-type (wt. AML1 were elevated in BC compared with CP. Functional analysis of representative AML1 mutants using mouse hematopoietic cells revealed the possible contribution of some, but not all, mutants for the BC-phenotype. Specifically, K83Q and R139G, but neither R80C nor D171N mutants, conferred upon BCR-ABL-expressing cells a growth advantage over BCR-ABL-alone control cells in cytokine-free culture, and the cells thus grown killed mice upon intravenous transfer. Unexpectedly, wt.AML1 behaved similarly to K83Q and R139G mutants. In a bone marrow transplantation assay, K83Q and wt.AML1s induced the emergence of blast-like cells. The overall findings suggest the roles of altered functions of AML1 imposed by some, but not all, mutants, and the elevated expression of wt.AML1 for the disease progression of CML.

  5. The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods

    International Nuclear Information System (INIS)

    Linka, Y; Ginzel, S; Krüger, M; Novosel, A; Gombert, M; Kremmer, E; Harbott, J; Thiele, R; Borkhardt, A; Landgraf, P

    2013-01-01

    The reciprocal translocation t(12;21)(p13;q22), the most common structural genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children, results in a chimeric transcription factor TEL-AML1 (ETV6-RUNX1). We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture, we identified 217 directly and 118 indirectly regulated targets of the TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were enriched in AML1-binding sites. The majority of promoter regions were specific for the fusion protein and not bound by native AML1 or TEL. Comparison with gene expression profiles from TEL-AML1-positive patients identified 56 concordantly misregulated genes with negative effects on proliferation and cellular transport mechanisms and positive effects on cellular migration, and stress responses including immunological responses. In summary, this work for the first time gives a comprehensive insight into how TEL-AML1 expression may directly and indirectly contribute to alter cells to become prone for leukemic transformation

  6. Utilization of Forward Error Correction (FEC) Techniques With Extensible Markup Language (XML) Schema-Based Binary Compression (XSBC) Technology

    Science.gov (United States)

    2004-12-01

    NY 7. Erik Chaum NUWC Newport, RI 8. David Bellino NPRI Newport, RI 9. Dick Nadolink NUWC Newport, RI 10. VADM Roger Bacon (Ret...Science Advisor Pearl Harbor, HI 16. LT Andrew Hurvitz, USN FNMOC Monterey, CA 17. ENS Darin Keeter, USN FNMOC Monterey, CA 18. CAPT David

  7. Producing a Data Dictionary from an Extensible Markup Language (XML) Schemain the Global Force Management Data Initiative

    Science.gov (United States)

    2017-02-01

    are not to be construed as an official Department of the Army position unless so designated by other authorized documents. Citation of manufacturer’s...FMID and EwID fields, and mandatory fields. Cascading Style Sheets (CSS)13 are used to provide this functionality. The comments in the style definitions...explain the color specifications. <!-- colors and other details are defined in CSS styles --> < style type="text/css"> body, th, td { font-family

  8. Federated Process Framework in a Virtual Enterprise Using an Object-Oriented Database and Extensible Markup Language.

    Science.gov (United States)

    Bae, Kyoung-Il; Kim, Jung-Hyun; Huh, Soon-Young

    2003-01-01

    Discusses process information sharing among participating organizations in a virtual enterprise and proposes a federated process framework and system architecture that provide a conceptual design for effective implementation of process information sharing supporting the autonomy and agility of the organizations. Develops the framework using an…

  9. Applying Semantic Web Concepts to Support Net-Centric Warfare Using the Tactical Assessment Markup Language (TAML)

    National Research Council Canada - National Science Library

    Childers, Candace M

    2006-01-01

    .... The current approach to automating data processing is to hard-code programs to parse particular data formats, but this approach is not flexible enough to handle the constantly changing data world...

  10. MRD in AML: it is time to change the definition of remission.

    Science.gov (United States)

    Ossenkoppele, Gert J; Schuurhuis, Gerrit Jan

    2014-01-01

    The possibility of defining residual disease far below the morphological level of 5% blast cells is changing the landscape of risk classification in acute myeloid leukemia (AML). The so-called minimal residual disease (MRD) approach at this time can establish the presence of leukemia cells down to levels of 1:1000-1:10(6) white blood cells, compared to 1:20 for morphology. Availability of the newer and more sensitive technology to quantify the level of leukemic burden raises the issue of whether MRD should emerge as a new definition of complete response. This paper explores some of the issues surrounding such a change in definition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Low-dose total body irradiation and G-CSF without hematopoietic stem cell support in the treatment of relapsed or refractory acute myelogenous leukemia (AML), or AML in second or subsequent remission

    International Nuclear Information System (INIS)

    Shulman, Lawrence N.; Tarbell, Nancy J.; Storen, Elizabeth; Marcus, Karen; Mauch, Peter M.

    1998-01-01

    Purpose: Patients with relapsed acute myelogenous leukemia (AML), who are not eligible for bone marrow transplantation, have a poor prognosis when treated with chemotherapy alone. Total body irradiation (TBI) is an effective modality against AML when used in doses of 1000-1400 cGy with hematopoietic stem cell support. We undertook a phase I study of TBI with granulocyte-colony-stimulating factor (G-CSF) support, without stem cell support in patients with AML either in relapse or second or subsequent remission. Methods and Materials: Patients with relapsed AML, or AML in second or subsequent remission were treated in a phase I study of TBI followed by G-CSF. The first dose level was 200 cGy. After the initial cohort of patients it was clear that patients with overt leukemia did not benefit from this treatment, and subsequent patients were required to be in remission at the time of TBI. Results: Eleven patients were treated, 4 in overt relapse, and 7 in remission. 200 cGy was used in all, and dose escalation was not possible due to prolonged thrombocytopenia in all patients but one. Neutrophil recovery was adequate in those patients who remained in remission after TBI. Patients with overt leukemia had transient reduction in blast counts, but rapid recurrence of their leukemia. Patients treated in remission had short remissions, with the exception of one patient who is in remission 32 months after treatment. Conclusion: There is some antileukemic effect of TBI even at 200 cGy, though this dose appears to be too low to help a significant number of patients. If TBI is to be escalated without stem cell support, then a thrombopoietic agent will need to be used

  12. Circumvention of ara-C resistance by aphidicolin in blast cells from patients with AML.

    Science.gov (United States)

    Sargent, J M; Elgie, A W; Williamson, C J; Lewandowicz, G M; Taylor, C G

    2001-03-02

    Treatment failure in AML is often attributed to P-glycoprotein-associated multidrug resistance. However, the importance of increased DNA repair in resistant cells is becoming more apparent. In order to investigate the ability of the DNA repair inhibitor aphidicolin to modulate drug resistance, we continually exposed blasts cells, isolated from 22 patients with AML, to a variety of agents +/- 15 microM aphidicolin for 48 hours. Cell survival was measured using the MTT assay. Overall, there was no significant effect of aphidicolin on sensitivity to daunorubicin, doxorubicin, etoposide or fludarabine. However, there was a marked increase in sensitivity to ara-C with a median 4.75-fold increase overall (range 0.8-80-fold;P< 0.005). The effect of aphidicolin was significantly greater in blast cells found resistant in vitro to ara-C (8.9-fold compared to 2.12-fold, P< 0.01). This observation was further validated by the correlation between ara-C LC(50)and extent of modulation effect (P< 0.05). Cells isolated from 10 cord blood samples were also tested in order to establish the haematological toxicity of combining ara-C and aphidicolin. The therapeutic index (LC(50)normal cells/tumour cells) for ara-C + aphidicolin was higher than that for ara-C alone suggesting no increased myelotoxicity for the combination. Increased cytotoxicity without increased haematotoxicity makes the combination of ara-C plus aphidicolin ideal for inclusion in future clinical trials. Copyright 2001 Cancer Research Campaign.

  13. ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia

    NARCIS (Netherlands)

    Martens, Joost H. A.; Mandoli, Amit; Simmer, Femke; Wierenga, Bart-Jan; Saeed, Sadia; Singh, Abhishek A.; Altucci, Lucia; Vellenga, Edo; Stunnenberg, Hendrik G.

    2012-01-01

    ERG and FLI1 are closely related members of the ETS family of transcription factors and have been identified as essential factors for the function and maintenance of normal hematopoietic stem cells. Here genome-wide analysis revealed that both ERG and FLI1 occupy similar genomic regions as AML1-ETO

  14. Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients

    Science.gov (United States)

    Fucikova, Jitka; Truxova, Iva; Hensler, Michal; Becht, Etienne; Kasikova, Lenka; Moserova, Irena; Vosahlikova, Sarka; Klouckova, Jana; Church, Sarah E.; Cremer, Isabelle; Kepp, Oliver; Kroemer, Guido; Galluzzi, Lorenzo; Salek, Cyril

    2016-01-01

    Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called “damage-associated molecular patterns,” DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from patients with acute myeloid leukemia (AML) exposed multiple DAMPs, including calreticulin (CRT), heat-shock protein 70 (HSP70), and HSP90 on their plasma membrane irrespective of treatment. In these patients, high levels of surface-exposed CRT correlated with an increased proportion of natural killer cells and effector memory CD4+ and CD8+ T cells in the periphery. Moreover, CRT exposure on the plasma membrane of malignant blasts positively correlated with the frequency of circulating T cells specific for leukemia-associated antigens, indicating that ecto-CRT favors the initiation of anticancer immunity in patients with AML. Finally, although the levels of ecto-HSP70, ecto-HSP90, and ecto-CRT were all associated with improved relapse-free survival, only CRT exposure significantly correlated with superior overall survival. Thus, CRT exposure represents a novel powerful prognostic biomarker for patients with AML, reflecting the activation of a clinically relevant AML-specific immune response. PMID:27802968

  15. Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    KAUST Repository

    Aldehaiman, Mansour M.

    2018-01-01

    the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell

  16. Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation

    NARCIS (Netherlands)

    Radivoyevitch, T.; Sachs, R. K.; Gale, R. P.; Molenaar, R. J.; Brenner, D. J.; Hill, B. T.; Kalaycio, M. E.; Carraway, H. E.; Mukherjee, S.; Sekeres, M. A.; Maciejewski, J. P.

    2016-01-01

    Risks of acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) are known to increase after cancer treatments. Their rise-and-fall dynamics and their associations with radiation have, however, not been fully characterized. To improve risk definition we developed SEERaBomb R software for

  17. The price of surgery: markup of operative procedures in the United States.

    Science.gov (United States)

    Gani, Faiz; Makary, Martin A; Pawlik, Timothy M

    2017-02-01

    Despite cost containment efforts, the price for surgery is not subject to any regulations. We sought to characterize and compare variability in pricing for commonly performed major surgical procedures across the United States. Medicare claims corresponding to eight major surgical procedures (aortic aneurysm repair, aortic valvuloplasty, carotid endartectomy, coronary artery bypass grafting, esophagectomy, pancreatectomy, liver resection, and colectomy) were identified using the Medicare Provider Utilization and Payment Data Physician and Other Supplier Public Use File for 2013. For each procedure, total charges, Medicare-allowable costs, and total payments were recorded. A procedure-specific markup ratio (MR; ratio of total charges to Medicare-allowable costs) was calculated and compared between procedures and across states. Variation in MR was compared using a coefficient of variation (CoV). Among all providers, the median MR was 3.5 (interquartile range: 3.1-4.0). MR was noted to vary by procedure; ranging from 3.0 following colectomy to 6.0 following carotid endartectomy (P < 0.001). MR also varied for the same procedure; varying the least after liver resection (CoV = 0.24), while coronary artery bypass grafting pricing demonstrated the greatest variation in MR (CoV = 0.53). Compared with the national average, MR varied by 36% between states ranging from 1.8 to 13.0. Variation in MR was also noted within the same state varying by 15% within the state of Arkansas (CoV = 0.15) compared with 51% within the state of Wisconsin (CoV = 0.51). Significant variation was noted for the price of surgery by procedure as well as between and within different geographical regions. Greater scrutiny and transparency in the price of surgery is required to promote cost containment. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells.

    Science.gov (United States)

    van Rhenen, Anna; van Dongen, Guus A M S; Kelder, Angèle; Rombouts, Elwin J; Feller, Nicole; Moshaver, Bijan; Stigter-van Walsum, Marijke; Zweegman, Sonja; Ossenkoppele, Gert J; Jan Schuurhuis, Gerrit

    2007-10-01

    In CD34(+) acute myeloid leukemia (AML), the malignant stem cells reside in the CD38(-) compartment. We have shown before that the frequency of such CD34(+)CD38(-) cells at diagnosis correlates with minimal residual disease (MRD) frequency after chemotherapy and with survival. Specific targeting of CD34(+)CD38(-) cells might thus offer therapeutic options. Previously, we found that C-type lectin-like molecule-1 (CLL-1) has high expression on the whole blast compartment in the majority of AML cases. We now show that CLL-1 expression is also present on the CD34(+)CD38(-) stem- cell compartment in AML (77/89 patients). The CD34(+)CLL-1(+) population, containing the CD34(+)CD38(-)CLL-1(+) cells, does engraft in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with outgrowth to CLL-1(+) blasts. CLL-1 expression was not different between diagnosis and relapse (n = 9). In remission, both CLL-1(-) normal and CLL-1(+) malignant CD34(+)CD38(-) cells were present. A high CLL-1(+) fraction was associated with quick relapse. CLL-1 expression is completely absent both on CD34(+)CD38(-) cells in normal (n = 11) and in regenerating bone marrow controls (n = 6). This AML stem-cell specificity of the anti-CLL-1 antibody under all conditions of disease and the leukemia-initiating properties of CD34(+)CLL-1(+) cells indicate that anti-CLL-1 antibody enables both AML-specific stem-cell detection and possibly antigen-targeting in future.

  19. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element.

    Science.gov (United States)

    Fukunaga, Junichi; Nomura, Yusuke; Tanaka, Yoichiro; Amano, Ryo; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Sakamoto, Taiichi; Kozu, Tomoko

    2013-07-01

    AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5'-NNCCAC-3' and 5'-GCGMGN'N'-3' (M:A or C; N and N' form Watson-Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.

  20. Language Contact.

    Science.gov (United States)

    Nelde, Peter Hans

    1995-01-01

    Examines the phenomenon of language contact and recent trends in linguistic contact research, which focuses on language use, language users, and language spheres. Also discusses the role of linguistic and cultural conflicts in language contact situations. (13 references) (MDM)

  1. Do state minimum markup/price laws work? Evidence from retail scanner data and TUS-CPS.

    Science.gov (United States)

    Huang, Jidong; Chriqui, Jamie F; DeLong, Hillary; Mirza, Maryam; Diaz, Megan C; Chaloupka, Frank J

    2016-10-01

    Minimum markup/price laws (MPLs) have been proposed as an alternative non-tax pricing strategy to reduce tobacco use and access. However, the empirical evidence on the effectiveness of MPLs in increasing cigarette prices is very limited. This study aims to fill this critical gap by examining the association between MPLs and cigarette prices. State MPLs were compiled from primary legal research databases and were linked to cigarette prices constructed from the Nielsen retail scanner data and the self-reported cigarette prices from the Tobacco Use Supplement to the Current Population Survey. Multivariate regression analyses were conducted to examine the association between MPLs and the major components of MPLs and cigarette prices. The presence of MPLs was associated with higher cigarette prices. In addition, cigarette prices were higher, above and beyond the higher prices resulting from MPLs, in states that prohibit below-cost combination sales; do not allow any distributing party to use trade discounts to reduce the base cost of cigarettes; prohibit distributing parties from meeting the price of a competitor, and prohibit distributing below-cost coupons to the consumer. Moreover, states that had total markup rates >24% were associated with significantly higher cigarette prices. MPLs are an effective way to increase cigarette prices. The impact of MPLs can be further strengthened by imposing greater markup rates and by prohibiting coupon distribution, competitor price matching, and use of below-cost combination sales and trade discounts. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism.

    Science.gov (United States)

    Rotin, Lianne E; Gronda, Marcela; MacLean, Neil; Hurren, Rose; Wang, XiaoMing; Lin, Feng-Hsu; Wrana, Jeff; Datti, Alessandro; Barber, Dwayne L; Minden, Mark D; Slassi, Malik; Schimmer, Aaron D

    2016-01-19

    Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease.

  3. The rarity of ALDH(+) cells is the key to separation of normal versus leukemia stem cells by ALDH activity in AML patients.

    Science.gov (United States)

    Hoang, Van T; Buss, Eike C; Wang, Wenwen; Hoffmann, Isabel; Raffel, Simon; Zepeda-Moreno, Abraham; Baran, Natalia; Wuchter, Patrick; Eckstein, Volker; Trumpp, Andreas; Jauch, Anna; Ho, Anthony D; Lutz, Christoph

    2015-08-01

    To understand the precise disease driving mechanisms in acute myeloid leukemia (AML), comparison of patient matched hematopoietic stem cells (HSC) and leukemia stem cells (LSC) is essential. In this analysis, we have examined the value of aldehyde dehydrogenase (ALDH) activity in combination with CD34 expression for the separation of HSC from LSC in 104 patients with de novo AML. The majority of AML patients (80 out of 104) had low percentages of cells with high ALDH activity (ALDH(+) cells; cells (≥1.9%; ALDH-numerous AML). In patients with ALDH-rare AML, normal HSC could be separated by their CD34(+) ALDH(+) phenotype, whereas LSC were exclusively detected among CD34(+) ALDH(-) cells. For patients with ALDH-numerous AML, the CD34(+) ALDH(+) subset consisted mainly of LSC and separation from HSC was not feasible. Functional analyses further showed that ALDH(+) cells from ALDH-numerous AML were quiescent, refractory to ARA-C treatment and capable of leukemic engraftment in a xenogenic mouse transplantation model. Clinically, resistance to chemotherapy and poor long-term outcome were also characteristic for patients with ALDH-numerous AML providing an additional risk-stratification tool. The difference in spectrum and relevance of ALDH activity in the putative LSC populations demonstrates, in addition to phenotypic and genetic, also functional heterogeneity of leukemic cells and suggests divergent roles for ALDH activity in normal HSC versus LSC. By acknowledging these differences our study provides a new and useful tool for prospective identification of AML cases in which separation of HSC from LSC is possible. © 2014 UICC.

  4. Informatics in radiology: An open-source and open-access cancer biomedical informatics grid annotation and image markup template builder.

    Science.gov (United States)

    Mongkolwat, Pattanasak; Channin, David S; Kleper, Vladimir; Rubin, Daniel L

    2012-01-01

    In a routine clinical environment or clinical trial, a case report form or structured reporting template can be used to quickly generate uniform and consistent reports. Annotation and image markup (AIM), a project supported by the National Cancer Institute's cancer biomedical informatics grid, can be used to collect information for a case report form or structured reporting template. AIM is designed to store, in a single information source, (a) the description of pixel data with use of markups or graphical drawings placed on the image, (b) calculation results (which may or may not be directly related to the markups), and (c) supplemental information. To facilitate the creation of AIM annotations with data entry templates, an AIM template schema and an open-source template creation application were developed to assist clinicians, image researchers, and designers of clinical trials to quickly create a set of data collection items, thereby ultimately making image information more readily accessible.

  5. Granulocytic Sarcoma by AML M4eo (inv16 after Allogeneic Stem Cell Transplantation without Bone Marrow Involvement

    Directory of Open Access Journals (Sweden)

    Stephan Zaenker

    2011-01-01

    Full Text Available Granulocytic sarcoma (GS represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML. We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT. The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.

  6. Incidence of extramedullary relapse after haploidentical SCT for advanced AML/myelodysplastic syndrome.

    Science.gov (United States)

    Yoshihara, S; Ikegame, K; Kaida, K; Taniguchi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Soma, T; Ogawa, H

    2012-05-01

    Extramedullary (EM) relapse of leukemia after allo-SCT in patients with AML/myelodysplastic syndrome has been increasingly reported. The reduced effectiveness of the GVL effect in EM sites, as compared with BM, has been suggested to underlie this problem. We retrospectively analyzed the pattern of relapse after haploidentical SCT (haplo-SCT), performed as the first or second SCT. Among 38 patients who received haplo-SCT as their first SCT, the cumulative incidences of BM and EM relapse at 3 years were 40.5 and 10.9%, respectively. Among 19 patients who received haplo-SCT as their second SCT, the cumulative incidences of BM and EM relapse were 30.9 and 31.9%, respectively. Moreover, most of the patients who underwent repeat haplo-SCT for the treatment of EM relapse had further EM relapse at other sites. Post-relapse survival did not differ significantly with different patterns of relapse. The frequent occurrence of EM relapse after haplo-SCT, particularly when performed as a second SCT, suggests that the potent GVL effect elicited by an HLA disparity also occurs preferentially in BM. Our findings emphasize the need for a treatment strategy for EM relapse that recognizes the reduced susceptibility of EM relapse to the GVL effect.

  7. Chemical Space of FLT3 Inhibitors as Potential Anti-AML Drugs.

    Science.gov (United States)

    Lan, Qing-Yuan; Zhi, Yan-Le; Heng, Hao; Tian, Jie-Yi; Guo, Xiao-Xing; Liu, Hai-Chun; Chen, Ya-Dong; Lu, Tao; Lu, Shuai

    2017-11-20

    FLT3 is a member of receptor tyrosine kinase III family, mainly expressed in hematopoietic cells. The aberrant expression and function of FLT3 are strongly related to leukemia, especially acute myeloid leukemia. Its varieties of amino-acid residues mutations, such as FLT3-ITDs and -TKDs, can induce constant proliferation of hematological tumor cells with poor prognosis. Hence FLT3 serves as a promising target in AML chemotherapy. This review focused on the progress of FLT3 inhibitors study including those that have entered clinical trials or were reported in numerous patents all over the world. Thus, we provided a useful reference for the development of new anti-leukemia drugs. Through a comprehensive retrospective study, FLT3 inhibitors in several patent applications were identified and classified into five categories, including quinolone-related, indole-related, ureas, pyrimidines and other compounds. For each category of compounds, the structural feature, SAR, biological activity and current research status were thoroughly reviewed and analyzed. Although some of those compounds expressed potent bioactivities and have reached the advanced clinical trials for the treatment of leukemia, there are still several problems need to be faced before they enter the market eventually, especially the drug resistance issue. The improvement of therapeutic potency for FLT3 inhibitors might depend on the useful combination therapy and further refinement of the intrinsic properties of FLT3 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups.

    Science.gov (United States)

    Luskin, Marlise R; Lee, Ju-Whei; Fernandez, Hugo F; Abdel-Wahab, Omar; Bennett, John M; Ketterling, Rhett P; Lazarus, Hillard M; Levine, Ross L; Litzow, Mark R; Paietta, Elisabeth M; Patel, Jay P; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Sun, Zhuoxin; Luger, Selina M

    2016-03-24

    The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m(2)) improved overall survival in adults cytogenetics or aFLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m(2)), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P= .001). Younger patients (cytogenetics (HR, 0.51;P= .03 and HR, 0.68;P= .01, respectively). Patients with unfavorable cytogenetics were shown to benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66;P= .04). Patients with FLT3-ITD (24%),DNMT3A(24%), and NPM1(26%) mutant AML all benefited from HD daunorubicin (HR, 0.61,P= .009; HR, 0.62,P= .02; and HR, 0.50,P= .002; respectively). HD benefit was seen in the subgroup of older patients (50-60 years) with the FLT3-ITD or NPM1 mutation. Additionally, the presence of an NPM1 mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction. © 2016 by The American Society of Hematology.

  9. The semantics of English Borrowings in Arabic Media Language: The case of Arab Gulf States Newspapers

    Directory of Open Access Journals (Sweden)

    Anwar A. H. Al-Athwary

    2016-07-01

    Full Text Available The present paper investigates the semantics of English loanwords in Arabic media language (AML. The loanword data are collected from a number of Arab Gulf states newspapers (AGSNs. They  are analyzed semantically from the points of view of semantic change, semantic domains, and the phenomenon of synonymy resulting from lexical borrowing. The semantic analysis has revealed that AML borrowings from English occur in fifteen distinctive semantic domains. Domains that are related to terms of technical and scientific nature are found ranking much higher (9% - 18% than those domains containing nontechnical elements (1% - 8% with the computer and technology category (18% is the most dominant domain. Almost all common mechanisms of semantic change (extension, restriction, amelioration, pejoration, and metaphorical extension are found at work in the context of AML borrowings. The tendency of semantic change in the overwhelming majority of AML borrowings is towards restriction.  Factors like need, semantic similarity, and factors of social and psychological considerations (e.g. prestige, taboo seem to be the potent factors at interplay in semantic change. The first two, i.e. need and semantic similarity, are the most common reasons in most types of semantic change. The problem of synonymy lies in those loanwords that have “Arabic equivalents” in the language. The study claims that this phenomenon could be attributed to the two simultaneous processes of lexical borrowing and?ištiqa:q (the modern efforts of deriving equivalent neologisms.

  10. Compliance with the AM+L4776L/CFT International Standard; Lessons from a Cross-Country Analysis

    OpenAIRE

    Concha Verdugo Yepes

    2011-01-01

    This paper assesses countries' compliance with the Anti-Money Laundering and Combating the Financing of Terrorism (AML/CFT) international standard during the period 2004 to 2011. We find that overall compliance is low; there is an adverse impact on financial transparency created by the cumulative effects of poor implementation of standards on customer identification; and the current measurements of compliance do not take into account an analysis of ML/FT risk, thereby undermining their credib...

  11. Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan

    2014-01-01

    Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in iden......-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients....

  12. Keep your mind off negative things: coping with long-term effects of acute myeloid leukemia (AML).

    Science.gov (United States)

    Ghodraty-Jabloo, Vida; Alibhai, Shabbir M H; Breunis, Henriette; Puts, Martine T E

    2016-05-01

    Acute myeloid leukemia (AML) is characterized by sudden onset, intensive treatment, a poor prognosis, and significant relapse risk. Quality of life (QOL) and well-being among AML survivors have been extensively studied during the 6 months of active treatment. However, it is not clear what survivors experience after active treatment. The purpose of our study was to explore how AML survivors describe their longer-term physical and psychosocial well-being and how they cope with these challenges. We conducted a prospective qualitative study and interviewed 19 adult participants (11 had completed treatment, 8 were receiving maintenance chemotherapy). Data were collected using semi-structured interviews that were audio-recorded and transcribed verbatim. The grounded theory approach was used for data analysis. A marked improvement in physical health was reported; however, psychosocial well-being was compromised by enduring emotional distress. A range of emotion- and problem-focused coping strategies were reported. Keeping one's mind off negative things through engaging in formal work or informal activities and seeking control were the two most commonly used coping strategies. Seeking social support for reassurance was also common. Problem-focused strategies were frequently described by the ongoing treatment group to manage treatment side effects. Although physical symptoms improved after completion of treatment, psychosocial distress persisted over longer period of time. In addition, essential needs of AML survivors shifted across survivorship as psychological burden gradually displaced physical concerns. The integral role of coping mechanisms in the adaptation process suggests a need for effective and ongoing psychological interventions.

  13. Nuclear accumulation of SHIP1 mutants derived from AML patients leads to increased proliferation of leukemic cells.

    Science.gov (United States)

    Nalaskowski, Marcus M; Ehm, Patrick; Rehbach, Christoph; Nelson, Nina; Täger, Maike; Modest, Kathrin; Jücker, Manfred

    2018-05-28

    The inositol 5-phosphatase SHIP1 acts as negative regulator of intracellular signaling in myeloid cells and is a tumor suppressor in myeloid leukemogenesis. After relocalization from the cytoplasm to the plasma membrane SHIP1 terminates PI3-kinase mediated signaling processes. Furthermore, SHIP1 is also found in distinct puncta in the cell nucleus and nuclear SHIP1 has a pro-proliferative function. Here we report the identification of five nuclear export signals (NESs) which regulate together with the two known nuclear localization signals (NLSs) the nucleocytoplasmic shuttling of SHIP1. Mutation of NLSs reduced the nuclear import and mutation of NESs decreased the nuclear export of SHIP1 in the acute myeloid leukemia (AML) cell line UKE-1. Interestingly, four SHIP1 mutants (K210R, N508D, V684E, Q1153L) derived from AML patients showed a nuclear accumulation after expression in UKE-1 cells. In addition, overexpression of the AML patient-derived mutation N508D caused an increased proliferation rate of UKE-1 cells in comparison to wild type SHIP1. Furthermore, we identified serine and tyrosine phosphorylation as a molecular mechanism for the regulation of nucleocytoplasmic shuttling of SHIP1 where tyrosine phosphorylation of distinct residues i.e. Y864, Y914, Y1021 reduces nuclear localization, whereas serine phosphorylation at S933 enhances nuclear localization of SHIP1. In summary, our data further implicate nuclear SHIP1 in cellular signaling and suggest that enhanced accumulation of SHIP1 mutants in the nucleus may be a contributory factor of abnormally high proliferation of AML cells. Copyright © 2017. Published by Elsevier Inc.

  14. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation

    DEFF Research Database (Denmark)

    Rishi, Loveena; Hannon, Maura; Salomè, Mara

    2014-01-01

    α (C/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop......The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein...... for E2F1, C/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPα-p42, and in normal granulocyte/macrophage progenitor cells, we detect C/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle...

  15. Functional analysis of P-glycoprotein and multidrug resistance associated protein related multidrug resistance in AML-blasts.

    Science.gov (United States)

    Brügger, D; Herbart, H; Gekeler, V; Seitz, G; Liu, C; Klingebiel, T; Orlikowsky, T; Einsele, H; Denzlinger, C; Bader, P; Niethammer, D; Beck, J F

    1999-05-01

    Despite the high effectiveness of various P-glycoprotein (P-gp) modulating substances in vitro their clinical value e.g. for combination treatment of acute myelogenous leukemias (AML) remains still unclear. This might be explainable by recent findings that other factors than P-gp (e.g. the multidrug resistance associated protein (MRP)) may also be involved in clinical occurring drug resistance. To study P-gp and MRP mediated MDR in AML blasts from patients with relapses at the functional level we measured rhodamine 123 (RHO) efflux in combination with a P-gp specific (SDZ PSC 833) or a MRP specific (MK571) modulator, respectively. Furthermore, direct antineoplastic drug action was monitored by determination of damaged cell fraction of a blast population using flow cytometry. We generally found strongly modulated RHO efflux by SDZ PSC 833 but slight RHO-efflux modulation by MK571 in blasts from relapsed states of AML expressing MDR1 or MRP mRNA at various levels. We could not demonstrate, though, significant PSC 833 or MK571 mediated modulation of the cytotoxic effects of etoposide. The results point to the possibility that combination of etoposide and a modulator might not improve responses to chemotherapy by targeting P-gp or MRP exclusively.

  16. Induced Mitogenic Activity in AML-12 Mouse Hepatocytes Exposed to Low-dose Ultra-Wideband Electromagnetic Radiation

    Directory of Open Access Journals (Sweden)

    P. B. Tchounwou

    2005-04-01

    Full Text Available Ultra–wideband (UWB technology has increased with the use of various civilian and military applications. In the present study, we hypothesized that low-dose UWB electromagnetic radiation (UWBR could elicit a mitogenic effect in AML-12 mouse hepatocytes, in vitro. To test this hypothesis, we exposed AML-12 mouse hepatocytes, to UWBR in a specially constructed gigahertz transverse electromagnetic mode (GTEM cell. Cells were exposed to UWBR for 2 h at a temperature of 23°C, a pulse width of 10 ns, a repetition rate of 1 kHz, and field strength of 5-20 kV/m. UWB pulses were triggered by an external pulse generator for UWBR exposure but were not triggered for the sham exposure. We performed an MTT Assay to assess cell viability for UWBR-treated and sham-exposed hepatocytes. Data from viability studies indicated a time-related increase in hepatocytes at time intervals from 8-24 h post exposure. UWBR exerted a statistically significant (p < 0.05 dose-dependent response in cell viability in both serum-treated and serum free medium (SFM -treated hepatocytes. Western blot analysis of hepatocyte lysates demonstrated that cyclin A protein was induced in hepatocytes, suggesting that increased MTT activity after UWBR exposure was due to cell proliferation. This study indicates that UWBR has a mitogenic effect on AML-12 mouse hepatocytes and implicates a possible role for UWBR in hepatocarcinoma.

  17. Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain.

    Science.gov (United States)

    Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi

    2013-12-01

    AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

  18. Exchange Transfusion and Leukapheresis in Pediatric Patients with AML With High Risk of Early Death by Bleeding and Leukostasis.

    Science.gov (United States)

    Creutzig, Ursula; Rössig, Claudia; Dworzak, Michael; Stary, Jan; von Stackelberg, Arend; Wössmann, Wilhelm; Zimmermann, Martin; Reinhardt, Dirk

    2016-04-01

    The risk of early death (ED) by bleeding/leukostasis is high in patients with AML with hyperleukocytosis (>100,000/μl). Within the pediatric AML-BFM (Berlin-Frankfurt-Münster) 98/04 studies, emergency strategies for these children included exchange transfusion (ET) or leukapheresis (LPh). Risk factors for ED and interventions performed were analyzed. Two hundred thirty-eight of 1,251 (19%) patients with AML presented with hyperleukocytosis; 23 of 1,251 (1.8%) patients died of bleeding/leukostasis. ED due to bleeding/leukostasis was highest at white blood cell (WBC) count >200,000/μl (14.3%). ED rates were even higher (20%) in patients with FAB (French-American-British) M4/M5 and hyperleukocytosis >200,000/μl. Patients with WBC >200,000/μl did slightly better with ET/LPh compared to those without ET/LPh (ED rate 7.5% vs. 21.2%, P = 0.055). Multivariate WBC >200,000/μl was of strongest prognostic significance for ED (P(χ(2) ) rate due to bleeding/leukostasis and is recommended at WBC >200,000/μl, and in FAB M4/M5 even at lower WBC. © 2015 Wiley Periodicals, Inc.

  19. Language Revitalization.

    Science.gov (United States)

    Hinton, Leanne

    2003-01-01

    Surveys developments in language revitalization and language death. Focusing on indigenous languages, discusses the role and nature of appropriate linguistic documentation, possibilities for bilingual education, and methods of promoting oral fluency and intergenerational transmission in affected languages. (Author/VWL)

  20. The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation.

    Science.gov (United States)

    de Laurentiis, A; Hiscott, J; Alcalay, M

    2015-12-03

    The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene. Many studies on TEL-AML1 describe specific properties of the fusion protein, but a thorough understanding of its function is lacking. We exploited a pluripotent hematopoietic stem/progenitor cell line, EML1, and generated a cell line (EML-TA) stably expressing the TEL-AML1 fusion protein. EML1 cells differentiate to mature B-cells following treatment with IL7; whereas EML-TA display an impaired differentiation capacity and remain blocked at an early stage of maturation. Global gene expression profiling of EML1 cells at different stages of B-lymphoid differentiation, compared with EML-TA, identified the interferon (IFN)α/β pathway as a primary target of repression by TEL-AML1. In particular, expression and phosphorylation of interferon-regulatory factor 3 (IRF3) was decreased in EML-TA cells; strikingly, stable expression of IRF3 restored the capacity of EML-TA cells to differentiate into mature B-cells. Similarly, IRF3 silencing in EML1 cells by siRNA was sufficient to block B-lymphoid differentiation. The ability of TEL-AML1 to block B-cell differentiation and downregulate the IRF3-IFNα/β pathway was confirmed in mouse and human primary hematopoietic precursor cells (Lin- and CD34+ cells, respectively), and in a patient-derived cell line expressing TEL-AML1 (REH). Furthermore, treatment of TEL-AML1 expressing cells with IFNα/β was sufficient to overcome the maturation block. Our data provide new insight on TEL-AML1 function and may offer a new therapeutic opportunity for B-ALL.

  1. SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML.

    Science.gov (United States)

    Kung Sutherland, May S; Walter, Roland B; Jeffrey, Scott C; Burke, Patrick J; Yu, Changpu; Kostner, Heather; Stone, Ivan; Ryan, Maureen C; Sussman, Django; Lyon, Robert P; Zeng, Weiping; Harrington, Kimberly H; Klussman, Kerry; Westendorf, Lori; Meyer, David; Bernstein, Irwin D; Senter, Peter D; Benjamin, Dennis R; Drachman, Jonathan G; McEarchern, Julie A

    2013-08-22

    Outcomes in acute myeloid leukemia (AML) remain unsatisfactory, and novel treatments are urgently needed. One strategy explores antibodies and their drug conjugates, particularly those targeting CD33. Emerging data with gemtuzumab ozogamicin (GO) demonstrate target validity and activity in some patients with AML, but efficacy is limited by heterogeneous drug conjugation, linker instability, and a high incidence of multidrug resistance. We describe here the development of SGN-CD33A, a humanized anti-CD33 antibody with engineered cysteines conjugated to a highly potent, synthetic DNA cross-linking pyrrolobenzodiazepine dimer via a protease-cleavable linker. The use of engineered cysteine residues at the sites of drug linker attachment results in a drug loading of approximately 2 pyrrolobenzodiazepine dimers per antibody. In preclinical testing, SGN-CD33A is more potent than GO against a panel of AML cell lines and primary AML cells in vitro and in xenotransplantation studies in mice. Unlike GO, antileukemic activity is observed with SGN-CD33A in AML models with the multidrug-resistant phenotype. Mechanistic studies indicate that the cytotoxic effects of SGN-CD33A involve DNA damage with ensuing cell cycle arrest and apoptotic cell death. Together, these data suggest that SGN-CD33A has CD33-directed antitumor activity and support clinical testing of this novel therapeutic in patients with AML.

  2. A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience.

    Science.gov (United States)

    Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen

    2017-07-01

    To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

  3. Semantically supporting data discovery, markup and aggregation in the European Marine Observation and Data Network (EMODnet)

    Science.gov (United States)

    Lowry, Roy; Leadbetter, Adam

    2014-05-01

    The semantic content of the NERC Vocabulary Server (NVS) has been developed over thirty years. It has been used to mark up metadata and data in a wide range of international projects, including the European Commission (EC) Framework Programme 7 projects SeaDataNet and The Open Service Network for Marine Environmental Data (NETMAR). Within the United States, the National Science Foundation projects Rolling Deck to Repository and Biological & Chemical Data Management Office (BCO-DMO) use concepts from NVS for markup. Further, typed relationships between NVS concepts and terms served by the Marine Metadata Interoperability Ontology Registry and Repository. The vast majority of the concepts publicly served from NVS (35% of ~82,000) form the British Oceanographic Data Centre (BODC) Parameter Usage Vocabulary (PUV). The PUV is instantiated on the NVS as a SKOS concept collection. These terms are used to describe the individual channels in data and metadata served by, for example, BODC, SeaDataNet and BCO-DMO. The PUV terms are designed to be very precise and may contain a high level of detail. Some users have reported that the PUV is difficult to navigate due to its size and complexity (a problem CSIRO have begun to address by deploying a SISSVoc interface to the NVS), and it has been difficult to aggregate data as multiple PUV terms can - with full validity - be used to describe the same data channels. Better approaches to data aggregation are required as a use case for the PUV from the EC European Marine Observation and Data Network (EMODnet) Chemistry project. One solution, proposed and demonstrated during the course of the NETMAR project, is to build new SKOS concept collections which formalise the desired aggregations for given applications, and uses typed relationships to state which PUV concepts contribute to a specific aggregation. Development of these new collections requires input from a group of experts in the application domain who can decide which PUV

  4. Semantic Web Services with Web Ontology Language (OWL-S) - Specification of Agent-Services for DARPA Agent Markup Language (DAML)

    Science.gov (United States)

    2006-08-01

    Sycara, and T. Nishimura, "Towards a Semantic Web Ecommerce ," in Proceedings of 6th Conference on Business Information Systems (BIS2003), Colorado...the ontology used is the fictitious ontology http://fly.com/Onto. The advantage of using concepts from Web-addressable ontologies, rather than XML...the advantage of the OWL-S approach compared with other approaches, namely BPEL4WS and WS-CDL, is that OWL-S allows the flexibility to change the

  5. Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies.

    Science.gov (United States)

    Graf, Michaela; Hecht, Karin; Reif, Susanne; Pelka-Fleischer, Renate; Pfister, Karin; Schmetzer, Helga

    2004-02-01

    Hemopoietic cytokines regulate hemopoietic cell functions via specific cell surface receptors. There is evidence to suggest, that those receptors (R) could play a role in leukemia with respect to cell differentiations and its regulation, prognosis, and pathobiology. Knowledge of individual cytokine receptor (CKR) profiles could provide new discoveries about CKR-supported therapeutic considerations. We have studied the expression of CKR on mononuclear bone marrow (BM) cells of 89 patients with acute myeloid leukemia (AML) at first diagnosis, three patients at relapse or with persisting AML and eight healthy probands by fluorescence-activated cell sorting (FACS) analysis using directly fluorescein-conjugated antibodies: CD114 (hG-CSF-R), CD116 (hGM-CSF-R), CD117 (hSCF-R), CD123 (hIL-3-R), CD130 (gp130subunit), CD135 (hFL-R). A case was defined as positive, if more than 20% of the cells expressed the regarding CKR. All investigated CKR were more frequently expressed in AML-samples than in healthy BM-samples, except CD130, which was only expressed on 5-6% of AML-blasts in all and with only one healthy BM-sample being CD130(+). Within the French-American-British (FAB) types we observed a maturation- and lineage (granulocytic/monocytic)-committed expression profile. Monocytic subtypes (FAB-type M4/M5) showed significantly more GM-CSF-R(+) (P = 0.001) and FL-R(+) (P = 0.001) and significantly less stem cell factor-R (SCF-R(+)) (P = 0.02) cases. Highest proportions of G-CSF-R(+) blasts were observed in FAB-type M3. In undifferentiated leukemias (FAB-type M1, M2) high amounts of SCF-R(+), IL-3-R(+), and FL-R(+) blasts could be detected. FL-R was the only CKR, which was positive in FAB-type M0 (n = 2). No differences in CKR-expression were detected between primary (p) and secondary (s). Separating our patient cohorts in cytogenetic risk groups we could detect a significant higher proportion of G-CSF-R(+) blasts in the cytogenetic good risk group than in the bad risk group (P

  6. Descriptive Analysis on the Impacts of Universal Zero-Markup Drug Policy on a Chinese Urban Tertiary Hospital.

    Directory of Open Access Journals (Sweden)

    Wei Tian

    Full Text Available Universal Zero-Markup Drug Policy (UZMDP mandates no price mark-ups on any drug dispensed by a healthcare institution, and covers the medicines not included in the China's National Essential Medicine System. Five tertiary hospitals in Beijing, China implemented UZMDP in 2012. Its impacts on these hospitals are unknown. We described the effects of UZMDP on a participating hospital, Jishuitan Hospital, Beijing, China (JST.This retrospective longitudinal study examined the hospital-level data of JST and city-level data of tertiary hospitals of Beijing, China (BJT 2009-2015. Rank-sum tests and join-point regression analyses were used to assess absolute changes and differences in trends, respectively.In absolute terms, after the UZDMP implementation, there were increased annual patient-visits and decreased ratios of medicine-to-healthcare-charges (RMOH in JST outpatient and inpatient services; however, in outpatient service, physician work-days decreased and physician-workload and inflation-adjusted per-visit healthcare charges increased, while the inpatient physician work-days increased and inpatient mortality-rate reduced. Interestingly, the decreasing trend in inpatient mortality-rate was neutralized after UZDMP implementation. Compared with BJT and under influence of UZDMP, JST outpatient and inpatient services both had increasing trends in annual patient-visits (annual percentage changes[APC] = 8.1% and 6.5%, respectively and decreasing trends in RMOH (APC = -4.3% and -5.4%, respectively, while JST outpatient services had increasing trend in inflation-adjusted per-visit healthcare charges (APC = 3.4% and JST inpatient service had decreasing trend in inflation-adjusted per-visit medicine-charges (APC = -5.2%.Implementation of UZMDP seems to increase annual patient-visits, reduce RMOH and have different impacts on outpatient and inpatient services in a Chinese urban tertiary hospital.

  7. Descriptive Analysis on the Impacts of Universal Zero-Markup Drug Policy on a Chinese Urban Tertiary Hospital.

    Science.gov (United States)

    Tian, Wei; Yuan, Jiangfan; Yang, Dong; Zhang, Lanjing

    2016-01-01

    Universal Zero-Markup Drug Policy (UZMDP) mandates no price mark-ups on any drug dispensed by a healthcare institution, and covers the medicines not included in the China's National Essential Medicine System. Five tertiary hospitals in Beijing, China implemented UZMDP in 2012. Its impacts on these hospitals are unknown. We described the effects of UZMDP on a participating hospital, Jishuitan Hospital, Beijing, China (JST). This retrospective longitudinal study examined the hospital-level data of JST and city-level data of tertiary hospitals of Beijing, China (BJT) 2009-2015. Rank-sum tests and join-point regression analyses were used to assess absolute changes and differences in trends, respectively. In absolute terms, after the UZDMP implementation, there were increased annual patient-visits and decreased ratios of medicine-to-healthcare-charges (RMOH) in JST outpatient and inpatient services; however, in outpatient service, physician work-days decreased and physician-workload and inflation-adjusted per-visit healthcare charges increased, while the inpatient physician work-days increased and inpatient mortality-rate reduced. Interestingly, the decreasing trend in inpatient mortality-rate was neutralized after UZDMP implementation. Compared with BJT and under influence of UZDMP, JST outpatient and inpatient services both had increasing trends in annual patient-visits (annual percentage changes[APC] = 8.1% and 6.5%, respectively) and decreasing trends in RMOH (APC = -4.3% and -5.4%, respectively), while JST outpatient services had increasing trend in inflation-adjusted per-visit healthcare charges (APC = 3.4%) and JST inpatient service had decreasing trend in inflation-adjusted per-visit medicine-charges (APC = -5.2%). Implementation of UZMDP seems to increase annual patient-visits, reduce RMOH and have different impacts on outpatient and inpatient services in a Chinese urban tertiary hospital.

  8. Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group.

    Science.gov (United States)

    Manara, E; Basso, G; Zampini, M; Buldini, B; Tregnago, C; Rondelli, R; Masetti, R; Bisio, V; Frison, M; Polato, K; Cazzaniga, G; Menna, G; Fagioli, F; Merli, P; Biondi, A; Pession, A; Locatelli, F; Pigazzi, M

    2017-01-01

    Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, <0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P<0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P<0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.

  9. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy☆

    Science.gov (United States)

    Alibhai, Shabbir M.H.; O’Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M.; Timilshina, Narhari; Tomlinson, George A.; Klepin, Heidi D.; Culos-Reed, S. Nicole

    2013-01-01

    Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. PMID:22726923

  10. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy.

    Science.gov (United States)

    Alibhai, Shabbir M H; O'Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M; Timilshina, Narhari; Tomlinson, George A; Klepin, Heidi D; Culos-Reed, S Nicole

    2012-10-01

    Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction

    DEFF Research Database (Denmark)

    Burnett, A. K.; Russell, N. H.; Hills, R. K.

    2015-01-01

    Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m(2) has shown benefit for some patient subgroups when compared with a dose of 45 mg/m(2), and has been...... = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at http://www.isrctn.com as #ISRCTN55675535....

  12. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia.

    Science.gov (United States)

    Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U

    2016-03-01

    DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

  13. Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML-BFM 2004.

    Science.gov (United States)

    Hassler, Angela; Bochennek, Konrad; Gilfert, Julia; Perner, Corinna; Schöning, Stefan; Creutzig, Ursula; Reinhardt, Dirk; Lehrnbecher, Thomas

    2016-06-01

    Children with acute myeloid leukemia (AML) and Down syndrome have high survival rates with intensity-reduced chemotherapeutic regimens, although the optimal balance between dose intensity and treatment toxicity has not been determined. We, therefore, characterized infectious complications in children with AML and Down syndrome treated according to AML-BFM 2004 study (ClinicalTrials.gov NCT00111345; amended 2006 for Down syndrome with reduced intensity). Data on infectious complications were gathered from the medical records in the hospital where the patient was treated. Infectious complications were categorized as fever without identifiable source (FUO), or as microbiologically or clinically documented infections. A total of 157 infections occurred in 61 patients (60.5% FUO, 9.6% and 29.9% clinically and microbiologically documented infections, respectively). Almost 90% of the pathogens isolated from the bloodstream were Gram-positive bacteria, and approximately half of them were viridans group streptococci. All seven microbiologically documented episodes of pneumonia were caused by viruses. Infection-related mortality was 4.9%, and all three patients died due to viral infection. Our data demonstrate that a reduced-intensity chemotherapeutic regimen in children with AML and Down syndrome is still associated with high morbidity. Although no patient died due to bacteria or fungi, viruses were responsible for all lethal events. Future studies, therefore, have to focus on the impact of viruses on morbidity and mortality of patients with AML and Down syndrome. © 2016 Wiley Periodicals, Inc.

  14. Acute myeloblastic leukemia with minimal myeloid differentiation (FAB AML-M0): a study of eleven cases.

    Science.gov (United States)

    Sempere, A; Jarque, I; Guinot, M; Palau, J; García, R; Sanz, G F; Gomis, F; Pérez-Sirvent, M L; Senent, L; Sanz, M A

    1993-12-01

    The main clinical, morphological, cytochemical, immunological features and therapy results of eleven patients diagnosed as acute myeloblastic leukemia M0 (AML-M0) are reported here. There were no clinical characteristics, abnormalities on physical examination or initial laboratory parameters that distinguished these eleven patients. Bone marrow aspirates were hypocellular in four patients. The leukemic cells were undifferentiated by light microscopy and myeloperoxidase (MPO) and/or Sudan Black B (SBB) stains were negative in all cases. Myeloid differentiation antigens were present on the leukemic cells of all eleven patients, whereas B and T cell markers were clearly negative except for CD4 and CD7 antigens. Whatever the treatment employed survival was very short. Eight of the eleven patients were treated and two achieved complete remission (CR) but only one of them is alive in continuous CR. Our results like those previously reported, suggest that AML-M0 patients have a very poor prognosis with standard induction therapies and should perhaps be considered for experimental therapeutic approaches.

  15. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT.

    Science.gov (United States)

    Sauer, T; Silling, G; Groth, C; Rosenow, F; Krug, U; Görlich, D; Evers, G; Albring, J; Besoke, R; Mesters, R M; Müller-Tidow, C; Kessler, T; Büchner, T; Berdel, W E; Stelljes, M

    2015-04-01

    Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.

  16. Geotourism and Sustainability: The Kızılcahamam – Çamlıdere Geopark Case

    Directory of Open Access Journals (Sweden)

    M. Sercan Gürsay

    2014-12-01

    Full Text Available Today, geotourism is one of the popular types of special interest tourism. On the other hand, poorly managed tourism can have some negative economic, environmental and socio-cultural impacts on destinations. Therefore, all types of tourism should be managed with a sustainable approach. The concept of sustainability, which had been first introduced in 1987, in the Report entitled “Our Common Future” as a fundamental of development, and has three dimensions of social, economic and environmental aspects. The purpose of this study is to evaluate sustainable tourism practices in Kızılcahamam - Çamlıdere Geopark. In this context, local stakeholders’ opinion on the importance of sustainable tourism in the management of the geopark area is determined. The qualitative method was used in this study. Data were collected through review of the related literature, observation and in-depth interviews. As a result of the study, physical and legal deficiencies in the protection and the management of the geopark area were identified. The lack of trained and qualified work force, sustainable financial resources, local participation, and education are the other major issues in terms of sustaining geotourismin Kızılcahamam - Çamlıdere Geopark. These deficiencies can be corrected under the UNESCO GGN (Global Geopark Network criteria.

  17. Dynamical Languages

    Science.gov (United States)

    Xie, Huimin

    The following sections are included: * Definition of Dynamical Languages * Distinct Excluded Blocks * Definition and Properties * L and L″ in Chomsky Hierarchy * A Natural Equivalence Relation * Symbolic Flows * Symbolic Flows and Dynamical Languages * Subshifts of Finite Type * Sofic Systems * Graphs and Dynamical Languages * Graphs and Shannon-Graphs * Transitive Languages * Topological Entropy

  18. A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML)

    Science.gov (United States)

    Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott

    2014-01-01

    Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

  19. Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E

    2013-01-01

    During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

  20. WaterML: an XML Language for Communicating Water Observations Data

    Science.gov (United States)

    Maidment, D. R.; Zaslavsky, I.; Valentine, D.

    2007-12-01

    One of the great impediments to the synthesis of water information is the plethora of formats used to publish such data. Each water agency uses its own approach. XML (eXtended Markup Languages) are generalizations of Hypertext Markup Language to communicate specific kinds of information via the internet. WaterML is an XML language for water observations data - streamflow, water quality, groundwater levels, climate, precipitation and aquatic biology data, recorded at fixed, point locations as a function of time. The Hydrologic Information System project of the Consortium of Universities for the Advancement of Hydrologic Science, Inc (CUAHSI) has defined WaterML and prepared a set of web service functions called WaterOneFLow that use WaterML to provide information about observation sites, the variables measured there and the values of those measurments. WaterML has been submitted to the Open GIS Consortium for harmonization with its standards for XML languages. Academic investigators at a number of testbed locations in the WATERS network are providing data in WaterML format using WaterOneFlow web services. The USGS and other federal agencies are also working with CUAHSI to similarly provide access to their data in WaterML through WaterOneFlow services.

  1. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Buchmann, I.

    2008-01-01

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90 Y, 188 Re and 131 I are the most frequently used β - -particles. Of these, 90 Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90 Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90 Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90 Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of

  2. OSI-211, a novel liposomal topoisomerase I inhibitor, is active in SCID mouse models of human AML and ALL.

    Science.gov (United States)

    Tomkinson, Blake; Bendele, Ray; Giles, Francis J; Brown, Eric; Gray, Atherton; Hart, Karen; LeRay, Jeremy D; Meyer, Denny; Pelanne, Michelle; Emerson, David L

    2003-11-01

    OSI-211 (liposomal lurtotecan), was evaluated using several different dose schedules (1mg/kg, d1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) in severe combined immunodeficient (SCID) mouse models of acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) with early treatment (ET, days 6-8) or late treatment (LT, days 15-19), examining early and advanced disease, respectively. Due to the aggressive nature of the Molt-4 model, the ET and LT were accelerated to day 3 or 4 and day 8 post-implant, respectively. For each model, 2 x 10(7) (KBM-3B) or 1 x 10(7) (Molt-4, HL-60 and CEM) leukemia cells were injected intravenously into the tail vein. Each control and test group consisted of eight animals. All three schedules (1mg/kg qd1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) increased the life span of OSI-211 treated animals in each model, with a tendency toward improved efficacy with the 6 mg/kg d1, 8 schedule. As a result, the activity of the 6 mg/kg d1, 8 schedule is detailed for each model. ET significantly (Pmodel with 86% long-term survivors (LTS). Using PRC analysis, human beta-globin gene sequences in one or several tissues were amplified in all but 3 LTS, suggesting minimal residual disease in 26 of the 29 LTS. LT also significantly (Pmodel, with an average ILS=196+/-11% and one LTS. Treatment of HL-60 leukemia animals significantly (Pmodel tested, significantly (Pmodel, ET resulted in a significantly (POSI-211, treatment with DaunoXome, the liposomal formulation of daunorubicin, a drug with clinical efficacy in AML and ALL, had no effect on survival in the KBM-3B, nor Molt-4 A4 leukemia models when administered at its maximum or near maximum tolerated doses of 3mg/kg d1, 8. These data demonstrate that OSI-211 has potent antileukemia activity in preclinical SCID mouse AML and ALL leukemia models, supporting the clinical investigation of OSI-211 for hematological malignancies.

  3. Gene expression profiling of acute myeloid leukemia samples from adult patients with AML-M1 and -M2 through boutique microarrays, real-time PCR and droplet digital PCR.

    Science.gov (United States)

    Handschuh, Luiza; Kaźmierczak, Maciej; Milewski, Marek C; Góralski, Michał; Łuczak, Magdalena; Wojtaszewska, Marzena; Uszczyńska-Ratajczak, Barbara; Lewandowski, Krzysztof; Komarnicki, Mieczysław; Figlerowicz, Marek

    2018-03-01

    Acute myeloid leukemia (AML) is the most common and severe form of acute leukemia diagnosed in adults. Owing to its heterogeneity, AML is divided into classes associated with different treatment outcomes and specific gene expression profiles. Based on previous studies on AML, in this study, we designed and generated an AML-array containing 900 oligonucleotide probes complementary to human genes implicated in hematopoietic cell differentiation and maturation, proliferation, apoptosis and leukemic transformation. The AML-array was used to hybridize 118 samples from 33 patients with AML of the M1 and M2 subtypes of the French-American‑British (FAB) classification and 15 healthy volunteers (HV). Rigorous analysis of the microarray data revealed that 83 genes were differentially expressed between the patients with AML and the HV, including genes not yet discussed in the context of AML pathogenesis. The most overexpressed genes in AML were STMN1, KITLG, CDK6, MCM5, KRAS, CEBPA, MYC, ANGPT1, SRGN, RPLP0, ENO1 and SET, whereas the most underexpressed genes were IFITM1, LTB, FCN1, BIRC3, LYZ, ADD3, S100A9, FCER1G, PTRPE, CD74 and TMSB4X. The overexpression of the CPA3 gene was specific for AML with mutated NPM1 and FLT3. Although the microarray-based method was insufficient to differentiate between any other AML subgroups, quantitative PCR approaches enabled us to identify 3 genes (ANXA3, S100A9 and WT1) whose expression can be used to discriminate between the 2 studied AML FAB subtypes. The expression levels of the ANXA3 and S100A9 genes were increased, whereas those of WT1 were decreased in the AML-M2 compared to the AML-M1 group. We also examined the association between the STMN1, CAT and ABL1 genes, and the FLT3 and NPM1 mutation status. FLT3+/NPM1- AML was associated with the highest expression of STMN1, and ABL1 was upregulated in FLT3+ AML and CAT in FLT3- AML, irrespectively of the NPM1 mutation status. Moreover, our results indicated that CAT and WT1

  4. Modelling language

    CERN Document Server

    Cardey, Sylviane

    2013-01-01

    In response to the need for reliable results from natural language processing, this book presents an original way of decomposing a language(s) in a microscopic manner by means of intra/inter‑language norms and divergences, going progressively from languages as systems to the linguistic, mathematical and computational models, which being based on a constructive approach are inherently traceable. Languages are described with their elements aggregating or repelling each other to form viable interrelated micro‑systems. The abstract model, which contrary to the current state of the art works in int

  5. Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3 inhibitor therapy with evolving actionable targets

    Directory of Open Access Journals (Sweden)

    Pashtoon M. Kasi

    2016-01-01

    Full Text Available For acute myeloid leukemia (AML, identification of activating mutations in the FMS-like tyrosine kinase-3 (FLT3 has led to the development of several FLT3-inhibitors. Here we present clinical and next generation sequencing data at the time of progression of a patient on a novel FLT3-inhibitor clinical trial (ASP2215 to show that employing therapeutic interventions with these novel targeted therapies can lead to consequences secondary to selective pressure and clonal evolution of cancer. We describe novel findings alongside data on treatment directed towards actionable aberrations acquired during the process. (Clinical Trial: NCT02014558; registered at: 〈https://clinicaltrials.gov/ct2/show/NCT02014558〉

  6. A case of AML with preceding hypoplastic stage after oophoro-hysterectomy and 60Co-irradiation

    International Nuclear Information System (INIS)

    Yoshida, Takashi; Nakamura, Shinobu; Hattori, Kenichi; Tanimoto, Kazuo.

    1975-01-01

    A case of AML (preceded by a hypoplastic stage) which developed after oophoro-hysterectomy and 60 Co-irradiation is presented, and related literature concerning irradiation-induced leukemia and the early diagnosis of leukemia and/or preleukemia are discussed. The patient, a 47 year old female had had surgery and irradiation with a subsequent normachromic anemia necessitating transfusions 11 years prior to her presenting herself at our hospital because of anemia. Her pancytopenic peripheral blood picture combined with a relatively hypererythroid marron led to a diagnosis of atypical hypoplastic anemia. Two years after this she suddenly developed a high fever, general fatigue and a severe anemia. Hematological studies revealed acute myeloblastic leukemia. A combination therapy consisting of DM, 6MP, prednisolon and blood transfusions was given with no effect and 3 months after the onset, the patient died of asphyxia resulting from gross hemoptysis. Autopsy revealed pulmonary hemorrhage secondary to the leukemia. (J. Evans)

  7. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML.

    Science.gov (United States)

    Swords, Ronan T; Coutre, Steven; Maris, Michael B; Zeidner, Joshua F; Foran, James M; Cruz, Jose; Erba, Harry P; Berdeja, Jesus G; Tam, Wayne; Vardhanabhuti, Saran; Pawlikowska-Dobler, Iwona; Faessel, Hélène M; Dash, Ajeeta B; Sedarati, Farhad; Dezube, Bruce J; Faller, Douglas V; Savona, Michael R

    2018-03-29

    Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We performed a phase 1b study of pevonedistat (PEV) with azacitidine (AZA) based on synergistic activity seen preclinically. Primary objectives included safety and tolerability, and secondary objectives included pharmacokinetics (PK) and disease response. Patients ≥60 years with treatment-naive AML (unfit for standard induction therapy) received PEV 20 or 30 mg/m 2 IV on days 1, 3, and 5 combined with fixed-dose AZA (75 mg/m 2 IV/subcutaneously) on days 1 to 5, 8, and 9, every 28 days. The most common treatment-emergent adverse events were constipation (48%), nausea (42%), fatigue (42%), and anemia (39%). In total, 11 deaths were observed and considered unrelated to study therapy by the investigators. Transient elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were dose limiting. The recommended phase 2 dose (RP2D) of PEV in this combination is 20 mg/m 2 PEV PK was not altered by the addition of AZA. Overall response rate (ORR) based on an intent-to-treat analysis was 50% (20 complete remissions [CRs], 5 complete remission with incomplete peripheral count recovery, 7 partial remissions [PRs]), with an 8.3-month median duration of remission. In patients receiving ≥6 cycles of therapy (n = 23, 44%), ORR was 83%. In patients with TP53 mutations, the composite CR/PR rate was 80% (4/5). Two of these patients stayed on study for >10 cycles. Baseline bone marrow blast percentage or cytogenetic/molecular risk did not influence ORR. This study was registered at www.clinicaltrials.gov as #NCT01814826. © 2018 by The American Society of Hematology.

  8. Identification of the Molecular Mechanisms Responsible for the Inhibition of Homing of AML Cells Triggered by CD44-Ligation

    KAUST Repository

    Al-Jifri, Ablah

    2011-08-03

    Acute Myeloid Leukemia (AML) is a cancerous disease that is defined by the inability to produce functional and mature blood cells, as well as the uncontrolled proliferation due to failure to undergo apoptosis of abnormal cells. The most common therapy for Leukemia, chemotherapy, has proven only to be partially efficient since it does not target the leukemic stem cells (LSCs) that have a high self-renewal and repopulation capacity and result in remission of the disease. Therefore targeting LSCs will provide more efficient therapy. One way to achieve this would be to inhibit their homing capability to the bone marrow. It has recently been shown that CD44, an adhesive molecule, plays a crucial role in cell trafficking and lodgement of both normal and leukemic stem cells. More importantly anti-CD44 monoclonal antibodies, along with its ability to induce differentiation of leukemic blasts, it inhibits specifically the homing capacity of LSCs to their micro-environmental niches. However, these molecular mechanisms that underlie the inhibition of homing have yet to be determined. To address these questions we conducted in vitro adhesion and blot-rolling assays to analyze the adherence and rolling capacity of these LSCs before and after treatment with anti-CD44 monoclonal antibody (mAb). Since glycosyltransferases play a crucial role in post translational carbohydrate decoration on adhesion molecules, we analyzed the expression (using quantitative PCR) of the different glycosyltransferases expressed in LSC\\'s before and after CD44 ligation (mAb treatment). Furthermore, we analyzed differentiation by flow cytometric analysis of treated and non-treated LSC\\'s. We anticipate that our results will set forth new insights into targeted therapies for AML.

  9. Transformation from refractory anemia with excess of blasts (RAEB) into acute myeloid leukemia (AML) obserbed in a heavily exposed atomic bomb survivor

    Energy Technology Data Exchange (ETDEWEB)

    Iwato, Koji; Kawano, Michio; Kimura, Akiro; Kuramoto, Atsushi; Tanaka, Kimio; Kamada, Nanao

    1987-01-01

    A heavily exposed atomic bomb survivor, 59-year-old man presented refractory anemia with excess of blasts (RAEB) terminating in acute myeloid leukemia (AML) 38 years after exposure. When he manifested AML, combination chemotherapy was started. But complete remission was not obtained even by B-DOMP regimen. Cytogenetic studies were performed, and their relation to the clinical course was analyzed. Peripheral blood T lymphocytes had 41.9 % non-clonal chromosomal abnormalities suggesting over 400 rad exposure. Bone marrow cells at RAEB exhibited a presence of mosaic clones of normal and abnormal chromosomal pattern, which supported the clinical diagnosis of RAEB and corresponded to the clinical features such as steady state and a low percentage of myeloblasts. At transformation into AML, clonal chromosomal abnormality was seen in bone marrow cells. It may explain a rapid increase of abnormal cells. This abnormal clone showed a little different karyotype seen at RAEB. But it was suspected to derive from a clone at RAEB, because of the same persistent chromosomal abnormalities. Then it aquired an additional chromosomal abnormalities at clinically drug-resistant phase of AML. In vivo selection assay of these leukemic cells revealed that transforming gene took part in this leukemogenesis. These data shown in this paper contribute to investigate a mechanism of leukemogenesis in atomic bomb survivors and establishment of new therapy.

  10. Detection of TET2, KRAS and CBL variants by Next Generation Sequencing and analysis of their correlation with JAK2 and FLT3 in childhood AML

    Directory of Open Access Journals (Sweden)

    Dilara Fatma Akin

    2016-04-01

    Conclusion: We found novel mutations for TET2, KRAS, and CBL. The detected variants in this article seem to be the first screening results of genes studied by NGS in childhood AML patients. Our results also showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations.

  11. Transformation from refractory anemia with excess of blasts (RAEB) into acute myeloid leukemia (AML) obserbed in a heavily exposed atomic bomb survivor

    International Nuclear Information System (INIS)

    Iwato, Koji; Kawano, Michio; Kimura, Akiro; Kuramoto, Atsushi; Tanaka, Kimio; Kamada, Nanao

    1987-01-01

    A heavily exposed atomic bomb survivor, 59-year-old man presented refractory anemia with excess of blasts (RAEB) terminating in acute myeloid leukemia (AML) 38 years after exposure. When he manifested AML, combination chemotherapy was started. But complete remission was not obtained even by B-DOMP regimen. Cytogenetic studies were performed, and their relation to the clinical course was analyzed. Peripheral blood T lymphocytes had 41.9 % non-clonal chromosomal abnormalities suggesting over 400 rad exposure. Bone marrow cells at RAEB exhibited a presence of mosaic clones of normal and abnormal chromosomal pattern, which supported the clinical diagnosis of RAEB and corresponded to the clinical features such as steady state and a low percentage of myeloblasts. At transformation into AML, clonal chromosomal abnormality was seen in bone marrow cells. It may explain a rapid increase of abnormal cells. This abnormal clone showed a little different karyotype seen at RAEB. But it was suspected to derive from a clone at RAEB, because of the same persistent chromosomal abnormalities. Then it aquired an additional chromosomal abnormalities at clinically drug-resistant phase of AML. In vivo selection assay of these leukemic cells revealed that transforming gene took part in this leukemogenesis. These data shown in this paper contribute to investigate a mechanism of leukemogenesis in atomic bomb survivors and establishment of new therapy. (author)

  12. The impact of center experience on results of reduced intensity:allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

    DEFF Research Database (Denmark)

    Giebel, S; Labopin, M; Mohty, M

    2013-01-01

    Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related...

  13. The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO

    Science.gov (United States)

    Chou, Fu-Sheng; Griesinger, Andrea; Wunderlich, Mark; Lin, Shan; Link, Kevin A.; Shrestha, Mahesh; Goyama, Susumu; Mizukawa, Benjamin; Shen, Shuhong; Marcucci, Guido

    2012-01-01

    AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL. PMID:22337712

  14. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more : results of a multicenter phase 3 study

    NARCIS (Netherlands)

    Lowenberg, Bob; Beck, Joachim; Graux, Carlos; van Putten, Wim; Schouten, Harry C.; Verdonck, Leo F.; Ferrant, Augustin; Sonneveld, Pieter; Jongen-Lavrencic, Mojca; von Lilienfeld-Toal, Marie; Biemond, Bart J.; Vellenga, Edo; Breems, Dimitri; de Muijnck, Hilde; Schaafsma, Ron; Verhoef, Gregor; Doehner, Hartmut; Gratwohl, Alois; Pabst, Thomas; Ossenkoppele, Gert J.; Maertens, Johan

    2010-01-01

    In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction

  15. XML: Ejemplos de uso (presentación)

    OpenAIRE

    Luján Mora, Sergio

    2011-01-01

    XML (eXtensible Markup Language, Lenguaje de marcas extensible) - Aplicación XML = Lenguaje de marcado = Vocabulario - Ejemplos: DocBook, Chemical Markup Language, Keyhole Markup Language, Mathematical Markup Language, Open Document, Open XML Format, Scalable Vector Graphics, Systems Byology Markup Language.

  16. XML: Ejemplos de uso

    OpenAIRE

    Luján Mora, Sergio

    2011-01-01

    XML (eXtensible Markup Language, Lenguaje de marcas extensible) - Aplicación XML = Lenguaje de marcado = Vocabulario - Ejemplos: DocBook, Chemical Markup Language, Keyhole Markup Language, Mathematical Markup Language, Open Document, Open XML Format, Scalable Vector Graphics, Systems Byology Markup Language.

  17. Endangered Languages.

    Science.gov (United States)

    Hale, Ken; And Others

    1992-01-01

    Endangered languages, or languages on the verge of becoming extinct, are discussed in relation to the larger process of loss of cultural and intellectual diversity. This article summarizes essays presented at the 1991 Linguistic Society of America symposium, "Endangered Languages and Their Preservation." (11 references) (LB)

  18. ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1-RUNX1T1 and associated with a better prognosis.

    Science.gov (United States)

    Yamato, Genki; Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Hara, Yusuke; Ohki, Kentaro; Okubo, Jun; Okuno, Haruna; Chiba, Kenichi; Tanaka, Hiroko; Kinoshita, Akitoshi; Moritake, Hiroshi; Kiyokawa, Nobutaka; Tomizawa, Daisuke; Park, Myoung-Ja; Sotomatsu, Manabu; Taga, Takashi; Adachi, Souichi; Tawa, Akio; Horibe, Keizo; Arakawa, Hirokazu; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

    2017-05-01

    ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event-free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild-type (5-year OS, 75% vs. 100% vs. 91% and 5-year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously. © 2017 Wiley Periodicals, Inc.

  19. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells.

    Science.gov (United States)

    Saenz, D T; Fiskus, W; Qian, Y; Manshouri, T; Rajapakshe, K; Raina, K; Coleman, K G; Crew, A P; Shen, A; Mill, C P; Sun, B; Qiu, P; Kadia, T M; Pemmaraju, N; DiNardo, C; Kim, M-S; Nowak, A J; Coarfa, C; Crews, C M; Verstovsek, S; Bhalla, K N

    2017-09-01

    The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.

  20. [Dexamethasone and vorinostat cooperatively promote differentiation and apoptosis in Kasumi-1 leukemia cells through ubiquitination and degradation of AML1-ETO].

    Science.gov (United States)

    Chen, Li-ping; Zhang, Jian-wei; Xu, Fa-mei; Xing, Hai-yan; Tian, Zheng; Wang, Min; Wang, Jian-xiang

    2013-09-01

    To probe the effects of dexamethasone (DEX) combined with histone deacetylase (HDAC) inhibitor vorinostat on inhibiting proliferation and inducing differentiation and apoptosis in Kasumi-1 leukemia cells, and its possible mechanisms in order to provide a theoretical basis for the treatment of AML1-ETO positive AML. The cell survival, differentiation and apoptosis rates were tested by MTT or flow cytometry analysis after Kasumi-1 cells were treated by DMSO, DEX (20 nmol/L), vorinostat (1 μmol/L) or DEX (20 nmol/L) in combination with vorinostat (1 μmol/L). WB and IP-WB were performed to detect AML1-ETO and its ubiquitination. Treatment with the combination of DEX and vorinostat for 48 h led to statistically significant differences of inhibited proliferation [(42.06±8.20)%], increased differentiation [(52.83±8.97)%] and apoptosis [(52.92±2.53)%] of Kasumi-1 cells when compared with vorinostat [(33.82±9.41)%, (43.93±9.04)% and (42.98±3.01)%, respectively], DEX [(17.30±3.49)%, (22.53±4.51)% and (19.57±2.17)%, respectively] or control [(6.96±0.39)%, (21.73±2.03)% and (6.96±0.39)%, respectively]. Also significant ubiquitination and decreased AML1-ETO protein in Kasumi-1 cells after the combination treatment over single agent or control were observed. The results indicated that DEX and vorinostat could synergistically inhibit the Kasumi-1 cells proliferation, induce Kasumi-1 cells differentiation and apoptosis through ubiquitination and degradation of AML1-ETO.

  1. DHX15 is associated with poor prognosis in acute myeloid leukemia (AML) and regulates cell apoptosis via the NF-kB signaling pathway.

    Science.gov (United States)

    Pan, Lili; Li, Yang; Zhang, Hai-Ying; Zheng, Yi; Liu, Xiao-Li; Hu, Zheng; Wang, Yi; Wang, Jing; Cai, Yuan-Hua; Liu, Qiao; Chen, Wan-Ling; Guo, Ying; Huang, Yuan-Mao; Qian, Feng; Jin, Li; Wang, Jiucun; Wang, Shao-Yuan

    2017-10-27

    The role of DHX15 , a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in DHX15 (NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally, DHX15 was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of DHX15 . DHX15 was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells. DHX15 was down-regulated when AML patients achieved disease remission or when leukemia cell lines were induced to differentiate. DHX15 silencing greatly inhibited leukemia cell proliferation and induced cell apoptosis and G1-phase arrest. In contrast, the restoration of DHX15 expression rescued cell viability and reduced cell apoptosis. In addition, we found that DHX15 was down-regulated when cell apoptosis was induced by ATO (arsenic trioxide); overexpression of DHX15 caused dramatic resistance to ATO-induced cell apoptosis, suggesting an important role for DHX15 in cell apoptosis. We further explored the mechanism of DHX15 in apoptosis and found that overexpression of DHX15 activated NF-kB transcription. Knockdown of DHX15 inhibited the nuclear translocation and activation of the NF-kB subunit P65 in leukemia cells. Several downstream targets of the NF-kB pathway were also down-regulated, and apoptosis-associated genes CASP3 and PARP were activated. In conclusion, this study represents the first demonstration that DHX15 plays an important role in leukemogenesis via the NF-kB signaling pathway and may serve as an independent prognostic marker for AML.

  2. The structure of an entry in the National corpus of Tuvan language

    Directory of Open Access Journals (Sweden)

    Mengi V. Ondar

    2016-12-01

    Full Text Available Contemporary information technologies and mathematical modelling has made creating corpora of natural languages significantly easier. A corpus is an information and reference system based on a collection of digitally processed texts. A corpus includes various written and oral texts in the given language, a set of dictionaries and markup – information on the properties of the text. It is the presence of the markup which distinguishes a corpus from an electronic library. At the moment, national corpora are being set up for many languages of the Russian Federation, including those of the Turkic peoples. Faculty members, postgraduate and undergraduate students at Tuvan State University and Siberian Federal University are working on the National corpus of Tuvan language. This article describes the structure of a dictionary entry in the National corpus of Tuvan language. The corpus database comprises the following tables: MAIN – the headword table, RUS, ENG, GER — translations of the headword into three languages, MORPHOLOGY — the table containing morphological data on the headword. The database is built in Microsoft Office Access. Working with the corpus dictionary includes the following functions: adding, editing and removing an entry, entry search (with transcription, setting and visualizing morphological features of a headword. The project allows us to view the corpus dictionary as a multi-structure entity with a complex hierarchical structure and a dictionary entry as its key component. The corpus dictionary we developed can be used for studying Tuvan language in its pronunciation, orthography and word analysis, as well as for searching for words and collocations in the texts included into the corpus.

  3. Language Acquisition and Language Revitalization

    Science.gov (United States)

    O'Grady, William; Hattori, Ryoko

    2016-01-01

    Intergenerational transmission, the ultimate goal of language revitalization efforts, can only be achieved by (re)establishing the conditions under which an imperiled language can be acquired by the community's children. This paper presents a tutorial survey of several key points relating to language acquisition and maintenance in children,…

  4. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)

    2008-06-15

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and

  5. [Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

    Science.gov (United States)

    Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian

    2015-06-01

    To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

  6. RIP Input Tables From WAPDEG for LA Design Selection: Repository Horizon Elevation - 2-Level AML 50% and Near Maximum

    International Nuclear Information System (INIS)

    B.E. Bullard

    1999-01-01

    The purpose of this calculation is to document the WAPDEG version 3.09 (CRWMS M and O 1998b). Software Routine Report for WAPDEG (Version 3.09) simulations used to analyze waste package degradation and failure under the repository exposure conditions characterized by a two-tier thermal loading repository design. Also documented is the post-processing of these results into tables of waste-package-degradation-time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) computer program. Specifically, the WAPDEG simulations discussed in this calculation correspond to waste package emplacement conditions (repository environment and design) as defined in the Total System Performance Assessment-Viability Assessment (CRWMS M and O 1998a). Total System Performance Assessment-Viability Assessment (TSPA-VA) Analyses Technical Basis Document--Chapter 5, Waste Package Degradation Modeling And Abstraction, pp. 5-27 to 5-29, with the exception that a two-tier thermal loading design feature as specified in the License Application Design Selection (LADS) study was analyzed. The particular design feature evaluated in this report is a modification of the repository horizon elevation and layout within the Topopah Springs Member of Yucca Mountain. Specifically, the modification consists of adding a second level, 50-m above the base case repository layout. Two options were considered, representing two variations in thermal loading. In Design Feature 25e (designated DF25e), each level has an Areal Mass Loading (AML) of 42.5 MTU/acre (i.e., half the VA base case). In Design Feature 25f (designated DF25), each level has an AML of 64MTU/acre. As a result of the change in waste package placement relative to the TSPA-VA base-case design, different temperature and relative humidity time histories at the waste package surface are calculated (input to the WAPDEG simulations), and consequently

  7. Faruk Nafiz Çamlıbel’in Suda Halkalar Adlı Eserinde Su İmajları ve Benzetmeler Water Images and Metaphors in Suda Halkalar Which Faruk Nafiz Çamlıbel’s Work

    Directory of Open Access Journals (Sweden)

    Hüseyin DOĞRAMACIOĞLU

    2012-09-01

    Full Text Available Suda Halkalar (Circles in Water which the poetry book of Faruk Nafiz Çamlıbel, has not been translated into the Latin alphabet to the present day. The images of the water and metaphors which used in this work brought new connotations and approaches to the Turkish poetry. The images of the water in the poetry book are used instead of the poet's soul and dreams sometimes. These images are thought with poet’s darling and sometimes are used as a background. The poetformed the images of the water in his poem sadly. There are the poetand his darling in these tables. The images of the water and thedreams of the poet form the background of the poem. The backgroundsin this poem are repeated as a leitmotiv. Visuality and individualitybecomes important feature in these tables created by the poet. Themetaphors in the work created differently from classical Turkish poetry.These metaphors brought a new meaning to the poem. The poem basedon the intellectual grounds via metaphors. This can be considered asone of the significant achievements of Turkish poetry. We can see thatthe past remembered and desired both in poetry and metaphors bypessimistic feeling. In this respect the past affects the poet's dreamscombining with a sense of mourning, water images and metaphors inpoetry. The metaphors can be grouped as imaginary, visual andstrongly poetic ground. The feelings of pessimism and sadness arepredominant in these metaphors. The images and metaphors used bythe poet can be considered as an improvement for Turkish poetry. It isthe first research done on Suda Halkalar (Circles in Water will help tobetter understand and identify Çamlıbel’s aspect of poetry and literaryline. Faruk Nafiz Çamlıbel’in Suda Halkalar adlı şiir kitabı günümüze kadar Latin harflerine aktarılmamıştır. Bu eserde kullanılan su imajları ve benzetmeler Türk şiirine yeni yaklaşımlar ve çağrışımlar getirmiştir. Eserdeki su imajları bazen şairin ruhu ve hayalleri

  8. Specialized languages

    DEFF Research Database (Denmark)

    Mousten, Birthe; Laursen, Anne Lise

    2016-01-01

    Across different fields of research, one feature is often overlooked: the use of language for specialized purposes (LSP) as a cross-discipline. Mastering cross-disciplinarity is the precondition for communicating detailed results within any field. Researchers in specialized languages work cross...... science fields communicate their findings. With this article, we want to create awareness of the work in this special area of language studies and of the inherent cross-disciplinarity that makes LSP special compared to common-core language. An acknowledgement of the importance of this field both in terms...... of more empirical studies and in terms of a greater application of the results would give language specialists in trade and industry a solid and updated basis for communication and language use....

  9. Fuzzy Languages

    Science.gov (United States)

    Rahonis, George

    The theory of fuzzy recognizable languages over bounded distributive lattices is presented as a paradigm of recognizable formal power series. Due to the idempotency properties of bounded distributive lattices, the equality of fuzzy recognizable languages is decidable, the determinization of multi-valued automata is effective, and a pumping lemma exists. Fuzzy recognizable languages over finite and infinite words are expressively equivalent to sentences of the multi-valued monadic second-order logic. Fuzzy recognizability over bounded ℓ-monoids and residuated lattices is briefly reported. The chapter concludes with two applications of fuzzy recognizable languages to real world problems in medicine.

  10. Language Policy

    DEFF Research Database (Denmark)

    Lauridsen, Karen M.

    2008-01-01

    Like any other text, instructive texts function within a given cultural and situational setting and may only be available in one language. However, the end users may not be familiar with that language and therefore unable to read and understand the instructions. This article therefore argues...... that instructive texts should always be available in a language that is understood by the end users, and that a corporate communication policy which includes a language policy should ensure that this is in fact the case for all instructive texts....

  11. Çamlıbel - Ulubey (Uşak) Beyaz Mermerinin Jeolojik ve Fiziko-Mekanik Özelliklerinin Araştırılması

    OpenAIRE

    ÇELİK, Mustafa Yavuz; KIRILIVEREN, Sabri

    2012-01-01

    Menderes Masifinde yer alan Uşak bölgesi önemli bir mermer potansiyeline sahiptir. Bölgede Karahallı, Sivaslı ve Ulubey ilçeleri civarında mermer blok üretimi yapılmaktadır. Bu makalede, Çamlıbel-Ulubey (Uşak) beyaz mermerinin, mermer olarak kullanılabilirliği irdelenmiş ve yöre mermerleriyle karşılaştırılmaları yapılmıştır. Çamlıbel-Ulubey (Uşak) beyaz mermerinin özelliklerini belirlemek amacıyla yapılan deneylerde özgül kütle 2,73 g/cm3, kütlece su emme oranı % 0,06, doluluk oranı % 99,3, b...

  12. A multiscale framework based on the physiome markup languages for exploring the initiation of osteoarthritis at the bone-cartilage interface.

    Science.gov (United States)

    Shim, Vickie B; Hunter, Peter J; Pivonka, Peter; Fernandez, Justin W

    2011-12-01

    The initiation of osteoarthritis (OA) has been linked to the onset and progression of pathologic mechanisms at the cartilage-bone interface. Most importantly, this degenerative disease involves cross-talk between the cartilage and subchondral bone environments, so an informative model should contain the complete complex. In order to evaluate this process, we have developed a multiscale model using the open-source ontologies developed for the Physiome Project with cartilage and bone descriptions at the cellular, micro, and macro levels. In this way, we can effectively model the influence of whole body loadings at the macro level and the influence of bone organization and architecture at the micro level, and have cell level processes that determine bone and cartilage remodeling. Cell information is then passed up the spatial scales to modify micro architecture and provide a macro spatial characterization of cartilage inflammation. We evaluate the framework by linking a common knee injury (anterior cruciate ligament deficiency) to proinflammatory mediators as a possible pathway to initiate OA. This framework provides a "virtual bone-cartilage" tool for evaluating hypotheses, treatment effects, and disease onset to inform and strengthen clinical studies.

  13. Mark-up bancário, conflito distributivo e utilização da capacidade produtiva: uma macrodinâmica pós-keynesiana

    Directory of Open Access Journals (Sweden)

    Lima Gilberto Tadeu

    2003-01-01

    Full Text Available Elabora-se um modelo macrodinâmico pós-keynesiano de utilização da capacidade, distribuição e inflação por conflito, no qual a oferta de moeda de crédito é endógena. A taxa nominal de juros é determinada pela aplicação de um mark-up sobre a taxa básica fixada pela autoridade monetária. Ao longo do tempo, o mark-up bancário varia com a taxa de lucro sobre o capital físico, enquanto a taxa básica varia com excessos de demanda que não são acomodáveis pela utilização da capacidade. São analisados os casos em que a demanda é suficiente ou não para gerar a plena utilização da capacidade.

  14. Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods.

    Science.gov (United States)

    Kremser, Andreas; Dressig, Julia; Grabrucker, Christine; Liepert, Anja; Kroell, Tanja; Scholl, Nina; Schmid, Christoph; Tischer, Johanna; Kufner, Stefanie; Salih, Helmut; Kolb, Hans Jochem; Schmetzer, Helga

    2010-01-01

    Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

  15. Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine.

    Science.gov (United States)

    Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette

    2018-05-02

    Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

    Directory of Open Access Journals (Sweden)

    Lisa Pleyer

    2017-02-01

    Full Text Available We recently published a clinically-meaningful improvement in median overall survival (OS for patients with acute myeloid leukaemia (AML, >30% bone marrow (BM blasts and white blood cell (WBC count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010. As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012 and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214 with AAR patients meeting the same inclusion criteria (“AAR (001-like” cohort; n = 95. The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616 for “AML-001” versus “AAR (001-like” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309 and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6 months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95 versus all AAR patients with World Health Organization (WHO-defined AML (

  17. Consecutive epigenetically-active agent combinations act in ID1-RUNX3-TET2 and HOXA pathways for Flt3ITD+ve AML.

    Science.gov (United States)

    Sayar, Hamid; Liu, Yan; Gao, Rui; Zaid, Mohammad Abu; Cripe, Larry D; Weisenbach, Jill; Sargent, Katie J; Nassiri, Mehdi; Li, Lang; Konig, Heiko; Suvannasankha, Attaya; Pan, Feng; Shanmugam, Rajasubramaniam; Goswami, Chirayu; Kapur, Reuben; Xu, Mingjiang; Boswell, H Scott

    2018-01-19

    Co-occurrence of Flt3ITD and TET2 mutations provoke an animal model of AML by epigenetic repression of Wnt pathway antagonists, including RUNX3, and by hyperexpression of ID1, encoding Wnt agonist. These affect HOXA over-expression and treatment resistance. A comparable epigenetic phenotype was identified among adult AML patients needing novel intervention. We chose combinations of targeted agents acting on distinct effectors, at the levels of both signal transduction and chromatin remodeling, in relapsed/refractory AML's, including Flt3ITD+ve, described with a signature of repressed tumor suppressor genes, involving Wnt antagonist RUNX3 , occurring along with ID1 and HOXA over-expressions. We tracked patient response to combination of Flt3/Raf inhibitor, Sorafenib, and Vorinostat, pan-histone deacetylase inhibitor, without or with added Bortezomib, in consecutive phase I trials. A striking association of rapid objective remissions (near-complete, complete responses) was noted to accompany induced early pharmacodynamic changes within patient blasts in situ, involving these effectors, significantly linking RUNX3 /Wnt antagonist de-repression (80%) and ID1 downregulation (85%), to a response, also preceded by profound HOXA9 repression. Response occurred in context of concurrent TET2 mutation/hypomorphy and Flt3ITD+ve mutation (83% of complete responses). Addition of Bortezomib to the combination was vital to attainment of complete response in Flt3ITD+ve cases exhibiting such Wnt pathway dysregulation.

  18. Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

    Science.gov (United States)

    Locatelli, F; Masetti, R; Rondelli, R; Zecca, M; Fagioli, F; Rovelli, A; Messina, C; Lanino, E; Bertaina, A; Favre, C; Giorgiani, G; Ripaldi, M; Ziino, O; Palumbo, G; Pillon, M; Pession, A; Rutella, S; Prete, A

    2015-02-01

    We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.

  19. Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Münster AML-study group

    Science.gov (United States)

    Coenen, Eva A.; Zwaan, C. Michel; Reinhardt, Dirk; Harrison, Christine J.; Haas, Oskar A.; de Haas, Valerie; Mihál, Vladimir; De Moerloose, Barbara; Jeison, Marta; Rubnitz, Jeffrey E.; Tomizawa, Daisuke; Johnston, Donna; Alonzo, Todd A.; Hasle, Henrik; Auvrignon, Anne; Dworzak, Michael; Pession, Andrea; van der Velden, Vincent H. J.; Swansbury, John; Wong, Kit-fai; Terui, Kiminori; Savasan, Sureyya; Winstanley, Mark; Vaitkeviciene, Goda; Zimmermann, Martin; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2013-01-01

    In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases. PMID:23974201

  20. CD4(+)and CD8(+)T-cell reactions against leukemia-associated- or minor-histocompatibility-antigens in AML-patients after allogeneic SCT.

    Science.gov (United States)

    Steger, Brigitte; Milosevic, Slavoljub; Doessinger, Georg; Reuther, Susanne; Liepert, Anja; Braeu, Marion; Schick, Julia; Vogt, Valentin; Schuster, Friedhelm; Kroell, Tanja; Busch, Dirk H; Borkhardt, Arndt; Kolb, Hans-Jochem; Tischer, Johanna; Buhmann, Raymund; Schmetzer, Helga

    2014-04-01

    T-cells play an important role in the remission-maintenance in AML-patients (pts) after SCT, however the role of LAA- (WT1, PR1, PRAME) or minor-histocompatibility (mHag, HA1) antigen-specific CD4(+) and CD8(+)T-cells is not defined. A LAA/HA1-peptide/protein stimulation, cloning and monitoring strategy for specific CD8(+)/CD4(+)T-cells in AML-pts after SCT is given. Our results show that (1) LAA-peptide-specific CD8+T-cells are detectable in every AML-pt after SCT. CD8(+)T-cells, recognizing two different antigens detectable in 5 of 7 cases correlate with long-lasting remissions. Clonal TCR-Vβ-restriction exemplarily proven by spectratyping in PRAME-specific CD8(+)T-cells; high PRAME-peptide-reactivity was CD4(+)-associated, as shown by IFN-γ-release. (2) Two types of antigen-presenting cells (APCs) were tested for presentation of LAA/HA1-proteins to CD4(+)T-cells: miniEBV-transduced lymphoblastoid cells (B-cell-source) and CD4-depleted MNC (source for B-cell/monocyte/DC). We provide a refined cloning-system for proliferating, CD40L(+)CD4(+)T-cells after LAA/HA1-stimulation. CD4(+)T-cells produced cytokines (GM-CSF, IFN-γ) upon exposure to LAA/HA1-stimulation until after at least 7 restimulations and demonstrated cytotoxic activity against naive blasts, but not fibroblasts. Antileukemic activity of unstimulated, stimulated or cloned CD4(+)T-cells correlated with defined T-cell-subtypes and the clinical course of the disease. In conclusion we provide immunological tools to enrich and monitor LAA/HA1-CD4(+)- and CD8(+)T-cells in AML-pts after SCT and generate data with relevant prognostic value. We were able to demonstrate the presence of LAA-peptide-specific CD8(+)T-cell clones in AML-pts after SCT. In addition, we were also able to enrich specific antileukemic reactive CD4(+)T-cells without GvH-reactivity upon repeated LAA/HA1-protein stimulation and limiting dilution cloning. Copyright © 2013 Elsevier GmbH. All rights reserved.

  1. Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Hanumantha Rao Madala

    2018-02-01

    Full Text Available Isocitrate dehydrogenases 1 and 2 (IDH1,2, the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs and gain an unusual new activity of reducing the α-ketoglutarate (α-KG to D-2 hydroxyglutarate (D-2HG in a NADPH-consuming reaction. The oncometabolite D-2HG, which accumulates >35 mM, is widely accepted to drive a progressive oncogenesis besides exacerbating the already increased oxidative stress in these cancers. More importantly, D-2HG competes with α-KG and inhibits a large number of α-KG-dependent dioxygenases such as TET (Ten-eleven translocation, JmjC domain-containing KDMs (histone lysine demethylases, and the ALKBH DNA repair proteins that ultimately lead to hypermethylation of the CpG islands in the genome. The resulting CpG Island Methylator Phenotype (CIMP accounts for major gene expression changes including the silencing of the MGMT (O6-methylguanine DNA methyltransferase repair protein in gliomas. Glioma patients with IDH1 mutations also show better therapeutic responses and longer survival, the reasons for which are yet unclear. There has been a great surge in drug discovery for curtailing the mutant IDH activities, and arresting tumor proliferation; however, given the unique and chronic metabolic effects of D-2HG, the promise of these compounds for glioma treatment is uncertain. This comprehensive review discusses the biology, current drug design and opportunities for improved therapies through exploitable synthetic lethality pathways, and an intriguing oncometabolite-inspired strategy for primary glioblastoma.

  2. Building Languages

    Science.gov (United States)

    ... Glossary Contact Information Information For… Media Policy Makers Building Languages Recommend on Facebook Tweet Share Compartir Communicating ... any speech and only very loud sounds. Close × “Building Blocks” “Building Blocks” refers to the different skills ...

  3. ScienceCentral: open access full-text archive of scientific journals based on Journal Article Tag Suite regardless of their languages.

    Science.gov (United States)

    Huh, Sun

    2013-01-01

    ScienceCentral, a free or open access, full-text archive of scientific journal literature at the Korean Federation of Science and Technology Societies, was under test in September 2013. Since it is a Journal Article Tag Suite-based full text database, extensible markup language files of all languages can be presented, according to Unicode Transformation Format 8-bit encoding. It is comparable to PubMed Central: however, there are two distinct differences. First, its scope comprises all science fields; second, it accepts all language journals. Launching ScienceCentral is the first step for free access or open access academic scientific journals of all languages to leap to the world, including scientific journals from Croatia.

  4. Report of a Phase II Study of Clofarabine and Cytarabine in De Novo and Relapsed and Refractory AML Patients and in Selected Elderly Patients at High Risk for Anthracycline Toxicity

    Science.gov (United States)

    Cooper, Barry; Holmes, Houston; Vance, Estil; Berryman, Robert Brian; Maisel, Christopher; Li, Sandy; Saracino, Giovanna; Tadic-Ovcina, Mirjana; Fay, Joseph

    2011-01-01

    Purpose. To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and in elderly patients with untreated AML and heart disease. Patients and Methods. Patients with relapsed/refractory AML and older patients for whom there was a concern over toxicity from additional anthracyclines received 5 days of clofarabine, 40 mg/m2 per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m2 per day i.v. over 2 hours. Results. Thirty patients were enrolled. The median age was 67 years (range, 38–82 years) and 18 (60%) had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for anthracycline toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, including a CR in 14 patients (47%). Responses were observed in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median disease-free survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation. Conclusions. Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML. PMID:21273514

  5. NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML.

    Science.gov (United States)

    Chretien, Anne-Sophie; Devillier, Raynier; Fauriat, Cyril; Orlanducci, Florence; Harbi, Samia; Le Roy, Aude; Rey, Jérôme; Bouvier Borg, Gaelle; Gautherot, Emmanuel; Hamel, Jean-François; Ifrah, Norbert; Lacombe, Catherine; Cornillet-Lefebvre, Pascale; Delaunay, Jacques; Toubert, Antoine; Arnoulet, Christine; Vey, Norbert; Blaise, Didier; Olive, Daniel

    2017-01-01

    NKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT). NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46 high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46 low phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46 high phenotype ( p = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression ( p = 0.303). In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness.

  6. Complementary Languages

    DEFF Research Database (Denmark)

    Preisler, Bent

    2009-01-01

    society is everywhere unproblematic. A case in point is Higher Education. I will also argue that the recently proposed solution to ‘domain loss' - Danish and English used ‘in parallel', ‘parallel languages' - because it is unrealistic as well as undesirable as a consistent principle - should be replaced......The Danish language debate is dominated by two key concepts: ‘domain loss' and its opposite, ‘parallel languages' (parallelsproglighed). The under­stood reference is to the relationship between Danish and English - i.e. the spread of English at the expense of Danish vs. the coexistence of Danish...... and English within relevant ‘domains' of Danish society. In this article I am going to argue that the concept of ‘domain loss' is not theoretically tenable - its usual depiction ranging from the vague to the nonsensical - which is not to say that the relationship between English and Danish within Danish...

  7. Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study

    Directory of Open Access Journals (Sweden)

    Ezz-Eldin Azza M

    2008-10-01

    Full Text Available Abstract Objectives We have analyzed t(12;21(p13:q22 in an attempt to evaluate the frequency and prognostic significance of TEL-AML1 fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH. Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD. Methods All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH for t(12;21 in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD. We determined the prognostic significance of TEL-AML1 fusion represented by disease course and survival. Results TEL-AML1 fusion gene was positive in (37.5% in newly diagnosed patients. There was a significant correlation between TEL-AML1 fusion gene both at diagnosis (r = 0.5, P = 0.003 and as a MRD (r = 0.4, P = 0.01 with favorable course. Kaplan-Meier curve for the presence of TEL-AML1 fusion at the diagnosis was associated with a better probability of overall survival (OS; mean survival time was 47 ± 1 month, in contrast to 28 ± 5 month in its absence (P = 0.006. Also, the persistence at TEL-AML1 fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 ± 2 months in the presence of MRD and it was 40 ± 1 months in its absence. So, persistence of TEL-AML1 fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS. Conclusion For most patients, the presence of TEL-AML1 fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of TEL-AML1 fusion as MRD has no additive prognostic value.

  8. Simplexity, languages and human languaging

    DEFF Research Database (Denmark)

    Cowley, Stephen; Gahrn-Andersen, Rasmus

    2018-01-01

    Building on a distributed perspective, the Special Issue develops Alain Berthoz's concept of simplexity. By so doing, neurophysiology is used to reach beyond observable and, specifically, 1st-order languaging. While simplexity clarifies how language uses perception/action, a community's ‘lexicon......’ (a linguistic 2nd order) also shapes human powers. People use global constraints to make and construe wordings and bring a social/individual duality to human living. Within a field of perception-action-language, the phenomenology of ‘words’ and ‘things’ drives people to sustain their own experience....... Simplex tricks used in building bodies co-function with action that grants humans access to en-natured culture where, together, they build human knowing....

  9. Local language

    NARCIS (Netherlands)

    Monique Turkenburg

    2002-01-01

    Original title: Taal lokaal. Children of immigrants living in the Netherlands have for years had the opportunity to receive lessons in their mother tongue at primary school. Since 1998 this has been referred to as minority language teaching (OALT in Dutch), and has been the responsibility

  10. Body Language.

    Science.gov (United States)

    Pollard, David E.

    1993-01-01

    Discusses how the use of body language in Chinese fiction strikes most Westerners as unusual, if not strange. Considers that, although this may be the result of differences in gestures or different conventions in fiction, it is a problem for translators, who handle the differences by various strategies, e.g., omission or expansion. (NKA)

  11. Language Pathology.

    Science.gov (United States)

    Fletcher, Paul

    1989-01-01

    Discusses the role of linguistics in the investigation of language disorders, focusing on the application of phonetics, descriptive grammatic frameworks, grammatical theory, and concepts from semantics and pragmatics to a variety of disorders and their remediation. Some trends and examples from the field of clinical linguistics are discussed. (GLR)

  12. EVALUATION OF SEMANTIC SIMILARITY FOR SENTENCES IN NATURAL LANGUAGE BY MATHEMATICAL STATISTICS METHODS

    Directory of Open Access Journals (Sweden)

    A. E. Pismak

    2016-03-01

    Full Text Available Subject of Research. The paper is focused on Wiktionary articles structural organization in the aspect of its usage as the base for semantic network. Wiktionary community references, article templates and articles markup features are analyzed. The problem of numerical estimation for semantic similarity of structural elements in Wiktionary articles is considered. Analysis of existing software for semantic similarity estimation of such elements is carried out; algorithms of their functioning are studied; their advantages and disadvantages are shown. Methods. Mathematical statistics methods were used to analyze Wiktionary articles markup features. The method of semantic similarity computing based on statistics data for compared structural elements was proposed.Main Results. We have concluded that there is no possibility for direct use of Wiktionary articles as the source for semantic network. We have proposed to find hidden similarity between article elements, and for that purpose we have developed the algorithm for calculation of confidence coefficients proving that each pair of sentences is semantically near. The research of quantitative and qualitative characteristics for the developed algorithm has shown its major performance advantage over the other existing solutions in the presence of insignificantly higher error rate. Practical Relevance. The resulting algorithm may be useful in developing tools for automatic Wiktionary articles parsing. The developed method could be used in computing of semantic similarity for short text fragments in natural language in case of algorithm performance requirements are higher than its accuracy specifications.

  13. Importance of No. 21 chromosome in translocation t(8:21) in acute myelocytic leukemia (AML) to the genesis of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, T; Minamihisamatsu, M

    1986-05-01

    The results are reported of the chromosome analysis of 17 cases of acute myelocytic leukemia (AML), mostly belonging to M2 of the FAB classification, especially on the translocation t(8:21) and its variant translocations. The presence of two cases with simple variant translocation not involving No. 8 chromosome seems to suggest that No. 21 chromosome is more important to the genesis of AML than the No. 8 chromosome. This assumption appears to be supported by findings on cases with complex translocation: In two cases with complex translocation, the portion translocated from No. 21 chromosome onto No. 8 was firmly maintained in the specific site (q21) on No. 8 whereas the portion translocated from No. 8 chromosome onto No. 21 was involved in further translocation with another chromosome, onto which it was re-translocated. The results of the present cytogenetic study indicate that the analysis of variant translocations in various specific chromosome translocations in leukemia and other malignant disorders is very useful to elucidate the problem as to whether the genesis of such disorders lies in either one or both of the pair of chromosomes involved in the specific translocations of the respective diseases.

  14. Early clearance of peripheral blasts measured by flow cytometry during the first week of AML induction therapy as a new independent prognostic factor: a GOELAMS study.

    Science.gov (United States)

    Lacombe, F; Arnoulet, C; Maynadié, M; Lippert, E; Luquet, I; Pigneux, A; Vey, N; Casasnovas, O; Witz, F; Béné, M C

    2009-02-01

    An early appreciation of treatment efficacy could be very useful in acute myeloblastic leukemia (AML), and a prognostic value has been suggested for the morphological assessment of decrease in blasts during induction therapy. More sensitive, multiparametric flow cytometry (FCM) can detect far lower blast counts, allowing for a precise and reliable calculation of blast cell decrease rate (BDR). Such a multiparametric FCM four-colours/single-tube protocol, combining CD11b, CD45-ECD and CD16-PC5, was applied to peripheral blood samples from 130 AML patients, collected daily during induction chemotherapy. Normalized blast cell percentages were used to calculate the relevant decrease slopes. Slope thresholds (-15), or the time required to reach 90% depletion of the peripheral blast load (5 days), was strongly associated with the achievement of complete remission (P<0.0001). Log-rank test and Cox model showed that they also carried high statistical significance (P<0.0001) for disease-free survival. The prognostic value of cytogenetic features, confirmed in this series, was refined by BDR, which allowed to discriminate between good- and poor-risk patients among those with intermediate or normal karyotypes. This simple FCM protocol allows for an accurate prognostic sequential approach adapted to the determination of decrease in peripheral blast cells during induction chemotherapy.

  15. Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML.

    Science.gov (United States)

    Zampini, Matteo; Tregnago, Claudia; Bisio, Valeria; Simula, Luca; Borella, Giulia; Manara, Elena; Zanon, Carlo; Zonta, Francesca; Serafin, Valentina; Accordi, Benedetta; Campello, Silvia; Buldini, Barbara; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe; Pigazzi, Martina

    2018-02-02

    The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.

  16. In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available?

    DEFF Research Database (Denmark)

    Peffault de Latour, R; Labopin, M; Cornelissen, J

    2015-01-01

    Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still...... unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010). The 3-year cumulative incidences (CIs) of non......-relapse mortality were 17% and 23% with MSD and MUD, respectively (P=0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P=0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P=0.51). The 3-year overall survival was 49% with both MSD and MUD. In conclusion, HLA...

  17. Normal karyotype mosaicism in adult AML patients with adverse-risk and undefined karyotype: preliminary report of treatment outcomes after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Yoon, Jae-Ho; Kim, Hee-Je; Shin, Seung-Hwan; Yahng, Seung-Ah; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won

    2013-06-01

    Karyotype analysis in acute myeloid leukemia (AML) is one of the powerful prognostic factors for complete remission (CR), relapse, and overall survival (OS). Cytogenetic mosaicism is considered to be one of the important characteristics in expression of phenotypic manifestations. However, it has not come into focus due to emerging molecular biological approaches and the results of a number of mutation studies. Clinical correlates and prognostic relevance of mosaicism were evaluated in 163 AML patients [adverse-risk karyotypes (n = 72) and undefined karyotypes (n = 91)]. All patients were treated by induction and consolidation chemotherapies and finally went on hematopoietic stem cell transplantations (HSCT). Patients were divided into two subgroups, either with or without normal karyotype (NK) mosaicism. Seventy patients exhibited NK mosaicism and 93 did not. There were no significant differences in age, gender, chemotherapy cycles to achieve CR, HSCT donor type, source or intensity properties between the two subgroups. We found that NK mosaicism remaining in adverse-risk and undefined karyotype at diagnosis significantly correlates with better OS (p = 0.001) and lower CIR (p = 0.021) rate after HSCT. Our data show that the poor prognostic properties of unfavorable risk karyotype can be overcome to a great extent by allogeneic HSCT and chronic GVHD, especially in the subgroup with NK mosaicism. Cytogenetic mosaicism at initial diagnosis can be an influential factor for survival outcomes, even after HSCT.

  18. Spatial Language Learning

    Science.gov (United States)

    Fu, Zhengling

    2016-01-01

    Spatial language constitutes part of the basic fabric of language. Although languages may have the same number of terms to cover a set of spatial relations, they do not always do so in the same way. Spatial languages differ across languages quite radically, thus providing a real semantic challenge for second language learners. The essay first…

  19. Language and the Law.

    Science.gov (United States)

    Gibbons, John

    1999-01-01

    Discusses the language of law and its general interest to the field of applied linguistics. Specific focus is on legal language, the problems and remedies of legal communication (e.g., language and disadvantage before the law, improving legal communication) the legislation of language (e.g., language rights, language crimes), and forensic…

  20. Language learning interventions | Kilfoil | Journal for Language ...

    African Journals Online (AJOL)

    The results for that intervention show that the hypothesis was correct and students need more time and structure if they are to improve their language competence sufficiently. Keywords: language learning interventions, English for specific purposes, language competence, fossilization. Journal for Language Teaching Vol.

  1. Language sampling

    DEFF Research Database (Denmark)

    Rijkhoff, Jan; Bakker, Dik

    1998-01-01

    This article has two aims: [1] to present a revised version of the sampling method that was originally proposed in 1993 by Rijkhoff, Bakker, Hengeveld and Kahrel, and [2] to discuss a number of other approaches to language sampling in the light of our own method. We will also demonstrate how our...... sampling method is used with different genetic classifications (Voegelin & Voegelin 1977, Ruhlen 1987, Grimes ed. 1997) and argue that —on the whole— our sampling technique compares favourably with other methods, especially in the case of exploratory research....

  2. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial

    DEFF Research Database (Denmark)

    Burnett, Alan K; Hills, Robert K; Milligan, Donald

    2011-01-01

    PURPOSE: Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously...... established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients. PATIENTS AND METHODS: In this open-label trial, 1,113 patients, predominantly younger...... in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit...

  3. A radiolabeled antibody targeting CD123+ leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

    Directory of Open Access Journals (Sweden)

    Jeffrey V. Leyton

    2015-01-01

    Full Text Available Radioimmunotherapy (RIT with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS peptides and labeled with the Auger electron-emitter, 111In (111In-NLS-CSL360 was studied in the prevalent NOD/SCID mouse AML engraftment assay. Significant decreases in CD123+ leukemic cells and impairment of leukemic stem cell self-renewal were achieved with high doses of RIT. However, NOD/SCID mice were very radiosensitive to these doses. At low non-toxic treatment doses, 111In-NLS-CSL360 demonstrated a trend towards improved survival associated with decreased spleen/body weight ratio, an indicator of leukemia burden, and almost complete eradication of leukemia from the bone marrow in some mice.

  4. Language training

    CERN Multimedia

    2015-01-01

    If one of your New Year’s resolutions is to learn a language, there is no excuse any more.    You can attend one of our English or French courses and you can practise the language with a tandem partner!   General & Professional French courses The next General & Professional French course will start on 26 January. These collective courses aim to bring participants who have at least level A1 to higher levels (up to C2). Each level consists of a combination of face-to-face sessions (40 hours) with personal work (20 hours) following a specially designed programme. A final progress test takes place at the end of the term. Please note that it is mandatory to take the placement test. Please sign up here. French courses for beginners The aim of this course is to give some basic skills to beginners in order to communicate in simple everyday situations in both social and professional life. These courses can start at any time during the year, as soon as a group of beg...

  5. Language Training

    CERN Multimedia

    HR Department

    Permanence A "permanence" for language Training has been set up. If anyone has a question or requires information on any aspect of English or French training please come to our office 5 4-016 at the following times. Lucette Fournier - French courses Monday 13.30 - 15.30 Tuesday\t10.30 - 12.30 Tessa Osborne - English courses Wednesday\t12.00 - 14.00 Thursday\t11.00 - 13.00   New courses Specific English and French courses - Exam preparation/ We are now offering specific courses in English and French leading to a recognised external examination (e.g. Cambridge, DELF, DALF). If you are interested in following one of these courses and have at least an upper intermediate level of English or French, please enrol through the following link:  English courses French courses Or contact: Tessa Osborne 72957 (English courses) Lucette Fournier 73483 (French courses) Language Training Nathalie Dumeaux Tel. 78144 nathalie.dumeaux@cern.ch

  6. Language Training

    CERN Multimedia

    HR Department

    2009-01-01

    PermanenceA "permanence" for language Training has been set up. If anyone has a question or requires information on any aspect of English or French training please come to our office 5 4-016 at the following times. Lucette Fournier French courses Monday 13.30 - 15.30 Tuesday\t10.30 - 12.30 Tessa Osborne English courses Wednesday\t12.00 - 14.00 Thursday\t11.00 - 13.00 New courses Specific English and French courses - Exam preparation/ We are now offering specific courses in English and French leading to a recognised external examination (e.g. Cambridge, DELF and BULATS). If you are interested in following one of these courses and have at least an upper intermediate level of English or French, please enrol through the following link: http://English courses http://French courses Or contact: Tessa Osborne 72957 (English courses) Lucette Fournier 73483 (French courses) Language Training Nathalie Dumeaux Tel. 78144 mailto:nathalie.dumeaux@cern.ch

  7. LANGUAGE TRAINING

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch FRENCH TRAINING General and Professional French Courses The next session will take place from 26 January to 02 April 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: Tel. 73127. Writing Professional Documents in French The next session will take place from 26 January to 02 April 2004. This course is designed for people wi...

  8. LANGUAGE TRAINING

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch FRENCH TRAINING General and Professional French Courses The next session will take place from 26 January to 02 April 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in French The next session will take place from 26 January to 02 April 2004. This course is designed for peop...

  9. Foreign Language Teachers' Language Proficiency and Their Language Teaching Practice

    Science.gov (United States)

    Richards, Heather; Conway, Clare; Roskvist, Annelies; Harvey, Sharon

    2013-01-01

    Teachers' subject knowledge is recognized as an essential component of effective teaching. In the foreign language context, teachers' subject knowledge includes language proficiency. In New Zealand high schools, foreign languages (e.g. Chinese, French, German, Japanese and Spanish) have recently been offered to learners earlier in their schooling,…

  10. Technology in Language Use, Language Teaching, and Language Learning

    Science.gov (United States)

    Chun, Dorothy; Smith, Bryan; Kern, Richard

    2016-01-01

    This article offers a capacious view of technology to suggest broad principles relating technology and language use, language teaching, and language learning. The first part of the article considers some of the ways that technological media influence contexts and forms of expression and communication. In the second part, a set of heuristic…

  11. BIBLIOGRAPHY ON LANGUAGE DEVELOPMENT.

    Science.gov (United States)

    Harvard Univ., Cambridge, MA. Graduate School of Education.

    THIS BIBLIOGRAPHY LISTS MATERIAL ON VARIOUS ASPECTS OF LANGUAGE DEVELOPMENT. APPROXIMATELY 65 UNANNOTATED REFERENCES ARE PROVIDED TO DOCUMENTS DATING FROM 1958 TO 1966. JOURNALS, BOOKS, AND REPORT MATERIALS ARE LISTED. SUBJECT AREAS INCLUDED ARE THE NATURE OF LANGUAGE, LINGUISTICS, LANGUAGE LEARNING, LANGUAGE SKILLS, LANGUAGE PATTERNS, AND…

  12. Inference in `poor` languages

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, S.

    1996-10-01

    Languages with a solvable implication problem but without complete and consistent systems of inference rules (`poor` languages) are considered. The problem of existence of finite complete and consistent inference rule system for a ``poor`` language is stated independently of the language or rules syntax. Several properties of the problem arc proved. An application of results to the language of join dependencies is given.

  13. Let There Be Languages!

    Science.gov (United States)

    Gunnarsson, Petur

    1992-01-01

    Examines the resilience of small languages in the face of larger ones. Highlights include the concept of one dominant language, such as Esperanto; the threat of television to small visual-language societies; the power of visual media; man's relationship to language; and the resilience of language. (LRW)

  14. Language as Pure Potential

    Science.gov (United States)

    Park, Joseph Sung-Yul

    2016-01-01

    Language occupies a crucial position in neoliberalism, due to the reimagination of language as commodified skill. This paper studies the role of language ideology in this transformation by identifying a particular ideology that facilitates this process, namely the ideology which views language as pure potential. Neoliberalism treats language as a…

  15. Linguistics in Language Education

    Science.gov (United States)

    Kumar, Rajesh; Yunus, Reva

    2014-01-01

    This article looks at the contribution of insights from theoretical linguistics to an understanding of language acquisition and the nature of language in terms of their potential benefit to language education. We examine the ideas of innateness and universal language faculty, as well as multilingualism and the language-society relationship. Modern…

  16. Language Teachers' Target Language Project: Language for Specific Purposes of Language Teaching

    Science.gov (United States)

    Korenev, Alexey; Westbrook, Carolyn; Merry, Yvonne; Ershova, Tatiana

    2016-01-01

    The Language Teachers' Target Language project (LTTL) aims to describe language teachers' target language use domain (Bachman & Palmer 2010) and to develop a language test for future teachers of English. The team comprises four researchers from Moscow State University (MSU) and Southampton Solent University.

  17. Foreign Language Attrition.

    Science.gov (United States)

    de Bot, Kees; Weltens, Bert

    1995-01-01

    Reviews recent research on language maintenance and language loss, focusing on the loss of a second language in a first language environment, the linguistic aspects of loss, and relearning a "lost" language. An annotated bibliography discusses nine important works in the field. (43 references) (MDM)

  18. A Case of AML Characterized by a Novel t(4;15(q31;q22 Translocation That Confers a Growth-Stimulatory Response to Retinoid-Based Therapy

    Directory of Open Access Journals (Sweden)

    Justin M. Watts

    2017-07-01

    Full Text Available Here we report the case of a 30-year-old woman with relapsed acute myeloid leukemia (AML who was treated with all-trans retinoic acid (ATRA as part of investigational therapy (NCT02273102. The patient died from rapid disease progression following eight days of continuous treatment with ATRA. Karyotype analysis and RNA-Seq revealed the presence of a novel t(4;15(q31;q22 reciprocal translocation involving the TMEM154 and RASGRF1 genes. Analysis of primary cells from the patient revealed the expression of TMEM154-RASGRF1 mRNA and the resulting fusion protein, but no expression of the reciprocal RASGRF1-TMEM154 fusion. Consistent with the response of the patient to ATRA therapy, we observed a rapid proliferation of t(4;15 primary cells following ATRA treatment ex vivo. Preliminary characterization of the retinoid response of t(4;15 AML revealed that in stark contrast to non-t(4;15 AML, these cells proliferate in response to specific agonists of RARα and RARγ. Furthermore, we observed an increase in the levels of nuclear RARγ upon ATRA treatment. In summary, the identification of the novel t(4;15(q31;q22 reciprocal translocation opens new avenues in the study of retinoid resistance and provides potential for a new biomarker for therapy of AML.

  19. Different impact of intermediate and unfavourable cytogenetics at the time of diagnosis on outcome of de novo AML after allo-SCT: a long-term retrospective analysis from a single institution.

    Science.gov (United States)

    Nahi, H; Remberger, M; Machaczka, M; Ungerstedt, J; Mattson, J; Ringden, O; Le-Blanc, Katarina; Ljungman, P; Hägglund, H

    2012-12-01

    Karyotype of myeloblasts at the time of AML diagnosis has been shown to be prognostic significant for pre-remission outcome and outcome after allo-SCT, but the latter requires further studies. We conducted a retrospective analysis of the impact of intermediate and unfavourable cytogenetics at the time of primary diagnosis on outcome after allo-SCT in de novo AML. The study included 169 patients who underwent allo-SCT at Karolinska University Hospital between 1980 and 2010. Intermediate and unfavourable cytogenetics were found in 129 (76%) and 40 patients (24%), respectively. Myeloablative and reduced-intensity conditioning were given to 120 (71%) and 49 (29%) patients, respectively. Allo-SCT was performed in CR1 in 122 patients (72%). TRM was 16% in both cytogenetics groups. Relapse occurred in 29% patients with intermediate and in 45% patients with unfavourable cytogenetics (P=0.01). The probabilities of 5-year OS for patients with intermediate and unfavourable cytogenetics were 60 and 43%, respectively (P=0.02). Multivariate analysis revealed intermediate cytogenetics, chronic GVHD, and recipient CMV-negative serostatus as variables associated with favourable OS. Our study showed that outcome after allo-SCT in de novo AML differs depending on cytogenetic risk-group; however its position in post-remission therapy of eligible AML patients is not threatened.

  20. A Jehovah’s Witness with Acute Myeloid Leukemia Successfully Treated with an Epigenetic Drug, Azacitidine: A Clue for Development of Anti-AML Therapy Requiring Minimum Blood Transfusions

    Directory of Open Access Journals (Sweden)

    Yumi Yamamoto

    2014-01-01

    Full Text Available Therapy for acute leukemia in Jehovah’s Witnesses patients is very challenging because of their refusal to accept blood transfusions, a fundamental supportive therapy for this disease. These patients are often denied treatment for fear of treatment-related death. We present the first Jehovah’s Witness patient with acute myeloid leukemia (AML treated successfully with azacitidine. After achieving complete remission (CR with one course of azacitidine therapy, the patient received conventional postremission chemotherapy and remained in CR. In the case of patients who accept blood transfusions, there are reports indicating the treatment of AML patients with azacitidine. In these reports, azacitidine therapy was less toxic, including hematoxicity, compared with conventional chemotherapy. The CR rate in azacitidine-treated patients was inadequate; however, some characteristics could be useful in predicting azacitidine responders. The present case is useful for treating Jehovah’s Witnesses patients with AML and provides a clue for anti-AML therapy requiring minimum blood transfusions.

  1. Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: A collaborative study by the International-Berlin- Frankfurt-Münster AML-study group

    NARCIS (Netherlands)

    E.A. Coenen (Eva); C.M. Zwaan (Christian Michel); D. Reinhardt (Dirk); C.J. Harrison (Christine); O.A. Haas (Oskar); V. de Haas (Valerie); V. Mihál (Vladimir); B. de Moerloose (Barbara); M. Jeison (Marta); J.E. Rubnitz (Jeffrey); D. Tomizawa (Daisuke); D. Johnston (Donna); T.A. Alonzo (Todd); H. Hasle (Henrik); A. Auvrignon (Anne); M.N. Dworzak (Michael); A. Pession (Andrea); V.H.J. van der Velden (Vincent); J. Swansbury (John); K.-F. Wong (Kit-Fai); N. Terui (Nobuhiko); S. Savasan (Sureyya); M. Winstanley (Mark); G. Vaitkeviciene (Goda); M. Zimmermann (Martin); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2013-01-01

    textabstractIn pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical

  2. Language variety, language hierarchy, and language choice in the international university

    DEFF Research Database (Denmark)

    Haberland, Hartmut; Mortensen, Janus

    2012-01-01

    Introduction to thematic issue on Language variety, language hierarchy, and language choice in the international university......Introduction to thematic issue on Language variety, language hierarchy, and language choice in the international university...

  3. Use of recombinant granulocyte-macrophage colony-stimulating factor during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia (AML) : Final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer (EORTC-LCG) and the Dutch Belgian Hemato-Oncology Cooperative Group (HOVON)

    NARCIS (Netherlands)

    Lowenberg, B; Suciu, S; Archimbaud, E; Ossenkoppele, G; Verhoef, GEG; Vellenga, E; Wijermans, P; Berneman, Z; Dekker, AW; Stryckmans, P; Jehn, U; Muus, P; Sonneveld, P; Dardenne, M; Zittoun, R

    1997-01-01

    We conducted a prospective randomized multicenter clinical trial comparing the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to intensive chemotherapy in patients of 61 years and older with untreated newly diagnosed acute myeloid leukemia (AML). Patients were

  4. Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region

    International Nuclear Information System (INIS)

    Sakamoto, K; Imamura, T; Yano, M; Yoshida, H; Fujiki, A; Hirashima, Y; Hosoi, H

    2014-01-01

    All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML–RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPε and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML

  5. Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123"+/CD131"− phenotype of leukemia stem cells

    International Nuclear Information System (INIS)

    Gao, Catherine; Leyton, Jeffrey V.; Schimmer, Aaron D.; Minden, Mark; Reilly, Raymond M.

    2016-01-01

    Chimeric IgG_1 monoclonal antibody CSL360 recognizes the CD123"+/CD131"− phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates incorporating nuclear translocation sequence (NLS) peptides bound specifically to Raji cells transfected with CD123 and exhibited a K_D of 11 nmols/L in a competition receptor-binding assay using CD123-transfected CHO cells. "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and transported to the nucleus of human AML-5 myeloid leukemia cells. The clonogenic survival of AML-5 cells was reduced by "1"1"1In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control "1"1"1In-DTPA-chIgG_1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free "1"1"1In acetate did not decrease cell survival. These results are promising for further evaluation of "1"1"1In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation. - Highlights: • "1"1"1In-DTPA-NLS-CSL360 the CD123"+/CD131"− phenotype of leukemic stem cells (LSC). • "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and imported into the nucleus of AML-5 leukemia cells. • "1"1"1In-DTPA-NLS-CSL360 reduced the clonogenic survival of AML-5 leukemia cells by 4-fold.

  6. Health Literacy - Multiple Languages

    Science.gov (United States)

    ... Here: Home → Multiple Languages → All Health Topics → Health Literacy URL of this page: https://medlineplus.gov/languages/ ... W XYZ List of All Topics All Health Literacy - Multiple Languages To use the sharing features on ...

  7. Cosmetic Dentistry - Multiple Languages

    Science.gov (United States)

    ... Here: Home → Multiple Languages → All Health Topics → Cosmetic Dentistry URL of this page: https://medlineplus.gov/languages/ ... W XYZ List of All Topics All Cosmetic Dentistry - Multiple Languages To use the sharing features on ...

  8. Atrial Fibrillation - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Atrial Fibrillation URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Atrial Fibrillation - Multiple Languages To use the sharing features on ...

  9. Journal for Language Teaching

    African Journals Online (AJOL)

    PROMOTING ACCESS TO AFRICAN RESEARCH ... Journal for Language Teaching = Ijenali Yekufundzisa Lulwimi = Tydskrif vir Taalonderrig ... SAALT was founded in 1964 for the benefit of language teaching and language teachers and ...

  10. Zika Virus - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Zika Virus URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Zika Virus - Multiple Languages To use the sharing features on ...

  11. Elder Abuse - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Elder Abuse URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Elder Abuse - Multiple Languages To use the sharing features on ...

  12. Herbal Medicine - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Herbal Medicine URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Herbal Medicine - Multiple Languages To use the sharing features on ...

  13. Introduction to formal languages

    CERN Document Server

    Révész, György E

    1991-01-01

    Covers all areas, including operations on languages, context-sensitive languages, automata, decidability, syntax analysis, derivation languages, and more. Numerous worked examples, problem exercises, and elegant mathematical proofs. 1983 edition.

  14. Domestic Violence - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Domestic Violence URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Domestic Violence - Multiple Languages To use the sharing features on ...

  15. Diabetic Foot - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Diabetic Foot URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Diabetic Foot - Multiple Languages To use the sharing features on ...

  16. Child Abuse - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Child Abuse URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Child Abuse - Multiple Languages To use the sharing features on ...

  17. A Natural Language Architecture

    OpenAIRE

    Sodiya, Adesina Simon

    2007-01-01

    Natural languages are the latest generation of programming languages, which require processing real human natural expressions. Over the years, several groups or researchers have trying to develop widely accepted natural language languages based on artificial intelligence (AI). But no true natural language has been developed. The goal of this work is to design a natural language preprocessing architecture that identifies and accepts programming instructions or sentences in their natural forms ...

  18. Language Assessment Literacy: Implications for Language Teachers

    Science.gov (United States)

    Giraldo, Frank

    2018-01-01

    Recently, the applied linguistics field has examined the knowledge, skills, and principles needed for assessment, defined as language assessment literacy. Two major issues in language assessment literacy have been addressed but not fully resolved--what exactly language assessment literacy is and how it differs among stakeholders (e.g., students…

  19. Discussion: Imagining the Languaged Worker's Language

    Science.gov (United States)

    Urciuoli, Bonnie

    2016-01-01

    What people perceive as "a language"--a named entity--is abstracted from practices and notions about those practices. People take for granted that language is somehow a "thing," an objectively distinct and bounded entity. How languages come to be thus imagined indexes the conditions under which they are imagined. The articles…

  20. Language and Language Policy in Singapore.

    Science.gov (United States)

    Baxter, William H., III

    1985-01-01

    Singapore's language policy must balance the wishes of the various ethnic groups, the political situation in the regions, and the needs of economic development. Malay, Mandarin Chinese, English, and Tamil are all recognized as official languages. Malay has special symbolic status as the national language. (RM)

  1. The Financial Impact of the ‘Zero-Markup Policy for Essential Drugs’ on Patients in County Hospitals in Western Rural China

    Science.gov (United States)

    Zhou, Zhongliang; Su, Yanfang; Campbell, Benjamin; Zhou, Zhiying; Gao, Jianmin; Yu, Qiang; Chen, Jiuhao; Pan, Yishan

    2015-01-01

    Objective With a quasi-experimental design, this study aims to assess whether the Zero-markup Policy for Essential Drugs (ZPED) reduces the medical expense for patients at county hospitals, the major healthcare provider in rural China. Methods Data from Ningshan county hospital and Zhenping county hospital, China, include 2014 outpatient records and 9239 inpatient records. Quantitative methods are employed to evaluate ZPED. Both hospital-data difference-in-differences and individual-data regressions are applied to analyze the data from inpatient and outpatient departments. Results In absolute terms, the total expense per visit reduced by 19.02 CNY (3.12 USD) for outpatient services and 399.6 CNY (65.60 USD) for inpatient services. In relative terms, the expense per visit was reduced by 11% for both outpatient and inpatient services. Due to the reduction of inpatient expense, the estimated reduction of outpatient visits is 2% among the general population and 3.39% among users of outpatient services. The drug expense per visit dropped by 27.20 CNY (4.47 USD) for outpatient services and 278.7 CNY (45.75 USD) for inpatient services. The proportion of drug expense out of total expense per visit dropped by 11.73 percentage points in outpatient visits and by 3.92 percentage points in inpatient visits. Conclusion Implementation of ZPED is a benefit for patients in both absolute and relative terms. The absolute monetary reduction of the per-visit inpatient expense is 20 times of that in outpatient care. According to cross-price elasticity, the substitution between inpatient and outpatient due to the change in inpatient price is small. Furthermore, given that the relative reductions are the same for outpatient and inpatient visits, according to relative thinking theory, the incentive to utilize outpatient or inpatient care attributed to ZPED is equivalent, regardless of the 20-times price difference in absolute terms. PMID:25790443

  2. The financial impact of the 'zero-markup policy for essential drugs' on patients in county hospitals in western rural China.

    Science.gov (United States)

    Zhou, Zhongliang; Su, Yanfang; Campbell, Benjamin; Zhou, Zhiying; Gao, Jianmin; Yu, Qiang; Chen, Jiuhao; Pan, Yishan

    2015-01-01

    With a quasi-experimental design, this study aims to assess whether the Zero-markup Policy for Essential Drugs (ZPED) reduces the medical expense for patients at county hospitals, the major healthcare provider in rural China. Data from Ningshan county hospital and Zhenping county hospital, China, include 2014 outpatient records and 9239 inpatient records. Quantitative methods are employed to evaluate ZPED. Both hospital-data difference-in-differences and individual-data regressions are applied to analyze the data from inpatient and outpatient departments. In absolute terms, the total expense per visit reduced by 19.02 CNY (3.12 USD) for outpatient services and 399.6 CNY (65.60 USD) for inpatient services. In relative terms, the expense per visit was reduced by 11% for both outpatient and inpatient services. Due to the reduction of inpatient expense, the estimated reduction of outpatient visits is 2% among the general population and 3.39% among users of outpatient services. The drug expense per visit dropped by 27.20 CNY (4.47 USD) for outpatient services and 278.7 CNY (45.75 USD) for inpatient services. The proportion of drug expense out of total expense per visit dropped by 11.73 percentage points in outpatient visits and by 3.92 percentage points in inpatient visits. Implementation of ZPED is a benefit for patients in both absolute and relative terms. The absolute monetary reduction of the per-visit inpatient expense is 20 times of that in outpatient care. According to cross-price elasticity, the substitution between inpatient and outpatient due to the change in inpatient price is small. Furthermore, given that the relative reductions are the same for outpatient and inpatient visits, according to relative thinking theory, the incentive to utilize outpatient or inpatient care attributed to ZPED is equivalent, regardless of the 20-times price difference in absolute terms.

  3. The financial impact of the 'zero-markup policy for essential drugs' on patients in county hospitals in western rural China.

    Directory of Open Access Journals (Sweden)

    Zhongliang Zhou

    Full Text Available With a quasi-experimental design, this study aims to assess whether the Zero-markup Policy for Essential Drugs (ZPED reduces the medical expense for patients at county hospitals, the major healthcare provider in rural China.Data from Ningshan county hospital and Zhenping county hospital, China, include 2014 outpatient records and 9239 inpatient records. Quantitative methods are employed to evaluate ZPED. Both hospital-data difference-in-differences and individual-data regressions are applied to analyze the data from inpatient and outpatient departments.In absolute terms, the total expense per visit reduced by 19.02 CNY (3.12 USD for outpatient services and 399.6 CNY (65.60 USD for inpatient services. In relative terms, the expense per visit was reduced by 11% for both outpatient and inpatient services. Due to the reduction of inpatient expense, the estimated reduction of outpatient visits is 2% among the general population and 3.39% among users of outpatient services. The drug expense per visit dropped by 27.20 CNY (4.47 USD for outpatient services and 278.7 CNY (45.75 USD for inpatient services. The proportion of drug expense out of total expense per visit dropped by 11.73 percentage points in outpatient visits and by 3.92 percentage points in inpatient visits.Implementation of ZPED is a benefit for patients in both absolute and relative terms. The absolute monetary reduction of the per-visit inpatient expense is 20 times of that in outpatient care. According to cross-price elasticity, the substitution between inpatient and outpatient due to the change in inpatient price is small. Furthermore, given that the relative reductions are the same for outpatient and inpatient visits, according to relative thinking theory, the incentive to utilize outpatient or inpatient care attributed to ZPED is equivalent, regardless of the 20-times price difference in absolute terms.

  4. GAIML: A New Language for Verbal and Graphical Interaction in Chatbots

    Directory of Open Access Journals (Sweden)

    Roberto Pirrone

    2008-01-01

    Full Text Available Natural and intuitive interaction between users and complex systems is a crucial research topic in human-computer interaction. A major direction is the definition and implementation of systems with natural language understanding capabilities. The interaction in natural language is often performed by means of systems called chatbots. A chatbot is a conversational agent with a proper knowledge base able to interact with users. Chatbots appearance can be very sophisticated with 3D avatars and speech processing modules. However the interaction between the system and the user is only performed through textual areas for inputs and replies. An interaction able to add to natural language also graphical widgets could be more effective. On the other side, a graphical interaction involving also the natural language can increase the comfort of the user instead of using only graphical widgets. In many applications multi-modal communication must be preferred when the user and the system have a tight and complex interaction. Typical examples are cultural heritages applications (intelligent museum guides, picture browsing or systems providing the user with integrated information taken from different and heterogenous sources as in the case of the iGoogle™ interface. We propose to mix the two modalities (verbal and graphical to build systems with a reconfigurable interface, which is able to change with respect to the particular application context. The result of this proposal is the Graphical Artificial Intelligence Markup Language (GAIML an extension of AIML allowing merging both interaction modalities. In this context a suitable chatbot system called Graphbot is presented to support this language. With this language is possible to define personalized interface patterns that are the most suitable ones in relation to the data types exchanged between the user and the system according to the context of the dialogue.

  5. Speech and Language Delay

    Science.gov (United States)

    ... OTC Relief for Diarrhea Home Diseases and Conditions Speech and Language Delay Condition Speech and Language Delay Share Print Table of Contents1. ... Treatment6. Everyday Life7. Questions8. Resources What is a speech and language delay? A speech and language delay ...

  6. The Mixed language Debate

    DEFF Research Database (Denmark)

    A range of views on mixed languages and their connections to phenomena such as secret languages, massive borrowing, codeswitching and codemixing, and thier origin.......A range of views on mixed languages and their connections to phenomena such as secret languages, massive borrowing, codeswitching and codemixing, and thier origin....

  7. Language Contact and Bilingualism

    NARCIS (Netherlands)

    Appel, René; Muysken, Pieter

    2006-01-01

    What happens - sociologically, linguistically, educationally, politically - when more than one language is in regular use in a community? How do speakers handle these languages simultaneously, and what influence does this language contact have on the languages involved? Although most people in the

  8. Creativity in Language Teaching

    Science.gov (United States)

    Richards, Jack C.

    2013-01-01

    One quality among the many that characterize effective teachers is the ability to bring a creative disposition to teaching. In second language teaching, creativity has also been linked to levels of attainment in language learning. Many of the language tasks favored by contemporary language teaching methods are believed to release creativity in…

  9. Language Policy and Planning.

    Science.gov (United States)

    Takala, Sauli; Sajavaara, Kari

    2000-01-01

    Focuses on foreign language planning, or the planned changes in foreign language instructional systems and in uses of languages in different social contexts with special reference to the Nordic and Baltic countries. Special attention is given to the relationship between language planning and evaluation. (Author/VWL)

  10. Language Literacy in Writing

    Directory of Open Access Journals (Sweden)

    Saeideh Ahangari

    2008-05-01

    Full Text Available This paper explores the ways in which the transfer of assumptions from first language (L1 writing can help the process of writing in second language (L2. In learning second language writing skills, learners have two primary sources from which they construct a second language system: knowledge and skills from first language and input from second language. To investigate the relative impact of first language literacy skills on second language writing ability, 60 EFL students from Tabriz Islamic Azad University were chosen as participants of this study, based on their language proficiency scores. The subjects were given two topics to write about: the experimental group subjects were asked to write in Persian and then translate their writing into English. The control group wrote in English. The results obtained in this study indicate that the content and vocabulary components of the compositions were mostly affected by the use of first language.

  11. Learning a Second Language

    OpenAIRE

    Murphy, Caroline; Hermann, Charlotte; Andersen, Signe Hvalsøe; Grigalauskyte, Simona; Tolsgaard, Mads; Holmegaard, Thorbjørn; Hajaya, Zaedo Musa

    2013-01-01

    This study examines the concept of second language learning in Denmark with focus on how second language learners negotiate their identities in relation to language learning and integration. By investigating three language learners’ acquisition of Danish through key theories on the field of second language learning, focus is centred on the subjects’ lived experiences of the learning process within their everyday lives and in the classroom. Through interviews and observations it can be conclud...

  12. Language&Learning

    OpenAIRE

    Saidi, Tamana; Djurhuus, Terji; Egeslund, Søren Due; Oikonomou, Anna Maria; Pietilä, Minerva

    2013-01-01

    This project aims to display how the process differs when acquiring a first language, two first languages simultaneously or a second language. The linguistic elements are presented in First Language and Second Language and in bilingualism. We will be looking at Chomsky’s Nativist approach, as well as Behaviorism by Skinner. Also, socio-cultural theory by Vygotsky and the cognitive approach are used. A study will be conducted to find out whether bilinguals can perform as well as native speaker...

  13. Language Revitalization and Language Pedagogy: New Teaching and Learning Strategies

    Science.gov (United States)

    Hinton, Leanne

    2011-01-01

    Language learning and teaching of endangered languages have many features and needs that are quite different from the teaching of world languages. Groups whose languages are endangered try to turn language loss around; many new language teaching and learning strategies are emerging, to suit the special needs and goals of language revitalization.…

  14. The role of C/EBPa in PD-1+ CD4+ T cells & modulation of RNR activity prolongs survival of mice with AML

    DEFF Research Database (Denmark)

    Norrie, Ida Christine

    of age-dependent PD-1+ CD4+ T cells was therefore investigated as well as its importance for development of PD-1+ CD4+ T cells during leukemic development. My results showed that loss of C/EBPα expression in the lymphoid compartment led to an increased amount of aged PD-1+ CD4+ T cells, but not of young...... PD-1+ CD4+ T cells, suggesting that C/EBPα repress the accumulation of these cells in old mice. Furthermore, C/EBPα-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells during development of leukemia. M data indicates......The Ph.D. thesis comprises two projects: (1) C/EBPα is dispensable for the ontogeny of PD1+ CD4+ memory T cells, but restricts their expansion in an age-dependent manner. (2) Modulation of RNR activity prolongs survival of mice with AML. Immunosenescence is a condition of the immune system...

  15. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine.

    Science.gov (United States)

    Sébert, Marie; Komrokji, Rami S; Sekeres, Mikkael A; Prebet, Thomas; Cluzeau, Thomas; Santini, Valeria; Gyan, Emmanuel; Sanna, Alessandro; Ali, Najla HAl; Hobson, Sean; Eclache, Virginie; List, Alan; Fenaux, Pierre; Adès, Lionel

    2017-12-01

    Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype. None of the cytogenetic abnormalities had significant impact on ORR (43.9%) or complete response (15.35%), except 3q abnormalities and complex karyotypes, which were associated with a lower ORR. OS differed significantly across all R-IPSS cytogenetic subgroups (pcytogenetics. CyR was achieved in 32% of the 281 evaluable patients with abnormal cytogenetics, was complete (CCyR) in 71 (25.3%) patients. We found no correlation between hematological response and cytogenetic response and 21% of the patients with CCyR did not achieve morphological response. In the 281 patients, we found no impact of CyR on survival, but when restricting to MDS (ie: <20% marrow blasts) achievement of CCyR was associated with better OS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. MINORITY LANGUAGES IN ESTONIAN SEGREGATIVE LANGUAGE ENVIRONMENTS

    Directory of Open Access Journals (Sweden)

    Elvira Küün

    2011-01-01

    Full Text Available The goal of this project in Estonia was to determine what languages are spoken by students from the 2nd to the 5th year of basic school at their homes in Tallinn, the capital of Estonia. At the same time, this problem was also studied in other segregated regions of Estonia: Kohtla-Järve and Maardu. According to the database of the population census from the year 2000 (Estonian Statistics Executive Office's census 2000, there are representatives of 142 ethnic groups living in Estonia, speaking a total of 109 native languages. At the same time, the database doesn’t state which languages are spoken at homes. The material presented in this article belongs to the research topic “Home Language of Basic School Students in Tallinn” from years 2007–2008, specifically financed and ordered by the Estonian Ministry of Education and Research (grant No. ETF 7065 in the framework of an international study called “Multilingual Project”. It was determined what language is dominating in everyday use, what are the factors for choosing the language for communication, what are the preferred languages and language skills. This study reflects the actual trends of the language situation in these cities.

  17. Teaching language arts to English language learners

    CERN Document Server

    Vásquez, Anete; Smith, Philip C

    2013-01-01

    This thoroughly revised and updated edition of Teaching Language Arts to English Language Learners provides readers with the comprehensive understanding of both the challenges that face ELLs and ways in which educators might address them in the language arts classroom. The authors offer proven techniques that teachers can readily use to teach reading, writing, grammar, and vocabulary as well as speaking, listening, and viewing skills. A complete section is also devoted to ways teachers can integrate all five strands of the language arts curriculum into a comprehensive unit of study w

  18. Local languages as the languages of internationalization

    DEFF Research Database (Denmark)

    Haberland, Hartmut

    2011-01-01

    . An ongoing research project tries to find out why this is the case. A preliminary result seems to be that it is not the academic motivation that starts the learning process of the local language, but once the students have stated to learn Danish, some of them also follow study courses in Danish, especially...... on offering programs rather in English than the local language. At Copenhagen Business School, 56.4% of the students at MA level followed courses in English in 2009. Many students come to Denmark from abroad, follow the English language programs offered, but are motivated to learn Danish, the local language...

  19. Language Management x 3

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum

    2017-01-01

    The term ‘language management’ has become a widely used expression in the sociolinguistic literature. Originally introduced by Jernudd and Neustupný in 1987, as a novel continuation of the language planning tradition stemming from the 1960/70s, language management along these lines has developed...... from the international management discipline, appear to have taken an interest in language as a variable in business and corporate management. It is also common to refer to this research field as language management. This conceptual article offers a theoretically based comparison of the three...... into the Language Management Theory (LMT). A second definition of language management, diverting from LMT, can be found in the work of Spolsky, who treats language management as a theoretical component of the wider concept of language policy. Furthermore, over the past 15 years a number of scholars, particularly...

  20. Language competence in movement

    DEFF Research Database (Denmark)

    Laursen, Helle Pia; Mogensen, Naja Dahlstrup

    2016-01-01

    multilingual children's language and literacy acquisition processes, we direct our focus to a single child's active exploration of what it means to know a language. Through analysis of interviews and researcher generated activities, we see how this child both describes and does language competence......This article examines how, in a multilingual perspective, language competence is experienced, talked about and practiced by language users themselves. By viewing children as active co-creators of the spaces in which language is used, this article contributes to a research tradition in which focus...... is shifted from viewing the individual's language competence as a mental linguistic or communicative property, to viewing language as a series of social and spatial practices. Looking at data from the research project Tegn på Sprog (in the following referred to as Signs of Language), which examines...

  1. Rights to Language

    DEFF Research Database (Denmark)

    Phillipson, Robert

    This work brings together cutting-edge scholarship in language, education and society from all parts of the world. Celebrating the 60th birthday of Tove Skutnabb-Kangas, it is inspired by her work in minority, indigenous and immigrant education; multilingualism; linguistic human rights; and global...... language and power issues. Drawn from all parts of the world, the contributors are active in a range of scientific and professional areas including bilingual education; sociolinguistics; the sociology of education, law and language; economics and language; linguistics; sign language; racism; communication......; discourse analysis; language policy; minority issues; and language pedagogy. The book situates issues of minorities and bilingual education in broader perspectives of human rights, power and the ecology of language. It aims at a distillation of themes that are central to an understanding of language rights...

  2. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

    Directory of Open Access Journals (Sweden)

    Irakli Dzneladze

    Full Text Available Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID, a tool which examines the relationship between a continuous variable (e.g. gene expression, and a test parameter (e.g. CoxPH or Fisher's exact P values. In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

  3. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

    Science.gov (United States)

    Dzneladze, Irakli; Woolley, John F; Rossell, Carla; Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D; Salmena, Leonardo

    2018-01-01

    Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher's exact P values). In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

  4. Safety and Pharmacokinetics of the Antisense Oligonucleotide (ASO) LY2181308 as a Single-Agent or in Combination with Idarubicin and Cytarabine in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML)

    Science.gov (United States)

    Erba, Harry P.; Sayar, Hamid; Juckett, Mark; Lahn, Michael; Andre, Valerie; Callies, Sophie; Schmidt, Shelly; Kadam, Sunil; Brandt, John T.; Van Bockstaele, Dirk; Andreeff, Michael

    2014-01-01

    Summary Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. Methods In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n=8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n=16). LY2181308 was administered with a loading dosage of 3 consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m2 was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m2 was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Results Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). Conclusions LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials. PMID:23397500

  5. Prognostic significance of flow-cytometry evaluation of minimal residual disease in children with acute myeloid leukaemia treated according to the AIEOP-AML 2002/01 study protocol.

    Science.gov (United States)

    Buldini, Barbara; Rizzati, Frida; Masetti, Riccardo; Fagioli, Franca; Menna, Giuseppe; Micalizzi, Concetta; Putti, Maria Caterina; Rizzari, Carmelo; Santoro, Nicola; Zecca, Marco; Disarò, Silvia; Rondelli, Roberto; Merli, Pietro; Pigazzi, Martina; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe

    2017-04-01

    In children with acute myeloid leukaemia (AML), assessment of initial treatment response is an essential prognostic factor; methods more sensitive than morphology are still under evaluation. We report on the measurement of minimal residual disease (MRD), by multicolour flow-cytometry in one centralized laboratory, in 142 children with newly diagnosed AML enrolled in the Associazione Italiana di EmatoOncologia Pediatrica-AML 2002/01 trial. At the end of the first induction course, MRD was 1% in 51 patients. The 8-year disease-free survival (DFS) of 125 children in morphological complete remission and with MRD <0·1%, 0·1-1% and ≥1% was 73·1 ± 5·6%, 37·8 ± 12·1% and 34·1 ± 8·8%, respectively (P < 0·01). MRD was also available after the second induction course in 92/142 patients. MRD was ≥0·1% at the end of the first induction course in 36 patients; 13 reached an MRD <0·1% after the second one and their DFS was 45·4 ± 16·7% vs. 22·8 ± 8·9% in patients with persisting MRD ≥0·1% (P = 0·037). Multivariate analysis demonstrated that MRD ≥0·1% after first induction course was, together with a monosomal karyotype, an independent adverse prognostic factor for DFS. Our results show that MRD detected by flow-cytometry after induction therapy predicts outcome in patients with childhood AML and can help stratifying post-remission treatment. © 2017 John Wiley & Sons Ltd.

  6. 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.

    Science.gov (United States)

    Büchner, Thomas; Hiddemann, Wolfgang; Berdel, Wolfgang E; Wörmann, Bernhard; Schoch, Claudia; Fonatsch, Christa; Löffler, Helmut; Haferlach, Torsten; Ludwig, Wolf-Dieter; Maschmeyer, Georg; Staib, Peter; Aul, Carlo; Gruneisen, Andreas; Lengfelder, Eva; Frickhofen, Norbert; Kern, Wolfgang; Serve, Hubert L; Mesters, Rolf M; Sauerland, Maria Cristina; Heinecke, Achim

    2003-12-15

    To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML). Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age or = 60 years) x 8 instead of maintenance. A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026). We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

  7. Amelie: A Recombinant Computing Framework for Ambient Awareness

    Science.gov (United States)

    Metaxas, Georgios; Markopoulos, Panos; Aarts, Emile

    This paper presents Amelie, a service oriented framework that supports the implementation of awareness systems. Amelie adopts the tenets of Recombinant computing to address an important non-functional requirement for Ambient Intelligence software, namely the heterogeneous combination of services and components. Amelie is founded upon FN-AAR an abstract model of Awareness Systems which enables the immediate expression and implementation of socially salient requirements, such as symmetry and social translucence. We discuss the framework and show how system behaviours can be specified using the Awareness Mark-up Language AML.

  8. Programming Language Pragmatics

    CERN Document Server

    Scott, Michael L

    2005-01-01

    Thoroughly updated to reflect the most current developments in language design and implementation, the second edition*Addresses key developments in programming language design:+ Finalized C99 standard+ Java 5+ C# 2.0+ Java concurrency package (JSR 166) and comparable mechanisms in C#+ Java and C# generics*Introduces and discusses scripting languages throughout the book and in an entire new chapter that covers:+ Application domains: shell languages, text processing and report generation, mathematics and statistics, "glue" languages and general purpose scripting, extension languages, scripting t

  9. Language, Mathematics and English Language Learners

    Science.gov (United States)

    Adoniou, Misty; Qing, Yi

    2014-01-01

    There is a correlation between language proficiency and achievement in mathematics (Riordain & O'Donoghue, 2009), and this is particularly evident for children who speak English as an additional language or dialect. More effort needs to be made in mathematics classrooms to develop cognitive competencies, including the ability to decode and…

  10. Languages contact and geopolitics of Romance languages

    Directory of Open Access Journals (Sweden)

    Louis-Jean Calvet

    2017-01-01

    Full Text Available In this article, we first conceive the contact between languages from different configurations to, secondly, analyze the geopolitics of the Romance languages, represented by the three great linguistic groups, that is, the French-speaking, Spanish-speaking and Portuguese-speaking groups.---Original in French.

  11. Languages contact and geopolitics of Romance languages

    OpenAIRE

    Louis-Jean Calvet

    2017-01-01

    In this article, we first conceive the contact between languages from different configurations to, secondly, analyze the geopolitics of the Romance languages, represented by the three great linguistic groups, that is, the French-speaking, Spanish-speaking and Portuguese-speaking groups.---Original in French.

  12. Language and identity: A case of Igbo language, Nigeria | Igbokwe ...

    African Journals Online (AJOL)

    Language is the most important information and communication characteristics of all the human beings. Language is power ... among the Igbo. The Igbo have embraced foreign languages in place of their mother tongue (Igbo language). This

  13. Coalition Battle Management Language

    National Research Council Canada - National Science Library

    Tolk, Andreas; Galvin, Kevin; Hieb, Michael; Khimeche, Lionel

    2004-01-01

    Battle Management Language (BML) is being developed as an unambiguous language to command and control forces and equipment conducting military operations and to provide for situational awareness and a shared common operational picture...

  14. Flexible Language Interoperability

    DEFF Research Database (Denmark)

    Ekman, Torbjörn; Mechlenborg, Peter; Schultz, Ulrik Pagh

    2007-01-01

    Virtual machines raise the abstraction level of the execution environment at the cost of restricting the set of supported languages. Moreover, the ability of a language implementation to integrate with other languages hosted on the same virtual machine typically constrains the features...... of the language. In this paper, we present a highly flexible yet efficient approach to hosting multiple programming languages on an object-oriented virtual machine. Our approach is based on extending the interface of each class with language-specific wrapper methods, offering each language a tailored view...... of a given class. This approach can be deployed both on a statically typed virtual machine, such as the JVM, and on a dynamic virtual machine, such as a Smalltalk virtual machine. We have implemented our approach to language interoperability on top of a prototype virtual machine for embedded systems based...

  15. Salmonella Infections - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Salmonella Infections URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Salmonella Infections - Multiple Languages To use the sharing features ...

  16. Balance Toward Language Mastery

    Directory of Open Access Journals (Sweden)

    Virginia R. Heslinga

    2017-01-01

    Full Text Available Problems in attaining language mastery with students from diverse language backgrounds and levels of ability confront educators around the world. Experiments, research, and experience see positive effects of adding sign language in communication methods to pre-school and K-12 education. Augmentative, alternative, interactive, accommodating, and enriching strategies using sign language aid learners in balancing the skills needed to mastery of one language or multiple languages. Theories of learning that embrace play, drama, motion, repetition, socializing, and self-efficacy connect to the options for using sign language with learners in inclusive and mainstream classes. The methodical use of sign language by this researcher-educator over two and a half decades showed signing does build thinking skills, add enjoyment, stimulate communication, expand comprehension, increase vocabulary acquisition, encourage collaboration, and helps build appreciation for cultural diversity.

  17. Higher Education Language Policy

    DEFF Research Database (Denmark)

    Lauridsen, Karen M.

    2013-01-01

    Summary of recommendations HEIs are encouraged, within the framework of their own societal context, mission, vision and strategies, to develop the aims and objectives of a Higher Education Language Policy (HELP) that allows them to implement these strategies. In this process, they may want......: As the first step in a Higher Education Language Policy, HEIs should determine the relative status and use of the languages employed in the institution, taking into consideration the answers to the following questions:  What is/are the official language(s) of the HEI?  What is/are the language...... and the level of internationalisation the HEI has or wants to have, and as a direct implication of that, what are the language proficiency levels expected from the graduates of these programme?  Given the profile of the HEI and its educational strategies, which language components are to be offered within...

  18. The Rudiments of Language.

    Science.gov (United States)

    Canfield, John V.

    1995-01-01

    Discusses the question of whether nonhuman species, such as apes, possess rudimentary language, focusing on the ideas of Ludwig Wittgenstein and Noam Chomsky in regard to the development of oral language in young children and apes. (51 references) (MDM)

  19. Language Management Tools

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum

    This paper offers a review of existing literature on the topic of language management tools – the means by which language is managed – in multilingual organisations. By drawing on a combination of sociolinguistics and international business and management studies, a new taxonomy of language...... management tools is proposed, differentiating between three categories of tools. Firstly, corporate policies are the deliberate control of issues pertaining to language and communication developed at the managerial level of a firm. Secondly, corporate measures are the planned activities the firm’s leadership...... may deploy in order to address the language needs of the organisation. Finally, front-line practices refer to the use of informal, emergent language management tools available to staff members. The language management tools taxonomy provides a framework for operationalising the management of language...

  20. Corporate Language Policies

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum

    This paper offers a review of literature dealing with language policies in general and corporate language policies in particular. Based on a discussion of various definitions of these concepts within two research traditions, i.e. sociolinguistics and international management, a three......-level definition of corporate language policies is presented, emphasising that a corporate language policy is a context-specific policy about language use. The three-level definition is based on the argument that in order to acquire a complete understanding of what corporate language policies involve, one needs...... to consider three progressive questions; 1) what is a policy? 2) what is a language policy?, and ultimately, 3) what is a corporate language policy?...

  1. Corporate Language Policies

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum

    2015-01-01

    This paper offers a review of literature dealing with language policies in general and corporate language policies in particular. Based on a discussion of various definitions of these concepts within two research traditions, i.e. sociolinguistics and international management, a three......-level definition of corporate language policies is presented, emphasising that a corporate language policy is a context-specific policy about language use. The three-level definition is based on the argument that in order to acquire a complete understanding of what corporate language policies involve, one needs...... to consider three progressive questions; 1) what is a policy? 2) what is a language policy?, and ultimately, 3) what is a corporate language policy?...

  2. Language disorder - children

    Science.gov (United States)

    ... disorders are rarely caused by a lack of intelligence. Language disorders are different than delayed language. With ... 2018, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing by ADAM ...

  3. Rotavirus Infections - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Rotavirus Infections URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Rotavirus Infections - Multiple Languages To use the sharing features ...

  4. Language Policy, Language Choice and Language Use in the ...

    African Journals Online (AJOL)

    systems across sentence boundaries within the same speech event… code- mixing is the ..... practice will inhibit the motivation for expanding the Swahili language through ..... 'Because of the reward with him, we call him contractor?' ...

  5. System programming languages

    OpenAIRE

    Šmit, Matej

    2016-01-01

    Most operating systems are written in the C programming language. Similar is with system software, for example, device drivers, compilers, debuggers, disk checkers, etc. Recently some new programming languages emerged, which are supposed to be suitable for system programming. In this thesis we present programming languages D, Go, Nim and Rust. We defined the criteria which are important for deciding whether programming language is suitable for system programming. We examine programming langua...

  6. Myanmar Language Search Engine

    OpenAIRE

    Pann Yu Mon; Yoshiki Mikami

    2011-01-01

    With the enormous growth of the World Wide Web, search engines play a critical role in retrieving information from the borderless Web. Although many search engines are available for the major languages, but they are not much proficient for the less computerized languages including Myanmar. The main reason is that those search engines are not considering the specific features of those languages. A search engine which capable of searching the Web documents written in those languages is highly n...

  7. The Origin of Language

    OpenAIRE

    Araki,Naoki

    2018-01-01

    There have been a lot of discussions of the origin of language. Some people think that the origin of words is onomatopoeias. Meanwhile, according to expressive theories, the origin of words and language is the innate cries of pain or pleasure produced by nonhuman animals. Others insist that language originated as a means of communication. Another theory holds that a learned vocalization systems, more like birdsong than innate calls, formed a middle term in language evolution. Others claim tha...

  8. Language: a social mirror

    Institute of Scientific and Technical Information of China (English)

    梁钰

    2015-01-01

    <正>Language and gender studies have experienced a long history in the field of linguistics.Sociolinguists did various kinds of research concerning gender-differentiated use of language.The differences between man’s and woman’s language has long been noticed by anthropologists,historians and linguistics.Then there gradually emerged great gap between male and

  9. Language and Culture

    Science.gov (United States)

    Kramsch, Claire

    2014-01-01

    This paper surveys the research methods and approaches used in the multidisciplinary field of applied language studies or language education over the last fourty years. Drawing on insights gained in psycho- and sociolinguistics, educational linguistics and linguistic anthropology with regard to language and culture, it is organized around five…

  10. Digital Language Death

    Science.gov (United States)

    Kornai, András

    2013-01-01

    Of the approximately 7,000 languages spoken today, some 2,500 are generally considered endangered. Here we argue that this consensus figure vastly underestimates the danger of digital language death, in that less than 5% of all languages can still ascend to the digital realm. We present evidence of a massive die-off caused by the digital divide. PMID:24167559

  11. Digital language death.

    Directory of Open Access Journals (Sweden)

    András Kornai

    Full Text Available Of the approximately 7,000 languages spoken today, some 2,500 are generally considered endangered. Here we argue that this consensus figure vastly underestimates the danger of digital language death, in that less than 5% of all languages can still ascend to the digital realm. We present evidence of a massive die-off caused by the digital divide.

  12. Language Policy in Slovenia

    Science.gov (United States)

    Novak-Lukanovic, Sonja; Limon, David

    2012-01-01

    The historical background, political changes, migration processes, EU membership and the current socio-linguistic situation have all influenced language policy and language planning in Slovenia. This article presents the most important aspects of language policy in Slovenia with a focus on the concept of linguistic diversity. The ethnic make-up of…

  13. COMMUNICATIVE LANGUAGE TEACHING

    Directory of Open Access Journals (Sweden)

    Angela JIREGHIE

    2012-06-01

    Full Text Available This paper focuses on the idea of an effective communication between teacher and students aiming to prove that classroom activities maximize opportunities for learners to use target language in a communicative way for meaningful activities. The emphasis lies on meaning (messages they are creating or tasks they are completing rather than form (correctness of language and language structure.

  14. Case in Language Comprehension

    NARCIS (Netherlands)

    Bader, Markus; Lamers, Monique

    2012-01-01

    Research on human language comprehension has been heavily influenced by properties of the English language. Since case plays only a minor role in English, its role for language comprehension has only recently become a topic for extensive research on psycholinguistics. In the psycholinguistic

  15. Minority Language Rights.

    Science.gov (United States)

    O Riagain, Padraig; Shuibhne, Niamh Nic

    1997-01-01

    A survey of literature since 1990 on minority languages and language rights focuses on five issues: definition of minorities; individual vs. collective rights; legal bases for minority linguistic rights; applications and interpretations of minority language rights; and assessments of the impact of minority rights legislation. A nine-item annotated…

  16. Language Anxiety and Achievement.

    Science.gov (United States)

    Horwitz, Elaine K.

    2001-01-01

    Considers the literature on language learning anxiety in an effort to clarify the relationship between anxiety and second language learning. Suggests that anxiety is indeed a cause of poor language learning in some individuals and discusses possible sources of this anxiety. (Author/VWL)

  17. Fuzzy Graph Language Recognizability

    OpenAIRE

    Kalampakas , Antonios; Spartalis , Stefanos; Iliadis , Lazaros

    2012-01-01

    Part 5: Fuzzy Logic; International audience; Fuzzy graph language recognizability is introduced along the lines of the established theory of syntactic graph language recognizability by virtue of the algebraic structure of magmoids. The main closure properties of the corresponding class are investigated and several interesting examples of fuzzy graph languages are examined.

  18. Cassirer's View of Language

    Science.gov (United States)

    Shen, Ying

    2009-01-01

    Myth is the breakthrough point of [Ernest] Cassirer's philosophy; Art is one of key words to understand his defined language; and Symbolism infiltrates into all aspects of human cultures especially language. The shift of Cassirer from great theories of science and philosophy to the world of art, language, myth, and culture mirrors his bold and…

  19. Modern programming language

    Science.gov (United States)

    Feldman, G. H.; Johnson, J. A.

    1980-01-01

    Structural-programming language is especially-tailored for producing assembly language programs for MODCOMP II and IV mini-computes. Modern programming language consists of set of simple and powerful control structures that include sequencing alternative selection, looping, sub-module linking, comment insertion, statement continuation, and compilation termination capabilities.

  20. Standardization of Sign Languages

    Science.gov (United States)

    Adam, Robert

    2015-01-01

    Over the years attempts have been made to standardize sign languages. This form of language planning has been tackled by a variety of agents, most notably teachers of Deaf students, social workers, government agencies, and occasionally groups of Deaf people themselves. Their efforts have most often involved the development of sign language books…