WorldWideScience

Sample records for macro language aml

  1. Growing Languages with Metamorphic Syntax Macros

    DEFF Research Database (Denmark)

    Brabrand, Claus; Schwartzbach, Michael Ignatieff

    2002-01-01

    "From now on, a main goal in designing a language should be to plan for growth." Guy Steele: Growing a Language, OOPSLA '98 invited talk.We present our experiences with a syntax macro language which we claim forms a general abstraction mechanism for growing (domain-specific) extensions of program......"From now on, a main goal in designing a language should be to plan for growth." Guy Steele: Growing a Language, OOPSLA '98 invited talk.We present our experiences with a syntax macro language which we claim forms a general abstraction mechanism for growing (domain-specific) extensions...

  2. The Agent Modeling Language AML A Comprehensive Approach to Modeling Multi-agent Systems

    CERN Document Server

    Cervenka, Radovan

    2007-01-01

    Multi-agent systems are already a focus of studies for more than 25 years. Despite substantial effort of an active research community, modeling of multi-agent systems still lacks complete and proper definition, general acceptance, and practical application. Due to the vast potential of these systems e.g., to improve the practice in software and to extent the applications that can feasibly be tackled, this book tries to provide a comprehensive modeling language - the Agent Modeling Language (AML) - as an extension of UML 2.0, concentrating on multi-agent systems and applications.

  3. Macro-Language Planning for Multilingual Education: Focus on Programmes and Provision

    Science.gov (United States)

    Taylor-Leech, Kerry; Liddicoat, Anthony J.

    2014-01-01

    This overview identifies some common features of macro-level language planning and briefly summarises the changing approaches to the analysis of macro-planning in the field. It previews six cases of language-in-education planning in response to linguistic diversity presented by the contributors to this issue. The cases show how macro-planning can…

  4. Macro-Language Planning for Multilingual Education: Focus on Programmes and Provision

    Science.gov (United States)

    Taylor-Leech, Kerry; Liddicoat, Anthony J.

    2014-01-01

    This overview identifies some common features of macro-level language planning and briefly summarises the changing approaches to the analysis of macro-planning in the field. It previews six cases of language-in-education planning in response to linguistic diversity presented by the contributors to this issue. The cases show how macro-planning can…

  5. The Interface between Macro and Micro-Level Language Policy and the Place of Language Pedagogies

    Science.gov (United States)

    Liddicoat, Anthony J.

    2014-01-01

    This paper investigates the place of pedagogy in language-in-education policy through an analysis of how the macro-level of government policy interacts with the micro-level of local educational practice. It argues that pedagogy is typically considered a micro-level activity and policy frequently devolves decision-making about pedagogy to…

  6. Balancing Macro- and Micro-Sociolinguistic Perspectives in Language Management: The Case of Singapore.

    Science.gov (United States)

    Kuo, Eddie C. Y.; Jernudd, Bjorn H.

    1993-01-01

    Shows how both macro- and microsociolinguistic perspectives are necessary to explain national language management. Macrolevel language planning is motivated by tasks of national consolidation by the state, notably in Singapore's case tasks of socio-ethnic integration and economic development. Microlevel language management pertains to individuals'…

  7. The Macro-and Micro-Language Learning Counseling: An Autoethnographic Account

    Directory of Open Access Journals (Sweden)

    Satomi Shibata

    2012-03-01

    Full Text Available This article describes an example of the counselor’s role in a relatively small Self-Access Center (SAC for language learning in universities in Japan. The author has been involved with establishing and running two SACs in Japanese universities. The study used autoethnography as its research method to look closely at the counselor’s role. This study eventually helped the author to analyze the counseling she has been providing and to realize that the counselor is required to provide not only macro-counseling but also micro-counseling. Micro-counseling consists of short, informal interactions with learners which connect the learner to elements in SACs, such as teaching assistants, other language learners, and language learning materials. These micro-counseling encounters can help to create a secure space which encourages learners to engage in macro-counseling sessions which support their language learning.

  8. Moving the Field Forward: A Micro-Meso-Macro Model for Critical Language Planning. The Case of Estonia

    Science.gov (United States)

    Skerrett, Delaney Michael

    2016-01-01

    This study investigates "de facto" language policy in Estonia. It investigates how language choices at the micro (or individual) level are negotiated within the macro (or social and historical) context: how official language policy and other features of the discursive environment surrounding language and its use in Estonia translate into…

  9. Moving the Field Forward: A Micro-Meso-Macro Model for Critical Language Planning. The Case of Estonia

    Science.gov (United States)

    Skerrett, Delaney Michael

    2016-01-01

    This study investigates "de facto" language policy in Estonia. It investigates how language choices at the micro (or individual) level are negotiated within the macro (or social and historical) context: how official language policy and other features of the discursive environment surrounding language and its use in Estonia translate into…

  10. 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...

  11. 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…

  12. Automated Microscopy: Macro Language Controlling a Confocal Microscope and its External Illumination: Adaptation for Photosynthetic Organisms.

    Science.gov (United States)

    Steinbach, Gábor; Kaňa, Radek

    2016-04-01

    Photosynthesis research employs several biophysical methods, including the detection of fluorescence. Even though fluorescence is a key method to detect photosynthetic efficiency, it has not been applied/adapted to single-cell confocal microscopy measurements to examine photosynthetic microorganisms. Experiments with photosynthetic cells may require automation to perform a large number of measurements with different parameters, especially concerning light conditions. However, commercial microscopes support custom protocols (through Time Controller offered by Olympus or Experiment Designer offered by Zeiss) that are often unable to provide special set-ups and connection to external devices (e.g., for irradiation). Our new system combining an Arduino microcontroller with the Cell⊕Finder software was developed for controlling Olympus FV1000 and FV1200 confocal microscopes and the attached hardware modules. Our software/hardware solution offers (1) a text file-based macro language to control the imaging functions of the microscope; (2) programmable control of several external hardware devices (light sources, thermal controllers, actuators) during imaging via the Arduino microcontroller; (3) the Cell⊕Finder software with ergonomic user environment, a fast selection method for the biologically important cells and precise positioning feature that reduces unwanted bleaching of the cells by the scanning laser. Cell⊕Finder can be downloaded from http://www.alga.cz/cellfinder. The system was applied to study changes in fluorescence intensity in Synechocystis sp. PCC6803 cells under long-term illumination. Thus, we were able to describe the kinetics of phycobilisome decoupling. Microscopy data showed that phycobilisome decoupling appears slowly after long-term (>1 h) exposure to high light.

  13. 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...

  14. Macros for Educational Research.

    Science.gov (United States)

    Woodrow, Janice E. J.

    1988-01-01

    Describes the design and operation of two macros written in the programming language of Microsoft's EXCEL for educational research applications. The first macro determines the frequency of responses to a Likert-type questionnaire or multiple-choice test; the second performs a one-way analysis of variance test. (Author/LRW)

  15. 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.

  16. Hygienic Macros for JavaScript

    OpenAIRE

    Disney, Timothy Charles

    2015-01-01

    Languages like Lisp, Scheme, and Racket have shown that powerful and expressive macro systems can give programmers the ability to grow their own language. Unfortunately, in languages with syntax like JavaScript, macros have had less success, due in part to the difficulty of integrating macro expansion and complex grammars.This dissertation describes sweet.js, a hygienic macro system for JavaScript that fixes long standing challenges in lexing JavaScript and provides expressive pattern matchi...

  17. Reasons for treating secondary AML as de novo AML

    DEFF Research Database (Denmark)

    Ostgård, Lene Sofie Granfeldt; Kjeldsen, Eigil; Holm, Mette Skov;

    2010-01-01

    ) in 77 cases (49%), CMPD (chronic myeloproliferative disorder) in 43 cases (27%) and was therapy-related AML (t-AML) in 37 cases (24%). Median age at diagnosis of AML was 69 yr in secondary cases when compared to 66 yr in de novo cases (P = 0.006). In univariate analyses, secondary AML was associated...... with an inferior complete remission (CR) rate (P = 0.008) and poorer overall survival (OS, P = 0.003) whereas in complete remitters, disease-free survival (DFS) of secondary cases was equal to that of de novo cases. Interestingly, in all further analyses of CR-rates, OS and DFS, when correcting for the influence...

  18. Writing Excel Macros with VBA

    CERN Document Server

    Roman, Steven

    2008-01-01

    To achieve the maximum control and flexibility from Microsoft® Excel often requires careful custom programming using the VBA (Visual Basic for Applications) language. Writing Excel Macros with VBA, 2nd Edition offers a solid introduction to writing VBA macros and programs, and will show you how to get more power at the programming level: focusing on programming languages, the Visual Basic Editor, handling code, and the Excel object model.

  19. 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...

  20. An Excel macro for generating trilinear plots.

    Science.gov (United States)

    Shikaze, Steven G; Crowe, Allan S

    2007-01-01

    This computer note describes a method for creating trilinear plots in Microsoft Excel. Macros have been created in MS Excel's internal language: Visual Basic for Applications (VBA). A simple form has been set up to allow the user to input data from an Excel worksheet. The VBA macro is used to convert the triangular data (which consist of three columns of percentage data) into X-Y data. The macro then generates the axes, labels, and grid for the trilinear plot. The X-Y data are plotted as scatter data in Excel. By providing this macro in Excel, users can create trilinear plots in a quick, inexpensive manner.

  1. Macro tree transducers

    NARCIS (Netherlands)

    Engelfriet, Joost; Vogler, Heiko

    1985-01-01

    Macro tree transducers are a combination of top-down tree transducers and macro grammars. They serve as a model for syntax-directed semantics in which context information can be handled. In this paper the formal model of macro tree transducers is studied by investigating typical automata theoretical

  2. Macro tree transducers

    NARCIS (Netherlands)

    Engelfriet, Joost; Vogler, Heiko

    1985-01-01

    Macro tree transducers are a combination of top-down tree transducers and macro grammars. They serve as a model for syntax-directed semantics in which context information can be handled. In this paper the formal model of macro tree transducers is studied by investigating typical automata theoretical

  3. Hyperdiploidy in Childhood AML Associated with Low Age and AML-M7. A NOPHO-AML Study and Literature Review

    DEFF Research Database (Denmark)

    Sandahl, Julie Damgaard; Abrahamson, Jonas; Heldrup, Jesper

    a literature study searching for hyperdiploid childhood AML (50+) cases using the Mitelman, PubMed, and Scopus databases. The 105 patients from the literature study were compared to the hyperdiploid NOPHO-AML patients. The total cohort of 134 hyperdiploid cases were used to characterize hyperdiploid AML...

  4. L'Approche Macro-Linguistique du Fonctionnement des Langues et Ses Implications Pedagogiques: Role du Visuel (The Macro-Linguistic Approach to Language Functions and Its Pedagogical Implications: Role of the Visual Component). Melanges Pedagogiques, 1975.

    Science.gov (United States)

    Holec, H.

    This article considers the function and choice of visual aids in the teaching of languages in the light of recent work on communicative competence. An analysis of cartoons, comic strips, and television drama demonstrates that authentic verbo-visual communication consists of a network of interactions between visual and verbal information. This…

  5. Ediacaran Macro Body Fossils

    OpenAIRE

    Huang, Timothy D.; Jei-Fu Shaw; Liang Zheng; Chun-Lan Huang; YiLung Chang; ChuanWei Yang

    2010-01-01

    This paper, Ediacaran Macro Body Fossils, reports a new discovery of well preserved three dimensional macro body fossils of the Ediacaran Period in central YunNan province in the People's Republic of China. These body fossils will enable more detailed and in-depth exploration of the evolution of multi-cellular macro organisms on this planet, whereas in the past, researches could only rely on cast or imprint fossils.

  6. The chimeric genes AML1/DS1 and AML1/EAP inhibit AML1B activation at the CSF1R promoter, but only AML1/MDS1 has tumor-promoter properties

    Energy Technology Data Exchange (ETDEWEB)

    Zent, C.S.; Matheiu, C.; Rowley, J.D. [Univ. of Chicago, IL (United States)] [and others

    1996-02-06

    The (3;21)(q26;q22) translocation associated with treatment-related myelodysplastic syndrome, treatment-related acute myeloid leukemia, and blast crisis of chronic myeloid leukemia results in the expression of the chimeric genes AML1/EAP, AML1MDS1, and AML1/EVI1. AML1 (CBFA2), which codes for the {alpha} subunit of the heterodimeric transcription factor CBF, is also involved in the t(8;21), and the gene coding for the {beta} subunit (CBFB) is involved in the inv(16). These are two of the most common recurring chromosomal rearrangements in acute myeloid leukemia. CBF corresponds to the murine Pebp2 factor, and CBF binding sites are found in a number of eukaryotic and viral enhancers and promoters. We studied the effects of AML1/EAP and AML1/MDS1 at the AML1 binding site of the CSF1R (macrophage-colony-stimulating factor receptor gene) promoter by using reporter gene assays, and we analyzed the consequences of the expression of both chimeric proteins in an embryonic rat fibroblast cell line (Rat1A) in culture and after injection into athymic nude mice. Unlike AML1, which is an activator of the CSF1R promoter, the chimeric proteins did not transactivate the CSF1R promoter site but acted as inhibitors of AMLI (CBFA2). AML1/EAP and AML1/MDS1 expressed in adherent Rat1A cells decreased contact inhibition of growth, and expression of AML1/MDS1 was associated with acquisition of the ability to grow in suspension culture. Expression of AML1/MDS1 increased the tumorigenicity of Rat1A cells injected into athymic nude mice, whereas AML1/EAP expression provented tumor growth. These results suggest that expression of AML1/MDS1 can interfere with normal AML1 function, and that AML1/MDS1 has tumor-promoting properties in an embryonic rat fibroblast cell line. 26 refs., 5 figs.

  7. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

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

    2015-01-01

    aberrations that were present in the fully transformed committed HPCs together with the prognostic driver aberration. Adding to this vast heterogeneity and complexity of AML genomes and their clonal evolution, a recent study of a murine AML model demonstrated that t(9;11) AML originating from HSCs responded...... poorly to in vivo chemotherapy treatment as compared with t(9;11) AML originating from HPCs....

  8. AML Guide: Information for Patients and Caregivers

    Science.gov (United States)

    ... be used to identify the type of AML cells. Immunotherapy. The treatments that are used to boost the body’s immune system. Leukemia. A cancer of the marrow and blood. Lymph nodes. Small bean-shaped organs around the body that are ...

  9. Azacitidine in AML: a treatment option?

    NARCIS (Netherlands)

    Huls, G.A.

    2015-01-01

    In this issue of Blood, Dombret et al report the final analysis of the international phase 3 study of azacitidine vs conventional care regimens in older (>/=65 years), newly diagnosed acute myeloid leukemia (AML) patients with >30% bone marrow blasts and white blood cell (WBC) counts

  10. 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......) (44%). In conclusion, the WHO classification allocated 15% to AML-MDS, 44% to NOS and grouped together entities with clearly different outcome, therefore limiting the applicability of the current WHO classification in children with AML....

  11. Macros for Educational Research: Part II.

    Science.gov (United States)

    Woodrow, Janice E. J.

    1989-01-01

    Describes the design and operation of four software packages, or macros, written in the programing language of Microsoft's EXCEL for use on the Macintosh computer for data manipulation and presentation used in educational research. Reordering tabulated data, reversing the scoring of tabulated data, and creating tables and graphs are explained.…

  12. Treatment of older patients with AML.

    Science.gov (United States)

    Büchner, Thomas; Berdel, Wolfgang E; Wörmann, Bernhard; Schoch, Claudia; Haferlach, Torsten; Schnittger, Susanne; Kern, Wolfgang; Aul, Carlo; Lengfelder, Eva; Schumacher, Andrea; Reichle, Albrecht; Staib, Peter; Balleisen, Leopold; Eimermacher, Hartmut; Grüneisen, Andreas; Rasche, Herbert; Sauerland, Maria Cristina; Heinecke, Achim; Mesters, Rolf M; Serve, Hubert L; Kienast, Joachim; Hiddemann, Wolfgang

    2005-11-01

    Undertreatment of the older patients with AML can explain, in part, their inferior outcome when compared with that in younger patients. In analogy to the benefit of patients under the age of 60 years from high-dose AraC there are dosage related therapeutic effects in the patients over 60 years in particular for daunorubicin in the induction treatment, and for maintenance versus no maintenance in the post-remission treatment. Utilizing these effects can partly overcome the mostly unfavorable disease biology in older age AML, whereas the role of risk factors involved is not completely understood and the concept of dose-response needs to be requestioned. We recommend an adequate dosage of 60 mg/(m2day) daunorubicin for 3 days in a combination with standard dose AraC and 6-thioguanine given for induction and consolidation and followed by a prolonged monthly maintenance chemotherapy. Further improvements in supportive care may help delivering additional anti-leukemic cytotoxicity. As a novel approach, reduced toxicity preparative regimens may open up allogeneic transplantation for older patients with AML. Other new options like MDR modulators, antibody targeted therapies and tyrosine kinase inhibitors are under clinical investigation. A questionnaire study in patients with AML showed that according to patients' self-assessment intensive and prolonged treatment did not result in decreasing quality of life. This finding did not vary by age under or above 60 years. Given the actual median age in this disease being more than 60 years the adequate management of older age AML remains as the major challenge.

  13. Why Macro Practice Matters

    Science.gov (United States)

    Reisch, Michael

    2016-01-01

    This article asserts that macro practice is increasingly important in today's rapidly changing and complex practice environment. It briefly explores the history of macro practice in U.S. social work, summarizes its major contributions to the profession and to U.S. society, and provides some suggestions for how social work programs can expand…

  14. Nonterminal Separating Macro Grammars

    NARCIS (Netherlands)

    Hogendorp, Jan Anne; Asveld, P.R.J.; Nijholt, A.; Verbeek, Leo A.M.

    1987-01-01

    We extend the concept of nonterminal separating (or NTS) context-free grammar to nonterminal separating $m$-macro grammar where the mode of derivation $m$ is equal to "unrestricted". "outside-in' or "inside-out". Then we show some (partial) characterization results for these NTS $m$-macro grammars.

  15. Programming macro tree transducers

    DEFF Research Database (Denmark)

    Bahr, Patrick; Day, Laurence E.

    2013-01-01

    A tree transducer is a set of mutually recursive functions transforming an input tree into an output tree. Macro tree transducers extend this recursion scheme by allowing each function to be defined in terms of an arbitrary number of accumulation parameters. In this paper, we show how macro tree...... transducers can be concisely represented in Haskell, and demonstrate the benefits of utilising such an approach with a number of examples. In particular, tree transducers afford a modular programming style as they can be easily composed and manipulated. Our Haskell representation generalises the original...... definition of (macro) tree transducers, abolishing a restriction on finite state spaces. However, as we demonstrate, this generalisation does not affect compositionality....

  16. Programming macro tree transducers

    DEFF Research Database (Denmark)

    Bahr, Patrick; Day, Laurence E.

    2013-01-01

    A tree transducer is a set of mutually recursive functions transforming an input tree into an output tree. Macro tree transducers extend this recursion scheme by allowing each function to be defined in terms of an arbitrary number of accumulation parameters. In this paper, we show how macro tree...... transducers can be concisely represented in Haskell, and demonstrate the benefits of utilising such an approach with a number of examples. In particular, tree transducers afford a modular programming style as they can be easily composed and manipulated. Our Haskell representation generalises the original...... definition of (macro) tree transducers, abolishing a restriction on finite state spaces. However, as we demonstrate, this generalisation does not affect compositionality....

  17. Where macro meets micro.

    Science.gov (United States)

    Berry, R Stephen; Smirnov, Boris M

    2014-06-01

    Reconciling or somehow linking the macroscopic and microscopic approaches to chemical and physical processes has been a challenge unaddressed for many years. One approach, presented here, treats the issue by examining individual phenomena well described by a macro approach that fails when applied to small systems. The key to the approach is determining the approximate system size below which the breakdown of the macro description is observable. The most developed example is the failure of the Gibbs phase rule for sufficiently small atomic clusters. Other examples, such as the onset, at sufficient size, of the insulator-to-metal transition, are discussed, as are some still more challenging phenomena.

  18. Macro Intentions, Micro Realities

    NARCIS (Netherlands)

    A.R. Muller (Allan); R.J.M. van Tulder (Rob)

    2001-01-01

    textabstractThe current understanding of Regional Integration is largely macro-economic and political in orientation and has tended to neglect, even ex post, the significance of the Single European Market (SEM) for the spatial restructuring of individual firms. The problem stems largely from a lopsi

  19. 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...... (P = 0.01). We conclude that population-based cytogenetic studies of adult s-AML and age- and sex-matched de novo AML show comparable distributions of chromosome abnormalities....

  20. Multilanguage function and user-macro function. Multi gengo kinoter dot user-macro kino

    Energy Technology Data Exchange (ETDEWEB)

    Fukui, Y.; Yatsuda, Y. (Fuji Electric Co. Ltd., Tokyo (Japan))

    1991-11-10

    The multilanguage function and user-macro function of programmable controllers (PCs), FLEX-PC N series, were outlined which have been developed for machine control. The multilanguage function was developed as an effective function for realizing the same familiar operational environments on FLEX-PC N series as those on other manufacturers{prime} PCs or programming tools. In a programming tool, it realized various operational environments with the common base hardware, several keyboards and several system softwares, while in a PC, it efficiently realized such environments with the common base hardware and several executive hardwares for programs. The user-macro function was developed to enhance a programming efficiency, and could be easily operated by programming tools. It included both macros written with the instructions of several PCs and the assembler language of several MPUs. 8 figs.

  1. Macro-Control Malady

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    An undeniable fact is that China practices macro-control more frequently than countries with a developed market economy. Since the country began to adopt the policy of reform and opening up in 1978, the Central Government has launched five adjustments to cool down the economy. Professor Li Yiping at the School of Economics, the Renmin University of China, attributes the frequent control practices to the immature economic system.

  2. KEGG DISEASE / Acute myeloid leukemia (AML) [KEGG DISEASE

    Lifescience Database Archive (English)

    Full Text Available DISEASE: H00003 Entry H00003Disease Name Acute myeloid leukemia (AML) Description Acute.... Category Cancer Brite Human diseases [BR:br08402] Cancers Cancers of haematopoietic and lymphoid tissues H00003Acute...atopoietic and related tissue C92Myeloid leukaemia H00003Acute myeloid leukemia (AML) Cancer-accociated carb...ohydrates [br08441.html] H00003 Pathway hsa05221Acute myeloid leukemiahsa05202Transcriptional misregulation ... or t(16; 16)(p13, q22), (CBF-beta/MYH11) ICD-O: 9866/3, Tumor type: Acute promyelocytic leukaemia (AML with

  3. Acute Myeloid Leukemia (AML) | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available cian’s Choice in Patients ≥ 60 Years Old with Relapsed/Refractory Acute Myeloid L....1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute... Myeloid Leukemia (AML) E.1.1.1Medical condition in easily understood language Acute My... condition or disease under investigation E.1.2Version 18.0 E.1.2Level LLT E.1.2Classification code 10000886 E.1.2Term Acute

  4. The Accelerator Markup Language and the Universal Accelerator Parser

    Energy Technology Data Exchange (ETDEWEB)

    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

    2006-10-06

    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.

  5. The Accelerator Markup Language and the Universal Accelerator Parser

    Energy Technology Data Exchange (ETDEWEB)

    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

    2006-10-06

    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.

  6. 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.

  7. Hyperdiploidy in Childhood AML Associated with Low Age and AML-M7. A NOPHO-AML Study and Literature Review

    DEFF Research Database (Denmark)

    Sandahl, Julie Damgaard; Abrahamson, Jonas; Heldrup, Jesper

    Introduction: High hyperdiploidy (51–67 chromosomes) is one of the most common cytogenetic abnormality patterns in childhood B-cell precursor acute lymphoblastic leukemia (ALL) and the clinical and cytogenetic features are well characterized. High hyperdiploidy in pediatric acute myeloid leukemia...... abnormalities among the pediatric hyperdiploid AML patients is relatively unknown. Current knowledge in this field is based on small adult series or case reports. In this descriptive study we describe the clinical - and cytogenetic features in childhood hyperdiploid AML with a modal chromosome number at 50...

  8. Screening for MLL tandem duplication in 387 unselected patients with AML identify a prognostically unfavorable subset of AML.

    Science.gov (United States)

    Schnittger, S; Kinkelin, U; Schoch, C; Heinecke, A; Haase, D; Haferlach, T; Büchner, T; Wörmann, B; Hiddemann, W; Griesinger, F

    2000-05-01

    Partial tandem duplications of the MLL gene have been associated with trisomy 11 in acute myeloid leukemia (AML) and recently, have also been reported for karyotypically normal AML. In order to test the incidence and prognostic importance of this molecular marker, we have analyzed eight cases of AML with trisomy 11 and 387 unselected consecutive cases with AML for partial duplications of the MLL gene. Patients with normal karyotypes and those with various chromosome aberrations were included. De novo as well as secondary leukemias including all FAB subtypes were analyzed. Performing a one-step RT-PCR with 35 cycles using an exon 9 forward primer and an exon 3 reverse primer partial tandem duplications of the MLL gene were demonstrated in 3/8 (37.5%) patients with trisomy 11. In addition, 13/387 (3.4%) of unselected cases revealed a tandem duplication. Ten of these 13 cases were cytogenetically normal, the other three cases had secondary AML after MDS, three were therapy-related AML (t-AML). Of the 16 MLL-duplication positive cases, seven were classified as FAB M2, two as M1, five as M4, one as M0, one as M5b. The mean age was 62.3 years for patients with MLL duplication vs 50.3 years for the control group. Of 15 adult patients, 12 received treatment. Of these, three were nonresponders, five had early relapse (common than previously reported; (2) are preferentially observed in AML with normal karyotypes, but can also be found in the presence of chromosome alterations; (3) are not strongly associated with an FAB subtype; (4) were not observed with the prognostically favorable t(8;21), inv(16), and t(15;17), other recurrent translocations, or in complex karyotypes; and (5) identifies a subgroup of patients with an unfavorable prognosis.

  9. Going "Macro": Exploring the Careers of Macro Practitioners.

    Science.gov (United States)

    Pritzker, Suzanne; Applewhite, Steven R

    2015-07-01

    Important benefits accrue to the profession and to its vulnerable clientele when social workers hold positions with substantial community or policy influence. However, fewer social workers are holding these positions than in the past, and student preferences to pursue macro-specific training have declined. To improve the social work profession's ability to recruit and educate students interested in competing for leadership positions in human services organizations, this article analyzes data from a survey of MSW graduates of a public school of social work located in the southwestern United States and currently working as macro practitioners. Findings indicate that macro social workers can successfully compete for mid-level and top-level administrative and policy positions, and provide evidence contrary to many of the concerns students express when deciding whether to pursue a macro concentration or career. The article concludes with a discussion of the implications for supporting and educating social work students interested in pursuing a macro practice career.

  10. The Construction of Macro-events. A typological perspective

    DEFF Research Database (Denmark)

    Pedersen, Johan

    2009-01-01

    In this paper Talmy's influential typology of macro-events (Talmy 1985, 1987, 1991, 2000) is discussed from the point of view of construction grammar (Goldberg 1995, 2006). Talmy has described typological differences of lexicalization between what he calls satellite framed languages and verb fram...

  11. 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

  12. 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...

  13. Mitochondrial BAX Determines the Predisposition to Apoptosis in Human AML.

    Science.gov (United States)

    Reichenbach, Frank; Wiedenmann, Cornelius; Schalk, Enrico; Becker, Diana; Funk, Kathrin; Scholz-Kreisel, Peter; Todt, Franziska; Wolleschak, Denise; Döhner, Konstanze; Marquardt, Jens U; Heidel, Florian; Edlich, Frank

    2017-08-15

    Purpose: Cell-to-cell variability in apoptosis signaling contributes to heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia, such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit mammalian cells to apoptosis and are inhibited by retrotranslocation from the mitochondria into the cytosol. The subcellular localization of BAX and BAK could determine the cellular predisposition to apoptotic death.Experimental Design: The relative localization of BAX and BAK was determined by fractionation of AML cell lines and patient samples of a test cohort and a validation cohort.Results: This study shows that relative BAX localization determines the predisposition of different AML cell lines to apoptosis. Human AML displays a surprising variety of relative BAX localizations. In a test cohort of 48 patients with AML, mitochondria-shifted BAX correlated with improved patient survival, FLT3-ITD status, and leukocytosis. Analysis of a validation cohort of 80 elderly patients treated with myelosuppressive chemotherapy confirmed that relative BAX localization correlates with probability of disease progression, FLT3-ITD status, and leukocytosis. Relative BAX localization could therefore be helpful to identify elderly or frail patients who may benefit from cytotoxic therapy.Conclusions: In this retrospective analysis of two independent AML cohorts, our data suggest that Bax localization may predict prognosis of patients with AML and cellular predisposition to apoptosis, combining the actual contribution of known and unknown factors to a final "common path." Clin Cancer Res; 23(16); 4805-16. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Clinical Results of Hypomethylating Agents in AML Treatment

    Directory of Open Access Journals (Sweden)

    Marjan Cruijsen

    2014-12-01

    Full Text Available Epigenetic changes play an important role in the development of acute myeloid leukemia (AML. Unlike gene mutations, epigenetic changes are potentially reversible, which makes them attractive for therapeutic intervention. Agents that affect epigenetics are the DNA methyltransferase inhibitors, azacitidine and decitabine. Because of their relatively mild side effects, azacitidine and decitabine are particularly feasible for the treatment of older patients and patients with co-morbidities. Both drugs have remarkable activity against AML blasts with unfavorable cytogenetic characteristics. Recent phase 3 trials have shown the superiority of azacitidine and decitabine compared with conventional care for older AML patients (not eligible for intensive treatment. Results of treatment with modifications of the standard azacitidine (seven days 75 mg/m2 SC; every four weeks and decitabine (five days 20 mg/m2 IV; every four weeks schedules have been reported. Particularly, the results of the 10-day decitabine schedule are promising, revealing complete remission (CR rates around 45% (CR + CRi (i.e., CR with incomplete blood count recovery around 64% almost comparable with intensive chemotherapy. Application of hypomethylating agents to control AML at the cost of minimal toxicity is a very promising strategy to “bridge” older patients with co-morbidities to the potential curative treatment of allogeneic hematopoietic cell transplantation. In this article, we discuss the role of DNA methyltransferase inhibitors in AML.

  15. Securinine, a myeloid differentiation agent with therapeutic potential for AML.

    Directory of Open Access Journals (Sweden)

    Kalpana Gupta

    Full Text Available As the defining feature of Acute Myeloid Leukemia (AML is a maturation arrest, a highly desirable therapeutic strategy is to induce leukemic cell maturation. This therapeutic strategy has the potential of avoiding the significant side effects that occur with the traditional AML therapeutics. We identified a natural compound securinine, as a leukemia differentiation-inducing agent. Securinine is a plant-derived alkaloid that has previously been used clinically as a therapeutic for primarily neurological related diseases. Securinine induces monocytic differentiation of a wide range of myeloid leukemia cell lines as well as primary leukemic patient samples. Securinine's clinical potential for AML can be seen from its ability to induce significant growth arrest in cell lines and patient samples as well as its activity in significantly impairing the growth of AML tumors in nude mice. In addition, securinine can synergize with currently employed agents such as ATRA and decitabine to induce differentiation. This study has revealed securinine induces differentiation through the activation of DNA damage signaling. Securinine is a promising new monocytic differentiation inducing agent for AML that has seen previous clinical use for non-related disorders.

  16. AML1/RUNX1 Phosphorylation by Cyclin-Dependent Kinases Regulates the Degradation of AML1/RUNX1 by the Anaphase-Promoting Complex‡

    Science.gov (United States)

    Biggs, Joseph R.; Peterson, Luke F.; Zhang, Youhong; Kraft, Andrew S.; Zhang, Dong-Er

    2006-01-01

    AML1 (RUNX1) regulates hematopoiesis, angiogenesis, muscle function, and neurogenesis. Previous studies have shown that phosphorylation of AML1, particularly at serines 276 and 303, affects its transcriptional activation. Here, we report that phosphorylation of AML1 serines 276 and 303 can be blocked in vivo by inhibitors of the cyclin-dependent kinases (CDKs) Cdk1 and Cdk2. Furthermore, these residues can be phosphorylated in vitro by purified Cdk1/cyclin B and Cdk2/cyclin A. Mutant AML1 protein which cannot be phosphorylated at these sites (AML1-4A) is more stable than wild-type AML1. AML-4A is resistant to degradation mediated by Cdc20, one of the substrate-targeting subunits of the anaphase-promoting complex (APC). However, Cdh1, another targeting subunit used by the APC, can mediate the degradation of AML1-4A. A phospho-mimic protein, AML1-4D, can be targeted by Cdc20 or Cdh1. These observations suggest that both Cdc20 and Cdh1 can target AML1 for degradation by the APC but that AML1 phosphorylation may affect degradation mediated by Cdc20-APC to a greater degree. PMID:17015473

  17. 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

  18. Macro finance early warning system

    Institute of Scientific and Technical Information of China (English)

    Guihuan ZHENG; Xun ZHANG; Wei SHANG; Shanying XU

    2009-01-01

    In this paper, a financial early warning informa-tion system is developed based on the multi-dimensional cli-mate approach that is featured with a multi-dimensional in-dex construction and the relevant multi-dimensional analy-sis. Requirement analysis and design issues of building an information system supporting this multi-dimensional cli-mate approach are discussed in detail. And a case using this system to study the macro financial issues is presented to illustrate how the proposed multi-dimensional approach works in the information system we design. This research is an interdisciplinary work of economic theories, macro finan-cial empirical studies, and software engineering. With ad-vanced macro financial early warning theories implemented in a web application, the Macro Financial Early Warning System (FEWS) developed in this research has been proved to be effective in a trial running in the Forecasting research institute of the Chinese Academy of Sciences.

  19. On Language Management in Multinational Companies in the Czech Republic

    Science.gov (United States)

    Nekvapil, Jiri; Nekula, Marek

    2006-01-01

    In this paper, we demonstrate the dialectical relationship between micro and macro language planning: macro planning influences micro planning and yet macro planning results (or should result) from micro planning. The relation between the two planning perspectives is illustrated within the framework of Language Management Theory (Jernudd &…

  20. LANGUAGE

    Institute of Scientific and Technical Information of China (English)

    朱妤

    2009-01-01

    @@ The word"language"comes from the Latin(拉丁语)word"lingua",which means"tongue".The tongue is used in more sound combinations(结合)than any other organ(器官)of speech.A broader(概括性的)interpretation(解释)of"language"is that it is any form of expression.This includes(包括)writing,sign(手势)language,dance,music,painting,and mathematics.But the basic(基本的)form of language is speech.

  1. Treatment results of three consecutive German childhood AML trials: BFM-78, -83, and -87. AML-BFM-Group.

    Science.gov (United States)

    Ritter, J; Creutzig, U; Schellong, G

    1992-01-01

    Acute myelogenous leukemia (AML) represents a heterogenous group of leukemias in adults as well as in children. The BFM group initiated 3 consecutive studies on the treatment of this disease. Between December 1978 and April 1991, 543 children under the age of 17 years entered the 3 consecutive multicenter studies, AML-BFM-78 (n = 151), AML-BFM-83 (n = 182), and the still ongoing study AML-BFM-87 (n = 210). The treatment strategy of BFM-78 consisted of an eight week induction/-consolidation regimen employing 7 different drugs together with cranial irradiation, followed by continuous maintenance for two years. The main alteration in the second study BFM-83 was the addition of an intensive 8-day ADE induction course (cytosine arabinoside, daunorubicin, etoposide). In the ongoing trial BFM-87 two courses of HD-ARA-C and etoposide are given after consolidation. CR rates were 80% in trials I and II, and 78% in trial III. The probability of a 4.5-year event-free survival was 35%, SD 4% in study I; 49%, SD 4% in study II, and 45%, SD 4% in study III. The probability of a 4.5-year event-free interval (EFI) was increased from 45%, SD 5% in study I to 61%, SD 4% in study II, it is in the same range in study III (58%, SD 5%). Seven of 10 children which underwent bone marrow transplantation (BMT) in 1. CR are still in first CR after a maximum follow-up time of 3.5 yrs. In summary, the addition of HD-ARA-C together with etoposide given after induction/consolidation treatment did not further reduce the incidence of relapses in childhood AML. So far, the results of study BFM-87 are in the same range than those of study BFM-83.

  2. 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......;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3-ITD mutations (58%). The 5-year event-free survival for patients with +8 alone was 50% and 5-year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML...

  3. Discussing Course Literature Online: Analysis of Macro Speech Acts in an Asynchronous Computer Conference

    Science.gov (United States)

    Kosunen, Riitta

    2009-01-01

    This paper presents a macro speech act analysis of computer-mediated conferencing on a university course on language pedagogy. Students read scholarly articles on language learning and discussed them online, in order to make sense of them collaboratively in preparation for a reflective essay. The study explores how the course participants made use…

  4. Progressive failure analysis of composite structure based on micro- and macro-mechanics models

    Institute of Scientific and Technical Information of China (English)

    孙志刚; 阮绍明; 陈磊; 宋迎东

    2015-01-01

    Based on parameter design language, a program of progressive failure analysis in composite structures is proposed. In this program, the relationship between macro- and micro-mechanics is established and the macro stress distribution of the composite structure is calculated by commercial finite element software. According to the macro-stress, the damaged point is found and the micro-stress distribution of representative volume element is calculated by finite-volume direct averaging micromechanics (FVDAM). Compared with the results calculated by failure criterion based on macro-stress field (the maximum stress criteria and Hashin criteria) and micro-stress field (Huang model), it is proven that the failure analysis based on macro- and micro-mechanics model is feasible and efficient.

  5. The language policy of the language teacher

    Directory of Open Access Journals (Sweden)

    Karen Risager

    2010-08-01

    Full Text Available Language policy has to do with how far and how one is to act in relation to this complexity. Language policy does not only take place at the macro-level: in international organisations, transnational companies, states, etc., but also at the micro-level; in the interaction between people.

  6. 101 Ready-To-Use Excel Macros

    CERN Document Server

    Alexander, Michael

    2012-01-01

    Save time and be more productive with this helpful guide to Excel macros! While most books about Excel macros offer only minor examples, usually aimed at illustrating a particular topic, this invaluable resource provides you with the tools needed to efficiently and effectively program Excel macros immediately. Step-by-step instructions show you how to create VBA macros and explain how to customize your applications to look and work exactly as you want them to. By the end of the book, you will understand how each featured macro works, be able to reuse the macros included in the book and online,

  7. Study of Rpl22 in MDS and AML

    Science.gov (United States)

    2015-10-01

    usually linked with bone marrow disease , our data doesn’t support p53 is the key player in MDS/AML caused by Rpl22 defect. 3. Uncovered a pathological...our lab and others supports that ribosomal proteins play a critical role in development(1) and diseases including bone marrow disease (2) in addition...that RP play a critical but poorly understood role in development as well as disease . Mutations in RP cause a group of diseases collectively termed

  8. [Research progress of epigenetic drug decitabine in AML].

    Science.gov (United States)

    Zhang, Rui; Li, Hui-Min

    2014-10-01

    Epigenetics is a gene regulation mechanism that can be reversible and heritable, but do not involve the DNA sequence changes. DNA methylation is one of the most important epigenetic modifications, which is closely correlate with tumorigenesis. Decitabine is a methylation inhibitor, which has different action mechanism and targeting characteristics from the traditional chemotherapy, representing a new therapeutic strategy. This review mainly focuses on the anti-leukemia mechanism of decitabine and its clinical efficacy for AML.

  9. Fusion of dendritic cells and CD34+CD38- acute myeloid leukemia (AML) cells potentiates targeting AML-initiating cells by specific CTL induction.

    Science.gov (United States)

    Lei, Zhang; Zhang, Gui-Mei; Hong, Mei; Feng, Zuo-Hua; Huang, Bo

    2009-05-01

    Distinct leukemia-initiating cells (L-ICs) represent a critical target for therapeutic intervention of acute myeloid leukemia (AML). A potential strategy to eradicate L-ICs is to generate L-IC-specific cytotoxic T lymphocytes (CTLs). However, owing to rarity and immortality of L-ICs, it is difficult for antigen-presenting cells to capture L-ICs for specific antigen presentation. Here, we report a novel approach by fusing allogeneic dendritic cells (DCs) and CD34CD38 AML progenitor cells, through which specific CTLs were effectively induced, leading to the cytolysis to AML-initiating cells. Fusion of either DC/CD34CD38 AML cell or DC/CD34 AML cell could effectively induce the proliferation and activation of CTLs. However, only the former CTLs could effectively attack AML progenitor cells, and result in the unkilled progenitor/initiating cells losing the abilities of active proliferation in vitro and engraftment in NOD-SCID mice. These findings suggest that AML progenitor/initiating cell-specific CTLs may be generated based on allogeneic DC/progenitor cell fusion strategy; the induced CTLs may potentially eradicate AML by targeting L-ICs directly or indirectly.

  10. Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial

    NARCIS (Netherlands)

    Aslanyan, M.G.; Kroeze, L.; Langemeijer, S.M.C.; Koorenhof-Scheele, T.N.; Massop, M.; Hoogen, P. van; Linders, E.H.P.; Locht, L.T.F. van de; Tonnissen, E.; Heijden, A. van der; Silva-Coelho, P.; Cilloni, D.; Saglio, G.; Marie, J.P.; Tang, R.; Labar, B.; Amadori, S.; Muus, P.; Willemze, R.; Marijt, E.W.; Witte, T.J. de; Reijden, B.A. van der; Suciu, S.; Jansen, J.H.

    2014-01-01

    We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients < 60 years of age enrolled in the European Organization For Research and Treatment of Cancer (EORTC)/Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) AML-12 06991 c

  11. The Protection of Minority Language in Macro Vision and Cognitive Mechanisms%少数民族语言保护的宏观视界与认知机制解构

    Institute of Scientific and Technical Information of China (English)

    周彦每

    2012-01-01

    Minority language bears the weight of regional culture, its side. At the same time, diversity of China's ethnic composition lays the s national minority language generation, therefore, protecting minority soil is to trace back the history of the other foundation of complex sample of our country' languages not only can protect our ethnic cul- rural diversity, but also help to xafeguard the languje rigits of the members of minority language rights. Therefore,in national linguistic study of macroscopic point of view, to re-examine the minority language, value perspective of mi- nority language generation environment, forming the national language and Chinese culture balance. On the language structure and cognitive mechanism, we should pay more attention to national language pronunciation structure, clarify the national languages vocabulary generation mechanism, draw the outline of minority language groups tillers. Return to save our national language and cultural heritage of the mission, innovation and national language of the original ecological structure and value of.%少数民族语言承载着区域文化,其生成土壤也是回溯历史的另一侧面。同时,我国民族构成的多样性,奠定了我国少数民族语言生成的复杂样本。可以说,保护少数民族语言不但保护了我国民族文化的多元化,而且有助于广大少数民族成员的语言表达权利。因此,在民族语言学研究的宏观视界内,要重新检视少数民族的语言价值,发掘少数民族语言的生成环境,型塑民族语言与汉语的文化平衡。在语言结构与认知机制上,要注重民族语言的发音结构,厘清民族语言词汇的生成机制,勾勒少数民族语言的语群分蘖。回归拯救我国民族语言文化遗产的使命,创新民族语言的原生态结构与价值。

  12. 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

  13. [Dendritic cells (DC) induced from acute myeloid leukemia (AML) cells with cytokine cocktails].

    Science.gov (United States)

    Yan, Kuang-hua; You, Sheng-guo; Bian, Shou-geng; Ma, Guan-jie; Ge, Wei; Ma, Shuang; Liu, Shi-he; Zhao, Chun-hua

    2003-07-01

    To explore the feasibility of DC being in vitro induced from AML cells with cytokine cocktails and their biological properties. AML cells were cultured in either presence or absence of cytokine cocktails. DC were studied for morphology, and cytochemical and immunofluorescent staining. Functions of DC were examined by MLC, FITC-conjugated dextran uptake test, and LDH release assay. RT-PCR and FISH were used to analyze the specific fusion genes of culture-derived DC. Classical DC morphological changes occurred in all 15 cultured AML cells. DC-associated surface molecules such as CD(1a), CD(80), CD(86), CD(106), CD(83) and HLA-DR were upregulated (P AML cells uncultured or cultured in the absence of cytokines (P CTL assay was performed in 5 of the 15 samples. At effector/target ratio of 20:1, auto-T lymphocytes primed with the culture-derived DC exhibited no more killing activity to auto-AML cells than those stimulated by IL-2 or uncultured AML cells. Culture-derived DC presenced the native AML-specific aberrant karyotype and related fusion gene. Cytokine cocktails could in vitro induce AML cells into DC with classical morphology, immunophenotype and function. DC maturity induced by different cytokine cocktails could be variable. Culture-derived DC were originated from the native AML cells. AML cells could make the auto-T lymphocyte anergy.

  14. Spontaneous Remission in an Older Patient with Relapsed FLT3 ITD Mutant AML

    Directory of Open Access Journals (Sweden)

    Pankit Vachhani

    2016-01-01

    Full Text Available Spontaneous remission (SR of acute myeloid leukemia (AML is a very rare phenomenon. AML characterized by FLT3 internal tandem duplication (FLT3 ITD is typically associated with an aggressive clinical course with rapid progression, relapse, and short overall survival in the absence of transplantation. We report here the first case of SR of FLT3 ITD mutant AML in the literature. Our patient was an elderly woman with relapsed NPM1 and FLT3 ITD mutant AML whose disease underwent SR for a brief duration without precipitating cause. We review the potential immune mechanisms underlying SR in AML and discuss the implications for novel immunotherapeutic approaches for FLT3 mutant AML.

  15. The role of therapeutic leukapheresis in hyperleukocytotic AML.

    Directory of Open Access Journals (Sweden)

    Friederike Pastore

    Full Text Available PURPOSE: 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. PATIENTS: 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. RESULTS: 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. DISCUSSION: 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.

  16. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts

    OpenAIRE

    Mehta, Rohtesh S.; Chen, Xiaohua; Antony, Jeyaraj; Boyiadzis, Michael; Szabolcs, Paul

    2016-01-01

    Expanding on our prior studies with cord blood T-cells, we hypothesized that primary AML-reactive autologous T-cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T-cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T-cells were stimulated with IFN-γ treated autologous AML weekly X 3, IL-15 and agonistic anti-CD28 antibody. CTL and ELISpot assays tested functionality; RT-qPCR tested AML and T-cell gene expression profiles. Based on co...

  17. Response properties of cat AMLS neurons to optic flow stimuli

    Institute of Scientific and Technical Information of China (English)

    LI; Baowang(李宝旺); LI; Bing(李兵); CHEN; Hui(陈辉); XU; Ying(徐颖); DIAO; Yuncheng(刁云程)

    2002-01-01

    Spiral and translation stimuli were used to investigate the response properties of cat AMLS (anteromedial lateral suprasylvian area) neurons to optic flow. The overwhelming majority of cells could be significantly excited by the two modes of stimuli and most responsive cells displayed obvious direction selectivity. It is the first time to find a visual area in mammalian brain preferring rotation stimuli. Two representative hypotheses are discussed here on the neural mechanism of optic flow analysis in visual cortex, and some new viewpoints are proposed to explain the experimental results.

  18. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......) 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...

  19. Transcription of the AML1/ETO chimera is guided by the P2 promoter of the AML1 gene in the Kasumi-1 cell line.

    Science.gov (United States)

    Markova, Elena N; Kantidze, Omar L; Razin, Sergey V

    2012-12-01

    Chromosomal translocation t (8;21)(q22;22) is one of the most frequent cytogenetic abnormalities found in acute myeloid leukaemia (AML). It generates the AML1/ETO fusion gene, which itself supports human haematopoietic stem cell self-renewal. However, the mechanism guiding transcription of this chimeric gene remains unclear. In our work, we attempted to shed light on this essential issue. We investigated the promoter from which transcription of the AML1/ETO gene is initiated and defined the three-dimensional structure of the whole rearranged locus. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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

  1. Isoform-Specific Potentiation of Stem and Progenitor Cell Engraftment by AML1/RUNX1

    Science.gov (United States)

    Tsuzuki, Shinobu; Hong, Dengli; Gupta, Rajeev; Matsuo, Keitaro; Seto, Masao; Enver, Tariq

    2007-01-01

    Background 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. Methods and Findings 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. Conclusions 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

  2. The Construction of Macro-events. A typological perspective

    DEFF Research Database (Denmark)

    Pedersen, Johan

    2009-01-01

    languages. The discussion originates in a contrastive analysis of a short story by H. C. Andersen available in six parallel versions: the original Danish version, an English, a German, a Spanish, an Italian and a French version. The paper argues that the generalized version of the typology (Talmy 1991, 2000......, as a device for organizing the information, and that the typology is anchored in this task. The interpretation of Talmy's descriptive typology is in this perspective that some pairs of MIC/SIC are more entrenched in the grammar of some languages than in others. The proposed framework is well suited......In this paper Talmy's influential typology of macro-events (Talmy 1985, 1987, 1991, 2000) is discussed from the point of view of construction grammar (Goldberg 1995, 2006). Talmy has described typological differences of lexicalization between what he calls satellite framed languages and verb framed...

  3. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts

    Science.gov (United States)

    Mehta, Rohtesh S.; Chen, Xiaohua; Antony, Jeyaraj; Boyiadzis, Michael; Szabolcs, Paul

    2015-01-01

    Expanding on our prior studies with cord blood T-cells, we hypothesized that primary AML-reactive autologous T-cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T-cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T-cells were stimulated with IFN-γ treated autologous AML weekly X 3, IL-15 and agonistic anti-CD28 antibody. CTL and ELISpot assays tested functionality; RT-qPCR tested AML and T-cell gene expression profiles. Based on combined positive ELIspot and CTL assays, T-cells reactive against AML were generated in 5/8 patients. Treg proportion declined post-co-cultures in reactive T-cell samples. AML-reactive T-cells displayed an activated gene expression profile. “Resistant” AML blasts displayed genes associated with immunosuppressive MDSC. We discuss our approach to creating primary AML-reactive autologous T-cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia reactive T-cells. PMID:26849076

  4. Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML with normal cytogenetics.

    Directory of Open Access Journals (Sweden)

    Marta Fernandez-Mercado

    Full Text Available Acute myeloid leukemia patients with normal cytogenetics (CN-AML account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8% and FLT3 (50.0%, and in secondary cases ASXL1 (48.5% and TET2 (30.3%. We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.

  5. Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML) with normal cytogenetics.

    Science.gov (United States)

    Fernandez-Mercado, Marta; Yip, Bon Ham; Pellagatti, Andrea; Davies, Carwyn; Larrayoz, María José; Kondo, Toshinori; Pérez, Cristina; Killick, Sally; McDonald, Emma-Jane; Odero, María Dolores; Agirre, Xabier; Prósper, Felipe; Calasanz, María José; Wainscoat, James S; Boultwood, Jacqueline

    2012-01-01

    Acute myeloid leukemia patients with normal cytogenetics (CN-AML) account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL) in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8%) and FLT3 (50.0%), and in secondary cases ASXL1 (48.5%) and TET2 (30.3%). We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.

  6. 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

    Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a k...

  7. Pipeline for macro- and microarray analyses

    Directory of Open Access Journals (Sweden)

    R. Vicentini

    2007-05-01

    Full Text Available The pipeline for macro- and microarray analyses (PMmA is a set of scripts with a web interface developed to analyze DNA array data generated by array image quantification software. PMmA is designed for use with single- or double-color array data and to work as a pipeline in five classes (data format, normalization, data analysis, clustering, and array maps. It can also be used as a plugin in the BioArray Software Environment, an open-source database for array analysis, or used in a local version of the web service. All scripts in PMmA were developed in the PERL programming language and statistical analysis functions were implemented in the R statistical language. Consequently, our package is a platform-independent software. Our algorithms can correctly select almost 90% of the differentially expressed genes, showing a superior performance compared to other methods of analysis. The pipeline software has been applied to 1536 expressed sequence tags macroarray public data of sugarcane exposed to cold for 3 to 48 h. PMmA identified thirty cold-responsive genes previously unidentified in this public dataset. Fourteen genes were up-regulated, two had a variable expression and the other fourteen were down-regulated in the treatments. These new findings certainly were a consequence of using a superior statistical analysis approach, since the original study did not take into account the dependence of data variability on the average signal intensity of each gene. The web interface, supplementary information, and the package source code are available, free, to non-commercial users at http://ipe.cbmeg.unicamp.br/pub/PMmA.

  8. Spreadsheet macros for coloring sequence alignments.

    Science.gov (United States)

    Haygood, M G

    1993-12-01

    This article describes a set of Microsoft Excel macros designed to color amino acid and nucleotide sequence alignments for review and preparation of visual aids. The colored alignments can then be modified to emphasize features of interest. Procedures for importing and coloring sequences are described. The macro file adds a new menu to the menu bar containing sequence-related commands to enable users unfamiliar with Excel to use the macros more readily. The macros were designed for use with Macintosh computers but will also run with the DOS version of Excel.

  9. Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Stams, Wendy A G; den Boer, Monique L; Holleman, Amy; Appel, Inge M; Beverloo, H Berna; van Wering, Elisabeth R; Janka-Schaub, Gritta E; Evans, William E; Pieters, Rob

    2005-06-01

    Resistance to L-asparaginase in leukemic cells may be caused by an elevated cellular expression of asparagine synthetase (AS). Previously, we reported that high AS expression did not correlate to L-asparaginase resistance in TEL-AML1-positive B-lineage acute lymphoblastic leukemia (ALL). In the present study we confirmed this finding in TEL-AML1-positive patients (n = 28) using microarrays. In contrast, 35 L-asparaginase-resistant TEL-AML1-negative B-lineage ALL patients had a significant 3.5-fold higher AS expression than 43 sensitive patients (P < .001). Using real-time quantitative polymerase chain reaction (RTQ-PCR), this finding was confirmed in an independent group of 39 TEL-AML1-negative B-lineage ALL patients (P = .03). High expression of AS was associated with poor prognosis (4-year probability of disease-free survival [pDFS] 58% +/- 11%) compared with low expression (4-year pDFS 83% +/- 7%; P = .009). We conclude that resistance to l-asparaginase and relapse risk are associated with high expression of AS in TEL-AML1-negative but not TEL-AML1-positive B-lineage ALL.

  10. 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...... the MDS/AML classification system, incorporating as yet unknown molecular genetic and epigenetic pathomechanisms, which are likely reflected by aberrant gene expression patterns. In this study, we provide a comprehensive review on how GEP has contributed to a refined molecular taxonomy of MDS and AML...... technologies, which will continue to improve our understanding of malignant transformation in myeloid malignancies and thereby contribute to individualized risk-adapted treatment strategies for MDS and AML patients....

  11. Analysis of Factors on Fluent Communication in English for Chinese Learners from Macro and Micro Perspectives

    Institute of Scientific and Technical Information of China (English)

    翟佳

    2014-01-01

    This paper will study on the factors that directly or indirectly influence the fluent communication in English for Chi-nese learners from both macro and micro perspectives, on the basis of some recent reports about English language learning. Ac-cording to the principles of language learning and teaching, the author analyses a theoretical framework for the willingness to Eng-lish language communication and puts forward the three kinds of factors, including personality factors, socio-cultural factors and styles and strategies that directly and indirectly influence the willingness to English language communication and then influence English communication. This study will further illustrate three aspects:first, the general tendency and characteristics of students ’ willingness to English language communication inside and outside the classroom; second, the influence of first language acquisi-tion and inter-language on English communication; third, the influence of communicative motivation, communicative anxiety, communicative competence, language evaluation on fluent English communication.

  12. Intertwining Lexical and Conceptual Learning Trajectories--A Design Research Study on Dual Macro-Scaffolding towards Percentages

    Science.gov (United States)

    Pöhler, Birte; Prediger, Susanne

    2015-01-01

    Monolingual or multilingual students with low academic language proficiency need to acquire conceptual understanding for percentages and the language to communicate about them. The design research study explores how these two learning goals can be fostered by a macro-scaffolding approach for seventh grade students. The dual hypothetical learning…

  13. Intertwining Lexical and Conceptual Learning Trajectories--A Design Research Study on Dual Macro-Scaffolding towards Percentages

    Science.gov (United States)

    Pöhler, Birte; Prediger, Susanne

    2015-01-01

    Monolingual or multilingual students with low academic language proficiency need to acquire conceptual understanding for percentages and the language to communicate about them. The design research study explores how these two learning goals can be fostered by a macro-scaffolding approach for seventh grade students. The dual hypothetical learning…

  14. 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.

  15. Cell line OCI/AML3 bears exon-12 NPM gene mutation-A and cytoplasmic expression of nucleophosmin.

    Science.gov (United States)

    Quentmeier, H; Martelli, M P; Dirks, W G; Bolli, N; Liso, A; Macleod, R A F; Nicoletti, I; Mannucci, R; Pucciarini, A; Bigerna, B; Martelli, M F; Mecucci, C; Drexler, H G; Falini, B

    2005-10-01

    We recently identified a new acute myeloid leukemia (AML) subtype characterized by mutations at exon-12 of the nucleophosmin (NPM) gene and aberrant cytoplasmic expression of NPM protein (NPMc+). NPMc+ AML accounts for about 35% of adult AML and it is associated with normal karyotype, wide morphological spectrum, CD34-negativity, high frequency of FLT3-ITD mutations and good response to induction therapy. In an attempt to identify a human cell line to serve as a model for the in vitro study of NPMc+ AML, we screened 79 myeloid cell lines for mutations at exon-12 of NPM. One of these cell lines, OCI/AML3, showed a TCTG duplication at exon-12 of NPM. This mutation corresponds to the type A, the NPM mutation most frequently observed in primary NPMc+ AML. OCI/AML3 cells also displayed typical phenotypic features of NPMc+ AML, that is, expression of macrophage markers and lack of CD34, and the immunocytochemical hallmark of this leukemia subtype, that is, the aberrant cytoplasmic expression of NPM. The OCI/AML3 cell line easily engrafts in NOD/SCID mice and maintains in the animals the typical features of NPMc+ AML, such as the NPM cytoplasmic expression. For all these reasons, the OCI/AML3 cell line represents a remarkable tool for biomolecular studies of NPMc+ AML.

  16. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML.

    NARCIS (Netherlands)

    Hollink, I.H.; Zwaan, C.M.; Zimmermann, M.; Arentsen-Peters, T.C.; Pieters, R.; Cloos, J.; Kaspers, G.J.L.; Graaf, S.S.N. de; Harbott, J.; Creutzig, U.; Reinhardt, D.; Heuvel-Eibrink, M.M. van den; Thiede, C.

    2009-01-01

    Nucleophosmin (NPM1) mutations occur frequently in adult cytogenetically normal acute myeloid leukemia (CN-AML) and confer favorable outcome. We investigated the frequency and prognostic significance of NPM1 mutations in childhood AML (n=298), specifically focusing on the CN-AML subgroup (n=100). Mu

  17. Study on Macro-traffic Model

    Institute of Scientific and Technical Information of China (English)

    FangGe; GuowuZhang; BaojunYuan; KepingLi

    2004-01-01

    Macro-traffic model is an effective tool for supporting traffic programmer to This article is based on the software products VISEM (demand model) and VISUM (supply model) from PTV Company of Germany, and studies macro-traffic model on the basis of considering that traffic system is an interactive system of between a supply system and a demand system.

  18. Compact Structural Test Generation for Analog Macros

    NARCIS (Netherlands)

    Kaal, V.; Kerkhoff, Hans G.

    1997-01-01

    A structural, fault-model based methodology for the generation of compact high-quality test sets for analog macros is presented. Results are shown for an IV-converter macro design. Parameters of so-called test configurations are optimized for detection of faults in a fault-list and an optimal

  19. Pushdown machines for the macro tree transducer

    NARCIS (Netherlands)

    Engelfriet, Joost; Vogler, Heiko

    1986-01-01

    The macro tree transducer can be considered as a system of recursive function procedures with parameters, where the recursion is on a tree (e.g., the syntax tree of a program). We investigate characterizations of the class of tree (tree-to-string) translations which is induced by macro tree transduc

  20. Pushdown machines for the macro tree transducer

    NARCIS (Netherlands)

    Engelfriet, Joost; Vogler, Heiko

    1986-01-01

    The macro tree transducer can be considered as a system of recursive function procedures with parameters, where the recursion is on a tree (e.g., the syntax tree of a program). We investigate characterizations of the class of tree (tree-to-string) translations which is induced by macro tree

  1. How Shall We Establish Macro-Language Teaching——Research of College Chinese Curriculum Reform in Independent College%我们应该树立怎样的大语文观——独立学院大学语文课程改革研究之一

    Institute of Scientific and Technical Information of China (English)

    张祥平

    2012-01-01

    "大语文"教学理念,在近些年的大学语文教育中鼓吹甚力,这种观念要求全面打通文、史、哲、艺术等学科之间的知识界限,实质上将大学语文变成了"非语文"课程。正确的"大语文观",应建立在课程设置的着眼点高、课程选文的覆盖面广、课程建构的立体性强、课程讲授的宏观性强等四个方面。%The teaching idea of "macro-language teaching" is vigorously advocated in the College Chinese education in recent years.This concept requires people to break the knowledge boundaries of other disciplines such as literature,history,philosophy,arts,actually turning the College Chinese into "non-Chinese" course.The correct "Chinese concept" should be based on the four aspects: the high starting point of curriculun design,the wide coverage of curriculum selection,the extensive ways of curriculum construction,and the powerful macroscopic views of course teaching.

  2. Epigenetic landscape of the TERT promoter: a potential biomarker for high risk AML/MDS.

    Science.gov (United States)

    Zhao, Xin; Tian, Xin; Kajigaya, Sachiko; Cantilena, Caroline R; Strickland, Stephen; Savani, Bipin N; Mohan, Sanjay; Feng, Xingmin; Keyvanfar, Keyvan; Dunavin, Neil; Townsley, Danielle M; Dumitriu, Bogdan; Battiwalla, Minoo; Rezvani, Katayoun; Young, Neal S; Barrett, A John; Ito, Sawa

    2016-11-01

    Although recent observations implicate the importance of telomerase activity in acute myeloid leukaemia (AML), the roles of epigenetic regulations of the TERT gene in leukaemogenesis, drug resistance and clinical prognosis in AML are not fully understood. We developed a quantitative pyrosequencing-based methylation assay covering the TERT proximal promoter and a partial exon 1 (TERTpro/Ex1) region and tested both cell lines and primary leukaemia cells derived from AML and AML with preceding myelodysplastic syndrome (AML/MDS) patients (n = 43). Prognostic impact of methylation status of the upstream TERT promoter region was assessed by the Kaplan-Meier method. The activity of the telomerase inhibitor, imetelstat, was measured using leukaemia cell lines. The TERTpro/Ex1 region was highly methylated in all cell lines and primary leukaemia cells showed diverse methylation profiles. Most cases showed hypermethylated regions at the upstream TERTpro/Ex1 region, which were associated with inferior patient survival. TERTpro/Ex1 methylation status was correlated with the cytotoxicity to imetelstat and its combination with hypomethylating agent enhanced the cytotoxicity of imetelstat. AML cell lines and primary blasts harbour distinct TERTpro/Ex1 methylation profiles that could serve as a prognostic biomarker of AML. However, validation in a large cohort of patients is necessary to confirm our findings.

  3. 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.

  4. A Rare Cytogenetic Presentation of Acute Myeloid Leukemia (AML-M2

    Directory of Open Access Journals (Sweden)

    Hanumanthappa Vijay Raghavendra

    2012-12-01

    Full Text Available Acute myeloid leukemia (AML with t(8;21(q22;q22 generating the AML1/ETO fusion gene on 8q22 is a distinct type of AML t(8;21 category (WHO/AML-M2 (FAB, generally associated with a favourable prognosis. Variant additional chromosomal abnormalities are frequently reported. We report three adult cases of this category with unusual karyotype. Bone marrow cytogenetics of case no. 1: 45,X,-Y, t(8;21(q13;q22 with a novel breakpoint of chromosome 8 at (q13. Case no. 2: 46,X,t(X;2(q22;q37,t(3;7(q21;q36,t(5;14(p15;q11,del(8(q22 a complex rearrangement without the involvement of chromosome 21. Case no. 3: 49,XX,+5, t(8;21(q22;q22, +16, +der(21t(8;21(q22;q22 with additional der(21. Endometrial in this case which was positive for myeloperoxidase (MPO and CD117 conforming the AML infiltration. All are morphologically AML with t(8;21. Relevant literature in cytogenetic of AML-M2 is reviewed. The molecular mechanism involved in unusual rearrangements and clinical significance of them are subjected for further studies

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

    Directory of Open Access Journals (Sweden)

    Eva Szegezdi

    2011-03-01

    Full Text Available 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.

  6. The Influence of Communicative Language Teaching on Teaching Material Development

    Institute of Scientific and Technical Information of China (English)

    王茂娟

    2012-01-01

    Communicative Language Teaching (CLT) is the generally accepted norm in the field of second language teaching. The language teaching material design is influenced by the views of language and language teaching at the macro level, and restricted by specific syllabus at the micro level.

  7. Language Planning and Implementation in Turkish Primary Schools

    Science.gov (United States)

    Kirkgoz, Yasemin

    2007-01-01

    This paper explores a major curriculum innovation in English language teaching in Turkish primary education from macro and micro perspectives. After an overview of the role of English in Turkey, macro-level planning underlying the introduction of English language teaching policy in state-owned primary education is presented. Then the diffusion of…

  8. Augmentation of autologous T cell reactivity with acute myeloid leukemia (AML) blasts by Toll-like receptor (TLR) agonists

    OpenAIRE

    Zhong, Ruikun; Li, Hongying; Messer, Karen; Lane, Thomas A.; Zhou, Jiehua; Ball, Edward D.

    2015-01-01

    This study investigated whether TNF-α, Toll-like receptors (TLRs) 7/8 agonist resiquimod (R848), the TLR4 agonist lipopolysaccharide (LPS) and their combinations can enhance autologous AML-reactive T cell generation in an in vitro culture. AML peripheral blood or bone marrow mononuclear cells were cultured in medium supplemented with GM-CSF/IL-4 to induce dendritic cell (DC) differentiation of AML blasts (AML-DC). The impact of TNF-α, LPS, R848 and their combinations on AML-DC cultures was an...

  9. 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 which...... the original convolution integrals are represented via two auxiliary displacement-like state-space variables. A parametric study of the AML parameters is conducted for optimizing the absorbing properties. The performance is demonstrated on a single- and a two-layered half-space for various velocities...

  10. Angiomyolipoma (AML) without visible fat: Ultrasound, CT and MR imaging features with pathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Hakim, Shaheed W.; Flood, Trevor A. [The Ottawa Hospital, University of Ottawa, Department of Anatomical Pathology, Ottawa, Ontario (Canada); Schieda, Nicola; Hodgdon, Taryn; McInnes, Matthew D.F.; Dilauro, Marc [The Ottawa Hospital, University of Ottawa, Department of Medical Imaging, Ottawa, Ontario (Canada)

    2016-02-15

    To compare imaging findings with histopathology in AML without visible fat (AML{sub wvf}). With IRB approval, we identified 18 AML{sub wvf} that underwent CT between 2002-2014. A radiologist measured NECT-attenuation, corticomedullary (CM) and nephrographic (NG) enhancement, echogenicity relative to renal cortex (RC) (N = 5), T2W (T2{sub AML}/T2{sub RC}) signal-intensity (SI), and chemical-shift SI ([SI{sub IN-PHASE} - SI{sub OPPOSED-PHASE}]/SI{sub IN-PHASE}) indices (N = 6). A pathologist re-evaluated 15/18 AML{sub wvf} for 1) < or > 25 % adipocytes/high-power-field (HPF), 2) ''many or few'' blood vessels. Comparisons were performed using chi-square and independent t-tests. 73.3 %(11/15) of AML{sub wvf} had <25 % adipocytes/HPF and 86.7 %(13/15) had ''many'' blood vessels. NECT-attenuation was 41.8(±6.9) HU. 61.1 %(11/18) of AML{sub wvf} were hyper-attenuating and 38.9 %(7/18) iso-attenuating; attenuation was associated with %-adipocytes/HPF, (p = 0.01). CM/NG enhancement were 63.3(±20.8)/51.7(±15.5) HU. 72.2 %(13/18) of AML{sub wvf} had wash-out enhancement, with no association with amount of blood vessels at pathology, (p = 0.68). No difference in echogenicity was noted by histology (p > 0.05). All AML{sub wvf} were T2-hypointense (SI ratio = 0.61 [±0.1]). 2/6 AML{sub wvf} showed SI drop on chemical-shift MRI; both were iso-attenuating and were associated with >25 % adipocytes/HPF (p = 0.04). AML{sub wvf} are typically T2-hypointense and hyper-attenuating with wash-out enhancement due to abundant smooth muscle and vessels respectively. Iso-attenuating AML{sub wvf} with microscopic fat on MRI contain more adipocytes/HPF. (orig.)

  11. Identification of novel genomic aberrations in AML-M5 in a level of array CGH.

    Directory of Open Access Journals (Sweden)

    Rui Zhang

    Full Text Available To assess the possible existence of unbalanced chromosomal abnormalities and delineate the characterization of copy number alterations (CNAs of acute myeloid leukemia-M5 (AML-M5, R-banding karyotype, oligonucelotide array CGH and FISH were performed in 24 patients with AML-M5. A total of 117 CNAs with size ranging from 0.004 to 146.263 Mb was recognized in 12 of 24 cases, involving all chromosomes other than chromosome 1, 4, X and Y. Cryptic CNAs with size less than 5 Mb accounted for 59.8% of all the CNAs. 12 recurrent chromosomal alterations were mapped. Seven out of them were described in the previous AML studies and five were new candidate AML-M5 associated CNAs, including gains of 3q26.2-qter and 13q31.3 as well as losses of 2q24.2, 8p12 and 14q32. Amplication of 3q26.2-qter was the sole large recurrent chromosomal anomaly and the pathogenic mechanism in AML-M5 was possibly different from the classical recurrent 3q21q26 abnormality in AML. As a tumor suppressor gene, FOXN3, was singled out from the small recurrent CNA of 14q32, however, it is proved that deletion of FOXN3 is a common marker of myeloid leukemia rather than a specific marker for AML-M5 subtype. Moreover, the concurrent amplication of MLL and deletion of CDKN2A were noted and it might be associated with AML-M5. The number of CNA did not show a significant association with clinico-biological parameters and CR number of the 22 patients received chemotherapy. This study provided the evidence that array CGH served as a complementary platform for routine cytogenetic analysis to identify those cryptic alterations in the patients with AML-M5. As a subtype of AML, AML-M5 carries both common recurrent CNAs and unique CNAs, which may harbor novel oncogenes or tumor suppressor genes. Clarifying the role of these genes will contribute to the understanding of leukemogenic network of AML-M5.

  12. Application software, domain-specific languages, and language design assistants

    NARCIS (Netherlands)

    J. Heering (Jan)

    2000-01-01

    textabstractWhile application software does the real work, domain-specific languages (DSLs) are tools to help produce it efficiently, and language design assistants in turn are meta-tools to help produce DSLs quickly. DSLs are already in wide use (HTML for web pages, Excel macros for spreadsheet

  13. Financial Imbalances and Macro-prudential Policies

    Directory of Open Access Journals (Sweden)

    Polikarpova Olga S.

    2015-11-01

    Full Text Available The credit crisis and its transformation into a sovereign debt crisis have illustrated the limited character of the traditional macro financial politics. The financial crisis has shown that the priority of price stability does not guarantee macroeconomic stability. Revision of the goals and objectives of the monetary and credit policy is being carried out in many countries. In order to ensure macroeconomic stability, central banks have to use new instruments considering financial stability as an additional object. Since 2009 the IMF recommends central banks to use macro-prudential instruments for reducing macro-financial risks and imbalances in the financial system structure. The effectiveness of macro-prudential policy depends on its calibration with the monetary and credit policy. The growth of financial imbalances in the first decade after the adoption of the euro, presence of contradictory fiscal policies, deployment of a spiral of rapid crediting and price inflation have led to apraxia in the monetary and credit policy, and fiscal policy was limited by institutional arrangements. Accumulating funds during the budget surplus the countries-members of the European Monetary System (EMS attempted to reduce asymmetric shocks. The priority of price stability in the EMS had been achieved but the economies of these countries suffered from financial imbalances. Macro-prudential policy is aimed at prevention and mitigation of systemic risk, plays a significant role in reforming the new policy of central banks. That is why European countries are developing new methods and an institutional framework for the implementation of a new macro-prudential policy. Problems of structural arbitration and the possibility of emergence of new financial imbalances in the EMS are becoming increasingly real. The flow of financial capitals and financial institutions to more lenient jurisdictions is connected with the establishment of macro-prudential policy. The macro

  14. Extending the reach of powder diffraction modelling by user defined macros

    CERN Document Server

    Scardi, Paolo

    2010-01-01

    The main focus of this special topic volume is the development and possibilities of the MACRO language within TOPAS, with a specific session dedicated to WPPM. The collection is presented here in the form of a ""macro tutorial"" for the benefit of the entire powder diffraction community. More than a collection of standard scientific papers, the contributions to this special issue provide methods, tutorials and practical suggestions and solutions for the proper use of TOPAS and WPPM in a number of applications; ranging from the most common to the most refined and specific cases.Readers will fin

  15. Timothy Ley, M.D., Advocates for Personalized Medicine in AML - TCGA

    Science.gov (United States)

    Oncologist Dr. Timothy Ley talks about how repurposing of existing drugs based on better understanding of the genetic basis of acute myeloid leukemia (AML) can help patients receive personalized care.

  16. Resource Curse: Micro and Macro Analysis

    African Journals Online (AJOL)

    Nneka Umera-Okeke

    corporate sub-levels, while at the macro level there are the state and the global ... development and good governance than do countries with fewer resources” ( .... Individuals can contribute to resource curse by acting as corrupt agents of the.

  17. MACRO constraints on violation of Lorentz invariance

    CERN Document Server

    Cozzi, M

    2007-01-01

    The energy spectrum of neutrino-induced upward-going muons in MACRO has been analysed in terms of relativity principles violating effects, keeping standard mass-induced atmospheric neutrino oscillations as the dominant source of $\

  18. Extramedullary Acute Myeloid Leukemia (AML: Leukemic Pleural Effusion, Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Naveen ePemmaraju

    2014-06-01

    Full Text Available Objective and Importance: Malignant pleural effusions occur in the setting of both solid and hematologic malignancies. Pleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML with fewer than 20 cases reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature. Clinical presentation: In this case, a 55 year old man with previous history of myeloproliferative neoplasm (MPN experienced transformation AML, heralded by appearance of leukemic pleural effusions. The patient was identified to have leukemic pleural effusion based upon extended cytogenetic analysis of the pleural fluid, as morphologic analysis alone was insufficient. Intervention: The patient was treated with hypomethylator-based and intensive chemotherapy strategies, both of which maintained resolution of the effusions in the remission setting. Conclusion: Due to the rarity of diagnosis of leukemic pleural effusions, both cytogenetic and fluorescence in situ hybridization (FISH testing are recommended. Futhermore, systemic chemotherapy directed at the AML can lead to complete resolution of leukemic pleural effusions. Objective and ImportancePleural effusion caused by leukemic infiltration is an unusual extramedullary manifestation of acute myeloid leukemia (AML, but may be more common than previously thought. Fewer than 20 cases have been reported.1-11 We report a case of pericardial and pleural effusions in a patient with AML and review the literature.

  19. Notch pathway activation targets AML-initiating cell homeostasis and differentiation.

    Science.gov (United States)

    Lobry, Camille; Ntziachristos, Panagiotis; Ndiaye-Lobry, Delphine; Oh, Philmo; Cimmino, Luisa; Zhu, Nan; Araldi, Elisa; Hu, Wenhuo; Freund, Jacquelyn; Abdel-Wahab, Omar; Ibrahim, Sherif; Skokos, Dimitris; Armstrong, Scott A; Levine, Ross L; Park, Christopher Y; Aifantis, Iannis

    2013-02-11

    Notch signaling pathway activation is known to contribute to the pathogenesis of a spectrum of human malignancies, including T cell leukemia. However, recent studies have implicated the Notch pathway as a tumor suppressor in myeloproliferative neoplasms and several solid tumors. Here we report a novel tumor suppressor role for Notch signaling in acute myeloid leukemia (AML) and demonstrate that Notch pathway activation could represent a therapeutic strategy in this disease. We show that Notch signaling is silenced in human AML samples, as well as in AML-initiating cells in an animal model of the disease. In vivo activation of Notch signaling using genetic Notch gain of function models or in vitro using synthetic Notch ligand induces rapid cell cycle arrest, differentiation, and apoptosis of AML-initiating cells. Moreover, we demonstrate that Notch inactivation cooperates in vivo with loss of the myeloid tumor suppressor Tet2 to induce AML-like disease. These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia.

  20. DEK oncogene expression during normal hematopoiesis and in Acute Myeloid Leukemia (AML).

    Science.gov (United States)

    Logan, Gemma E; Mor-Vaknin, Nirit; Braunschweig, Till; Jost, Edgar; Schmidt, Pia Verena; Markovitz, David M; Mills, Ken I; Kappes, Ferdinand; Percy, Melanie J

    2015-01-01

    DEK is important in regulating cellular processes including proliferation, differentiation and maintenance of stem cell phenotype. The translocation t(6;9) in Acute Myeloid Leukemia (AML), which fuses DEK with NUP214, confers a poor prognosis and a higher risk of relapse. The over-expression of DEK in AML has been reported, but different studies have shown diminished levels in pediatric and promyelocytic leukemias. This study has characterized DEK expression, in silico, using a large multi-center cohort of leukemic and normal control cases. Overall, DEK was under-expressed in AML compared to normal bone marrow (NBM). Studying specific subtypes of AML confirmed either no significant change or a significant reduction in DEK expression compared to NBM. Importantly, the similarity of DEK expression between AML and NBM was confirmed using immunohistochemistry analysis of tissue mircorarrays. In addition, stratification of AML patients based on median DEK expression levels indicated that DEK showed no effect on the overall survival of patients. DEK expression during normal hematopoiesis did reveal a relationship with specific cell types implicating a distinct function during myeloid differentiation. Whilst DEK may play a potential role in hematopoiesis, it remains to be established whether it is important for leukemagenesis, except when involved in the t(6;9) translocation. Copyright © 2014. Published by Elsevier Inc.

  1. The Aryl Hydrocarbon Receptor Pathway: A Key Component of the microRNA-Mediated AML Signalisome

    Directory of Open Access Journals (Sweden)

    Julia E. Rager

    2012-05-01

    Full Text Available Recent research has spotlighted the role of microRNAs (miRNAs as critical epigenetic regulators of hematopoietic stem cell differentiation and leukemia development. Despite the recent advances in knowledge surrounding epigenetics and leukemia, the mechanisms underlying miRNAs’ influence on leukemia development have yet to be clearly elucidated. Our aim was to identify high ranking biological pathways altered at the gene expression level and under epigenetic control. Specifically, we set out to test the hypothesis that miRNAs dysregulated in acute myeloid leukemia (AML converge on a common pathway that can influence signaling related to hematopoiesis and leukemia development. We identified genes altered in AML patients that are under common regulation of seven key miRNAs. By mapping these genes to a global interaction network, we identified the “AML Signalisome”. The AML Signalisome comprises 53 AML-associated molecules, and is enriched for proteins that play a role in the aryl hydrocarbon receptor (AhR pathway, a major regulator of hematopoiesis. Furthermore, we show biological enrichment for hematopoiesis-related proteins within the AML Signalisome. These findings provide important insight into miRNA-regulated pathways in leukemia, and may help to prioritize targets for disease prevention and treatment.

  2. MARKAL-MACRO: An overview

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, L.D.; Goldstein, G.A.; Lee, J.; Marcuse, W.; Morris, S.C. [Brookhaven National Lab., Upton, NY (US); Manne, A.S. [Stanford Univ., CA (US); Wene, C.O. [Brookhaven National Lab., Upton, NY (US)]|[Chalmers Univ. of Technology, Goeteborg (SE)

    1992-11-12

    MARKAL-MACRO is an experiment in model linkage. This new tool is intended as an improvement over existing methods for energy policy assessment. It is designed specifically for estimating the costs and analyzing alternative technologies and policies proposed for reducing environmental risks such as global climate change or regional air pollution. The greenhouse gas debate illustrates the usefulness of linked energy-economy models. A central issue is the coupling between economic growth, the level of energy demands, and the evolution of an energy system to supply these demands. The debate is often connected with alternative modeling approaches. The competing philosophies may be labeled {open_quotes}top-down macroeconomic{close_quotes} and {open_quotes}bottom-up engineering{close_quotes} perspectives. Do macroeconomic models, with their descriptions of effects within the total economy but few technical details on the energy system, tend to overestimate future energy demands? Conversely, do engineering models, ignoring feedbacks to the general economy and non-technical market factors but containing rich descriptions of technology options, tend to take too optimistic a view of conservation and the use of renewable energy sources? Or is the principal difference that the engineering models ignore new sources of energy demands, and that the macroeconomic models ignore saturation effects for old categories of demands? An efficient modeling tool must have the scope and detail to match the width and depth of the policy problem being analyzed. In order to respond to major environmental risks (e.g., the possibility of global climate changes), there must be long-range, fundamental changes in the energy system. For an analysis of these changes and an understanding of their nature, the modeling tool must be able to capture the complex network of relations within the energy system, as well as the opportunities of new or improved technologies.

  3. MARKAL-MACRO: An overview

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, L.D.; Goldstein, G.A.; Lee, J.; Marcuse, W.; Morris, S.C. (Brookhaven National Lab., Upton, NY (United States)); Manne, A.S. (Stanford Univ., CA (United States)); Wene, C.O. (Brookhaven National Lab., Upton, NY (United States) Chalmers Univ. of Technology, Goeteborg (Sweden))

    1992-11-12

    MARKAL-MACRO is an experiment in model linkage. This new tool is intended as an improvement over existing methods for energy policy assessment. It is designed specifically for estimating the costs and analyzing alternative technologies and policies proposed for reducing environmental risks such as global climate change or regional air pollution. The greenhouse gas debate illustrates the usefulness of linked energy-economy models. A central issue is the coupling between economic growth, the level of energy demands, and the evolution of an energy system to supply these demands. The debate is often connected with alternative modeling approaches. The competing philosophies may be labeled [open quotes]top-down macroeconomic[close quotes] and [open quotes]bottom-up engineering[close quotes] perspectives. Do macroeconomic models, with their descriptions of effects within the total economy but few technical details on the energy system, tend to overestimate future energy demands Conversely, do engineering models, ignoring feedbacks to the general economy and non-technical market factors but containing rich descriptions of technology options, tend to take too optimistic a view of conservation and the use of renewable energy sources Or is the principal difference that the engineering models ignore new sources of energy demands, and that the macroeconomic models ignore saturation effects for old categories of demands An efficient modeling tool must have the scope and detail to match the width and depth of the policy problem being analyzed. In order to respond to major environmental risks (e.g., the possibility of global climate changes), there must be long-range, fundamental changes in the energy system. For an analysis of these changes and an understanding of their nature, the modeling tool must be able to capture the complex network of relations within the energy system, as well as the opportunities of new or improved technologies.

  4. The Hematopoietic Transcription Factor AML1 (RUNX1) Is Negatively Regulated by the Cell Cycle Protein Cyclin D3

    Science.gov (United States)

    Peterson, Luke F.; Boyapati, Anita; Ranganathan, Velvizhi; Iwama, Atsushi; Tenen, Daniel G.; Tsai, Schickwann; Zhang, Dong-Er

    2005-01-01

    The family of cyclin D proteins plays a crucial role in the early events of the mammalian cell cycle. Recent studies have revealed the involvement of AML1 transactivation activity in promoting cell cycle progression through the induction of cyclin D proteins. This information in combination with our previous observation that a region in AML1 between amino acids 213 and 289 is important for its function led us to investigate prospective proteins associating with this region. We identified cyclin D3 by a yeast two-hybrid screen and detected AML1 interaction with the cyclin D family by both in vitro pull-down and in vivo coimmunoprecipitation assays. Furthermore, we demonstrate that cyclin D3 negatively regulates the transactivation activity of AML1 in a dose-dependent manner by competing with CBFβ for AML1 association, leading to a decreased binding affinity of AML1 for its target DNA sequence. AML1 and its fusion protein AML1-ETO have been shown to shorten and prolong the mammalian cell cycle, respectively. In addition, AML1 promotes myeloid cell differentiation. Thus, our observations suggest that the direct association of cyclin D3 with AML1 functions as a putative feedback mechanism to regulate cell cycle progression and differentiation. PMID:16287839

  5. Language Contact and Language Conflict in Autochthonous Language Minority Settings in the EU: A Preliminary Round-Up of Guiding Principles and Research Desiderata

    Science.gov (United States)

    Darquennes, Jeroen

    2010-01-01

    This contribution deals with language contact and language conflict in autochthonous language minority settings in the European Union. It rounds up a number of concepts that guide macro-socio-linguistic and macrocontact-linguistic research on language minorities. The description of these concepts results in a list of research desiderata.

  6. Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial.

    Science.gov (United States)

    Aslanyan, Mariam G; Kroeze, Leonie I; Langemeijer, Saskia M C; Koorenhof-Scheele, Theresia N; Massop, Marion; van Hoogen, Patricia; Stevens-Linders, Ellen; van de Locht, Louis T; Tönnissen, Evelyn; van der Heijden, Adrian; da Silva-Coelho, Pedro; Cilloni, Daniela; Saglio, Giuseppe; Marie, Jean-Pierre; Tang, Ruoping; Labar, Boris; Amadori, Sergio; Muus, Petra; Willemze, Roel; Marijt, Erik W A; de Witte, Theo; van der Reijden, Bert A; Suciu, Stefan; Jansen, Joop H

    2014-08-01

    We assessed the prognostic impact of TET2 mutations and mRNA expression in a prospective cohort of 357 adult AML patients Adulto (GIMEMA) AML-12 06991 clinical trial. In addition the co-occurrence with other genetic defects and the functional consequences of TET2 mutations were investigated. TET2 mutations occurred in 7.6 % of the patients and were an independent marker of poor prognosis (p = 0.024). TET2 and IDH1/2 mutations strongly associated with aberrations in the DNA methyltransferase DNMT3A. Functional studies confirmed previous work that neither nonsense truncations, nor missense TET2 mutations, induced 5-hydroxymethylcytosine formation. In addition, we now show that mutant TET2 forms did not act in a dominant negative manner when co-expressed with the wild-type protein. Finally, as loss-of-function TET2 mutations predicted poor outcome, we questioned whether low TET2 mRNA expression in cases of AML without TET2 mutations would affect overall survival. Notably, also AML patients with low TET2 mRNA expression levels showed inferior overall survival.

  7. Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials.

    NARCIS (Netherlands)

    Rao, A.; Hills, R.K.; Stiller, C.; Gibson, B.E.; Graaf, S.S.N. de; Hann, I.M.; O'Marcaigh, A.; Wheatley, K.; Webb, D.K.

    2006-01-01

    Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience

  8. CD14 mediated endogenous TNF-alpha release in HL60 AML cells: a potential model for CD14 mediated endogenous cytokine release in the treatment of AML.

    Science.gov (United States)

    Treon, S P; Anand, B; Ulevitch, R; Broitman, S A

    1994-01-01

    In previous studies, HL60 AML cells treated with tumor necrosis factor-alpha (TNF), interferon-gamma (IFN), and lipopolysaccharides (LPS) displayed decreased growth and viability, enhanced monocytic pathway differentiation and endogenous TNF release. Endogenous TNF release by LPS/TNF/IFN treated HL60 cells was postulated to play a role with the above findings. In these studies, HL60 cells expressed CD14 when treated with TNF, IFN, and LPS. CD14 mediates TNF release in monocytes/macrophages in response to binding of LPS with LPS binding protein (LBP). CD14 was not expressed in either untreated or LPS only treated HL60 cells. CD14 expression was present and greater with HL60 cells cultured with LPS/TNF/IFN vs TNF/IFN (47.47% vs 9.07% positive, respectively) suggesting synergism for LPS in CD14 induction. CD14 expression was associated with endogenous TNF release, and with significantly higher levels by HL60 cells treated with LPS/TNF/IFN vs TNF/IFN (p < 0.001). Addition of anti-CD14 antibody significantly reduced release of TNF in TNF/IFN (p < 0.001) and LPS/TNF/IFN (p = 0.0013) treated cells. KG1 and U937 AML cells treated with LPS, TNF, and IFN did not express CD14, nor release TNF. A model for inducing release of endogenous growth inhibitory cytokines by CD14 bearing AML cells is proposed as an approach to AML therapy.

  9. Micro-processus et macro-structures

    Directory of Open Access Journals (Sweden)

    Aaron Victor Cicourel

    2008-10-01

    Full Text Available Des approches sociologiques traditionnelles ont défini des macro-structures sociales comme un niveau particulier de la réalité sociale, à distinguer des micro-épisodes de l’action sociale. Cela les a conduits à concevoir ces macro-structures et à mener des recherches sur elles de manière plus ou moins indépendante des pratiques observables de la vie quotidienne. Cicourel soutient que les faits (macro-sociaux ne sont pas simplement donnés, mais émergent de pratiques routinières de la vie de tous les jours. Le macro, au sens de descriptions résumées, hors contexte, normalisées et typifiées, est un produit typique des procédures interactives et organisationnelles qui transforment les micro-événements en structures macro-sociales. Ainsi une précondition pour l’intégration des phénomènes micro- et macro-sociaux dans notre théorie et dans notre méthodologie renvoie à l’identification des processus contribuant à la création de macro-structures par des inférences routinières, des interprétations et des procédure de résumé. Le texte montre aussi que les différences entre approches micro-sociologiques apparaissent parallèles à celles existant entre approches micro et macro. On se centrant sur de petits fragments d’interactions conversationnelles, certains travaux micro-sociologiques tendent à ignorer ce qui informe ces interactions conversationnelles pour les participants eux-mêmes. Les comptes rendus décontextualisés produits par de telles méthodes ressemblent à la décontextualisation résultant des procédures macro-sociologiques d’agrégation. Contre cela, Cicourel défend la constitution de bases de données comparatives n’incluant pas seulement le contexte des interactions de face à face, mais étudiant aussi les phénomènes sociaux de manière systématique à travers différents contextes.Micro-processes and macro-structures. Notes on articulation between different levels of analysis

  10. Macro-modelling of a double-gimballed electrostatic torsional micromirror

    Science.gov (United States)

    Zhou, Guangya; Tay, Francis E. H.; Chau, Fook Siong

    2003-09-01

    This paper presents the development of a reduced-order macro-model for the double-gimballed electrostatic torsional micromirror using the hierarchical circuit-based approach. The proposed macro-model permits extremely fast simulation while providing nearly FEM accuracy. The macro-model is coded in MAST analog hardware description language (AHDL), and the simulations are implemented in the SABERTM simulator. Both the static and dynamic behaviour of the double-gimballed electrostatic torsional micromirror have been investigated. The dc and frequency analysis results obtained by the proposed macro-model are in good agreement with CoventorWareTM finite element analysis results. Based on the macro-model we developed, system-level simulation of a closed-loop controlled double-gimballed torsional micromirror is also performed. Decentralized PID controllers are proposed for the control of the micromirror. A sequential-loop-closing method is used for tuning the multiple control loops during the simulation. After tuning, the closed-loop controlled double-gimballed torsional micromirror demonstrates an improved transient performance and satisfactory disturbance rejection ability.

  11. TET2 exon 2 skipping is an independent favorable prognostic factor for cytogenetically normal acute myelogenous leukemia (AML): TET2 exon 2 skipping in AML.

    Science.gov (United States)

    Mohamed, Aminetou Mint; Balsat, Marie; Koering, Catherine; Maucort-Boulch, Delphine; Boissel, Nicolas; Payen-Gay, Lea; Cheok, Meyling; Mortada, Hussein; Auboeuf, Didier; Pinatel, Christiane; El-Hamri, Mohamed; Tigaud, Isabelle; Hayette, Sandrine; Dumontet, Charles; Cros, Emeline; Flandrin-Gresta, Pascale; Nibourel, Olivier; Preudhomme, Claude; Thomas, Xavier; Nicolini, Franck-Emmanuel; Solly, Françoise; Guyotat, Denis; Campos, Lydia; Michallet, Mauricette; Ceraulo, Antony; Mortreux, Franck; Wattel, Eric

    2017-01-16

    In AML, approximately one-third of expressed genes are abnormally spliced, including aberrant TET2 exon 2 expression. In a discovery cohort (n=99), TET2 exon 2 skipping (TET2E2S) was found positively associated with a significant reduction in the cumulative incidence of relapse (CIR). Age, cytogenetics, and TET2E2S were independent prognostic factors for disease-free survival (DFS), and favorable effects on outcomes predominated in cytogenetic normal (CN)-AML and younger patients. Using the same cutoff in a validation cohort of 86 CN-AML patients, TET2E2S(high) patients were found to be younger than TET2(low) patients without a difference in the rate of complete remission. However, TET2E2S(high) patients exhibited a significantly lower CIR (p<10(-4)). TET2E2S and FLT3-ITD, but not age or NPM1 mutation status were independent prognostic factors for DFS and event-free survival (EFS), while TET2E2S was the sole prognostic factor that we identified for overall survival (OS). In both the intermediate-1 and favorable ELN genetic categories, TET2E2S remained significantly associated with prolonged survival. There was no correlation between TET2E2S status and outcomes in 34 additional AML patients who were unfit for IC. Therefore our results suggest that assessments of TET2 exon 2 splicing status might improve risk stratification in CN-AML patients treated with IC.

  12. 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.

  13. A stable transcription factor complex nucleated by oligomeric AML1–ETO controls leukaemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xiao-Jian; Wang, Zhanxin; Wang, Lan; Jiang, Yanwen; Kost, Nils; Soong, T. David; Chen, Wei-Yi; Tang, Zhanyun; Nakadai, Tomoyoshi; Elemento, Olivier; Fischle, Wolfgang; Melnick, Ari; Patel, Dinshaw J.; Nimer, Stephen D.; Roeder, Robert G.

    2013-06-30

    Transcription factors are frequently altered in leukaemia through chromosomal translocation, mutation or aberrant expression. AML1–ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukaemia, is a transcription factor implicated in both gene repression and activation. AML1–ETO oligomerization, mediated by the NHR2 domain, is critical for leukaemogenesis, making it important to identify co-regulatory factors that ‘read’ the NHR2 oligomerization and contribute to leukaemogenesis. Here we show that, in human leukaemic cells, AML1–ETO resides in and functions through a stable AML1–ETO-containing transcription factor complex (AETFC) that contains several haematopoietic transcription (co)factors. These AETFC components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, co-localize genome wide, cooperatively regulate gene expression, and contribute to leukaemogenesis. Within the AETFC complex, AML1–ETO oligomerization is required for a specific interaction between the oligomerized NHR2 domain and a novel NHR2-binding (N2B) motif in E proteins. Crystallographic analysis of the NHR2–N2B complex reveals a unique interaction pattern in which an N2B peptide makes direct contact with side chains of two NHR2 domains as a dimer, providing a novel model of how dimeric/oligomeric transcription factors create a new protein-binding interface through dimerization/oligomerization. Intriguingly, disruption of this interaction by point mutations abrogates AML1–ETO-induced haematopoietic stem/progenitor cell self-renewal and leukaemogenesis. These results reveal new mechanisms of action of AML1–ETO, and provide a potential therapeutic target in t(8;21)-positive acute myeloid leukaemia.

  14. Identification of transcription factor AML-1 binding site upstream of human cytomegalovirus UL111A gene.

    Directory of Open Access Journals (Sweden)

    Xiaoqun Zheng

    Full Text Available Human cytomegalovirus (HCMV interleukin-10 (hcmvIL-10, encoded by HCMV UL111A gene, is a homolog of human IL-10. It exerts immunomodulatory effects that allow HCMV to evade host defense mechanisms. However, the exact mechanism underlying the regulation of hcmvIL-10 expression is not well understood. The transcription factor acute myeloid leukemia 1 (AML-1 plays an important role in the regulation of various genes involved in the differentiation of hematopoietic lineages. A putative AML-1 binding site is present within the upstream regulatory region (URR of UL111A gene. To provide evidence that AML-1 is involved in regulating UL111A gene expression, we examined the interaction of AML-1 with the URR of UL111A in HCMV-infected human monocytic THP-1 cells using a chromatin immunoprecipitation assay. HcmvIL-10 transcription was detected in differentiated THP-1 cells, but not in undifferentiated ones. Furthermore, the URR of UL111A showed a higher intensity of AML-1 binding, a higher level of histone H3 acetyl-K9, but a lower level of histone H3 dimethyl-K9 in differentiated THP-1 cells than undifferentiated cells. Down-regulation of AML1 by RNA interference decreased the expression of the UL111A gene. Our results suggest that AML-1 may contribute to the epigenetic regulation of UL111A gene via histone modification in HCMV-infected differentiated THP-1 cells. This finding could be useful for the development of new anti-viral therapies.

  15. Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study.

    Science.gov (United States)

    Boehrer, Simone; Adès, Lionel; Braun, Thorsten; Galluzzi, Lorenzo; Grosjean, Jennifer; Fabre, Claire; Le Roux, Génèviève; Gardin, Claude; Martin, Antoine; de Botton, Stéphane; Fenaux, Pierre; Kroemer, Guido

    2008-02-15

    Erlotinib, an inhibitor of the epidermal growth factor receptor (EGFR), induces differentiation, cell-cycle arrest, and apoptosis of EGFR-negative myeloblasts of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), as well as in EGFR-negative cell lines representing these diseases (P39, KG-1, and HL 60). This off-target effect can be explained by inhibitory effects on JAK2. Apoptosis induction coupled to mitochondrial membrane permeabilization occurred independently from phenotypic differentiation. In apoptosis-sensitive AML cells, erlotinib caused a rapid (within less than 1 hour) nucleocytoplasmic translocation of nucleophosmin-1 (NPM-1) and p14(ARF). Apoptosis-insensitive myeloblasts failed to manifest this translocation yet became sensitive to apoptosis induction by erlotinib when NPM-1 was depleted by RNA interference. Moreover, erlotinib reduced the growth of xenografted human AML cells in vivo. Erlotinib also killed CD34(+) bone marrow blasts from MDS and AML patients while sparing normal CD34(+) progenitors. This ex vivo therapeutic effect was once more associated with the nucleocytoplasmic translocation of NPM-1 and p14(ARF). One patient afflicted with both MDS and non-small cell lung cancer manifested hematologic improvement in response to erlotinib. In summary, we here provide novel evidence in vitro, ex vivo, and in vivo for the potential therapeutic efficacy of erlotinib in the treatment of high-risk MDS and AML.

  16. CHK1 as a therapeutic target to bypass chemoresistance in AML.

    Science.gov (United States)

    David, Laure; Fernandez-Vidal, Anne; Bertoli, Sarah; Grgurevic, Srdana; Lepage, Benoît; Deshaies, Dominique; Prade, Naïs; Cartel, Maëlle; Larrue, Clément; Sarry, Jean-Emmanuel; Delabesse, Eric; Cazaux, Christophe; Didier, Christine; Récher, Christian; Manenti, Stéphane; Hoffmann, Jean-Sébastien

    2016-09-13

    The nucleoside analog cytarabine, an inhibitor of DNA replication fork progression that results in DNA damage, is currently used in the treatment of acute myeloid leukemia (AML). We explored the prognostic value of the expression of 72 genes involved in various aspects of DNA replication in a set of 198 AML patients treated by cytarabine-based chemotherapy. We unveiled that high expression of the DNA replication checkpoint gene CHEK1 is a prognostic marker associated with shorter overall, event-free, and relapse-free survivals and determined that the expression of CHEK1 can predict more frequent and earlier postremission relapse. CHEK1 encodes checkpoint kinase 1 (CHK1), which is activated by the kinase ATR when DNA replication is impaired by DNA damage. High abundance of CHK1 in AML patient cells correlated with higher clonogenic ability and more efficient DNA replication fork progression upon cytarabine treatment. Exposing the patient cells with the high abundance of CHK1 to SCH900776, an inhibitor of the kinase activity of CHK1, reduced clonogenic ability and progression of DNA replication in the presence of cytarabine. These results indicated that some AML cells rely on an efficient CHK1-mediated replication stress response for viability and that therapeutic strategies that inhibit CHK1 could extend current cytarabine-based treatments and overcome drug resistance. Furthermore, monitoring CHEK1 expression could be used both as a predictor of outcome and as a marker to select AML patients for CHK1 inhibitor treatments.

  17. Coordinate regulation of residual bone marrow function by paracrine trafficking of AML exosomes.

    Science.gov (United States)

    Huan, J; Hornick, N I; Goloviznina, N A; Kamimae-Lanning, A N; David, L L; Wilmarth, P A; Mori, T; Chevillet, J R; Narla, A; Roberts, C T; Loriaux, M M; Chang, B H; Kurre, P

    2015-12-01

    We recently demonstrated that acute myeloid leukemia (AML) cell lines and patient-derived blasts release exosomes that carry RNA and protein; following an in vitro transfer, AML exosomes produce proangiogenic changes in bystander cells. We reasoned that paracrine exosome trafficking may have a broader role in shaping the leukemic niche. In a series of in vitro studies and murine xenografts, we demonstrate that AML exosomes downregulate critical retention factors (Scf, Cxcl12) in stromal cells, leading to hematopoietic stem and progenitor cell (HSPC) mobilization from the bone marrow. Exosome trafficking also regulates HSPC directly, and we demonstrate declining clonogenicity, loss of CXCR4 and c-Kit expression, and the consistent repression of several hematopoietic transcription factors, including c-Myb, Cebp-β and Hoxa-9. Additional experiments using a model of extramedullary AML or direct intrafemoral injection of purified exosomes reveal that the erosion of HSPC function can occur independent of direct cell-cell contact with leukemia cells. Finally, using a novel multiplex proteomics technique, we identified candidate pathways involved in the direct exosome-mediated modulation of HSPC function. In aggregate, this work suggests that AML exosomes participate in the suppression of residual hematopoietic function that precedes widespread leukemic invasion of the bone marrow directly and indirectly via stromal components.

  18. Micro and macro factors affecting childbearing aspirations.

    Science.gov (United States)

    He, Y

    1992-01-01

    The conclusion of the discussion of factors affecting childbearing aspirations is that both a micro and a macro perspective must be included in an empirical analysis which would be useful for policy decisions. Micro factors tend to the economic function of the family, the economic value of children, cost of labor training, women's occupation, social security, household consumption, and education level. Attention to micro factors is important in the link between individual interests and state family planning (FP) policy. Macro factors tend to be ignored, but also impact on childbearing decisions. Macro factors are economic conditions, social and political factors, culture, and environmental factors such as ecology, natural resources, employment, economic development, and education. Macro factors affect the population as a whole and indirectly impact on individuals and the family. China's achievements in FP policy have been identified as a reduction of 200 million people, a shift in the population reproduction cycle downwards, increased standard of living, reduction in the burden of working people, and stabilization of macro factors. Successful policy should not rely on forced implementation. The past and present policies were successful not because of forced implementation, but because of awareness of macro and micro factors and voluntary use of FP. The voluntary nature of acceptance of FP suggests support for the FP policies. The current focus is on rural areas, and farmers in particular who are only aware of their needs and may feel state policy may interfere with their own interests. Implementation of FP among the rural population would be enhanced with an emphasis on their concerns such as social security in old age, the practical issues of having only daughters, and educational status. Educational campaigns promoting awareness of population pressure are needed and will benefit all the people. Social democratic doctrines can be introduced only from the outside

  19. Injection moulding for macro and micro products

    DEFF Research Database (Denmark)

    Islam, Mohammad Aminul

    used for macro products but with the ages it is going deep into the micro areas having machine and process improvements. Extensive research work on injection moulding is going on all over the world. New ideas are flowing into the machines, materials and processes. The technology has made significant......The purpose of the literature survey is to investigate the injection moulding technology in the macro and micro areas from the basic to the state-of-the-art recent technology. Injection moulding is a versatile production process for the manufacturing of plastic parts and the process is extensively...

  20. Higher Order Macro Coefficients in Periodic Homogenization

    Energy Technology Data Exchange (ETDEWEB)

    Conca, Carlos; San Martin, Jorge [Departamento de IngenierIa Matematica, Facultad de Ciencias Fisicas y Matematicas, Universidad de Chile and Centro de Modelamiento Matematico, UMR 2071 CNRS-UChile, Casilla 170/3 - Correo 3, Santiago (Chile); Smaranda, Loredana [Department of Mathematics, Faculty of Mathematics and Computer Science, University of Pitesti, 110040 Pitesti, Str. Targu din Vale Nr.1, Arges (Romania); Vanninathan, Muthusamy, E-mail: cconca@dim.uchile.cl, E-mail: jorge@dim.uchile.cl, E-mail: smaranda@dim.uchile.cl, E-mail: vanni@math.tifrbng.res.in [TIFR-CAM, Post Bag 6503, GKVK Post, Bangalore - 560065 (India)

    2011-09-15

    A first set of macro coefficients known as the homogenized coefficients appear in the homogenization of PDE on periodic structures. If energy is increased or scale is decreased, these coefficients do not provide adequate approximation. Using Bloch decomposition, it is first realized that the above coefficients correspond to the lowest energy and the largest scale. This naturally paves the way to introduce other sets of macro coefficients corresponding to higher energies and lower scales which yield better approximation. The next task is to compare their properties with those of the homogenized coefficients. This article reviews these developments along with some new results yet to be published.

  1. Macro-Controls Take the Helm

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The Chinese economy has maintained a bullish run for decades. But in recent years inflation has become more threatening. Worries therefore grow that the robust economy may slump due to the overwhelming macro-economic controls. How should China rein in inflation and at the same time hedge against economic freefall? What differentiates the country’s macro-economic controls in recent years from those in the past? Liu Shucheng and Zhang Xiaojing, researchers with the Institute of Economics under the Chinese Academy of Social Sciences, gave their opinions in the following excerpts:

  2. OML macros Web presentation guidelines and source list

    CERN Document Server

    Sheau Hwang, Chang

    1999-01-01

    More than 100 macros have been written and made available on the Web since the debut of PFW in 1996. Evidently, OML has benefited many OCLC system users in automating their jobs. Nevertheless, finding the desired macros takes considerable time and effort because Web sites that provide macros present them in widely varied formats. This article presents the Web sites that currently provide macros for sharing, initiates the discussion on Web macro presentation guidelines, evaluates the presented Web sites based on these guidelines, and provides a source list of useful macros specifically for OCLC subsystem applications. (0 refs).

  3. Survival benefits with transplantation in secondary AML evolving from myelodysplastic syndrome with hypomethylating treatment failure.

    Science.gov (United States)

    Shin, S-H; Yahng, S-A; Yoon, J-H; Lee, S-E; Cho, B-S; Eom, K-S; Lee, S; Min, C-K; Kim, H-J; Cho, S-G; Kim, D-W; Lee, J-W; Min, W-S; Park, C-W; Kim, Y-J

    2013-05-01

    The prognosis for patients with myelodysplastic syndrome with hypomethylating treatment failure (MDS-HTF) has been known to be poor. However, the clinical outcomes and optimal treatment options for secondary AML evolving from MDS-HTF (sAML/MDS-HTF) are not well known. This retrospective analysis was conducted to evaluate the clinical outcomes and influences of treatment options on survival in 46 consecutive patients with sAML/MDS-HTF. The median OS rates were 1.4 months in the best supportive care group (n=15) and 9.4 months in the active treatment group (n=31). One-year OS rates were 13.3% and 36.8%, respectively (P=0.001). Active treatment (PHTF if the patient is medically fit.

  4. Dual-fuel versus single-fuel propulsion systems for AMLS applications. [Advanced Manned Launch System

    Science.gov (United States)

    Stanley, Douglas O.; Talay, T. A.

    1989-01-01

    The results of using a computerized preliminary design system to integrate propulsion systems examined as a part of the Space Transportation Main Engine (STME) and Space Transportation Booster Engine (STBE) studies with reference vehicle concepts from the Advanced Manned Launch System (AMLS) study are presented. The major trade study presented is an analysis of the effect of using a single fuel for both stages of two-stage AMLS reference vehicles as opposed to using a separate fuel for the boosters. Other trade studies presented examine the effect of varying relevant engine parameters in an attempt to optimize the reference engines for use with the AMLS launch vehicles. In each propulsion trade discussed, special attention is given to the major vehicle performance and operational issues involved.

  5. An Implementation and Evaluation of the AMLS Method for SparseEigenvalue Problems

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Weiguo; Li, Xiaoye S.; Yang, Chao; Bai, Zhaojun

    2006-02-14

    We describe an efficient implementation and present aperformance study of an algebraic multilevel sub-structuring (AMLS)method for sparse eigenvalue problems. We assess the time and memoryrequirements associated with the key steps of the algorithm, and compareitwith the shift-and-invert Lanczos algorithm in computational cost. Oureigenvalue problems come from two very different application areas: theaccelerator cavity design and the normal mode vibrational analysis of thepolyethylene particles. We show that the AMLS method, when implementedcarefully, is very competitive with the traditional method in broadapplication areas, especially when large numbers of eigenvalues aresought.

  6. Postpartum Diagnosis of AML-M3: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Manjula Biradar

    2016-07-01

    Full Text Available A 27 year old female gravid 2, para 1, presented at 39 weeks of gestation with pain in abdomen going in for labour, and delivered healthy baby. The patient later had post-partum haemorrhage with Prothrombin Time (PT 10min, platelet count 70,000 cells/cumm. Peripheral smear showed shift to left with myeloblasts, promyelocytes. The diagnosis of Acute Myeloid Leukemia (AML was given and advised for bone marrow examination. The diagnosis AML-M3 was confirmed by marrow study. Unfortunately, patient went in for Disseminated Intravascular Coagulation (DIC and died 2 days after the diagnosis.

  7. Macro News, Riskfree Rates, and the Intermediary

    NARCIS (Netherlands)

    Menkveld, Albert J.; Sarkar, Asani; Wel, van der Michel

    2007-01-01

    Signed customer order flow correlates with permanent price changes in equity and nonequity markets. We exploit macro news events in the 30Y treasury futures market to identify causality from customer flow to riskfree rates. We remove the positive feedback trading part and establish that, in the 15 m

  8. Teaching Macro Principles "after" the Financial Crisis

    Science.gov (United States)

    Blinder, Alan

    2010-01-01

    Recent events should force everyone who teaches macroeconomics (or finance, for that matter) to reconsider their curriculums. In this short article, the author shares his thoughts about what should and should not be changed in the way economists teach macro principles to beginning students. Two tradeoffs are paramount and must be faced by every…

  9. Neutrino physics and astrophysics with MACRO

    CERN Document Server

    Bakari, D; Giorgini, M; Sioli, M

    2002-01-01

    Summary form only given. The study of the multiple Coulomb scattering of muons in the MACRO absorbers yield a distribution in L/E/sub nu / in agreement with nu /sub mu / from or to nu /sub tau / oscillations with the above parameters. (1 refs).

  10. Gender as a Macro Economic Variable

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2014-01-01

    markdownabstract__Abstract__ This chapter will analyse how gender can be used in a meaningful way in macroeconomic analysis. The challenge is that gender cannot be measured easily at the macro level. This is either because current gender variables are one-dimensional and miss out much gender –relev

  11. The Mechanics of CSCL Macro Scripts

    Science.gov (United States)

    Dillenbourg, Pierre; Hong, Fabrice

    2008-01-01

    Macro scripts structure collaborative learning and foster the emergence of knowledge-productive interactions such as argumentation, explanations and mutual regulation. We propose a pedagogical model for the designing of scripts and illustrate this model using three scripts. In brief, a script disturbs the natural convergence of a team and in doing…

  12. Gender as a Macro Economic Variable

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2013-01-01

    markdownabstract__Abstract__ This chapter will analyse how gender can be used in a meaningful way in macroeconomic analysis. The challenge is that gender cannot be measured easily at the macro level. This is either because current gender variables are one-dimensional and miss out much gender –relev

  13. A SAS IML Macro for Loglinear Smoothing

    Science.gov (United States)

    Moses, Tim; von Davier, Alina

    2011-01-01

    Polynomial loglinear models for one-, two-, and higher-way contingency tables have important applications to measurement and assessment. They are essentially regarded as a smoothing technique, which is commonly referred to as loglinear smoothing. A SAS IML (SAS Institute, 2002a) macro was created to implement loglinear smoothing according to…

  14. Micro-Macro Paradoxes of Entrepreneurship

    DEFF Research Database (Denmark)

    Søgaard, Villy

    2008-01-01

    Artiklen tager afsæt i det såkaldte micro-macro paradox fra Aids-Efficiency litteraturen og argumenterer for, at en tilsvarende problemstilling bør inddrages i vurderingen af f.eks. de beskæftigelsesmæssige konsekvenser af entrepreneuriel virksomhed. Den påviser også i en gennemgang af litteraturen...

  15. ELMO1 is upregulated in AML CD34+ stem/progenitor cells, mediates chemotaxis and predicts poor prognosis in normal karyotype AML.

    Directory of Open Access Journals (Sweden)

    Marta E Capala

    Full Text Available Both normal as well leukemic hematopoietic stem cells critically depend on their microenvironment in the bone marrow for processes such as self-renewal, survival and differentiation, although the exact pathways that are involved remain poorly understood. We performed transcriptome analysis on primitive CD34+ acute myeloid leukemia (AML cells (n = 46, their more differentiated CD34- leukemic progeny, and normal CD34+ bone marrow cells (n = 31 and focused on differentially expressed genes involved in adhesion and migration. Thus, Engulfment and Motility protein 1 (ELMO1 was identified amongst the top 50 most differentially expressed genes. ELMO1 is a crucial link in the signaling cascade that leads to activation of RAC GTPases and cytoskeleton rearrangements. We confirmed increased ELMO1 expression at the mRNA and protein level in a panel of AML samples and showed that high ELMO1 expression is an independent negative prognostic factor in normal karyotype (NK AML in three large independent patient cohorts. Downmodulation of ELMO1 in human CB CD34+ cells did not significantly alter expansion, progenitor frequency or differentiation in stromal co-cultures, but did result in a decreased frequency of stem cells in LTC-IC assays. In BCR-ABL-transduced human CB CD34+ cells depletion of ELMO1 resulted in a mild decrease in proliferation, but replating capacity of progenitors was severely impaired. Downregulation of ELMO1 in a panel of primary CD34+ AML cells also resulted in reduced long-term growth in stromal co-cultures in two out of three cases. Pharmacological inhibition of the ELMO1 downstream target RAC resulted in a severely impaired proliferation and survival of leukemic cells. Finally, ELMO1 depletion caused a marked decrease in SDF1-induced chemotaxis of leukemic cells. Taken together, these data show that inhibiting the ELMO1-RAC axis might be an alternative way to target leukemic cells.

  16. Cameleon language Part 1: Processor

    CERN Document Server

    de Sevricourt, O Cugnon

    2011-01-01

    Emergence is the way complex systems arise out of a multiplicity of relatively simple interactions between primitives. Since programming problems become more and more complexes and transverses, our vision is that application development should be process at two scales: micro- and macro-programming where at the micro-level the paradigm is step-by-step and at macro-level the paradigm is emergence. For micro-programming, which focuses on how things happen, popular languages, Java, C++, Python, are imperative writing languages where the code is a sequence of sentences executed by the computer. For macro-programming, which focuses on how things connect, popular languages, labVIEW, Blender, Simulink, are graphical data flow languages such that the program is a composition of operators, a unit-process consuming input data and producing output data, and connectors, a data-flow between an output data and an input data of two operators. However, despite their fruitful applications, these macro-languages are not transve...

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

    Science.gov (United States)

    2017-08-21

    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

  18. Azacitidine results in comparable outcome in newly diagnosed AML patients with more or less than 30% bone marrow blasts.

    NARCIS (Netherlands)

    Helm, L.H. van der; Veeger, N.J.; Kooy, M.v.; Beeker, A.; Weerdt, O. de; Groot, M. de; Alhan, C.; Hoogendoorn, M.; Laterveer, L.; Loosdrecht, A.A. van de; Koedam, J.; Vellenga, E.; Huls, G.A.

    2013-01-01

    The efficacy of azacitidine has been demonstrated in acute myeloid leukemia (AML) patients with 20-30% bone marrow (BM) blasts, but limited data is available on patients with >/=30% blasts. We analyzed 55 newly diagnosed AML patients, treated with azacitidine. The overall response rate was 42%. M

  19. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12.

    NARCIS (Netherlands)

    Harrison, C.J.; Hills, R.K.; Moorman, A.V.; Grimwade, D.J.; Hann, I.; Webb, D.K.; Wheatley, K.; Graaf, S.S.N. de; Berg, E. van den; Burnett, A.K.; Gibson, B.E.

    2010-01-01

    PURPOSE: Karyotype is an independent indicator of prognosis in acute myeloid leukemia (AML) that is widely applied to risk-adapted therapy. Because AML is rare in children, the true prognostic significance of individual chromosomal abnormalities in this age group remains unclear. PATIENTS AND METHOD

  20. [Reversed effect of valproic acid on transcription inhibition of AML1-ETO fusion protein of kasumi-1 leukemic cell line].

    Science.gov (United States)

    Zhao, Lei; Zhu, Cui-Min; Zhang, Zhi-Hua; Tian, Wen-Liang; Hao, Chang-Lai

    2009-04-01

    This study was aimed to investigate the mechanism of histone deacetylase (HDAC) inhibitor, valproic acid (VPA), reversing transcription inhibition of AML1-ETO fusion protein in Kasumi-1 cell line. The mRNA expressions of AML1-ETO, AML1 and cyclin D2 were detected by semi-quantitation RT-PCR after treating kasumi-1 cells with VPA at different doses/and different time points. The results indicated that the mRNA expression of AML1-ETO showed no obvious change, when kasumi-1 cells were treated with VPA. Compared with control group, the expression level of AML1 mRNA significantly increased in a dose-dependent manner. Compared with control group, the expression level of cyclin D2 mRNA significantly decreased when kasumi-1 cells had been treated with 3 mmol/L VPA as well as kasumi-1 cells were treated with different concentrations of VPA for 3 days. In conclusion, VPA could remove transcription inhibition of AML1-ETO fusion protein, increase transcription of AML1 and down-regulate mRNA expression of AML1 target gene cyclin D2 through HDAC inhibiting activity.

  1. Photodiode Circuit Macro-model for SPICE Simulation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    An accurate photodiode circuit macro-model is proposed for SPICE simulation. The definition and implementation of the macro-model is based on carrier stationary continuity equation. In this macro-model, the photodiode is a device of three pins, one for light intensity input and the other two for photocurrent output, which represent the relationship between photocurrent and incident light. The validity of the proposed macro-model is demonstrated with its PSPICE simulation result compared with reported experimental data.

  2. Macro-economic Impact Study for Bio-based Malaysia

    NARCIS (Netherlands)

    Meijl, van H.; Smeets, E.M.W.; Dijk, van M.; Powell, J.P.; Tabeau, A.A.

    2012-01-01

    Deze macro-economische impactstudie (MES) biedt kwantitatieve inzichten in de macro-economische effecten van de invoering tussen nu en 2030 van groene, op palmolie gebaseerde alternatieven voor de productie van elektriciteit, brandstoffen, chemicaliën en materialen in Maleisië.This Macro-economic Im

  3. Macro-economic Impact Study for Bio-based Malaysia

    NARCIS (Netherlands)

    Meijl, van H.; Smeets, E.M.W.; Dijk, van M.; Powell, J.P.; Tabeau, A.A.

    2012-01-01

    Deze macro-economische impactstudie (MES) biedt kwantitatieve inzichten in de macro-economische effecten van de invoering tussen nu en 2030 van groene, op palmolie gebaseerde alternatieven voor de productie van elektriciteit, brandstoffen, chemicaliën en materialen in Maleisië.This Macro-economic

  4. Intake of macro- and micronutrients in Danish vegans

    DEFF Research Database (Denmark)

    Kristensen, Nadja B; Madsen, Mia L; H Hansen, Tue

    2015-01-01

    Since information about macro- and micronutrient intake among vegans is limited we aimed to determine and evaluate their dietary and supplementary intake. Seventy 18-61 years old Danish vegans completed a four-day weighed food record from which their daily intake of macro- and micronutrients...... and the general Danish population in all measured macro- and micronutrients (p ...

  5. Language Treatment and Language Planning in Canada. Part 2: The Provinces. Language Planning Newsletter, Vol. 3, No. 4.

    Science.gov (United States)

    McConnell, Grant

    As stated in Part 1 of this discussion, Canada is a hybrid, making use of both the macro, or policy, model and the micro, or cultivation, model of language treatment. Some concrete measures are taking place in language status and corpus planning on the inter-federal-provincial level and the provincial level, particularly in Quebec. One such…

  6. 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.

  7. Decitabine enhances anti-CD33 monoclonal antibody BI 836858-mediated natural killer ADCC against AML blasts.

    Science.gov (United States)

    Vasu, Sumithira; He, Shun; Cheney, Carolyn; Gopalakrishnan, Bhavani; Mani, Rajeswaran; Lozanski, Gerard; Mo, Xiaokui; Groh, Veronica; Whitman, Susan P; Konopitzky, Renate; Kössl, Christian; Bucci, Donna; Lucas, David M; Yu, Jianhua; Caligiuri, Michael A; Blum, William; Adam, Paul J; Borges, Eric; Rueter, Bjoern; Heider, Karl-Heinz; Marcucci, Guido; Muthusamy, Natarajan

    2016-06-09

    Acute myeloid leukemia (AML) is the most common type of acute leukemia, affecting older individuals at a median age of 67 years. Resistance to intensive induction chemotherapy is the major cause of death in elderly AML; hence, novel treatment strategies are warranted. CD33-directed antibody-drug conjugates (gemtuzumab ozogamicin) have been shown to improve overall survival, validating CD33 as a target for antibody-based therapy of AML. Here, we report the in vitro efficacy of BI 836858, a fully human, Fc-engineered, anti-CD33 antibody using AML cell lines and primary AML blasts as targets. BI 836858-opsonized AML cells significantly induced both autologous and allogeneic natural killer (NK)-cell degranulation and NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In vitro treatment of AML blasts with decitabine (DAC) or 5-azacytidine, 2 hypomethylating agents that show efficacy in older patients, did not compromise BI 836858-induced NK-cell-mediated ADCC. Evaluation of BI 836858-mediated ADCC in serial marrow AML aspirates in patients who received a 10-day course of DAC (pre-DAC, days 4, 11, and 28 post-DAC) revealed significantly higher ADCC in samples at day 28 post-DAC when compared with pre-DAC treatment. Analysis of ligands to activating receptors (NKG2D) showed significantly increased NKG2D ligand [NKG2DL] expression in day 28 post-DAC samples compared with pre-DAC samples; when NKG2DL receptor was blocked using antibodies, BI 836858-mediated ADCC was significantly decreased, suggesting that DAC enhances AML blast susceptibility to BI 836858 by upregulating NKG2DL. These data provide a rationale for combination therapy of Fc-engineered antibodies such as BI 836858 with azanucleosides in elderly patients with AML.

  8. SECOND LANGUAGE ACQUISITION AND LANGUAGE TEACHING

    Directory of Open Access Journals (Sweden)

    Elsa Tragant

    2004-06-01

    Full Text Available After discussing the ties between language teaching and second language acquisition research, the present paper reviews the role that second language acquisition research has played on two recent pedagogical proposals. First, communicative language teaching, advocated in the early eighties, in which focus on the code was excluded, and then the more recent research-based proposals of integrating some degree of focus on form in meaning-based curricula. Following Ellis (1998, four macro-options of focus-on-form interventions and their theoretical motivations are presented, followed by recent research evidence: input processing, input enhancement, formfocused output and negative feedback. The last section of the paper deals with two related pedagogical issues: the choice of linguistic forms in focused instruction and its benefits depending on individual factors and the learning context.

  9. A Comparison of Alternative Estimators of Linearly Aggregated Macro Models

    Directory of Open Access Journals (Sweden)

    Fikri Akdeniz

    2012-07-01

    Full Text Available Normal 0 false false false TR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Times New Roman","serif"; mso-ansi-language:TR; mso-fareast-language:TR;} This paper deals with the linear aggregation problem. For the true underlying micro relations, which explain the micro behavior of the individuals, no restrictive rank conditions are assumed. Thus the analysis is presented in a framework utilizing generalized inverses of singular matrices. We investigate several estimators for certain linear transformations of the systematic part of the corresponding macro relations. Homogeneity of micro parameters is discussed. Best linear unbiased estimation for micro parameters is described.

  10. Histological and immunohistochemical features of gingival enlargement in a patient with AML.

    Science.gov (United States)

    Sonoi, Norihiro; Soga, Yoshihiko; Maeda, Hiroshi; Ichimura, Koichi; Yoshino, Tadashi; Aoyama, Kazutoshi; Fujii, Nobuharu; Maeda, Yoshinobu; Tanimoto, Mitsune; Logan, Richard; Raber-Durlacher, Judith; Takashiba, Shogo

    2012-07-01

    Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells.

  11. Inhibition of FLT3 expression by green tea catechins in FLT3 mutated-AML cells.

    Directory of Open Access Journals (Sweden)

    Bui Thi Kim Ly

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous disease characterized by a block in differentiation and uncontrolled proliferation. FLT3 is a commonly mutated gene found in AML patients. In clinical trials, the presence of a FLT3-ITD mutation significantly correlates with an increased risk of relapse and dismal overall survival. Therefore, activated FLT3 is a promising molecular target for AML therapies. In this study, we have shown that green tea polyphenols including (--epigallocatechin-3-gallate (EGCG, (--epigallocatechin (EGC, and (--epicatechin-3-gallate (ECG suppress the proliferation of AML cells. Interestingly, EGCG, EGC and ECG showed the inhibition of FLT3 expression in cell lines harboring FLT3 mutations. In the THP-1 cells harboring FLT3 wild-type, EGCG showed the suppression of cell proliferation but did not suppress the expression of FLT3 even at the concentration that suppress 100% cell proliferation. Moreover, EGCG-, EGC-and ECG-treated cells showed the suppression of MAPK, AKT and STAT5 phosphorylation. Altogether, we suggest that green tea polyphenols could serve as reagents for treatment or prevention of leukemia harboring FLT3 mutations.

  12. Histological and immunohistochemical features of gingival enlargement in a patient with AML

    NARCIS (Netherlands)

    Sonoi, N.; Soga, Y.; Maeda, H.; Ichimura, K.; Yoshino, T.; Aoyama, K.; Fujii, N.; Maeda, Y.; Tanimoto, M.; Logan, R.; Raber-Durlacher, J.; Takashiba, S.

    2012-01-01

    Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed bo

  13. NK cell-mediated killing of AML blasts. Role of histamine, monocytes and reactive oxygen metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Brune, M.; Mellqvist, U.H. [Sahlgren`s Univ. Hospital, Dept. of Medicine, Haematology Section, Goeteborg (Sweden); Hansson, M.; Hermodsson, S.; Hellstrand, K. [Sahlgren`s Univ. Hospital, Dept. of Virology, Goeteborg (Sweden)

    1996-10-01

    Blasts recovered from patients with acute myelogenous leukaemia (AML) were lysed by heterologeous natural killer (NK) cells treated with NK cell-activating cytokine-induced killing of AML blasts was inhibited by monocytes, recovered from peripheral blood by counterflow centrifugal elutriation. Histamine, at concentrations exceeding 0.1 {mu}M, abrogated the monocyte-induced inhibition of NK cells; thereby, histamine and IL-2 or histamine and IFN-{alpha} synergistically induced NK cell-mediated destruction of AML blasts. The effect of histamine was completely blocked by the histamine H2-receptor (H2R) antagonist ranitidine but not by its chemical control AH20399AA. Catalase, a scavenger of reactive oxygen metabolites (ROM), reversed the monocyte-induced inhibition of NK cell-mediated killing of blast cells, indicating that the inhibitory signal was mediated by products of the respiratory burst of monocytes. It is concluded that (i) monocytes inhibit anti-leukemic properties of NK cells, (ii) the inhibition is conveyed by monocyte-derived ROM, and (iii) histamine reverses the inhibitory signal and, thereby, synergizes with NK cell-activating cytokines to induce killing of AML blasts. (au) 19 refs.

  14. 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...

  15. Histological and immunohistochemical features of gingival enlargement in a patient with AML

    NARCIS (Netherlands)

    Sonoi, N.; Soga, Y.; Maeda, H.; Ichimura, K.; Yoshino, T.; Aoyama, K.; Fujii, N.; Maeda, Y.; Tanimoto, M.; Logan, R.; Raber-Durlacher, J.; Takashiba, S.

    2012-01-01

    Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed

  16. Long-term survival after allogeneic haematopoietic cell transplantation for AML in remission

    DEFF Research Database (Denmark)

    Sengeløv, H; Gerds, T A; Brændstrup, P

    2013-01-01

    We report the results of non-myeloablative (NM) and myeloablative (MA) conditioning for haematopoietic cell transplantation in 207 consecutive AML patients at a single institution. A total of 122 patients were transplanted in first CR (CR1) and 67 in second CR (CR2). MA conditioning was given to ...

  17. 基于PMAC的MACRO Station 的应用%The Application of MACRO Station Based on PMAC

    Institute of Scientific and Technical Information of China (English)

    王宏; 王斌; 弓清忠; 祁玉宁

    2004-01-01

    介绍了PMAC运动控制器及MACRO Station(宏运动控制站)的概念.阐述MACRO Station的设置及映射的建立,结合轧辊磨床专用数控系统的建立,介绍MACRO Station的应用及其实际意义.

  18. Analysis of Macro-Structure of Why Historians DisagreeLesson 3 of Contemporary College English Book4

    Institute of Scientific and Technical Information of China (English)

    Wang Li

    2009-01-01

    With the development of the study of text analysis and ihnctional grammar,text teaching has gradually become an important method in foreign language teaching.In the field of text analysis,textual structure has always been linguists' focus.After introducing researches on macro-structure of text,this paper gives a brief introduction to the text Why Historians Disagree,and then discusses how different macro-structure patterns are adopted in the text,at last draws implications for the teaching of intensive reading course.

  19. Macro-institutional Complexity in Logistics

    DEFF Research Database (Denmark)

    Wessel, Frederic; Kinra, Aseem; Kotzab, Herbert

    2016-01-01

    structure and transactional costs, the concept of environmental complexity is applied to the logistics management perspective. Thereby, the impacts which a given framework on a macro-institutional level might have on the situation and leeway in decision-making at the firm (micro) or the supply chain (meso......In this paper, the interlink between the concept of macro-institutional complexity in logistics and the dynamics in the logistics practice of Eastern Europe will be examined. Referring to the importance of different authors having ascribed to the external environmental uncertainty on organizational......) levels will be analysed. Furthermore, a quantitative modelling approach will be presented and exemplified by using the case of logistics infrastructure in Eastern Europe....

  20. Injection moulding for macro and micro products

    DEFF Research Database (Denmark)

    Islam, Mohammad Aminul

    The purpose of the literature survey is to investigate the injection moulding technology in the macro and micro areas from the basic to the state-of-the-art recent technology. Injection moulding is a versatile production process for the manufacturing of plastic parts and the process is extensively...... used for macro products but with the ages it is going deep into the micro areas having machine and process improvements. Extensive research work on injection moulding is going on all over the world. New ideas are flowing into the machines, materials and processes. The technology has made significant...... advancement in the area of micro injection moulding, multi-component and two component injection mounding. In near future it is likely to be the way of manufacturing moulded interconnects devices (MID) for a low cost integration of electrical and mechanical functionalities on a single device. This paper...

  1. Joint Macro and Femto Field Performance and Interference Measurements

    DEFF Research Database (Denmark)

    Jørgensen, Niels T.K.; Isotalo, Tero; Pedersen, Klaus

    2012-01-01

    Signal Code Power (RSCP) is stronger than femto RSCP. We also conclude that a macro escape carrier is a robust DL interference management solution. In uplink (UL) direction it is shown that a single femto UE close to macro cell potentially can cause a noise rise of 6 dB in the surrounding macro cell...... radius smaller than 5 meter – with realistic power settings. This makes co-channel femto deployment less promising in dense macro environments with good macro RSCP coverage....

  2. Underground Muon Physics with the MACRO experiment

    CERN Document Server

    Sioli, M

    2000-01-01

    Underground muon events detected by the MACRO experiment at Gran Sasso havebeen studied for different purposes. The studies include the vertical muonintensity measurement, multiplicity distribution, lateral and angular muondistribution and searches for substructures inside muon bundles. These analyseshave contributed to bring new insights in cosmic ray physics, in particular inthe framework of primary cosmic ray composition studies. Moreover, thisactivity allows the testing and tuning of Monte Carlo simulations, inparticular for aspects associated with models of hadronic interactions and muonpropagation through the rock.

  3. Introduction to macro-econophysics and finance

    Science.gov (United States)

    Mimkes, Jürgen

    2012-11-01

    Closed integrals in physics lead to equations for sources and vortices in fluid mechanics, electrodynamics and thermodynamics. In economics, the Stokes integral of economic circuits leads to new fundamental equations of macro-econophysics. These equations differ significantly from the laws of neoclassical theory. Entropy of markets replaces of the economic Cobb Douglas function and leads to stochastic processes and micro-econophysics of financial markets.

  4. Macro-FF: Improving AI Planning with Automatically Learned Macro-Operators

    CERN Document Server

    Botea, A; Mueller, M; Schaeffer, J; 10.1613/jair.1696

    2011-01-01

    Despite recent progress in AI planning, many benchmarks remain challenging for current planners. In many domains, the performance of a planner can greatly be improved by discovering and exploiting information about the domain structure that is not explicitly encoded in the initial PDDL formulation. In this paper we present and compare two automated methods that learn relevant information from previous experience in a domain and use it to solve new problem instances. Our methods share a common four-step strategy. First, a domain is analyzed and structural information is extracted, then macro-operators are generated based on the previously discovered structure. A filtering and ranking procedure selects the most useful macro-operators. Finally, the selected macros are used to speed up future searches. We have successfully used such an approach in the fourth international planning competition IPC-4. Our system, Macro-FF, extends Hoffmanns state-of-the-art planner FF 2.3 with support for two kinds of macro-operato...

  5. Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model

    Institute of Scientific and Technical Information of China (English)

    Petar Ivanovski; Ivan Ivanovski; Dimitrije Nikoli(c); Ivana Jovanovi(c)

    2012-01-01

    Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations.The bottleneck is evidence that leukemia initiation,by in utero acquired chromosome translocations that generate functional fusion genes,is far more common than the incidence rate of corresponding leukemia.For childhood TEL-AML1+ acute lymphoblastic leukemia (ALL) this equates to approximately 100 times.Practically this means that among a hundred children born with TEL-AML1 fusion gene,only one child will later in its life develop ALL.The key data necessary for unraveling of this mystery were discovered in 2002.It was the level of TEL-AML1 + cells' frequency.The bottleneck is caused by the very low body TEL-AML1 + cell count.Only one out of a thousand B cells carries TEL-AML1 fusion gene.TEL-AML1+ body cell count is low because TEL-AML1 fusion is generated at cell level of 10a to 10-4 just during the late fetal lymphopoiesis i.e.after the 36th gestational week.

  6. Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model.

    Science.gov (United States)

    Ivanovski, Petar; Ivanovski, Ivan; Nikolić, Dimitrije; Jovanović, Ivana

    2012-03-01

    Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations. The bottleneck is evidence that leukemia initiation, by in utero acquired chromosome translocations that generate functional fusion genes, is far more common than the incidence rate of corresponding leukemia. For childhood TEL-AML1(+) acute lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically this means that among a hundred children born with TEL-AML1 fusion gene, only one child will later in its life develop ALL. The key data necessary for unraveling of this mystery were discovered in 2002. It was the level of TEL-AML1(+) cells’ frequency. The bottleneck is caused by the very low body TEL-AML1(+) cell count. Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1(+) body cell count is low because TEL-AML1 fusion is generated at cell level of 10(-3) to 10(-4) just during the late fetal lymphopoiesis i.e. after the 36th gestational week.

  7. Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression

    Institute of Scientific and Technical Information of China (English)

    Guogen Mao; Fenghua Yuan; Kimberly Absher; C Darrell Jennings; Dianna S Howard; Craig T Jordan; Liya Gu

    2008-01-01

    Acute myeloid leukemia (AML) is an aggressive hematological cancer. Despite therapeutic regimens that lead to complete remission, the vast majority of patients undergo relapse. The molecular mechanisms underlying AML development and relapse remain incompletely defined. To explore whether loss of DNA mismatch repair (MMR) function is involved in AML, we screened two key MMR genes, MSH2 and MLH1, for mutations and promoter hypermethylation in leukemia specimens from 53 AML patients and blood from 17 non-cancer controls. We show here that whereas no amino acid alteration or promoter hypermethylation was detected in all control samples, 18 AML patients exhibited either mutations in MMR genes or hypermethylation in the MLH1 promoter. In vitro functional MMR analysis revealed that almost all the mutations analyzed resulted in loss of MMR function. MMR defects were significantly more frequent in patients with refractory or relapsed AML compared with newly diagnosed patients. These observations suggest for the first time that the loss of MMR function is associated with refractory and relapsed AML and may contribute to disease pathogenesis.

  8. Micro Declared Language Policy or Not?: Language-Policy-Like Statements in the Rules of Procedure of the Rwandan Parliament

    Science.gov (United States)

    Gafaranga, Joseph; Niyomugabo, Cyprien; Uwizeyimana, Valentin

    2013-01-01

    An invitation to integrate macro and micro level analyses has been extended to researchers as this integration is felt to be the way forward for language policy research (Ricento, Ideology, politics and language policies: Focus on english, John Benjamins, Amsterdam, 2000). In turn, the notion of 'micro' in language policy has been specified as…

  9. Chemogenomic landscape of RUNX1-mutated AML reveals importance of RUNX1 allele dosage in genetics and glucocorticoid sensitivity.

    Science.gov (United States)

    Simon, Laura; Lavallée, Vincent-Philippe; Bordeleau, Marie-Eve; Krosl, Jana; Baccelli, Irene; Boucher, Geneviève; Lehnertz, Bernhard; Chagraoui, Jalila; MacRae, Tara; Ruel, Réjean; Chantigny, Yves A; Lemieux, Sébastien; Marinier, Anne; Hébert, Josée; Sauvageau, Guy

    2017-08-30

    RUNX1-mutated (RUNX1mut) Acute Myeloid Leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Towards this goal, we further dissected the mutational spectrum and gene expression profile of RUNX1mut AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup. RNA-sequencing of 47 RUNX1mut primary AML specimens was performed and sequencing results were compared to those of RUNX1 wild-type samples. Chemical screens were also conducted using RUNX1mut specimens to identify compounds selectively affecting the viability of RUNX1mut AML. We show that samples with no remaining RUNX1 wild-type allele are clinically and genetically distinct and display a more homogeneous gene expression profile. Chemical screening revealed that most RUNX1mut specimens are sensitive to glucocorticoids (GCs) and we confirmed that GCs inhibit AML cell proliferation through their interaction with the Glucocorticoid Receptor (GR). We observed that specimens harboring RUNX1 mutations expected to result in low residual RUNX1 activity are most sensitive to GCs, and that co-associating mutations as well as that GR levels contribute to GC sensitivity. Accordingly, acquired glucocorticoid sensitivity was achieved by negatively regulating RUNX1 expression in human AML cells. Our findings show the profound impact of RUNX1 allele dosage on gene expression profile and glucocorticoid sensitivity in AML, thereby opening opportunities for preclinical testing which may lead to drug repurposing and improved disease characterization. Copyright ©2017, American Association for Cancer Research.

  10. Classification of Acute Myelogenous Leukemia (AML M2 and AML M3) using Momentum Back Propagation from Watershed Distance Transform Segmented Images

    Science.gov (United States)

    Suryani, Esti; Wiharto; Palgunadi, Sarngadi; Nurcahya Pradana, TP

    2017-01-01

    This study uses image processing to analyze white blood cell with leukemia indicated that includes the identification, analysis of shapes and sizes, as well as white blood cell count indicated the symptoms of leukemia. A case study in this research was blood cells, from the type of leukemia Acute Myelogenous Leukemia (AML), M2 and M3 in particular. Image processing operations used for segmentation by utilizing the color conversion from RGB (Red, Green dab Blue) to obtain white blood cell candidates. Furthermore, the white blood cells candidates are separated by other cells with active contour without edge. WBC (White Blood Cell) results still have intersected or overlap condition. Watershed distance transform method can separate overlap of WBC. Furthermore, the separation of the nucleus from the cytoplasm using the HSI (Hue Saturation Intensity). The further characteristic extraction process is done by calculating the area WBC, WBC edge, roundness, the ratio of the nucleus, the mean and standard deviation of pixel intensities. The feature extraction results are used for training and testing in determining the classification of AML: M2 and M3 by using the momentum backpropagation algorithm. The classification process is done by testing the numeric data input from the feature extraction results that have been entered in the database. K-Fold validation is used to divide the amount of training data and to test the classification of AML M2 and M3. The experiment results of eight images trials, the result, was 94.285% per cell accuracy and 75% per image accuracy

  11. Nano/macro porous bioactive glass scaffold

    Science.gov (United States)

    Wang, Shaojie

    Bioactive glass (BG) and ceramics have been widely studied and developed as implants to replace hard tissues of the musculo-skeletal system, such as bones and teeth. Recently, instead of using bulk materials, which usually do not degrade rapidly enough and may remain in the human body for a long time, the idea of bioscaffold for tissue regeneration has generated much interest. An ideal bioscaffold is a porous material that would not only provide a three-dimensional structure for the regeneration of natural tissue, but also degrade gradually and, eventually be replaced by the natural tissue completely. Among various material choices the nano-macro dual porous BG appears as the most promising candidate for bioscaffold applications. Here macropores facilitate tissue growth while nanopores control degradation and enhance cell response. The surface area, which controls the degradation of scaffold can also be tuned by changing the nanopore size. However, fabrication of such 3D structure with desirable nano and macro pores has remained challenging. In this dissertation, sol-gel process combined with spinodal decomposition or polymer sponge replication method has been developed to fabricate the nano-macro porous BG scaffolds. Macropores up to 100microm are created by freezing polymer induced spinodal structure through sol-gel transition, while larger macropores (>200um) of predetermined size are obtained by the polymer sponge replication technique. The size of nanopores, which are inherent to the sol-gel method of glass fabrication, has been tailored using several approaches: Before gel point, small nanopores are generated using acid catalyst that leads to weakly-branched polymer-like network. On the other hand, larger nanopores are created with the base-catalyzed gel with highly-branched cluster-like structure. After the gel point, the nanostructure can be further modified by manipulating the sintering temperature and/or the ammonia concentration used in the solvent

  12. Rolle der gemeinsamen Expression von AML1-ETO und weiteren Onkogenen für die Induktion von Leukämie

    OpenAIRE

    Eichwald, Viktoria

    2014-01-01

    Akute Leukämien treten in allen Altersstufen auf. Akute lymphatische Leukämie (ALL) ist die häufigste Leukämie bei Kindern, während akute myeloischen Leukämien (AML) mit verschiedenen Untergruppen etwa 80% aller akuten Leukämien bei Erwachsenen ausmachen. Die Translokation t(8;21) resultiert in der Entstehung des Fusionsgens AML1-ETO und zählt zu den häufigen Translokationen bei der AML. Dabei fusioniert die DNA-bindende Domäne des AML1 mit dem fast kompletten ETO-Protein. AML1-ETO wirkt als ...

  13. Augmentation of autologous T cell reactivity with acute myeloid leukemia (AML) blasts by Toll-like receptor (TLR) agonists.

    Science.gov (United States)

    Zhong, RuiKun; Li, Hongying; Messer, Karen; Lane, Thomas A; Zhou, Jiehua; Ball, Edward D

    2015-06-01

    This study investigated whether TNF-α, Toll-like receptors (TLRs) 7/8 agonist resiquimod (R848), the TLR4 agonist lipopolysaccharide (LPS) and their combinations can enhance autologous AML-reactive T cell generation in an in vitro culture. AML peripheral blood or bone marrow mononuclear cells were cultured in medium supplemented with GM-CSF/IL-4 to induce dendritic cell (DC) differentiation of AML blasts (AML-DC). The impact of TNF-α, LPS, R848 and their combinations on AML-DC cultures was analyzed. Significantly enhanced CD80, CD40, CD83, CD54, HLA-DR and CD86 expression of AML cells was observed by addition of TNF-α, LPS, R848 alone or combinations. Induced CD80 expression of AML cells was significantly higher through the combination of TNF-α, LPS and R848 (T + L + R) than that by T alone. CTL induced from T + L + R, T + R, T + L, L + R and R, but not T, L alone stimulated cultures showed significantly higher IFN-γ release than the medium control in response to autologous AML cells. IFN-γ release by T + L + R was significantly higher than T or L alone, and T + R was significantly higher than T alone. CTL generated from T + L + R, T + L, T + R, L + R and L alone exerted significantly higher AML cell killing than medium control. AML cell killing by T + L + R and T + R was significantly higher than T or R alone. These results indicate that the combination of T + L + R induces a significantly enhanced antigen presentation effect of AML-DC. We speculate that the complementary effects of reagent combinations may better address the heterogeneity of responses to any single agent in AML cells from different patients.

  14. Two splice-factor mutant leukemia subgroups uncovered at the boundaries of MDS and AML using combined gene expression and DNA-methylation profiling.

    Science.gov (United States)

    Taskesen, Erdogan; Havermans, Marije; van Lom, Kirsten; Sanders, Mathijs A; van Norden, Yvette; Bindels, Eric; Hoogenboezem, Remco; Reinders, Marcel J T; Figueroa, Maria E; Valk, Peter J M; Löwenberg, Bob; Melnick, Ari; Delwel, Ruud

    2014-05-22

    Mutations in splice factor (SF) genes occur more frequently in myelodysplastic syndromes (MDS) than in acute myeloid leukemias (AML). We sequenced complementary DNA from bone marrow of 47 refractory anemia with excess blasts (RAEB) patients, 29 AML cases with low marrow blast cell count, and 325 other AML patients and determined the presence of SF-hotspot mutations in SF3B1, U2AF35, and SRSF2. SF mutations were found in 10 RAEB, 12 AML cases with low marrow blast cell count, and 25 other AML cases. Our study provides evidence that SF-mutant RAEB and SF-mutant AML are clinically, cytologically, and molecularly highly similar. An integrated analysis of genomewide messenger RNA (mRNA) expression profiling and DNA-methylation profiling data revealed 2 unique patient clusters highly enriched for SF-mutant RAEB/AML. The combined genomewide mRNA expression profiling/DNA-methylation profiling signatures revealed 1 SF-mutant patient cluster with an erythroid signature. The other SF-mutant patient cluster was enriched for NRAS/KRAS mutations and showed an inferior survival. We conclude that SF-mutant RAEB/AML constitutes a related disorder overriding the artificial separation between AML and MDS, and that SF-mutant RAEB/AML is composed of 2 molecularly and clinically distinct subgroups. We conclude that SF-mutant disorders should be considered as myeloid malignancies that transcend the boundaries of AML and MDS.

  15. 成人急性髓系白血病患者AML1融合基因的快速检测及其临床意义%Rapid Detection of AML1 Associated Fusion Genes in Patients with Adult Acute Myeloid Leukemia and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    姜孟孟; 高丽; 靖彧; 丁一; 徐媛媛; 周敏航; 马超; 王楠; 王蔚

    2013-01-01

    This study was aimed to detect the expression of AML1 fusion genes in the paitents with adult acute myeloid leukemia (AML) and further to investigate their association with the progression and prognosis of AML.Bone marrow samples were collected from 168 patients with de novo adult AML,and the expression ofAML1-ETO,AML1-EVI1,AML1-MDS1,AML1-MTG16,AML1-PRDM16,AML1-LRP16,AML1-CLCA2 and AML1-PRDX4 was analyzed by a novel multiplex nested RT-PCR.Positive samples and minimal residual disease were further examined by real-time fluorescent quantitative PCR.The results showed that the AML1 fusion genes were found in 10.7% (18/168) patients.Among them,AML1-ETO in 12 (7.1%) cases were detected,AML1-EVI1 in 2 cases (1.2%),and AML1-MDS1,AML1MTG16,AML1-PRDM16,and AML1-CLCA2 in 1 case (0.6%) each were detected.Among the patients with AML1ETO,10 patients (10/12,83.33%) achieved complete remission (CR) after one cycle of chemotherapy,while 2 patients achieved CR after 2 cycles of chemotherapy.The 2 patients with AML1-EVI1 failed to achieve CR after one cycle of chemotherapy.Patients with AML1-MDS1,AML1-MTG16,AML1-PRDM16,or AML1-CACL2 did not achieve CR after one cycle of chemotherapy.It is concluded that AML1 fusion genes are more frequent and can provide the molecular markers for diagnostis and prognosis evaluation of AML and for monitorying MRD.%本研究旨在检测AML1相关融合基因在成人急性髓系白血病(AML)患者中的发生率,并初步分析AML1融合基因与AML发生、发展及预后的相关性.利用多重巢式RT-PCR方法对168例初治AML患者的骨髓标本进行AML融合基因(AML1-ETO,AML1-EVI,AML1-MDS1,ML1-M TG16,AML1-PRDM16,AML1-LRP16,AML1-CLCA2和AML1-PRDX4)的快速检测.结果表明,168例AML初治患者的骨髓标本中,有18例出现AML1融合基因,其阳性率为10.7%,其中12例AML1-ETO阳性(7.14%),2例AML1-EVI1阳性(1.19%),1例AML1-MDS1阳性(0.6%),1例AML1-MTG16阳性(0.6%),1例AML1-PRDM16阳性(0.6%),1例AML1

  16. Mediating National Language Management: The Discourse of Citizenship Categorization in Norwegian Media

    Science.gov (United States)

    Lane, Pia

    2009-01-01

    The dimension of language policing that is the focus in this article refers to the management of micro-level language use by a macro-level institution, in this context the Norwegian Language Council, co-constructed with media actors. An important aspect of language policing is the official definition of terms, carried out by bodies like the…

  17. 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.

  18. YKL-40 in allogeneic hematopoietic cell transplantation after AML and myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Kornblit, B; Wang, T; Lee, S J;

    2016-01-01

    YKL-40, also called chitinase-3-like-1 protein, is an inflammatory biomarker that has been associated with disease severity in inflammatory and malignant diseases, including AML, multiple myeloma and lymphomas. The objective of the current study was to assess the prognostic value of pretransplant......, otherwise equal, donors are available.Bone Marrow Transplantation advance online publication, 18 July 2016; doi:10.1038/bmt.2016.192....... recipient and donor plasma YKL-40 concentrations in patients with AML (n=624) or myelodysplastic syndrome (n=157) treated with allogeneic hematopoietic cell transplantation (HCT). In recipients, the plasma YKL-40 concentrations were increased when the HCT-comorbidity index was ⩾5 (P=0.028). There were...

  19. 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.

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

    Science.gov (United States)

    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.

    2017-01-01

    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. PMID:27895058

  1. Machining Challenges: Macro to Micro Cutting

    Science.gov (United States)

    Shunmugam, M. S.

    2016-04-01

    Metal cutting is an important machining operation in the manufacture of almost all engineering components. Cutting technology has undergone several changes with the development of machine tools and cutting tools to meet challenges posed by newer materials, complex shapes, product miniaturization and competitive environments. In this paper, challenges in macro and micro cutting are brought out. Conventional and micro end-milling are included as illustrative examples and details are presented along with discussion. Lengthy equations are avoided to the extent possible, as the emphasis is on the basic concepts.

  2. Macros y atajos para el traductor

    OpenAIRE

    José Luis Heredero

    2007-01-01

    Sin necesidad de recurrir a los productos comerciales de ayuda a la traducción que se han ido generalizando en muchas grandes empresas y organizaciones, el traductor independiente puede ver considerablemente facilitado su trabajo si sabe explotar las muchas posibilidades que brindan Visual Basic y otros lenguajes poco conocidos de dominio público. Se presentan aquí varias macros de Word y pequeñas aplicaciones desarrolladas en los últimos años para acelerar tanto las búsquedas de términos —ba...

  3. Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies.

    Science.gov (United States)

    Oosterveld, Margriet; Suciu, Stefan; Muus, Petra; Germing, Ulrich; Delforge, Michel; Belhabri, Amin; Aul, Carlo; Selleslag, Dominik; Ferrant, Augustin; Marie, Jean-Pierre; Amadori, Sergio; Jehn, Ulrich; Mandelli, Franco; Hess, Uwe; Hellström-Lindberg, Eva; Cakmak-Wollgast, Songuel; Vignetti, Marco; Labar, Boris; Willemze, Roel; de Witte, Theo

    2015-01-01

    High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-specific prognostic factors and to develop prognostic scores for both patient groups. A total of 692 patients in the EORTC/GIMEMA AML-10 study and 289 patients in the CRIANT study received identical remission-induction and consolidation treatment. Estimated 5-year survival rate was 34 % in the AML-10 versus 27 % in the CRIANT study, and estimated disease-free survival was 40 % versus 28 %, respectively. In multivariate analysis, cytogenetic characteristics, white blood count, and age appeared prognostic for survival in both studies. French-American-British (FAB) subtype and performance status were prognostic in the AML-10 study only, whereas number of cytopenias and duration of antecedent hematologic disorder >6 months were prognostic in the CRIANT study only. The prognostic scores distinguish three groups with a 5-year survival rate of 54, 38, and 19 % in the AML-10 study versus 69, 37, and 5 % in the CRIANT study. The prognostic value of these scores has been validated on two external series. The new scoring systems form a practical tool to predict the outcome of individual MDS and AML patients treated with intensive antileukemic therapy.

  4. Results of a randomized trial in children with Acute Myeloid Leukaemia : Medical Research Council AML12 trial

    NARCIS (Netherlands)

    Gibson, Brenda E. S.; Webb, David K. H.; Howman, Andrew J.; De Graaf, Siebold S. N.; Harrison, Christine J.; Wheatley, Keith

    2011-01-01

    The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial (children) addressed the optimal anthracenedione/anthracycline in induction and the optimal number of courses of consolidation chemotherapy. 504 children (

  5. Macro-Integration for Solving Large Data Reconciliation Problems

    Directory of Open Access Journals (Sweden)

    Nino Mushkudiani

    2014-04-01

    Full Text Available Macro-integration technique is a well established method forreconciliation of large, high-dimensional tables, especially applied to macroeconomic data at national statistical oces (NSO. This technique is mainly used when data obtained from dierent sources should be reconciled on a macro level. New areas of applications for this technique arise as new data sources become available to NSO's. Often these new data sources cannot be combined on a micro level, while macro integration could provide a solution for such problems. Yet, more research should be carried out to investigate if in such situations macro integration could indeed be applied. In this paper we propose two applications of macro-integration techniques in other domains than the traditional macro-economic applications. In particular: reconciliation of tables of a virtual census and reconciliation of monthly series of short term statistics gures with the quarterly gures of structural business statistics.

  6. Chimeric antigen receptor T cell therapy in AML: How close are we?

    Science.gov (United States)

    Gill, Saar

    2016-12-01

    The majority of patients presenting with acute myeloid leukemia (AML) initially respond to chemotherapy but post-remission therapy is required to consolidate this response and achieve long-term disease-free survival. The most effective form of post-remission therapy relies on T cell immunotherapy in the form of allogeneic hematopoietic cell transplantation (HCT). However, patients with active disease cannot usually expect to be cured with HCT. This inherent dichotomy implies that traditional T cell-based immunotherapy in the form of allogeneic HCT stops being efficacious somewhere between the measurable residual disease (MRD) and the morphologically obvious range. This is in part because the full power of T cells must be restrained in order to avoid lethal graft-versus-host disease (GVHD) and partly because only a sub-population of donor T cells are expected to be able to recognize AML cells via their T cell receptor. Chimeric antigen receptor (CAR) T cell therapy, most advanced in the treatment of patients with B-cell malignancies, may circumvent some of these limitations. However, major challenges remain to be overcome before CAR T cell therapy can be safely applied to AML.

  7. AML-loaded DC generate Th1-type cellular immune responses in vitro.

    Science.gov (United States)

    Xing, D; Decker, W K; Li, S; Robinson, S N; Yang, H; Segal, H; O'Connor, S; Yao, X; Komanduri, K V; McMannis, J D; Jones, R B; de Lima, M; Champlin, R E; Shpall, E J

    2006-01-01

    The generation of AML-specific T-lymphocyte responses by leukemia-derived DC has been documented by multiple investigators and is being pursued clinically. An obstacle to widespread use of this strategy is that it has not been possible to generate leukemic DC from all patients, and an alternative approach is needed if the majority of leukemia patients are to receive therapeutic vaccination in conjunction with other treatment protocols. In the present study, we generated DC from CD14-selected monocytes isolated from healthy donor PBPC and loaded them with a total cell lysate from AML patient blasts. Immature in vitro-derived DC exhibited robust phagocytic activity, and mature DC demonstrated high expression of CD80, CD83, CD86 and the chemokine receptor CCR7, important for DC migration to local lymph nodes. Mature, Ag-loaded DC were used as APC for leukemia-specific cytotoxic T-lymphocyte (CTL) induction and demonstrated cytotoxic activity against leukemic targets. CTL lysis was Ag-specific, with killing of both allogeneic leukemic blasts and autologous DC loaded with allogeneic AML lysate. HLA-matched controls were not lysed in our system. These data support further research into the use of this strategy as an alternative approach to leukemia-derived DC vaccination.

  8. Mutation Analysis of hCDC4 in AML Cells Identifies a New Intronic Polymorphism

    Directory of Open Access Journals (Sweden)

    Daniel Nowak, Maximilian Mossner, Claudia D. Baldus, Olaf Hopfer, Eckhard Thiel, Wolf-Karsten Hofmann

    2006-01-01

    Full Text Available hCDC4 (FBW7, FBXW7 is a new potential tumor suppressor gene which provides substrate specificity for SCF (Skp–Cullin–F-box ubiquitin ligases and thereby regulates the degradation of potent oncogenes such as cyclin E, Myc, c-Jun and Notch. Mutations in the hCDC4 gene have been found in several solid tumors such as pancreas, colorectal or endometrial cancer. We carried out a mutation analysis of the hCDC4 gene in 35 samples of patients with Acute Myeloid Leukemia (AML to elucidate a possible role of hCDC4 mutations in this disease. By direct DNA sequencing and digestion with Surveyor nuclease one heterozygous mutation in the 5' untranslated region of exon 1, transcript variant 3 was detected. Additionally, we could identify a new intronic SNP downstream of exon 10. The new variation was present in 20% of AML samples and was furthermore confirmed in a panel of 51 healthy individuals where it displayed a frequency of 14%. In conclusion we provide first data that in contrast to several solid tumors, mutations in the hCDC4 gene may not play a pivotal role in the pathogenesis of AML. Furthermore, we describe a new intronic polymorphism with high frequency in the intron sequence of the hCDC4 gene.

  9. A visual basic spreadsheet macro for geochemical background analysis.

    Science.gov (United States)

    Nakić, Zoran; Posavec, Kristijan; Bacani, Andrea

    2007-01-01

    A Visual Basic macro entitled BACKGROUND calculates geochemical background values of chemical parameters and estimates threshold values separating background data from anomalies. The macro uses two statistical methods, the iterative 2-sigma technique and the calculated distribution function, and integrates these model-based objective methods into a widely accessible platform (i.e., MS Excel). The macro offers the possibility for automated processing of geochemical data and enables an automated generation of background range and threshold values for chemical parameters.

  10. How is Macro News Transmitted to Exchange Rates? (December 2003)

    OpenAIRE

    Martin D.D. Evans

    2005-01-01

    This paper tests whether macroeconomic news is transmitted to exchange rates via the transactions process and if so, what share occurs via transactions versus the traditional direct channel. We identify the link between order flow and macro news using a heteroskedasticity-based approach, a la Rigobon and Sack (2002). In both daily and intra-daily data, order flow varies considerably with macro news flow. At least half of the effect of macro news on exchange rates is transmitted via order flow.

  11. How is Macro News Transmitted to Exchange Rates?

    OpenAIRE

    Martin D.D. Evans; Lyons, Richard K.

    2003-01-01

    This paper tests whether macroeconomic news is transmitted to exchange rates via the transactions process and if so, what share occurs via transactions versus the traditional direct channel. We identify the link between order flow and macro news using a heteroskedasticity-based approach, a la Rigobon and Sack (2002). In both daily and intra-daily data, order flow varies considerably with macro news flow. At least half of the effect of macro news on exchange rates is transmitted via order flow.

  12. Search for rare particles with MACRO

    CERN Document Server

    Cozzi, M; Rrhioua, A

    2002-01-01

    Massive rare particles have been searched for in the penetrating cosmic radiation using the MACRO detector located at the Gran Sasso laboratory. Liquid scintillators, streamer tubes and nuclear track detectors have been used, in a stand-alone and in combined way to search for GUT magnetic monopoles (MMs) in the velocity range 4 10 /sup -5/ < beta < 1. The search for MMs exploits their energy loss mechanisms in each of the three MACRO subdetectors. No monopole was observed and the global flux upper limit obtained is phi = 6.3 * 10 /sup -16/ cm/sup -2/ s/sup -1/ sr/sup -1/ for 5 * 10/sup -3/ < beta < 0.99. This limit is below the extended Parker limit. Scintillator and nuclear track subdetectors are also used to search for nuclearites (strange quark matter). Based on no observation of nuclearites signals, stringent flux upper limits are established, phi < 1.7 * 10 /sup -16/ cm/sup -2/ s/sup -1/ sr/sup -1/, beta ~ 10/sup -2/. We compared also the results of different experiments searching for MMs ...

  13. The MACRO detector at Gran Sasso

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosio, M.; Antolini, R.; Assiro, R.; Auriemma, G.; Bakari, D.; Baldini, A.; Barbarino, G.C.; Barbarito, E.; Barish, B.C.; Battistoni, G.; Becherini, Y.; Bellotti, R.; Bemporad, C.; Bernardini, P. E-mail: paolo.bernardini@le.infn.it; Bilokon, H.; Bisi, V.; Bloise, C.; Bottazzi, E.; Bower, C.; Brigida, M.; Bussino, S.; Cafagna, F.; Calicchio, M.; Campana, D.; Candela, A.; Carboni, M.; Cecchini, S.; Cei, F.; Ceres, A.; Chiarella, V.; Choudhary, B.C.; Coutu, S.; Cozzi, M.; Creti, P.; De Cataldo, G.; Esposti, L.D.L. Degli; Dekhissi, H.; Marzo, C. De; Mitri, I. De; Derkaoui, J.; Vincenzi, M. De; Credico, A. Di; Ferdinando, D. Di; Diotallevi, R.; Erriquez, O.; Favuzzi, C.; Forti, C.; Fusco, P.; Gebhard, M.; Giacomelli, G.; Giacomelli, R.; Giannini, G.; Giglietto, N.; Giorgini, M.; Giuliani, R.; Goretti, M.; Grassi, M.; Grau, H.; Gray, L.; Grillo, A.; Guarino, F.; Gustavino, C.; Habig, A.; Hanson, J.; Hanson, K.; Hawthorne, A.; Heinz, R.; Hong, J.T.; Iarocci, E.; Katsavounidis, E.; Katsavounidis, I.; Kearns, E.; Kim, H.; Kyriazopoulou, S.; Lamanna, E.; Lane, C.; Leone, A.; Levin, D.S.; Lipari, P.; Liu, G.; Liu, R.; Longley, N.P.; Longo, M.J.; Loparco, F.; Maaroufi, F.; Mancarella, G.; Mandrioli, G.; Manzoor, S.; Marrelli, V.; Margiotta, A.; Marini, A.; Martello, D.; Marzari-Chiesa, A.; Mazziotta, M.N.; Michael, D.G.; Mikheyev, S.; Miller, L.; Monacelli, P.; Mongelli, M.; Montaruli, T.; Monteno, M.; Mossbarger, L.; Mufson, S.; Musser, J.; Nicolo, D.; Nolty, R.; Okada, C.; Orsini, M.; Orth, C.; Osteria, G.; Ouchrif, M.; Palamara, O.; Parlati, S.; Patera, V.; Patrizii, L.; Pazzi, R.; Peck, C.W. E-mail: peck@hep.caltech.edu; Pellizzoni, G.; Perchiazzi, M.; Perrone, L.; Petrakis, J.; Petrera, S.; Pignatano, N.; Pinto, C.; Pistilli, P.; Popa, V.; Raino, A.; Reynoldson, J.; Ronga, F.; Rrhioua, A.; Sacchetti, A.; Saggese, P.; Satriano, C.; Satta, L.; Scapparone, E.; Scholberg, K.; Sciubba, A.; Serra, P.; Sioli, M.; Sirri, G.; Sitta, M.; Sondergaard, S.; Spinelli, P.[and others

    2002-07-01

    MACRO was an experiment that ran in the Laboratori Nazionali del Gran Sasso from 1988 to 2000. Its principal goal was to observe magnetic monopoles or set significantly lower experimental flux limits than had been previously available in the velocity range from about {beta}=10{sup -4} to unity. In addition it made a variety of other observations. Examples are: setting flux limits on other so far unobserved particles such as nuclei and lightly ionizing particles, searching for WIMP annihilations in the Earth and the Sun and for neutrino bursts from stellar collapses in or near our Galaxy, and making measurements relevant to high energy muon and neutrino astronomy and of the flux of up-going muons as a function of nadir angle showing evidence for neutrino oscillations. The apparatus consisted of three principal types of detectors: liquid scintillator counters, limited streamer tubes, and nuclear track etch detectors. In addition, over part of its area it contained a transition radiation detector. The general design philosophy emphasized redundancy and complementarity. This paper describes the technical aspects of the complete MACRO detector, its operational performance, and the techniques used to calibrate it and verify its proper operation. It supplements a previously published paper which described the first portion of the detector that was built and operated.

  14. China Strengthens Macro-management in Petrochemical Branches

    Institute of Scientific and Technical Information of China (English)

    Xu Hui

    1997-01-01

    @@ China will strengthen macro-management in petrochemical branches in order to reasonably utilize the national petroleum resources and improve its competitive capacity in international refinery industrial market.

  15. 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.

  16. 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.

  17. 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.

    2015-01-01

    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. PMID:26642852

  18. Narrative skills in deaf children who use spoken English: Dissociations between macro and microstructural devices.

    Science.gov (United States)

    Jones, A C; Toscano, E; Botting, N; Marshall, C R; Atkinson, J R; Denmark, T; Herman, R; Morgan, G

    2016-12-01

    Previous research has highlighted that deaf children acquiring spoken English have difficulties in narrative development relative to their hearing peers both in terms of macro-structure and with micro-structural devices. The majority of previous research focused on narrative tasks designed for hearing children that depend on good receptive language skills. The current study compared narratives of 6 to 11-year-old deaf children who use spoken English (N=59) with matched for age and non-verbal intelligence hearing peers. To examine the role of general language abilities, single word vocabulary was also assessed. Narratives were elicited by the retelling of a story presented non-verbally in video format. Results showed that deaf and hearing children had equivalent macro-structure skills, but the deaf group showed poorer performance on micro-structural components. Furthermore, the deaf group gave less detailed responses to inferencing probe questions indicating poorer understanding of the story's underlying message. For deaf children, micro-level devices most strongly correlated with the vocabulary measure. These findings suggest that deaf children, despite spoken language delays, are able to convey the main elements of content and structure in narrative but have greater difficulty in using grammatical devices more dependent on finer linguistic and pragmatic skills.

  19. Macro influencers of electronic health records adoption.

    Science.gov (United States)

    Raghavan, Vijay V; Chinta, Ravi; Zhirkin, Nikita

    2015-01-01

    While adoption rates for electronic health records (EHRs) have improved, the reasons for significant geographical differences in EHR adoption within the USA have remained unclear. To understand the reasons for these variations across states, we have compiled from secondary sources a profile of different states within the USA, based on macroeconomic and macro health-environment factors. Regression analyses were performed using these indicator factors on EHR adoption. The results showed that internet usage and literacy are significantly associated with certain measures of EHR adoption. Income level was not significantly associated with EHR adoption. Per capita patient days (a proxy for healthcare need intensity within a state) is negatively correlated with EHR adoption rate. Health insurance coverage is positively correlated with EHR adoption rate. Older physicians (>60 years) tend to adopt EHR systems less than their younger counterparts. These findings have policy implications on formulating regionally focused incentive programs.

  20. Diffusiophoresis at the macro-scale

    CERN Document Server

    Mauger, C; Machicoane, N; Bourgoin, M; Cottin-Bizonne, C; Ybert, C; Raynal, F

    2015-01-01

    Diffusiophoresis, a ubiquitous phenomenon which induces particle transport whenever solute gradients are present, was recently put forward in the context of microsystems and shown to strongly impact colloidal transport (from patterning to mixing) at such scales. In the present work, we show experimentally that this nanoscale-rooted mechanism can actually induce changes in the \\textit{macro-scale mixing} of colloids by chaotic advection. Rather than the usual decay of standard deviation of concentration, which is a global parameter, we use different multi-scale tools available for chaotic flows or intermittent turbulent mixing, like concentration spectra, or second and fourth moments of probability density functions of scalar gradients. Not only those tools can be used in open flows (when the mean concentration is not constant), but also they allow for a scale by scale analysis. Strikingly, diffusiophoresis is shown to affect all scales, although more particularly the smallest one, resulting in a change of sca...

  1. Particle size distribution in ferrofluid macro-clusters

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Wah-Keat, E-mail: wklee@bnl.gov [X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, 9700S. Cass Avenue, Argonne, IL 60439 (United States); Ilavsky, Jan [X-ray Science Division, Advanced Photon Source, Argonne National Laboratory, 9700S. Cass Avenue, Argonne, IL 60439 (United States)

    2013-03-15

    Under an applied magnetic field, many commercial and concentrated ferrofluids agglomerate and form large micron-sized structures. Although large diameter particles have been implicated in the formation of these macro-clusters, the question of whether the particle size distribution of the macro-clusters are the same as the original fluid remains open. Some studies suggest that these macro-clusters consist of larger particles, while others have shown that there is no difference in the particle size distribution between the macro-clusters and the original fluid. In this study, we use X-ray imaging to aid in a sample (diluted EFH-1 from Ferrotec) separation process and conclusively show that the average particle size in the macro-clusters is significantly larger than those in the original sample. The average particle size in the macro-clusters is 19.6 nm while the average particle size of the original fluid is 11.6 nm. - Highlights: Black-Right-Pointing-Pointer X-ray imaging was used to isolate ferrofluid macro-clusters under an applied field. Black-Right-Pointing-Pointer Small angle X-ray scattering was used to determine particle size distributions. Black-Right-Pointing-Pointer Results show that macro-clusters consist of particles that are larger than average.

  2. Estimating Dynamic Equilibrium Models using Macro and Financial Data

    DEFF Research Database (Denmark)

    Christensen, Bent Jesper; Posch, Olaf; van der Wel, Michel

    We show that including financial market data at daily frequency, along with macro series at standard lower frequency, facilitates statistical inference on structural parameters in dynamic equilibrium models. Our continuous-time formulation conveniently accounts for the difference in observation...... of the estimators and estimate the model using 20 years of U.S. macro and financial data....

  3. Quantifying causal emergence shows that macro can beat micro.

    Science.gov (United States)

    Hoel, Erik P; Albantakis, Larissa; Tononi, Giulio

    2013-12-01

    Causal interactions within complex systems can be analyzed at multiple spatial and temporal scales. For example, the brain can be analyzed at the level of neurons, neuronal groups, and areas, over tens, hundreds, or thousands of milliseconds. It is widely assumed that, once a micro level is fixed, macro levels are fixed too, a relation called supervenience. It is also assumed that, although macro descriptions may be convenient, only the micro level is causally complete, because it includes every detail, thus leaving no room for causation at the macro level. However, this assumption can only be evaluated under a proper measure of causation. Here, we use a measure [effective information (EI)] that depends on both the effectiveness of a system's mechanisms and the size of its state space: EI is higher the more the mechanisms constrain the system's possible past and future states. By measuring EI at micro and macro levels in simple systems whose micro mechanisms are fixed, we show that for certain causal architectures EI can peak at a macro level in space and/or time. This happens when coarse-grained macro mechanisms are more effective (more deterministic and/or less degenerate) than the underlying micro mechanisms, to an extent that overcomes the smaller state space. Thus, although the macro level supervenes upon the micro, it can supersede it causally, leading to genuine causal emergence--the gain in EI when moving from a micro to a macro level of analysis.

  4. Micro-macro analysis of complex networks.

    Science.gov (United States)

    Marchiori, Massimo; Possamai, Lino

    2015-01-01

    Complex systems have attracted considerable interest because of their wide range of applications, and are often studied via a "classic" approach: study a specific system, find a complex network behind it, and analyze the corresponding properties. This simple methodology has produced a great deal of interesting results, but relies on an often implicit underlying assumption: the level of detail on which the system is observed. However, in many situations, physical or abstract, the level of detail can be one out of many, and might also depend on intrinsic limitations in viewing the data with a different level of abstraction or precision. So, a fundamental question arises: do properties of a network depend on its level of observability, or are they invariant? If there is a dependence, then an apparently correct network modeling could in fact just be a bad approximation of the true behavior of a complex system. In order to answer this question, we propose a novel micro-macro analysis of complex systems that quantitatively describes how the structure of complex networks varies as a function of the detail level. To this extent, we have developed a new telescopic algorithm that abstracts from the local properties of a system and reconstructs the original structure according to a fuzziness level. This way we can study what happens when passing from a fine level of detail ("micro") to a different scale level ("macro"), and analyze the corresponding behavior in this transition, obtaining a deeper spectrum analysis. The obtained results show that many important properties are not universally invariant with respect to the level of detail, but instead strongly depend on the specific level on which a network is observed. Therefore, caution should be taken in every situation where a complex network is considered, if its context allows for different levels of observability.

  5. Macro-economic impact of loss of health; Macro-economische impact van gezondheidsverlies

    Energy Technology Data Exchange (ETDEWEB)

    Franchimon, F. [BAM Techniek, Capelle a/d IJssel (Netherlands); Ament, H.J.A. [Universiteit Maastricht, Maastricht (Netherlands); Knies, J.; Pernot, C.E.E. [Pernot Consulting, Heeze (Netherlands); Van Bronswijk, J.M.H. [Technische Universiteit Eindhoven TUE, Eindhoven (Netherlands)

    2010-11-15

    More healthy life years are achievable by dwelling improvements. This article computes the healthy life years that may be gained by increased ventilation rates. It concerns the diseases Asthma, COPD en lung cancer. Increased ventilation removes house dust mites and their allergens, as well as tobacco smoke, which are associated with these diseases. Costs and savings are computes and compared in order to test the macro-economical feasibility of increased ventilation in dwellings. [Dutch] Door verbetering van woningen zijn veel gezonde levensjaren te behalen. In dit artikel worden de gewonnen gezonde levensjaren uitgerekend door meer ventileren voor de ziekten astma, COPD en longkanker. Zowel huisstofmijtallergeen als tabaksrook zijn geassocieerd met astma, COPD en longkanker. De kosten en de opbrengsten van meer ventileren worden met elkaar vergeleken om de macro-economische haalbaarheid te toetsen.

  6. The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR.

    Science.gov (United States)

    Zhou, Liang; Chen, Shuang; Zhang, Yu; Kmieciak, Maciej; Leng, Yun; Li, Lihong; Lin, Hui; Rizzo, Kathryn A; Dumur, Catherine I; Ferreira-Gonzalez, Andrea; Rahmani, Mohamed; Povirk, Lawrence; Chalasani, Sri; Berger, Allison J; Dai, Yun; Grant, Steven

    2016-05-05

    Two classes of novel agents, NEDD8-activating enzyme (NAE) and histone deacetylase (HDAC) inhibitors, have shown single-agent activity in acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS). Here we examined mechanisms underlying interactions between the NAE inhibitor pevonedistat (MLN4924) and the approved HDAC inhibitor belinostat in AML/MDS cells. MLN4924/belinostat coadministration synergistically induced AML cell apoptosis with or without p53 deficiency or FLT3-internal tandem duplication (ITD), whereas p53 short hairpin RNA (shRNA) knockdown or enforced FLT3-ITD expression significantly sensitized cells to the regimen. MLN4924 blocked belinostat-induced antiapoptotic gene expression through nuclear factor-κB inactivation. Each agent upregulated Bim, and Bim knockdown significantly attenuated apoptosis. Microarrays revealed distinct DNA damage response (DDR) genetic profiles between individual vs combined MLN4924/belinostat exposure. Whereas belinostat abrogated the MLN4924-activated intra-S checkpoint through Chk1 and Wee1 inhibition/downregulation, cotreatment downregulated multiple homologous recombination and nonhomologous end-joining repair proteins, triggering robust double-stranded breaks, chromatin pulverization, and apoptosis. Consistently, Chk1 or Wee1 shRNA knockdown significantly sensitized AML cells to MLN4924. MLN4924/belinostat displayed activity against primary AML or MDS cells, including those carrying next-generation sequencing-defined poor-prognostic cancer hotspot mutations, and CD34(+)/CD38(-)/CD123(+) populations, but not normal CD34(+) progenitors. Finally, combined treatment markedly reduced tumor burden and significantly prolonged animal survival (P DDR in AML/MDS cells. This strategy warrants further consideration in AML/MDS, particularly in disease with unfavorable genetic aberrations.

  7. 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).

  8. South Africa; Financial Sector Assessment Program-Anti-Money Laundering and Combating the Financing of Terrorism (AML/CFT)-Technical Note

    OpenAIRE

    International Monetary Fund.

    2015-01-01

    This Technical Note discusses findings and recommendations made in the Financial Sector Assessment Program (FSAP) for South Africa in the areas of anti-money laundering and combating the financing of terrorism (AML/CFT). The AML/CFT supervisory framework for the financial sector, in particular the banking sector, has been strengthened by the amended Financial Intelligence Center (FIC) Act that took effect in 2010 and the creation of the AML/CFT supervision team within Banking Supervision Depa...

  9. Cytarabine and clofarabine after high-dose cytarabine in relapsed or refractory AML patients.

    Science.gov (United States)

    Scappini, Barbara; Gianfaldoni, Giacomo; Caracciolo, Francesco; Mannelli, Francesco; Biagiotti, Caterina; Romani, Claudio; Pogliani, Enrico M; Simonetti, Federico; Borin, Lorenza; Fanci, Rosa; Cutini, Ilaria; Longo, Giovanni; Susini, Maria Chiara; Angelucci, Emanuele; Bosi, Alberto

    2012-12-01

    Clofarabine has been shown to be effective in AML patients, either as single agent or, mainly, in association with intermediate dose cytarabine. Based on these reports, we conducted a preliminary study combining clofarabine and intermediate dose cytarabine in AML patients who relapsed or failed to respond to at least two induction therapies. We treated 47 patients affected by relapsed/refractory AML with a regimen including clofarabine at 22.5 mg/m(2) daily on days 1-5, followed after 3 hr by cytarabine at 1 g/m(2) daily on days 1-5. Ten patients received a further consolidation cycle with clofarabine at 22.5 mg/m(2) and cytarabine at 1 g/m(2) day 1-4. Among the 47 patients, 24/47 (51%) achieved a complete remission, 5/47 (10.5%) a partial response, 10/47 (21%) had a resistant disease, and 6/47 (13%) died of complications during the aplastic phase. The most frequent nonhematologic adverse events were vomiting, diarrhea, transient liver toxicity, febrile neutropenia, and infections microbiologically documented. Among the 24 patients who obtained a CR 13 underwent allogeneic bone marrow transplantation. In 14 patients, complete remission duration was shorter than 12 months, whereas 10 patients experienced longer complete remission duration. These very preliminary results suggest that clofarabine-cytarabine regimen is effective in this particularly poor prognosis category of patients, representing a potential "bridge" toward bone marrow transplant procedures. Safety data were consistent with previously reported salvage therapies. Further studies and a longer follow up are warranted.

  10. Monitoring response and resistance to the novel arsenical darinaparsin in an AML patient

    Directory of Open Access Journals (Sweden)

    Torsten Holm eNielsen

    2013-02-01

    Full Text Available Acute myeloid leukemia (AML with inversion of chromosome 3 is characterized by overexpression of EVI1 and carries a dismal prognosis. Arsenic-containing compounds have been described to be efficacious in malignancies overexpressing EVI1. Here we describe a case of AML with inv(3(q21q26.2 treated with the organic arsenical darinaparsin. Using a personalized medicine approach, different arsenicals were screened for anti-leukemic effect against the patient’s cells ex vivo. The most promising compound, darinaparsin, was selected for in vivo treatment. Clinical effect was almost immediate, with a normalization of temperature, a stabilization of white blood cell (WBC counts and an increased quality of life. Longitudinal monitoring of patient response and resistance incorporating significant correlative studies on patient derived blood samples over the two cycles of darinaparsin given to this patient allowed us to evaluate potential mechanisms of response and resistance. The anti-leukemic effects of darinaparsin correlated with inhibition of the alternative NF-κB pathway and production of the inflammatory cytokine IL-8. Emergence of resistance was suspected during treatment cycle 2 and supported by xenograft studies in nude mice. Darinaparsin resistance correlated with an attenuation of the effect of treatment on the alternative NF-κB pathway. The results from this patient indicate that darinaparsin may be a good treatment option for inv(3 AML and that inhibition of the alternative NF-κB pathway may be predictive of response. Longitudinal monitoring of disease response as well as several correlative parameters allowed for the generation of novel correlations and predictors of response to experimental therapy in a heavily pretreated patient.

  11. Optimizing outcomes following allogeneic hematopoietic progenitor cell transplantation in AML: the role of hypomethylating agents.

    Science.gov (United States)

    Martino, Massimo; Fedele, Roberta; Moscato, Tiziana; Ronco, Francesca

    2013-07-01

    Aberrant DNA methylation is a key pathological mechanism in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and provides rationale for the clinical development of hypomethylating agents (HMAs) for the treatment of these diseases. One HMA, azacitidine (Vidaza®, Celgene Corp.), has demonstrated improved survival versus conventional care regimens in patients with intermediate-2/high-risk MDS and AML (20-30% blasts) and has a favorable tolerability profile. Emerging evidence indicates that azacitidine can have an immunomodulatory effect by, for example, increasing functional regulatory T-cell (Treg) numbers and killer-cell-immunoglobulin-like receptor expression. Allogeneic hematopoietic progenitor cell transplantation (allo HPCT) is the only potentially curative treatment approach in patients with advanced MDS or AML. Unfortunately, allo HPCT in these settings is limited because most patients are ineligible due to age/comorbidities, or are at a high risk of treatment failure due to disease relapse. Recent studies have shown that azacitidine after allo HPCT increases Treg numbers while inducing a cytotoxic CD8+ T-cell response, suggesting a potential mechanism for augmenting the graft-versus-leukemia (GvL) effect without increasing graft-versushost- disease (GVHD). In patients at a high risk of relapse following allo HPCT, pre-emptive azacitidine may help prevent/delay relapse. For patients who have relapsed following allo HPCT, azacitidine may be a salvage therapy option, either as monotherapy or in combination with donor lymphocyte infusions (DLI). In this mini-review, we discuss these emerging clinical data for HMAs in the post-allo HPCT regimens and highlight the possible future role of azacitidine in this setting.

  12. Detailed Characterization of Mesenchymal Stem/Stromal Cells from a Large Cohort of AML Patients Demonstrates a Definitive Link to Treatment Outcomes

    Directory of Open Access Journals (Sweden)

    Rafael Diaz de la Guardia

    2017-06-01

    Full Text Available Bone marrow mesenchymal stem/stromal cells (BM-MSCs are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR, intermediate-risk (IR, and high-risk (HR subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup. AML-derived BM-MSCs never harbored tumor-specific cytogenetic/molecular alterations present in blasts, but displayed higher clonogenic potential than healthy donor (HD-derived BM-MSCs. Although HD- and AML-derived BM-MSCs equally provided chemoprotection to AML cells in vitro, AML-derived BM-MSCs were more immunosuppressive/anti-inflammatory, enhanced suppression of lymphocyte proliferation, and diminished secretion of pro-inflammatory cytokines. Multivariate analysis revealed that the level of interleukin-10 produced by AML-derived BM-MSCs as an independent prognostic factor negatively affected overall survival. Collectively our data show that AML-derived BM-MSCs are not tumor related, but display functional differences contributing to therapy resistance and disease evolution.

  13. Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA.

    Science.gov (United States)

    Sawney, Sharad; Arora, Rashi; Aggarwal, Kamal K; Saluja, Daman

    2015-01-01

    One of the most frequent genetic aberrations in acute myeloid leukemia (AML) is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21) translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21) translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application.

  14. Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA

    Directory of Open Access Journals (Sweden)

    Sharad Sawney

    2015-01-01

    Full Text Available One of the most frequent genetic aberrations in acute myeloid leukemia (AML is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21 translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21 translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application.

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

    DEFF Research Database (Denmark)

    Tawana, Kiran; Wang, Jun; Renneville, Aline

    2015-01-01

    therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long-term outcomes.......In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were...

  16. La lutte des classes des unités linguistiques : micro- et macro-syntaxe

    Directory of Open Access Journals (Sweden)

    María Luisa Fernández-Echevarría

    2015-12-01

    Full Text Available In a synchronic approach to discourse we postulate a dynamic unit that constructs macro-syntactic meaning as it is uttered. This conventionalised segment (fr. période énonciative, elaborated in order to anticipate the reactions of the hearer, forms part of a linguistic repertory (vocabulary while at the same time behaving as a space-time module (syllabification. Conceived in this way, this unit is flexible enough to undergo possible deformation and accentual attrition in the evolution of a given language. It is also the basis of a meta-language capable of generating progressively more precise linguistic objects whose categorial membership is a matter of debate. We may observe this conventionalised segment in the analysis of set expressions (paremies that testify to shared meanings and, by default, in automatic deviant sub-titles that reveal the shortcomings of a virtual translator.

  17. SAS-macros for estimation and prediction in an model of the electricity consumption

    DEFF Research Database (Denmark)

    1998-01-01

    SAS-macros for estimation and prediction in an model of the electricity consumption'' is a large collection of SAS-macros for handling a model of the electricity consumption in the Eastern Denmark. The macros are installed at Elkraft, Ballerup.......SAS-macros for estimation and prediction in an model of the electricity consumption'' is a large collection of SAS-macros for handling a model of the electricity consumption in the Eastern Denmark. The macros are installed at Elkraft, Ballerup....

  18. 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.

  19. Meningioma 1 (MN1) expression: refined risk stratification in acute myeloid leukemia with normal cytogenetics (CN-AML).

    Science.gov (United States)

    Aref, Salah; Ibrahim, Lamiaa; Morkes, Hana; Azmy, Emad; Ebrahim, Maha

    2013-09-01

    Prognostic stratification of cytogenetic normal acute myeloid leukemia (CN-AML) is an area of active research. The aim of this study was to determine the prognostic importance of the meningioma 1 (MN1) gene expression levels in CN-AML. One hundred patients with CN-AML were diagnosed; MN1 expressions were analyzed using quantitative real-time polymerase chain reaction. High expressions were detected in 48 (48%) patients (expression range: 2.35-31.99, mean: 13.9 ± 8.49) in comparison with 52 (52%) patients with low expression (expression range: 0.02-2.3, mean: 0.68 ± 0.77). The course of the disease in patients with high MN1 expression was unfavorable. Patients with high MN1 expression was associated with significant low complete remission rate (62.5 vs. 8.4%, high vs. low MN1, P = 0.001) and high mortality rate (75% vs. 46.1, P = 0.03). AML patients with high MN1 expression tended to be refractory (37.5 vs. 19.2%, P = 0.00) and relapse risk (54.1 vs. 23%, P = 0.02). Multivariable analysis confirmed high MN1 expression as an independent risk factor for disease-free survival and overall survival. In conclusion, MN1 overexpression independently predicts bad clinical outcome in CN-AML patients.

  20. Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Yotnda, P; Garcia, F; Peuchmaur, M; Grandchamp, B; Duval, M; Lemonnier, F; Vilmer, E; Langlade-Demoyen, P

    1998-07-15

    Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > 25% of ALL-patients. In this study, we have examined whether the chimeric ETV6-AML1 protein could serve as a tumor specific antigen for CTL in HLA-A2.1 individuals. We have identified a nonapeptide (RIAECILGM), encoded by the fusion region of the ETV6-AML1 protein, that binds to HLA-A2.1 molecules and induces specific primary CTL in peripheral blood lymphocytes from healthy donors. These CTL specifically lysed HLA-A2.1 tumor cells endogeneously expressing the ETV6-AML fusion protein. CTL with similar functional capacities were found with high frequencies and cloned from one patient's bone marrow indicating that ETV6-AML1-specific anti-ALL CTL are, at least in some patients, spontaneously stimulated and might participate to host antileukemia defense.

  1. EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs.

    Science.gov (United States)

    Bindels, Eric M J; Havermans, Marije; Lugthart, Sanne; Erpelinck, Claudia; Wocjtowicz, Elizabeth; Krivtsov, Andrei V; Rombouts, Elwin; Armstrong, Scott A; Taskesen, Erdogan; Haanstra, Jurgen R; Beverloo, H Berna; Döhner, Hartmut; Hudson, Wendy A; Kersey, John H; Delwel, Ruud; Kumar, Ashish R

    2012-06-14

    The proto-oncogene EVI1 (ecotropic viral integration site-1), located on chromosome band 3q26, is aberrantly expressed in human acute myeloid leukemia (AML) with 3q26 rearrangements. In the current study, we showed, in a large AML cohort carrying 11q23 translocations, that ∼ 43% of all mixed lineage leukemia (MLL)-rearranged leukemias are EVI1(pos). High EVI1 expression occurs in AMLs expressing the MLL-AF6, -AF9, -AF10, -ENL, or -ELL fusion genes. In addition, we present evidence that EVI1(pos) MLL-rearranged AMLs differ molecularly, morphologically, and immunophenotypically from EVI1(neg) MLL-rearranged leukemias. In mouse bone marrow cells transduced with MLL-AF9, we show that MLL-AF9 fusion protein maintains Evi1 expression on transformation of Evi1(pos) HSCs. MLL-AF9 does not activate Evi1 expression in MLL-AF9-transformed granulocyte macrophage progenitors (GMPs) that were initially Evi1(neg). Moreover, shRNA-mediated knockdown of Evi1 in an Evi1(pos) MLL-AF9 mouse model inhibits leukemia growth both in vitro and in vivo, suggesting that Evi1 provides a growth-promoting signal. Using the Evi1(pos) MLL-AF9 mouse leukemia model, we demonstrate increased sensitivity to chemotherapeutic agents on reduction of Evi1 expression. We conclude that EVI1 is a critical player in tumor growth in a subset of MLL-rearranged AMLs.

  2. Application of macro material flow modeling to the decision making process for integrated waste management systems

    Energy Technology Data Exchange (ETDEWEB)

    Vigil, S.A. [California Polytechnic State Univ., San Luis Obispo, CA (United States); Holter, G.M. [Battelle Pacific Northwest Laboratory, Richland, WA (United States)

    1995-04-01

    Computer models have been used for almost a decade to model and analyze various aspects of solid waste management Commercially available models exist for estimating the capital and operating costs of landfills, waste-to-energy facilities and compost systems and for optimizing system performance along a single dimension (e.g. cost or transportation distance). An alternative to the use of currently available models is the more flexible macro material flow modeling approach in which a macro scale or regional level approach is taken. Waste materials are tracked through the complete integrated waste management cycle from generation through recycling and reuse, and finally to ultimate disposal. Such an approach has been applied by the authors to two different applications. The STELLA simulation language (for Macintosh computers) was used to model the solid waste management system of Puerto Rico. The model incorporated population projections for all 78 municipalities in Puerto Rico from 1990 to 2010, solid waste generation factors, remaining life for the existing landfills, and projected startup time for new facilities. The Pacific Northwest Laboratory has used the SimScript simulation language (for Windows computers) to model the management of solid and hazardous wastes produced during cleanup and remediation activities at the Hanford Nuclear Site.

  3. Language, Language Teaching and Language Testing

    Institute of Scientific and Technical Information of China (English)

    吴文华

    2002-01-01

    Departing from a brief presentation of the various views of language, this article elaborates the influence of views of languageon language teaching and language testing. This will help us have background knowledge on language teaching and language testing.

  4. Miniature Piezoelectric Macro-Mass Balance

    Science.gov (United States)

    Sherrit, Stewart; Trebi-Ollennu, Ashitey; Bonitz, Robert G.; Bar-Cohen, Yoseph

    2010-01-01

    Mass balances usually use a strain gauge that requires an impedance measurement and is susceptible to noise and thermal drift. A piezoelectric balance can be used to measure mass directly by monitoring the voltage developed across the piezoelectric balance, which is linear with weight or it can be used in resonance to produce a frequency change proportional to the mass change (see figure). The piezoelectric actuator/balance is swept in frequency through its fundamental resonance. If a small mass is added to the balance, the resonance frequency shifts down in proportion to the mass. By monitoring the frequency shift, the mass can be determined. This design allows for two independent measurements of mass. Additionally, more than one sample can be verified because this invention allows for each sample to be transported away from the measuring device upon completion of the measurement, if required. A piezoelectric actuator, or many piezoelectric actuators, was placed between the collection plate of the sampling system and the support structure. As the sample mass is added to the plate, the piezoelectrics are stressed, causing them to produce a voltage that is proportional to the mass and acceleration. In addition, a change in mass delta m produces a change in the resonance frequency with delta f proportional to delta m. In a microgravity environment, the spacecraft could be accelerated to produce a force on the piezoelectric actuator that would produce a voltage proportional to the mass and acceleration. Alternatively, the acceleration could be used to force the mass on the plate, and the inertial effects of the mass on the plate would produce a shift in the resonance frequency with the change in frequency related to the mass change. Three prototypes of the mass balance mechanism were developed. These macro-mass balances each consist of a solid base and an APA 60 Cedrat flextensional piezoelectric actuator supporting a measuring plate. A similar structure with 3 APA

  5. Establishment and evaluation of AML-SCID mice model%AML-SCID 小鼠模型的建立及鉴定*

    Institute of Scientific and Technical Information of China (English)

    贾秀红; 张艳君

    2013-01-01

    目的:筛选出高表达HOXA9、HOXA10基因的急性髓系白血病( Acute myeloid leukemia ,AML)细胞株,并建立AML模型,为研究HOXA9、HOXA10与AML的关系奠定基础。方法经RT-PCR检测HOXA9、HOXA10在U937、HL-60、NB4、Jur-kat中的表达情况,筛选出高表达的细胞株;外周血瑞氏染色、骨髓流式细胞仪、脏器HE染色鉴定移植性U937人白血病重度联合免疫缺陷( Severe combined immunodeficiency ,SCID)小鼠模型。结果 HOXA9、HOXA10在U937中均高表达,在HL-60、Jurkat中不表达(或表达水平较低),NB4高表达HOXA10;U937细胞在濒死小鼠骨髓细胞所占的比例为(20.62±9.66%)%,与对照组比较差异有统计学意义( P <0.05);病理检查发现 U937细胞可浸润肝、脾、肺、肾器官。结论 U937高表达HOXA9、HOXA10,是研究HOXA9、HOXA10基因与白血病关系的合适细胞株,并成功建立U937-SCID人M5型急性髓性白血病模型。%Objective To filter out the AML cell line with the HOXA9,HOXA10 gene high expression and establish the AML mod-el,so to lay the foundation for the study of the relationship between HOXA 9,HOXA10,and AML.Methods The expression of HOXA9 and HOXA10 mRNA in U937,HL-60,NB4,Jurkat were detected by reverse transcription PCR .A human leukemia model with severe combined immunodeficiency ( SCID) was intravenously inoculated with U 937 cells.Peripheral blood cells were stained by Wright stain , flow cytometry instrument analyze the ration of CD 45 positive cells in Bone marrow;organs were made into paraffin sections and then stained by Hematoxylin-eosin.Results HOXA9,HOXA10 mRNA level is high in U937 cells,whereas they cannot be detected in HL-60 or Jurkat cells.HOXA10 mRNA level was high in NB4 cells.The proportion of human CD45+cells reached(20.62 ±9.66%)% of bone marrow cells just prior to death of mice ,which was different from the control group obviously ( P﹤0.05 ) .Pathological examina

  6. Multimedia Macros for Portable Optimized Programs

    Science.gov (United States)

    2007-11-02

    SUM2_U32x4(dst, src) \\ dst = src##_0 + src##_2; Other Approaches Parallelizing compilers Optimized kernel libraries BLAS , Intel® IPP, VSIPL Data-parallel...languages Fortran 90, SWARC, Vector Pascal C++ SIMD classes Automatic code generators SPIRAL, FFTW, ATLAS None of these approaches achieves

  7. CATIA V5 macro programming with Visual Basic Script

    CERN Document Server

    Ziethen, Dieter R

    2013-01-01

    CATIA V5 Macro Programming with Visual Basic Script shows you, step by step, how to create your own macros that automate repetitive tasks, accelerate design procedures, and automatically generate complex geometries. Filled with full-color screenshots and illustrations, this practical guide walks you through the entire process of writing, storing, and executing reusable macros for CATIA® V5. Sample Visual Basic Script code accompanies the book’s hands-on exercises and real-world case studies demonstrate key concepts and best practices.

  8. In vitro generation of tumor specific T cells that recognize a shared antigen of AML: molecular characterization of TCR genes.

    Science.gov (United States)

    Coppage, Myra; Belanger, Todd; Zauderer, Maurice; Sahasrabudhe, Deepak

    2007-02-01

    The identification of immunologically relevant tumor antigens is hampered by the difficulty of generating tumor-specific cytotoxic T cells (CTL). We present data demonstrating in vitro induction of autologous acute myelogenous leukemia (AML)-specific CTL. The specific T cell receptor has been identified and cloned. The CTL demonstrated specific lysis to autologous tumor blasts, but not to autologous BLCL or the NK-sensitive target K562. The clone secreted GM-CSF, TNFa, and IFNg when stimulated with AML blasts from 3 of 11 patients or cell lines tested, but not with K562 or autologous B-LCL. These three AML samples share a single HLA Class I antigen, HLA-A24. The T cell receptor genes identified by molecular methods are Vbeta7.9-J2.3-Cbeta2 and Valpha17-J49-Calpha.

  9. Micro and Macro Causes of Violence

    Directory of Open Access Journals (Sweden)

    Randall Collins

    2009-05-01

    Full Text Available The dominant emotion in violence-threatening situations is confrontational tension/fear (ct/f, which causes most violence to abort, or to be carried out inaccurately and incompetently. For violence to be successful, there must be a pathway around the barrier of ct/f. These pathways include: attacking the weak; audience-oriented staged and controlled fair fights; confrontation-avoiding remote violence; confrontation-avoiding by deception; confrontation-avoiding by absorption in technique. Successfully violent persons, on both sides of the law, are those who have developed these skilled interactional techniques. Since successful violence involves dominating the emotional attention space, only a small proportion of persons can belong to the elite which does most of each type of violence. Macro-violence, including victory and defeat in war, and in struggles of paramilitaries and social movements, is shaped by both material resources and social/emotional resources for maintaining violent organizations and forcing their opponents into organizational breakdown. Social and emotional destruction generally precedes physical destruction.

  10. Muon astronomy with the MACRO detector

    CERN Document Server

    Ahlen, S P; Antolini, R; Auriemma, G; Baldini, A; Bam, B B; Barbarino, G C; Barish, B C; Battistoni, G; Bellotti, R; Bemporad, C; Bernardini, P; Bilokon, H; Bisi, V; Bloise, C; Bussino, S; Cafagna, F; Calicchio, M; Campana, P; Campana, D; Carboni, M; Cecchini, S; Cei, F; Chiarella, V; Chiera, C; Cobis, A; Cormack, R; Corona, A; Coutu, S; De Cataldo, G; Dekhissi, H; De Marzo, C; De Vincenzi, M; Di Credico, A; Diehl, E; Erriquez, O; Favuzzi, C; Ficenec, D; Forti, C; Foti, L; Fusco, P; Giacomelli, G; Giannini, G; Giglietto, N; Giubellino, P; Grassi, M; Green, P; Grillo, A; Guarino, F; Gustavino, C; Habig, A; Heinz, R; Hong, J T; Iarocci, Enzo; Katsavounidis, E; Kearns, E T; Klein, S; Kyriazopoulou, S; Lamanna, E; Lane, C; Lee, C; Levin, D S; Lipari, P; Liu, G; Liu, R; Longo, M J; Ludlam, G; Mancarella, G; Mandrioli, G; Margiotta-Neri, A; Marin, A; Marini, A; Martello, D; Martellotti, G; Marzari-Chiesa, A; Masera, M; Matteuzzi, P; Michael, D; Miller, L; Monacelli, P; Monteno, M; Mufson, S L; Musser, J; Nutter, S L; Okada, C; Osteria, G; Palamara, O; Parlati, S; Patera, V; Patrizii, L; Pazzi, R; Peck, C W; Petrakis, J; Petrera, S; Pignatano, N D; Pistilli, P; Predieri, F; Ramello, L; Reynoldson, J; Ronga, F; Rosa, G; Satriano, C; Satta, L; Scapparone, E; Scholberg, K; Sciubba, A; Serra-Lugaresi, P; Severi, M; Sitta, M; Spinelli, P; Spinetti, M; Spurio, M; Steele, J V; Steinberg, R; Stone, J L; Sulak, Lawrence R; Surdo, A; Tarlé, G; Togo, V; Valente, V; Verdone, G R; Walter, C W; Webb, R; Worstell, W

    1993-01-01

    Summary form only given. An all-sky survey for cosmic point sources yielding a DC excess of cosmic ray muons above the expected background has been performed using the single plus double muon events collected between June 1991 and 20 September 2000 by the streamer tube system of MACRO. A total of 45.192 million selected muons, single plus double, were collected in 60775.5 h of effective livetime. No statistically significant DC excess has been found. For selected sources we made a search for DC excesses, and upper flux limits were established; they are at the level of 10/sup -13/cm/sup -2/S/sup -1/. Periodicity (AC) analyses have been performed for Cygnus X-3 and Hercules X-1; the AC limits are at the level of 10/sup -13/cm/sup -2/S/sup -1/. Searches for bursts were made for CygX-3, Mrk 421, Mrk 501 and the Crab. (1 refs).

  11. Macro mineral requirements by grazing zebu bovines

    Directory of Open Access Journals (Sweden)

    Eduardo Henrique Bevitori Kling de Moraes

    2012-02-01

    Full Text Available The objective of this study was to determine requirements of calcium (Ca, phosphorus (P, magnesium (Mg, potassium (K and sodium (Na for grazing zebu bovines. The experiment area was composed of Brachiaria decumbens paddocks. Twenty-seven non-castrated animals, with initial live weight of 311.0 kg and at an average age of 14 months were used. Three animals were slaughtered, after adaptation period, so they were used as control for estimates of empty body weight and initial body composition of animals in the experiment. Out of the 24 remaining animals, four were sent to the maintenance group with restrict grazing time to limit energy intake close to the maintenance level. The other 20 animals were distributed in four treatments: mineral mixture, self-control intake and three-times-a-week-offer frequency (offered on Mondays, Wednesdays and Fridays and daily. Concentrations of all studied macro elements in empty body and empty body gain decreased as live weight increased. The ratios obtained for g Ca/100 g of retained protein and g P/100 g of retained protein were 9.18 and 4.72, respectively. Total dietary requirement of calcium was lower than the one recommended by NRC (2000, but P requirement was very close to that.

  12. Compressed digital holography: from micro towards macro

    Science.gov (United States)

    Schretter, Colas; Bettens, Stijn; Blinder, David; Pesquet-Popescu, Béatrice; Cagnazzo, Marco; Dufaux, Frédéric; Schelkens, Peter

    2016-09-01

    signal processing methods from software-driven computer engineering and applied mathematics. The compressed sensing theory in particular established a practical framework for reconstructing the scene content using few linear combinations of complex measurements and a sparse prior for regularizing the solution. Compressed sensing found direct applications in digital holography for microscopy. Indeed, the wave propagation phenomenon in free space mixes in a natural way the spatial distribution of point sources from the 3-dimensional scene. As the 3-dimensional scene is mapped to a 2-dimensional hologram, the hologram samples form a compressed representation of the scene as well. This overview paper discusses contributions in the field of compressed digital holography at the micro scale. Then, an outreach on future extensions towards the real-size macro scale is discussed. Thanks to advances in sensor technologies, increasing computing power and the recent improvements in sparse digital signal processing, holographic modalities are on the verge of practical high-quality visualization at a macroscopic scale where much higher resolution holograms must be acquired and processed on the computer.

  13. MACRO-REGIONAL DISPARITIES IN ROMANIA

    Directory of Open Access Journals (Sweden)

    MARIA OŢIL

    2010-01-01

    Full Text Available Economic disparities are disparities between levels of economicdevelopment of the areas or regions within a national economy. If economic literature hasfailed to explain the causes of inequalities in economic development of different regions of theEU, this issue became a priority in EU economic policy, especially after the adhesion ofGreece, Spain and Portugal, countries characterized by a lower level of development fromother EU countries and also marked by significant regional imbalances. European Unionsupports reducing disparities between different regions of Member States so that all regionsand their people to benefit from economic and social advantages of the Union. This paper aimsto highlight disparities between the macro-regions in Romania. Regional demarcation criterionin the NUTS system is the population’s number within a territory. Most pertinent argument isthat the goal of all activities in a society lies in meeting the needs of the individual and of thecommunity. This possibility is ensured by a certain level of economic development in the region.Less developed areas of Romania are located in Northern Moldova and in the South EasternRomanian Plain and the more developed areas include, in addition to Bucharest andConstanta, Transylvania and Banat regions.

  14. macro-regional, local y micro- regional

    Directory of Open Access Journals (Sweden)

    José Guadalupe Vargas Hernández

    2006-01-01

    Full Text Available Este trabajo se propone analizar las implicaciones del desarrollo en los niveles macro-regional, local y micro- regional, a partir de la hipótesis central de la teoría del desarrollo que plantea que el desarrollo económico traerá consigo el desarrollo político y social. Después de hacer de un acercamiento conceptual al desarrollo, se repasan brevemente las teorías del desarrollo existentes como herramientas de análisis de la realidad. En la discusión se concluye que los procesos de desarrollo locales y regionales requieren de una transformación sustancial de las relaciones negociadas entre los agentes económicos y los actores políticos. Ante el paulatino retroceso que en las sociedades contemporáneas está teniendo el Estado de bienestar, uno de los principales retos es el empoderamiento de las organizaciones sociales y comunitarias para que desempeñen activamente su rol en los procesos de desarrollo local y regional.

  15. [Macro- and microelements in canned sprats].

    Science.gov (United States)

    Polak-Juszczak, Lucyna; Usydus, Zygmunt

    2006-01-01

    The content of macro- and microelements and toxic metals in the most popular canned sprat was described in this paper. The research included the following canned sprat: sprat in tomato, smoked and steamed sprat in oil. The following analyses were carried out: content of calcium, phosphorus, potassium, magnesium, copper, zinc, iron, manganese, chromium, selenium, fluorine, iodine, cadmium, lead, mercury and arsenic. Fluorine, iodine, selenium, and calcium and phosphorous are provided to customer organism in large amount by canned sprat, however canned sprat cannot be considered as a source of copper, chromium, and manganese. On the base of assessment data one canned sprat (weight 170 g) provides to customer organism more than 50% recommended daily intake of calcium and phosphorus, 85-233% fluorine, 62.5% iodine, 43% recommended selenium, more than 25% zinc, about 15% daily intake of magnesium, potassium and iron. It was found that all of the analyzed canned sprat contained relatively low content of cadmium, lead, mercury and arsenic, thus confirming the established safety standards.

  16. [Features of Immunophenotypes and Characteristics of Molecular Biology and Cellular Genetics of AML Patients with CD4 and CD7 Expression].

    Science.gov (United States)

    Liu, Tie-Qiang; Huang, Shan; Yao, Bo; Liu, Zhi-Qing; Yu, Chang-Lin; Qiao, Jian-Hui; Sun, Qi-Yun; Hu, Kai-Xun; Huang, Ya-Jing; Zhang, Rui; Li, Yu-Fang; Bai, Juan; Sun, Yu-Jing; Li, Bing-Xia; Wang, Dong-Mei; Wang, Yi; Guo, Mei

    2016-12-01

    To explore the features of immunophenotypes and the characteristics of molecular biology and cellular genetics of AML patients with CD7 and CD4 expression. The immunophenotypical markers of AML cells were detected by multiple parameter flow cytometry; the expression of WT1, MDK, ETO, PML-RaRa and BCR-ABL were detected by RT-PCR; and cellular features were analyzed by R-band in 304 patients. The patients were divided into three groups according to their immunophenotypes: AML with CD7 expression (CD7 group), AML with CD4 expression(CD4 group) and AML without CD7 and CD4 expression (common AML group). The expression rate and level of HLA-DR in CD7 group were higher than those in the common AML group, and the expression rate of CD33 and CD34 was higher than that in the other two groups. The expression rate and level of CD15, CD64 in the CD4 group were higher than those in the other 2 groups, and the expression rate and level of CD33 were higher than those in the common AML group. WT1 expression in the CD7 group was lower than that in the common AML group. PML-RaRa was not detected in the CD7 group. AML with co-expression of CD4 or CD7 showed more normal karyotype. (15;17) was not found in AML with CD7 expression. AML cells with CD7 expression originate from precursor cells and are blocked in the early phase of hematological development; AML cells with CD4 expression originate from more mature stage of hematological devevelopment and with CD33, CD64 and CD15 high expression; AML cells with CD7 and CD4 expression are characterized by no-specific change of cellular genetics. According to the expression level and intesity of CD4 and CD7, and together with other specific lineage markers, the MRD in AML patients can be quantitatively detected.

  17. 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.

  18. Peripheral Blood WT1 Expression Predicts Relapse in AML Patients Undergoing Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Michele Malagola

    2014-01-01

    Full Text Available To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB and bone marrow (BM before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 104 from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM. Eight out of 11 (73% patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31% patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P = 0.04. The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%; P = 0.43 and at the 6th month (71% versus 20%; P = 0.03. Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20% (P = 0.02. Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk.

  19. Apoptosis-inducing activity of Helleborus niger in ALL and AML.

    Science.gov (United States)

    Jesse, Patrick; Mottke, Gritt; Eberle, Jürgen; Seifert, Georg; Henze, Günter; Prokop, Aram

    2009-04-01

    Helleborus niger is used in the adjuvant treatment of different tumors in anthroposophical medicine. Indications include various types of brain tumors in children, as well as prostate cancer, leukemia and lymphoma. Our aim was to investigate the therapeutic effects of these extracts apart from the traditional use. : We used an aqueous whole plant extract of H. niger in different cancer and leukemia cell lines and primary cells of patients with childhood ALL and AML and identified the main mechanisms of action. A strong inhibition of proliferation is caused by specific apoptosis induction, which is executed via the mitochondrial pathway and caspase-3 processing. Apoptosis could be detected in lymphoma (BJAB), leukemia (Reh, Nalm6, Sup-B15) and melanoma (Mel-HO) cells and overcomes a Bcl-2-mediated block of apoptosis. In primary cells of patients with childhood ALL and AML, which were partly poor responding to doxorubicin and daunorubicin, a strong apoptosis induction was determined. In combination with the vinca alkaloid vincristine, strong synergistic effects were detected in BJAB cells. We demonstrate in vitro efficacy of H. niger extract in cells of hematological malignancies; these studies should encourage in vivo experiments. Copyright 2008 Wiley-Liss, Inc.

  20. Dis-integrating Perspectives of Language Acquisition.

    Science.gov (United States)

    Jacobs, Bob

    1995-01-01

    Responds to L. Eubank and K. R. Gregg article (this issue), suggesting they have misinterpreted and misrepresented claims made by B. Jacobs and J. Schumann. Claims discussed include the micro- and macro-organization of neurobiology and language, the Explananda, Jacobs and Schumann's acquisition mechanism, and reductionism. The single acquisition…

  1. 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.

  2. The clinical importance of myeloid antigen coexpression and TEL-AML1 mutation in patients with childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ayşen Türedi Yıldırım

    2013-03-01

    Full Text Available Objective: In this study, we aim to investigate the relationship,if any, between clinical features, prognosis, and thecoexpressions and TEL-AML1 mutation in patients withacute lymphoblastic leukemia (ALL.Methods: Eigthy-three patients with acute lymphoblasticleukemia were retrospectively examined. Age, gender,White blood cell count, hemoglobin level, platelet count,ALL subtypei (B or T ALL, risk groups, surface antigensdeteceted by flow cytometry, existence of TEL-AML1 mutations,response, remission and relapse status at 8., 15.ve 33. Days of treatment were recorded and analyzed.Results: 15 (18% out of 83 were identified with aberrantantigen expression. Of these patients, twelve (14.4%had myeloid antigen coexpression (CD13 and/or CD33,two with B cell ALL had CD2 and CD7 coexpressions respectively,one with T cell ALL had CD19 coexpression.No significant differences were found between patientswith and without myeloid antigen coexpression in terms ofhemoglobin levels, white blood cells and platelet counts,responses given on the 8th, 15th, and 30th days on the treatment,risk groups, and relapse (p>0.05. Myeloid antigencoexpression was found in 4 of 13 patients who were identifiedwith TEL-AML1 mutation. No significant relationshipwas found between this mutation and coexpressions. Norelapse and exitus were observed in four patients with coexpressionand TEL-AML1.Conclusion: The prognosis and clinical features showsno statistically significant relationship with the presence ofneither Myeloid antigen expression nor TEL-AML1 mutation.We believe, however, the future studies involving biggersample sizes will prove to be useful in terms of moreconvincing results. J Clin Exp Invest 2013; 4(1: 90-94Key words: Acute lenfoblastic leukemia, coexpression,TEL-AML1 mutation, prognosis

  3. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3

    Directory of Open Access Journals (Sweden)

    Hulya Gunbatar

    2015-01-01

    Full Text Available A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3. During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.

  4. Successful management of pulmonary hemorrhage and aspergillosis in a patient with acute myeloid leukemia (AML-M3).

    Science.gov (United States)

    Gunbatar, Hulya; Demir, Cengiz; Kara, Erdal; Esen, Ramazan; Sertogullarindan, Bunyamin; Asker, Selvi

    2015-01-01

    A 35-year-old man presented with a one month history of gingival bleeding. He was diagnosed with Acute Myeloid Leukemia (AML-M3). During treatment he developed alveolar hemorrhage for which he was treated with a steroid. After the steroid treatment he developed a nodule, a cavitary lesion and atelectasia in the left lung. He was treated with voriconazole. After therapy with voriconazole his lesion significantly decreased. This case illustrates the efficacy and safety of antifungal therapy with voriconazole for aspergillosis complicated by AML.

  5. Clofarabine, Idarubicin, and Cytarabine (CIA) as Frontline Therapy for Patients ≤60 Years with Newly Diagnosed Acute Myeloid Leukemia (AML)

    Science.gov (United States)

    Nazha, Aziz; Ravandi, Farhad; Kantarjian, Hagop; Huang, Xuelin; Choi, Sangbum; Garcia-Manero, Guillermo; Jabbour, Elias; Borthakur, Gautam; Kadia, Tapan; Konopleva, Marina; Cortes, Jorge; Ferrajoli, Alessandra; Kornblau, Steve; Andreeff, Michael; Du, Min; Brandt, Mark; Faderl, Stefan

    2014-01-01

    Purpose To explore the combination of clofarabine, cytarabine, and idarubicin (CIA) in patients with newly diagnosed acute myeloid leukemia (AML) 40 years. Compared to historical patients treated with IA combination, the OS and EFS were significantly higher (P = 0.005, 0.0001, respectively) for CIA treated patients. In multivariate analysis, CIA retained its superior impact on OS and EFS compared to IA. Conclusion CIA is an effective combination for patients AML. Patients ≤ 40 years had better OS and EFS. CIA achieved longer OS and EFS compared to IA alone. PMID:23877926

  6. Macro policy reform, labour market, poverty and inequality in urban ...

    African Journals Online (AJOL)

    Macro policy reform, labour market, poverty and inequality in urban Ethiopia: a Micro-simulation approach. ... why incomes and inequality largely remained stable at a time of fundamental changes in macroeconomic policy environment.

  7. Three Macro Controls Over China’s Real Estate Market

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The first macro control: to cool overheated real estate investment June 2003: The People’s Bank of China issued the Notice on Further Strengthening Credit and Loan Business Management of Real Estate

  8. The Generalist Model: Where do the Micro and Macro Converge?

    Directory of Open Access Journals (Sweden)

    Shari E. Miller

    2008-12-01

    Full Text Available Although macro issues are integral to social work, students continue to struggle with the acquisition of knowledge and skills pertaining to larger systems. Educators have developed innovative methods to integrate learning across systems of various sizes however it appears an imbalance persists. This challenge is supported by baccalaureate student responses to a social work program evaluation. Four years of data from 295 undergraduate students revealed that they felt less prepared to practice with larger, macro systems. Changes in curriculum to reflect collaboration and holism, and more research are needed to adequately provide macro learning and macro practice opportunities within the generalist model and in the context of the current socio-economic-political environment.

  9. Cochlear Macro- and Micromechanics—A Moderated Discussion

    Science.gov (United States)

    Dong, Wei; Ruggero, Mario A.

    2011-11-01

    A discussion moderated by the authors on the topic "Cochlear Macro- and Micromechanics" was held on 19 July 2011 at the 11th International Mechanics of Hearing Workshop in Williamstown, Massachusetts. The paper provides an edited transcript of the session.

  10. Macro-invertebrate and Avian Species Survey : Biological Summary Report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This was a survey effort to determine species diversity and density of macro-invertebrates and avian species inhabiting playa systems located in SW regions of Baca...

  11. THE CULTURE AND ARTS ORGANIZATION: MACRO-SOCIOLOGICAL ASPECT

    Directory of Open Access Journals (Sweden)

    Margarita Rasimovna Pashaeva

    2013-11-01

    Full Text Available In this study we analyze the macro-sociological aspect of culture and arts organization. The subject of research is reputation policy and communication technologies in  macro-sociological aspect of culture and arts organization. The target is the research the effects of macro-sociological aspect in the activities of such organization. In the study were used such methods of research: theoretical study and  synthesis; quantative method of elicitation: questionnaire; information processing methods of primary analysis; interpretation. The results of research can be applied in the activities of different culture and arts organization. The research identified the negative and positive tendencies in the context of the macro-sociological aspect.DOI: http://dx.doi.org/10.12731/2218-7405-2013-8-49

  12. Usual Dietary Intakes: SAS Macros for the NCI Method

    Science.gov (United States)

    SAS macros are currently available to facilitate modeling of a single dietary component, whether consumed daily or episodically; ratios of two dietary components that are consumed nearly every day; multiple dietary components, whether consumed daily or episodically.

  13. Breast Cancer Risk Assessment SAS Macro (Gail Model)

    Science.gov (United States)

    A SAS macro (commonly referred to as the Gail Model) that projects absolute risk of invasive breast cancer according to NCI’s Breast Cancer Risk Assessment Tool (BCRAT) algorithm for specified race/ethnic groups and age intervals.

  14. Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: Results of an international study

    NARCIS (Netherlands)

    E.A. Coenen (Eva); S. Raimondi (Susana); J. Harbott (Jochen); M. Zimmermann (Martin); H.B. Beverloo (Berna); M. Chang (Myron); U. Creutzig (Ursula); M.N. Dworzak (Michael); E. Forestier (Erik); B. Gibson (Brenda); H. Hasle (Henrik); C.J. Harrison (Christine); N.A. Heerema (Nyla); G.J. Kaspers (Gertjan); A. Leszl (Anna); N. Litvinko (Nathalia); L.L. Nigro (Luca); A. Morimoto (Akira); C. Perot (Christine); A. Auvrignon (Anne); D. Reinhardt (Dirk); J.E. Rubnitz (Jeffrey); F.O. Smith (Franklin); J. Stary (Jan); I. Stasevich (Irina); S. Strehl (Sabine); T. Taga (Takashi); D. Tomizawa (Daisuke); Z. Zemanová (Zuzana); D.K.H. Webb (David); T.A. Alonzo (Todd); R. Pieters (Rob); C.M. Zwaan (Christian Michel); M.M. van den Heuvel-Eibrink (Marry)

    2011-01-01

    textabstractWe previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLL-rearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had

  15. RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML

    NARCIS (Netherlands)

    Loke, J. (Justin); S.A. Assi (Salam); Imperato, M.R. (Maria Rosaria); Ptasinska, A. (Anetta); Cauchy, P. (Pierre); Grabovska, Y. (Yura); Soria, N.M. (Natalia Martinez); Raghavan, M. (Manoj); Delwel, H.R. (H. Ruud); P.N. Cockerill (Peter); O. Heidenreich; C. Bonifer (Constanze)

    2017-01-01

    textabstractAcute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations

  16. Coal Mines, Abandoned - COAL_AML_HIGHWALLS_IN: Abandoned Mine Lands, Dangerous Highwalls in Indiana (Indiana Geological Survey, 1:24,000, PolyLine Shapefile)

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — AML_HIGHWALLS, the predecessor of COAL_AML_HIGHWAYS_IN, is a 1:24,000-scale PolyLine-based ESRI ArcView shapefile that shows the locations and extents of dangerous...

  17. Coal Mines, Abandoned - COAL_AML_MISC_IN: Abandoned Mine Lands, Entrances, Equipment, Facilities, and Dangerous Gasses in Indiana (Indiana Geological Survey, 1:24,000, Point Shapefile)

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — AML_POINT, the predecessor of COAL_AML_MISC_IN, is a 1:24,000-scale point-based ESRI ArcView shapefile that shows the locations of point features associated with...

  18. Establishment of xenotransplantation model of human CN-AML with FLT3-ITD (mut) /NPM1 (-) in NOD/SCID mice.

    Science.gov (United States)

    Shang, Zhen; Wang, Jue; Wang, Di; Xiao, Min; Li, Tong-juan; Wang, Na; Huang, Liang; Zhou, Jian-feng

    2013-06-01

    Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.

  19. Changes in the MALT1-A20-NF-κB expression pattern may be related to T cell dysfunction in AML.

    Science.gov (United States)

    Shi, Li; Chen, Shaohua; Lu, Yuhong; Wang, Xu; Xu, Ling; Zhang, Fan; Yang, Lijian; Wu, Xiuli; Li, Bo; Li, Yangqiu

    2013-04-30

    To elucidate the characteristics of T-cell receptor (TCR) signal transduction in T-cells from acute myeloid leukemia (AML), the mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1), A20, NF-κB and MALT1-V1 gene expression levels in CD3+ T cells sorted from the peripheral blood of patients with AML were analyzed by real-time PCR. A significantly lower MALT1 and A20 expression level was found in T cells from patients with AML compared with healthy controls (p = 0.045, p MALT1-V1 (variant 1) was significantly higher in the AML group than in the healthy control group (p = 0.006), and the expression level of NF-κB was increased in the AML group. In conclusion, the characteristics of the expression pattern of MALT1-A20-NF-κB and the distribution of MALT1 variants in T cells from AML were first characterized. Overall, low TCR-CD3 signaling is related to low MALT1 expression, which may related to T cell immunodeficiency, while the up-regulation of MALT1-V1 may play a role in overcoming the T cell activity by downregulating A20 in patients with AML, which may be related to a specific response to AML-associated antigens.

  20. Coal Mines, Abandoned - COAL_AML_FEATURES_IN: Abandoned Mine Lands, Miscellaneous Site Features in Indiana (Indiana Geological Survey, 1:24,000, Polygon Shapefile)

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — AML_POLY, the predecessor of COAL_AML_FEATURES_IN, is a 1:24,000-scale polygon-based ESRI ArcView shapefile that shows the locations and extents of Abandoned Mine...

  1. 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.

  2. A statistical mechanics model of carbon nanotube macro-films

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Carbon nanotube macro-films are two-dimensional films with micrometer thickness and centimeter by centimeter in-plane dimension.These carbon nanotube macroscopic assemblies have attracted significant attention from the material and mechanics communities recently because they can be easily handled and tailored to meet specific engineering needs.This paper reports the experimental methods on the preparation and characterization of single-walled carbon nanotube macro-films,and a statistical mechanics model on ...

  3. Tutorial: simulating chromatography with Microsoft Excel Macros.

    Science.gov (United States)

    Kadjo, Akinde; Dasgupta, Purnendu K

    2013-04-22

    Chromatography is one of the cornerstones of modern analytical chemistry; developing an instinctive feeling for how chromatography works will be invaluable to future generation of chromatographers. Specialized software programs exist that handle and manipulate chromatographic data; there are also some that simulate chromatograms. However, the algorithm details of such software are not transparent to a beginner. In contrast, how spreadsheet tools like Microsoft Excel™ work is well understood and the software is nearly universally available. We show that the simple repetition of an equilibration process at each plate (a spreadsheet row) followed by discrete movement of the mobile phase down by a row, easily automated by a subroutine (a "Macro" in Excel), readily simulates chromatography. The process is readily understood by a novice. Not only does this permit simulation of isocratic and simple single step gradient elution, linear or multistep gradients are also easily simulated. The versatility of a transparent and easily understandable computational platform further enables the simulation of complex but commonly encountered chromatographic scenarios such as the effects of nonlinear isotherms, active sites, column overloading, on-column analyte degradation, etc. These are not as easily simulated by available software. Views of the separation as it develops on the column and as it is seen by an end-column detector are both available in real time. Excel 2010™ also permits a 16-level (4-bit) color gradation of numerical values in a column/row; this permits visualization of a band migrating down the column, much as Tswett may have originally observed, but in a numerical domain. All parameters of relevance (partition constants, elution conditions, etc.) are readily changed so their effects can be examined. Illustrative Excel spreadsheets are given in the Supporting Information; these are easily modified by the user or the user can write his/her own routine.

  4. Specific scoring systems to predict survival of patients with high-risk myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) after intensive antileukemic treatment based on results of the EORTC-GIMEMA AML-10 and intergroup CRIANT studies

    NARCIS (Netherlands)

    Oosterveld, M.; Suciu, S.; Muus, P.; Germing, U.; Delforge, M.; Belhabri, A.; Aul, C.; Selleslag, D.; Ferrant, A.; Marie, J.P.; Amadori, S.; Jehn, U.; Mandelli, F.; Hess, U.; Hellstrom-Lindberg, E.; Cakmak-Wollgast, S.; Vignetti, M.; Labar, B.; Willemze, R.; Witte, T.J. de

    2015-01-01

    High-risk myelodysplastic syndrome (MDS) patients have usually a less favorable outcome after intensive treatment compared with de novo acute myeloid leukemia (AML) patients. This may reflect different disease-related and patient-related factors. The purpose of this analysis is to identify disease-s

  5. Lemons to Lemonade: How Five Challenges in Teaching Macro Practice Helped to Strengthen Our Course

    Science.gov (United States)

    Dooley, Joe; Sellers, Sherril; Gordon-Hempe, Cornelia

    2009-01-01

    Teaching macro practice can be challenging. While students have some concepts of what macro practice entails, their knowledge may be limited and sometimes inaccurate. Moreover, students may be reluctant to engage in macro change efforts. Given the scarcity of literature regarding teaching macro practice and the growing importance of it in social…

  6. Acute myeloid leukemia (AML)-reactive cytotoxic T lymphocyte clones rapidly expanded from CD8(+) CD62L((high)+) T cells of healthy donors prevent AML engraftment in NOD/SCID IL2Rgamma(null) mice.

    Science.gov (United States)

    Distler, Eva; Wölfel, Catherine; Köhler, Sylvia; Nonn, Marion; Kaus, Nina; Schnürer, Elke; Meyer, Ralf G; Wehler, Thomas C; Huber, Christoph; Wölfel, Thomas; Hartwig, Udo F; Herr, Wolfgang

    2008-04-01

    Current in vitro techniques for isolating leukemia-reactive cytotoxic T lymphocytes (CTLs) from healthy donors are of relatively low efficiency and yield responder populations with unknown biological significance. This study aimed at the development of a more reliable approach, allowing generation and expansion of acute myeloid leukemia (AML)-reactive CTLs using primary in vitro stimulation. We established allogeneic mini-mixed lymphocyte-leukemia cultures (mini-MLLCs) by stimulating donor CD8(+) T cells with human leukocyte antigen (HLA) class I-matched AML blasts in microtiter plates. Before culture, CD8(+) T cells were separated into CD62L((high)+) and CD62L((low)+/neg) subsets enriched for naive/central memory and effector memory cells, respectively. In eight different related and unrelated donor/AML pairs, numerous CTL populations were isolated that specifically lysed myeloid leukemias in association with various HLA-A, -B, or -C alleles. These CTLs expressed T-cell receptors of single Vbeta-chain families, indicating their clonal origin. The majority of CTL clones were obtained from mini-MLLCs initiated with CD62L((high)+) cells. Using antigen-specific stimulation, multiple CTL populations were amplified to 10(8)-10(10) cells within 6 to 8 weeks. Three of four representative CTL clones were capable of completely preventing engraftment of human primary AML blasts in nonobese diabetic/severe combined immune deficient IL2Rgamma(null) mice. The mini-MLLC approach allows the efficient in vitro expansion of AML-reactive CTL clones from CD8(+)CD62L((high)+) precursors of healthy donors. These CTLs can inhibit leukemia engraftment in immunodeficient mice, suggesting their potential biological relevance.

  7. Computability, complexity, and languages fundamentals of theoretical computer science

    CERN Document Server

    Davis, Martin D; Rheinboldt, Werner

    1983-01-01

    Computability, Complexity, and Languages: Fundamentals of Theoretical Computer Science provides an introduction to the various aspects of theoretical computer science. Theoretical computer science is the mathematical study of models of computation. This text is composed of five parts encompassing 17 chapters, and begins with an introduction to the use of proofs in mathematics and the development of computability theory in the context of an extremely simple abstract programming language. The succeeding parts demonstrate the performance of abstract programming language using a macro expa

  8. 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)

  9. 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

  10. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero

    NARCIS (Netherlands)

    Wiemels, JL; Ford, AM; Van Wering, ER; Postma, A; Greaves, M

    1999-01-01

    We report a pair of identical twins with concordant acute lymphoblastic leukemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14, Leukemic cells in both twins had a TEL-AML1 rearrangement, which was characterized at the DNA level by an adaptation of a long distance polym

  11. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis

    NARCIS (Netherlands)

    B.V. Balgobind (Brian); P. van Vlierberghe (Pieter); A.M.W. van den Ouweland (Ans); H.B. Beverloo (Berna); J.N.R. Terlouw-Kromosoeto (Joan); E.R. van Wering (Elisabeth); D. Reinhardt (Dirk); M.A. Horstmann (Martin); G.J. Kaspers (Gertjan); R. Pieters (Rob); C.M. Zwaan (Christian Michel); M.M. van den Heuvel-Eibrink (Marry); J.P.P. Meijerink (Jules)

    2008-01-01

    textabstractNeurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Patients with NF1 have a higher risk to develop juvenile myelomonocytic leukemia (JMML) with a possible progression toward acute myeloid leukemia (AML). In an oligo array compara

  12. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis

    NARCIS (Netherlands)

    Balgobind, Brian V.; Van Vlierberghe, Pieter; van den Ouweland, Ans M. W.; Beverloo, H. Berna; Terlouw-Kromosoeto, Joan N. R.; van Wering, Elisabeth R.; Reinhardt, Dirk; Horstmann, Martin; Kaspers, Gertjan J. L.; Pieters, Rob; Zwaan, C. Michel; Van den Heuvel-Eibrink, Marry M.; Meijerink, Jules P. P.

    2008-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Patients with NF1 have a higher risk to develop juvenile myelomonocytic leukemia (JMML) with a possible progression toward acute myeloid leukemia (AML). In an oligo array comparative genomic

  13. High-affinity FRβ-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity.

    Science.gov (United States)

    Lynn, R C; Feng, Y; Schutsky, K; Poussin, M; Kalota, A; Dimitrov, D S; Powell, D J

    2016-06-01

    Acute myeloid leukemia (AML) is an aggressive malignancy, and development of new treatments to prolong remissions is warranted. Chimeric antigen receptor (CAR) T-cell therapies appear promising but on-target, off-tumor recognition of antigen in healthy tissues remains a concern. Here we isolated a high-affinity (HA) folate receptor beta (FRβ)-specific single-chain variable fragment (2.48 nm KD) for optimization of FRβ-redirected CAR T-cell therapy for AML. T cells stably expressing the HA-FRβ CAR exhibited greatly enhanced antitumor activity against FRβ(+) AML in vitro and in vivo compared with a low-affinity FRβ CAR (54.3 nm KD). Using the HA-FRβ immunoglobulin G, FRβ expression was detectable in myeloid-lineage hematopoietic cells; however, expression in CD34(+) hematopoietic stem cells (HSCs) was nearly undetectable. Accordingly, HA-FRβ CAR T cells lysed mature CD14(+) monocytes, while HSC colony formation was unaffected. Because of the potential for elimination of mature myeloid lineage, mRNA CAR electroporation for transient CAR expression was evaluated. mRNA-electroporated HA-FRβ CAR T cells retained effective antitumor activity in vitro and in vivo. Together, our results highlight the importance of antibody affinity in target protein detection and CAR development and suggest that transient delivery of potent HA-FRβ CAR T cells is highly effective against AML and reduces the risk for long-term myeloid toxicity.

  14. Oncogenic fusion proteins expressed in immature hematopoietic cells fail to recapitulate the transcriptional changes observed in human AML

    DEFF Research Database (Denmark)

    Rapin, N; Porse, B T

    2014-01-01

    in acute promyelocytic leukemia. Hematopoietic stem/progenitor (HSPCs) cells transduced with oncogenic fusion genes are regarded as promising in vitromodels of their corresponding AML subtypes. Here, we critically assessed the potential of such in vitro models using an integrative bioinformatics approach...

  15. LIN28B Activation by PRL-3 Promotes Leukemogenesis and a Stem Cell-like Transcriptional Program in AML.

    Science.gov (United States)

    Zhou, Jianbiao; Chan, Zit-Liang; Bi, Chonglei; Lu, Xiao; Chong, Phyllis S Y; Chooi, Jing-Yuan; Cheong, Lip-Lee; Liu, Shaw-Cheng; Ching, Ying Qing; Zhou, Yafeng; Osato, Motomi; Tan, Tuan Zea; Ng, Chin Hin; Ng, Siok-Bian; Wang, Shi; Zeng, Qi; Chng, Wee-Joo

    2017-03-01

    PRL-3 (PTP4A3), a metastasis-associated phosphatase, is also upregulated in patients with acute myeloid leukemia (AML) and is associated with poor prognosis, but the underlying molecular mechanism is unknown. Here, constitutive expression of PRL-3 in human AML cells sustains leukemogenesis in vitro and in vivo Furthermore, PRL-3 phosphatase activity dependently upregulates LIN28B, a stem cell reprogramming factor, which in turn represses the let-7 mRNA family, inducing a stem cell-like transcriptional program. Notably, elevated levels of LIN28B protein independently associate with worse survival in AML patients. Thus, these results establish a novel signaling axis involving PRL-3/LIN28B/let-7, which confers stem cell-like properties to leukemia cells that is important for leukemogenesis.Implications: The current study offers a rationale for targeting PRL-3 as a therapeutic approach for a subset of AML patients with poor prognosis. Mol Cancer Res; 15(3); 294-303. ©2016 AACR.

  16. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi

    2011-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services...

  17. Overproduction of NOX-derived ROS in AML promotes proliferation and is associated with defective oxidative stress signaling.

    Science.gov (United States)

    Hole, Paul S; Zabkiewicz, Joanna; Munje, Chinmay; Newton, Zarabeth; Pearn, Lorna; White, Paul; Marquez, Nuria; Hills, Robert K; Burnett, Alan K; Tonks, Alex; Darley, Richard L

    2013-11-07

    Excessive production of reactive oxygen species (ROS) is frequently observed in cancer and is known to strongly influence hematopoietic cell function. Here we report that extracellular ROS production is strongly elevated (mean >10-fold) in >60% of acute myeloid leukemia (AML) patients and that this increase is attributable to constitutive activation of nicotinamide adenine dinucleotide phosphate oxidases (NOX). In contrast, overproduction of mitochondrial ROS was rarely observed. Elevated ROS was found to be associated with lowered glutathione levels and depletion of antioxidant defense proteins. We also show for the first time that the levels of ROS generated were able to strongly promote the proliferation of AML cell lines, primary AML blasts, and, to a lesser extent, normal CD34(+) cells, and that the response to ROS is limited by the activation of the oxidative stress pathway mediated though p38(MAPK). Consistent with this, we observed that p38(MAPK) responses were attenuated in patients expressing high levels of ROS. These data show that overproduction of NOX-derived ROS can promote the proliferation of AML blasts and that they also develop mechanisms to suppress the stress signaling that would normally limit this response. Together these adaptations would be predicted to confer a competitive advantage to the leukemic clone.

  18. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis.

    Science.gov (United States)

    Balgobind, Brian V; Van Vlierberghe, Pieter; van den Ouweland, Ans M W; Beverloo, H Berna; Terlouw-Kromosoeto, Joan N R; van Wering, Elisabeth R; Reinhardt, Dirk; Horstmann, Martin; Kaspers, Gertjan J L; Pieters, Rob; Zwaan, C Michel; Van den Heuvel-Eibrink, Marry M; Meijerink, Jules P P

    2008-04-15

    Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Patients with NF1 have a higher risk to develop juvenile myelomonocytic leukemia (JMML) with a possible progression toward acute myeloid leukemia (AML). In an oligo array comparative genomic hybridization-based screening of 103 patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL) and 71 patients with MLL-rearranged AML, a recurrent cryptic deletion, del(17)(q11.2), was identified in 3 patients with T-ALL and 2 patients with MLL-rearranged AML. This deletion has previously been described as a microdeletion of the NF1 region in patients with NF1. However, our patients lacked clinical NF1 symptoms. Mutation analysis in 4 of these del(17)(q11.2)-positive patients revealed that mutations in the remaining NF1 allele were present in 3 patients, confirming its role as a tumor-suppressor gene in cancer. In addition, NF1 inactivation was confirmed at the RNA expression level in 3 patients tested. Since the NF1 protein is a negative regulator of the RAS pathway (RAS-GTPase activating protein), homozygous NF1 inactivation represent a novel type I mutation in pediatric MLL-rearranged AML and T-ALL with a predicted frequency that is less than 10%. NF1 inactivation may provide an additional proliferative signal toward the development of leukemia.

  19. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation

    NARCIS (Netherlands)

    C. Schmid (Christoph); M. Labopin (Myriam); A. Nagler (Arnon); D. Niederwieser (Dietger); L. Castagna (Luca); R. Tabrizi (Reza); M. Stadler (Michael); J. Kuball (Jürgen); J.J. Cornelissen (Jan); J. Vorlicek (Jiri); G. Socié (Gerard); M. Falda (M.); L. Vindelov (Lars); P. Ljungman (Per); G. Jackson (Graham); N. Kröger; A. Rank (Andreas); E. Polge (Emmanuelle); V. Rocha (Vanderson); M. Mohty (Mohamad)

    2012-01-01

    textabstractBecause information on management and outcome of AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) is scarce, a retrospective registry study was performed by the Acute LeukemiaWorking Party of EBMT. Among 2815 RIC

  20. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Schmid, Christoph; Labopin, Myriam; Nagler, Arnon

    2012-01-01

    Since information on management and outcome of adults with AML relapsing after allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning (RIC HSCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC tran...

  1. Silencing AML1-ETO gene expression leads to simultaneous activation of both pro-apoptotic and proliferation signaling.

    Science.gov (United States)

    Spirin, P V; Lebedev, T D; Orlova, N N; Gornostaeva, A S; Prokofjeva, M M; Nikitenko, N A; Dmitriev, S E; Buzdin, A A; Borisov, N M; Aliper, A M; Garazha, A V; Rubtsov, P M; Stocking, C; Prassolov, V S

    2014-11-01

    The t(8;21)(q22;q22) rearrangement represents the most common chromosomal translocation in acute myeloid leukemia (AML). It results in a transcript encoding for the fusion protein AML1-ETO (AE) with transcription factor activity. AE is considered to be an attractive target for treating t(8;21) leukemia. However, AE expression alone is insufficient to cause transformation, and thus the potential of such therapy remains unclear. Several genes are deregulated in AML cells, including KIT that encodes a tyrosine kinase receptor. Here, we show that AML cells transduced with short hairpin RNA vector targeting AE mRNAs have a dramatic decrease in growth rate that is caused by induction of apoptosis and deregulation of the cell cycle. A reduction in KIT mRNA levels was also observed in AE-silenced cells, but silencing KIT expression reduced cell growth but did not induce apoptosis. Transcription profiling of cells that escape cell death revealed activation of a number of signaling pathways involved in cell survival and proliferation. In particular, we find that the extracellular signal-regulated kinase 2 (ERK2; also known as mitogen-activated protein kinase 1 (MAPK1)) protein could mediate activation of 23 out of 29 (79%) of these upregulated pathways and thus may be regarded as the key player in establishing the t(8;21)-positive leukemic cells resistant to AE suppression.

  2. RUNX1 and CBFβ Mutations and Activities of Their Wild-Type Alleles in AML.

    Science.gov (United States)

    Hyde, R Katherine; Liu, Paul; Friedman, Alan D

    2017-01-01

    Mutations in RUNX1 and CBFB have long been recognized as important in hematological malignancies. Point mutations and deletions of RUNX1 are frequently found in myelodysplastic syndrome, myeloproliferative disease, and acute myeloid leukemia. Germline mutations in RUNX1 are associated with familial platelet disorder with predisposition to AML. In addition, as will be discussed in other chapters, both RUNX1 and CBFB are involved in recurrent chromosomal rearrangements in leukemia. More recently, roles for the non-mutated RUNX1 and CBFB genes have been identified in multiple leukemia subtypes. This chapter will discuss the roles of RUNX1 and CBFB, both in diseases caused by their mutations or deletions, as well as in the context of chromosomal rearrangements.

  3. 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

    BACKGROUND: High-dose cytarabine has been associated with a high frequency of viridans group streptococcal (VGS) bacteraemia. VGS bacteraemia causes considerable morbidity and mortality. The Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML protocols use higher cumulated doses...... following courses with low-dose cytarabine versus courses with high-dose cytarabine. CONCLUSIONS: VGS were the most commonly isolated pathogens causing the most severe infections and the majority of life-threatening infections. A substantial proportion of the strains were resistant to penicillin. The high...... 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....

  4. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Science.gov (United States)

    Fiala, Mark; Slade, Michael; Westervelt, Peter

    2017-01-01

    Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM. PMID:28316846

  5. Application of dual-fuel propulsion to a single stage AMLS vehicle

    Science.gov (United States)

    Lepsch, Roger A., Jr.; Stanley, Douglas O.; Unal, Resit

    1993-01-01

    As part of NASA's Advanced Manned Launch System (AMLS) study to determine a follow-on, or complement, to the Space Shuttle, a reusable single-stage-to-orbit concept utilizing dual-fuel rocket propulsion has been examined. Several dual-fuel propulsion concepts were investigated. These include: a separate engine concept combining Russian RD-170 kerosene-fueled engines with SSME-derivative engines; the kerosene and hydrogen-fueled Russian RD-701 engine concept; and a dual-fuel, dual-expander engine concept. Analysis to determine vehicle weight and size characteristics was performed using conceptual level design techniques. A response surface methodology for multidisciplinary design was utilized to optimize the dual-fuel vehicle concepts with respect to several important propulsion system and vehicle design parameters in order to achieve minimum empty weight. Comparisons were then made with a hydrogen-fueled reference, single-stage vehicle. The tools and methods employed in the analysis process are also summarized.

  6. Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

    Directory of Open Access Journals (Sweden)

    Bita Fakhri

    2017-01-01

    Full Text Available Posttransplant Lymphoproliferative Disorder (PTLD is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT. Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML. Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM; thus a diagnosis of smoldering multiple myeloma (SMM was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

  7. Macro Issues of Mikro Primary School

    Directory of Open Access Journals (Sweden)

    E Bray

    2007-05-01

    Full Text Available Mikro Primary School is an Afrikaans medium public school whose governing body refused to accede to an order of the Western Cape Department of Education to change the language policy of the school so as to convert it into a parallel medium Afrikaans/English school. The Supreme Court of Appeal held that section 29(2 of the Constitution of the Republic of South Africa, 1996, means that everyone has a right to be educated in an official language of his or her choice at a public educational institution to be provided by the State if reasonably practicable, but not the right to be so instructed at each and every public educational institution, subject only to it being reasonably practicable to do so. The court held that the language policy and admission policy of Mikro were not contrary to any provision of the Constitution, the South African Schools Act 84 of 1996, the Western Cape Provincial School Education Act 12 of 1997 or the Norms and Standards. The MEC and the department were prohibited and restrained from compelling or attempting to compel the school or its principal to admit learners for instruction otherwise than in compliance with its language policy and applicable provisions of the Schools Act and the Norms and Standards. The court declared the conduct of the department’s officials to be an unlawful interference with the government and professional management of the school in contravention of section 16 of the Schools Act and prohibited and restrained them from interfering unlawfully. The court rejected a previous interpretation of the term “organ of state” and relied on the Constitution which determines that any institution exercising a public power or performing a public function in terms of any legislation is an organ of state (section 239(b(ii. This means that the public school (acting through its governing body is clearly an organ of state because as an institution it exercises a public-education power and performs public

  8. Treosulfan, Fludarabine and 2 Gy Total Body Irradiation Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with MDS and AML

    Science.gov (United States)

    Gyurkocza, Boglarka; Gutman, Jonathan; Nemecek, Eneida R.; Bar, Merav; Milano, Filippo; Ramakrishnan, Aravind; Scott, Bart; Fang, Min; Wood, Brent; Pagel, John M.; Baumgart, Joachim; Delaney, Colleen; Maziarz, Richard T.; Sandmaier, Brenda M.; Estey, Elihu H.; Appelbaum, Frederick R.; Storer, Barry E.; Deeg, H. Joachim

    2014-01-01

    Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial we assessed the efficacy and toxicity of treosulfan, fludarabine and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n=36; 15 RMCD; 10 RAEB-1; 10 RAEB-2; 1 CMML-1) or AML (n=60; 35 CR1; 18 CR2; 3 advanced CR; 4 refractory relapse) were enrolled; median age was 51 (range: 1–60) years. Twelve patients had undergone a prior HCT with high intensity conditioning. Patients received intravenous (IV) treosulfan, 14 g/m2/day on days −6 to −4, IV fludarabine, 30 mg/m2/day on days −6 to −2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n=27) or unrelated (n=69) donors. Graft-vs.-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence and non-relapse mortality were 73%, 27% and 8%, respectively. The incidences of grades II–IV (III–IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor risk and good/intermediate risk cytogenetics (69% and 85%, respectively), or between AML patients with unfavorable and favorable/intermediate risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n=10) at the time of HCT predicted higher relapse incidence (70% vs. 18%) and lower OS (41% vs. 79%) at 2 years, when compared to patients without MRD. In conclusion, treosulfan, fludarabine and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML, and resulted in low relapse incidence, regardless

  9. WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides.

    Science.gov (United States)

    Brayer, Jason; Lancet, Jeffrey E; Powers, John; List, Alan; Balducci, Lodovico; Komrokji, Rami; Pinilla-Ibarz, Javier

    2015-07-01

    Peptide vaccines are capable of eliciting immune responses targeting tumor-associated antigens such as the Wilms' Tumor 1 (WT1) antigen, often overexpressed in myeloid malignancies. Here, we assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine. Individuals with WT1-positive acute myeloid leukemia (AML) in first (CR1) or second (CR2) remission or with higher-risk myelodysplastic syndrome (MDS) following at least 1 prior line of therapy were vaccinated with a mixture of peptides derived from the WT1 protein, with sargramostim injections before vaccination to amplify immunogenicity. Six vaccinations were delivered biweekly, continuing then monthly until patients received 12 vaccinations or showed disease relapse or progression. Therapeutic efficacy was evaluated by progression-free and overall survival. Immune responses were evaluated by delayed-type hypersensitivity testing and T-cell IFNγ ELISPOT at specified intervals. In 16 patients who received at least one vaccination, 10 completed the planned course of six vaccinations and six continued for up to six additional monthly vaccinations. Vaccinations were well tolerated, with no patients discontinuing due to toxicity. One of two patients with high-risk MDS experienced a prolonged decrease in transfusion dependence. Two of 14 AML patients demonstrated relapse-free survival >1 year. Both patients were in CR2 at time of vaccination, with duration of their remission exceeding duration of their first remission, suggesting a potential benefit. Our WT1 vaccine was well-tolerated. The clinical benefit that we observed in several patients suggests engagement of a protective immune response, indicating a need for further trials.

  10. Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial.

    Science.gov (United States)

    Goldstone, A H; Burnett, A K; Wheatley, K; Smith, A G; Hutchinson, R M; Clark, R E

    2001-09-01

    In an attempt to improve induction chemotherapy for older patients with acute myeloid leukemia (AML),1314 patients were randomized to 1 of 3 induction treatments for 2 courses of DAT (daunorubicin, cytarabine, and thioguanine) 3 + 10, ADE (daunorubicin, cytarabine, and etoposide) 10 + 3 + 5, or MAC (mitoxantrone-cytarabine). The remission rate in the DAT arm was significantly better than ADE (62% vs 50%; P =.002) or MAC (62% vs 55%; P =.04). This benefit was seen in patients younger and older than 70 years. There were no differences between the induction schedules with respect to overall survival at 5 years (12% vs 8% vs 10%). A total of 226 patients were randomized to receive granulocyte colony-stimulating factor (G-CSF) or placebo as supportive care from day 8 after the end of treatment course 1. The remission rate or survival were not improved by G-CSF, although the median number of days to recover neutrophils to 1.0 x 10(9)/L was reduced by 5 days. Patients who entered remission (n = 371) were randomized to stop after a third course (DAT 2 + 7) or after 6 courses, ie, a subsequent COAP (cyclophosphamide, vincristine, cytarabine, and prednisolone), DAT 2 + 5, and COAP. The relapse risk (81% vs 73%), disease-free survival (16% vs 23%), and overall survival at 5 years (23% vs 22%) did not differ between the 3-course or 6-course arms. In addition to a treatment duration randomization, 362 patients were randomized to receive 12-month maintenance treatment with low-dose interferon, but no benefit was seen with respect to relapse risk, disease-free survival, or overall survival.

  11. Measuring structural-functional correspondence: spatial variability of specialised brain regions after macro-anatomical alignment.

    Science.gov (United States)

    Frost, Martin A; Goebel, Rainer

    2012-01-16

    The central question of the relationship between structure and function in the human brain is still not well understood. In order to investigate this fundamental relationship we create functional probabilistic maps from a large set of mapping experiments and compare the location of functionally localised regions across subjects using different whole-brain alignment schemes. To avoid the major problems associated with meta-analysis approaches, all subjects are scanned using the same paradigms, the same scanner and the same analysis pipeline. We show that an advanced, curvature driven cortex based alignment (CBA) scheme largely removes macro-anatomical variability across subjects. Remaining variability in the observed spatial location of functional regions, thus, reflects the "true" functional variability, i.e. the quantified variability is a good estimator of the underlying structural-functional correspondence. After localising 13 widely studied functional areas, we found a large variability in the degree to which functional areas respect macro-anatomical boundaries across the cortex. Some areas, such as the frontal eye fields (FEF) are strongly bound to a macro-anatomical location. Fusiform face area (FFA) on the other hand, varies in its location along the length of the fusiform gyrus even though the gyri themselves are well aligned across subjects. Language areas were found to vary greatly across subjects whilst a high degree of overlap was observed in sensory and motor areas. The observed differences in functional variability for different specialised areas suggest that a more complete estimation of the structure-function relationship across the whole cortex requires further empirical studies with an expanded test battery.

  12. A new model to predict remission status in AML patients based on day 14 bone marrow biopsy.

    Science.gov (United States)

    Norkin, Maxim; Chang, Myron; An, Qi; Leather, Helen; Katragadda, Lakshmikanth; Li, Ying; Moreb, Jan S; May, W Stratford; Brown, Randy A; Hsu, Jack W; Hiemenz, John W; Wingard, John R; Cogle, Christopher R

    2016-07-01

    Although bone marrow evaluation on day 14 after initiation of induction chemotherapy (D14 BM) is a widely accepted practice in patients with acute myeloid leukemia (AML), it has suboptimal predictive value for predicting complete remission. We retrospectively analyzed pretreatment characteristics and post-induction response in a cohort of AML patients to determine if adding clinical and laboratory characteristics can improve the predictive value of the D14 BM evaluation. Among 297 patients treated for AML at the single institution 183 patients (61%) had leukemia-positive D14 BM. Of those, 94 were given reinduction chemotherapy and 89 were not. Of the 89 patients who did not receive reinduction, 32 (36%) subsequently achieved complete remission (CR) or complete remission with incomplete count recovery (CRi), and 57 (64%) had persistent disease. Persistent disease after positive D14 BM was more likely associated with higher percentage of D14 myeloblasts, a history of relapsed disease before induction, and higher risk disease compared to patients who subsequently achieved CR. Age, diagnostic white blood cell count, and the D14 BM cellularity did not influence the subsequent likelihood of achieving remission in patients with a positive D14 BM. A new mathematical equation was created and resulted in a positive predictive value of 83%, negative predictive value 90% and accuracy 88% for correctly identifying remission status after positive D14 BM in AML. The accuracy of predicting response using these additional parameters was significantly higher than without (0.88 vs. 0.80, P=0.002). Our new model provides better accuracy for predicting the likelihood of achieving remission and if validated in future studies may be useful for managing AML patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. AKT signaling as a novel factor associated with in vitro resistance of human AML to gemtuzumab ozogamicin.

    Directory of Open Access Journals (Sweden)

    David B Rosen

    Full Text Available Gemtuzumab ozogamicin (GO, an immunoconjugate between an anti-CD33 antibody and a calicheamicin-γ(1 derivative, induces remissions and improves survival in a subset of patients with acute myeloid leukemia (AML. As the mechanisms underlying GO and calicheamicin-γ(1 resistance are incompletely understood, we herein used flow cytometry-based single cell network profiling (SCNP assays to study cellular responses of primary human AML cells to GO. Our data indicate that the extent of DNA damage is quantitatively impacted by CD33 expression and drug efflux activity. However, although DNA damage is required for GO-induced cytotoxicity, it is not sufficient for effective cell kill, suggesting that downstream anti-apoptotic pathways may function as relevant resistance mechanisms. Supporting this notion, we found activated PI3K/AKT signaling to be associated with GO resistance in vitro in primary AML cells. Consistently, the investigational AKT inhibitor MK-2206 significantly sensitized various human AML cells to GO or free calicheamicin-γ(1 with particularly pronounced effects in otherwise GO or free calicheamicin-γ(1-resistant cells. Likewise, MK-2206 also sensitized primary AML cells to calicheamicin-γ(1. Together, our findings illustrate the capacity of SCNP assays to discover chemotherapy-related biological pathways and signaling networks relevant to GO-induced genotoxic stress. The identification of AKT signaling as being associated with GO resistance in vitro may provide a novel approach to improve the in vivo efficacy of GO/calicheamicin-γ(1 and, by extrapolation, other DNA damage-based therapeutics.

  14. FLT3 internal tandem duplication and FLT3-D835 mutation in 80 AML patients categorized into cytogenetic risk groups

    Directory of Open Access Journals (Sweden)

    Ewa Mały DEF

    2010-10-01

    Full Text Available Background:Acute myeloid leukemia (AML is a clonal disorder characterized by various genetic abnormalities and variable response to treatment. About 50�0of patients with AML have no cytogenetic aberrations, presenting normal karyotype, and are categorized in the intermediate risk group. In this group detection of FLT3 mutations move a patient from the intermediate to the adverse risk group.Material/Methods:Bone marrow from 80 AML patients was cultured to obtain chromosome slides and then karyotype. Simultaneously DNA was isolated from bone marrow and PCR reaction was conducted to test the FLT3 mutation status (ITD and D835. For statistical analysis Chi squared test was used.Results:From the group of 80 AML patients seven were classified as a favorable risk group and FLT3/ITD was found only in one of these patients (14.28� and FLT3/D835 in another one (14.28� Fifteen patients showed a complex karyotype with more than three aberrations or with any aberration known as a poor prognosis. Among the adverse group FLT3/ITD was detected in three patients (20�20and D835 mutation in two other patients (13.33� Among 58 patients with normal karyotype in GTG banding FLT3/ITD occurred in six cases (10.34�20and D835 mutation in two cases (3.45� No significant difference was found among these three risk groups regarding presence or absence of FLT3/ITD and FLT/D835.Discussion:Molecular characterization of mutations in several genes, such as FLT3, NPM1, MLL, CEBPA, in acute myeloid leukemia, especially in normal karyotype cases, could be another factor after cytogenetic analysis to stratify AML patients into different prognostic categories.

  15. Core-binding factor acute myeloid leukemia in first relapse: a retrospective study from the French AML Intergroup.

    Science.gov (United States)

    Hospital, Marie-Anne; Prebet, Thomas; Bertoli, Sarah; Thomas, Xavier; Tavernier, Emmanuelle; Braun, Thorsten; Pautas, Cécile; Perrot, Aurore; Lioure, Bruno; Rousselot, Philippe; Tamburini, Jérôme; Cluzeau, Thomas; Konopacki, Johanna; Randriamalala, Edouard; Berthon, Céline; Gourin, Marie-Pierre; Recher, Christian; Cahn, Jean-Yves; Ifrah, Norbert; Dombret, Hervé; Boissel, Nicolas

    2014-08-21

    Although core-binding factor-acute myeloid leukemia (CBF-AML) (t[8;21] or inv[16]/t[16;16]) represents a favorable cytogenetic AML subgroup, 30% to 40% of these patients relapse after standard intensive chemotherapy. The encouraging results of gemtuzumab ozogamicin (GO) in newly diagnosed AML, and particularly in CBF-AML, incited us to retrospectively investigate the impact of GO-based salvage in these patients. We retrospectively analyzed the outcome of 145 patients with CBF-AML (59 t[8;21], 86 inv[16]/t[16;16]) in first relapse. As salvage, 48 patients received GO-based chemotherapy and 97 patients received conventional chemotherapy. Median age was 43 years (range, 16-76). Median first complete remission duration was 12.1 months (range, 2.1-93.6). Overall, second complete remission (CR2) rate was 88%. With a median follow-up from relapse of 3.5 years, the estimated 5-year disease-free survival (DFS) was 50% and 5-year overall survival (OS) was 51%. Older age and shorter first complete remission duration was associated with a shorter OS. Patients treated with GO had similar CR2 rate but significantly higher 5-year DFS (68% vs 42%; P = .05) and OS (65% vs 44%; P = .02). In multivariate analysis, GO salvage was still associated with a significant benefit in DFS and OS. In the 78 patients who received allogeneic hematopoietic stem cell transplantation in CR2, GO before transplant significantly improved posttransplant DFS and OS without excess of treatment-related mortality.

  16. 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

    2013-01-01

    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. PMID:23709277

  17. EVI1 is critical for the pathogenesis of a subset of MLL-AF9–rearranged AMLs

    Science.gov (United States)

    Bindels, Eric M. J.; Havermans, Marije; Lugthart, Sanne; Erpelinck, Claudia; Wocjtowicz, Elizabeth; Krivtsov, Andrei V.; Rombouts, Elwin; Armstrong, Scott A.; Taskesen, Erdogan; Haanstra, Jurgen R.; Beverloo, H. Berna; Döhner, Hartmut; Hudson, Wendy A.; Kersey, John H.; Kumar, Ashish R.

    2012-01-01

    The proto-oncogene EVI1 (ecotropic viral integration site-1), located on chromosome band 3q26, is aberrantly expressed in human acute myeloid leukemia (AML) with 3q26 rearrangements. In the current study, we showed, in a large AML cohort carrying 11q23 translocations, that ∼ 43% of all mixed lineage leukemia (MLL)–rearranged leukemias are EVI1pos. High EVI1 expression occurs in AMLs expressing the MLL-AF6, -AF9, -AF10, -ENL, or -ELL fusion genes. In addition, we present evidence that EVI1pos MLL-rearranged AMLs differ molecularly, morphologically, and immunophenotypically from EVI1neg MLL-rearranged leukemias. In mouse bone marrow cells transduced with MLL-AF9, we show that MLL-AF9 fusion protein maintains Evi1 expression on transformation of Evi1pos HSCs. MLL-AF9 does not activate Evi1 expression in MLL-AF9–transformed granulocyte macrophage progenitors (GMPs) that were initially Evi1neg. Moreover, shRNA-mediated knockdown of Evi1 in an Evi1pos MLL-AF9 mouse model inhibits leukemia growth both in vitro and in vivo, suggesting that Evi1 provides a growth-promoting signal. Using the Evi1pos MLL-AF9 mouse leukemia model, we demonstrate increased sensitivity to chemotherapeutic agents on reduction of Evi1 expression. We conclude that EVI1 is a critical player in tumor growth in a subset of MLL-rearranged AMLs. PMID:22553314

  18. Micro and macro contact mechanics for interacting asperities

    Indian Academy of Sciences (India)

    M Ramesh; Satish V Kailas; K R Y Simha

    2008-06-01

    Contact of rough surfaces at micro and macro scales is studied in this paper. The asperities at micro scale are characterised by small radius of curvature whereas the waviness is characterised by large radius of curvature. When two rough surfaces come in contact, on the micro scale, of asperities contacts in a very small area leave large gaps between the surfaces; whereas on the macro scale the surfaces conform to each other under the application of load without gaps. Contact at micro scale is modelled by superposition of Hertzian stress fields of individual asperity contacts and the waviness at macro scale is modelled as a mixed boundary problem of rough punch indentation where displacements of uneven profile are prescribed along the region of contact. In both the cases for simplification the roughness is assigned to one surface making the other surface perfectly flat an assumption often made in contact mechanics of rough bodies. The motivation for modelling the asperities at micro scales comes from the preliminary results obtained from photoelastic experiments. Numerical results are presented based on the analytical results available for Hertzian contacts. The motivation for modelling the asperities at macro scales comes from the results available in literature for flat contacts from solving mixed boundary elasticity problems. A condition of full stick is assumed along the contact which is a common assumption made for rough contacts. The numerical results are presented for both the cases of rough contact at micro and macro scales.

  19. Performance evaluation of macro lens in digital close range photogrammetry

    Science.gov (United States)

    Yanagi, H.; Chikatsu, H.

    2009-08-01

    Recently, the documentation and visualization of various cultural heritages have been receiving attention, and a small Buddha such as less than 10 cm tall which was stored in the womb of Buddha is also included in cultural heritages. Zoom lenses are generally used to document these small objects and thus conserve the cultural heritage. However, there exist certain issues pertaining to the use of zoom lenses for such digital documentation. These issues include image sharpness and distortions that occur with changes in focal length setting, and in particular, the depth of field is issue from application standpoint such as documentation of the small cultural heritage. On the other hand, macro lenses can be used to capture sharp images of small objects from the view point of working distance, and its depth of field is related to the aperture of the camera. In order to evaluate the effectiveness of macro lenses in digital close range photogrammetry, macro lens and zoom lens were mounted on a digital single lens reflex camera (Canon EOS20D, 8.2 Mega pixels). This paper deals in a first part with comparative evaluations for both lenses with respect to their lens distortion, imaging mode, and calibration aspects. The results indicated that macro lenses were more suitable for digital close range photogrammetry. Calibration tests are performed to demonstrate the effectiveness and practicability of macro lens in close range photogrammetic applications.

  20. Characteristics of soil water retention curve at macro-scale

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Scale adaptable hydrological models have attracted more and more attentions in the hydrological modeling research community, and the constitutive relationship at the macro-scale is one of the most important issues, upon which there are not enough research activities yet. Taking the constitutive relationships of soil water movement--soil water retention curve (SWRC) as an example, this study extends the definition of SWRC at the micro-scale to that at the macro-scale, and aided by Monte Carlo method we demonstrate that soil property and the spatial distribution of soil moisture will affect the features of SWRC greatly. Furthermore, we assume that the spatial distribution of soil moisture is the result of self-organization of climate, soil, ground water and soil water movement under the specific boundary conditions, and we also carry out numerical experiments of soil water movement at the vertical direction in order to explore the relationship between SWRC at the macro-scale and the combinations of climate, soil, and groundwater. The results show that SWRCs at the macro-scale and micro-scale presents totally different features, e.g., the essential hysteresis phenomenon which is exaggerated with increasing aridity index and rising groundwater table. Soil property plays an important role in the shape of SWRC which will even lead to a rectangular shape under drier conditions, and power function form of SWRC widely adopted in hydrological model might be revised for most situations at the macro-scale.

  1. Genomic DNA breakpoints in AML1/RUNX1 and ETO cluster with topoisomerase II DNA cleavage and DNase I hypersensitive sites in t(8;21) leukemia

    Science.gov (United States)

    Zhang, Yanming; Strissel, Pamela; Strick, Reiner; Chen, Jianjun; Nucifora, Giuseppina; Le Beau, Michelle M.; Larson, Richard A.; Rowley, Janet D.

    2002-01-01

    The translocation t(8;21)(q22;q22) is one of the most frequent chromosome translocations in acute myeloid leukemia (AML). AML1/RUNX1 at 21q22 is involved in t(8;21), t(3;21), and t(16;21) in de novo and therapy-related AML and myelodysplastic syndrome as well as in t(12;21) in childhood B cell acute lymphoblastic leukemia. Although DNA breakpoints in AML1 and ETO (at 8q22) cluster in a few introns, the mechanisms of DNA recombination resulting in t(8;21) are unknown. The correlation of specific chromatin structural elements, i.e., topoisomerase II (topo II) DNA cleavage sites, DNase I hypersensitive sites, and scaffold-associated regions, which have been implicated in chromosome recombination with genomic DNA breakpoints in AML1 and ETO in t(8;21) is unknown. The breakpoints in AML1 and ETO were clustered in the Kasumi 1 cell line and in 31 leukemia patients with t(8;21); all except one had de novo AML. Sequencing of the breakpoint junctions revealed no common DNA motif; however, deletions, duplications, microhomologies, and nontemplate DNA were found. Ten in vivo topo II DNA cleavage sites were mapped in AML1, including three in intron 5 and seven in intron 7a, and two were in intron 1b of ETO. All strong topo II sites colocalized with DNase I hypersensitive sites and thus represent open chromatin regions. These sites correlated with genomic DNA breakpoints in both AML1 and ETO, thus implicating them in the de novo 8;21 translocation. PMID:11867721

  2. Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner.

    Science.gov (United States)

    Nabissi, Massimo; Morelli, Maria Beatrice; Amantini, Consuelo; Liberati, Sonia; Santoni, Matteo; Ricci-Vitiani, Lucia; Pallini, Roberto; Santoni, Giorgio

    2015-10-15

    Glioma stem-like cells (GSCs) correspond to a tumor cell subpopulation, involved in glioblastoma multiforme (GBM) tumor initiation and acquired chemoresistance. Currently, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population. Recently, the effect of cannabinoids (CBs) in promoting glial differentiation and inhibiting gliomagenesis has been evidenced. Herein, we demonstrated that cannabidiol (CBD) by activating transient receptor potential vanilloid-2 (TRPV2) triggers GSCs differentiation activating the autophagic process and inhibits GSCs proliferation and clonogenic capability. Above all, CBD and carmustine (BCNU) in combination overcome the high resistance of GSCs to BCNU treatment, by inducing apoptotic cell death. Acute myeloid leukemia (Aml-1) transcription factors play a pivotal role in GBM proliferation and differentiation and it is known that Aml-1 control the expression of several nociceptive receptors. So, we evaluated the expression levels of Aml-1 spliced variants (Aml-1a, b and c) in GSCs and during their differentiation. We found that Aml-1a is upregulated during GSCs differentiation, and its downregulation restores a stem cell phenotype in differentiated GSCs. Since it was demonstrated that CBD induces also TRPV2 expression and that TRPV2 is involved in GSCs differentiation, we evaluated if Aml-1a interacted directly with TRPV2 promoters. Herein, we found that Aml-1a binds TRPV2 promoters and that Aml-1a expression is upregulated by CBD treatment, in a TRPV2 and PI3K/AKT dependent manner. Altogether, these results support a novel mechanism by which CBD inducing TRPV2-dependent autophagic process stimulates Aml-1a-dependent GSCs differentiation, abrogating the BCNU chemoresistance in GSCs.

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

    Science.gov (United States)

    Mahmud, Hasan; Scherpen, Frank J.G.; de Boer, Tiny Meeuwsen; 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 previous peptide microarray. PLC-γ1 is known to play a role in cancer progression, however, the impact of PLC-γ1 in AML is currently unknown. Therefore, we aimed to study the functional role of PLC-γ1 by investigating the cellular growth, survival and its underlying mechanism in t(8;21) AML. In this study, PLC-γ1 expression was significantly higher in t(8;21) AML compared to other karyotypes. The PLC-γ1 protein expression was suppressed in AML1-ETO knock down cells indicating that it might induce kasumi-1 cell death. ShRNA-mediated PLC-γ1 knockdown in kasumi-1 cells significantly blocked cell growth, induced apoptosis and cell cycle arrest which was explained by the increased activation of apoptotic related and cell cycle regulatory protein expressions. Gene expression array analysis showed the up-regulation of apoptotic and DNA damage response genes together with the downregulation of cell growth, proliferation and differentiation genes in the PLC-γ1 suppressed kasumi-1 cells, consistent with the observed phenotypic effects. Importantly, PLC-γ1 suppressed kasumi-1 cells showed higher chemosensitivity to the chemotherapeutic drug treatments and lower cell proliferation upon hypoxic stress. Taken together, these in vitro finding strongly support an important role for PLC-γ1 in the survival of t(8;21) AML mimicking kasumi-1 cells and identify PLC-γ1 as a potential therapeutic target for t(8;21) AML treatment.

  4. Brain in macro experiential context: biocultural co-construction of lifespan neurocognitive development.

    Science.gov (United States)

    Li, Shu-Chen

    2009-01-01

    For more than a century, neuroscientists have recognized that the brain is an open, adaptive system and that the organism's experiences are environmentally contextualized. However, the proposition that socio-cultural contexts may exert reciprocal influences on neurobiological mechanisms is rarely considered and could not be empirically explored until very recently. This article reviews the emerging trend of interdisciplinary research aiming at exploring the effects of socio-cultural influences on human brain functioning. Recent co-constructive views of brain development and functioning and empirical evidence of developmental plasticity at different levels are reviewed. Empirical findings that are indicative of reciprocal influences of social contexts, culture-specific language environment, and expertise training are highlighted. The quest to understand how individual brains get personalized through lifespan development that takes place in the macro socio-cultural experiential context is still at an embryonic stage. Nevertheless, studies reviewed here indicate that new conceptual and empirical opportunities for this endeavor are emerging.

  5. A macro-micro robot for precise force applications

    Science.gov (United States)

    Marzwell, Neville I.; Wang, Yulun

    1993-01-01

    This paper describes an 8 degree-of-freedom macro-micro robot capable of performing tasks which require accurate force control. Applications such as polishing, finishing, grinding, deburring, and cleaning are a few examples of tasks which need this capability. Currently these tasks are either performed manually or with dedicated machinery because of the lack of a flexible and cost effective tool, such as a programmable force-controlled robot. The basic design and control of the macro-micro robot is described in this paper. A modular high-performance multiprocessor control system was designed to provide sufficient compute power for executing advanced control methods. An 8 degree of freedom macro-micro mechanism was constructed to enable accurate tip forces. Control algorithms based on the impedance control method were derived, coded, and load balanced for maximum execution speed on the multiprocessor system.

  6. Micro-origin of Macro-strength: Friction

    CERN Document Server

    Jerves, Alex X

    2012-01-01

    This paper presents an analytical study about the behavior of arbitrary shaped and sized non-cohesive two-dimensional granular materials. Several mechanical properties and relations are unraveled by connecting micro and macro scales in an explicit fashion that, at the same time, provides the basis of an analytical-theoretical framework for the development of new multi-scale techniques. Furthermore, the work herein presented is based on three main ideas that are developed and connected progressively; namely, the obtention of explicit expressions that enable us to relate micro-scale parameters, such as contact forces and fabric, to stress as a macro (continuum) physical property. Then, with these powerful tools, physical connections and relations between the mentioned micro-parameters and macro-constitutive parameters, in specific, Mohr-Coulomb's mobilized internal friction angle, are established. Finally, a non-linear optimization problem, which includes physical constraints at the contact point level, is prop...

  7. A Macro for Reusing Abstract Functions and Theorems

    Directory of Open Access Journals (Sweden)

    Sebastiaan J. C. Joosten

    2013-04-01

    Full Text Available Even though the ACL2 logic is first order, the ACL2 system offers several mechanisms providing users with some operations akin to higher order logic ones. In this paper, we propose a macro, named instance-of-defspec, to ease the reuse of abstract functions and facts proven about them. Defspec is an ACL2 book allowing users to define constrained functions and their associated properties. It contains macros facilitating the definition of such abstract specifications and instances thereof. Currently, lemmas and theorems derived from these abstract functions are not automatically instantiated. This is exactly the purpose of our new macro. instance-of-defspec will not only instantiate functions and theorems within a specification but also many more functions and theorems built on top of the specification. As a working example, we describe various fold functions over monoids, which we gradually built from arbitrary functions.

  8. Micro and Macro Segregation in Alloys Solidifying with Equiaxed Morphology

    Science.gov (United States)

    Stefanescu, Doru M.; Curreri, Peter A.; Leon-Torres, Jose; Sen, Subhayu

    1996-01-01

    To understand macro segregation formation in Al-Cu alloys, experiments were run under terrestrial gravity (1g) and under low gravity during parabolic flights (10(exp -2) g). Alloys of two different compositions (2% and 5% Cu) were solidified at two different cooling rates. Systematic microscopic and SEM observations produced microstructural and segregation maps for all samples. These maps may be used as benchmark experiments for validation of microstructure evolution and segregation models. As expected, the macro segregation maps are very complex. When segregation was measured along the central axis of the sample, the highest macro segregation for samples solidified at 1g was obtained for the lowest cooling rate. This behavior is attributed to the longer time available for natural convection and shrinkage flow to affect solute redistribution. In samples solidified under low-g, the highest macro-segregation was obtained at the highest cooling rate. In general, low-gravity solidification resulted in less segregation. To explain the experimental findings, an analytical (Flemings-Nereo) and a numerical model were used. For the numerical model, the continuum formulation was employed to describe the macroscopic transports of mass, energy, and momentum, associated with the microscopic transport phenomena, for a two-phase system. The model proposed considers that liquid flow is driven by thermal and solutal buoyancy, and by solidification shrinkage. The Flemings-Nereo model explains well macro segregation in the initial stages of low-gravity segregation. The numerical model can describe the complex macro segregation pattern and the differences between low- and high-gravity solidification.

  9. Trivariate Local Lagrange Interpolation and Macro Elements of Arbitrary Smoothness

    CERN Document Server

    Matt, Michael Andreas

    2012-01-01

    Michael A. Matt constructs two trivariate local Lagrange interpolation methods which yield optimal approximation order and Cr macro-elements based on the Alfeld and the Worsey-Farin split of a tetrahedral partition. The first interpolation method is based on cubic C1 splines over type-4 cube partitions, for which numerical tests are given. The second is the first trivariate Lagrange interpolation method using C2 splines. It is based on arbitrary tetrahedral partitions using splines of degree nine. The author constructs trivariate macro-elements based on the Alfeld split, where each tetrahedron

  10. Inverse kinematics model of parallel macro-micro manipulator system

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    An improved design, which employs the integration of optic, mechanical and electronic technologies for the next generation large radio telescope, is presented in this note. The authors propose the concept of parallel macro-micro manipulator system from the feed support structure with a rough tuning subsystem based on a cable structure and a fine tuning subsystem based on the Stewart platform. According to the requirement of astronomical observation, the inverse kinematics model of this parallel macro-micro manipulator system is deduced. This inverse kinematics model is necessary for the computer-controlled motion of feed.

  11. STUDENTS OF ECONOMICS’ ANXIETY TOWARDS ENGLISH LANGUAGE LEARNING

    Directory of Open Access Journals (Sweden)

    Gulnara Faritovna Kalganova

    2016-02-01

    Full Text Available This study explores language anxiety which has shown a substantially negative impact on performance. This paper reveals four related levels of language anxiety such as communication apprehension, test anxiety, fear of negative evaluation, level of language performance, and their correlations with macro and micro social variables like age, gender, bilingual environment.A total 103 male and female English-language learners of the Economic faculty, Federal Kazan University, completed two questionnaires: a background questionnaire and the Foreign Language Classroom Anxiety Scale.The results showed that girls experience greater psychological discomfort in the process of foreign language learning; the greatest concern of students is language anxiety in test situations; first-year students as a whole are more susceptible to language anxiety.The task of a teacher is to create a favorable psychological climate in the classroom of a foreign language in order to removing barriers to development and a better perception of the subject matter.

  12. 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)

  13. RELATIVIZATION IN KAINGANG LANGUAGE

    Directory of Open Access Journals (Sweden)

    Luciana Pereira TABOSA

    2013-12-01

    Full Text Available This paper it´s about the description and analysis of relative clauses of kaingang language, which belongs to the linguistic family Ge, trunk Macro-Ge. The theoretical framework adopted to investigate the relative clauses of that language is based on authors who address their thinking under the functional perspective, such as Givón (1979, Keenan (1985, Keenan and Comrie (1997, Payne (1997 and Andrews (2007. According to these authors, the relative clause is a subordinate clause that functions as a modifier of the core of a noun phrase. The analysis and description of relative clauses aim to see how these clauses are manifested into those parameters that distinguish the relative clauses in languages . The corpus consists of data collected with indigenous informants from Apucaraninha Indigenous Land, located in the city of Tamarana-PR. The analysis indicates that the kaingang language does not present a formal relativization, in other words, with the use of any relativizing, the subordination of phrases on the main clause occurs in semantic terms. Although there are no grammatical marks in the relativized noun phrase, relative clause fulfills its role of modifier, giving communicative purposes to phrases.

  14. Will we think in programming languages?

    Directory of Open Access Journals (Sweden)

    Jiří Fišer

    2012-12-01

    Full Text Available Modern science commonly uses computer modelling. Thousands of scientific model are daily transformed to computers programs and tested. The transformation must overcome the gap between abstract human formal notation and low level semantics of contemporary programming languages. The simultaneous knowledge of specific scientific models and programming languages is an unpleasant necessity for a significant proportion of scientists and practitioners (engineers, economist, etc.. But a solution exists — accommodation of programming languages to mental models of their users. The article discuss one partial solution — implementation of domain specific languages in the heart of existing universal languages by mechanisms of metaprogramming. This mechanism overcomes limitations of classical programming languages and complexity of creation new languages from scratch. However, the support of metaprogramming in contemporary languages is limited to isolated and peripheral constructs in very few languages. These constructs are demonstrated by simplified but real examples (metaobject system of Python, monads in F# and macro-based metaprogramming of Boo language together with discussion of their advantages and disadvantages. The discussion of examples is aimed to finding requirements for new languages and their implementation in a original (parent language.

  15. 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.

  16. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice.

    Science.gov (United States)

    Etchin, J; Montero, J; Berezovskaya, A; Le, B T; Kentsis, A; Christie, A L; Conway, A S; Chen, W C; Reed, C; Mansour, M R; Ng, C E L; Adamia, S; Rodig, S J; Galinsky, I A; Stone, R M; Klebanov, B; Landesman, Y; Kauffman, M; Shacham, S; Kung, A L; Wang, J C Y; Letai, A; Look, A T

    2016-01-01

    Currently available combination chemotherapy for acute myeloid leukemia (AML) often fails to result in long-term remissions, emphasizing the need for novel therapeutic strategies. We reasoned that targeted inhibition of a prominent nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating cells (LICs) whose survival depends on timely XPO1-mediated transport of specific protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral antagonist of XPO1 that is currently in clinical trials, has strong activity against primary AML cells while sparing normal stem and progenitor cells. Importantly, limiting dilution transplantation assays showed that this cytotoxic activity is not limited to the rapidly proliferating bulk population of leukemic cells but extends to the LICs, whose inherent drug resistance and unrestricted self-renewal capacity has been implicated in the difficulty of curing AML patients with conventional chemotherapy alone.

  17. 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

    of Pediatric Hematology and Oncology (NOPHO). METHODS: A population-based cohort of children treated for AML according to the NOPHO-AML-84, -88, and -93 trials included 138 eligible survivors of whom 102 (74%) completed a questionnaire and 104 (75%) had a clinical examination and blood sampling performed....... Eighty-five of 94 (90%) eligible sibling controls completed a similar questionnaire. Siblings had no clinical examination or blood sampling performed. RESULTS: At a median of 11 years (range 4-25) after diagnosis, renal, gastrointestinal, and hepatic disorders were rare both in survivors of childhood AML...... pressure, and eight survivors had slightly elevated diastolic blood pressure. These persons all had normal creatinine and cystatin C levels. Marginal abnormalities in potassium, magnesium, calcium, or bicarbonate levels were found in 34 survivors. CONCLUSION: Survivors of childhood AML treated...

  18. Celastrol Induces Cell Apoptosis and Inhibits the Expression of the AML1-ETO/C-KIT Oncoprotein in t(8;21 Leukemia

    Directory of Open Access Journals (Sweden)

    Xianjun Yu

    2016-04-01

    Full Text Available Resistance to chemotherapy is a major challenge to improving overall survival in Acute Myeloid Leukemia (AML. Therefore, the development of innovative therapies and the identification of more novel agents for AML are urgently needed. Celastrol, a compound extracted from the Chinese herb Tripterygium wilfordii Hook, exerts anticancer activity. We investigated the effect of celastrol in the t(8;21 AML cell lines Kasumi-1 and SKNO-1. We demonstrated that inhibition of cell proliferation activated caspases and disrupted mitochondrial function. In addition, we found that celastrol downregulated the AML1-ETO fusion protein, therefore downregulating C-KIT kinases and inhibiting AKT, STAT3 and Erk1/2. These findings provide clear evidence that celastrol might provide clinical benefits to patients with t(8;21 leukemia.

  19. AML-M2 with der(18t(1;18(q2?;p11.3 in addition to t(8;21 and del(9q

    Directory of Open Access Journals (Sweden)

    Bakshi Sonal

    2004-01-01

    Full Text Available We report a case of Acute Myeloid Leukemia with clinical features suggestive of AML-M3 and 46,XX,t(8;21,del(9q,der(18t(1;18 karyotype leading to the final diagnosis AML-M2 in light of t(8;21. The Deletion (9q is a frequent secondary anomaly to the t(8;21(q22;q22 in AML-M2. In addition to these two AML-M2 related rearrangements we also observed der(18t(1;18(q2?;p11.3 which may be an unusual rearrangement. This rearrangement resulted into partial trisomy of chromosome #1(q2? without the loss of any part of chromosome 18, morphologically. Rearrangements of long arm of chromosome 1 that result in complete or partial trisomy for 1q mostly involved the region q25-q32, which may confer a proliferation advantage.

  20. 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

    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...... as an epigenetically silenced growth suppressor, suggesting a possible role of ROS in the malignant phenotype in AML....

  1. Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

    OpenAIRE

    Yotnda, P.; Garcia,F.; Peuchmaur, M.; Grandchamp, B.; Duval, M.; Lemonnier, F; Vilmer, E; Langlade-Demoyen, P

    1998-01-01

    Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > ...

  2. Reproductive decision-making in a macro-micro environment

    NARCIS (Netherlands)

    Philipov, D.; Liefbroer, A.C.; Klobas, J.E.

    2015-01-01

    - Takes a new approach to understanding Europe’s fertility gap - Demonstrates how the macro-level environment affects micro-level decision-making - Provides new insights into how people make decisions about having children as well as how policies affect fertility This book provides new insights into

  3. Pigment encapsulation by emulsion polymerization using macro-RAFT copolymers.

    Science.gov (United States)

    Nguyen, Duc; Zondanos, Hollie S; Farrugia, Jason M; Serelis, Algirdas K; Such, Chris H; Hawkett, Brian S

    2008-03-04

    A new method is described, based on living amphipathic random macro-RAFT copolymers, which enables the efficient polymeric encapsulation of both inorganic and organic particulate materials via free-radical polymerization. The mechanism for this new approach is examined in the context of the polymer coating of zirconia- and alumina-coated titanium dioxide particles and its breadth of application demonstrated by the coating of organic phthalocyanine blue pigment particles. The particulate materials were first dispersed in water using a macro-RAFT copolymer as a stabilizer. Monomer and water-soluble initiator were then added to the system, and the monomer polymerized to form the coating. If nucleation of new polymer particles in the aqueous phase was to be avoided, it was found necessary to use a macro-RAFT copolymer that did not form micelles; within this constraint, a broad range of RAFT agents could be used. The macro-RAFT agents used in this work were found not to transfer competitively in the aqueous phase and therefore did not support growth of aqueous-phase polymer. Successful encapsulation of particles was demonstrated by TEM. The process described enables 100% of the particles to be encapsulated with greater than 95% of the polymer finishing up in the polymeric shells around the particles. Moreover, the coating reaction can be carried out at greater than 50% solids in many cases and avoids the agglomeration of particles during the coating step.

  4. Exploring the Macro-Micro Dynamic in Data Use Practice

    Science.gov (United States)

    Moss, Pamela A.

    2012-01-01

    In their opening comments to this special issue on data use, Coburn and Turner point to "one of the most central questions in social theory: the interrelationship between macro-social structure and micro-level action." Questions about data use--which entail social phenomena that range from federal policy to moment-to-moment interactions…

  5. Le pilotage macro-budgétaire des finances locales

    OpenAIRE

    Husson, Jean-François; Steckel, Marie-Christine

    2009-01-01

    Ce bref article présente les justifications et modalités de mise en oeuvre du pilotage macro-budgétaire des finances locales, c.-à-d. de leur intégration dans le pilotage global du secteur des administrations publiques tant en termes de solde de financement que de dette.

  6. Portraying Monsters: Framing School Bullying through a Macro Lens

    Science.gov (United States)

    Horton, Paul

    2016-01-01

    This article critically considers the discourse on school bullying through the conceptual framework of lenses and argues that a macro lens has been utilised by school bullying researchers to bring into focus the characteristics of the individuals involved and the types of actions used. By considering earlier understandings of bullying, the article…

  7. Micro, meso and macro issues emerging from focus group ...

    African Journals Online (AJOL)

    To understand the perceptions and experiences of HIV management in ... curriculum design; underlying concerns relating to HIV management and ... At a macro level, participants felt that the political nature of HIV and curriculum structure were ... AJOL jobs · More about AJOL · AJOL's Partners · Contact AJOL · Terms and ...

  8. Heralded generation of a micro-macro entangled state

    DEFF Research Database (Denmark)

    Andersen, Ulrik Lund; Neergaard-Nielsen, Jonas Schou

    2013-01-01

    Using different optical setups based on squeezed state and photon subtraction we show how optical entanglement between a macroscopic and a microscopic state-the so-called Schro¨dinger cat state or micro-macro state-can be generated. The entangled state is heralded and is thus produced a priori...

  9. A macro-mechanical constitutive model for shape memory polymer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    It is of theoretical and engineering interest to establish a macro-mechanical constitutive model of the shape memory polymer (SMP), which includes the mechanical constitutive equation and the material parameter function, from the viewpoint of practical application. In this paper, a new three-dimensional macro-mechanical constitutive equation, which describes the mechanical behaviors associated with the shape memory effect of SMP, is developed based on solid mechanics and the viscoelasticity theorem. According to the results of the DMA test, a new material parameter function is established to express the relationship of the material parameters and temperature during the glass transition of SMP. The new macro-mechanical constitutive equation and material parameter function are used to numerically simulate the process producing the shape memory effect of SMP, which includes deforming at high temperature, stress freezing, unloading at low temperature and shape recovery. They are also used to investigate and analyze the influences of loading rate and temperature change rate on the thermo-mechanical behaviors of SMP. The numerical results and the comparisons with Zhou’s material parameter function and Tobushi’s mechanical constitutive equation illustrate that the proposed three-dimensional macro-mechanical constitutive model can effectively predict the thermo-mechanical behaviors of SMP under the state of complex stress.

  10. Macro-Prudential Policies to Mitigate Financial System Vulnerabilities

    NARCIS (Netherlands)

    Claessens, S.; Ghosh, S.R.; Mihet, R.

    2014-01-01

    Macro-prudential policies aimed at mitigating systemic financial risks have become part of the policy toolkit in many emerging markets and some advanced countries. Their effectiveness and efficacy are not well-known, however. Using panel data regressions, we analyze how changes in balance sheets of

  11. Study of atmospheric neutrinos with the MACRO detector

    CERN Document Server

    Scapparone, E

    2003-01-01

    The MACRO experiment detected different categories of atmospheric muon neutrinos. We describe in this paper the energy estimate of upward throughgoing muons by using the multiple coulomb scattering. Combining the results of such analysis with the upgoing muon angular distribution, both not using the absolute nu flux normalization information, an evidence above 4 sigma for atmospheric neutrino oscillation is found. (7 refs).

  12. Macro-pyramid in GaN Film

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jing; YANG Zhi-Jian; XU Shi-Fa; ZHU Xing; ZHANG Guo-Yi

    2001-01-01

    A thin film of GaN with the thickness of 1.0μm was grown on α-Al2Oa substrate by metal organic chemical vapour disposition and then a thick GaN film with thickness of 12μm was grown in the halide vapour phase epitaxy system. Some macro-pyramids appeared on the surface of the sample. The macro-pyramids made the surfaceof the GaN film rough, which was harmful to the devices made by GaN materials. These defects changed the distribution of carrier concentration and affected the optical properties of GaN. The step height of the pyramids was about 30-40 nm measured by atomic force microscopy. A simple model was proposed to explain the macro- pyramid phenomenon compared with the growth spiral The growth of the macro-pyramid was relative to the physical conditions in the reaction zone. Both increasing growth temperature and low pressure may reduce the pyramid size.

  13. A Calculus of Macro-Events: Progress Report

    Science.gov (United States)

    2000-01-01

    1410, USA iliano@itd.nrl.navy.mil Angelo Montanari Dipartimento di Matematica e Informatica Universita di Udine Via delle Scienze, 206 { 33100 Udine...nition of ECTD-structure only by the following points: M MT is a set of macro-events over T . The codomain of [jji and hjj] are rede ned to be

  14. Macro-Prudential Policies to Mitigate Financial System Vulnerabilities

    NARCIS (Netherlands)

    Claessens, S.; Ghosh, S.R.; Mihet, R.

    2014-01-01

    Macro-prudential policies aimed at mitigating systemic financial risks have become part of the policy toolkit in many emerging markets and some advanced countries. Their effectiveness and efficacy are not well-known, however. Using panel data regressions, we analyze how changes in balance sheets of

  15. The MARKAL-MACRO model and the climate change

    Energy Technology Data Exchange (ETDEWEB)

    Kypreos, S. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1996-07-01

    MARKAL-MACRO and its extensions is a model appropriate to study partial and general equilibrium in the energy markets and the implications of the carbon dioxide mitigation policy. The main advantage of MM is the explicit treatment of energy demand, supply and conversion technologies, including emission control and conservation options, within a general equilibrium framework. The famous gap between top-down and bottom-up models is resolved and the economic implications of environmental and supply policy constraints can be captured either in an aggregated (Macro) or in a sectorial (Micro) level. The multi-regional trade version of the model allows to study questions related to efficient and equitable allocation of cost and benefits associated with the climate change issue. Finally, the stochastic version of the model allows to assess policies related to uncertain and even catastrophic effects and define appropriate hedging strategies. The report is divided in three parts: - the first part gives an overview of the new model structure. It describes its macro economic part and explains its calibration, - the second part refers to the model applications for Switzerland when analyzing the economic implications of curbing CO{sub 2} emissions or policies related to the introduction of a carbon tax, including a hedging strategy, - the last part is organized in form of Appendices and gives a mathematical description and some potential extensions of the model. It describes also a sensitivity analysis done with MARKAL-MACRO in 1992. (author) figs., tabs., refs.

  16. Portraying Monsters: Framing School Bullying through a Macro Lens

    Science.gov (United States)

    Horton, Paul

    2016-01-01

    This article critically considers the discourse on school bullying through the conceptual framework of lenses and argues that a macro lens has been utilised by school bullying researchers to bring into focus the characteristics of the individuals involved and the types of actions used. By considering earlier understandings of bullying, the article…

  17. Integrating a macro emission model with a macroscopic traffic model

    NARCIS (Netherlands)

    Klunder, G.A.; Stelwagen, U.; Taale, H.

    2013-01-01

    This paper presents a macro emission module for macroscopic traffic models to be used for assessment of ITS and traffic management. It especially focuses on emission estimates for different intersection types. It provides emission values for CO, CO2, HC, NOx, and PM10. It is applied and validated fo

  18. Reclaiming and Reimagining Macro Social Work Education: A Collective Biography

    Science.gov (United States)

    Netting, F. Ellen; O'Connor, Mary Katherine; Cole, Portia L.; Hopkins, Karen; Jones, Jenny L.; Kim, Youngmi; Leisey, Monica; Mulroy, Elizabeth A.; Rotabi, Karen Smith; Thomas, M. Lori; Weil, Marie O.; Wike, Traci L.

    2016-01-01

    The authors focus on a collective biography of 12 women social work educators, all either tenured or in tenure lines, from five different universities at the time of the study. The participants represent several aspects of macro practice including administration, planning, community practice, and policy. Beginning with reflections about coming…

  19. Operationalizing Macro-Scripts in CSCL Technological Settings

    Science.gov (United States)

    Tchounikine, Pierre

    2008-01-01

    This paper presents a conceptual analysis of the technological dimensions related to the operationalization of CSCL macro-scripts. CSCL scripts are activity models that aim at enhancing the probability that knowledge generative interactions such as conflict resolution, explanation or mutual regulation occur during the collaboration process. We…

  20. Restoration of Benthic Macro-endofauna after Reforestation of ...

    African Journals Online (AJOL)

    ... sediments and the forest densities, community composition and diversity of macro-endofauna. ... mangrove degradation leads to drastic changes in sediment characteristics as well ... biodiversity of estuarine and nearshore areas and act as .... Sand (%). 43 ± 5. 27 ± 9. 59 ± 14. 79 ± 5. Temperature (oC). 29 ± 0.5. 28 ± 0.2.

  1. Intake of macro- and micronutrients in Danish vegans.

    Science.gov (United States)

    Kristensen, Nadja B; Madsen, Mia L; Hansen, Tue H; Allin, Kristine H; Hoppe, Camilla; Fagt, Sisse; Lausten, Mia S; Gøbel, Rikke J; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf

    2015-10-30

    Since information about macro- and micronutrient intake among vegans is limited we aimed to determine and evaluate their dietary and supplementary intake. Seventy 18-61 years old Danish vegans completed a four-day weighed food record from which their daily intake of macro- and micronutrients was assessed and subsequently compared to an age-range-matched group of 1,257 omnivorous individuals from the general Danish population. Moreover, the vegan dietary and supplementary intake was compared to the 2012 Nordic Nutrition Recommendations (NNR). Dietary intake differed significantly between vegans and the general Danish population in all measured macro- and micronutrients (p vegans the intake of macro- and micronutrients (including supplements) did not reach the NNR for protein, vitamin D, iodine and selenium. Among vegan women vitamin A intake also failed to reach the recommendations. With reference to the NNR, the dietary content of added sugar, sodium and fatty acids, including the ratio of PUFA to SFA, was more favorable among vegans. At the macronutrient level, the diet of Danish vegans is in better accordance with the NNR than the diet of the general Danish population. At the micronutrient level, considering both diet and supplements, the vegan diet falls short in certain nutrients, suggesting a need for greater attention toward ensuring recommended daily intake of specific vitamins and minerals.

  2. Predicting Bond Betas using Macro-Finance Variables

    DEFF Research Database (Denmark)

    Aslanidis, Nektarios; Christiansen, Charlotte; Cipollini, Andrea

    We conduct in-sample and out-of-sample forecasting using the new approach of combining explanatory variables through complete subset regressions (CSR). We predict bond CAPM betas and bond returns conditioning on various macro-fi…nance variables. We explore differences across long-term government...

  3. Bridging the Micro-Macro Gap in Population Forecasting

    NARCIS (Netherlands)

    NIDI, .

    2011-01-01

    MicMac - Bridging the micro-macro gap in population forecasting: a study funded by the European Commission under the 6th Framework Programme "Integrating and strengthening the European Research Area". In an ageing population, the demand for adequate health care services, pension systems and other

  4. Reproductive decision-making in a macro-micro environment

    NARCIS (Netherlands)

    Philipov, D.; Liefbroer, A.C.; Klobas, J.E.

    2015-01-01

    - Takes a new approach to understanding Europe’s fertility gap - Demonstrates how the macro-level environment affects micro-level decision-making - Provides new insights into how people make decisions about having children as well as how policies affect fertility This book provides new insights into

  5. Effective Macro Control Eases Up The Economic Development

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ The outlook of the macro economic operation in 2007 cannot be separated from the comprehensive, accurate and scientific observation on the economic operation in 2006. We conclude three main issues to be illustrated on the basic characteristics of the national economic operation in 2006.

  6. Bridging the Micro-Macro Gap in Population Forecasting

    NARCIS (Netherlands)

    NIDI, .

    2011-01-01

    MicMac - Bridging the micro-macro gap in population forecasting: a study funded by the European Commission under the 6th Framework Programme "Integrating and strengthening the European Research Area". In an ageing population, the demand for adequate health care services, pension systems and other so

  7. Low-dose salinomycin induces anti-leukemic responses in AML and MLL.

    Science.gov (United States)

    Roulston, Gary D R; Burt, Charlotte L; Kettyle, Laura M J; Matchett, Kyle B; Keenan, Heather L; Mulgrew, Nuala M; Ramsey, Joanne M; Dougan, Caoifa; McKiernan, John; Grishagin, Ivan V; Mills, Ken I; Thompson, Alexander

    2016-11-08

    Development of anti-cancer drugs towards clinical application is costly and inefficient. Large screens of drugs, efficacious for non-cancer disease, are currently being used to identify candidates for repurposing based on their anti-cancer properties. Here, we show that low-dose salinomycin, a coccidiostat ionophore previously identified in a breast cancer screen, has anti-leukemic efficacy. AML and MLLr cell lines, primary cells and patient samples were sensitive to submicromolar salinomycin. Most strikingly, colony formation of normal hematopoietic cells was unaffected by salinomycin, demonstrating a lack of hemotoxicity at the effective concentrations. Furthermore, salinomycin treatment of primary cells resulted in loss of leukemia repopulation ability following transplantation, as demonstrated by extended recipient survival compared to controls. Bioinformatic analysis of a 17-gene signature identified and validated in primary MLLr cells, uncovered immunomodulatory pathways, hubs and protein interactions as potential transducers of low dose salinomycin treatment. Additionally, increased protein expression of p62/Sqstm1, encoded for by one of the 17 signature genes, demonstrates a role for salinomycin in aggresome/vesicle formation indicative of an autophagic response.Together, the data support the efficacy of salinomycin as an anti-leukemic at non-hemotoxic concentrations. Further investigation alone or in combination with other therapies is warranted for future clinical trial.

  8. 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.

  9. A Polyethylenimine-Containing and Transferrin-Conjugated Lipid Nanoparticle System for Antisense Oligonucleotide Delivery to AML

    Directory of Open Access Journals (Sweden)

    Yiming Yuan

    2016-01-01

    Full Text Available Limited success of antisense oligonucleotides (ASO in clinical anticancer therapy calls for more effective delivery carriers. The goal of this study was to develop a nanoparticle system for delivery of ASO G3139, which targets mRNA of antiapoptotic protein Bcl-2, to acute myeloid leukemia (AML cells. The synthesized nanoparticle Tf-LPN-G3139 contained a small molecular weight polyethylenimine and two cationic lipids as condensing agents, with transferrin on its surface for selective binding and enhanced cellular uptake. The optimized nitrogen to phosphate (N/P ratio was 4 to achieve small particle size and high G3139 entrapment efficiency. The Tf-LPN-G3139 exhibited excellent colloidal stability during storage for at least 12 weeks and remained intact for 4 hours in nuclease-containing serum. The cellular uptake results showed extensive internalization of fluorescence-labelled G3139 in MV4-11 cells through Tf-LPN. Following transfection, Tf-LPN-G3139 at 1 µM ASO level induced 54% Bcl-2 downregulation and >20-fold apoptosis compared to no treatment. When evaluated in mice bearing human xenograft AML tumors, Tf-LPN-G3139 suppressed tumor growth by ~60% at the end of treatment period, accompanied by remarkable pharmacological effect of Bcl-2 inhibition in tumor. In conclusion, Tf-LPN-G3139 is a promising nanoparticle system for ASO G3139 delivery to AML and warrants further investigations.

  10. RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT

    Science.gov (United States)

    Beohou, Eric; Labopin, Myriam; Sanz, Guillermo; Milpied, Noel; Michallet, Mauricette; Bacigalupo, Andrea; Blaise, Didier; Sierra, Jorge; Socié, Gérard; Cornelissen, Jan J.; Schmid, Christoph; Giebel, Sebastian; Gorin, Norbert-Claude; Esteve, Jordi; Ciceri, Fabio; Savani, Bipin N.; Mohty, Mohamad; Gluckman, Eliane; Nagler, Arnon

    2016-01-01

    Nonrelapse mortality (NRM) is the first cause of treatment failure after unrelated cord blood transplantation (UCBT) following myeloablative conditioning (MAC). In the last decade, reduced-intensity conditioning (RIC) regimens have been developed with the aim of reducing NRM and allowing older patients and those with medical comorbidities to benefit from UCBT. The aim of the current retrospective study was to compare transplantation outcomes of acute myeloid leukemia (AML) patients given UCBT after either RIC or MAC. Data from 894 adults with AML receiving a single or double UCBT as first allograft from 2004 to 2013 at EBMT centers were included in this study. 415 patients were given UCBT after RIC while 479 patients following a MAC. In comparison to MAC recipients, RIC recipients had a similar incidence of neutrophil engraftment and of acute and chronic graft-versus-host disease (GVHD). However, RIC recipients had a higher incidence of disease relapse and a lower NRM, translating to comparable leukemia-free (LFS), GVHD-free, relapse-free survival (GRFS) and overall survival (OS). These observations remained qualitatively similar after adjusting for differences between groups in multivariate analyses. In conclusion, these data suggest that LFS and OS are similar with RIC or with MAC in adults AML patients transplanted with UCBT. These observations could serve as basis for a future prospective randomized study. PMID:27250025

  11. Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia.

    Science.gov (United States)

    Pession, Andrea; Masetti, Riccardo; Rizzari, Carmelo; Putti, Maria Caterina; Casale, Fiorina; Fagioli, Franca; Luciani, Matteo; Lo Nigro, Luca; Menna, Giuseppe; Micalizzi, Concetta; Santoro, Nicola; Testi, Anna Maria; Zecca, Marco; Biondi, Andrea; Pigazzi, Martina; Rutella, Sergio; Rondelli, Roberto; Basso, Giuseppe; Locatelli, Franco

    2013-07-11

    We evaluated the outcome of 482 children with acute myeloid leukemia (AML) enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 trial. Treatment was stratified according to risk group; hematopoietic stem cell transplantation (HSCT) was used in high-risk (HR) children. Patients with core binding factor leukemia achieving complete remission (CR) after the first induction course were considered standard risk (SR; 99 patients), whereas the others (n = 383) were assigned to the HR group. Allogeneic (ALLO) or autologous (AUTO) HSCT was employed, respectively, in 141 and 102 HR patients after consolidation therapy. CR, early death, and induction failure rates were 87%, 3%, and 10%, respectively. Relapse occurred in 24% of patients achieving CR. The 8-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 68%, 55%, and 63%, respectively. OS, EFS, and DFS for SR and HR patients were 83%, 63%, and 66% and 64%, 53%, and 62%. DFS was 63% and 73% for HR patients given AUTO-HSCT and ALLO-HSCT, respectively. In multivariate analysis, risk group, white blood cell >100 × 10(9)/L at diagnosis, and monosomal karyotype predicted poorer EFS. Risk-oriented treatment and broad use of HSCT result in a long-term EFS comparing favorably with previously published studies on childhood AML.

  12. Mapping of the mouse homolog of the human runt domain gene, AML2, to the distal region of mouse chromosome 4

    Energy Technology Data Exchange (ETDEWEB)

    Avraham, K.B.; Copeland, N.G.; Jenkins, N.A. [National Cancer Institute-Frederick Cancer Research and Development Center, MD (United States)] [and others

    1995-01-20

    AML2 is a runt domain belonging to a group of transcription factors that appear to play a role in Drosophila embryogenesis and mammalian oncogenic transformation. AML2 maps to human chromosome 1p36, a region involved in the t(1;3)(p36;q21) translocation found in association with myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), and acute nonlymphocytic leukemia. 9 refs., 1 fig.

  13. CD8(+)T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients.

    Science.gov (United States)

    Wang, Mengjie; Bu, Jin; Zhou, Maohua; Sido, Jessica; Lin, Yu; Liu, Guanfang; Lin, Qiwen; Xu, Xiuzhang; Leavenworth, Jianmei W; Shen, Erxia

    2017-09-08

    Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults with an overall poor prognosis and very limited treatment management. Immune checkpoint blockade of PD-1 alone or combined with other immune checkpoint blockade has gained impressive results in murine AML models by improving anti-leukemia CD8(+)T cell function, which has greatly promoted the strategy to utilize combined immune checkpoint inhibitors to treat AML patients. However, the expression profiles of these inhibitory receptors in T cells from AML patients have not been clearly defined. Here we have defined subsets of CD8(+) and CD4(+) T cells in the peripheral blood (PB) from newly diagnosed AML patients and healthy controls (HCs). We have observed increased frequencies of PD-1- and TIGIT expressing CD8(+) T cells but decreased occurrence of CD226-expressing CD8(+)T cells in AML patients. Further analysis of these CD8(+) T cells revealed a unique CD8(+) T cell subset that expressed PD-1 and TIGIT but displayed lower levels of CD226 was associated with failure to achieve remission after induction chemotherapy and FLT3-ITD mutations which predict poor clinical prognosis in AML patients. Importantly, these PD-1(+)TIGIT(+)CD226(-)CD8(+)T cells are dysfunctional with lower expression of intracellular IFN-γ and TNF-α than their counterparts in HCs. Therefore, our studies revealed that an increased frequency of a unique CD8(+) T cell subset, PD-1(+)TIGIT(+)CD226(-)CD8(+) T cells, is associated with CD8(+)T cell dysfunction and poor clinical prognosis of AML patients, which may reveal critical diagnostic or prognostic biomarkers and direct more efficient therapeutic strategies. Copyright © 2017. Published by Elsevier Inc.

  14. Effect of the histone deacetylase inhibitor depsipeptide on B-cell differentiation in both TEL-AML1-positive and negative childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Stams, Wendy A G; den Boer, Monique L; Beverloo, H Berna; Kazemier, Karin M; van Wering, Elisabeth R; Janka-Schaub, Gritta E; Pieters, Rob

    2005-12-01

    The fusion protein TEL-AML1 in t(12;21)+ acute lymphoblastic leukemia (ALL) recruits co-repressors and histone deacetylases (HDAC), which transrepress AML1 target genes. Normal bone marrow cells were more resistant to HDAC inhibitor FK228 induced cell killing than were cells from ALL patients with or without t(12;21). FK228 induced differentiation in ALL, irrespective of the presence of t(12;21).

  15. Epigenetic priming of AML blasts for all-trans retinoic acid-induced differentiation by the HDAC class-I selective inhibitor entinostat.

    Directory of Open Access Journals (Sweden)

    Nadja Blagitko-Dorfs

    Full Text Available All-trans retinoic acid (ATRA has only limited single agent activity in AML without the PML-RARα fusion (non-M3 AML. In search of a sensitizing strategy to overcome this relative ATRA resistance, we investigated the potency of the HDAC class-I selective inhibitor entinostat in AML cell lines Kasumi-1 and HL-60 and primary AML blasts. Entinostat alone induced robust differentiation of both cell lines, which was enhanced by the combination with ATRA. This "priming" effect on ATRA-induced differentiation was at least equivalent to that achieved with the DNA hypomethylating agent decitabine, and could overall be recapitulated in primary AML blasts treated ex vivo. Moreover, entinostat treatment established the activating chromatin marks acH3, acH3K9, acH4 and H3K4me3 at the promoter of the RARβ2 gene, an essential mediator of retinoic acid (RA signaling in different solid tumor models. Similarly, RARβ2 promoter hypermethylation (which in primary blasts from 90 AML/MDS patients was surprisingly infrequent could be partially reversed by decitabine in the two cell lines. Re-induction of the epigenetically silenced RARβ2 gene was achieved only when entinostat or decitabine were given prior to ATRA treatment. Thus in this model, reactivation of RARβ2 was not necessarily required for the differentiation effect, and pharmacological RARβ2 promoter demethylation may be a bystander phenomenon rather than an essential prerequisite for the cellular effects of decitabine when combined with ATRA. In conclusion, as a "priming" agent for non-M3 AML blasts to the differentiation-inducing effects of ATRA, entinostat is at least as active as decitabine, and both act in part independently from RARβ2. Further investigation of this treatment combination in non-M3 AML patients is therefore warranted, independently of RARβ2 gene silencing by DNA methylation.

  16. Visual compression of workflow visualizations with automated detection of macro motifs.

    Science.gov (United States)

    Maguire, Eamonn; Rocca-Serra, Philippe; Sansone, Susanna-Assunta; Davies, Jim; Chen, Min

    2013-12-01

    This paper is concerned with the creation of 'macros' in workflow visualization as a support tool to increase the efficiency of data curation tasks. We propose computation of candidate macros based on their usage in large collections of workflows in data repositories. We describe an efficient algorithm for extracting macro motifs from workflow graphs. We discovered that the state transition information, used to identify macro candidates, characterizes the structural pattern of the macro and can be harnessed as part of the visual design of the corresponding macro glyph. This facilitates partial automation and consistency in glyph design applicable to a large set of macro glyphs. We tested this approach against a repository of biological data holding some 9,670 workflows and found that the algorithmically generated candidate macros are in keeping with domain expert expectations.

  17. [Heavy metal pollution ecology of macro-fungi: research advances and expectation].

    Science.gov (United States)

    Zhou, Qi-xing; An, Xin-long; Wei, Shu-he

    2008-08-01

    Macro-fungi are the main component of biosphere and one of the ecological resources, and play very important roles in matter cycling and in maintaining ecological balances. This paper summarized and reviewed the research advances in the eco-toxicological effects of heavy metals on macro-fungi, the bioaccumulation function of macro-fungi on heavy metals, the ecological adaptation mechanisms of macro-fungi to heavy metal pollution, the role of macro-fungi as a bio-indicator of heavy metal pollution, and the potential of macro-fungi in the ecological remediation of contaminated environment. To strengthen the researches on the heavy metal pollution ecology of macro-fungi would be of practical significance in the reasonable utilization of macro-fungi resources and in the ecological remediation of contaminated environment.

  18. The characteristic of marketing macro environment of European developing countries and Ukraine for company's marketing activity

    OpenAIRE

    Peresadko, Galina; Bakastov, Ihor

    2013-01-01

    Іn the report the comparative analysis of different European macro-marketing in developing countries and Ukraine. The analysis of the demographic, economic, natural, technological, political and cultural factors. Also the perspectives for Ukraine's marketing macro environment.

  19. Usual Dietary Intakes: SAS Macros for Fitting Multivariate Measurement Error Models & Estimating Multivariate Usual Intake Distributions

    Science.gov (United States)

    The following SAS macros can be used to create a multivariate usual intake distribution for multiple dietary components that are consumed nearly every day or episodically. A SAS macro for performing balanced repeated replication (BRR) variance estimation is also included.

  20. 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.

  1. A Call for (Trans)languaging: The Language Profiles at Roskilde University

    DEFF Research Database (Denmark)

    Daryai-Hansen, Petra; Barfod, Sonja; Schwarz, Lena

    2016-01-01

    is put into educational practice, thereby bridging the gap between plurilingual theory and monolingual practice. Roskilde University offers, as part of its internationalisation strategy, supplementary, curriculum-related courses in French and German to all students in the bachelor programs...... objectives of RUC’s language profiles. Furthermore we discuss, based on the language profiles as an example, how translanguaging practices and policies can be described on a supra, macro, meso, micro and nano level. The analysis focuses on teachers’ and students’ translanguaging practices and their attitudes...... towards translanguaging in language teaching/learning....

  2. Social Positioning, Participation, and Second Language Learning: Talkative Students in an Academic ESL Classroom

    Science.gov (United States)

    Kayi-Aydar, Hayriye

    2014-01-01

    Guided by positioning theory and poststructural views of second language learning, the two descriptive case studies presented in this article explored the links between social positioning and the language learning experiences of two talkative students in an academic ESL classroom. Focusing on the macro- and micro-level contexts of communication,…

  3. Simultaneous and Successive Second Language Learning: Integral Ingredients of the Human Development Process.

    Science.gov (United States)

    Mushi, Selina L. P.

    2002-01-01

    Draws from sociolinguistic perspective, human development, school learning, and language policy to discuss conflicting claims about second-language learning in school. Differentiates between cultural context within micro cultures and school content within global macro culture. Asserts that educators should ensure that learners have access to the…

  4. Social Positioning, Participation, and Second Language Learning: Talkative Students in an Academic ESL Classroom

    Science.gov (United States)

    Kayi-Aydar, Hayriye

    2014-01-01

    Guided by positioning theory and poststructural views of second language learning, the two descriptive case studies presented in this article explored the links between social positioning and the language learning experiences of two talkative students in an academic ESL classroom. Focusing on the macro- and micro-level contexts of communication,…

  5. Detection and Protection of Macro-Users in Dominant Area of Co-channel CSG Cells

    DEFF Research Database (Denmark)

    Wang, Yuanye; Pedersen, Klaus; Frederiksen, Frank

    2012-01-01

    Co-channel deployment of Closed Subscriber Group (CSG) home-cells or Home E-UTRAN NodeBs (HeNBs) will create coverage holes for macro connected user that is not part of the CSG. In this paper, we address the problem of detecting the macro-cell coverage hole and protecting the macro-users that are...

  6. Impedance control of flexible macro/mini manipulators

    Science.gov (United States)

    Schubert, Heidi Christine

    Construction and maintenance of on-orbit crew-operated hardware is currently done mostly by extra-vehicular astronauts. Use of robotics for some of these tasks provides the opportunity for both increased safety for the astronauts and major cost savings. An effective space robotic manipulator must be lightweight, have a large workspace, and be capable of fine dexterous control. A large lightweight manipulator will necessarily be quite flexible, limiting the achievable end-point bandwidth. One way to achieve all of the objectives is via advanced control of a macro/mini manipulator: a large lightweight manipulator carrying a small dexterous manipulator, such as is planned for the International Space Station. The goal of this work is to control a flexible-joint macro carrying a two-arm mini manipulator. For ease of use, a low-level controller should be designed such that the user or automated planner need only command the desired end-point motions and forces. Designing an end-point controller for a macro/mini manipulator presents many challenges. Such a manipulator system is non-linear, has low frequency flexibility, and has dynamic coupling between the macro and mini. A smart method for controlling manipulators is impedance control, which specifies a desired force-velocity relationship at the end-point of the manipulator, enabling smooth contact with the environment. Using operational space control, the dynamics of the manipulator are transformed into operational coordinates for implementation of the impedance law. The operational space method also enables a secondary control of the redundant degrees of freedom, without degrading the end-point impedance task. This thesis presents new theoretical advances that enable extending the concepts of operational space and impedance control to redundant joint-flexible robots. Important advances include a new method for choosing the end-point impedance and a null-space controller that performs much better. The new control

  7. Silence in the Second Language Classrooms of Japanese Universities

    Science.gov (United States)

    King, Jim

    2013-01-01

    Japanese language learners' proclivity for silence has been alluded to by various writers (e.g. Anderson 1993; Korst 1997; Greer 2000) and is supported by plenty of anecdotal evidence, but large-scale, empirical studies aimed at measuring the extent of macro-level silence within Japanese university L2 classrooms are notably lacking. This article…

  8. Silence in the Second Language Classrooms of Japanese Universities

    Science.gov (United States)

    King, Jim

    2013-01-01

    Japanese language learners' proclivity for silence has been alluded to by various writers (e.g. Anderson 1993; Korst 1997; Greer 2000) and is supported by plenty of anecdotal evidence, but large-scale, empirical studies aimed at measuring the extent of macro-level silence within Japanese university L2 classrooms are notably lacking. This article…

  9. 基于PMAC的MACRO station的应用及设置%The Applying and the Setting of MACRO station Based on PMAC

    Institute of Scientific and Technical Information of China (English)

    王宏; 弓清忠; 王斌

    2006-01-01

    简单介绍PMAC运动控制器及MACRO station(宏运动控制站)后,结合轧辊磨床专用数控系统的建立,介绍MACRO station的应用.阐述PMAC和MACRO station中各个模块间的内在关系,以及它们和外部设备间的关系;PMAC中相关Ⅰ变量的设置方法;各种映射关系的建立,以及MACRO STATION的应用实际意义.

  10. Automation of the Weighting and its Register Using Macros; Automatizacion de la Pesada y su Registro mediante el Uso de Macro-Instrucciones

    Energy Technology Data Exchange (ETDEWEB)

    Gasco, C.; Ampudia, J.

    2005-07-01

    Macros automate a repetitive or complex task that oneself otherwise would have to execute manually. Macros have been implemented (based on Visual Basic Applications) on the laboratory calculation sheets to obtain automatically the weight-registers from the Balances. The combined utilization of the programme Balint (trademark Precisa) and macros has allowed us to transfer in real time the weight data to the sheets and later information storage. The method for using these macros has been summarised in this report. This way of working permits: to register the data of all the laboratory samples and to be available for auditory purposes. (Author) 4 refs.

  11. d Macro and (3)He macro production in square root of s(NN) = 130 GeV Au+Au collisions.

    Science.gov (United States)

    Adler, C; Ahammed, Z; Allgower, C; Amonett, J; Anderson, B D; Anderson, M; Averichev, G S; Balewski, J; Barannikova, O; Barnby, L S; Baudot, J; Bekele, S; Belaga, V V; Bellwied, R; Berger, J; Bichsel, H; Bland, L C; Blyth, C O; Bonner, B E; Boucham, A; Brandin, A; Cadman, R V; Caines, H; Calderón de la Barca Sánchez, M; Cardenas, A; Carroll, J; Castillo, J; Castro, M; Cebra, D; Chattopadhyay, S; Chen, M L; Chen, Y; Chernenko, S P; Cherney, M; Chikanian, A; Choi, B; Christie, W; Coffin, J P; Cormier, T M; Cramer, J G; Crawford, H J; DeMello, M; Deng, W S; Derevschikov, A A; Didenko, L; Draper, J E; Dunin, V B; Dunlop, J C; Eckardt, V; Efimov, L G; Emelianov, V; Engelage, J; Eppley, G; Erazmus, B; Fachini, P; Faine, V; Finch, E; Fisyak, Y; Flierl, D; Foley, K J; Fu, J; Gagunashvili, N; Gans, J; Gaudichet, L; Germain, M; Geurts, F; Ghazikhanian, V; Grabski, J; Grachov, O; Greiner, D; Grigoriev, V; Guedon, M; Gushin, E; Hallman, T J; Hardtke, D; Harris, J W; Heffner, M; Heppelmann, S; Herston, T; Hippolyte, B; Hirsch, A; Hjort, E; Hoffmann, G W; Horsley, M; Huang, H Z; Humanic, T J; Hümmler, H; Igo, G; Ishihara, A; Ivanshin, Y I; Jacobs, P; Jacobs, W W; Janik, M; Johnson, I; Jones, P G; Judd, E; Kaneta, M; Kaplan, M; Keane, D; Kisiel, A; Klay, J; Klein, S R; Klyachko, A; Konstantinov, A S; Kotchenda, L; Kovalenko, A D; Kramer, M; Kravtsov, P; Krueger, K; Kuhn, C; Kulikov, A I; Kunde, G J; Kunz, C L; Kutuev, R K; Kuznetsov, A A; Lakehal-Ayat, L; Lamas-Valverde, J; Lamont, M A; Landgraf, J M; Lange, S; Lansdell, C P; Lasiuk, B; Laue, F; Lebedev, A; LeCompte, T; Lednický, R; Leontiev, V M; LeVine, M J; Li, Q; Li, Q; Lindenbaum, S J; Lisa, M A; Ljubicic, T; Llope, W J; LoCurto, G; Long, H; Longacre, R S; Lopez-Noriega, M; Love, W A; Lynn, D; Majka, R; Margetis, S; Martin, L; Marx, J; Matis, H S; Matulenko, Y A; McShane, T S; Meissner, F; Melnick, Y; Meschanin, A; Messer, M; Miller, M L; Milosevich, Z; Minaev, N G; Mitchell, J; Moiseenko, V A; Moltz, D; Moore, C F; Morozov, V; de Moura, M M; Munhoz, M G; Mutchler, G S; Nelson, J M; Nevski, P; Nikitin, V A; Nogach, L V; Norman, B; Nurushev, S B; Odyniec, G; Ogawa, A; Okorokov, V; Oldenburg, M; Olson, D; Paic, G; Pandey, S U; Panebratsev, Y; Panitkin, S Y; Pavlinov, A I; Pawlak, T; Perevoztchikov, V; Peryt, W; Petrov, V A; Platner, E; Pluta, J; Porile, N; Porter, J; Poskanzer, A M; Potrebenikova, E; Prindle, D; Pruneau, C; Radomski, S; Rai, G; Ravel, O; Ray, R L; Razin, S V; Reichhold, D; Reid, J G; Retiere, F; Ridiger, A; Ritter, H G; Roberts, J B; Rogachevski, O V; Romero, J L; Roy, C; Russ, D; Rykov, V; Sakrejda, I; Sandweiss, J; Saulys, A C; Savin, I; Schambach, J; Scharenberg, R P; Schmitz, N; Schroeder, L S; Schüttauf, A; Schweda, K; Seger, J; Seliverstov, D; Seyboth, P; Shahaliev, E; Shestermanov, K E; Shimanskii, S S; Shvetcov, V S; Skoro, G; Smirnov, N; Snellings, R; Sowinski, J; Spinka, H M; Srivastava, B; Stephenson, E J; Stock, R; Stolpovsky, A; Strikhanov, M; Stringfellow, B; Struck, C; Suaide, A A; Sugarbaker, E; Suire, C; Sumbera, M; Symons, T J; de Toledo, A S; Szarwas, P; Takahashi, J; Tang, A H; Thomas, J H; Tikhomirov, V; Trainor, T A; Trentalange, S; Tokarev, M; Tonjes, M B; Trofimov, V; Tsai, O; Turner, K; Ullrich, T; Underwood, D G; Van Buren, G; VanderMolen, A M; Vanyashin, A; Vasilevski, I M; Vasiliev, A N; Vigdor, S E; Voloshin, S A; Wang, F; Ward, H; Watson, J W; Wells, R; Wenaus, T; Westfall, G D; Whitten, C; Wieman, H; Willson, R; Wissink, S W; Witt, R; Xu, N; Xu, Z; Yakutin, A E; Yamamoto, E; Yang, J; Yepes, P; Yokosawa, A; Yurevich, V I; Zanevski, Y V; Zborovský, I; Zhang, H; Zhang, W M; Zoulkarneev, R; Zubarev, A N

    2001-12-24

    The first measurements of light antinucleus production in Au+Au collisions at the Relativistic Heavy-Ion Collider are reported. The observed production rates for d macro and (3)He macro are much larger than in lower energy nucleus-nucleus collisions. A coalescence model analysis of the yields indicates that there is little or no increase in the antinucleon freeze-out volume compared to collisions at CERN SPS energy. These analyses also indicate that the (3)He macro freeze-out volume is smaller than the d macro freeze-out volume.

  12. Political Strategies and Language Policies: The European Union Lisbon Strategy and Its Implications for the EU's Language and Multilingualism Policy

    Science.gov (United States)

    Krzyzanowski, Michal; Wodak, Ruth

    2011-01-01

    This paper explores the interplay between the politics and policies of multilingualism by looking at the role of political macro-strategies in shaping language and multilingualism policies within the European Union. The paper focuses on the relationship between the European Union's 2000-2010 Lisbon Strategy on the European Knowledge-Based Economy…

  13. Discrete-element method simulations: from micro to macro scales.

    Science.gov (United States)

    Heyes, D M; Baxter, J; Tüzün, U; Qin, R S

    2004-09-15

    Many liquid systems encountered in environmental science are often complex mixtures of many components which place severe demands on traditional computational modelling techniques. A meso scale description is required to account adequately for their flow behaviour on the meso and macro scales. Traditional techniques of computational fluid dynamics and molecular simulation are not well suited to tackling these systems, and researchers are increasingly turning to a range of relatively new computational techniques that offer the prospect of addressing the factors relevant to multicomponent multiphase liquids on length- and time-scales between the molecular level and the macro scale. In this category, we discuss the off-lattice techniques of 'smooth particle hydrodynamics' (SPH) and 'dissipative particle dynamics' (DPD), and the grid-based techniques of 'lattice gas' and 'lattice Boltzmann' (LB). We highlight the main conceptual and technical features underpinning these methods, their strengths and weaknesses, and provide a few examples of the applications of these techniques that illustrate their utility.

  14. Macro and micro challenges for talent retention in South Africa

    Directory of Open Access Journals (Sweden)

    Berenice Kerr-Phillips

    2009-04-01

    Full Text Available The aim of the study was to explore the challenges presented in retaining South Africa’s talent at both macro (country and micro (organisational levels. Using a web-based survey placed on eight New Zealand sites, the reasons for emigration of South African talent during the period 1994–2006 were explored with 84 respondents. Utilising a purposive sampling technique, 20 semi-structured interviews were undertaken with identified ‘top talent’ in two financial services companies. Content analysis of the responses from both samples was employed. Reasons for emigration (macro issues included uncertainty about the future of the country, job insecurity and fears regarding both corruption and violent crime. Reasons for talent loss amongst identified top talent (micro issues were found to be linked to leadership, organisational culture and employment equity.

  15. Characterizing micro-macro transitions with slow light

    CERN Document Server

    Zhou, Zhifan; Glasser, Ryan T; Qin, Zhongzhong; Fang, Yami; Jing, Jietai; Zhang, Weiping

    2016-01-01

    The transition between the microscopic to the macroscopic world is of broad fundamental and technological significance. Optical parametric amplifiers allow for amplifying single photons to the macroscopic level, but the underlying temporal dynamics are still not well understood. Slow light, in which the group velocity is delayed via quantum interference, is an effective tool to interrogate the temporal dynamics of light-matter interactions. Here, we demonstrate a scheme to characterize micro-macro transitions with slow light based on a four-wave mixing linear amplification process in a hot rubidium vapour. The scheme exhibits strong dispersion which is sensitive to the input's change at the single-photon level, resulting in a nonlinear decay of the micro-macro transition time with the increased microscopic input. The present system is suitable for the study of the relevant time scale of quantum-to-classical transitions and the potential impact from fundamental effects such as gravity, as indicated by recent p...

  16. Macro-motion detection using ultra-wideband impulse radar.

    Science.gov (United States)

    Xin Li; Dengyu Qiao; Ye Li

    2014-01-01

    Radar has the advantage of being able to detect hidden individuals, which can be used in homeland security, disaster rescue, and healthcare monitoring-related applications. Human macro-motion detection using ultra-wideband impulse radar is studied in this paper. First, a frequency domain analysis is carried out to show that the macro-motion yields a bandpass signal in slow-time. Second, the FTFW (fast-time frequency windowing), which has the advantage of avoiding the measuring range reduction, and the HLF (high-pass linear-phase filter), which can preserve the motion signal effectively, are proposed to preprocess the radar echo. Last, a threshold decision method, based on the energy detector structure, is presented.

  17. Philosophy of technology and macro-ethics in engineering.

    Science.gov (United States)

    Son, Wha-Chul

    2008-09-01

    The purpose of this paper is to diagnose and analyze the gap between philosophy of technology and engineering ethics and to suggest bridging them in a constructive way. In the first section, I will analyze why philosophy of technology and engineering ethics have taken separate paths so far. The following section will deal with the so-called macro-approach in engineering ethics. While appreciating the initiative, I will argue that there are still certain aspects in this approach that can be improved. In the third, fourth, and fifth sections, I will point out three shortcomings of engineering ethics in terms of its macro-level discourse and argue that a number of certain insights taken from the study of philosophy of technology could be employed in overcoming those problems. In the concluding section, a final recommendation is made that topics of philosophy of technology be included in the curriculum of engineering ethics.

  18. Drops bouncing off macro-textured superhydrophobic surfaces

    CERN Document Server

    Moqaddam, Ali Mazloomi; Karlin, Ilya

    2016-01-01

    Recent experiments with droplets impacting a macro-textured superhydrophobic surfaces revealed new regimes of bouncing with a remarkable reduction of the contact time. We present here a comprehensive numerical study that reveals the physics behind these new bouncing regimes and quantify the role played by various external and internal forces that effect the dynamics of a drop impacting a complex surface. For the first time, three-dimensional simulations involving macro-textured surfaces are performed. Aside from demonstrating that simulations reproduce experiments in a quantitative manner, the study is focused on analyzing the flow situations beyond current experiments. We show that the experimentally observed reduction of contact time extends to higher Weber numbers, and analyze the role played by the texture density. Moreover, we report a non-linear behavior of the contact time with the increase of the Weber number for application relevant imperfectly coated textures, and also study the impact on tilted sur...

  19. Final results of magnetic monopole searches with the MACRO experiment

    CERN Document Server

    Ambrosio, M; Auriemma, G; Bakari, D; Baldini, A; Barbarino, G C; Barish, B C; Battistoni, G; Becherini, Y; Bellotti, R; Bemporad, C; Bernardini, P; Bilokon, H; Bloise, C; Bower, C; Brigida, M; Bussino, S; Cafagna, F; Calicchio, M; Campana, D; Carboni, M; Caruso, R; Cecchini, S; Cei, F; Chiarella, V; Chiarusi, T; Choudhary, B C; Coutu, S; Cozzi, M; De Cataldo, G; Dekhissi, H; De Marzo, C; De Mitri, I; Derkaoui, J E; De Vincenzi, M; Di Credico, A; Erriquez, O; Favuzzi, C; Forti, C; Fusco, P; Giacomelli, G; Giannini, G; Giglietto, N; Giorgini, M; Grassi, M; Grillo, A; Guarino, F; Gustavino, C; Habig, A; Hanson, K; Heinz, R; Iarocci, E; Katsavounidis, E; Katsavounidis, I; Kearns, E; Kim, H; Kyriazopoulou, S; Kumar, A; Lamanna, E; Lane, C; Levin, D S; Lipari, P; Longley, N P; Longo, M J; Loparco, F; Maaroufi, F; Mancarella, G; Mandrioli, G; Manzoor, S; Margiotta, A; Marini, A; Martello, D; Marzari-Chiesa, A; Matteuzzi, D; Mazziotta, M N; Michael, D G; Monacelli, P; Montaruli, T; Monteno, M; Mufson, S L; Musser, J; Nicolò, D; Nolty, R; Orth, C; Osteria, G; Palamara, O; Patera, V; Patrizii, L; Pazzi, R; Peck, C W; Perrone, L; Petrera, S; Pistilli, P; Popa, V; Rainó, A; Reynoldson, J; Ronga, F; Rrhioua, A; Satriano, C; Scapparone, E; Scholberg, K; Sciubba, A; Serra, P; Sioli, M; Sirri, G; Sitta, M; Spinelli, P; Spinetti, M; Spurio, M; Steinberg, R; Stone, J L; Sulak, L R; Surdo, A; Tarle, G; Togo, V; Vakili, M; Walter, C W; Webb, R

    2002-01-01

    We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range 4*10/sup -5/< beta <1. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of 1.4*10/sup -16/ cm/sup -2/ s/sup -1/ sr /sup -1/. This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole beta range in which GUT magnetic monopoles are expected. (37 refs).

  20. Biplot and Singular Value Decomposition Macros for Excel©

    Directory of Open Access Journals (Sweden)

    Ilya A. Lipkovich

    2002-06-01

    Full Text Available The biplot display is a graph of row and column markers obtained from data that forms a two-way table. The markers are calculated from the singular value decomposition of the data matrix. The biplot display may be used with many multivariate methods to display relationships between variables and objects. It is commonly used in ecological applications to plot relationships between species and sites. This paper describes a set of Excel macros that may be used to draw a biplot display based on results from principal components analysis, correspondence analysis, canonical discriminant analysis, metric multidimensional scaling, redundancy analysis, canonical correlation analysis or canonical correspondence analysis. The macros allow for a variety of transformations of the data prior to the singular value decomposition and scaling of the markers following the decomposition.

  1. From micro-correlations to macro-correlations

    Science.gov (United States)

    Eliazar, Iddo

    2016-11-01

    Random vectors with a symmetric correlation structure share a common value of pair-wise correlation between their different components. The symmetric correlation structure appears in a multitude of settings, e.g. mixture models. In a mixture model the components of the random vector are drawn independently from a general probability distribution that is determined by an underlying parameter, and the parameter itself is randomized. In this paper we study the overall correlation of high-dimensional random vectors with a symmetric correlation structure. Considering such a random vector, and terming its pair-wise correlation "micro-correlation", we use an asymptotic analysis to derive the random vector's "macro-correlation" : a score that takes values in the unit interval, and that quantifies the random vector's overall correlation. The method of obtaining macro-correlations from micro-correlations is then applied to a diverse collection of frameworks that demonstrate the method's wide applicability.

  2. Macro-residual strains due to cyclic loading of composites

    CERN Document Server

    Hashin, Z

    1999-01-01

    Macro-residual strains produced by load cycles on elastic-brittle composites are analytically expressed in terms of the effective thermal expansion coefficients of the composite as affected by the damage states developing during the $9 cycling. Limiting values of residual strain are evaluated for unidirectional fiber composites and cross-ply laminates. Frictional losses due to internal sliding are not considered. (17 refs).

  3. Essays in Agent-Based Macro and Monetary Economics

    OpenAIRE

    Lengnick, Matthias

    2015-01-01

    This dissertation consists of three major parts. The first part (chapter 2 and 3) presents different models which integrate macroeconomics with agent-based financial markets. These models feature bounded rational expectations. They are applied to analyse the impact of financial market speculation on the macro economy in general and the performance of several kinds of financial transaction taxes as well as conventional and unconventional monetary policy in particular. The second part (chapter ...

  4. Comprehensive country energy assessments using the MARKAL-MACRO model

    Energy Technology Data Exchange (ETDEWEB)

    Reisman, A.W.

    1997-07-01

    A number of comprehensive country energy assessments were performed in the late 1970s and early 1980s in cooperation with the governments of various countries. The assessments provided a framework for analyzing the impacts of various national strategies for meeting energy requirements. These analyses considered the total energy framework. Economics, energy supply, national resources, energy use, environmental impacts, technologies, energy efficiencies, and sociopolitical impacts were some of the factors addressed. These analyses incorporated the best available data bases and computer models to facilitate the analyses. National policy makers identified the various strategies to examine. The results of the analyses were provided to the national policy makers to support their decision making. Almost 20 years have passed since these assessments were performed. There have been major changes in energy supply and use, technologies, economics, available resources, and environmental concerns. The available tools for performing the assessments have improved drastically. The availability of improved computer modeling, i.e., MARKAL-MACRO, and improved data collection methods and data bases now permit such assessments to be performed in a more sophisticated manner to provide state of the art support to policy makers. The MARKAL-MACRO model was developed by Brookhaven National Laboratory over the last 25 years to support strategic energy planning. It is widely used in the international community for integrating analyses of environmental options, such as reduction of greenhouse gas emissions. It was used to perform the analyses in the least cost energy strategy study for the Energy Policy Act of 1992. Improvements continue to be made to MARKAL-MACRO and its capabilities extended. A methodology to conduct Country Energy Assessments using MARKAL-MACRO is discussed.

  5. Modeling Regional Recycling and Remanufacturing Processes: From Micro to Macro

    OpenAIRE

    Joyce Cooper; Randall Jackson; Nancey Green Leigh

    2008-01-01

    This paper reports progress in modeling recycling and remanufacturing processes within metropolitan regional economies at the micro and macro levels. The paper presents interim results from a multi-year, inter-institutional research project funded by the National Science Foundation. We identify a number of issues that have arisen from an in-depth industry level analysis of obsolete and waste products generated in the Seattle, WA and Atlanta, GA metro regions from waste electronics (e-waste) a...

  6. Macro System Model (MSM) User Guide, Version 1.3

    Energy Technology Data Exchange (ETDEWEB)

    Ruth, M.; Diakov, V.; Sa, T.; Goldsby, M.

    2011-09-01

    This user guide describes the macro system model (MSM). The MSM has been designed to allow users to analyze the financial, environmental, transitional, geographical, and R&D issues associated with the transition to a hydrogen economy. Basic end users can use the MSM to answer cross-cutting questions that were previously difficult to answer in a consistent and timely manner due to various assumptions and methodologies among different models.

  7. MACRO ECONOMICS FACTORS AND BANK LENDING BEHAVIOUR IN INDONESIA

    OpenAIRE

    Rofikoh Rokhim; Yinylia Rusli

    2014-01-01

    AbstractThis study examines the influencing macro economics factor in lending distribution and observes the comparison of each factor based on lending type which are investment, working capital and domestic consumption lending. Using data of Indonesian commercial banks between 2003-2011 and a balanced panel method, it finds that bank liquidity and inflation rate have significant negative effect, while number of banks has strong positive influence to stimulate lending distribution. Moreover, s...

  8. %HPGLIMMIX: A High-Performance SAS Macro for GLMM Estimation

    Directory of Open Access Journals (Sweden)

    Liang Xie

    2014-06-01

    Full Text Available Generalized linear mixed models (GLMMs comprise a class of widely used statistical tools for data analysis with fixed and random effects when the response variable has a conditional distribution in the exponential family. GLMM analysis also has a close relationship with actuarial credibility theory. While readily available programs such as the GLIMMIX procedure in SAS and the lme4 package in R are powerful tools for using this class of models, these progarms are not able to handle models with thousands of levels of fixed and random effects. By using sparse-matrix and other high performance techniques, procedures such as HPMIXED in SAS can easily fit models with thousands of factor levels, but only for normally distributed response variables. In this paper, we present the %HPGLIMMIX SAS macro that fits GLMMs with large number of sparsely populated design matrices using the doubly-iterative linearization (pseudo-likelihood method, in which the sparse-matrix-based HPMIXED is used for the inner iterations with the pseudo-variable constructed from the inverse-link function and the chosen model. Although the macro does not have the full functionality of the GLIMMIX procedure, time and memory savings can be large with the new macro. In applications in which design matrices contain many zeros and there are hundreds or thousands of factor levels, models can be fitted without exhausting computer memory, and 90% or better reduction in running time can be observed. Examples with a Poisson, binomial, and gamma conditional distribution are presented to demonstrate the usage and efficiency of this macro.

  9. Macro photography with a tablet: applications on Science Teaching

    CERN Document Server

    Vieira, Leonardo Pereira

    2013-01-01

    In this work we present a simple way to get Macro photography (enlarged photographs) using a tablet or phone. We initially discuss the technique, which is essentially the accommodation of a drop of water on the camera lens. Next, we explore some applications to science teaching in primary and secondary levels. As discussed in the text, the simplicity and power of the technique may make it a good teaching tool for use in various disciplines such as Science, Biology and Physics.

  10. Understanding co-movements in macro and financial variables

    OpenAIRE

    D'Agostino, Antonello

    2007-01-01

    Over the last years, the growing availability of large datasets and the improvements in the computational speed of computers have further fostered the research in the fields of both macroeconomic modeling and forecasting analysis. A primary focus of these research areas is to improve the models performance by exploiting the informational content of several time series. Increasing the dimension of macro models is indeed crucial for a detailed structural understanding of the economic environmen...

  11. The effect of haemopoietic growth factors on the cell cycle of AML progenitors and their sensitivity to cytosine arabinoside in vitro.

    Science.gov (United States)

    Smith, M A; Singer, C R; Pallister, C J; Smith, J G

    1995-08-01

    This study examines the effect of pretreatment in liquid culture of acute myeloid leukaemic (AML) progenitors with recombinant human IL-3 or G and GM-CSF. Prior to and following cytokine priming, the sensitivity of cells to cytosine arabinoside (Ara-C) at concentrations ranging from 10(-12) to 10(-4) M was assessed in clonogenic culture. In addition, the initial percentage of AML cells in S phase was assessed and their subsequent kinetic response to cytokine treatment evaluated by FACScan analysis. Light-density marrow cells (LDMCs) from 19 AML patients were initially T-cell and monocyte depleted in order to remove potential sources of endogenous cytokine production prior to in vitro investigation. LDMCs were incubated in liquid phase for 7 d in a chemically defined complete medium with or without cytokines. Clonogenic data from fresh AML LDMCs not pretreated with growth factors demonstrated a heterogenous response to Ara-C. In only 4/15 marrows tested clonogenically was there any improvement in sensitivity to Ara-C following cytokine priming. S-phase data on all 19 marrows were similarly variable either before or after cytokine preincubation. There was no discernible correlation between clonogenic and kinetic data, nor could any relationship be established between in vitro findings and the FAB subtypes of patients or clinical outcomes. In summary, it would appear that the cell-cycle status of AML cells is likely to be only one of many contributory factors governing the sensitivity of AML progenitors to Ara-C. The clinical response of AML patients to cytokine therapy in association with cell-cycle-specific cytotoxic agents may therefore be variable and unpredictable.

  12. Micro- and macro-level correlates of adiposity in children.

    Science.gov (United States)

    Yin, Zenong; Moore, Justin B; Johnson, Maribeth H; Vernon, Marlo M; Grimstvedt, Megan; Gutin, Bernard

    2012-01-01

    Recently, studies using a social ecological perspective have identified important micro- and macro-level risk factors for excessive adiposity in youth. Although considerable research exists examining these relationships, few studies have applied a socioecological approach to simultaneously examine both micro- and macro-level factors in young children while objectively assessing adiposity via dual-energy x-ray absorptiometry (DXA). To examine race and sex differences in adiposity measured by DXA in a large sample of young children and to identify both micro- and macro-level correlates of adiposity. Cross-sectional. Elementary school children (N = 495) from the southeastern United States participated. Anthropometrics, percentage body fat via DXA, and psychosocial variables via questionnaire were assessed in the Fall of 2003. Community-level sociodemographic data and built-environment variables via geographic information system were collected in Spring 2009. Data analyses were completed in the Spring of 2010. Percentage body fat in white children was higher than in nonwhite children. Higher percentage body fat and poorer cardiovascular fitness were found in females compared with males. Percentage body fat was higher in children who had lower athletic competence and lived in neighborhoods with higher percentages of minority residents. This study provides preliminary support for the social-ecological model to explain variance in adiposity in children. Developers of health promotion programs for children living in minority neighborhoods should consider factors at multiple levels of the ecological model when designing and implementing programs.

  13. Determinants of The Application of Macro Prudential Instruments

    Directory of Open Access Journals (Sweden)

    Zakaria Firano

    2017-09-01

    Full Text Available The use of macro prudential instruments today gives rise to a major debate within the walls of central banks and other authorities in charge of financial stability. Contrary to micro prudential instruments, whose effects remain limited, macro prudential instruments are different in nature and can affect the stability of the financial system. By influencing the financial cycle and the financial structure of financial institutions, the use of such instruments should be conducted with great vigilance as well as macroeconomic and financial expertise. But the experiences of central banks in this area are sketchy, and only some emerging countries have experience using these types of instruments in different ways. This paper presents an analysis of instruments of macro prudential policy and attempts to empirically demonstrate that these instruments should be used only in specific economic and financial situations. Indeed, the results obtained, using modeling bivariate panel, confirm that these instruments are more effective when used to mitigate the euphoria of financial and economic cycles. In this sense, the output gap, describing the economic cycle, and the Z-score are the intermediate variables for the activation of capital instruments. Moreover, the liquidity ratio and changes in bank profitability are the two early warning indicators for activation of liquidity instruments.

  14. Macro Study of Spatial Development Area on Tourism Village

    Directory of Open Access Journals (Sweden)

    Widhianthini Widhianthini

    2016-10-01

    Full Text Available Macro study is one approach that combines the rational method based on the results of previous studies by the authority with the empirical method utilizing the survey techniques. The purpose of this macro study is to identify and analyze the potentials, problems, and the limiting factors, and the needs of the regency; and to recommend the programs and models required by the community to achieve the sustainable development. This research uses the Participatory Rural Appraisal method, the  interview techniques (Semi Structured Interview, the technique of focused group discussion (FGD, the Rapid District Appraisal (RDA, then it is analyzed by the empirical and dynamical systems. The overview of macro studies is particularly relevant in developing the regions, especially the rural areas, based on the existing advantages, such as in Tabanan Regency. Tabanan Regency is a granary in Bali Province and the zoning of agricultural commodities in quadrant III,which is the rural farming area with combined functions between the cultivated and rural areas supported by the tourism department. The studies of the areas in the form of potential analysis, problem analysis, requirement analysis become the guidelines for preparing the development scenarios and program formats. The studies will then constitute the factors driving the realization of sustainable development of tourism villages in supporting the sustainable agriculture.

  15. A boundary matching micro/macro decomposition for kinetic equations

    CERN Document Server

    Lemou, Mohammed

    2010-01-01

    We introduce a new micro/macro decomposition of collisional kinetic equations which naturally incorporates the exact space boundary conditions. The idea is to write the distribution fonction $f$ in all its domain as the sum of a Maxwellian adapted to the boundary (which is not the usual Maxwellian associated with $f$) and a reminder kinetic part. This Maxwellian is defined such that its 'incoming' velocity moments coincide with the 'incoming' velocity moments of the distribution function. Important consequences of this strategy are the following. i) No artificial boundary condition is needed in the micro/macro models and the exact boundary condition on $f$ is naturally transposed to the macro part of the model. ii) It provides a new class of the so-called 'Asymptotic preserving' (AP) numerical schemes: such schemes are consistent with the original kinetic equation for all fixed positive value of the Knudsen number $\\eps$, and if $\\eps \\to 0 $ with fixed numerical parameters then these schemes degenerate into ...

  16. Performance Evaluation Of Macro amp Micro Mobility In HMIP Networks

    Directory of Open Access Journals (Sweden)

    Osama Ali Abdelgadir

    2015-08-01

    Full Text Available Abstract Changing the location of mobile node during transmission or receiving of data always caused changing of the address of the mobile node which results in packet loss as well as delay in time taken to locate the new address of the Mobile Node therefore delay of data receiving is caused this problem was known as micro-mobility issue. To resolve this problem and ascurrently mobile IP is the most promising solution for mobility management in the Internet. Several IP micro mobility approaches have been proposed to enhance the performance of mobile IP which supports quality of service minimum packet loss limited handoff delay and scalability and power conservation but they are not scalable for macro mobility. A practical solution would therefore require integration of mobile IP and micro mobility protocols where mobile IP handles macro mobility and HMIP cellular IP HAWAII handles micro mobility. In this paper an integrated mobility management protocol for IP based wireless networks is proposed and analyzed.HIERARCHICAL MICRO MOBILITY PROTOCOL is used. To identify the impact of micro-mobility in IP based Wireless Network to implement selected micro-mobility model of Hierarchal Micro Mobility Protocol in network simulator and for more analysis and measurements results and for the purpose of performance comparison between both Macro and Micro mobility Protocol Management.. Simulation results presented in this paper are based on ns 2

  17. Macro Cell Muting Coordination for Non-Uniform Topologies in LTE-A HetNets

    DEFF Research Database (Denmark)

    Soret, Beatriz; Pedersen, Klaus I.

    2013-01-01

    Enhanced Inter Cell Interference Coordination (eICIC) for co-channel deployments of pico cells throughout a macro cell layout is studied. In particular, we analyze a scenario where only some macro cells have picos deployed, while other macro cells have no small cells. The challenge for such highly...... irregular scenarios is how to operate eICIC, and especially how to coordinate macro-cell muting. Our analysis shows that for eICIC to provide gain in such scenarios, it is recommended to use fully time aligned traditional Almost Blank Subframes (ABS) in the macro-cells with picos, while first tier...... surrounding macro cells shall use low-power ABS. For such cases, user throughput gains of 30%-40% are still achievable. Moreover, it is demonstrated that if macro muting patterns are not fully time aligned, it causes additional interference fluctuations in the network, resulting in less efficient link...

  18. Task Space Division and Trajectory Planning for a Flexible Macro-Micro Manipulator System

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper deals with a flexible macro-micro manipulator system, which includes a long flexible manipulator and a relatively short rigid manipulator attached to the tip of the macro manipulator. A flexible macro manipulator possesses the advantages of wide operating range, high speed, and low energy consumption, but the disadvantage of a low tracking precision. The macro-micro manipulator system improves tracking performance by compensating for the endpoint tracking error while maintaining the advantages of the flexible macro manipulator. A trajectory planning scheme was built utilizing the task space division method. The division point is chosen to optimize the error compensation and energy consumption for the whole system. Then movements of the macro-micro manipulator can be determined using separate inverse kinematic models. Simulation results for a planar 4-DOF macro-micro manipulator system are presented to show the effectiveness of the control system.

  19. Problemes theoriques et methodologiques dans l'etude des langues/dialectes en contact aux niveaux macrologique et micrologique = Theoretical and Methodological Issues in the Study of Languages/Dialects in Contact at Macro- and Micro-Logical Levels of Analysis. Proceedings of the International Conference DALE (University of London)/ICRB (Laval University, Quebec)/ICSBT (Vrije Universiteit te Brussel) (London, England, May 23-26, 1985).

    Science.gov (United States)

    Blanc, Michel, Ed.; Hamers, Josiane F., Ed.

    Papers from an international conference on the interaction of languages and dialects in contact are presented in this volume. Papers include: "Quelques reflexions sur la variation linguistique"; "The Investigation of 'Language Continuum' and 'Diglossia': A Macrological Case Study and Theoretical Model"; "A Survey of…

  20. Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation.

    Science.gov (United States)

    Armand, Philippe; Kim, Haesook T; DeAngelo, Daniel J; Ho, Vincent T; Cutler, Corey S; Stone, Richard M; Ritz, Jerome; Alyea, Edwin P; Antin, Joseph H; Soiffer, Robert J

    2007-06-01

    Cytogenetics has an important impact on the prognosis of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). However, it is unclear whether currently accepted cytogenetic risk groups, which were established for patients treated mostly with standard therapy, are optimally discriminating for patients undergoing HSCT. Also, the impact of cytogenetics in the growing population of patients with therapy-related disease has not been completely elucidated. In this study, we retrospectively analyzed data on 556 patients with AML or MDS transplanted at our institution. We examined, in multivariate analyses, the contribution of cytogenetics to survival, relapse, and nonrelapse mortality for the 476 patients with de novo disease. We used these results to establish an optimal cytogenetic grouping scheme. We then applied this grouping scheme to the 80 patients with therapy-related disease. Our proposed 3-group cytogenetic classification outperformed the established grouping schemes for both de novo and therapy-related disease. When classified by this new scheme, cytogenetics was the strongest prognostic factor for overall survival in our cohort, through its impact on the risk of relapse (and not on nonrelapse mortality). After accounting for cytogenetics, patients with therapy-related AML or MDS had an equivalent outcome to those with de novo disease. This study demonstrates the impact of cytogenetics on the risk of relapse and death for patients with both de novo and therapy-related disease undergoing transplantation; it also emphasizes the necessity of using cytogenetics to stratify patients entering clinical trials, and provides a system for doing so, which can be validated in a multi-institutional database.

  1. Dicentric chromosomes and 20q11.2 amplification in MDS/AML with apparent monosomy 20.

    Science.gov (United States)

    Mackinnon, R N; Campbell, L J

    2007-01-01

    FISH analysis of 41 previously karyotyped cases of MDS and AML with apparent monosomy of chromosome 20 revealed a variety of dicentric abnormalities involving chromosome 20. These usually, but not always, involved a breakpoint in the long arm of chromosome 20 and loss of the common deleted region at 20q12. Not one case of true monosomy 20 was confirmed. We found evidence for dicentric chromosome formation in 21 of 24 unbalanced translocations containing chromosome 20 and that were studied in more detail. Subsequent loss of one of the centromeres had occurred in eight of these 24 cases, and was more frequent than centromere inactivation as a means of resolving the inherent instability of a dicentric chromosome. In the three cases with dicentric chromosomes from which proximal 20q had been excised along with the 20 centromere, the excised segment was retained, and in two of these it was amplified. Proximal 20q was clearly retained in all but three cases, and present in three or more copies in 17 of 41 cases. The retention and amplification of proximal 20q provides support for the hypothesis that there is an oncogene located in this region of 20q that is activated in cases of MDS/AML with del(20q). Apparent monosomy 20 in MDS/AML should be treated as evidence of unidentified chromosome 20 abnormalities, and familiarity with the typical G-banded morphology of these derivatives can help with their identification. The reported incidence of dicentric chromosomes is clearly an under-estimate but is increasing in myeloid disorders as more cases are studied with methods allowing their detection.

  2. 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.

  3. High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients.

    Science.gov (United States)

    Barjesteh van Waalwijk van Doorn-Khosrovani, Sahar; Erpelinck, Claudia; van Putten, Wim L J; Valk, Peter J M; van der Poel-van de Luytgaarde, Sonja; Hack, Ronald; Slater, Rosalyn; Smit, Elisabeth M E; Beverloo, H Berna; Verhoef, Gregor; Verdonck, Leo F; Ossenkoppele, Gert J; Sonneveld, Pieter; de Greef, Georgine E; Löwenberg, Bob; Delwel, Ruud

    2003-02-01

    The proto-oncogene EVI1 encodes a DNA binding protein and is located on chromosome 3q26. The gene is aberrantly expressed in acute myeloid leukemia (AML) patients carrying 3q26 abnormalities. Two mRNAs are transcribed from this locus: EVI1 and a fusion of EVI1 with MDS1 (MDS1-EVI1), a gene located 5' of EVI1. The purpose of this study was to investigate which of the 2 gene products is involved in transformation in human AML. To discriminate between EVI1 and MDS1-EVI1 transcripts, distinct real-time quantitative polymerase chain reaction (PCR) assays were developed. Patients with 3q26 abnormalities often showed high EVI1 and MDS1-EVI1 expression. In a cohort of 319 AML patients, 4 subgroups could be distinguished: EVI1(+) and MDS1-EVI1(-) (6 patients; group I), EVI1(+) and MDS1-EVI1(+) (26 patients; group II), EVI1(-) and MDS1-EVI1(+) (12 patients; group III), and EVI1(-) and MDS1-EVI1(-) (275 patients; group IV). The only 4 patients with a 3q26 aberration belonged to groups I and II. Interestingly, high EVI1 and not MDS1-EVI1 expression was associated with unfavorable karyotypes (eg, -7/7q-) or complex karyotypes. Moreover, a significant correlation was observed between EVI1 expression and 11q23 aberrations (mixed lineage leukemia [MLL] gene involvement). Patients from groups I and II had significantly shorter overall and event-free survival than patients in groups III and IV. Our data demonstrate that high EVI1 expression is an independent poor prognostic marker within the intermediate- risk karyotypic group.

  4. Macro-aspartate aminotransferase (macro-AST). A 12-year follow-up study in a young female.

    Science.gov (United States)

    Orlando, Rocco; Carbone, Aniello; Lirussi, Flavio

    2003-12-01

    We describe a case of chronic elevation of serum aspartate aminotransferase (AST) activity due to the presence of a macro-enzyme form of AST (macro-AST) in a young female followed up for 12 years. This biochemical abnormality, although generally detected in acute and chronic hepatitis, malignancies and autoimmune disease, was not associated with any particular illness and did not seem to be congenital, as normal AST concentrations were reported in the patient's family members. Moreover, the normal or quasi-normal values of AST associated with peak levels observed in our case suggest that this phenomenon has a fluctuating behaviour rather than persisting for many months or years. In conclusion, we believe that it is important: 1) to reassure the patient with macro-AST, as this condition has a benign evolution and does not require any specific treatment; 2) to keep in mind this biochemical abnormality in all cases of unexplained AST elevation in order to avoid unnecessary invasive diagnostic procedures.

  5. Core binding factor acute myeloid leukemia (CBF-AML) in México: a single institution experience.

    Science.gov (United States)

    Ruiz-Delgado, Guillermo J; Macías-Gallardo, Julio; Lutz-Presno, Julia; Garcés-Eisele, Javier; Hernández-Arizpe, Ana; Montes-Montiel, Maryel; Ruiz-Argüelles, Guillermo J

    2011-01-01

    Twenty one patients with CBF-AML presented prospectively in the Centro de Hematología y Medicina Interna de Puebla (Puebla, México) between February 1995 and March 2010, 14 with the t(8;21)(q22;q22) and 7 with the inv(16)(p13;q22)/t(16;16)(p13;q22); they represent 13% of all cases of AML. The median age of the patients was 24 years (range 1 to 61). Seven of 14 patients with t(8;21)(q22;q22) had an M2 morphology whereas 3/7 with the inv(16) had an M4 morphology; in addition to the myeloid markers identified by flow-cytometry (surface CD13, surface CD33, and cytoplasmic myeloperoxidase) lymphoid markers were identified in the blast cells of 8/14 cases of the t(8;21) patients, but in no patient with the inv(16). Nineteen patients were treated with combined chemotherapy and 16 (84%) achieved a complete molecular remission. Seven patients were auto or allografted. Relapses presented in 10/16 patients. The median probability of overall survival (OS) has not been reached being above 165 months, whereas the 165-month probability of OS and leukemia-free survival was 52%; despite a tendency for a better outcome of patients with the t(8;21), there were no significant differences in survival of patients with either the t(8;21) or the inv(16). In this single institution experience in México, we found that the CBF variants of AML have a similar prevalence as compared with Caucasian populations, that the co-expression of lymphoid markers in the blast cells was frequent in the t(8;21) and that these two AML subtypes were associated with a relatively good long-term prognosis. Further studies are needed to describe with more detail the precise biological features of these molecular subtypes of acute leukemia.

  6. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi

    2010-01-01

    BACKGROUND: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health...... services was limited. Reported health and social outcomes were comparable to those of their siblings. Many survivors were smoking which may increase the risk of late effects. Pediatr Blood Cancer © 2010 Wiley-Liss, Inc....

  7. Language Acquisition and Language Learning

    Institute of Scientific and Technical Information of China (English)

    蔡红

    2007-01-01

    Language is at the center of human life. This essay tries to seek similarities and differences between language acquisition and language learning from the theory achievements of some linguists. On this basis, it is pointed out that language acquisition is the effect of sub consciousness, while language learning is connected with conscious system. Thereby this paper analyzes the interaction between them and the influence on the present situation of foreign language teaching in China.

  8. Language Acquisition and Language Learning

    Institute of Scientific and Technical Information of China (English)

    蔡红

    2007-01-01

    Language is at the center of human life.This essay tries to seek similarities and differences between language acquisition and language learning from the theory achievements of some linguists.On this basis,it is pointed out that language acquisition is the effect of sub consciousness,while language learning is connected with conscious system.Thereby this paper analyzes the interaction between them and the influence on the present situation of foreign language teaching in China.

  9. 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.

  10. A call for (trans)languaging: The language profiles at Roskilde University

    DEFF Research Database (Denmark)

    Daryai-Hansen, Petra; Barfod, Sonja; Schwarz, Lena

    2016-01-01

    While the idea of a plurilingual, integrated and individualized competence is well accepted in research on language education and recommended in language policies, it is not established in education in general. The chapter introduces Roskilde University’s language profiles, where the new paradigm...... objectives of RUC’s language profiles. Furthermore we discuss, based on the language profiles as an example, how translanguaging practices and policies can be described on a supra, macro, meso, micro and nano level. The analysis focuses on teachers’ and students’ translanguaging practices and their attitudes...... is put into educational practice, thereby bridging the gap between plurilingual theory and monolingual practice. Roskilde University offers, as part of its internationalisation strategy, supplementary, curriculum-related courses in French and German to all students in the bachelor programs...

  11. Biolinguistics and the Implication for Teaching Language on Young Learners

    Directory of Open Access Journals (Sweden)

    Abbas Achmad Badib

    1998-01-01

    Full Text Available Abstract: The majority of foreign language teachers tend to believe that there is a significant different approach in terms of a teaching strategy dealing with the first and second language instructions. Can those different approaches be substantiated by our sound justifica­tions based on our proper understanding and essential knowledge of language processes? Generally speaking, our understanding of the nature of language acquisition in terms of biolinguistics is only par­tial. Therefore, this paper attempts to explore the biological aspects of the process of language acquisition by a child and then compare it with the developments of the birth of language. In other words this paper will examine very briefly the micro and macro evolutions of language. Central to this discussion are the neurological develop­ments in the brain, which are responsible for language planning and the speech apparatus responsible for language productions. By ex­amining the two related activities, we can then study how language is actually carried out by human beings, both first and second language acquisitions. After developing a proper understanding of the bio­logical aspects of language, we can thus explore further the best way of language processes. This may constitute a new insight of lan­guage teaching because so far, relying on linguistic theories alone, it is often difficult to obtain the most acceptable information regarding the nature of first and second language teaching.

  12. 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.Keywords: loanwords, semantic change, semantic domains, synonymy, Arabic media language

  13. Wave equation modelling using Julia programming language

    Science.gov (United States)

    Kim, Ahreum; Ryu, Donghyun; Ha, Wansoo

    2016-04-01

    Julia is a young high-performance dynamic programming language for scientific computations. It provides an extensive mathematical function library, a clean syntax and its own parallel execution model. We developed 2d wave equation modeling programs using Julia and C programming languages and compared their performance. We used the same modeling algorithm for the two modeling programs. We used Julia version 0.3.9 in this comparison. We declared data type of function arguments and used inbounds macro in the Julia program. Numerical results showed that the C programs compiled with Intel and GNU compilers were faster than Julia program, about 18% and 7%, respectively. Taking the simplicity of dynamic programming language into consideration, Julia can be a novel alternative of existing statically typed programming languages.

  14. Overview of the Force Scientific Parallel Language

    Directory of Open Access Journals (Sweden)

    Gita Alaghband

    1994-01-01

    Full Text Available The Force parallel programming language designed for large-scale shared-memory multiprocessors is presented. The language provides a number of parallel constructs as extensions to the ordinary Fortran language and is implemented as a two-level macro preprocessor to support portability across shared memory multiprocessors. The global parallelism model on which the Force is based provides a powerful parallel language. The parallel constructs, generic synchronization, and freedom from process management supported by the Force has resulted in structured parallel programs that are ported to the many multiprocessors on which the Force is implemented. Two new parallel constructs for looping and functional decomposition are discussed. Several programming examples to illustrate some parallel programming approaches using the Force are also presented.

  15. Study of t(8;21 )/AML1 - ETO- positive childhood acute myeloid leukemia%伴t(8;21)/AML1-ETO的儿童急性髓系白血病的临床研究

    Institute of Scientific and Technical Information of China (English)

    陈玉梅; 赵要顺; 邹尧; 陈晓娟; 张乃红; 刘天峰; 竺晓凡

    2005-01-01

    目的探讨伴t(8;21)/AML1-ETO的儿童急性髓系白血病(AML)的临床及生物学特征.方法52例初治患儿,男34例,女18例,中位年龄12(4~18)岁,均进行了遗传学和/或AML1-ETO融合基因检测.诱导缓解治疗采用HA/DA/HAD方案,缓解后进行异基因造血干细胞移植或7~12疗程的联合化疗.结果 24%的儿童AML伴t(8;21)/AML1-ETO,男女比例1.9,FAB分型为M250例(96%);初诊时伴中枢神经系统浸润7.7%(4/52);WBC17.2(1.8~146.3)×10 9/L,初诊时WBC大于10×10 9/L者50.0%(26/52),大于50×10 9/L者3.8%(2/52),血清乳酸脱氢酶升高者85.7%(36/42);细胞免疫分型CD19(44.4%),CD56(58.9%);单独为t(8;21)异常的13例(28.9%),Y染色体丢失22例,占男性患儿的64.7%;X染色体丢失3例,占女性患儿的16.7%,del(9q)6例;1疗程及2疗程完全缓解(CR)率分别为71.8%(28/39)和94.4%(34/36),4年的EFS率、DFS率和OS率分别为(25.4±9.6)%、(28.4±10.4)%和37.9±10.3)%.结论近1/4的儿童AML伴t(8;21)/AML-ETO,多见于FAB分型的M2型,男性居多,年长儿多发,易发生髓外浸润;高白细胞者少见,血清乳酸脱氢酶增高,细胞免疫分型较多表达CD19和CD56;细胞遗传学检查常伴有性染色体丢失和del(9q);诱导缓解治疗完全缓解率高,应用联合化疗进行巩固强化远期疗效好.

  16. Language Awareness

    NARCIS (Netherlands)

    White, Lana; Maylath, J. Bruce; Adams, Anthony; Couzijn, Michel

    2000-01-01

    Language Awareness: A History and Implementations offers teachers of mother tongue and foreign languages a view of the beginnings and the ramifications of the language-teaching movement called Language Awareness. The philosophy held in common among the teachers in this international movement is twof

  17. Language Awareness

    NARCIS (Netherlands)

    White, Lana; Maylath, J. Bruce; Adams, Anthony; Couzijn, Michel

    2000-01-01

    Language Awareness: A History and Implementations offers teachers of mother tongue and foreign languages a view of the beginnings and the ramifications of the language-teaching movement called Language Awareness. The philosophy held in common among the teachers in this international movement is

  18. 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

  19. Understanding Cognitive Language Learning Strategies

    Directory of Open Access Journals (Sweden)

    Sergio Di Carlo

    2017-01-01

    Full Text Available Over time, definitions and taxonomies of language learning strategies have been critically examined. This article defines and classifies cognitive language learning strategies on a more grounded basis. Language learning is a macro-process for which the general hypotheses of information processing are valid. Cognitive strategies are represented by the pillars underlying the encoding, storage and retrieval of information. In order to understand the processes taking place on these three dimensions, a functional model was elaborated from multiple theoretical contributions and previous models: the Smart Processing Model. This model operates with linguistic inputs as well as with any other kind of information. It helps to illustrate the stages, relations, modules and processes that occur during the flow of information. This theoretical advance is a core element to classify cognitive strategies. Contributions from cognitive neuroscience have also been considered to establish the proposed classification which consists of five categories. Each of these categories has a different predominant function: classification, preparation, association, elaboration and transfer-practice. This better founded taxonomy opens the doors to potential studies that would allow a better understanding of the interdisciplinary complexity of language learning. Pedagogical and methodological implications are also discussed. Keywords: cognitive processes, cognitive neuroscience, information processing, second and foreign language acquisition, Smart Processing Model

  20. Activated leukemic oncogenes AML1-ETO and c-kit: role in development of acute myeloid leukemia and current approaches for their inhibition.

    Science.gov (United States)

    Rulina, A V; Spirin, P V; Prassolov, V S

    2010-12-01

    Acute myeloid leukemia (AML) is a malignant blood disease caused by different mutations that enhance the proliferative activity and survival of blood cells and affect their differentiation and apoptosis. The most frequent disorders in AML are translocations between chromosomes 21 and 8 leading to production of a chimeric oncogene, AML1-ETO, and hyperexpression of the receptor tyrosine kinase KIT. Mutations in these genes often occur jointly. The presence in cells of two activated oncogenes is likely to trigger their malignization. The current approaches for treatment of oncologic diseases (bone marrow transplantation, radiotherapy, and chemotherapy) have significant shortcomings, and thus many laboratories are intensively developing new approaches against leukemias. Inhibiting expression of activated leukemic oncogenes based on the principle of RNA interference seems to be a promising approach in this field.

  1. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial

    Science.gov (United States)

    Platzbecker, U; Wermke, M; Radke, J; Oelschlaegel, U; Seltmann, F; Kiani, A; Klut, I-M; Knoth, H; Röllig, C; Schetelig, J; Mohr, B; Graehlert, X; Ehninger, G; Bornhäuser, M; Thiede, C

    2012-01-01

    This study evaluated azacitidine as treatment of minimal residual disease (MRD) determined by a sensitive donor chimerism analysis of CD34+ blood cells to pre-empt relapse in patients with CD34+ myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). At a median of 169 days after HSCT, 20/59 prospectively screened patients experienced a decrease of CD34+ donor chimerism to <80% and received four azacitidine cycles (75 mg/m2/day for 7 days) while in complete hematologic remission. A total of 16 patients (80%) responded with either increasing CD34+ donor chimerism to ⩾80% (n=10; 50%) or stabilization (n=6; 30%) in the absence of relapse. Stabilized patients and those with a later drop of CD34+ donor chimerism to <80% after initial response were eligible for subsequent azacitidine cycles. A total of 11 patients (55%) received a median of 4 (range, 1–11) additional cycles. Eventually, hematologic relapse occurred in 13 patients (65%), but was delayed until a median of 231 days (range, 56–558) after initial decrease of CD34+ donor chimerism to <80%. In conclusion, pre-emptive azacitidine treatment has an acceptable safety profile and can substantially prevent or delay hematologic relapse in patients with MDS or AML and MRD after allogeneic HSCT. PMID:21886171

  2. 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.......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 identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal...

  3. Exposure to armament wastes and leukemia: a case-control study within a cluster of AML and CML in Germany.

    Science.gov (United States)

    Kilian, P H; Skrzypek, S; Becker, N; Havemann, K

    2001-10-01

    An unusually high incidence of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) concentrated in a specific locality of a region in Germany motivated a descriptive incidence study in that region which showed a near 10-fold increased risk of CML among males but not among females (Kolb G, Becker N, Scheller S, Zugmaier G, Pralle H, Wahrendorf J, Havemann K. Increased risk of acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in a County of Hesse, Germany, Soc Prev Med 1993;38:190-195). Since a serious environmental contamination of areas in this locality with armament wastes containing toluene-derivatives has been known for a long time, the hypothesis arose that TNT production and the related severe contamination of soil and water might be responsible for the observed higher risk. We carried out a case-control study within the cluster to test this hypothesis. Overall, the results do not confirm the hypothesis. There is an indication of a relationship of an increased odds ratio with the exposure for a small group of persons who lived at a particular site in one of the two communities involved during the peak phase of TNT production during the 1940s. However, this finding is spurious and cannot explain the large majority of cases which occurred in that area in the 1980s. At the moment, no other explanation can be given for the increased risk of leukemias in that area.

  4. 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.

  5. Immune responses to WT1 in patients with AML or MDS after chemotherapy and allogeneic stem cell transplantation.

    Science.gov (United States)

    Casalegno-Garduño, Rosaely; Schmitt, Anita; Spitschak, Alf; Greiner, Jochen; Wang, Lei; Hilgendorf, Inken; Hirt, Carsten; Ho, Anthony D; Freund, Mathias; Schmitt, Michael

    2016-04-01

    Wilms' tumor gene 1 (WT1) is overexpressed in leukemia and WT1-derived CD8(+) T-cell epitopes for immunotherapies targeting WT1 have been defined. Here, we analyzed expression of WT1 in 226 peripheral blood and bone marrow samples from patients with acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) before and after allogeneic stem cell transplantation (SCT). Transcripts were assessed by quantitative polymerase chain reaction, and WT1-specific CD8+ cytotoxic T cells (CTL) were monitored by tetramer staining and enzyme-linked immunospot (ELISPOT) assays. Reduction of WT1 levels correlated with a longer survival (p CTL than in patients developing a relapse were detected. These cells were effector T cells secreting interferon gamma and granzyme B. In summary, WT1 is a suitable marker for the detection of minimal residual disease after SCT or chemotherapy. A rising WT1 signal correlated with a dismal prognosis of the patients. WT1-specific CD8(+) T cells might contribute to the maintenance of a cCR. Targeting WT-1 by peptide/protein vaccination as well as adoptive transfer of genetically modified T cells are future options in the individualized therapy for AML/MDS patients. © 2015 UICC.

  6. The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells.

    Science.gov (United States)

    Staber, Philipp B; Zhang, Pu; Ye, Min; Welner, Robert S; Levantini, Elena; Di Ruscio, Annalisa; Ebralidze, Alexander K; Bach, Christian; Zhang, Hong; Zhang, Junyan; Vanura, Katrina; Delwel, Ruud; Yang, Henry; Huang, Gang; Tenen, Daniel G

    2014-10-01

    Runx transcription factors contribute to hematopoiesis and are frequently implicated in hematologic malignancies. All three Runx isoforms are expressed at the earliest stages of hematopoiesis; however, their function in hematopoietic stem cells (HSCs) is not fully elucidated. Here, we show that Runx factors are essential in HSCs by driving the expression of the hematopoietic transcription factor PU.1. Mechanistically, by using a knockin mouse model in which all three Runx binding sites in the -14kb enhancer of PU.1 are disrupted, we observed failure to form chromosomal interactions between the PU.1 enhancer and its proximal promoter. Consequently, decreased PU.1 levels resulted in diminished long-term HSC function through HSC exhaustion, which could be rescued by reintroducing a PU.1 transgene. Similarly, in a mouse model of AML/ETO9a leukemia, disrupting the Runx binding sites resulted in decreased PU.1 levels. Leukemia onset was delayed, and limiting dilution transplantation experiments demonstrated functional loss of leukemia-initiating cells. This is surprising, because low PU.1 levels have been considered a hallmark of AML/ETO leukemia, as indicated in mouse models and as shown here in samples from leukemic patients. Our data demonstrate that Runx-dependent PU.1 chromatin interaction and transcription of PU.1 are essential for both normal and leukemia stem cells.

  7. 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

    remission rate (73% vs 75%; odds ratio, 1.07 [0.83-1.39]; P = .6) or in any recognized subgroup. The 60-day mortality was increased in the 90 mg/m(2) arm (10% vs 5% (hazard ratio [HR] 1.98 [1.30-3.02]; P = .001), which resulted in no difference in overall 2-year survival (59% vs 60%; HR, 1.16 [0.95-1.43]; P...... recommended as a standard of care. However, 60 mg/m(2) is widely used and has never been directly compared with 90 mg/m(2). As part of the UK National Cancer Research Institute (NCRI) AML17 trial, 1206 adults with untreated AML or high-risk myelodysplastic syndrome, mostly younger than 60 years of age, were...... randomized to a first-induction course of chemotherapy, which delivered either 90 mg/m(2) or 60 mg/m(2) on days 1, 3, and 5 combined with cytosine arabinoside. All patients then received a second course that included daunorubicin 50 mg/m(2) on days 1, 3, and 5. There was no overall difference in complete...

  8. Japanese Language, Standard Language, National Language: Rethinking Language and Nation

    Directory of Open Access Journals (Sweden)

    Luka CULIBERG

    2013-11-01

    Full Text Available The paper examines the relationship between language and nation through the historical process by which the modern Japanese language came to exist and proposes a tentative answer as to what this says about the nature of phenomena such as language and nation themselves. The paper suggests that if language is understood as an actually existing natural and definable object, it must indeed be claimed that the Japanese language is no more than a hundred years old.

  9. Standardization of phaseolus vulgaris valves by macro- and microscopic characteristics

    Directory of Open Access Journals (Sweden)

    Анна Ігорівна Крюкова

    2016-03-01

    Full Text Available During the last years on the Ukrainian pharmaceutical market a tendency to increase the range of the national herbal remedies is observed. Native flora herbs, having a sufficient resource base, deserve special attention and are characterized by a number of economic benefits for manufacturers. The implementation of herbal remedies in medical practice is accompanied by the necessity to improve the quality control of herbal material and to develop normative documents. Macro- and microscopy analysis becomes important at standardization of herbal material especially cut and powdered.Aim. The aim of our work was to carry out macro- and microscopy research of Phaseolus vulgaris and to determine its diagnostic morphologic and anatomic features.Methods. The conventional research methods in pharmacognosy have been used; photomicrography has been taken by using microscope MC-10 and Samsung PL 50 camera.Results. As a result of research, the microscopic diagnostic characteristics for Phaseolus vulgaris valves have been proposed, e.g.: the valves are elongated, straight, navicular or grooved, twisted to some extent; the external surface is smooth or slightly undulating, mat, pale yellow or yellow; the internal surface is shiny, white or yellowish-white. Sometimes carpophore (stalk may occur. The microscopic diagnostic features have been determined and offered, e.g.: cells of outer epidermis are pentagonal and hexagonal, with plicated cuticle; stomata are surrounded by 3–4 subsidiary narrow cells, additionally surrounded by 5–6 narrow cells; cover trichomes and glandular trichomes are elongated, pointed and unbranched; xylem vessels and tracheids; non-bundled structure stalk fragments with pericyclic sclerenchyma and secretory cells in the phloem.Conclusion. Research on determination of the macro- and microscopic characteristics of Phaseolus vulgaris valves has been carried out. The diagnostic morphological and anatomic elements in herbal material have

  10. Search for stellar gravitational collapses with the MACRO detector

    CERN Document Server

    Ambrosio, M; Baldini, A; Barbarino, G C; Barish, B C; Battistoni, G; Bellotti, R; Bemporad, C; Bernardini, P; Bilokon, H; Bloise, C; Bower, C; Brigida, M; Bussino, S; Cafagna, F; Campana, D; Carboni, M; Cecchini, S; Cei, F; Chiarella, V; Choudhary, B C; Coutu, S; Cozzi, M; De Cataldo, G; De Marzo, C; De Mitri, I; De Vincenzi, M; Dekhissi, H; Derkaoui, J; Di Credico, A; Favuzzi, C; Forti, C; Fusco, P; Giacomelli, G; Giannini, G; Giglietto, N; Giorgini, M; Grassi, M; Grillo, A; Gustavino, C; Habig, A; Hanson, K; Heinz, R; Iarocci, E; Katsavounidis, E; Katsavounidis, I; Kearns, E; Kim, H; Kyriazopoulou, S; Lamanna, E; Lane, C; Levin, D S; Lipari, P; Longley, N P; Longo, M J; Loparco, F; Maaroufi, F; Mancarella, G; Mandrioli, G; Margiotta, A; Marini, A; Martello, D; Marzari-Chiesa, A; Mazziotta, M N; Michael, D G; Monacelli, P; Montaruli, T; Monteno, M; Mufson, S; Musser, J; Nicolò, D; Nolty, R; Orth, C; Osteria, G; Palamara, O; Patera, V; Patrizii, L; Pazzi, R; Peck, C W; Perrone, L; Petrera, S; Popa, V; Raino, J A; Reynoldson, J; Ronga, F; Satriano, C; Scapparone, E; Scholberg, K; Sciubba, A; Sioli, M; Sirri, G; Sitta, M; Spinelli, P; Spinetti, M; Spurio, M; Steinberg, R; Stone, J L; Sulak, L R; Surdo, A; Tarle, G; Togo, V; Vakili, M; Walter, C W; Webb, R; 10.1140/epjc/s2004-01981-3

    2004-01-01

    We present the final results of the search for stellar gravitational collapses obtained by the MACRO experiment. The detector was active for a stellar collapse search for more than 11 years and it was sensitive to collapses occurring all over in our galaxy for 8.6 years. A real time system for a prompt recognition of neutrino bursts was developed and was operating on-line for almost the whole life of the experiment. No signal compatible with a neutrino burst from a galactic supernova was observed.

  11. Macro and micro view on steady states in state space

    CERN Document Server

    Sobota, Branislav

    2010-01-01

    This paper describes visualization of chaotic attractor and elements of the singularities in 3D space. 3D view of these effects enables to create a demonstrative projection about relations of chaos generated by physical circuit, the Chua's circuit. Via macro views on chaotic attractor is obtained not only visual space illustration of representative point motion in state space, but also its relation to planes of singularity elements. Our created program enables view on chaotic attractor both in 2D and 3D space together with plane objects visualization -- elements of singularities.

  12. A VISUAL BASIC PPREADSHEET MACRO FOR ESTIMATING GROUNDWATER RECHARGE

    Directory of Open Access Journals (Sweden)

    Kristijan Posavec

    2009-12-01

    Full Text Available A Visual Basic spreadsheet macro was written to automate the estimation of groundwater recharge from stream or spring hydrographs using the adapted Meyboom’s method. The program fits exponential regression model available in widely accessible platform (i.e. MS Excel to baseflow recessions that precede and follow groundwater recharge, and uses regression equations to calculate recharge volume that occur between these recessions. An example of field data from Croatia (Bulaž spring is given to illustrate its application.

  13. Macro-ecología de los Andes peruanos

    OpenAIRE

    Salaverry Llosa, José A.

    2015-01-01

    El libro presenta los aspectos referidos a la dinámica de cambio que ha impuesto la naturaleza sobre las condiciones macro-ecológicas de los Andes desde la era arcaica y formativa de las culturas agrarias andinas peruanas que ocuparon el territorio peruano. Principalmente se ocupa de las modificaciones en las condiciones geo-hidrográficas y de clima-vegetación que se han producido, relacionadas a los periodos de cambio climático universales repercutiendo en el paisaje y el Hombre en las zona...

  14. Interaction of Macro-particles with LHC proton beam

    CERN Document Server

    Zimmermann, F; Xagkoni, A

    2010-01-01

    We study the interaction of macro-particles residing inside the LHC vacuum chamber, e.g. soot or thermalinsulation fragments, with the circulating LHC proton beam. The coupled equations governing the motion and charging rate of metallic or dielectric micron-size macroparticles are solved numerically to determine the time spent by such “dust” particles close to the path of the beam as well as the resulting proton-beam losses, which could lead to a quench of superconducting magnets and, thereby, to a premature beam abort.

  15. Pulsars: Macro-nuclei with 3-flavour symmetry

    CERN Document Server

    Xu, Renxin

    2015-01-01

    A pulsar-like compact star is the rump left behind after a supernova where normal baryonic matter is intensely compressed by gravity, but the real state of such compressed baryonic matter is still not well understood because of the non-perturbative nature of the fundamental color interaction. We argue that pulsars could be of condensed matter of quark clusters, i.e., "quark-cluster stars" which distinguish from conventional neutron and quark stars. In comparison with 2-flavour symmetric micro-nuclei, a quark-cluster star could simply be considered as a macro-nucleus with 3-flavour symmetry. New research achievements both theoretical and observational are briefly presented.

  16. Macro- to microscale heat transfer the lagging behavior

    CERN Document Server

    Tzou, D Y

    2014-01-01

    Physical processes taking place in micro/nanoscale strongly depend on the material types and can be very complicated. Known approaches include kinetic theory and quantum mechanics, non-equilibrium and irreversible thermodynamics, molecular dynamics, and/or fractal theory and fraction model. Due to innately different physical bases employed, different approaches may involve different physical properties in describing micro/nanoscale heat transport. In addition, the parameters involved in different approaches, may not be mutually inclusive. Macro- to Microscale Heat Transfer: The Lagging Behav

  17. [Clinical efficacy of decitabine combined with modified CAG regimen for relapsed-refractory acute myeloid leukemia with AML1-ETO⁺].

    Science.gov (United States)

    Jing, Yu; Zhu, Cheng-Ying; Zhang, Qi; Niu, Jian-Hua; Yang, Hua; Liu, Shi-Yan; Zhu, Hai-Yan; Yu, Li

    2014-10-01

    This study was aimed to investigate the clinical characteristics of relapsed-refractory acute myeloid leukemia (AML) with AML1-ETO⁺, and its therapeutic efficacy and side effects when decitabine combined with modified CAG regimen was used. Clinical data of 5 cases of AML with AML1-ETO⁺ from January 2013 to Agust 2013 were analyzed retrospectively. The analyzed data included age, sex, initial symptoms, peripheral blood and bone marrow characteristics. Meanwhile, the therapeutic effecacy and side effects of decitabine combined with modified CAG regimen were evaluated. The 5 patients were with median age of 35 (17-43) years. Among these 5 patients, 2 patients were relapsed and other 3 patients were relapsed-refractory patients, their median white blood cell count was 12.55 (7.8-66.55) × 10⁹/L, median platelets count was 44 (20-72) × 10⁹/L, median hemoglobin level was 110 (77-128) g/L, median lactate dehydrogenase level was 312.9 U/L (123.6-877.8) at the initial diagnosis. The results showed that after decitabine combined with modified CAG regimen was administered, 4 patients achieved complete remission, 1 patient did not achieve remission, the overall remission rate was 80% (4/5). The main side effects of this regimen was myelosuppression, these were no new lung infection and other serious complications, one case without complete remission treated with FLAG once again died of heart failure when being mobilized for transplantation. It is concluded that according to preliminary results of decitabine combined with modified CAG regimen for relapsed and refractory AML patients with AML1-ETO⁺ displays higher remission rate and lower side effects, which worthy to further explore for clinal application.

  18. Nuclear factor E2-related factor 2 knockdown enhances glucose uptake and alters glucose metabolism in AML12 hepatocytes.

    Science.gov (United States)

    Yuan, Xiaoyang; Huang, Huijing; Huang, Yi; Wang, Jinli; Yan, Jinhua; Ding, Ling; Zhang, Cuntai; Zhang, Le

    2017-05-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce the expression of a variety of antioxidant and detoxification genes. Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 ± 11.1% ( P glucose metabolism were then examined in AML12 cells under both high-glucose (33 mmol/L) and low-glucose (4.5 mmol/L) conditions. NK lowered the gene and protein expression of the anti-oxidases heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1 and increased p-eukaryotic initiation factor-2α(S51), p-nuclear factor-κB p65(S276), and its downstream proinflammatory factors, including interleukin-1 beta, tumor necrosis factor-α, matrix metalloproteinase 2, and matrix metalloproteinase 9, at the protein level. NK also altered the protein expression of fibroblast growth factor 21, glucose transporter type 4, insulin-like growth factor 1, forkhead box protein O1, p-AKT(S473), and p-GSK3α/β(Y279/Y216), which are involved in glucose uptake, glycogenesis, and gluconeogenesis in AML12 cells. Our results provide a comprehensive understanding of the central role of Nrf2 in the regulation of glucose metabolism in AML12 hepatocytes, in addition to its classical roles in the regulation of redox signaling, endoplasmic reticulum stress and proinflammatory responses, and support the potential of Nrf2 as a therapeutic target for the prevention and treatment of obesity and other associated metabolic syndromes. Impact statement Increasing evidence supports the complexity of Nrf2 functions beyond the antioxidant and detoxification response. Previous in vivo studies employing either Nrf2-knockout or Nrf2-activated mice have achieved a similar endpoint: protection against an obese and

  19. Leyes de atenuación de la intensidad macrosísmica en Colombia

    Directory of Open Access Journals (Sweden)

    Gómez Capera Augusto Antonio

    2002-08-01

    Full Text Available

    language: EN-US;" lang="EN-US">In order to establish the regional model of attenuation of macro seismic intensity with distance in the Colombian territory, the isoseismal maps of thirty four strong earthquakes were analysed in this paper. Using some teorical models of attenuation and the macroseismic focal depth we chose three different intervals (h < 20 km, h < 60 km and h > 60 km. From here the following three attenuation relations were obtained:

    language: EN-US;" lang="EN-US"> 

    language: EN-US;" lang="EN-US">[Mathematical Formula]

    language: EN-US;" lang="EN-US">[Mathematical Formula]

    language: EN-US;" lang="EN-US">[Mathematical Formula]

    language: EN-US;" lang="EN-US"> 

  20. The asymmetric effect of coal price on the China's macro economy using NARDL model

    Science.gov (United States)

    Hou, J. C.; Yang, M. C.

    2016-08-01

    The present work endeavors to explore the asymmetric effect of coal price on the China's macro economy by applying nonlinear autoregressive distributed lag (NARDL) model for the period of January 2005 to June 2015. The obtained results indicate that the coal price has a strong asymmetric effect on China's macro economy in the long-run. Namely one percent increase in coal price leads to 0.6194 percent of the China's macro economy increase; and while the coal price is reduces by 1 percent, the China's macro economy will decrease by 0.008 percent. These data indicate that when coal price rises, the effect on China's macro economy is far greater than the price decline. In the short-run, coal price fluctuation has a positive effect on the China's macro economy.

  1. 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...

  2. Different macro- and micro-rheological properties of native porcine respiratory and intestinal mucus.

    Science.gov (United States)

    Bokkasam, Harish; Ernst, Matthias; Guenther, Marco; Wagner, Christian; Schaefer, Ulrich F; Lehr, Claus-Michael

    2016-08-20

    Aim of this study was to investigate the similarities and differences at macro- and microscale in the viscoelastic properties of mucus that covers the epithelia of the intestinal and respiratory tract. Natural mucus was collected from pulmonary and intestinal regions of healthy pigs. Macro-rheological investigations were carried out through conventional plate-plate rheometry. Microrheology was investigated using optical tweezers. Our data revealed significant differences both in macro- and micro-rheological properties between respiratory and intestinal mucus.

  3. 实时定量荧光反转录-聚合酶链反应检测急性白血病AML1/ETO融合基因%Real-time RT-PCR for detection and quantification of AML1/ETO leukemia fusion gene

    Institute of Scientific and Technical Information of China (English)

    李斌; 喻镁佳; 梁洋; 李晓进; 胡杰; 陈琪; 李惠民

    2009-01-01

    Objective To set up real-time quantitative RT-PCR technique and measure leukemia fusion gene transcripts in patients with AML of FAB-M_2 subtype,and also to investigate the positive rate in patients and the relationship between the AMLI/ETO mRNA levels and the response rate after chemical therapy.Methods The plasmid containing the AMLI/ETO fusion gene sequences were constructed from myeloid cell lines Kasumi-1 (expressing AML1/ETO)to establish the standard curves,A TaqMan based realtime quantitative RT-PCR was performed to measure aberrant fusion gene transcripts in 45 samples of peripheral blood(PB) or bone marrow (BM) from 25 newly diagnosed patients with AML-M_2.All these 25 patients were diagnosed by the FCM(flow cytometry)and bone marrow molecular cytogenetics,and received the induce remission therapy with MA (Mitoxantrone+Ara-C).Results As a result,the AML1/ETO fusion gene transcripts were detected in 7(28%)out of 25 AML-M_2 patients (the ratios of AML1/ETO/ABL vary from 0.01 to 19.2),in which 5 patients were found t(8;21)(q22;q22).The transcript level of AML1/ETO fusion gene varied from the clinical situation of patients.These 7 patients with AML1/ETO fusion gene got complete remission(CR) after the first MA therapy,and the fusion gene reduced by 3 log in AML1/ETO/ABL.Only 11 patients got CR in 18 patients without AML1/ETO fusion gene.By following up these 7 patients with AML1/ ETO fusion gene kept persistent CR for 6 months.Conclusion It was concluded that real-time quantitative PCR is a reliable,innovative and promising technology with high sensitivity and speciality.It has potential clinical value for diagnosis,tumor typing,treatment selection,measuring the tumor load,monitoring fusion gene expression level and evaluating therapeutic strategy.It is worthy to apply in the clinical practice.%目的 建立实时定量荧光反转录-聚合酶链反应(RQ RT-PCR)的方法并用来检测急性髓系白血病(AML)-M_2:患者中 AML1/ETO融合基因的拷贝

  4. Macro-Historical Parallelism and the China “Puzzle”

    Directory of Open Access Journals (Sweden)

    Ruan Wei

    2010-05-01

    Full Text Available China’s rapid development in recent years has puzzled notonly the world but also the Chinese themselves. Growth on such a massive scale and at such an astonishing speed might seem miraculous and incomprehensible to many. Confronting the ‘puzzle’, it could bemeaningful for us to notice the fact that between China’s sinking to its nadir toward the end of the 19th century and its unmistakablerejuvenation after 1949, there was a lapse of only about fifty years. This is a very short time indeed in macro-historical terms. Or we could adopt a different way of periodizing, putting this period of time between the Opium Wars of the 1840s, when China was defeated by Britain and signed unequal treaties with the Western powers, and the 1990s, when China’s economy began decidedly to take off. In the latter case, a lapse of one hundred and fifty years is still a very short time macro-historically.

  5. Drops bouncing off macro-textured superhydrophobic surfaces

    Science.gov (United States)

    Mazloomi Moqaddam, Ali; Chikatamarla, Shyam S.; Karlin, Iliya V.

    2017-08-01

    Recent experiments with droplets impacting a macro-textured superhydrophobic surfaces revealed new regimes of bouncing with a remarkable reduction of the contact time. We present here a comprehensive numerical study that reveals the physics behind these new bouncing regimes and quantify the role played by various external and internal forces that effect the dynamics of a drop impacting a complex surface. For the first time, three-dimensional simulations involving macro-textured surfaces are performed. Aside from demonstrating that simulations reproduce experiments in a quantitative manner, the study is focused on analyzing the flow situations beyond current experiments. We show that the experimentally observed reduction of contact time extends to higher Weber numbers, and analyze the role played by the texture density. Moreover, we report a non-linear behavior of the contact time with the increase of the Weber number for application relevant imperfectly coated textures, and also study the impact on tilted surfaces in a wide range of Weber numbers. Finally, we present novel energy analysis techniques that elaborate and quantify the interplay between the kinetic and surface energy, and the role played by the dissipation for various Weber numbers.

  6. Macro Trends and the Future of Public Health Practice.

    Science.gov (United States)

    Erwin, Paul Campbell; Brownson, Ross C

    2016-12-15

    Public health practice in the twenty-first century is in a state of significant flux. Several macro trends are impacting the current practice of governmental public health and will likely have effects for many years to come. These macro trends are described as forces of change, which are changes that affect the context in which the community and its public health system operate. This article focuses on seven such forces of change: the Patient Protection and Affordable Care Act, public health agency accreditation, climate change, health in all policies, social media and informatics, demographic transitions, and globalized travel. Following the description of each of these, this article then turns to possible approaches to measuring, tracking, and understanding the impact of these forces of change on public health practice, including the use of evidence-based public health, practice-based research, and policy surveillance. Expected final online publication date for the Annual Review of Public Health Volume 38 is March 20, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  7. The Sensor Web: A Macro-Instrument for Coordinated Sensing

    Directory of Open Access Journals (Sweden)

    Kevin A. Delin

    2002-07-01

    Full Text Available The Sensor Web is a macro-instrument concept that allows for the spatiotemporal understanding of an environment through coordinated efforts between multiple numbers and types of sensing platforms, including both orbital and terrestrial and both fixed and mobile. Each of these platforms, or pods, communicates within their local neighborhood and thus distributes information to the instrument as a whole. Much as intelligence in the brain is a result of the myriad of connections between dendrites, it is anticipated that the Sensor Web will develop a macro-intelligence as a result of its distributed information with the pods reacting and adapting to their environment in a way that is much more than their individual sum. The sharing of data among individual pods will allow for a global perception and purpose of the instrument as a whole. The Sensor Web is to sensors what the Internet is to computers, with different platforms and operating systems communicating via a set of shared, robust protocols. This paper will outline the potential of the Sensor Web concept and describe the Jet Propulsion Laboratory (JPL Sensor Webs Project (http://sensorwebs.jpl.nasa.gov/. In particular, various fielded Sensor Webs will be discussed.

  8. The effects of macro-level interventions on addictive behavior.

    Science.gov (United States)

    Pacula, R L; Chaloupka, F J

    2001-12-01

    Drug addictions are often viewed as compulsive behaviors, not sensitive to the typical rules of self-discipline or market forces. Nonetheless, many governments try to discourage consumption of addictive substances through macro policy tools, such as taxation, regulation and prohibition, in an effort to reduce the harmful consequences that result from their consumption. The government's ability to discourage this type of behavior through these macro policies depends critically on the responsiveness of addictive consumption to market interventions. This paper reviews the growing literature that applies economic principles to the analysis of "substance abuse." Specifically, we review the impact of prices and public policies on the demands for tobacco, alcohol, and illicit drugs. The findings from these studies clearly demonstrate that even addictive behaviors are sensitive to changes in the price of substances being abused. When the full price of the addictive good rises, consumption of that good falls, even among abusers. Therefore, public policies that raise the full price of a drug to a consumer, particularly youth, are likely to result in long run reductions in rates of addiction.

  9. Health-related Quality of Life (HR-QOL) and Chronic Health Conditions in Survivors of Childhood Acute Myeloid Leukemia (AML) with Down Syndrome (DS): A Report From the Children's Oncology Group.

    Science.gov (United States)

    Schultz, Kris Ann P; Chen, Lu; Kunin-Batson, Alicia; Chen, Zhengjia; Woods, William G; Gamis, Alan; Kawashima, Toana; Oeffinger, Kevin C; Nicholson, H Stacy; Neglia, Joseph P

    2017-01-01

    Survival rates for children with Down syndrome (DS) and acute myeloid leukemia (AML) are high; however, little is known regarding the health-related quality of life (HR-QOL) of these survivors. Individuals who survived ≥5 years following diagnosis of childhood AML were invited to complete parent or patient-report surveys measuring HR-QOL and chronic health conditions. In total, 26 individuals with DS had a median age at diagnosis of 1.8 years (range, 0.77 to 10.9 y) and median age at interview of 15 years (range, 8.3 to 27.6 y). Participants with DS and AML were compared with AML survivors without DS whose caregiver completed a HR-QOL survey (CHQ-PF50). In total, 77% of survivors with DS reported ≥1 chronic health condition compared with 50% of AML survivors without DS (P=0.07). Mean physical and psychosocial QOL scores for children with DS and AML were statistically lower than the population mean, though not discrepant from AML survivors without DS. Although the overall prevalence of chronic health conditions in survivors with DS is higher than in survivors without DS, prior studies of children with DS have reported similarly high rates of chronic health conditions, suggesting that AML therapy may not substantially increase this risk.

  10. Fabrication of Macro-porous β-zeolite by Using Colloidal Polystyrene Spheres as a Template

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A β-zeolite/polystyrene composite material was synthesized by co-deposition of mono-disperse polystyrene spheres and nano β-zeolite particles in aqueous suspension on a vertical substrate. Macro-porous β-zeolite was obtained after the polystyrene template was removed by calcination. The micro/macro-pore structure of the prepared β-zeolite was highly ordered. In comparison with other assembly methods, the co-deposition method could obtain a highly ordered macro-porous material with relatively large zeolite filling particles, and therefore the co-deposition of particles with different size is a promising method for the fabrication of macro-porous materials.

  11. Heat Transfer and Energy Performance of a PVA Wall Tile Containing Macro-Encapsulated PCM

    Directory of Open Access Journals (Sweden)

    Pin-Feng Liu

    2016-08-01

    Full Text Available This study integrated building material engineering, building construction practices, and heat transfer mechanisms to develop a polyvinyl acetate (PVA based wall tile, containing macro-encapsulated phase change material (macro-encapsulated PCM, macroPCM and PVA. The heat transfer characteristics and energy performances of the proposed prototype were investigated experimentally. The results indicated that the PVA-based macroPCM wall tile is suitable for use in exterior walls to enhance the thermal performance. The tile shows a lower heat indoor heat flux than other tested similar building materials and increases the time lag of peak load, effectively shifting the summer peak demand.

  12. NMR assignments of the macro domain from Middle East respiratory syndrome coronavirus (MERS-CoV).

    Science.gov (United States)

    Huang, Yi-Ping; Cho, Chao-Cheng; Chang, Chi-Fon; Hsu, Chun-Hua

    2016-10-01

    The newly emerging human pathogen, Middle East respiratory syndrome coronavirus (MERS-CoV), contains a macro domain in the highly conserved N-terminal region of non-structural protein 3. Intense research has shown that macro domains bind ADP-ribose and other derivatives, but it still remains intangible about their exact function. In this study we report the preliminary structural analysis through solution NMR spectroscopy of the MERS-CoV macro domain. The near complete NMR assignments of MERS-CoV macro domain provide the basis for subsequent structural and biochemical investigation in the context of protein function.

  13. Macro histone variants are critical for the differentiation of human pluripotent cells.

    Science.gov (United States)

    Barrero, María J; Sese, Borja; Martí, Mercè; Izpisua Belmonte, Juan Carlos

    2013-05-31

    We have previously shown that macro histone variants (macroH2A) are expressed at low levels in stem cells and are up-regulated during differentiation. Here we show that the knockdown of macro histone variants impaired the in vitro and in vivo differentiation of human pluripotent cells, likely through defects in the silencing of pluripotency-related genes. ChIP experiments showed that during differentiation macro histone variants are recruited to the regulatory regions of pluripotency and developmental genes marked with H3K27me3 contributing to the silencing of these genes.

  14. A SAS-macro for estimation of the cumulative incidence using Poisson regression

    DEFF Research Database (Denmark)

    Waltoft, Berit Lindum

    2009-01-01

    the hazard rates, and the hazard rates are often estimated by the Cox regression. This procedure may not be suitable for large studies due to limited computer resources. Instead one uses Poisson regression, which approximates the Cox regression. Rosthøj et al. presented a SAS-macro for the estimation...... of the cumulative incidences based on the Cox regression. I present the functional form of the probabilities and variances when using piecewise constant hazard rates and a SAS-macro for the estimation using Poisson regression. The use of the macro is demonstrated through examples and compared to the macro presented...

  15. 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

  16. Chromatin organization as a possible factor in the control of susceptibility to radiation-induced AML in mice

    Science.gov (United States)

    Maranon, David G.

    The studies described in this dissertation involve the use and comparison of two mouse strains: one sensitive (CBA/CaJ) and another resistant (C57BL/6J) to radiation-induced acute myeloid leukemia (AML). The purpose of these studies was to identify factors that may account for the large difference in the susceptibility of these strains to radiation-induced AML. The present study was initiated to determine whether the distances between breakpoint clusters on chromosome 2 are in closer proximity in the bone marrow cells of the CBA/CaJ mouse strain than in the C57BL/6J strain. Bacterial artificial chromosomes (BACs) were selected as markers of the central portion of the proximal and distal deletion breakpoint clusters as well as mdr on chromosome 2, where the preponderance of breaks occurs. Distance measurements were made by three dimensional fluorescent in situ hybridization (3DFISH) image analysis of hundreds of cells using Metamorph and ImageJ for data collection and Autoquant software for deconvolution and reconstruction of the three dimensional cell nuclei. Comparing bone marrow cells of CBA/CaJ and C57BL/6J mice, no differences were found between the proximity of the two regions represented for the selected markers compared in both murine strains. For the markers chosen the distribution of the distances showed similarities between the same cell types from both mouse strains; namely, fibroblasts, whole bone marrow (WBM), and hematopoietic stem cells (HSC). However, there was not found a change in the distance distributions toward the closer distances expected between the clusters in HSC and WBM compared with fibroblasts in both mouse strains. There was; however, a tissue-dependent distance distribution between the markers Specifically, the average distances of the clusters in fibroblasts (2.55 um for CBA/CaJ and 3.09 um for C57BL/6) were larger than the distance in blood cells (1.74 um in BM and 1.53 um in HSC for CBA/CaJ; and 1.79 um in BM and 1.77 um in HSC for

  17. Therapy-related myelodysplastic syndrome/acute myeloid leukemia with del(7)(q22) in a patient with de novo AML.

    Science.gov (United States)

    Kim, Yang Gyun; Cho, Sun Young; Park, Tae Sung; Oh, Seung Hwan; Yoon, Hwi-Joong

    2011-01-01

    A 55-year-old Korean woman was initially diagnosed with acute myelomonocytic leukemia (AML). After induction chemotherapy was performed using cytarabine, idarubicin, and G-CSF, complete remission (CR) was subsequently achieved following reinduction chemotherapy using the same chemotherapeutic agents. Thirty-six months after the initial CR, an increase in immature cells (up to 12.0%) was observed in the patient's bone marrow. Because chromosome analysis revealed a karyotype of 46,XX,del(7)(q22) in all of the analyzed cells, the patient was diagnosed with therapy-related myelodysplastic syndrome (t-MDS). Although the patient subsequently received chemotherapy and G-CSF for neutropenia, t-MDS rapidly progressed after 3 months to therapy-related acute myeloid leukemia (t-AML). Although very rare, de novo AML can progress to a secondary MDS/AML with del(7q) after chemotherapy with cytarabine, idarubicin, and G-CSF. Further investigation into the role of genes located in 7q22 may provide more information about the mechanisms of leukemogenesis.

  18. Value of routine bone marrow examination in pediatric acute myeloid leukemia (AML) : A study of the Dutch Childhood Oncology Group (DCOG)

    NARCIS (Netherlands)

    Hageman, Ilse M. G.; Peek, Annemarie M. L.; de Haas, Valerie; Damen-Korbijn, Carin M.; Kaspers, Gertjan J. L.

    2012-01-01

    Background The outcome of the treatment of pediatric acute myeloid leukemia (AML) is still disappointing, due to relatively high treatment-related mortality and relapse rates (3040%). Past treatment protocols have called for routine screening via bone marrow aspiration (BMA) after achievement of fir

  19. RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML.

    Science.gov (United States)

    Loke, Justin; Assi, Salam A; Imperato, Maria Rosaria; Ptasinska, Anetta; Cauchy, Pierre; Grabovska, Yura; Soria, Natalia Martinez; Raghavan, Manoj; Delwel, H Ruud; Cockerill, Peter N; Heidenreich, Olaf; Bonifer, Constanze

    2017-05-23

    Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21 and t(3;21 AML

    Directory of Open Access Journals (Sweden)

    Justin Loke

    2017-05-01

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21 expressing RUNX1-ETO and the t(3;21 expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML.

  1. PRL-3, a metastasis associated tyrosine phosphatase, is involved in FLT3-ITD signaling and implicated in anti-AML therapy.

    Directory of Open Access Journals (Sweden)

    Jianbiao Zhou

    Full Text Available Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation of PTP4A3 (PRL-3 played a role in this synergism. PRL-3 is downstream of FLT3 signaling and ectopic expression of PRL-3 conferred therapeutic resistance through upregulation of STAT (signal transducers and activators of transcription pathway activity and anti-apoptotic Mcl-1 protein. PRL-3 interacts with HDAC4 and SAHA downregulates PRL-3 via a proteasome dependent pathway. In addition, PRL-3 protein was identified in 47% of AML cases, but was absent in myeloid cells in normal bone marrows. Our results suggest such combination therapies may significantly improve the therapeutic efficacy of FLT3 inhibitors. PRL-3 plays a potential pathological role in AML and it might be a useful therapeutic target in AML, and warrant clinical investigation.

  2. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10.

    NARCIS (Netherlands)

    Mandelli, F.; Vignetti, M.; Suciu, S.; Stasi, R.; Petti, M.C.; Meloni, G.; Muus, P.; Marmont, F.; Marie, J.P.; Labar, B.; Thomas, X.; Raimondo, F. Di; Willemze, R.; Liso, V.; Ferrara, F.; Baila, L.; Fazi, P.; Zittoun, R.; Amadori, S.; Witte, T.J.M. de

    2009-01-01

    PURPOSE: To compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia (AML). PATIENTS AND METHODS: We randomly assigned 2,157 patients (age range, 15 to 60 years) to receive intensive

  3. Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO-AML 2004 study

    DEFF Research Database (Denmark)

    Tierens, Anne; Bjørklund, Elizabeth; Siitonen, Sanna;

    2016-01-01

    Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society...

  4. c-Myc regulates expression of NKG2D ligands ULBP1/2/3 in AML and modulates their susceptibility to NK-mediated lysis.

    Science.gov (United States)

    Nanbakhsh, Arash; Pochon, Cécile; Mallavialle, Aude; Amsellem, Sophie; Bourhis, Jean Henri; Chouaib, Salem

    2014-06-05

    Cytarabine (cytosine arabinoside) is one of the most effective drugs for the treatment of patients diagnosed with acute myeloid leukemia (AML). Despite its efficiency against AML cells, the emergence of drug resistance due to prolonged chemotherapy in most patients is still a major obstacle. Several studies have shown that drug resistance mechanisms alter the sensitivity of leukemia cells to immune system effector cells. To investigate this phenomenon, parental acute myeloid cell lines, HL-60 and KG-1, were continuously exposed to increasing doses of cytarabine in order to establish equivalent resistant cell lines, HL-60(R) and KG-1(R). Our data indicate that cytarabine-resistant cells are more susceptible to natural killer (NK)-mediated cell lysis as compared with parental cytarabine-sensitive cells. The increased susceptibility correlates with the induction of UL-16 binding proteins (ULBP) 1/2/3 and NK group 2, member D (NKG2D) ligands on target cells by a mechanism involving c-Myc induction. More importantly, chromatin immunoprecipitation assay revealed that ULBP1/3 are direct targets of c-Myc. Using drug-resistant primary AML blasts as target cells, inhibition of c-Myc resulted in decreased expression of NKG2D ligands and the subsequent impairment of NK cell lysis. This study provides for the first time, the c-Myc dependent regulation of NKG2D ligands in AML. © 2014 by The American Society of Hematology.

  5. Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Qiu, Xiangning; Søgaard, Alexandra

    2012-01-01

    hypomethylation. AML patients without methylation of VTRNA2-1 have a considerably better outcome than those with monoallelic or biallelic methylation (n = 101, P = .001). We show that methylation is inversely correlated with vtRNA2-1 expression, and that 5-azanucleosides induce vtRNA2-1 and down...

  6. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10.

    NARCIS (Netherlands)

    Mandelli, F.; Vignetti, M.; Suciu, S.; Stasi, R.; Petti, M.C.; Meloni, G.; Muus, P.; Marmont, F.; Marie, J.P.; Labar, B.; Thomas, X.; Raimondo, F. Di; Willemze, R.; Liso, V.; Ferrara, F.; Baila, L.; Fazi, P.; Zittoun, R.; Amadori, S.; Witte, T.J.M. de

    2009-01-01

    PURPOSE: To compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia (AML). PATIENTS AND METHODS: We randomly assigned 2,157 patients (age range, 15 to 60 years) to receive intensive in

  7. CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age

    NARCIS (Netherlands)

    van den Heuvel-Eibrink, Marry M.; van der Holt, Bronno; Burnett, Alan K.; Knauf, Wolfgang U.; Fey, Martin F.; Verhoef, Gregor E. G.; Vellenga, Edo; Ossenkoppele, Gert J.; Lowenberg, Bob; Sonneveld, Pieter

    Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance (MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault

  8. 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.

  9. PRL-3, a metastasis associated tyrosine phosphatase, is involved in FLT3-ITD signaling and implicated in anti-AML therapy.

    Science.gov (United States)

    Zhou, Jianbiao; Bi, Chonglei; Chng, Wee-Joo; Cheong, Lip-Lee; Liu, Shaw-Cheng; Mahara, Sylvia; Tay, Kian-Ghee; Zeng, Qi; Li, Jie; Guo, Ke; Tan, Cheng Peow Bobby; Yu, Hanry; Albert, Daniel H; Chen, Chien-Shing

    2011-05-12

    Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation of PTP4A3 (PRL-3) played a role in this synergism. PRL-3 is downstream of FLT3 signaling and ectopic expression of PRL-3 conferred therapeutic resistance through upregulation of STAT (signal transducers and activators of transcription) pathway activity and anti-apoptotic Mcl-1 protein. PRL-3 interacts with HDAC4 and SAHA downregulates PRL-3 via a proteasome dependent pathway. In addition, PRL-3 protein was identified in 47% of AML cases, but was absent in myeloid cells in normal bone marrows. Our results suggest such combination therapies may significantly improve the therapeutic efficacy of FLT3 inhibitors. PRL-3 plays a potential pathological role in AML and it might be a useful therapeutic target in AML, and warrant clinical investigation.

  10. 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 establ...

  11. Chidamide, a novel histone deacetylase inhibitor, inhibits the viability of MDS and AML cells by suppressing JAK2/STAT3 signaling

    Science.gov (United States)

    Zhao, Sida; Guo, Juan; Zhao, Youshan; Fei, Chengming; Zheng, Qingqing; Li, Xiao; Chang, Chunkang

    2016-01-01

    Many studies have indicated that histone deacetylase (HDAC) activity is always increased in a lot of human tumors, and inhibition of HDAC activity is a promising new strategy in the treatment of cancers. Chidamide, a novel HDAC inhibitor of the benzamide class, is currently under clinical trials. In this study, we aimed to investigate the antitumor activity of Chidamide on myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) cell lines and explore the possible mechanism. Chidamide exhibited efficient anti-proliferative activity on MDS and AML cells in a time- and dose-dependent manner, accompanied by cell cycle arrest at G0/G1 phase and cell apoptosis. Importantly, Chidamide possessed potent HDAC inhibition property, as evaluated by HDAC activity analysis and acetylation of histone H3 and H4. Moreover, Chidamide significantly increased the expression of Suppressors of cytokine signaling 3 (SOCS3), reduced the expression of Janus activated kinases 2 (JAK2) and Signal transducer and activator of transcription 3 (STAT3), and inhibited STAT3 downstream genes, including c-Myc, Bcl-xL, and Mcl-1, which are involved in cell cycle progression and anti-apoptosis. Therefore, we demonstrate that Chidamide exhibits potent inhibitory effect on cell viability of MDS and AML cells, and the possible mechanism may lie in the downregulation of JAK2/STAT3 signaling through SOCS3 upregulation. Our data provide rationale for clinical investigations of Chidamide in MDS and AML. PMID:27508038

  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

    NARCIS (Netherlands)

    Giebel, S.; Labopin, M.; Mohty, M.; Mufti, G. J.; Niederwieser, D.; Cornelissen, J. J.; Janssen, J. J. W. M.; Milpied, N.; Vindelov, L.; Petersen, E.; Arnold, R.; Bacigalupo, A.; Blaise, D.; Craddock, C.; Nagler, A.; Frassoni, F.; Sadus-Wojciechowska, M.; Rocha, V.

    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 or

  13. Implication of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin-3 (IL-3) in Children with Acute Myeloid Leukaemia (AML).

    Science.gov (United States)

    Elbaz, O; Shaltout, A

    2000-01-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin-3 (IL-3) are increasingly used to stimulate granulopoiesis in neutropenic patients but these are rarely used in the lights of knowledge of the endogenous CSF-levels. In this study we measured serum levels of GM-CSF and IL-3 at diagnosis and after remission in children with acute leukaemia, using an enzyme linked immuno-sorbent assay (ELISA) techniques in 14 patients with acute myeloid leukaemia (AML) and 27 patients with acute lymphoblastic leukaemia (ALL). Twelve healthy age-matched children were used as a reference group. AML patients showed a highly significant increase in serum levels of GM-CSF and IL-3 before induction of therapy (p 0.5), with no significant difference between preinduction and postinduction serum levels of either (p > 0.5). Since these cytokines are known to be fundamental for the growth of AML cells, we postulate that the pretreatment levels of both GM-CSF and IL-3 could play a role in the pathogenesis of AML.

  14. Implication of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin-3 (IL-3) in Children with Acute Myeloid Leukaemia (AML); Malignancy.

    Science.gov (United States)

    Elbaz, Osama; Shaltout, Ali

    2001-01-01

    Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin-3 (IL-3) are increasingly used to stimulate granulopoiesis in neutropenic patients but these are rarely used in the lights of knowledge of the endogenous CSF-levels. In this study we measured serum levels of GM-CSF and IL-3 at diagnosis and after remission in children with acute leukaemia, using an enzyme linked immuno-sorbent assay (ELISA) techniques in 14 patients with acute myeloid leukaemia (AML) and 27 patients with acute lymphoblastic leukaemia (ALL). Twelve healthy age-matched children were used as a reference group. AML patients showed a highly significant increase in serum levels of GM-CSF and IL-3 before induction of therapy (p 0.5), with no significant difference between preinduction and postinduction serum levels of either (p > 0.5). Since these cytokines are known to be fundamental for the growth of AML cells, we postulate that the pretreatment levels of both GM-CSF and IL-3 could play a role in the pathogenesis of AML.

  15. Non-intensive treatment with low-dose 5-aza-2'-deoxycytidine (DAC) prior to allogeneic blood SCT of older MDS/AML patients.

    Science.gov (United States)

    Lübbert, M; Bertz, H; Rüter, B; Marks, R; Claus, R; Wäsch, R; Finke, J

    2009-11-01

    Novel, non-intensive treatment options in older MDS/AML patients planned for allografting, with the goal of down-staging the underlying disease and bridging time to transplantation, are presently being developed. 5-azacytidine and decitabine (DAC) are of particular interest, as they can be given repetitively, with very limited non-hematologic toxicity and result in responses both in MDS and AML even at low doses. We describe 15 consecutive patients (median age 69 years, range 60-75 years) with MDS (n=10) or AML (n=5) who all received first-line treatment with DAC and subsequent allografting (from sibling donor in four patients, unrelated donor in 11) after reduced-intensity conditioning with the FBM regimen. Successful engraftment was attained in 14/15 patients, all of whom achieved a CR, with a median duration of 5 months (range 1+ to 51+). Six of these 14 patients are alive (4 with complete donor chimerism), 8 have died either from relapse (n=4) or treatment-related complications while in CR (n=4). We conclude that allografting after low-dose DAC and subsequent conditioning with FBM is feasible, with no unexpected toxicities and appears as a valid alternative to standard chemotherapy ('InDACtion instead of induction') in elderly patients with MDS/AML.

  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 unanswe...

  17. 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...

  18. The global impact of non-communicable diseases on macro-economic productivity: a systematic review.

    Science.gov (United States)

    Chaker, Layal; Falla, Abby; van der Lee, Sven J; Muka, Taulant; Imo, David; Jaspers, Loes; Colpani, Veronica; Mendis, Shanthi; Chowdhury, Rajiv; Bramer, Wichor M; Pazoki, Raha; Franco, Oscar H

    2015-05-01

    Non-communicable diseases (NCDs) have large economic impact at multiple levels. To systematically review the literature investigating the economic impact of NCDs [including coronary heart disease (CHD), stroke, type 2 diabetes mellitus (DM), cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD)] on macro-economic productivity. Systematic search, up to November 6th 2014, of medical databases (Medline, Embase and Google Scholar) without language restrictions. To identify additional publications, we searched the reference lists of retrieved studies and contacted authors in the field. Randomized controlled trials, cohort, case-control, cross-sectional, ecological studies and modelling studies carried out in adults (>18 years old) were included. Two independent reviewers performed all abstract and full text selection. Disagreements were resolved through consensus or consulting a third reviewer. Two independent reviewers extracted data using a predesigned data collection form. Main outcome measure was the impact of the selected NCDs on productivity, measured in DALYs, productivity costs, and labor market participation, including unemployment, return to work and sick leave. From 4542 references, 126 studies met the inclusion criteria, many of which focused on the impact of more than one NCD on productivity. Breast cancer was the most common (n = 45), followed by stroke (n = 31), COPD (n = 24), colon cancer (n = 24), DM (n = 22), lung cancer (n = 16), CVD (n = 15), cervical cancer (n = 7) and CKD (n = 2). Four studies were from the WHO African Region, 52 from the European Region, 53 from the Region of the Americas and 16 from the Western Pacific Region, one from the Eastern Mediterranean Region and none from South East Asia. We found large regional differences in DALYs attributable to NCDs but especially for cervical and lung cancer. Productivity losses in the USA ranged from 88 million

  19. Community Languages.

    Science.gov (United States)

    Landon, John

    2001-01-01

    Presents historical and political contexts for discussing language maintenance and development in Scotland, explaining that research findings rarely have an impact on policy. While good practice exists in the maintenance of Gaelic and British Sign Language, these is a significant lack of support for other languages, and provision for all community…

  20. Learning Languages.

    Science.gov (United States)

    Black, Susan

    1993-01-01

    Foreign language study is finding a niche in the elementary school curriculum. Schools now offer Chinese, Russian, Arabic, Swedish, and Japanese, instead of teaching mostly German and the Romance languages. Studies agree that children pursuing foreign languages show more creativity, divergent thinking, and higher-order thinking skills and score…