WorldWideScience

Sample records for macro language aml

  1. Recursive macro generator for the TAS-86 language. First part: the macro generator language. Second part: system internal logics

    International Nuclear Information System (INIS)

    Zraick, Samir

    1970-01-01

    A macro-generator is a translator which is able to interpret and translate a programme written in a macro-language. After a first part presenting the main notions and proposing a brief description of the TAS-86 language, the second part of this research thesis reports the development of the macro-generator language, and notably presents the additional functionalities provided by the macro generator. The development is illustrated by logical flowcharts and programming listings

  2. MORTRAN-2, FORTRAN Language Extension with User-Supplied Macros

    International Nuclear Information System (INIS)

    Cook, A. James; Shustek, L.J.

    1980-01-01

    1 - Description of problem or function: MORTRAN2 is a FORTRAN language extension that permits a relatively easy transition from FORTRAN to a more convenient and structured language. Its features include free-field format; alphanumeric statement labels; flexible comment convention; nested block structure; for-by-to, do, while, until, loop, if-then-else, if-else, exit, and next statements; multiple assignment statements; conditional compilation; and automatic listing indentation. The language is implemented by a macro-based pre-processor and is further extensible by user-defined macros. 2 - Method of solution: The MORTRAN2 pre-processor may be regarded as a compiler whose object code is ANSI Standard FORTRAN. The MORTRAN2 language is dynamically defined by macros which are input at each use of the pre-processor. 3 - Restrictions on the complexity of the problem: The pre-processor output must be accepted by a FORTRAN compiler

  3. MACRO

    International Nuclear Information System (INIS)

    Rogner, H.H.

    1989-01-01

    The description is given to MACRO which is a numerically formulated macroeconomic model constructed to reflect the economy of the European Community. The model belongs to the group of general equilibrium models often applied in long-term macroeconomic energy modeling. Furthermore, MACRO was designed so as to interact with other more technically oriented energy demand and supply models. It's main objective is to provide consistency checks between assumptions concerning energy trade, energy prices, resource availability and energy-related capital requirements. 5 figs

  4. 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…

  5. 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...

  6. STRCMACS: An extensive set of Macros for structured programming in OS/360 assembly language

    Science.gov (United States)

    Barth, C. W.

    1974-01-01

    Two techniques are discussed that have been most often referred to as structured programming. One is that of programming with high level control structures (such as the if and while) replacing the branch instruction (goto-less programming); the other is the process of developing a program by progressively refining descriptions of components in terms of more primitive components (called stepwise refinement or top-down programming). In addition to discussing what these techniques are, it is shown why their use is advised and how both can be implemented in OS assembly language by the use of a special macro instruction package.

  7. Non-linear algorithms solved with the help of the GIBIANE macro-language

    International Nuclear Information System (INIS)

    Ebersolt, L.; Combescure, A.; Millard, A.; Verpeaux, P.

    1987-01-01

    Non linear finite element problems are often solved with the help of iteratives procedures. In the finite element program CASTEM 2000, the syntax of the dataset permits the user to derive his own algorithm and tune it to his problem. These basic ideas, simple to imagine, needed a proper frame to be materialized in a general purpose finite element program, and three concepts emerged: Operators, the Gibiane macro-language. In the two first paragraphs, we will detail these concepts, in the third paragraph, we will describe the different possibilities of the program, in the fourth paragraph, we will show, by combining operators in a proper order, how to obtain the desired algorithm. (orig./GL)

  8. 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…

  9. Gender differences in second language motivation: An investigation of micro- and macro-level influences

    Directory of Open Access Journals (Sweden)

    Scott Kissau

    2006-06-01

    Full Text Available Abstract The present article is part of a large-scale study conducted in Ontario that investigated gender differences in motivation to learn French. However, for this particular article second language (L2 motivation theory is the primary focus. Over the past 30 years of research, the study of L2 motivation has evolved. There appears to be a definite shift away from the societal (macro-level approaches that dominated the research of the 1970s and 1980s toward an approach that emphasizes the influence of the L2 classroom. The researcher calls into question this evolution in research. A mixed methodology was used to determine if gender differences in a variety of motivational factors exist among Grade 9 French as a second language (FSL students. Approximately 500 students in Grade 9 completed a questionnaire. The significant findings of the questionnaire were then explored in interviews with students and teachers. Quantitative results indicated significant differences in regard to several motivational factors. However, the qualitative data emphasized that at the root of these differences were societal influences.

  10. 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...

  11. 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.

  12. 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.

  13. Parser Macros for Scala

    OpenAIRE

    Duhem, Martin; Burmako, Eugene

    2015-01-01

    Parser macros are a new kind of macros that allow developers to create new language constructs and to define their own syntax for using them. In this report, we present why parser macros are useful and the kind of problems that they help to solve. We will also see how they are implemented and gain insight about how they take advantage from scala.meta, the new metaprogramming toolkit for Scala. Finally, we will discuss what are the current limitations of parser macros and what is left for futu...

  14. English Language Teacher Educators' Pedagogical Knowledge Base: The Macro and Micro Categories

    Science.gov (United States)

    Moradkhani, Shahab; Akbari, Ramin; Samar, Reza Ghafar; Kiany, Gholam Reza

    2013-01-01

    The aim of this study was to determine the major categories of English language teacher educators' pedagogical knowledge base. To this end, semi-structured interviews were conducted with 5 teachers, teacher educators, and university professors (15 participants in total). The results of data analysis indicated that teacher educators' pedagogical…

  15. A generalized macro-assembler

    International Nuclear Information System (INIS)

    Kaul, Mohan Lai

    1970-01-01

    The objective of this research is to study existing macro assemblers, and to create a generalized macro assembler, MAG-I, which is a system independent of a source language, and provides the following possibilities: development of any existing language, translation from a language to another, and creation of a new language. The user can choose his own notations to define macros. The system is implemented on an IBM 360/91 computer. Programs are written in symbolic language and the input/output software is written in Fortran [fr

  16. ZEUS - standardized macros for the TPA computer

    International Nuclear Information System (INIS)

    Winde, M.

    1976-01-01

    An existing cross-assembler with macro-option was modified to allow the usage of the ZEUS macros. The ZEUS macros are understood by the assembler without prior definition by the user. ZEUS macros allow the programmer, who is obliged to code his TPA (PDP-8) programs on the assembler level to formulate his program logic as in a higher level language. ZEUS macros offer all basic elements necessary for structured programming. (author)

  17. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  1. WHO HAS THERAPY-RELATED AML?

    Directory of Open Access Journals (Sweden)

    Robert Gale

    2017-03-01

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

  2. AML (Advanced Mud Logging: First Among Equals

    Directory of Open Access Journals (Sweden)

    T. Loermans

    2017-09-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Time and Space Complexity of Inside-Out Macro Grammars

    NARCIS (Netherlands)

    Asveld, P.R.J.

    1980-01-01

    Starting form Fischer's IO Standard Form Theorem we show that for each inside-out (or IO-) macro language $L$ there exists a $\\lambda$-free IO macro grammar with the following property: for each $x$ in $L$ there is a derivation of $x$ of length at most linear in the length of $x$. Then we construct

  5. 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…

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

    Science.gov (United States)

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

    2016-10-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  8. 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.

  9. 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...

  10. The Accelerator Markup Language and the Universal Accelerator Parser

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  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. 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...

  13. 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...

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

    Science.gov (United States)

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

    2017-09-01

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

  15. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  16. 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

  17. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  18. Macro Dark Matter

    CERN Document Server

    Jacobs, David M; Lynn, Bryan W.

    2015-01-01

    Dark matter is a vital component of the current best model of our universe, $\\Lambda$CDM. There are leading candidates for what the dark matter could be (e.g. weakly-interacting massive particles, or axions), but no compelling observational or experimental evidence exists to support these particular candidates, nor any beyond-the-Standard-Model physics that might produce such candidates. This suggests that other dark matter candidates, including ones that might arise in the Standard Model, should receive increased attention. Here we consider a general class of dark matter candidates with characteristic masses and interaction cross-sections characterized in units of grams and cm$^2$, respectively -- we therefore dub these macroscopic objects as Macros. Such dark matter candidates could potentially be assembled out of Standard Model particles (quarks and leptons) in the early universe. A combination of earth-based, astrophysical, and cosmological observations constrain a portion of the Macro parameter space; ho...

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

    Science.gov (United States)

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

    2013-03-01

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

  20. REXX: The universal macro and scripting language

    International Nuclear Information System (INIS)

    Dager, C.B.

    1993-03-01

    The speaker, who is the founder of the annual REXX symposium, will share her perspective on the status of REXX within and beyond IBM. In this session, current uses of REXX will be cited and implications for the future will be explored

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Geetha N.

    2015-02-01

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

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

    Science.gov (United States)

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

    2009-11-01

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

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

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

    DEFF Research Database (Denmark)

    Knapper, Steven; Russell, Nigel; Gilkes, Amanda

    2017-01-01

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

  6. 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

  7. The role of therapeutic leukapheresis in hyperleukocytotic AML.

    Directory of Open Access Journals (Sweden)

    Friederike Pastore

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

  8. Macro-economic environmental models

    International Nuclear Information System (INIS)

    Wier, M.

    1993-01-01

    In the present report, an introduction to macro-economic environmental models is given. The role of the models as a tool for policy analysis is discussed. Future applications, as well as the limitations given by the data, are brought into focus. The economic-ecological system is described. A set of guidelines for implementation of the system in a traditional economic macro-model is proposed. The characteristics of empirical national and international environmental macro-economic models so far are highlighted. Special attention is paid to main economic causalities and their consequences for the environmental policy recommendations sat by the models. (au) (41 refs.)

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

    Science.gov (United States)

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

    2016-11-03

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

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  11. 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

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

    DEFF Research Database (Denmark)

    Madsen, Stine Skov; Krenk, Steen

    2017-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-05-14

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

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

    Science.gov (United States)

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

    2001-10-13

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

  16. 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.

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  18. 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,

  19. EAI 8400 - Manual of the D5LA-2-2 macro-assembler

    International Nuclear Information System (INIS)

    Roux, Pierre

    1968-01-01

    The assembly language is a symbolic language specific to the EAI 8400 calculation system. This manual presents the overall rules to write a program with this language. However, the symbolic code of machine instructions and their effect are not given in this manual. The language described here corresponds to the specifications of the version 5B of the assembler. This manual presents first the general rules of the symbolic language writing (the source language) and details the pseudo- and macro-instructions. The assembler's job is briefly described in the introduction

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

    Science.gov (United States)

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

    2016-02-18

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

  1. 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.

  2. Macro-elementwise preconditioning methods

    Czech Academy of Sciences Publication Activity Database

    Axelsson, Owe

    2012-01-01

    Roč. 82, č. 10 (2012), s. 1952-1963 ISSN 0378-4754 Institutional research plan: CEZ:AV0Z30860518 Keywords : heterogeniety * elementwise preconditioning * block matrix partitioning * macro-elements Subject RIV: BA - General Mathematics Impact factor: 0.836, year: 2012 http://www.sciencedirect.com/science/journal/03784754

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

    Science.gov (United States)

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

    2017-12-01

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

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

    OpenAIRE

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    International Nuclear Information System (INIS)

    Yanada, Masamitsu

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Virginie Marcel

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

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  12. Macro-Micro Interlocked Simulator

    International Nuclear Information System (INIS)

    Sato, Tetsuya

    2005-01-01

    Simulation Science is now standing on a turning point. After the appearance of the Earth Simulator, HEC is struggling with several severe difficulties due to the physical limit of LSI technologies and the so-called latency problem. In this paper I would like to propose one clever way to overcome these difficulties from the simulation algorithm viewpoint. Nature and artificial products are usually organized with several nearly autonomously working internal systems (organizations, or layers). The Earth Simulator has gifted us with a really useful scientific tool that can deal with the entire evolution of one internal system with a sufficient soundness. In order to make a leap jump of Simulation Science, therefore, it is desired to design an innovative simulator that enables us to deal with simultaneously and as consistently as possible a real system that evolves cooperatively with several internal autonomous systems. Three years experience of the Earth Simulator Project has stimulated to come up with one innovative simulation algorithm to get rid of the technological barrier standing in front of us, which I would like to call 'Macro-Micro Interlocked Algorithm', or 'Macro-Micro Multiplying Algorithm', and present a couple of such examples to validate the proposed algorithm. The first example is an aurora-arc formation as a result of the mutual interaction between the macroscopic magnetosphere-ionosphere system and the microscopic field-aligned electron and ion system. The second example is the local heavy rain fall resulting from the interaction between the global climate evolution and the microscopic raindrop growth process. Based on this innovative feasible algorithm, I came up with a Macro-Micro Multiplying Simulator

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

    Science.gov (United States)

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

    2007-07-01

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

  14. 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

  15. Macro-Fiber Composite Based Transduction

    Science.gov (United States)

    2016-03-01

    substrate Material properties of single crystal macro fiber composite actuators for active twist rotor blades Park, Jae-Sang (Seoul National...Passive Smart Structures and Integrated Systems 2007 Material properties of single crystal macro fiber composite actuators for active twist rotor ...19b. TELEPHONE NUMBER (Include area code) 10-03-20 16 Final Report 01 Jan 2013 - 31 Dec 2015 Macro-Fiber Composite Based Transduction N000-14-13-1-0212

  16. High macro rubber band ligature

    Directory of Open Access Journals (Sweden)

    José A. Reis Neto

    2013-07-01

    Full Text Available Purpose: The goal of a rubber band ligature is to promote fibrosis of the submucosa with subsequent fixation of the anal epithelium to the underlying sphincter. Following this principle, a new technique of ligature was developed based on two aspects: 1. macro banding: to have a better fibrosis and fixation by banding a bigger volume of mucosa and 2. higher ligature: to have this fixation at the origin of the hemorrhoidal cushion displacement. Methods: 1634 patients with internal hemorrhoidal disease grade II or III were treated by the technique called high macro rubber band. There was no distinction as to age, gender or race. To perform this technique a new hemorrhoidal device was specially designed with a larger diameter and a bigger capacity for mucosal volume aspiration. It is recommended to utilize a longer and wider anoscope to obtain a better view of the anal canal, which will facilitate the injection of submucosa higher in the anal canal and the insertion of the rubber band device. The hemorrhoidal cushion must be banded higher in the anal canal (4 cm above the pectinate line. It is preferable to treat all the hemorrhoids in one single session (maximum of three areas banded. Results: The analysis was retrospective without any comparison with conventional banding. The period of evaluation extended from one to twelve years. The analysis of the results showed perianal edema in 1.6% of the patients, immediate tenesmus in 0.8%, intense pain (need for parenteral analgesia in 1.6%, urinary retention in 0.1% of the patients and a symptomatic recurrence rate of 4.2%. All patients with symptomatic recurrence were treated with a new session of macro rubber banding. None of the patients developed anal or rectal sepsis. Small post-ligature bleeding was observed only in 0.8% of the patients. Conclusions: The high macro rubber banding technique represents an alternative method for the treatment of hemorrhoidal disease grades II or III, with good

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Science.gov (United States)

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

    2014-04-01

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

  19. 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.

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

    Science.gov (United States)

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

    2018-06-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    DEFF Research Database (Denmark)

    Tawana, Kiran; Wang, Jun; Renneville, Aline

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    OpenAIRE

    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 applications, VHDL for hardware design, ...), but many more will be needed for both new as well as existing application domains. Language design assistants to help develop them currently exist only in...

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

    Science.gov (United States)

    2018-03-05

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2001-03-01

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

  9. 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...

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2018-02-26

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

  12. 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

  13. Parents as Stakeholders: Language Management in Urban Galician Homes

    Science.gov (United States)

    Nandi, Anik

    2018-01-01

    Macro-level policy makers, perceived as stakeholders of language management, employ a range of language policy strategies to legitimise hegemonic control over meso- (i.e. family) and micro- (i.e. individual) level language ideologies (Cassels-Johnson 2013). However, language policies of an individual are often difficult to detect because they are…

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

    NARCIS (Netherlands)

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

    2017-01-01

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

  15. Macro scale models for freight railroad terminals.

    Science.gov (United States)

    2016-03-02

    The project has developed a yard capacity model for macro-level analysis. The study considers the detailed sequence and scheduling in classification yards and their impacts on yard capacities simulate typical freight railroad terminals, and statistic...

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

    Science.gov (United States)

    Guan, Y; Hogge, D E

    2000-12-01

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

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

    Science.gov (United States)

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

    2013-10-01

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

  18. 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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  20. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    1994-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-05-18

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

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

    Science.gov (United States)

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

    2017-03-28

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

  6. 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.

  7. Macro-prudentiality and financial stability

    Directory of Open Access Journals (Sweden)

    Cristian Ionescu

    2012-12-01

    Full Text Available Taking into consideration the fact that financial crises, as a manifestation form of the financial instability, are becoming more and more frequent, complex and severe, it is important to discuss about the macroeconomic prudentiality, in order to protect and save the economy of a country or of a region by the inherent fragility of a very developed financial system. Therefore, the paper aims to analyze the following aspects: the macro-prudential regulation (in order to a better understanding of the financial instability process, the development of the macro-prudential vision and instruments (but emphasizing the existing limits and economic policies (in order to implement an operational macro-prudential regulation.

  8. 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.

  9. 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...

  10. Software support for Motorola 68000 microprocessor at CERN. M68MIL cross macro assembler

    International Nuclear Information System (INIS)

    Eicken, H. von.

    1983-01-01

    This document is a user's guide for programming the Motorola 68000 microprocessor in assembly language. It describes the programming model, addressing modes and instruction set of the M 68000 as well as the use of the M68mil cross macro assembler. Version 3.6 of the assembler has been installed at CERN on CDC, DEC VAX, IBM, Norsk Data and Siemens computers. The source code of the assembler is available from CERN on request. (orig.)

  11. 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 litteratur...

  12. 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

  13. Description and performances of MACRO TRD

    International Nuclear Information System (INIS)

    Bellotti, R.; Barbarito, E.; Cafagna, F.; Castellano, M.; De Cataldo, G.; De Marzo, C.; Favuzzi, C.; Fusco, P.; Giglietto, N.; Mazziotta, M.N.; Perchiazzi, M.; Raino', A.; Sacchetti, A.; Spinelli, P.

    1995-01-01

    We discuss the applications of a transition radiation detector (TRD) to measure the residual energy of cosmic rays muons in underground laboratories and present the first MACRO TRD module. Results from prototypes operated in a test beam at CERN PS are also given. (orig.)

  14. An efficient macro-cell placement algorithm

    NARCIS (Netherlands)

    Aarts, E.H.L.; Bont, de F.M.J.; Korst, J.H.M.; Rongen, J.M.J.

    1991-01-01

    A new approximation algorithm is presented for the efficient handling of large macro-cell placement problems. The algorithm combines simulated annealing with new features based on a hierarchical approach and a divide-and-conquer technique. Numerical results show that these features can lead to a

  15. 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…

  16. 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

  17. 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

  18. 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…

  19. Joint Macro and Femto Field Performance and Interference Measurements

    DEFF Research Database (Denmark)

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

    2012-01-01

    In this paper macro performance in a co-channel macro and femto setup is studied. Measurements are performed in a live Universal Mobile Telecommunication System (UMTS) network. It is concluded that femto interference does not affect macro downlink (DL) performance as long as the macro Received Si...... 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.......In this paper macro performance in a co-channel macro and femto setup is studied. Measurements are performed in a live Universal Mobile Telecommunication System (UMTS) network. It is concluded that femto interference does not affect macro downlink (DL) performance as long as the macro Received...... 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...

  20. 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…

  1. 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).

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

    Vyas, Chintan; Jain, Sandeep; Kapoor, Gauri

    2018-01-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

  5. 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

    This Macro-economic Impact Study (MES) provides quantitative insights into the macro-economic effects of introducing green, palmbased alternatives for electricity, fuels, chemicals and materials industries in Malaysia between now and 2030.

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

    International Nuclear Information System (INIS)

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

    1999-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Chana L. Glasser, MD

    2017-01-01

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

  9. Corporate Language: The Blind Spot of Language Policy? Reflections on France's Loi Toubon

    Science.gov (United States)

    Saulière, Jérôme

    2014-01-01

    This article looks at France's Loi Toubon, which mandates the use of French in private companies, to illustrate how macro-level language planning reaches a dead end if it fails to consider local contexts and involve micro-level agents. The motivations, limitations and contradictions of France's language policy in relation to companies are…

  10. 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.

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

    KAUST Repository

    Aldehaiman, Mansour M.

    2018-04-01

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

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

    Science.gov (United States)

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

    2016-08-19

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

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

    International Nuclear Information System (INIS)

    Harada, Yuka; Kimura, Akiro; Harada, Hironori

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Merk Martina

    2011-09-01

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

  16. 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.

  17. Evolution: Language Use and the Evolution of Languages

    Science.gov (United States)

    Croft, William

    Language change can be understood as an evolutionary process. Language change occurs at two different timescales, corresponding to the two steps of the evolutionary process. The first timescale is very short, namely, the production of an utterance: this is where linguistic structures are replicated and language variation is generated. The second timescale is (or can be) very long, namely, the propagation of linguistic variants in the speech community: this is where certain variants are selected over others. At both timescales, the evolutionary process is driven by social interaction and the role language plays in it. An understanding of social interaction at the micro-level—face-to-face interactions—and at the macro-level—the structure of speech communities—gives us the basis for understanding the generation and propagation of language structures, and understanding the nature of language itself.

  18. 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…

  19. Technology strategy as macro-actor

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2003-01-01

    -human entities to the explanatory repertoire of strategy research, another line of inquiry is pursued. The performative perspective thus proposed, is inspired by the classical work of Von Clausewitz and the recent anthropology of science, technology and organizational identities. In the proposed perspective...... case account for how the strategic technology and the strategic collective emerge and co-produce each other as a macro-actor, only to become transformed in unexpected ways - as common technology and reflective human subjects.In the concluding section, it is argued that the humanity of the reflective...... outcomes, as providers of explanations and observations. The expression `technological strategy as macro-actor' summarizes these findings and the associated implications for research and practice....

  20. Macro factors in oil futures returns

    International Nuclear Information System (INIS)

    Le Pen, Yannick; Sevi, Benoit

    2012-01-01

    We investigate the macro factors that can explain the monthly oil futures return for the NYMEX WTI futures contract for the time period 1993:11 to 2010:03. We build a new database of 187 real and nominal macro-economic variables from developed and emerging countries and resort to the large factor approximate model to extract 9 factors from this dataset. We then regress crude oil return on several combinations of these factors. Our best model explains around 38% of the variability of oil futures return. More interestingly, the factor which has the largest influence on crude oil price is related to real variables from emerging countries. This result confirms the latest finding in the literature that the recent evolution in oil price is attributable to change in supply and demand conditions and not to the large increase in trading activity from speculators. (authors)

  1. 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....

  2. 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.

  3. A muon trigger for the MACRO apparatus

    International Nuclear Information System (INIS)

    Barbarito, E.; Bellotti, R.; Calicchio, M.; Castellano, M.; DeCataldo, G.; DeMarzo, C.; Erriquez, O.; Favuzzi, C.; Giglietto, N.; Liuzzi, R.; Spinelli, P.

    1991-01-01

    A trigger circuit based on EPROM components, able to manage up to 30 lines from independent counters, is described. The circuit has been designed and used in the MACRO apparatus at the Gran Sasso Laboratory for triggering on fast particles. The circuit works with standard TTL positive logic and is assembled in a double standard CAMAC module. It has a high triggering capacity and a high flexibility. (orig.)

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

    Science.gov (United States)

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

    2007-04-01

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

  5. 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.

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

    Science.gov (United States)

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

    2017-06-20

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

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

    Science.gov (United States)

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

    2015-12-14

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

  8. 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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  10. 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.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

    Ossenkoppele, Gert J; Schuurhuis, Gerrit Jan

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    1998-01-01

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

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

    Science.gov (United States)

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

    2001-03-02

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

  15. 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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    KAUST Repository

    Aldehaiman, Mansour M.

    2018-01-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  19. 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. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  20. The International Macro-Environment of an Organization

    OpenAIRE

    Ileana (Badulescu) Anastase; Cornel Grigorut

    2016-01-01

    The international macro-environment (supranational macro-environment) brings together allthe uncontrollable factors with a global impact, and it is related to the organization’s indirectrelationships on international markets. Romania’s globalization and the EU integration increasedthe importance of the macro-environment for all organizations, regardless of their degree ofinternationalization. In marketing, we must master the main agreements between countries and theregulations emanating from ...

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

    Science.gov (United States)

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

    2007-10-01

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

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

    Science.gov (United States)

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

    2013-07-01

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

  3. The MACRO detector at Gran Sasso

    International Nuclear Information System (INIS)

    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.; 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.; 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.; Spinetti, M.; Spurio, M.; Stalio, S.; Steinberg, R.; Stone, J.L.; Sulak, L.R.; Surdo, A.; Tarle, G.; Togo, V.; Vakili, M.; Valieri, C.; Walter, C.W.; Webb, R.; Zaccheo, N.

    2002-01-01

    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 β=10 -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

  4. A comparison between MARKAL-MACRO and MARKAL

    International Nuclear Information System (INIS)

    Schepers, E.

    1995-11-01

    Differences between CO 2 -reduction scenarios of the MARKAL-MACRO model and the MARKAL model are studied. Also attention is paid to the rebound effect, i.e. the effect on a price decrease leads to an increase of the energy demand, and energy savings will result in a redistribution of saved income over other goods and services. MARKAL is an energy supply model and MACRO is a macro-economic model. The combination of the two is an example of a hard-linked model between a top-down model (MACRO) and a bottom-up model (MARKAL). 15 figs., 5 tabs., 18 refs., 2 appendices

  5. 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)

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

    Science.gov (United States)

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

    2016-01-19

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

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

    Science.gov (United States)

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

    2015-08-01

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

  8. Study on developing energy-macro model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Duk [Korea Energy Economics Institute, Euiwang (Kenya)

    1999-12-01

    It analyzed the effect of international oil price on domestic economy and its path, time difference and degree of effect. First of all, it analyzed whether the long-term relationship between international oil price and price exists focusing on integral relationship, and estimated dynamic price fluctuation by using error correction model. Moreover, using structural VAR model, it analyzed what kind of shocking reactions are showed when the increase of international oil price affects on domestic macro economic variables. Commonly it is estimated that price is increasing in a long term not in a short term as the international oil price is increasing. When the international oil price increases, it is estimated that its effect in a short term is insignificant because of direct price control by the government and then its spreading effect on economy shows a long-term effect by deepening the price control. (author). 16 refs., 3 figs., 10 tabs.

  9. Macro-environmental policy: Principles and design

    International Nuclear Information System (INIS)

    Huppes, G.

    1993-01-01

    The central theme of this book is how macro-environmental policy can be developed, which does not prescribe or suggest specific technologies and products bu realizes the environmental quality desired by changing the general context. The publication is composed of four main parts. The framework for analysis and the normative principles for policy design and evaluation, the first two parts, form the analytic core. The framework for analysis gives a classification of instruments in terms of permutations of a limited number of defining elements. The normative principles guide choices in instrument design and, as the flexible response strategy, guide their application in specific policies. Detailing two main new instruments (the standard method for life cycle analysis and the substance deposit, and applying the instrument strategy as developed to the cases make up the next two parts

  10. 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.

  11. 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 was ...

  12. 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....

  13. 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.

  14. 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.

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

    Science.gov (United States)

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

    2012-05-01

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

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

    Science.gov (United States)

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

    2017-11-20

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

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

    Science.gov (United States)

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

    2016-03-24

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

  18. 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.

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

    OpenAIRE

    Concha Verdugo Yepes

    2011-01-01

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

  20. 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....

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2018-05-28

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

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

    International Nuclear Information System (INIS)

    Vigil, S.A.; Holter, G.M.

    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

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

    DEFF Research Database (Denmark)

    Rishi, Loveena; Hannon, Maura; Salomè, Mara

    2014-01-01

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

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

    Science.gov (United States)

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

    1999-05-01

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

  6. 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.

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

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

    2016-04-01

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

  9. 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

    in the humanities and social sciences. The students in the programme are explicitly asked to use translanguaging in order to enhance their languaging, i.e. they are invited to use translanguaging strategies in order to achieve interactional and social aims. The chapter introduces the design and the learning...... 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....

  10. 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

  11. 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....

  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. 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

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

    Science.gov (United States)

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

    2015-12-03

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

  15. 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.

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

    Science.gov (United States)

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

    2017-07-01

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

  17. Massive computation methodology for reactor operation (MACRO)

    International Nuclear Information System (INIS)

    Gustavsson, Cecilia; Pomp, Stephan; Sjoestrand, Henrik; Wallin, Gustav; Oesterlund, Michael; Koning, Arjan; Rochman, Dimitri; Bejmer, Klaes-Hakan; Henriksson, Hans

    2010-01-01

    Today, nuclear data libraries do not handle uncertainties from nuclear data in a consistent manner and the reactor codes do not request uncertainties in nuclear data input. Thus, the output from these codes have unknown uncertainties. The plan is to use a method proposed by Koning and Rochman to investigate the propagation of nuclear data uncertainties into reactor physics codes and macroscopic parameters. A project (acronym MACRO) has started at Uppsala University in collaboration with A. Koning and with financial support from Vattenfall AB and the Swedish Research Council within the GENIUS (Generation IV research in universities of Sweden) project. In the proposed method the uncertainties in nuclear model parameters will be derived from theoretical considerations and comparisons of nuclear model results with experimental cross-section data. Given the probability distribution in the model parameters a large set of random, complete ENDF-formatted nuclear data libraries will be created using the TALYS code. The generated nuclear data libraries will then be used in neutron transport codes to obtain macroscopic reactor parameters. For this, models of reactor systems with proper geometry and elements will be used. This will be done for all data libraries and the variation of the final results will be regarded as a systematic uncertainty in the investigated reactor parameter. The understanding of these systematic uncertainties is especially important for the design and intercomparison of new reactor concepts, i.e., Generation IV, and optimization applications for current generation reactors is envisaged. (authors)

  18. Opportunistic Relay Selection with Cooperative Macro Diversity

    Directory of Open Access Journals (Sweden)

    Yu Chia-Hao

    2010-01-01

    Full Text Available We apply a fully opportunistic relay selection scheme to study cooperative diversity in a semianalytical manner. In our framework, idle Mobile Stations (MSs are capable of being used as Relay Stations (RSs and no relaying is required if the direct path is strong. Our relay selection scheme is fully selection based: either the direct path or one of the relaying paths is selected. Macro diversity, which is often ignored in analytical works, is taken into account together with micro diversity by using a complete channel model that includes both shadow fading and fast fading effects. The stochastic geometry of the network is taken into account by having a random number of randomly located MSs. The outage probability analysis of the selection differs from the case where only fast fading is considered. Under our framework, distribution of the received power is formulated using different Channel State Information (CSI assumptions to simulate both optimistic and practical environments. The results show that the relay selection gain can be significant given a suitable amount of candidate RSs. Also, while relay selection according to incomplete CSI is diversity suboptimal compared to relay selection based on full CSI, the loss in average throughput is not too significant. This is a consequence of the dominance of geometry over fast fading.

  19. Massive computation methodology for reactor operation (MACRO)

    Energy Technology Data Exchange (ETDEWEB)

    Gustavsson, Cecilia; Pomp, Stephan; Sjoestrand, Henrik; Wallin, Gustav; Oesterlund, Michael [Division of applied nuclear physics, Department of physics and astronomy, Uppsala University, Laegerhyddsvaegen 1, 751 20 Uppsala (Sweden); Koning, Arjan; Rochman, Dimitri [Nuclear Research and consultancy Group (NRG) Westerduinweg 3, Petten (Netherlands); Bejmer, Klaes-Hakan [Vattenfall Nuclear Fuel AB, Jaemtlandsgatan 99, Vaellingby (Sweden); Henriksson, Hans [Vattenfall Research and Development AB, Jaemtlandsgatan 99, Vaellingby (Sweden)

    2010-07-01

    Today, nuclear data libraries do not handle uncertainties from nuclear data in a consistent manner and the reactor codes do not request uncertainties in nuclear data input. Thus, the output from these codes have unknown uncertainties. The plan is to use a method proposed by Koning and Rochman to investigate the propagation of nuclear data uncertainties into reactor physics codes and macroscopic parameters. A project (acronym MACRO) has started at Uppsala University in collaboration with A. Koning and with financial support from Vattenfall AB and the Swedish Research Council within the GENIUS (Generation IV research in universities of Sweden) project. In the proposed method the uncertainties in nuclear model parameters will be derived from theoretical considerations and comparisons of nuclear model results with experimental cross-section data. Given the probability distribution in the model parameters a large set of random, complete ENDF-formatted nuclear data libraries will be created using the TALYS code. The generated nuclear data libraries will then be used in neutron transport codes to obtain macroscopic reactor parameters. For this, models of reactor systems with proper geometry and elements will be used. This will be done for all data libraries and the variation of the final results will be regarded as a systematic uncertainty in the investigated reactor parameter. The understanding of these systematic uncertainties is especially important for the design and intercomparison of new reactor concepts, i.e., Generation IV, and optimization applications for current generation reactors is envisaged. (authors)

  20. The International Macro-Environment of an Organization

    Directory of Open Access Journals (Sweden)

    Ileana (Badulescu Anastase

    2016-01-01

    Full Text Available The international macro-environment (supranational macro-environment brings together allthe uncontrollable factors with a global impact, and it is related to the organization’s indirectrelationships on international markets. Romania’s globalization and the EU integration increasedthe importance of the macro-environment for all organizations, regardless of their degree ofinternationalization. In marketing, we must master the main agreements between countries and theregulations emanating from general international bodies, reflecting on their business, on differentforeign markets. Knowledge of the international environment is possible only through an analysisof its components (Anastase, I., 2012, p.41.

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

    Science.gov (United States)

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

    2004-02-01

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

  2. Revolutionary Transformation in the Macro-Regional Modernities

    Czech Academy of Sciences Publication Activity Database

    Hrubec, Marek

    2015-01-01

    Roč. 11, č. 6 (2015), s. 79-91 ISSN 1841-0464 Institutional support: RVO:67985955 Keywords : macro-regional * modernities * revolutionary transformations * intercultural * global Subject RIV: AA - Philosophy ; Religion

  3. Evaluation of vitrification factors from DWPF's macro-batch 1

    International Nuclear Information System (INIS)

    Edwards, T.B.

    2000-01-01

    The Defense Waste Processing Facility (DWPF) is evaluating new sampling and analytical methods that may be used to support future Slurry Mix Evaporator (SME) batch acceptability decisions. This report uses data acquired during DWPF's processing of macro-batch 1 to determine a set of vitrification factors covering several SME and Melter Feed Tank (MFT) batches. Such values are needed for converting the cation measurements derived from the new methods to a ''glass'' basis. The available data from macro-batch 1 were used to examine the stability of these vitrification factors, to estimate their uncertainty over the course of a macro-batch, and to provide a recommendation on the use of a single factor for an entire macro-batch. The report is in response to Technical Task Request HLW/DWPF/TTR-980015

  4. 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

  5. Complex fluids with mobile charge-regulating macro-ions

    Science.gov (United States)

    Markovich, Tomer; Andelman, David; Podgornik, Rudi

    2017-10-01

    We generalize the concept of charge regulation of ionic solutions, and apply it to complex fluids with mobile macro-ions having internal non-electrostatic degrees of freedom. The suggested framework provides a convenient tool for investigating systems where mobile macro-ions can self-regulate their charge (e.g., proteins). We show that even within a simplified charge-regulation model, the charge dissociation equilibrium results in different and notable properties. Consequences of the charge regulation include a positional dependence of the effective charge of the macro-ions, a non-monotonic dependence of the effective Debye screening length on the concentration of the monovalent salt, a modification of the electric double-layer structure, and buffering by the macro-ions of the background electrolyte.

  6. 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

  7. Role of Ceratophyllum demersum in recycling macro elements from ...

    African Journals Online (AJOL)

    Michael Horsfall

    Role of Ceratophyllum demersum in recycling macro elements from wastewater ... wastewater and could be the best biosorption method for protecting the water pollution in the environment. .... Calcium concentration in plants: Analysis.

  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. Variation in composition of macro-benthic invertebrates as an ...

    African Journals Online (AJOL)

    Mo

    1 Makerere University Institute of Environment & Natural Resources, P.O. Box 7062 Kampala-Uganda ... benthic macro-invertebrates communities were evaluated using GIS techniques along an ...... Kendall Hunt Publishing Company, Iowa.

  10. Ultrafast pulse lasers jump to macro applications

    Science.gov (United States)

    Griebel, Martin; Lutze, Walter; Scheller, Torsten

    2016-03-01

    Ultrafast Lasers have been proven for several micro applications, e.g. stent cutting, for many years. Within its development of applications Jenoptik has started to use ultrafast lasers in macro applications in the automotive industry. The JenLas D2.fs-lasers with power output control via AOM is an ideal tool for closed loop controlled material processing. Jenoptik enhanced his well established sensor controlled laser weakening process for airbag covers to a new level. The patented process enables new materials using this kind of technology. One of the most sensitive cover materials is genuine leather. As a natural product it is extremely inhomogeneous and sensitive for any type of thermal load. The combination of femtosecond pulse ablation and closed loop control by multiple sensor array opens the door to a new quality level of defined weakening. Due to the fact, that the beam is directed by scanning equipment the process can be split in multiple cycles additionally reducing the local energy input. The development used the 5W model as well as the latest 10W release of JenLas D2.fs and achieved amazing processing speeds which directly fulfilled the requirements of the automotive industry. Having in mind that the average cycle time of automotive processes is about 60s, trials had been done of processing weakening lines in genuine leather of 1.2mm thickness. Parameters had been about 15 cycles with 300mm/s respectively resulting in an average speed of 20mm/s and a cycle time even below 60s. First samples had already given into functional and aging tests and passed successfully.

  11. 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. Copyright

  12. Learning to Solve Problems by Searching for Macro-Operators

    Science.gov (United States)

    1983-07-01

    executing generalized robot plans. Aritificial Intelligence 3:25 1-288, 1972. [Frey 821 Frey, Alexander Ii. Jr., and David Singmaster. Handbook of Cubik...and that searching for macros may be a useful general learning paradigm. 1.1. Introduction One view of die die field of artificial intelligence is that... intelligence literature [Schofield 67, Gaschnig 79, Ericsson 761 and provides one of the simplest examples of the operation of the Macro Problem Solver. It

  13. 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.

  14. 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

  15. The histone variant macroH2A is an epigenetic regulator of key developmental genes

    DEFF Research Database (Denmark)

    Buschbeck, Marcus; Uribesalgo, Iris; Wibowo, Indra

    2009-01-01

    The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes is poorly understood. Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A ...

  16. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  20. DISTRIBUTIONAND DIVERSITY OF MACRO ALGAE COMMUNITIES IN THE AMBON BAY

    Directory of Open Access Journals (Sweden)

    Christina Litaay

    2014-11-01

    Full Text Available Water conditions affected by natural and anthropogenic parameters such as sedimentation and solid waste disposal can influence the growth and distribution of macro algae. Sustainable management efforts can reduce damage on the Gulf coast of Ambon due to human activities and land clearing. This study was conducted in October 2008 using the transect method with 3 replicates in five locations i.e., Tantui, Air Salobar, Hative Besar, Halong, and Lateri. The interior and exterior waters of Ambon Bay contained different habitat conditions due to  sedimentation processes. The purpose of this study was to determine the distribution and diversity of macro algae communities in the Ambon Bay. The results found 21 species of macro- algae consisting of 10 species of Rhodhophyceae, 6 species of Chlorophyceae, and 5 species of Phaeophyceae. The highest density value of seaweed in Tantui was 389.0 g/m² of Chlorophyceae of Halimeda genus. In Air Salobar and Halong, the highest density value was Rhodophyceae of Gracilaria genus of 172.0 g/m² and 155.0 g/m², respectively. For the other genus in the Tantui and Lateri regions were dominated by Ulva at 92.10 gr/m2 and Padina of 20.0 gr/m2, respectively. The highest dominance of macro algae in the Hative Besar was found Chlorophyceae of Halimeda genus of 2.93 %, in the Air Salobar of Phaeophyceae of Turbinaria genus of 1.43 %. The difference values in density and the dominance of macro algae indicated an influence of habitat and environment due to seasons, sediment, and solid waste disposal to the diversity of macro algae. Keywords: Diversity, macro algae, Ambon Bay.

  1. 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.

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

    Science.gov (United States)

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

    2016-06-01

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

  3. Scaling up: Assessing social impacts at the macro-scale

    International Nuclear Information System (INIS)

    Schirmer, Jacki

    2011-01-01

    Social impacts occur at various scales, from the micro-scale of the individual to the macro-scale of the community. Identifying the macro-scale social changes that results from an impacting event is a common goal of social impact assessment (SIA), but is challenging as multiple factors simultaneously influence social trends at any given time, and there are usually only a small number of cases available for examination. While some methods have been proposed for establishing the contribution of an impacting event to macro-scale social change, they remain relatively untested. This paper critically reviews methods recommended to assess macro-scale social impacts, and proposes and demonstrates a new approach. The 'scaling up' method involves developing a chain of logic linking change at the individual/site scale to the community scale. It enables a more problematised assessment of the likely contribution of an impacting event to macro-scale social change than previous approaches. The use of this approach in a recent study of change in dairy farming in south east Australia is described.

  4. Three hitherto unreported macro-fungi from Kashmir Himalaya

    International Nuclear Information System (INIS)

    Pala, S.A.; Wana, A.H.; Boda, R.H.

    2012-01-01

    The Himalayan state, Jammu and Kashmir due to its climate ranging from tropical deciduous forests to temperate and coniferous forests provides congenial habitat for the growth of diverse macro fungal species which in turn gives it the status of 'hub' of macro-fungal species. The macro fungal species richness of the state is directly related to its expansive forest communities and diverse weather patterns, but all the regions of the state have not been extensively surveyed till now. In this backdrop, a systematic survey for exploration and inventorization of macro fungal species of Western Kashmir Himalaya was undertaken during the year 2009 and 2010, which in turn resulted identification of the three species viz., Thelephora caryophyllea (Schaeff.) Pers., Coltricia cinnamomea (Pers.) Murr., and Guepinia helvelloides Fr. as new reports from the Kashmir. These species were identified on the basis of macro and microscopic characters and also the aid of taxonomic keys, field manuals, mushroom herbaria and help from expert taxonomists in the related field was taken into account. (author)

  5. 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.

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

    Science.gov (United States)

    Sempere, A; Jarque, I; Guinot, M; Palau, J; García, R; Sanz, G F; Gomis, F; Pérez-Sirvent, M L; Senent, L; Sanz, M A

    1993-12-01

    The main clinical, morphological, cytochemical, immunological features and therapy results of eleven patients diagnosed as acute myeloblastic leukemia M0 (AML-M0) are reported here. There were no clinical characteristics, abnormalities on physical examination or initial laboratory parameters that distinguished these eleven patients. Bone marrow aspirates were hypocellular in four patients. The leukemic cells were undifferentiated by light microscopy and myeloperoxidase (MPO) and/or Sudan Black B (SBB) stains were negative in all cases. Myeloid differentiation antigens were present on the leukemic cells of all eleven patients, whereas B and T cell markers were clearly negative except for CD4 and CD7 antigens. Whatever the treatment employed survival was very short. Eight of the eleven patients were treated and two achieved complete remission (CR) but only one of them is alive in continuous CR. Our results like those previously reported, suggest that AML-M0 patients have a very poor prognosis with standard induction therapies and should perhaps be considered for experimental therapeutic approaches.

  7. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT.

    Science.gov (United States)

    Sauer, T; Silling, G; Groth, C; Rosenow, F; Krug, U; Görlich, D; Evers, G; Albring, J; Besoke, R; Mesters, R M; Müller-Tidow, C; Kessler, T; Büchner, T; Berdel, W E; Stelljes, M

    2015-04-01

    Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.

  8. 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.

  9. Language-learning disabilities: Paradigms for the nineties.

    Science.gov (United States)

    Wiig, E H

    1991-01-01

    We are beginning a decade, during which many traditional paradigms in education, special education, and speech-language pathology will undergo change. Among paradigms considered promising for speech-language pathology in the schools are collaborative language intervention and strategy training for language and communication. This presentation introduces management models for developing a collaborative language intervention process, among them the Deming Management Method for Total Quality (TQ) (Deming 1986). Implementation models for language assessment and IEP planning and multicultural issues are also introduced (Damico and Nye 1990; Secord and Wiig in press). While attention to processes involved in developing and implementing collaborative language intervention is paramount, content should not be neglected. To this end, strategy training for language and communication is introduced as a viable paradigm. Macro- and micro-level process models for strategy training are featured and general issues are discussed (Ellis, Deshler, and Schumaker 1989; Swanson 1989; Wiig 1989).

  10. Simultaneous Feedback Models with Macro-Comparative Cross-Sectional Data

    Directory of Open Access Journals (Sweden)

    Nate Breznau

    2018-06-01

    Full Text Available Social scientists often work with theories of reciprocal causality. Sometimes theories suggest that reciprocal causes work simultaneously, or work on a time-scale small enough to make them appear simultaneous. Researchers may employ simultaneous feedback models to investigate such theories, although the practice is rare in cross-sectional survey research. This paper discusses the certain conditions that make these models possible if not desirable using such data. This methodological excursus covers the construction of simultaneous feedback models using a structural equation modeling perspective. This allows the researcher to test if a simultaneous feedback theory fits survey data, test competing hypotheses and engage in macro-comparisons. This paper presents methods in a manner and language amenable to the practicing social scientist who is not a statistician or matrix mathematician. It demonstrates how to run models using three popular software programs (MPlus, Stata and R, and an empirical example using International Social Survey Program data.

  11. Collaboration potentials in micro and macro politics of audience creativity

    DEFF Research Database (Denmark)

    Brites, Maria José; Chimirri, Niklas Alexander; Amaral, Inês

    2017-01-01

    In our stakeholder consultation following up on trends concerning the micro and macropolitics of audience action, we explore the potential impact of audiences’ micro-participation and connection to macro-actions. We address this issue taking into consideration intrinsic continuities and discontin...... and discontinuities between academia and the stakeholders’ perspectives. Our findings continue to emphasise the • (dis)connections between micro and macro actions • a technological appeal for action • collaboration potentials between academia and other stakeholders.......In our stakeholder consultation following up on trends concerning the micro and macropolitics of audience action, we explore the potential impact of audiences’ micro-participation and connection to macro-actions. We address this issue taking into consideration intrinsic continuities...

  12. Ordered macro-microporous metal-organic framework single crystals

    Science.gov (United States)

    Shen, Kui; Zhang, Lei; Chen, Xiaodong; Liu, Lingmei; Zhang, Daliang; Han, Yu; Chen, Junying; Long, Jilan; Luque, Rafael; Li, Yingwei; Chen, Banglin

    2018-01-01

    We constructed highly oriented and ordered macropores within metal-organic framework (MOF) single crystals, opening up the area of three-dimensional–ordered macro-microporous materials (that is, materials containing both macro- and micropores) in single-crystalline form. Our methodology relies on the strong shaping effects of a polystyrene nanosphere monolith template and a double-solvent–induced heterogeneous nucleation approach. This process synergistically enabled the in situ growth of MOFs within ordered voids, rendering a single crystal with oriented and ordered macro-microporous structure. The improved mass diffusion properties of such hierarchical frameworks, together with their robust single-crystalline nature, endow them with superior catalytic activity and recyclability for bulky-molecule reactions, as compared with conventional, polycrystalline hollow, and disordered macroporous ZIF-8.

  13. Ordered macro-microporous metal-organic framework single crystals

    KAUST Repository

    Shen, Kui

    2018-01-16

    We constructed highly oriented and ordered macropores within metal-organic framework (MOF) single crystals, opening up the area of three-dimensional-ordered macro-microporous materials (that is, materials containing both macro- and micropores) in single-crystalline form. Our methodology relies on the strong shaping effects of a polystyrene nanosphere monolith template and a double-solvent-induced heterogeneous nucleation approach. This process synergistically enabled the in situ growth of MOFs within ordered voids, rendering a single crystal with oriented and ordered macro-microporous structure. The improved mass diffusion properties of such hierarchical frameworks, together with their robust single-crystalline nature, endow them with superior catalytic activity and recyclability for bulky-molecule reactions, as compared with conventional, polycrystalline hollow, and disordered macroporous ZIF-8.

  14. Ordered macro-microporous metal-organic framework single crystals

    KAUST Repository

    Shen, Kui; Zhang, Lei; Chen, Xiaodong; Liu, Lingmei; Zhang, Daliang; Han, Yu; Chen, Junying; Long, Jilan; Luque, Rafael; Li, Yingwei; Chen, Banglin

    2018-01-01

    We constructed highly oriented and ordered macropores within metal-organic framework (MOF) single crystals, opening up the area of three-dimensional-ordered macro-microporous materials (that is, materials containing both macro- and micropores) in single-crystalline form. Our methodology relies on the strong shaping effects of a polystyrene nanosphere monolith template and a double-solvent-induced heterogeneous nucleation approach. This process synergistically enabled the in situ growth of MOFs within ordered voids, rendering a single crystal with oriented and ordered macro-microporous structure. The improved mass diffusion properties of such hierarchical frameworks, together with their robust single-crystalline nature, endow them with superior catalytic activity and recyclability for bulky-molecule reactions, as compared with conventional, polycrystalline hollow, and disordered macroporous ZIF-8.

  15. Narrative Abilities of Monolingual and Bilingual Children with and without Language Impairment: Implications for Clinical Practice

    Science.gov (United States)

    Boerma, Tessel; Leseman, Paul; Timmermeister, Mona; Wijnen, Frank; Blom, Elma

    2016-01-01

    Background: Understanding and expressing a narrative's macro-structure is relatively independent of experience in a specific language. A narrative task is therefore assumed to be a less biased method of language assessment for bilingual children than many other norm-referenced tests and may thus be particularly valuable to identify language…

  16. 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,…

  17. Dynamical Languages

    Science.gov (United States)

    Xie, Huimin

    The following sections are included: * Definition of Dynamical Languages * Distinct Excluded Blocks * Definition and Properties * L and L″ in Chomsky Hierarchy * A Natural Equivalence Relation * Symbolic Flows * Symbolic Flows and Dynamical Languages * Subshifts of Finite Type * Sofic Systems * Graphs and Dynamical Languages * Graphs and Shannon-Graphs * Transitive Languages * Topological Entropy

  18. 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.

  19. Macro-Micro Simulation for Polymer Crystallization in Couette Flow

    Directory of Open Access Journals (Sweden)

    Chunlei Ruan

    2017-12-01

    Full Text Available Polymer crystallization in manufacturing is a process where quiescent crystallization and flow-induced crystallization coexists, and heat/mass transfer on a macroscopic level interacts with crystal morphology evolution on a microscopic level. Previous numerical studies on polymer crystallization are mostly concentrated at a single scale; they only calculate macroscale parameters, e.g., temperature and relative crystallinity, or they only predict microstructure details, e.g., crystal morphology and mean size of crystals. The multi-scale numerical works that overcome these disadvantages are unfortunately based on quiescent crystallization, in which flow effects are neglected. The objective of this work is to build up a macro-micro model and a macro-micro algorithm to consider both the thermal and flow effects on the crystallization. Our macro-micro model couples two parts: mass and heat transfer of polymeric flow at the macroscopic level, and nucleation and growth of spherulites and shish-kebabs at the microscopic level. Our macro-micro algorithm is a hybrid finite volume/Monte Carlo method, in which the finite volume method is used at the macroscopic level to calculate the flow and temperature fields, while the Monte Carlo method is used at the microscopic level to capture the development of spherulites and shish-kebabs. The macro-micro model and the macro-micro algorithm are applied to simulate polymer crystallization in Couette flow. The effects of shear rate, shear time, and wall temperature on the crystal morphology and crystallization kinetics are also discussed.

  20. El debate micro-macro: dilemas y contextos

    Directory of Open Access Journals (Sweden)

    Vania Salles

    2001-06-01

    Full Text Available This paper discusses the general terms of the sociological debate on the micro macro question. Not only the main trends organizing the debate are examined, but also some ways to solve the dichotomies present in some proposals. It is held that contemporary theoretical practice produces —after the classics and with different focuses— a reflexivecorpus and research practices rooted in the blurring of the micro macro as polar questions, by the way of offering integrating proposals and overcoming reducing positions.

  1. A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML)

    Science.gov (United States)

    Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott

    2014-01-01

    Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

  2. 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...

  3. 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…

  4. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Buchmann, I.

    2008-01-01

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90 Y, 188 Re and 131 I are the most frequently used β - -particles. Of these, 90 Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90 Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90 Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90 Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of

  5. OSI-211, a novel liposomal topoisomerase I inhibitor, is active in SCID mouse models of human AML and ALL.

    Science.gov (United States)

    Tomkinson, Blake; Bendele, Ray; Giles, Francis J; Brown, Eric; Gray, Atherton; Hart, Karen; LeRay, Jeremy D; Meyer, Denny; Pelanne, Michelle; Emerson, David L

    2003-11-01

    OSI-211 (liposomal lurtotecan), was evaluated using several different dose schedules (1mg/kg, d1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) in severe combined immunodeficient (SCID) mouse models of acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) with early treatment (ET, days 6-8) or late treatment (LT, days 15-19), examining early and advanced disease, respectively. Due to the aggressive nature of the Molt-4 model, the ET and LT were accelerated to day 3 or 4 and day 8 post-implant, respectively. For each model, 2 x 10(7) (KBM-3B) or 1 x 10(7) (Molt-4, HL-60 and CEM) leukemia cells were injected intravenously into the tail vein. Each control and test group consisted of eight animals. All three schedules (1mg/kg qd1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) increased the life span of OSI-211 treated animals in each model, with a tendency toward improved efficacy with the 6 mg/kg d1, 8 schedule. As a result, the activity of the 6 mg/kg d1, 8 schedule is detailed for each model. ET significantly (Pmodel with 86% long-term survivors (LTS). Using PRC analysis, human beta-globin gene sequences in one or several tissues were amplified in all but 3 LTS, suggesting minimal residual disease in 26 of the 29 LTS. LT also significantly (Pmodel, with an average ILS=196+/-11% and one LTS. Treatment of HL-60 leukemia animals significantly (Pmodel tested, significantly (Pmodel, ET resulted in a significantly (POSI-211, treatment with DaunoXome, the liposomal formulation of daunorubicin, a drug with clinical efficacy in AML and ALL, had no effect on survival in the KBM-3B, nor Molt-4 A4 leukemia models when administered at its maximum or near maximum tolerated doses of 3mg/kg d1, 8. These data demonstrate that OSI-211 has potent antileukemia activity in preclinical SCID mouse AML and ALL leukemia models, supporting the clinical investigation of OSI-211 for hematological malignancies.

  6. Potential of dynamic spectrum allocation in LTE macro networks

    NARCIS (Netherlands)

    Hoffmann, H.; Ramachandra, P.; Kovacs, I.Z.; Jorguseski, L.; Gunnarsson, F.; Kurner, T.

    2015-01-01

    In recent years Mobile Network Operators (MNOs) worldwide are extensively deploying LTE networks in different spectrum bands and utilising different bandwidth configurations. Initially, the deployment is coverage oriented with macro cells using the lower LTE spectrum bands. As the offered traffic

  7. 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…

  8. Fertilization of Earth Ponds. III: Effects on Benthic Macro ...

    African Journals Online (AJOL)

    Organic fertilizers in form of cow and chicken manure were applied in oligotrophic or unproductive pond water over a period of one year to stimulate the production of benthic macro invertebrates for the benefit of trout culture, while maintaining adequate water quality. Development of aquatic macrophytes during both ...

  9. An Alternative Macro-economic Model for the Classroom

    Science.gov (United States)

    Holmes, Bryan

    1976-01-01

    Presents Michal Kalecki's macro-economic model and two-sector version of the model by Robinson and Eatwell as circular flow diagrams. Advantages of using this approach in first-year undergraduate economics programs are discussed. Available from: General Secretary, Economics Association, Room 340, Hamilton House, Mabledon Place, London WC1H 9BH,…

  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. 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.

  12. The Impact of Macro-adjustment Programmes on Housing ...

    African Journals Online (AJOL)

    The Impact of Macro-adjustment Programmes on Housing Investment in Kampala City, Uganda: Shelter Implications for the Urban Poor. ... Eastern Africa Social Science Research Review ... The adjustment methodology has side-lined and gravely undermined the housing sector thereby aggravating the shelter problem.

  13. South African tourism: An historic evaluation of macro tourism policies

    African Journals Online (AJOL)

    ... namely Rugby, Cricket and Soccer, and numerous other sporting, cultural and business events have successfully been hosted in the country. Macro policies governing tourism at the national level have been introduced to stimulate and guide tourism growth in such a way that the public at large can benefit. Furthermore ...

  14. Conceptualizing Educational Leadership: Does Exploring Macro-Level Facets Matters?

    Science.gov (United States)

    Sinha, Chetan

    2013-01-01

    The present review attempts to examine the present status of educational leadership highlighting the role of macro-level facets in Asian Pacific context. The conceptualization of educational leadership among researchers so far had been found to vary according to different contexts and situations. Theoretical perspectives associated with…

  15. 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

  16. Reproductive Decision-Making in a Macro-Micro Perspective

    NARCIS (Netherlands)

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

    2015-01-01

    This book provides new insights into the significant gap that currently exists between desired and actual fertility in Europe. It examines how people make decisions about having children and demonstrates how the macro-level environment affects micro-level decision-making. Written by an international

  17. Effecting Organizational Change at the Macro Level of Professions

    Science.gov (United States)

    Green, Robert Anthony

    2017-01-01

    Much has been written in academic and popular publications about organizational change. Topics have ranged from case studies to anecdotal stories of how leaders can change an organization. There is little written on changing the culture and vision of a profession at the macro level. This dissertation shows that one key to effecting change within a…

  18. Development of an automated desktop procedure for defining macro ...

    African Journals Online (AJOL)

    methods (Von Neumann mean square error, CUSUM plots or unweighted values and the Worsley Likelihood Ratio Test (WLRT)) were used to define macro-reach breaks for four South African rivers (Crocodile, Olifants, Mhlathuze and Seekoei Rivers) and were compared to ... Water SA Vol.32 (3) 2006: pp.395-402 ...

  19. The MARKAL-MACRO model and the climate change

    International Nuclear Information System (INIS)

    Kypreos, S.

    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 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

  20. Gene expression profiling of acute myeloid leukemia samples from adult patients with AML-M1 and -M2 through boutique microarrays, real-time PCR and droplet digital PCR.

    Science.gov (United States)

    Handschuh, Luiza; Kaźmierczak, Maciej; Milewski, Marek C; Góralski, Michał; Łuczak, Magdalena; Wojtaszewska, Marzena; Uszczyńska-Ratajczak, Barbara; Lewandowski, Krzysztof; Komarnicki, Mieczysław; Figlerowicz, Marek

    2018-03-01

    Acute myeloid leukemia (AML) is the most common and severe form of acute leukemia diagnosed in adults. Owing to its heterogeneity, AML is divided into classes associated with different treatment outcomes and specific gene expression profiles. Based on previous studies on AML, in this study, we designed and generated an AML-array containing 900 oligonucleotide probes complementary to human genes implicated in hematopoietic cell differentiation and maturation, proliferation, apoptosis and leukemic transformation. The AML-array was used to hybridize 118 samples from 33 patients with AML of the M1 and M2 subtypes of the French-American‑British (FAB) classification and 15 healthy volunteers (HV). Rigorous analysis of the microarray data revealed that 83 genes were differentially expressed between the patients with AML and the HV, including genes not yet discussed in the context of AML pathogenesis. The most overexpressed genes in AML were STMN1, KITLG, CDK6, MCM5, KRAS, CEBPA, MYC, ANGPT1, SRGN, RPLP0, ENO1 and SET, whereas the most underexpressed genes were IFITM1, LTB, FCN1, BIRC3, LYZ, ADD3, S100A9, FCER1G, PTRPE, CD74 and TMSB4X. The overexpression of the CPA3 gene was specific for AML with mutated NPM1 and FLT3. Although the microarray-based method was insufficient to differentiate between any other AML subgroups, quantitative PCR approaches enabled us to identify 3 genes (ANXA3, S100A9 and WT1) whose expression can be used to discriminate between the 2 studied AML FAB subtypes. The expression levels of the ANXA3 and S100A9 genes were increased, whereas those of WT1 were decreased in the AML-M2 compared to the AML-M1 group. We also examined the association between the STMN1, CAT and ABL1 genes, and the FLT3 and NPM1 mutation status. FLT3+/NPM1- AML was associated with the highest expression of STMN1, and ABL1 was upregulated in FLT3+ AML and CAT in FLT3- AML, irrespectively of the NPM1 mutation status. Moreover, our results indicated that CAT and WT1

  1. 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

  2. Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3 inhibitor therapy with evolving actionable targets

    Directory of Open Access Journals (Sweden)

    Pashtoon M. Kasi

    2016-01-01

    Full Text Available For acute myeloid leukemia (AML, identification of activating mutations in the FMS-like tyrosine kinase-3 (FLT3 has led to the development of several FLT3-inhibitors. Here we present clinical and next generation sequencing data at the time of progression of a patient on a novel FLT3-inhibitor clinical trial (ASP2215 to show that employing therapeutic interventions with these novel targeted therapies can lead to consequences secondary to selective pressure and clonal evolution of cancer. We describe novel findings alongside data on treatment directed towards actionable aberrations acquired during the process. (Clinical Trial: NCT02014558; registered at: 〈https://clinicaltrials.gov/ct2/show/NCT02014558〉

  3. A case of AML with preceding hypoplastic stage after oophoro-hysterectomy and 60Co-irradiation

    International Nuclear Information System (INIS)

    Yoshida, Takashi; Nakamura, Shinobu; Hattori, Kenichi; Tanimoto, Kazuo.

    1975-01-01

    A case of AML (preceded by a hypoplastic stage) which developed after oophoro-hysterectomy and 60 Co-irradiation is presented, and related literature concerning irradiation-induced leukemia and the early diagnosis of leukemia and/or preleukemia are discussed. The patient, a 47 year old female had had surgery and irradiation with a subsequent normachromic anemia necessitating transfusions 11 years prior to her presenting herself at our hospital because of anemia. Her pancytopenic peripheral blood picture combined with a relatively hypererythroid marron led to a diagnosis of atypical hypoplastic anemia. Two years after this she suddenly developed a high fever, general fatigue and a severe anemia. Hematological studies revealed acute myeloblastic leukemia. A combination therapy consisting of DM, 6MP, prednisolon and blood transfusions was given with no effect and 3 months after the onset, the patient died of asphyxia resulting from gross hemoptysis. Autopsy revealed pulmonary hemorrhage secondary to the leukemia. (J. Evans)

  4. Potential of dynamic spectrum allocation in LTE macro networks

    Science.gov (United States)

    Hoffmann, H.; Ramachandra, P.; Kovács, I. Z.; Jorguseski, L.; Gunnarsson, F.; Kürner, T.

    2015-11-01

    In recent years Mobile Network Operators (MNOs) worldwide are extensively deploying LTE networks in different spectrum bands and utilising different bandwidth configurations. Initially, the deployment is coverage oriented with macro cells using the lower LTE spectrum bands. As the offered traffic (i.e. the requested traffic from the users) increases the LTE deployment evolves with macro cells expanded with additional capacity boosting LTE carriers in higher frequency bands complemented with micro or small cells in traffic hotspot areas. For MNOs it is crucial to use the LTE spectrum assets, as well as the installed network infrastructure, in the most cost efficient way. The dynamic spectrum allocation (DSA) aims at (de)activating the available LTE frequency carriers according to the temporal and spatial traffic variations in order to increase the overall LTE system performance in terms of total network capacity by reducing the interference. This paper evaluates the DSA potential of achieving the envisaged performance improvement and identifying in which system and traffic conditions the DSA should be deployed. A self-optimised network (SON) DSA algorithm is also proposed and evaluated. The evaluations have been carried out in a hexagonal and a realistic site-specific urban macro layout assuming a central traffic hotspot area surrounded with an area of lower traffic with a total size of approximately 8 × 8 km2. The results show that up to 47 % and up to 40 % possible DSA gains are achievable with regards to the carried system load (i.e. used resources) for homogenous traffic distribution with hexagonal layout and for realistic site-specific urban macro layout, respectively. The SON DSA algorithm evaluation in a realistic site-specific urban macro cell deployment scenario including realistic non-uniform spatial traffic distribution shows insignificant cell throughput (i.e. served traffic) performance gains. Nevertheless, in the SON DSA investigations, a gain of up

  5. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML.

    Science.gov (United States)

    Swords, Ronan T; Coutre, Steven; Maris, Michael B; Zeidner, Joshua F; Foran, James M; Cruz, Jose; Erba, Harry P; Berdeja, Jesus G; Tam, Wayne; Vardhanabhuti, Saran; Pawlikowska-Dobler, Iwona; Faessel, Hélène M; Dash, Ajeeta B; Sedarati, Farhad; Dezube, Bruce J; Faller, Douglas V; Savona, Michael R

    2018-03-29

    Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We performed a phase 1b study of pevonedistat (PEV) with azacitidine (AZA) based on synergistic activity seen preclinically. Primary objectives included safety and tolerability, and secondary objectives included pharmacokinetics (PK) and disease response. Patients ≥60 years with treatment-naive AML (unfit for standard induction therapy) received PEV 20 or 30 mg/m 2 IV on days 1, 3, and 5 combined with fixed-dose AZA (75 mg/m 2 IV/subcutaneously) on days 1 to 5, 8, and 9, every 28 days. The most common treatment-emergent adverse events were constipation (48%), nausea (42%), fatigue (42%), and anemia (39%). In total, 11 deaths were observed and considered unrelated to study therapy by the investigators. Transient elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were dose limiting. The recommended phase 2 dose (RP2D) of PEV in this combination is 20 mg/m 2 PEV PK was not altered by the addition of AZA. Overall response rate (ORR) based on an intent-to-treat analysis was 50% (20 complete remissions [CRs], 5 complete remission with incomplete peripheral count recovery, 7 partial remissions [PRs]), with an 8.3-month median duration of remission. In patients receiving ≥6 cycles of therapy (n = 23, 44%), ORR was 83%. In patients with TP53 mutations, the composite CR/PR rate was 80% (4/5). Two of these patients stayed on study for >10 cycles. Baseline bone marrow blast percentage or cytogenetic/molecular risk did not influence ORR. This study was registered at www.clinicaltrials.gov as #NCT01814826. © 2018 by The American Society of Hematology.

  6. Identification of the Molecular Mechanisms Responsible for the Inhibition of Homing of AML Cells Triggered by CD44-Ligation

    KAUST Repository

    Al-Jifri, Ablah

    2011-08-03

    Acute Myeloid Leukemia (AML) is a cancerous disease that is defined by the inability to produce functional and mature blood cells, as well as the uncontrolled proliferation due to failure to undergo apoptosis of abnormal cells. The most common therapy for Leukemia, chemotherapy, has proven only to be partially efficient since it does not target the leukemic stem cells (LSCs) that have a high self-renewal and repopulation capacity and result in remission of the disease. Therefore targeting LSCs will provide more efficient therapy. One way to achieve this would be to inhibit their homing capability to the bone marrow. It has recently been shown that CD44, an adhesive molecule, plays a crucial role in cell trafficking and lodgement of both normal and leukemic stem cells. More importantly anti-CD44 monoclonal antibodies, along with its ability to induce differentiation of leukemic blasts, it inhibits specifically the homing capacity of LSCs to their micro-environmental niches. However, these molecular mechanisms that underlie the inhibition of homing have yet to be determined. To address these questions we conducted in vitro adhesion and blot-rolling assays to analyze the adherence and rolling capacity of these LSCs before and after treatment with anti-CD44 monoclonal antibody (mAb). Since glycosyltransferases play a crucial role in post translational carbohydrate decoration on adhesion molecules, we analyzed the expression (using quantitative PCR) of the different glycosyltransferases expressed in LSC\\'s before and after CD44 ligation (mAb treatment). Furthermore, we analyzed differentiation by flow cytometric analysis of treated and non-treated LSC\\'s. We anticipate that our results will set forth new insights into targeted therapies for AML.

  7. Transformation from refractory anemia with excess of blasts (RAEB) into acute myeloid leukemia (AML) obserbed in a heavily exposed atomic bomb survivor

    Energy Technology Data Exchange (ETDEWEB)

    Iwato, Koji; Kawano, Michio; Kimura, Akiro; Kuramoto, Atsushi; Tanaka, Kimio; Kamada, Nanao

    1987-01-01

    A heavily exposed atomic bomb survivor, 59-year-old man presented refractory anemia with excess of blasts (RAEB) terminating in acute myeloid leukemia (AML) 38 years after exposure. When he manifested AML, combination chemotherapy was started. But complete remission was not obtained even by B-DOMP regimen. Cytogenetic studies were performed, and their relation to the clinical course was analyzed. Peripheral blood T lymphocytes had 41.9 % non-clonal chromosomal abnormalities suggesting over 400 rad exposure. Bone marrow cells at RAEB exhibited a presence of mosaic clones of normal and abnormal chromosomal pattern, which supported the clinical diagnosis of RAEB and corresponded to the clinical features such as steady state and a low percentage of myeloblasts. At transformation into AML, clonal chromosomal abnormality was seen in bone marrow cells. It may explain a rapid increase of abnormal cells. This abnormal clone showed a little different karyotype seen at RAEB. But it was suspected to derive from a clone at RAEB, because of the same persistent chromosomal abnormalities. Then it aquired an additional chromosomal abnormalities at clinically drug-resistant phase of AML. In vivo selection assay of these leukemic cells revealed that transforming gene took part in this leukemogenesis. These data shown in this paper contribute to investigate a mechanism of leukemogenesis in atomic bomb survivors and establishment of new therapy.

  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. Transformation from refractory anemia with excess of blasts (RAEB) into acute myeloid leukemia (AML) obserbed in a heavily exposed atomic bomb survivor

    International Nuclear Information System (INIS)

    Iwato, Koji; Kawano, Michio; Kimura, Akiro; Kuramoto, Atsushi; Tanaka, Kimio; Kamada, Nanao

    1987-01-01

    A heavily exposed atomic bomb survivor, 59-year-old man presented refractory anemia with excess of blasts (RAEB) terminating in acute myeloid leukemia (AML) 38 years after exposure. When he manifested AML, combination chemotherapy was started. But complete remission was not obtained even by B-DOMP regimen. Cytogenetic studies were performed, and their relation to the clinical course was analyzed. Peripheral blood T lymphocytes had 41.9 % non-clonal chromosomal abnormalities suggesting over 400 rad exposure. Bone marrow cells at RAEB exhibited a presence of mosaic clones of normal and abnormal chromosomal pattern, which supported the clinical diagnosis of RAEB and corresponded to the clinical features such as steady state and a low percentage of myeloblasts. At transformation into AML, clonal chromosomal abnormality was seen in bone marrow cells. It may explain a rapid increase of abnormal cells. This abnormal clone showed a little different karyotype seen at RAEB. But it was suspected to derive from a clone at RAEB, because of the same persistent chromosomal abnormalities. Then it aquired an additional chromosomal abnormalities at clinically drug-resistant phase of AML. In vivo selection assay of these leukemic cells revealed that transforming gene took part in this leukemogenesis. These data shown in this paper contribute to investigate a mechanism of leukemogenesis in atomic bomb survivors and establishment of new therapy. (author)

  10. 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...

  11. The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO

    Science.gov (United States)

    Chou, Fu-Sheng; Griesinger, Andrea; Wunderlich, Mark; Lin, Shan; Link, Kevin A.; Shrestha, Mahesh; Goyama, Susumu; Mizukawa, Benjamin; Shen, Shuhong; Marcucci, Guido

    2012-01-01

    AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL. PMID:22337712

  12. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more : results of a multicenter phase 3 study

    NARCIS (Netherlands)

    Lowenberg, Bob; Beck, Joachim; Graux, Carlos; van Putten, Wim; Schouten, Harry C.; Verdonck, Leo F.; Ferrant, Augustin; Sonneveld, Pieter; Jongen-Lavrencic, Mojca; von Lilienfeld-Toal, Marie; Biemond, Bart J.; Vellenga, Edo; Breems, Dimitri; de Muijnck, Hilde; Schaafsma, Ron; Verhoef, Gregor; Doehner, Hartmut; Gratwohl, Alois; Pabst, Thomas; Ossenkoppele, Gert J.; Maertens, Johan

    2010-01-01

    In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction

  13. 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.

  14. 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.

  15. [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.

  16. Endangered Languages.

    Science.gov (United States)

    Hale, Ken; And Others

    1992-01-01

    Endangered languages, or languages on the verge of becoming extinct, are discussed in relation to the larger process of loss of cultural and intellectual diversity. This article summarizes essays presented at the 1991 Linguistic Society of America symposium, "Endangered Languages and Their Preservation." (11 references) (LB)

  17. ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1-RUNX1T1 and associated with a better prognosis.

    Science.gov (United States)

    Yamato, Genki; Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Hara, Yusuke; Ohki, Kentaro; Okubo, Jun; Okuno, Haruna; Chiba, Kenichi; Tanaka, Hiroko; Kinoshita, Akitoshi; Moritake, Hiroshi; Kiyokawa, Nobutaka; Tomizawa, Daisuke; Park, Myoung-Ja; Sotomatsu, Manabu; Taga, Takashi; Adachi, Souichi; Tawa, Akio; Horibe, Keizo; Arakawa, Hirokazu; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

    2017-05-01

    ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event-free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild-type (5-year OS, 75% vs. 100% vs. 91% and 5-year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously. © 2017 Wiley Periodicals, Inc.

  18. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells.

    Science.gov (United States)

    Saenz, D T; Fiskus, W; Qian, Y; Manshouri, T; Rajapakshe, K; Raina, K; Coleman, K G; Crew, A P; Shen, A; Mill, C P; Sun, B; Qiu, P; Kadia, T M; Pemmaraju, N; DiNardo, C; Kim, M-S; Nowak, A J; Coarfa, C; Crews, C M; Verstovsek, S; Bhalla, K N

    2017-09-01

    The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.

  19. [Dexamethasone and vorinostat cooperatively promote differentiation and apoptosis in Kasumi-1 leukemia cells through ubiquitination and degradation of AML1-ETO].

    Science.gov (United States)

    Chen, Li-ping; Zhang, Jian-wei; Xu, Fa-mei; Xing, Hai-yan; Tian, Zheng; Wang, Min; Wang, Jian-xiang

    2013-09-01

    To probe the effects of dexamethasone (DEX) combined with histone deacetylase (HDAC) inhibitor vorinostat on inhibiting proliferation and inducing differentiation and apoptosis in Kasumi-1 leukemia cells, and its possible mechanisms in order to provide a theoretical basis for the treatment of AML1-ETO positive AML. The cell survival, differentiation and apoptosis rates were tested by MTT or flow cytometry analysis after Kasumi-1 cells were treated by DMSO, DEX (20 nmol/L), vorinostat (1 μmol/L) or DEX (20 nmol/L) in combination with vorinostat (1 μmol/L). WB and IP-WB were performed to detect AML1-ETO and its ubiquitination. Treatment with the combination of DEX and vorinostat for 48 h led to statistically significant differences of inhibited proliferation [(42.06±8.20)%], increased differentiation [(52.83±8.97)%] and apoptosis [(52.92±2.53)%] of Kasumi-1 cells when compared with vorinostat [(33.82±9.41)%, (43.93±9.04)% and (42.98±3.01)%, respectively], DEX [(17.30±3.49)%, (22.53±4.51)% and (19.57±2.17)%, respectively] or control [(6.96±0.39)%, (21.73±2.03)% and (6.96±0.39)%, respectively]. Also significant ubiquitination and decreased AML1-ETO protein in Kasumi-1 cells after the combination treatment over single agent or control were observed. The results indicated that DEX and vorinostat could synergistically inhibit the Kasumi-1 cells proliferation, induce Kasumi-1 cells differentiation and apoptosis through ubiquitination and degradation of AML1-ETO.

  20. DHX15 is associated with poor prognosis in acute myeloid leukemia (AML) and regulates cell apoptosis via the NF-kB signaling pathway.

    Science.gov (United States)

    Pan, Lili; Li, Yang; Zhang, Hai-Ying; Zheng, Yi; Liu, Xiao-Li; Hu, Zheng; Wang, Yi; Wang, Jing; Cai, Yuan-Hua; Liu, Qiao; Chen, Wan-Ling; Guo, Ying; Huang, Yuan-Mao; Qian, Feng; Jin, Li; Wang, Jiucun; Wang, Shao-Yuan

    2017-10-27

    The role of DHX15 , a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in DHX15 (NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally, DHX15 was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of DHX15 . DHX15 was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells. DHX15 was down-regulated when AML patients achieved disease remission or when leukemia cell lines were induced to differentiate. DHX15 silencing greatly inhibited leukemia cell proliferation and induced cell apoptosis and G1-phase arrest. In contrast, the restoration of DHX15 expression rescued cell viability and reduced cell apoptosis. In addition, we found that DHX15 was down-regulated when cell apoptosis was induced by ATO (arsenic trioxide); overexpression of DHX15 caused dramatic resistance to ATO-induced cell apoptosis, suggesting an important role for DHX15 in cell apoptosis. We further explored the mechanism of DHX15 in apoptosis and found that overexpression of DHX15 activated NF-kB transcription. Knockdown of DHX15 inhibited the nuclear translocation and activation of the NF-kB subunit P65 in leukemia cells. Several downstream targets of the NF-kB pathway were also down-regulated, and apoptosis-associated genes CASP3 and PARP were activated. In conclusion, this study represents the first demonstration that DHX15 plays an important role in leukemogenesis via the NF-kB signaling pathway and may serve as an independent prognostic marker for AML.

  1. Language Acquisition and Language Revitalization

    Science.gov (United States)

    O'Grady, William; Hattori, Ryoko

    2016-01-01

    Intergenerational transmission, the ultimate goal of language revitalization efforts, can only be achieved by (re)establishing the conditions under which an imperiled language can be acquired by the community's children. This paper presents a tutorial survey of several key points relating to language acquisition and maintenance in children,…

  2. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)

    2008-06-15

    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and

  3. 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.

  4. Clinimetrics and clinical psychometrics: macro- and micro-analysis.

    Science.gov (United States)

    Tomba, Elena; Bech, Per

    2012-01-01

    Clinimetrics was introduced three decades ago to specify the domain of clinical markers in clinical medicine (indexes or rating scales). In this perspective, clinical validity is the platform for selecting the various indexes or rating scales (macro-analysis). Psychometric validation of these indexes or rating scales is the measuring aspect (micro-analysis). Clinical judgment analysis by experienced psychiatrists is included in the macro-analysis and the item response theory models are especially preferred in the micro-analysis when using the total score as a sufficient statistic. Clinical assessment tools covering severity of illness scales, prognostic measures, issues of co-morbidity, longitudinal assessments, recovery, stressors, lifestyle, psychological well-being, and illness behavior have been identified. The constructive dialogue in clinimetrics between clinical judgment and psychometric validation procedures is outlined for generating developments of clinical practice in psychiatry. Copyright © 2012 S. Karger AG, Basel.

  5. Processing and Mechanical Properties of Macro Polyamide Fiber Reinforced Concrete.

    Science.gov (United States)

    Jeon, Joong Kyu; Kim, WooSeok; Jeon, Chan Ki; Kim, Jin Cheol

    2014-11-26

    This study developed a macro-sized polyamide (PA) fiber for concrete reinforcement and investigated the influence of the PA fiber on flexural responses in accordance with ASTM standards. PA fibers are advantageous compared to steel fibers that are corrosive and gravitated. The macro-sized PA fiber significantly improved concrete ductility and toughness. Unlike steel fibers, the PA fibers produced two peak bending strengths. The first-peaks occurred near 0.005 mm of deflection and decreased up to 0.5 mm of deflection. Then the bending strength increased up to second-peaks until the deflections reached between 1.0 and 1.5 mm. The averaged flexural responses revealed that PA fiber content did not significantly influence flexural responses before L /600, but had significant influence thereafter. Toughness performance levels were also determined, and the results indicated more than Level II at L /600 and Level IV at others.

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

    Directory of Open Access Journals (Sweden)

    Berenice Kerr-Phillips

    2009-08-01

    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.

  7. Lead macro-encapsulation conceptual and experimental studies

    International Nuclear Information System (INIS)

    Orebaugh, E.G.

    1993-01-01

    Macro-encapsulation, the regulatory treatment for radioactively contaminated lead (mixed) waste has been conceptually and experimentally evaluated for practical application. Epoxy encapsulants molded around lead billets have proven to be exceptionally rugged, easily applied, have high radiation and chemical stability, and minimize required process equipment and production of secondary wastes. This technology can now be considered developed, and can be applied as discussed in this report

  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

    OpenAIRE

    Vieira, Leonardo Pereira; Lara, Vitor de Oliveira Moraes

    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. Wage flexibility in Britain: some micro and macro evidence

    OpenAIRE

    Mark E Schweitzer

    2007-01-01

    This paper uses the British New Earnings Survey (NES) to derive both macro and micro measures of wage rigidities. The data set spans the 1975-2000 period, with wage observations covering approximately 1% of the British workforce. Using this data set, we consider whether wages have become more flexible in recent years. Evidence drawn from macroeconomic wage equation estimates suggests that, while the relationship between wages and unemployment seems to have changed, the responsiveness of wages...

  11. Macro-defect free cements. State of art

    International Nuclear Information System (INIS)

    Holanda, J.N.F.; Povoa, G.E.A.M.; Souza, G.P.; Pinatti, D.G.

    1998-01-01

    The purpose of this work is to prevent a state of art about macro-defect-free cement pastes (MDF cement ) of high mechanical strength. This new type of cement paste is obtained through addition of a water-soluble polymer, followed by intense shear mixing and application of low compacting pressure. It is presented fundamental aspects related to the processing of this MDF paste, as well as its main properties and applications are discussed. (author)

  12. Adsorption of copper onto char derived macro alga, Undaria pinnatifida

    International Nuclear Information System (INIS)

    Cho, Hye Jung; Ko, Jeong Huy; Heo, Hyeon Su; Park, Hye Jin; BAe, Yoon Ju; Kim, Jung Hwan; Park, Young-Kwon

    2010-01-01

    Full text: A release of heavy metals into the environment by industrial activities raises much environmental problems because they tend to remain indefinitely, circulating and eventually accumulating throughout the food chain. Copper is essential to human life and health but, like all heavy metals, is potentially toxic as well. The excessive intakes of copper result in its accumulation in the liver and produce gastrointestinal problems, kidney damage, anemia, and continued inhalation of copper-containing sprays is linked with an increase in lung cancer among exposed people. Consequently, we need to eliminate the copper in drinking water. Also, growth rates of marine macro algae far exceed those of terrestrial biomass, without water limitations, so annual primary production rates are higher for the major marine macro algae than for most terrestrial biomass. According to these reasons, we try to use the macro alga, Undaria pinnatifida. Adsorption of heavy metals is one of the possible technologies involved in the removal of toxic metals from industrial waste streams and mining waste water using low-cost adsorbents. In recent years, many low-cost adsorbents such as seaweeds, activated carbon, etc. have been investigated, but the char by macro alga, Undaria pinnatifida, have not proven to be the most effective and promising substrates. The aim of this study is to remove copper from its aqueous solution by Undaria pinnatifida char for various parameters like pH, contact time, and Cu(II) concentration. The adsorption capacity of Cu(II) by Undaria pinnatifida char was investigated as a function of pH, contact time, and Cu(II) concentration at room temperature. And it was verified using equilibrium studies. (author)

  13. Distributionand Diversity of Macro Algae Communities in the Ambon Bay

    OpenAIRE

    Litaay, Christina

    2014-01-01

    Water conditions affected by natural and anthropogenic parameters such as sedimentation and solid waste disposal can influence the growth and distribution of macro algae. Sustainable management efforts can reduce damage on the Gulf coast of Ambon due to human activities and land clearing. This study was conducted in October 2008 using the transect method with 3 replicates in five locations i.e., Tantui, Air Salobar, Hative Besar, Halong, and Lateri. The interior and exterior waters of Ambon B...

  14. 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....... Furthermore, we show that the state can be used to map a microscopic qubit onto a macroscopic one thereby linking a qubit processor with a qumode processor....

  15. 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.

  16. ECONOMIC SAFETY PROBLEM IN MODERN MACRO AND MICRO CONCEPTS

    Directory of Open Access Journals (Sweden)

    I. I. Rekun

    2014-01-01

    Full Text Available Purpose. Security is an important component of economic security and the guaranteeing of appropriate national interests in the state. All these things are closely related to the economic efficiency of operations of economic entities, with economic independence, stability and security of a society. In addition, economic security is a part of national security, its foundation and material basis. The problem of economic security in modern conditions at the micro and macro levels requires determining the main directions of its formation. Methodology. To achieve this goal, basic directions of a security mechanism of the economic system, in particular on the macro level were grounded. Findings. Economic security is such state of the state economy operation in which the order of equilibrium occurred in certain organizational and legal norms on the basis of social life. These regulations are created be the state, principles of coexistence, which are transmitted from generation to generation. The current state of economic security guaranteeing at the macro and micro levels was analyzed. The system of indicators that can be used in the assessment of the security system was determined. Originality. Propositions concerning necessary changes in the policy of economic security in a state were formulated. The system of indicators which can be used in the assessment of the security system was offered. Practical value. Using of the proposed system of economic security indicators will expand the list of important factors affecting on its status and allow us determining the main directions of its formation.

  17. 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

  18. 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.

  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.

  20. [Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

    Science.gov (United States)

    Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian

    2015-06-01

    To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

  1. RIP Input Tables From WAPDEG for LA Design Selection: Repository Horizon Elevation - 2-Level AML 50% and Near Maximum

    International Nuclear Information System (INIS)

    B.E. Bullard

    1999-01-01

    The purpose of this calculation is to document the WAPDEG version 3.09 (CRWMS M and O 1998b). Software Routine Report for WAPDEG (Version 3.09) simulations used to analyze waste package degradation and failure under the repository exposure conditions characterized by a two-tier thermal loading repository design. Also documented is the post-processing of these results into tables of waste-package-degradation-time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) computer program. Specifically, the WAPDEG simulations discussed in this calculation correspond to waste package emplacement conditions (repository environment and design) as defined in the Total System Performance Assessment-Viability Assessment (CRWMS M and O 1998a). Total System Performance Assessment-Viability Assessment (TSPA-VA) Analyses Technical Basis Document--Chapter 5, Waste Package Degradation Modeling And Abstraction, pp. 5-27 to 5-29, with the exception that a two-tier thermal loading design feature as specified in the License Application Design Selection (LADS) study was analyzed. The particular design feature evaluated in this report is a modification of the repository horizon elevation and layout within the Topopah Springs Member of Yucca Mountain. Specifically, the modification consists of adding a second level, 50-m above the base case repository layout. Two options were considered, representing two variations in thermal loading. In Design Feature 25e (designated DF25e), each level has an Areal Mass Loading (AML) of 42.5 MTU/acre (i.e., half the VA base case). In Design Feature 25f (designated DF25), each level has an AML of 64MTU/acre. As a result of the change in waste package placement relative to the TSPA-VA base-case design, different temperature and relative humidity time histories at the waste package surface are calculated (input to the WAPDEG simulations), and consequently

  2. Faruk Nafiz Çamlıbel’in Suda Halkalar Adlı Eserinde Su İmajları ve Benzetmeler Water Images and Metaphors in Suda Halkalar Which Faruk Nafiz Çamlıbel’s Work

    Directory of Open Access Journals (Sweden)

    Hüseyin DOĞRAMACIOĞLU

    2012-09-01

    Full Text Available Suda Halkalar (Circles in Water which the poetry book of Faruk Nafiz Çamlıbel, has not been translated into the Latin alphabet to the present day. The images of the water and metaphors which used in this work brought new connotations and approaches to the Turkish poetry. The images of the water in the poetry book are used instead of the poet's soul and dreams sometimes. These images are thought with poet’s darling and sometimes are used as a background. The poetformed the images of the water in his poem sadly. There are the poetand his darling in these tables. The images of the water and thedreams of the poet form the background of the poem. The backgroundsin this poem are repeated as a leitmotiv. Visuality and individualitybecomes important feature in these tables created by the poet. Themetaphors in the work created differently from classical Turkish poetry.These metaphors brought a new meaning to the poem. The poem basedon the intellectual grounds via metaphors. This can be considered asone of the significant achievements of Turkish poetry. We can see thatthe past remembered and desired both in poetry and metaphors bypessimistic feeling. In this respect the past affects the poet's dreamscombining with a sense of mourning, water images and metaphors inpoetry. The metaphors can be grouped as imaginary, visual andstrongly poetic ground. The feelings of pessimism and sadness arepredominant in these metaphors. The images and metaphors used bythe poet can be considered as an improvement for Turkish poetry. It isthe first research done on Suda Halkalar (Circles in Water will help tobetter understand and identify Çamlıbel’s aspect of poetry and literaryline. Faruk Nafiz Çamlıbel’in Suda Halkalar adlı şiir kitabı günümüze kadar Latin harflerine aktarılmamıştır. Bu eserde kullanılan su imajları ve benzetmeler Türk şiirine yeni yaklaşımlar ve çağrışımlar getirmiştir. Eserdeki su imajları bazen şairin ruhu ve hayalleri

  3. Specialized languages

    DEFF Research Database (Denmark)

    Mousten, Birthe; Laursen, Anne Lise

    2016-01-01

    Across different fields of research, one feature is often overlooked: the use of language for specialized purposes (LSP) as a cross-discipline. Mastering cross-disciplinarity is the precondition for communicating detailed results within any field. Researchers in specialized languages work cross...... science fields communicate their findings. With this article, we want to create awareness of the work in this special area of language studies and of the inherent cross-disciplinarity that makes LSP special compared to common-core language. An acknowledgement of the importance of this field both in terms...... of more empirical studies and in terms of a greater application of the results would give language specialists in trade and industry a solid and updated basis for communication and language use....

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

    Czech Academy of Sciences Publication Activity Database

    Steinbach, Gabor; Kaňa, Radek

    2016-01-01

    Roč. 22, č. 2 (2016), s. 258-263 ISSN 1431-9276 R&D Projects: GA ČR GAP501/12/0304; GA MŠk EE2.3.30.0059; GA MŠk ED2.1.00/03.0110; GA MŠk(CZ) LO1416 Institutional support: RVO:61388971 Keywords : automated microscopy * remote controlled microscopy * confocal microscopy Subject RIV: BH - Optics, Masers, Lasers Impact factor: 1.891, year: 2016

  5. Fuzzy Languages

    Science.gov (United States)

    Rahonis, George

    The theory of fuzzy recognizable languages over bounded distributive lattices is presented as a paradigm of recognizable formal power series. Due to the idempotency properties of bounded distributive lattices, the equality of fuzzy recognizable languages is decidable, the determinization of multi-valued automata is effective, and a pumping lemma exists. Fuzzy recognizable languages over finite and infinite words are expressively equivalent to sentences of the multi-valued monadic second-order logic. Fuzzy recognizability over bounded ℓ-monoids and residuated lattices is briefly reported. The chapter concludes with two applications of fuzzy recognizable languages to real world problems in medicine.

  6. Language Policy

    DEFF Research Database (Denmark)

    Lauridsen, Karen M.

    2008-01-01

    Like any other text, instructive texts function within a given cultural and situational setting and may only be available in one language. However, the end users may not be familiar with that language and therefore unable to read and understand the instructions. This article therefore argues...... that instructive texts should always be available in a language that is understood by the end users, and that a corporate communication policy which includes a language policy should ensure that this is in fact the case for all instructive texts....

  7. Macro-IML manual for DEC PDP 11 computer with controller DEC CA 11-A/BORER type 1,533 A

    International Nuclear Information System (INIS)

    Kubitz, M.; Kind, R.

    1975-03-01

    The IML-implementations follow the Macro-Syntax as given in Appendix A of the document 'CAMAC. The Definitior of IML (A Language For Use in CAMAC Systems)'. This document has been adopted as a description by ESONE and AEC NIM in August/September 74 and has been published in October 74. They have been designed for the DEC PDP 11 computer with the branch controller DEC CA 11-A and the Single Crate Controller BORER Type 1,533 A. For both DEC operating systems, DOS V08/09 and RSX-11D/M a full set of macros has been implemented except the block transfer on special LAM, X-error control statements and the subscript mode. Transfer modes not implemented by the hardware of the CA 11-A are simulated by software. (orig.) [de

  8. Çamlıbel - Ulubey (Uşak) Beyaz Mermerinin Jeolojik ve Fiziko-Mekanik Özelliklerinin Araştırılması

    OpenAIRE

    ÇELİK, Mustafa Yavuz; KIRILIVEREN, Sabri

    2012-01-01

    Menderes Masifinde yer alan Uşak bölgesi önemli bir mermer potansiyeline sahiptir. Bölgede Karahallı, Sivaslı ve Ulubey ilçeleri civarında mermer blok üretimi yapılmaktadır. Bu makalede, Çamlıbel-Ulubey (Uşak) beyaz mermerinin, mermer olarak kullanılabilirliği irdelenmiş ve yöre mermerleriyle karşılaştırılmaları yapılmıştır. Çamlıbel-Ulubey (Uşak) beyaz mermerinin özelliklerini belirlemek amacıyla yapılan deneylerde özgül kütle 2,73 g/cm3, kütlece su emme oranı % 0,06, doluluk oranı % 99,3, b...

  9. Semantic computing and language knowledge bases

    Science.gov (United States)

    Wang, Lei; Wang, Houfeng; Yu, Shiwen

    2017-09-01

    As the proposition of the next-generation Web - semantic Web, semantic computing has been drawing more and more attention within the circle and the industries. A lot of research has been conducted on the theory and methodology of the subject, and potential applications have also been investigated and proposed in many fields. The progress of semantic computing made so far cannot be detached from its supporting pivot - language resources, for instance, language knowledge bases. This paper proposes three perspectives of semantic computing from a macro view and describes the current status of affairs about the construction of language knowledge bases and the related research and applications that have been carried out on the basis of these resources via a case study in the Institute of Computational Linguistics at Peking University.

  10. Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods.

    Science.gov (United States)

    Kremser, Andreas; Dressig, Julia; Grabrucker, Christine; Liepert, Anja; Kroell, Tanja; Scholl, Nina; Schmid, Christoph; Tischer, Johanna; Kufner, Stefanie; Salih, Helmut; Kolb, Hans Jochem; Schmetzer, Helga

    2010-01-01

    Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

  11. Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine.

    Science.gov (United States)

    Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette

    2018-05-02

    Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. The integrated evaluation of the macro environment of companies providing transport services

    Directory of Open Access Journals (Sweden)

    A. Žvirblis

    2008-09-01

    Full Text Available The article presents the main principles of the integrated evaluation of macro environment components and factors influencing the performance of transport companies as well as providing the validated quantitative evaluation models and results obtained in evaluating the macro environment of Lithuanian companies providing transport services. Since quantitative evaluation is growing in importance, the process of developing the principles and methods of business macro environment quantitative evaluation is becoming relevant from both theoretical and practical perspectives. The created methodology is based on the concept of macro environment as an integrated whole of components, formalization and the principle of three-stage quantitative evaluation. The methodology suggested involves the quantitative evaluation of primary factors and macro environment components as an integral dimension (expressed in points. On the basis of this principle, an integrated macro environment evaluation parameter is established as its level index. The methodology integrates the identification of significant factors, building scenarios, a primary analysis of factors, expert evaluation, the quantitative evaluation of macro environment components and their whole. The application of the multi-criteria Simple Additive Weighting (SAW method is validated. The integrated evaluation of the macro environment of Lithuanian freight transportation companies was conducted. As a result, the level indices of all components as well as the level index of macro environment considered as a whole of components were identified. The latter reflects the extent of deviation from an average level of a favourable macro environment. This is important for developing strategic marketing decisions and expanding a strategic area.

  13. Linking ground motion measurements and macro-seismic observations in France: A case study based on the RAP (accelerometric) and BCSF (macro-seismic) databases

    International Nuclear Information System (INIS)

    Lesueur, Ch.

    2011-01-01

    Comparison between accelerometric and macro-seismic observations is made for three mw∼4.5 earthquakes of eastern France between 2003 and 2005. Scalar and spectral instrumental parameters are processed from the accelerometric data recorded by nine accelerometric stations located between 29 km and 180 km from the epicentres. Macro-seismic data are based on the French internet reports. In addition to the individual macro-seismic intensity, analysis of the internal correlation between the encoded answers highlights four predominant fields of questions, bearing different physical meanings: 1) 'vibratory motions of small objects', 2) 'displacement and fall of objects', 3) 'acoustic noise', and 4) 'personal feelings'. Best correlations between macro-seismic and instrumental observations are obtained when the macro-seismic parameters are averaged over 10 km radius circles around each station. macro-seismic intensities predicted by published pgv-intensity relationships quite agree with the observed intensities, contrary to those based on pga. The correlations between the macro-seismic and instrumental data, for intensities between ii and v (ems-98), show that pgv is the instrumental parameter presenting the best correlation with all macro-seismic parameters. The correlation with response spectra, exhibits clear frequency dependence over a limited frequency range [0.5-33 hz]. Horizontal and vertical components are significantly correlated with macro-seismic parameters between 1 and 10 hz, a range corresponding to both natural frequencies of most buildings and high energy content in the seismic ground motion. Between 10 and 25 hz, a clear lack of correlation between macro-seismic and instrumental data is observed, while beyond 25 hz the correlation coefficient increases, approaching that of the PGA correlation level. (author)

  14. Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

    Directory of Open Access Journals (Sweden)

    Lisa Pleyer

    2017-02-01

    Full Text Available We recently published a clinically-meaningful improvement in median overall survival (OS for patients with acute myeloid leukaemia (AML, >30% bone marrow (BM blasts and white blood cell (WBC count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010. As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012 and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214 with AAR patients meeting the same inclusion criteria (“AAR (001-like” cohort; n = 95. The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616 for “AML-001” versus “AAR (001-like” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309 and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6 months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95 versus all AAR patients with World Health Organization (WHO-defined AML (

  15. Consecutive epigenetically-active agent combinations act in ID1-RUNX3-TET2 and HOXA pathways for Flt3ITD+ve AML.

    Science.gov (United States)

    Sayar, Hamid; Liu, Yan; Gao, Rui; Zaid, Mohammad Abu; Cripe, Larry D; Weisenbach, Jill; Sargent, Katie J; Nassiri, Mehdi; Li, Lang; Konig, Heiko; Suvannasankha, Attaya; Pan, Feng; Shanmugam, Rajasubramaniam; Goswami, Chirayu; Kapur, Reuben; Xu, Mingjiang; Boswell, H Scott

    2018-01-19

    Co-occurrence of Flt3ITD and TET2 mutations provoke an animal model of AML by epigenetic repression of Wnt pathway antagonists, including RUNX3, and by hyperexpression of ID1, encoding Wnt agonist. These affect HOXA over-expression and treatment resistance. A comparable epigenetic phenotype was identified among adult AML patients needing novel intervention. We chose combinations of targeted agents acting on distinct effectors, at the levels of both signal transduction and chromatin remodeling, in relapsed/refractory AML's, including Flt3ITD+ve, described with a signature of repressed tumor suppressor genes, involving Wnt antagonist RUNX3 , occurring along with ID1 and HOXA over-expressions. We tracked patient response to combination of Flt3/Raf inhibitor, Sorafenib, and Vorinostat, pan-histone deacetylase inhibitor, without or with added Bortezomib, in consecutive phase I trials. A striking association of rapid objective remissions (near-complete, complete responses) was noted to accompany induced early pharmacodynamic changes within patient blasts in situ, involving these effectors, significantly linking RUNX3 /Wnt antagonist de-repression (80%) and ID1 downregulation (85%), to a response, also preceded by profound HOXA9 repression. Response occurred in context of concurrent TET2 mutation/hypomorphy and Flt3ITD+ve mutation (83% of complete responses). Addition of Bortezomib to the combination was vital to attainment of complete response in Flt3ITD+ve cases exhibiting such Wnt pathway dysregulation.

  16. Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

    Science.gov (United States)

    Locatelli, F; Masetti, R; Rondelli, R; Zecca, M; Fagioli, F; Rovelli, A; Messina, C; Lanino, E; Bertaina, A; Favre, C; Giorgiani, G; Ripaldi, M; Ziino, O; Palumbo, G; Pillon, M; Pession, A; Rutella, S; Prete, A

    2015-02-01

    We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.

  17. Linking Resilience and Transformation as Micro- and Macro Adaptation

    Science.gov (United States)

    Friedman, E.; Breitzer, R.; Solecki, W. D.

    2017-12-01

    The concept of resiliency within climate adaptation planning and practice is widespread, but in some ways it has begun to suffer from its own success. While resiliency provides a valuable frame for understanding the conditions and opportunities for localized responses to increasing climate risks, the concept's ubiquitous use leads to it being applied to often conflicting policy agendas, which can mask or limit the capacity to connect efforts focused on near term risk to longer term and emergent climate threats in communities. These challenges are particularly evident in the context of extreme events and in the post extreme event policy windows. To overcome these issues and take advantage of the post-event policy window, the NOAA RISA Climate Change Risk in the Urban Northeast (CCRUN) project has been developing two specific, "boutique", policy tools. These include the PELT (Post-event learning toolkit) and MART (Macro-adaptation Resilience toolkit) toolkits. Embedded in these toolkits are two approaches to small scale strategies often associated with near term action (i.e., micro-adaptation) and large scale strategies associated with broad longer term needs (i.e., macro-adaptation). In this paper, these two approaches - micro and macro adaptation - are theoretically defined and presented in practice through the beta-testing of the PELT and MART toolkits. Most importantly, we illustrate how the theoretical links between resiliency and transformation can be operationalized through the use of these approaches, and how these approaches can be implemented in everyday risk management practice. We present our work through selected case studies in the Northeast US region, specifically in Jamaica Bay, New York, and Eastwick neighborhood in Philadelphia.

  18. 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"> 

  19. 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.

  20. Graphene macro-assembly-fullerene composite for electrical energy storage

    Science.gov (United States)

    Campbell, Patrick G.; Baumann, Theodore F.; Biener, Juergen; Merrill, Matthew; Montalvo, Elizabeth; Worsley, Marcus A.; Biener, Monika M.; Hernandez, Maira Raquel Ceron

    2018-01-16

    Disclosed here is a method for producing a graphene macro-assembly (GMA)-fullerene composite, comprising providing a GMA comprising a three-dimensional network of graphene sheets crosslinked by covalent carbon bonds, and incorporating at least 20 wt. % of at least one fullerene compound into the GMA based on the initial weight of the GMA to obtain a GMA-fullerene composite. Also described are a GMA-fullerene composite produced, an electrode comprising the GMA-fullerene composite, and a supercapacitor comprising the electrode and optionally an organic or ionic liquid electrolyte in contact with the electrode.

  1. The role of money in modern macro models

    OpenAIRE

    Seitz, Franz; Schmidt, Markus A.

    2013-01-01

    This paper is the starting point of a series of analyses aiming at re-discovering the role of money for monetary policy purposes. It provides an overview of the role of money in modern macro models. In particular, we are focussing on New Keynesian and New Monetarist models to investigate their main findings and most significant shortcomings in considering money properly. As a further step, we ask about the role of financial intermediaries in this respect. In dealing with these issues, we dist...

  2. Macro economic profitability of hourly measurements and binary communications

    International Nuclear Information System (INIS)

    Andersen, Christian; Lund, Arne-Christian

    2005-11-01

    There are several actors that are subject to hourly measurements and dynamic pricing. The effects are registered in several analyses. A typical division would be effects connected to power producers, power deliverers, network companies and end users. In a macro economic analysis the goal would be to identify alterations in total benefits and costs. The transition from studying isolated effects for single actors to a macro economic perspective produces several principal problems. When the analysis is based on the effects for various actors it would be important to identify transitions between various actors that in itself does not contribute to alterations in the macro economic profit. At the same time it will be important that effects to be valued are evaluated in a consistent an consequential way. In this context it may be beneficial to use a model for the actors adaptation to the power market where various effects may be used. This working paper describes utility and cost elements that is a basis for Norwegian and foreign analysis of hourly measurements and dynamic prices. The survey shows that it is a large agreement between different investigations with respect to principle effects to be emphasized. There is however, variation with respect to what effects actually are in operation and quantified. There may also be large deviances in the valuation of various utility and cost components. Some single effects are studied closer. An effort is made to compare certain figures from the literature. However, this comparison has been difficult because it is not always clear what conditions have lead to the figures in use. There are large variations between the various analysis estimates. There may be several reasons. The technical products to be priced may vary. It is also evident that the costs for changing measuring equipment may be dependent of the management strategy. The paper refers to newer theoretical literature about the effects of hourly measurements and dynamic

  3. 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

  4. 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.

  5. 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 ...... bonds, investment grade corporate bonds, and high-yield corporate bonds. The CSR method performs well in predicting bond betas, especially in-sample, and, mainly high-yield bond betas when the focus is out-of-sample. Bond returns are less predictable than bond betas....

  6. Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Münster AML-study group

    Science.gov (United States)

    Coenen, Eva A.; Zwaan, C. Michel; Reinhardt, Dirk; Harrison, Christine J.; Haas, Oskar A.; de Haas, Valerie; Mihál, Vladimir; De Moerloose, Barbara; Jeison, Marta; Rubnitz, Jeffrey E.; Tomizawa, Daisuke; Johnston, Donna; Alonzo, Todd A.; Hasle, Henrik; Auvrignon, Anne; Dworzak, Michael; Pession, Andrea; van der Velden, Vincent H. J.; Swansbury, John; Wong, Kit-fai; Terui, Kiminori; Savasan, Sureyya; Winstanley, Mark; Vaitkeviciene, Goda; Zimmermann, Martin; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2013-01-01

    In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases. PMID:23974201

  7. 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.

  8. CD4(+)and CD8(+)T-cell reactions against leukemia-associated- or minor-histocompatibility-antigens in AML-patients after allogeneic SCT.

    Science.gov (United States)

    Steger, Brigitte; Milosevic, Slavoljub; Doessinger, Georg; Reuther, Susanne; Liepert, Anja; Braeu, Marion; Schick, Julia; Vogt, Valentin; Schuster, Friedhelm; Kroell, Tanja; Busch, Dirk H; Borkhardt, Arndt; Kolb, Hans-Jochem; Tischer, Johanna; Buhmann, Raymund; Schmetzer, Helga

    2014-04-01

    T-cells play an important role in the remission-maintenance in AML-patients (pts) after SCT, however the role of LAA- (WT1, PR1, PRAME) or minor-histocompatibility (mHag, HA1) antigen-specific CD4(+) and CD8(+)T-cells is not defined. A LAA/HA1-peptide/protein stimulation, cloning and monitoring strategy for specific CD8(+)/CD4(+)T-cells in AML-pts after SCT is given. Our results show that (1) LAA-peptide-specific CD8+T-cells are detectable in every AML-pt after SCT. CD8(+)T-cells, recognizing two different antigens detectable in 5 of 7 cases correlate with long-lasting remissions. Clonal TCR-Vβ-restriction exemplarily proven by spectratyping in PRAME-specific CD8(+)T-cells; high PRAME-peptide-reactivity was CD4(+)-associated, as shown by IFN-γ-release. (2) Two types of antigen-presenting cells (APCs) were tested for presentation of LAA/HA1-proteins to CD4(+)T-cells: miniEBV-transduced lymphoblastoid cells (B-cell-source) and CD4-depleted MNC (source for B-cell/monocyte/DC). We provide a refined cloning-system for proliferating, CD40L(+)CD4(+)T-cells after LAA/HA1-stimulation. CD4(+)T-cells produced cytokines (GM-CSF, IFN-γ) upon exposure to LAA/HA1-stimulation until after at least 7 restimulations and demonstrated cytotoxic activity against naive blasts, but not fibroblasts. Antileukemic activity of unstimulated, stimulated or cloned CD4(+)T-cells correlated with defined T-cell-subtypes and the clinical course of the disease. In conclusion we provide immunological tools to enrich and monitor LAA/HA1-CD4(+)- and CD8(+)T-cells in AML-pts after SCT and generate data with relevant prognostic value. We were able to demonstrate the presence of LAA-peptide-specific CD8(+)T-cell clones in AML-pts after SCT. In addition, we were also able to enrich specific antileukemic reactive CD4(+)T-cells without GvH-reactivity upon repeated LAA/HA1-protein stimulation and limiting dilution cloning. Copyright © 2013 Elsevier GmbH. All rights reserved.

  9. Effects of macro nutrient concentration on biological N2 fixation by Azotobacter vinelandii ATCC 12837

    International Nuclear Information System (INIS)

    Liew Pauline Woan Ying; Nazalan Najimudin; Jong Bor Chyan; Latiffah Noordin; Khairuddin Abdul Rahim; Amir Hamzah Ahmad Ghazali

    2010-01-01

    The dynamic changes of biological N 2 fixation by Azotobacter vinelandii ATCC 12837 under the influence of various macro nutrients, specifically phosphorus (P) and potassium (K), was investigated. In this attempt, Oryza sativa L. var. MR 219 was used as the model plant. Results obtained showed changes in the biological N 2 fixation activities with different macro nutrient(s) manipulations. The research activity enables optimisation of macro nutrients concentration for optimal/ enhanced biological N 2 fixation by A. vinelandii ATCC 12837. (author)

  10. Search for stellar collapse with the MACRO detector at Gran Sasso

    International Nuclear Information System (INIS)

    1989-01-01

    The first MACRO supermodule commenced data taking in February 1989. Two complementary trigger and readout systems have been used to monitor the horizontal scintillation counters, which contain 42 tonnes (∼1 ktonne for the full MACRO detector) of liquid scintillator, for bursts of low energy anti-neutrinos from gravitational stellar collapses. This paper reports on an initial search and discusses the present as well as ultimate sensitivity of MACRO to this class of events. 4 figs

  11. Macro Security Methodology for Conducting Facility Security and Sustainability Assessments

    International Nuclear Information System (INIS)

    Herdes, Greg A.; Freier, Keith D.; Wright, Kyle A.

    2007-01-01

    Pacific Northwest National Laboratory (PNNL) has developed a macro security strategy that not only addresses traditional physical protection systems, but also focuses on sustainability as part of the security assessment and management process. This approach is designed to meet the needs of virtually any industry or environment requiring critical asset protection. PNNL has successfully demonstrated the utility of this macro security strategy through its support to the NNSA Office of Global Threat Reduction implementing security upgrades at international facilities possessing high activity radioactive sources that could be used in the assembly of a radiological dispersal device, commonly referred to as a 'dirty bomb'. Traditional vulnerability assessments provide a snap shot in time of the effectiveness of a physical protection system without significant consideration to the sustainability of the component elements that make up the system. This paper describes the approach and tools used to integrate technology, plans and procedures, training, and sustainability into a simple, quick, and easy-to-use security assessment and management tool.

  12. Muon energy estimate through multiple scattering with the MACRO detector

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosio, M.; Antolini, R.; 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.; Candela, A.; Carboni, M.; Caruso, R.; Cassese, F.; Cecchini, S.; Cei, F.; Chiarella, V.; Choudhary, B.C.; Coutu, S.; Cozzi, M.; De Cataldo, G.; De Deo, M.; Dekhissi, H.; De Marzo, C.; De Mitri, I.; Derkaoui, J.; De Vincenzi, M.; Di Credico, A.; Dincecco, M.; Erriquez, O.; Favuzzi, C.; Forti, C.; Fusco, P.; Giacomelli, G.; Giannini, G.; Giglietto, N.; Giorgini, M.; Grassi, M.; Gray, L.; Grillo, A.; Guarino, F.; 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.; Lindozzi, M.; 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.; Nicolo, 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.; Raino, A.; Reynoldson, J.; Ronga, F.; Rrhioua, A.; Satriano, C.; Scapparone, E. E-mail: eugenio.scapparone@bo.infn.it; Scholberg, K.; Sciubba, A.; Serra, P.; Sioli, M. E-mail: maximiliano.sioli@bo.infn.it; Sirri, G.; Sitta, M.; Spinelli, P.; Spinetti, M.; Spurio, M.; Steinberg, R.; Stone, J.L.; Sulak, L.R.; Surdo, A.; Tarle, G.; Tatananni, E.; Togo, V.; Vakili, M.; Walter, C.W.; Webb, R

    2002-10-21

    Muon energy measurement represents an important issue for any experiment addressing neutrino-induced up-going muon studies. Since the neutrino oscillation probability depends on the neutrino energy, a measurement of the muon energy adds an important piece of information concerning the neutrino system. We show in this paper how the MACRO limited streamer tube system can be operated in drift mode by using the TDCs included in the QTPs, an electronics designed for magnetic monopole search. An improvement of the space resolution is obtained, through an analysis of the multiple scattering of muon tracks as they pass through our detector. This information can be used further to obtain an estimate of the energy of muons crossing the detector. Here we present the results of two dedicated tests, performed at CERN PS-T9 and SPS-X7 beam lines, to provide a full check of the electronics and to exploit the feasibility of such a multiple scattering analysis. We show that by using a neural network approach, we are able to reconstruct the muon energy for E{sub {mu}}<40 GeV. The test beam data provide an absolute energy calibration, which allows us to apply this method to MACRO data.

  13. Anti-Phytopathogenic Activities of Macro-Algae Extracts

    Directory of Open Access Journals (Sweden)

    Ingrid Ramírez

    2011-05-01

    Full Text Available Aqueous and ethanolic extracts obtained from nine Chilean marine macro-algae collected at different seasons were examined in vitro and in vivo for properties that reduce the growth of plant pathogens or decrease the injury severity of plant foliar tissues following pathogen infection. Particular crude aqueous or organic extracts showed effects on the growth of pathogenic bacteria whereas others displayed important effects against pathogenic fungi or viruses, either by inhibiting fungal mycelia growth or by reducing the disease symptoms in leaves caused by pathogen challenge. Organic extracts obtained from the brown-alga Lessonia trabeculata inhibited bacterial growth and reduced both the number and size of the necrotic lesion in tomato leaves following infection with Botrytis cinerea. Aqueous and ethanolic extracts from the red-alga Gracillaria chilensis prevent the growth of Phytophthora cinnamomi, showing a response which depends on doses and collecting-time. Similarly, aqueous and ethanolic extracts from the brown-alga Durvillaea antarctica were able to diminish the damage caused by tobacco mosaic virus (TMV in tobacco leaves, and the aqueous procedure is, in addition, more effective and seasonally independent. These results suggest that macro-algae contain compounds with different chemical properties which could be considered for controlling specific plant pathogens.

  14. From micro-correlations to macro-correlations

    International Nuclear Information System (INIS)

    Eliazar, Iddo

    2016-01-01

    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.

  15. 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.

  16. Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Hanumantha Rao Madala

    2018-02-01

    Full Text Available Isocitrate dehydrogenases 1 and 2 (IDH1,2, the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs and gain an unusual new activity of reducing the α-ketoglutarate (α-KG to D-2 hydroxyglutarate (D-2HG in a NADPH-consuming reaction. The oncometabolite D-2HG, which accumulates >35 mM, is widely accepted to drive a progressive oncogenesis besides exacerbating the already increased oxidative stress in these cancers. More importantly, D-2HG competes with α-KG and inhibits a large number of α-KG-dependent dioxygenases such as TET (Ten-eleven translocation, JmjC domain-containing KDMs (histone lysine demethylases, and the ALKBH DNA repair proteins that ultimately lead to hypermethylation of the CpG islands in the genome. The resulting CpG Island Methylator Phenotype (CIMP accounts for major gene expression changes including the silencing of the MGMT (O6-methylguanine DNA methyltransferase repair protein in gliomas. Glioma patients with IDH1 mutations also show better therapeutic responses and longer survival, the reasons for which are yet unclear. There has been a great surge in drug discovery for curtailing the mutant IDH activities, and arresting tumor proliferation; however, given the unique and chronic metabolic effects of D-2HG, the promise of these compounds for glioma treatment is uncertain. This comprehensive review discusses the biology, current drug design and opportunities for improved therapies through exploitable synthetic lethality pathways, and an intriguing oncometabolite-inspired strategy for primary glioblastoma.

  17. 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...

  18. Dynamic Resource Partitioning for Downlink Femto-to-Macro-Cell Interference Avoidance

    Directory of Open Access Journals (Sweden)

    Zubin Bharucha

    2010-01-01

    Full Text Available Femto-cells consist of user-deployed Home Evolved NodeBs (HeNBs that promise substantial gains in system spectral efficiency, coverage, and data rates due to an enhanced reuse of radio resources. However, reusing radio resources in an uncoordinated, random fashion introduces potentially destructive interference to the system, both, in the femto and macro layers. An especially critical scenario is a closed-access femto-cell, cochannel deployed with a macro-cell, which imposes strong downlink interference to nearby macro user equipments (UEs that are not permitted to hand over to the femto-cell. In order to maintain reliable service of macro-cells, it is imperative to mitigate the destructive femto-cell to macro-cell interference. The contribution in this paper focuses on mitigating downlink femto-cell to macro-cell interference through dynamic resource partitioning, in the way that HeNBs are denied access to downlink resources that are assigned to macro UEs in their vicinity. By doing so, interference to the most vulnerable macro UEs is effectively controlled at the expense of a modest degradation in femto-cell capacity. The necessary signaling is conveyed through downlink high interference indicator (DL-HII messages over the wired backbone. Extensive system level simulations demonstrate that by using resource partitioning, for a sacrifice of 4% of overall femto downlink capacity, macro UEs exposed to high HeNB interference experience a tenfold boost in capacity.

  19. Multi-scale-nonlinear interactions among macro-MHD mode, micro-turbulence, and zonal flow

    International Nuclear Information System (INIS)

    Ishizawa, Akihiro; Nakajima, Noriyoshi

    2007-01-01

    This is the first numerical simulation demonstrating that macro-magnetohydrodynamic (macro-MHD) mode is exited as a result of multi-scale interaction in a quasi-steady equilibrium formed by a balance between zonal flow and micro-turbulence via reduced-two-fluid simulation. Only after obtaining the equilibrium which includes zonal flow and the turbulence caused by kinetic ballooning mode is this simulation of macro-MHD mode, double tearing mode, accomplished. In the quasi-steady equilibrium a macro-fluctuation which has the same helicity as that of double tearing mode is a part of the turbulence until it grows as a macro-MHD mode finally. When the macro-MHD grows it effectively utilize free energy of equilibrium current density gradient because of positive feedback loop between suppression of zonal flow and growth of the macro-fluctuation causing magnetic reconnection. Thus once the macro-MHD grows from the quasi-equilibrium, it does not go back. This simulation is more comparable with experimental observation of growing macro-fluctuation than traditional MHD simulation of linear instabilities in a static equilibrium. (author)

  20. Building Languages

    Science.gov (United States)

    ... Glossary Contact Information Information For… Media Policy Makers Building Languages Recommend on Facebook Tweet Share Compartir Communicating ... any speech and only very loud sounds. Close × “Building Blocks” “Building Blocks” refers to the different skills ...

  1. Extending network approach to language dynamics and human cognition. Comment on "Approaching human language with complex networks" by Cong and Liu

    Science.gov (United States)

    Gong, Tao; Shuai, Lan; Wu, Yicheng

    2014-12-01

    By analyzing complex networks constructed from authentic language data, Cong and Liu [1] advance linguistics research into the big data era. The network approach has revealed many intrinsic generalities and crucial differences at both the macro and micro scales between human languages. The axiom behind this research is that language is a complex adaptive system [2]. Although many lexical, semantic, or syntactic features have been discovered by means of analyzing the static and dynamic linguistic networks of world languages, available network-based language studies have not explicitly addressed the evolutionary dynamics of language systems and the correlations between language and human cognition. This commentary aims to provide some insights on how to use the network approach to study these issues.

  2. The FORCE: A highly portable parallel programming language

    Science.gov (United States)

    Jordan, Harry F.; Benten, Muhammad S.; Alaghband, Gita; Jakob, Ruediger

    1989-01-01

    Here, it is explained why the FORCE parallel programming language is easily portable among six different shared-memory microprocessors, and how a two-level macro preprocessor makes it possible to hide low level machine dependencies and to build machine-independent high level constructs on top of them. These FORCE constructs make it possible to write portable parallel programs largely independent of the number of processes and the specific shared memory multiprocessor executing them.

  3. The FORCE - A highly portable parallel programming language

    Science.gov (United States)

    Jordan, Harry F.; Benten, Muhammad S.; Alaghband, Gita; Jakob, Ruediger

    1989-01-01

    This paper explains why the FORCE parallel programming language is easily portable among six different shared-memory multiprocessors, and how a two-level macro preprocessor makes it possible to hide low-level machine dependencies and to build machine-independent high-level constructs on top of them. These FORCE constructs make it possible to write portable parallel programs largely independent of the number of processes and the specific shared-memory multiprocessor executing them.

  4. 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

  5. Hidden Bilingualism: Ideological Influences on the Language Practices of Multilingual Migrant Mothers in Japan

    Science.gov (United States)

    Nakamura, Janice

    2016-01-01

    This study examines the challenges of minority language transmission in exogamous families in a society where linguistic and cultural homogeneity still prevails. Specifically, it investigates the macro and micro ideological influences that lead multilingual migrant mothers in Japan to speak Japanese to their children. Interview data with six Thai…

  6. LANGUAGE COMPETENCE OF STUDENT TOWARD RIGHT HEMISPHER BRAIN FUNCTION : A Neuropragmatic Study

    OpenAIRE

    Handoko, Handoko; Sastra, Gusdi; Revita, Ike

    2015-01-01

    It has been known that the right hemisphere is contributed to language processing, especially in macro level, including macrostructure or discourse processing. This research is aimed at evaluating the students’ ability in language processing concerning macrostructure and the right hemispher brain function. This research is based on Dharmaperwira-prins method “Right Hemisphere Communication Assessment” (Pemeriksaan Komunikasi Hemisfer Kanan/PKHK). Research on students’ ability in macrostructur...

  7. Report of a Phase II Study of Clofarabine and Cytarabine in De Novo and Relapsed and Refractory AML Patients and in Selected Elderly Patients at High Risk for Anthracycline Toxicity

    Science.gov (United States)

    Cooper, Barry; Holmes, Houston; Vance, Estil; Berryman, Robert Brian; Maisel, Christopher; Li, Sandy; Saracino, Giovanna; Tadic-Ovcina, Mirjana; Fay, Joseph

    2011-01-01

    Purpose. To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and in elderly patients with untreated AML and heart disease. Patients and Methods. Patients with relapsed/refractory AML and older patients for whom there was a concern over toxicity from additional anthracyclines received 5 days of clofarabine, 40 mg/m2 per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m2 per day i.v. over 2 hours. Results. Thirty patients were enrolled. The median age was 67 years (range, 38–82 years) and 18 (60%) had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for anthracycline toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, including a CR in 14 patients (47%). Responses were observed in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median disease-free survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation. Conclusions. Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML. PMID:21273514

  8. CTTITEM: SAS macro and SPSS syntax for classical item analysis.

    Science.gov (United States)

    Lei, Pui-Wa; Wu, Qiong

    2007-08-01

    This article describes the functions of a SAS macro and an SPSS syntax that produce common statistics for conventional item analysis including Cronbach's alpha, item difficulty index (p-value or item mean), and item discrimination indices (D-index, point biserial and biserial correlations for dichotomous items and item-total correlation for polytomous items). These programs represent an improvement over the existing SAS and SPSS item analysis routines in terms of completeness and user-friendliness. To promote routine evaluations of item qualities in instrument development of any scale, the programs are available at no charge for interested users. The program codes along with a brief user's manual that contains instructions and examples are downloadable from suen.ed.psu.edu/-pwlei/plei.htm.

  9. Atmospheric neutrino-induced muons in the MACRO detector

    CERN Document Server

    Ronga, F

    1999-01-01

    A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.

  10. Macro and Micro Remote Viewing of Objects in Sealed Gloveboxes

    International Nuclear Information System (INIS)

    Heckendorn, F.M.

    2004-01-01

    The Savannah River Site uses sophisticated glovebox facilities to process and analyze material that is radiologically contaminated or that must be protected from contamination by atmospheric gases. The analysis can be visual, non destructive measurement, or destructive measurement, and allows for the gathering of information that would otherwise not be obtainable. Macro and Micro systems that cover a range of 2X to 400X magnifications with a robust system compatible with the harsh glovebox environment were installed. Remote video inspection systems were developed and deployed in Savannah River Site glovebox facilities that provide high quality or mega-pixel quality remote views, for remote inspections. The specialized video systems that are the subject of this report exhibited specialized field application of remote video/viewing techniques by expanding remote viewing to high and very high quality viewing in gloveboxes. This technological enhancement will allow the gathering of precision information that is otherwise not available

  11. Explanatory IRT Analysis Using the SPIRIT Macro in SPSS

    Directory of Open Access Journals (Sweden)

    DiTrapani, Jack

    2018-04-01

    Full Text Available Item Response Theory (IRT is a modeling framework that can be applied to a large variety of research questions spanning several disciplines. To make IRT models more accessible for the general researcher, a free tool has been created that can easily conduct one-parameter logistic IRT (1PL analyses using the convenient point-and-click interface in SPSS without any required downloads or add-ons. This tool, the SPIRIT macro, can fit 1PL models with person and item covariates, DIF analyses, multidimensional models, multigroup models, rating scale models, and several other variations. Example explanatory models are presented with an applied dataset containing responses to an ADHD rating scale. Illustrations of how to fit basic 1PL models as well as two more complicated analyses using SPIRIT are given.

  12. Respiratory monitoring system based on fiber optic macro bending

    Science.gov (United States)

    Purnamaningsih, Retno Wigajatri; Widyakinanti, Astari; Dhia, Arika; Gumelar, Muhammad Raditya; Widianto, Arif; Randy, Muhammad; Soedibyo, Harry

    2018-02-01

    We proposed a respiratory monitoring system for living activities in human body based on fiber optic macro-bending for laboratory scale. The respiration sensor consists of a single-mode optical fiber and operating on a wavelength at around 1550 nm. The fiber optic was integrated into an elastic fabric placed on the chest and stomach of the monitored human subject. Deformations of the flexible textile involving deformations of the fiber optic bending curvature, which was proportional to the chest and stomach expansion. The deformation of the fiber was detected using photodetector and processed using microcontroller PIC18F14K50. The results showed that this system able to display various respiration pattern and rate for sleeping, and after walking and running activities in real time.

  13. Search for lightly ionizing particles with the MACRO detector

    CERN Document Server

    Ambrosio, M; Auriemma, G; Bakari, D; Baldini, A; Barbarino, G C; Barish, B C; Battistoni, G; Bellotti, R; Bemporad, C; Bernardini, P; Bilokon, H; Bisi, V; Bloise, C; Bower, C; Brigida, M; Bussino, S; Cafagna, F; Calicchio, M; Campana, D; Carboni, M; Cecchini, S; Cei, F; Chiarella, V; Choudhary, B C; Coutu, S; De Cataldo, M A A; 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; Gray, L; Grillo, A; Guarino, F; Gustavino, C; Habig, A; Hanson, K; Heinz, R; Iarocci, Enzo; Katsavounidis, E; Katsavounidis, I; Kearns, E T; 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; Mikheyev, S P; Miller, L; Monacelli, P; Montaruli, T; Monteno, M; Mufson, S L; Musser, J; Nicolò, D; Nolty, R; Orth, C; Okada, C; Osteria, G; Ouchrif, M; 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; Satriano, C; Satta, L; Scapparone, E; Scholberg, K; Sciubba, A; Serra, P; Sioli, M; Sitta, M; Spinelli, P; Spinetti, M; Spurio, M; Steinberg, R; Stone, J L; Sulak, Lawrence R; Surdo, A; Tarle, G; Togo, V; Vakili, M; Vilela, E; Walter, C W; Webb, R

    2000-01-01

    A search for lightly ionizing particles has been performed with the MACRO detector. This search was sensitive to particles with charges between 1/5 e and close to the charge of an electron, with beta between approximately 0.25 and 1.0. Unlike previous searches both single track events and tracks buried within high multiplicity muon showers were examined. In a period of approximately one year no candidates were observed. Assuming an isotropic flux, for the single track sample this corresponds to a 90% C.L. upper flux limit Phi

  14. Macro Data Analysis of Traffic Accidents in Indonesia

    Directory of Open Access Journals (Sweden)

    Annisa Jusuf

    2017-04-01

    Full Text Available This paper presents a macro data analysis of Indonesian road accidents in the form of statistical data. Traffic accidents and their subsequent fatalities bring enormous social and economic consequences. A good understanding of the problem is expected to initiate major action toward the improvement of road and vehicle safety. One important milestone is the collection and analysis of road accident data. The results from this study portray the ‘tangled threads’ problem of traffic in Indonesia. The population number and number of vehicles have increased steadily, as has been accurately predicted by experts. Meanwhile, there is not enough infrastructure growth. Motorcycles are the main contributor to traffic accidents and fatalities due to their popularity as an effective vehicle to jump traffic jams. The ‘tangled threads’ need an extremely creative and comprehensive solution.

  15. Macro-invertebrate decline in surface water polluted with imidacloprid.

    Directory of Open Access Journals (Sweden)

    Tessa C Van Dijk

    Full Text Available Imidacloprid is one of the most widely used insecticides in the world. Its concentration in surface water exceeds the water quality norms in many parts of the Netherlands. Several studies have demonstrated harmful effects of this neonicotinoid to a wide range of non-target species. Therefore we expected that surface water pollution with imidacloprid would negatively impact aquatic ecosystems. Availability of extensive monitoring data on the abundance of aquatic macro-invertebrate species, and on imidacloprid concentrations in surface water in the Netherlands enabled us to test this hypothesis. Our regression analysis showed a significant negative relationship (P<0.001 between macro-invertebrate abundance and imidacloprid concentration for all species pooled. A significant negative relationship was also found for the orders Amphipoda, Basommatophora, Diptera, Ephemeroptera and Isopoda, and for several species separately. The order Odonata had a negative relationship very close to the significance threshold of 0.05 (P = 0.051. However, in accordance with previous research, a positive relationship was found for the order Actinedida. We used the monitoring field data to test whether the existing three water quality norms for imidacloprid in the Netherlands are protective in real conditions. Our data show that macrofauna abundance drops sharply between 13 and 67 ng l(-1. For aquatic ecosystem protection, two of the norms are not protective at all while the strictest norm of 13 ng l(-1 (MTR seems somewhat protective. In addition to the existing experimental evidence on the negative effects of imidacloprid on invertebrate life, our study, based on data from large-scale field monitoring during multiple years, shows that serious concern about the far-reaching consequences of the abundant use of imidacloprid for aquatic ecosystems is justified.

  16. A zwitterionic macro-crosslinker for durable non-fouling coatings.

    Science.gov (United States)

    Wang, Wei; Lu, Yang; Xie, Jinbing; Zhu, Hui; Cao, Zhiqiang

    2016-03-28

    A novel zwitterionic macro-crosslinker was developed and applied to fabricate durable non-fouling coatings on a polyurethane substrate. The zwitterionic macro-crosslinker coating exhibited superior durability over the traditional brush polymer coating and was able to retain its non-fouling property even after weeks of shearing in flowing liquid.

  17. Teaching Note--Incorporating Social Innovation Content into Macro Social Work Education

    Science.gov (United States)

    Pitt-Catsouphes, Marcie; Cosner Berzin, Stephanie

    2015-01-01

    The practice of social innovation offers promising approaches for addressing social issues. Although many social innovation strategies are congruent with macro social work theory and practice, some of the insights and tactics that have emerged in the social innovation field have the potential to strengthen current macro practice. Based on our…

  18. Evolutionary modelling of the macro-economic impacts of catastrophic flood events

    NARCIS (Netherlands)

    Safarzynska, K.E.; Brouwer, R.; Hofkes, M.

    2013-01-01

    This paper examines the possible contribution of evolutionary economics to macro-economic modelling of flood impacts to provide guidance for future economic risk modelling. Most macro-economic models start from a neoclassical economic perspective and focus on equilibrium outcomes, either in a static

  19. SPSS Macros for Assessing the Reliability and Agreement of Student Evaluations of Teaching

    Science.gov (United States)

    Morley, Donald D.

    2009-01-01

    This article reports and demonstrates two SPSS macros for calculating Krippendorff's alpha and intraclass reliability coefficients in repetitive situations where numerous coefficients are needed. Specifically, the reported SPSS macros were used to evaluate the interrater agreement and reliability of student evaluations of teaching in thousands of…

  20. Investigation of porous concrete through macro and meso-scale testing

    NARCIS (Netherlands)

    Agar Ozbek, A.S.; Weerheijm, J.; Schlangen, H.E.J.G.

    2010-01-01

    In designing a porous concrete, containing a high volume of air pores, the effects of its mesoscale phases on its macro level properties have to be known. For this purpose, porous concretes having different aggregate gradings and cement paste compositions were investigated through macro-scale

  1. A Macro-Micro-Symbolic Teaching to Promote Relational Understanding of Chemical Reactions

    Science.gov (United States)

    Jaber, Lama Ziad; Boujaoude, Saouma

    2012-01-01

    The purpose of this research is threefold: (1) to identify the difficulties that Grade 10 students in a Lebanese school have that hinder their conceptual understanding at the micro-macro-symbolic interface in chemistry, (2) to investigate the effect of a macro-micro-symbolic teaching approach on students' relational understanding of chemical…

  2. Comprehensive comparison of macro-strain mode and displacement mode based on different sensing technologies

    Science.gov (United States)

    Hong, Wan; Zhang, Jian; Wu, Gang; Wu, Zhishen

    2015-01-01

    A comprehensive comparison of macro-strain mode and displacement mode obtained from distributed macro-strain sensing and high-density point sensing (such as accelerometers) technologies is presented in this paper. Theoretical derivation reveals that displacement mode shape from accelerometers and modal macro-strain from distributed macro-strain sensors can be converted into each other. However, it is realized that displacement mode shape as global behavior of a structure can still be calculated with high-precision from modal macro-strain considering measurement errors in practical monitoring, whereas modal macro-strain can hardly be accurately achieved from displacement mode shape when signals are corrupted with noise in practical monitoring. Simulation and experiment results show that the calculated displacement mode shapes are very close to the actual ones even if the noise level reaches 5%. Meanwhile, damage index using measured modal macro-strain is still effective when the measurements are corrupted with 5% noise which is reliable for damage detection in practical monitoring. Calculating modal macro-strain from noise-polluted displacement mode shape will cause an unacceptable error if the noise level reaches only 0.5%, which has been verified in the simulation.

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

    DEFF Research Database (Denmark)

    Soret, Beatriz; Pedersen, Klaus I.

    2013-01-01

    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...

  4. Comparing the photocatalytic activity of TiO2 at macro- and microscopic scales

    DEFF Research Database (Denmark)

    Torras-Rosell, Antoni; Johannsen, Sabrina Rostgaard; Dirscherl, Kai

    2016-01-01

    . The photocatalytic properties of TiO2 at macro- and microscopic scales are investigated by comparing photocatalytic degradation of acetone and electrochemical experiments to Kelvin probe force microscopy. The good agreement between the macro- and microscopic experiments suggests that Kelvin probe force microscopy...

  5. Studying neighborhood crime across different macro spatial scales: The case of robbery in 4 cities.

    Science.gov (United States)

    Hipp, John R; Wo, James C; Kim, Young-An

    2017-11-01

    Whereas there is a burgeoning literature focusing on the spatial distribution of crime events across neighborhoods or micro-geographic units in a specific city, the present study expands this line of research by selecting four cities that vary across two macro-spatial dimensions: population in the micro-environment, and population in the broader macro-environment. We assess the relationship between measures constructed at different spatial scales and robbery rates in blocks in four cities: 1) San Francisco (high in micro- and macro-environment population); 2) Honolulu (high in micro- but low in macro-environment population); 3) Los Angeles (low in micro- but high in macro-environment population); 4) Sacramento (low in micro- and macro-environment population). Whereas the socio-demographic characteristics of residents further than ½ mile away do not impact robbery rates, the number of people up to 2.5 miles away are related to robbery rates, especially in the two cities with smaller micro-environment population, implying a larger spatial scale than is often considered. The results show that coefficient estimates differ somewhat more between cities differing in micro-environment population compared to those differing based on macro-environment population. It is therefore necessary to consider the broader macro-environment even when focusing on the level of crime across neighborhoods or micro-geographic units within an area. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML.

    Science.gov (United States)

    Chretien, Anne-Sophie; Devillier, Raynier; Fauriat, Cyril; Orlanducci, Florence; Harbi, Samia; Le Roy, Aude; Rey, Jérôme; Bouvier Borg, Gaelle; Gautherot, Emmanuel; Hamel, Jean-François; Ifrah, Norbert; Lacombe, Catherine; Cornillet-Lefebvre, Pascale; Delaunay, Jacques; Toubert, Antoine; Arnoulet, Christine; Vey, Norbert; Blaise, Didier; Olive, Daniel

    2017-01-01

    NKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT). NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46 high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46 low phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46 high phenotype ( p = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression ( p = 0.303). In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness.

  7. Complementary Languages

    DEFF Research Database (Denmark)

    Preisler, Bent

    2009-01-01

    society is everywhere unproblematic. A case in point is Higher Education. I will also argue that the recently proposed solution to ‘domain loss' - Danish and English used ‘in parallel', ‘parallel languages' - because it is unrealistic as well as undesirable as a consistent principle - should be replaced......The Danish language debate is dominated by two key concepts: ‘domain loss' and its opposite, ‘parallel languages' (parallelsproglighed). The under­stood reference is to the relationship between Danish and English - i.e. the spread of English at the expense of Danish vs. the coexistence of Danish...... and English within relevant ‘domains' of Danish society. In this article I am going to argue that the concept of ‘domain loss' is not theoretically tenable - its usual depiction ranging from the vague to the nonsensical - which is not to say that the relationship between English and Danish within Danish...

  8. Holismo metodológico moderado: uma interpretação weberiana do modelo macro-micro-macro

    Directory of Open Access Journals (Sweden)

    Gert Albert

    2016-12-01

    Full Text Available DOI: http://dx.doi.org/10.5007/2175-7984.2016v15n34p43 O artigo identifica uma clara e indiscutível tendência antirreducionista na sociologia weberiana que coloca em igual posição tanto o nível da ação quanto o nível da estrutura social. Com base nesse pressuposto sugere-se que um paradigma weberiano poderia ser designado como um holismo metodológico moderado. Essa posição combina uma ontologia holista restrita com o modelo explicativo macro-micro-macro. Com base nas atuais reflexões sobre emergência, distingue-se o holismo metodológico moderado de outras posições metodológicas, além de desenvolvê-lo adotando como modelo explicativo os estudos weberianos sobre a ética protestante e a tipologia da dominação. Em seguida demonstra-se que uma teoria da ação de tipo weberiano que adota o princípio “motivos como causa” possui uma orientação fundamentalmente holista que, consequentemente, não exclui da análise o nível da ordem social. Essa versão de um paradigma weberiano possui uma inclinação de base ontológica com uma sociologia de orientação histórica e empírica.

  9. Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study

    Directory of Open Access Journals (Sweden)

    Ezz-Eldin Azza M

    2008-10-01

    Full Text Available Abstract Objectives We have analyzed t(12;21(p13:q22 in an attempt to evaluate the frequency and prognostic significance of TEL-AML1 fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH. Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD. Methods All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH for t(12;21 in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD. We determined the prognostic significance of TEL-AML1 fusion represented by disease course and survival. Results TEL-AML1 fusion gene was positive in (37.5% in newly diagnosed patients. There was a significant correlation between TEL-AML1 fusion gene both at diagnosis (r = 0.5, P = 0.003 and as a MRD (r = 0.4, P = 0.01 with favorable course. Kaplan-Meier curve for the presence of TEL-AML1 fusion at the diagnosis was associated with a better probability of overall survival (OS; mean survival time was 47 ± 1 month, in contrast to 28 ± 5 month in its absence (P = 0.006. Also, the persistence at TEL-AML1 fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 ± 2 months in the presence of MRD and it was 40 ± 1 months in its absence. So, persistence of TEL-AML1 fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS. Conclusion For most patients, the presence of TEL-AML1 fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of TEL-AML1 fusion as MRD has no additive prognostic value.

  10. 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....... Constructions of the main information (MIC) and the supportive information (SIC), of varying degree of specificity, are the basic constituents of the typology. From this point of view, Germanic languages tend to map the main information (MI) onto a complex schematic construction and the supportive information...... (SI) onto a lexical (verbal) construction. Romance languages tend to map the MI onto the verb, while the SI may be mapped onto a complex schematic construction. The paper hypothesizes that MIC and SIC stem from generalizations from usage, that they have their own, procedural role in grammar...

  11. Simplexity, languages and human languaging

    DEFF Research Database (Denmark)

    Cowley, Stephen; Gahrn-Andersen, Rasmus

    2018-01-01

    Building on a distributed perspective, the Special Issue develops Alain Berthoz's concept of simplexity. By so doing, neurophysiology is used to reach beyond observable and, specifically, 1st-order languaging. While simplexity clarifies how language uses perception/action, a community's ‘lexicon......’ (a linguistic 2nd order) also shapes human powers. People use global constraints to make and construe wordings and bring a social/individual duality to human living. Within a field of perception-action-language, the phenomenology of ‘words’ and ‘things’ drives people to sustain their own experience....... Simplex tricks used in building bodies co-function with action that grants humans access to en-natured culture where, together, they build human knowing....

  12. Local language

    NARCIS (Netherlands)

    Monique Turkenburg

    2002-01-01

    Original title: Taal lokaal. Children of immigrants living in the Netherlands have for years had the opportunity to receive lessons in their mother tongue at primary school. Since 1998 this has been referred to as minority language teaching (OALT in Dutch), and has been the responsibility

  13. Body Language.

    Science.gov (United States)

    Pollard, David E.

    1993-01-01

    Discusses how the use of body language in Chinese fiction strikes most Westerners as unusual, if not strange. Considers that, although this may be the result of differences in gestures or different conventions in fiction, it is a problem for translators, who handle the differences by various strategies, e.g., omission or expansion. (NKA)

  14. Language Pathology.

    Science.gov (United States)

    Fletcher, Paul

    1989-01-01

    Discusses the role of linguistics in the investigation of language disorders, focusing on the application of phonetics, descriptive grammatic frameworks, grammatical theory, and concepts from semantics and pragmatics to a variety of disorders and their remediation. Some trends and examples from the field of clinical linguistics are discussed. (GLR)

  15. Community-level Language Planning for Chinese Heritage Language Maintenance in the United States

    Directory of Open Access Journals (Sweden)

    An Chung Cheng

    2012-08-01

    Full Text Available This paper investigates the development of Chinese heritage language in the United States from the perspective of language policy and planning. The case study examines the Chinese heritage language maintenance through community-based Chinese schools (CHS, and CHS’s relationships with Chinese American community, as well as governments and non-government organizations in China, Taiwan, and the United States. The paper starts with a theoretical discussion on the definition of language policy and planning, and then describes the history and heritage language education of Chinese Americans in the United States. The paper also presents micro-level planning activities initiated by CHSs in the Chinese American community and non-government organizations. Special focus is placed on the interaction between non-government organizations in the US and governmental bodies in Taiwan and mainland China and in the United States. This paper suggests that micro planning of heritage language maintenance is beneficial when initiated in the community, but it can only be developed and sustained within the wider scope of macro-level planning from governments

  16. Macro and micro minerals: are frozen fruits a good source?

    Directory of Open Access Journals (Sweden)

    Patricia D.S. Spada

    2010-12-01

    Full Text Available Fruits are rich in minerals, which are essential for a wide variety of metabolic and physiologic processes in the human body. The use of frozen fruits has greatly spread in the last years not only in the preparation of juices, but also as raw material for yogurts, candies, cookies, cakes, ice creams, and children's food. However, up to now there is no data about the mineral profile of frozen fruits. This is the first database to quantify the levels of minerals in 23 samples of frozen fruits, including the most used around the world and some native fruits from the Amazon rainforest in Brazil. Considering the Dietary Reference Intakes, 100g of frozen fruits can provide 0.2 to 2.8% of macro and 2.5 to 100% of microminerals for adults (31-50 years old. Although geographical differences should be considered, these data can help to plan diets and to develop population interventions aiming to prevent chronic diseases.As frutas são ricas em minerais, sendo estes essenciais para uma grande variedade de processos metabólicos e fisiológicos no corpo humano. A utilização de frutas congeladas tem se ampliado nos últimos anos, não só na preparação de sucos, mas também como matéria-prima para iogurtes, doces, biscoitos, bolos, sorvetes e alimentos infantis. No entanto, até o momento não há dados sobre o perfil mineral de frutas congeladas. Este trabalho é o primeiro banco de dados para quantificar os níveis de minerais em 23 amostras de frutas congeladas, bastante consumidas em todo o mundo e de algumas frutas nativas da floresta amazônica, Brasil. Considerando-se as Referências de Ingestão Diárias, 100g de frutas congeladas podem fornecer 0,2-2,8% de macro e de 2,5 a 100% dos mi-crominerais para adultos (31-50 anos. Embora as diferenças geográficas devam ser consideradas, estes dados ajudam para o plano de dietas e desenvolvimento de intervenções junto à população co o objetivo de prevenir doenças crônicas.

  17. Macro issues of Mikro Primary School | Bray | Potchefstroom ...

    African Journals Online (AJOL)

    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 ...

  18. Importance of No. 21 chromosome in translocation t(8:21) in acute myelocytic leukemia (AML) to the genesis of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, T; Minamihisamatsu, M

    1986-05-01

    The results are reported of the chromosome analysis of 17 cases of acute myelocytic leukemia (AML), mostly belonging to M2 of the FAB classification, especially on the translocation t(8:21) and its variant translocations. The presence of two cases with simple variant translocation not involving No. 8 chromosome seems to suggest that No. 21 chromosome is more important to the genesis of AML than the No. 8 chromosome. This assumption appears to be supported by findings on cases with complex translocation: In two cases with complex translocation, the portion translocated from No. 21 chromosome onto No. 8 was firmly maintained in the specific site (q21) on No. 8 whereas the portion translocated from No. 8 chromosome onto No. 21 was involved in further translocation with another chromosome, onto which it was re-translocated. The results of the present cytogenetic study indicate that the analysis of variant translocations in various specific chromosome translocations in leukemia and other malignant disorders is very useful to elucidate the problem as to whether the genesis of such disorders lies in either one or both of the pair of chromosomes involved in the specific translocations of the respective diseases.

  19. Early clearance of peripheral blasts measured by flow cytometry during the first week of AML induction therapy as a new independent prognostic factor: a GOELAMS study.

    Science.gov (United States)

    Lacombe, F; Arnoulet, C; Maynadié, M; Lippert, E; Luquet, I; Pigneux, A; Vey, N; Casasnovas, O; Witz, F; Béné, M C

    2009-02-01

    An early appreciation of treatment efficacy could be very useful in acute myeloblastic leukemia (AML), and a prognostic value has been suggested for the morphological assessment of decrease in blasts during induction therapy. More sensitive, multiparametric flow cytometry (FCM) can detect far lower blast counts, allowing for a precise and reliable calculation of blast cell decrease rate (BDR). Such a multiparametric FCM four-colours/single-tube protocol, combining CD11b, CD45-ECD and CD16-PC5, was applied to peripheral blood samples from 130 AML patients, collected daily during induction chemotherapy. Normalized blast cell percentages were used to calculate the relevant decrease slopes. Slope thresholds (-15), or the time required to reach 90% depletion of the peripheral blast load (5 days), was strongly associated with the achievement of complete remission (P<0.0001). Log-rank test and Cox model showed that they also carried high statistical significance (P<0.0001) for disease-free survival. The prognostic value of cytogenetic features, confirmed in this series, was refined by BDR, which allowed to discriminate between good- and poor-risk patients among those with intermediate or normal karyotypes. This simple FCM protocol allows for an accurate prognostic sequential approach adapted to the determination of decrease in peripheral blast cells during induction chemotherapy.

  20. Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML.

    Science.gov (United States)

    Zampini, Matteo; Tregnago, Claudia; Bisio, Valeria; Simula, Luca; Borella, Giulia; Manara, Elena; Zanon, Carlo; Zonta, Francesca; Serafin, Valentina; Accordi, Benedetta; Campello, Silvia; Buldini, Barbara; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe; Pigazzi, Martina

    2018-02-02

    The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.

  1. In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available?

    DEFF Research Database (Denmark)

    Peffault de Latour, R; Labopin, M; Cornelissen, J

    2015-01-01

    Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still...... unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010). The 3-year cumulative incidences (CIs) of non......-relapse mortality were 17% and 23% with MSD and MUD, respectively (P=0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P=0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P=0.51). The 3-year overall survival was 49% with both MSD and MUD. In conclusion, HLA...

  2. Normal karyotype mosaicism in adult AML patients with adverse-risk and undefined karyotype: preliminary report of treatment outcomes after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Yoon, Jae-Ho; Kim, Hee-Je; Shin, Seung-Hwan; Yahng, Seung-Ah; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won

    2013-06-01

    Karyotype analysis in acute myeloid leukemia (AML) is one of the powerful prognostic factors for complete remission (CR), relapse, and overall survival (OS). Cytogenetic mosaicism is considered to be one of the important characteristics in expression of phenotypic manifestations. However, it has not come into focus due to emerging molecular biological approaches and the results of a number of mutation studies. Clinical correlates and prognostic relevance of mosaicism were evaluated in 163 AML patients [adverse-risk karyotypes (n = 72) and undefined karyotypes (n = 91)]. All patients were treated by induction and consolidation chemotherapies and finally went on hematopoietic stem cell transplantations (HSCT). Patients were divided into two subgroups, either with or without normal karyotype (NK) mosaicism. Seventy patients exhibited NK mosaicism and 93 did not. There were no significant differences in age, gender, chemotherapy cycles to achieve CR, HSCT donor type, source or intensity properties between the two subgroups. We found that NK mosaicism remaining in adverse-risk and undefined karyotype at diagnosis significantly correlates with better OS (p = 0.001) and lower CIR (p = 0.021) rate after HSCT. Our data show that the poor prognostic properties of unfavorable risk karyotype can be overcome to a great extent by allogeneic HSCT and chronic GVHD, especially in the subgroup with NK mosaicism. Cytogenetic mosaicism at initial diagnosis can be an influential factor for survival outcomes, even after HSCT.

  3. ANIBAL - a Hybrid Computer Language for EAI 680-PDP 8/I, FPP 12

    DEFF Research Database (Denmark)

    Højberg, Kristian Søe

    1974-01-01

    and special hybrid computer commands. ANIBAL consists of a general-purpose analog interface subroutine ANI and the macro processor 8BAL (DECUS NO 8-497A.1). When a source program with FORTRAN and 8BAL statements is processed, the FORTRAN statements are transferred unchanged, while the 8BAL code is translated...... essentially to ANI sub-routine calls, which are defined in a macro library. The resulting code is translated by the standard FORTRAN compiler. The language is very flexible as the instructions can be changed and commands can be added to or excluded from the library ....

  4. Muon energy estimate through multiple scattering with the MACRO detector

    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; Candela, A; Carboni, M; Caruso, R; Cassese, F; Cecchini, S; Cei, F; Chiarella, V; Choudhary, B C; Coutu, S; Cozzi, M; De Cataldo, G; De Deo, M; Dekhissi, H; De Marzo, C; De Mitri, I; Derkaoui, J; De Vincenzi, M; Di Credico, A; Dincecco, M; Erriquez, O; Favuzzi, C; Forti, C; Fusco, P; Giacomelli, G; Giannini, G; Giglietto, N; Giorgini, M; Grassi, M; Gray, L; Grillo, A; Guarino, F; 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; Lindozzi, M; 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; 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; Tatananni, E; Togo, V; Vakili, M; Walter, C W; Webb, R

    2002-01-01

    Muon energy measurement represents an important issue for any experiment addressing neutrino-induced up-going muon studies. Since the neutrino oscillation probability depends on the neutrino energy, a measurement of the muon energy adds an important piece of information concerning the neutrino system. We show in this paper how the MACRO limited streamer tube system can be operated in drift mode by using the TDCs included in the QTPs, an electronics designed for magnetic monopole search. An improvement of the space resolution is obtained, through an analysis of the multiple scattering of muon tracks as they pass through our detector. This information can be used further to obtain an estimate of the energy of muons crossing the detector. Here we present the results of two dedicated tests, performed at CERN PS-T9 and SPS-X7 beam lines, to provide a full check of the electronics and to exploit the feasibility of such a multiple scattering analysis. We show that by using a neural network approach, we are able to r...

  5. Mean centering helps alleviate "micro" but not "macro" multicollinearity.

    Science.gov (United States)

    Iacobucci, Dawn; Schneider, Matthew J; Popovich, Deidre L; Bakamitsos, Georgios A

    2016-12-01

    There seems to be confusion among researchers regarding whether it is good practice to center variables at their means prior to calculating a product term to estimate an interaction in a multiple regression model. Many researchers use mean centered variables because they believe it's the thing to do or because reviewers ask them to, without quite understanding why. Adding to the confusion is the fact that there is also a perspective in the literature that mean centering does not reduce multicollinearity. In this article, we clarify the issues and reconcile the discrepancy. We distinguish between "micro" and "macro" definitions of multicollinearity and show how both sides of such a debate can be correct. To do so, we use proofs, an illustrative dataset, and a Monte Carlo simulation to show the precise effects of mean centering on both individual correlation coefficients as well as overall model indices. We hope to contribute to the literature by clarifying the issues, reconciling the two perspectives, and quelling the current confusion regarding whether and how mean centering can be a useful practice.

  6. Predicting EEG complexity from sleep macro and microstructure

    International Nuclear Information System (INIS)

    Chouvarda, I; Maglaveras, N; Mendez, M O; Rosso, V; Parrino, L; Grassi, A; Terzano, M; Bianchi, A M; Cerutti, S

    2011-01-01

    This work investigates the relation between the complexity of electroencephalography (EEG) signal, as measured by fractal dimension (FD), and normal sleep structure in terms of its macrostructure and microstructure. Sleep features are defined, encoding sleep stage and cyclic alternating pattern (CAP) related information, both in short and long term. The relevance of each sleep feature to the EEG FD is investigated, and the most informative ones are depicted. In order to quantitatively assess the relation between sleep characteristics and EEG dynamics, a modeling approach is proposed which employs subsets of the sleep macrostructure and microstructure features as input variables and predicts EEG FD based on these features of sleep micro/macrostructure. Different sleep feature sets are investigated along with linear and nonlinear models. Findings suggest that the EEG FD time series is best predicted by a nonlinear support vector machine (SVM) model, employing both sleep stage/transitions and CAP features at different time scales depending on the EEG activation subtype. This combination of features suggests that short-term and long-term history of macro and micro sleep events interact in a complex manner toward generating the dynamics of sleep

  7. Radionuclides in macro algae at Monaco following the Chernobyl accident

    International Nuclear Information System (INIS)

    Holm, E.; Ballestra, S.; Lopez, J.J.; Bulos, A.; Whitehead, N.E.; Barci-Funel, G.; Ardisson, G.

    1994-01-01

    Samples of macro algae, Codmium tomentosum (green), Corallina mediterranea (red), Sphaerococcus coronopifolius (red) and Dictyota dichotoma (brown), were collected off Monaco during 1984 and 1988 and analysed for gamma-emitting radionuclides and transuranium elements. Due to the Chernobyl accident, increased radioactivity in the atmosphere at Monaco was recorded on 30 April 1986 with maximal activity concentrations on 2-3 May. The maximal activity concentrations in sea water occurred on 5-6 May and in the algae on 11 May. The decrease of activity concentrations can be described after May 11 as a single exponential relationship, where elimination rates for different radionuclides and different species specific to the environment can be calculated. The elimination rates thus observed correspond to mean residence times between 70 and 370 days corrected for physical decay. The concentration factors were also estimated and the highest values were found for 131 I, 129 Te m , and 110 Ag m and lowest for radiocesium and 140 Ba. The red algae Sphaerococcus coronopifoius showed generally higher concentration factors than green and brown algae. Regarding transuranium elements, a theoretical contribution from the Chernobyl accident can be made but only 242 Cm was detected in the algae above previous levels before the accident, due to the relatively small fallout of transuranics. (author) 23 refs.; 9 figs.; 4 tabs

  8. Macro elemental analysis of food samples by nuclear analytical technique

    Science.gov (United States)

    Syahfitri, W. Y. N.; Kurniawati, S.; Adventini, N.; Damastuti, E.; Lestiani, D. D.

    2017-06-01

    Energy-dispersive X-ray fluorescence (EDXRF) spectrometry is a non-destructive, rapid, multi elemental, accurate, and environment friendly analysis compared with other detection methods. Thus, EDXRF spectrometry is applicable for food inspection. The macro elements calcium and potassium constitute important nutrients required by the human body for optimal physiological functions. Therefore, the determination of Ca and K content in various foods needs to be done. The aim of this work is to demonstrate the applicability of EDXRF for food analysis. The analytical performance of non-destructive EDXRF was compared with other analytical techniques; neutron activation analysis and atomic absorption spectrometry. Comparison of methods performed as cross checking results of the analysis and to overcome the limitations of the three methods. Analysis results showed that Ca found in food using EDXRF and AAS were not significantly different with p-value 0.9687, whereas p-value of K between EDXRF and NAA is 0.6575. The correlation between those results was also examined. The Pearson correlations for Ca and K were 0.9871 and 0.9558, respectively. Method validation using SRM NIST 1548a Typical Diet was also applied. The results showed good agreement between methods; therefore EDXRF method can be used as an alternative method for the determination of Ca and K in food samples.

  9. Desarrollo multinivel: Implicaciones macro-regional, local y micro- regional

    Directory of Open Access Journals (Sweden)

    José Guadalupe Vargas Hernández

    2006-11-01

    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.

  10. Credit Spread Modeling: Macro-financial versus HOC Approach

    Directory of Open Access Journals (Sweden)

    Sanja Dudaković

    2014-12-01

    Full Text Available The aim of this paper is to throw light on the relationship between credit spread changes and past changes of U.S. macro-financial variables when invariants do not have Gaussian distribution. The first part presents the empirical analysis which is based on 10-year AAA corporate bond yields and 10-year Treasury bond yields. Explanatory variables include lagged U.S. leading index, Russell 2000 returns, BBB bond price changes interest rate swaps, exchange rates EUR/ USD, Repo rates, S& P 500 returns and S&P 500 volatility, Treasury bill changes, liquidity index-TRSW, LIBOR rates, Moody’s default rates; credit spread volatility and Treasury bills volatility. The proposed dynamical model explains 73% of the U.S. credit spread variance for the period 1999:07-2013:07. The second part of the article introduces the parameter estimation method based on higher order cumulants. It is demonstrated empirically that much of the information about variability of Credit Spread can be extracted from higher order cumulant function (85%.

  11. MACRO NUTRIENTS UPTAKE OF FORAGE GRASSES AT DIFFERENT SALINITY STRESSES

    Directory of Open Access Journals (Sweden)

    F. Kusmiyati

    2014-10-01

    Full Text Available The high concentration of sodium chloride (NaCl in saline soils has negative effects on the growth ofmost plants. The experiment was designed to evaluate macro nutrient uptake (Nitrogen, Phosphorus andPotassium of forage grasses at different NaCl concentrations in growth media. The experiment wasconducted in a greenhouse at Forage Crops Laboratory of Animal Agriculture Faculty, Diponegoro University.Split plot design was used to arrange the experiment. The main plot was forage grasses (Elephant grass(Pennisetum purpureum and King grass (Pennisetum hybrida. The sub plot was NaCl concentrationin growth media (0, 150, and 300 mM. The nitrogen (N, phosphorus (P and potassium (K uptake in shootand root of plant were measured. The result indicated increasing NaCl concentration in growth mediasignificantly decreased the N, P and K uptake in root and shoot of the elephant grass and king grass. Thepercentage reduction percentage of N, P and K uptake at 150 mM and 300 mM were high in elephant grassand king grass. It can be concluded that based on nitrogen, phosphorus and potassium uptake, elephantgrass and king grass are not tolerant to strong and very strong saline soil.

  12. Macro testing for group constant library TPLIB-95

    International Nuclear Information System (INIS)

    Yao Dong; Zeng Daogui; Liu Jingbo; Wang Yingming; Li Huiyun

    1996-04-01

    A macro test of the group constant library TPLIB-95 was introduced. The TPLIB-95 is an updated group constant library created by China Nuclear Data Center for LWR fuel assembly calculation program package TPFAP based on the JENDL-3.1 evaluation nuclear data library. The calculations and analyses were carried out by using five thermal reactor benchmark issues, a set of PWR zero-power critical experiments, the first cycle reactor core of 300 MW Qinshan NPP as well as the first cycle reactor core of 900 MW Daya Bay NPP. The calculation results for the thermal reactor benchmark issues showed that the maximum deviation between the calculated and measured values for spectrum indexes is large, like 6.7% for ρ 28 of BAPL-2. However, the maximum deviation for k eff is only 0.29% for TRX-2. The calculation results for zero-power critical experiments showed that the calculated value of k eff obtained by using TPLIB-95 is closer to the measured value compared with the one obtained by using the original library TPLIB. The agreement between the calculated and measured values for critical boron concentration in the first cycle reactor cores in Qinshan NPP and Daya Bay NPP is quite good. The maximum deviation for the critical boron concentration is only 15 x 10 -6 /L. (8 figs., 5 tabs.)

  13. Corporate governance in Macedonia – micro and macro analysis

    Directory of Open Access Journals (Sweden)

    Mico Apostolov

    2011-03-01

    Full Text Available The corporate governance issue in Macedonian companies has been brought forward during the recent few years. The main reason is the fact that the privatization process completion of socially-owned and partly state-owned enterprises has put emphasis to the challenge to reasonably regulate relationships established within companies on one hand, and relationships between companies and larger society on the other. All market economies, including those with longest tradition, have faced this kind of challenge so far. Corporate governance becomes an increasingly important issue for the Macedonian economy. It is being taken with greater consideration by the companies, regulators and government. The strong wave of privatization programs from mid-90’ have resulted in an altered business environment, and new legal and institutional frameworks have been established. Indeed, corporate governance contributes to sustainable economic development by enhancing the performance of companies and increasing their access to external sources of capital. In this paper we will make attempt to analyze the predominant factors that Create a prolific corporate governance environment in two terms; a micro level and macro level.

  14. The double capsules in macro-textured breast implants.

    Science.gov (United States)

    Giot, Jean-Philippe; Paek, Laurence S; Nizard, Nathanael; El-Diwany, Mostafa; Gaboury, Louis A; Nelea, Monica; Bou-Merhi, Joseph S; Harris, Patrick G; Danino, Michel A

    2015-10-01

    Breast implants are amongst the most widely used types of permanent implants in modern medicine and have both aesthetic and reconstructive applications with excellent biocompatibility. The double capsule is a complication associated with textured prostheses that leads to implant displacement; however, its etiology has yet to be elucidated. In this study, 10 double capsules were sampled from breast expander implants for in-depth analysis; histologically, the inner capsular layer demonstrated highly organized collagen in sheets with delamination of fibers. At the prosthesis interface (PI) where the implant shell contacts the inner capsular layer, scanning electron microscopy (SEM) revealed a thin layer which mirrored the three-dimensional characteristics of the implant texture; the external surface of the inner capsular layer facing the intercapsular space (ICS) was flat. SEM examination of the inner capsule layer revealed both a large bacterial presence as well as biofilm deposition at the PI; a significantly lower quantity of bacteria and biofilm were found at the ICS interface. These findings suggest that the double capsule phenomenon's etiopathogenesis is of mechanical origin. Delamination of the periprosthetic capsule leads to the creation of the ICS; the maintained separation of the 2 layers subsequently alters the biostability of the macro-textured breast implant. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. MACRO DEFECT FREE MATERIALS; THE CHALLENGE OF MECHANOCHEMICAL ACTIVATION

    Directory of Open Access Journals (Sweden)

    MILAN DRÁBIK

    2012-12-01

    Full Text Available Macro-defect-free (MDF materials belong, according to Odler’s categorisation, to the type of materials where polymers may be successfully combined with cements and water to produce also the parameters of technological novelty and interests. A challenge, which has not been followed or indicated by now, is the option to intensify mixing of dry cement and polymer. The mechanochemical pre-reactions of dry MDF raw mixes consisting of Portland cement and polyphosphate, together with the model of atomic-level interpretations of the formed functional interfaces are proposed, experimentally tested and discussed in the present paper. The results ultimately show the activation of studied system due to the mechanochemical treatment, which consists in the initiation and measurable formation of Al(Fe–O–P cross-links already in the treated raw mixes. The mechanochemical activation of raw mixes in the high energy planetary mill for the duration of 5 minutes is proposed as the specific mixing and activation / pre-reaction step within the entire MDF synthesis procedure.

  16. Macro to microfluidics system for biological environmental monitoring.

    Science.gov (United States)

    Delattre, Cyril; Allier, Cédric P; Fouillet, Yves; Jary, Dorothée; Bottausci, Frederic; Bouvier, Denis; Delapierre, Guillaume; Quinaud, Manuelle; Rival, Arnaud; Davoust, Laurent; Peponnet, Christine

    2012-01-01

    Biological environmental monitoring (BEM) is a growing field of research which challenges both microfluidics and system automation. The aim is to develop a transportable system with analysis throughput which satisfies the requirements: (i) fully autonomous, (ii) complete protocol integration from sample collection to final analysis, (iii) detection of diluted molecules or biological species in a large real life environmental sample volume, (iv) robustness and (v) flexibility and versatility. This paper discusses all these specifications in order to define an original fluidic architecture based on three connected modules, a sampling module, a sample preparation module and a detection module. The sample preparation module highly concentrates on the pathogens present in a few mL samples of complex and unknown solutions and purifies the pathogens' nucleic acids into a few μL of a controlled buffer. To do so, a two-step concentration protocol based on magnetic beads is automated in a reusable macro-to-micro fluidic system. The detection module is a PCR based miniaturized platform using digital microfluidics, where reactions are performed in 64 nL droplets handled by electrowetting on dielectric (EWOD) actuation. The design and manufacture of the two modules are reported as well as their respective performances. To demonstrate the integration of the complete protocol in the same system, first results of pathogen detection are shown. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Active vertical tail buffeting suppression based on macro fiber composites

    Science.gov (United States)

    Zou, Chengzhe; Li, Bin; Liang, Li; Wang, Wei

    2016-04-01

    Aerodynamic buffet is unsteady airflow exerting forces onto a surface, which can lead to premature fatigue damage of aircraft vertical tail structures, especially for aircrafts with twin vertical tails at high angles of attack. In this work, Macro Fiber Composite (MFC), which can provide strain actuation, was used as the actuator for the buffet-induced vibration control, and the positioning of the MFC patches was led by the strain energy distribution on the vertical tail. Positive Position Feedback (PPF) control algorithm has been widely used for its robustness and simplicity in practice, and consequently it was developed to suppress the buffet responses of first bending and torsional mode of vertical tail. However, its performance is usually attenuated by the phase contributions from non-collocated sensor/actuator configuration and plants. The phase lag between the input and output signals of the control system was identified experimentally, and the phase compensation was considered in the PPF control algorithm. The simulation results of the amplitude frequency of the closed-loop system showed that the buffet response was alleviated notably around the concerned bandwidth. Then the wind tunnel experiment was conducted to verify the effectiveness of MFC actuators and compensated PPF, and the Root Mean Square (RMS) of the acceleration response was reduced 43.4%, 28.4% and 39.5%, respectively, under three different buffeting conditions.

  18. Macro-Fiber Composite actuated simply supported thin airfoils

    International Nuclear Information System (INIS)

    Bilgen, Onur; Kochersberger, Kevin B; Inman, Daniel J; Ohanian, Osgar J III

    2010-01-01

    A piezoceramic composite actuator known as Macro-Fiber Composite (MFC) is used for actuation in the design of a variable camber airfoil intended for a ducted fan aircraft. The study focuses on response characterization under aerodynamic loads for circular arc airfoils with variable pinned boundary conditions. A parametric study of fluid–structure interaction is employed to find pin locations along the chordwise direction that result in high lift generation. Wind tunnel experiments are conducted on a 1.0% thick, 127 mm chord MFC actuated bimorph airfoil that is simply supported at 5% and 50% of the chord. Aerodynamic and structural performance results are presented for a flow rate of 15 m s −1 and a Reynolds number of 127 000. Non-linear effects due to aerodynamic and piezoceramic hysteresis are identified and discussed. A lift coefficient change of 1.46 is observed, purely due to voltage actuation. A maximum 2D L/D ratio of 17.8 is recorded through voltage excitation

  19. Library macro-environment: New technological and economic rules

    Directory of Open Access Journals (Sweden)

    Karmen Štular-Sotošek

    2003-01-01

    Full Text Available Fast and flexible adaptation to changes in the macro-environment is also crucial for libraries, which have to review them, respond to them and become a part of them. Consequently, the application of marketing science and tools helps libraries to find out how to survive in the competitive world and how to become better and stronger. The article, which draws from marketing, economic and information disciplines, introduces the main principles in the technological and economic environment of libraries and finds the knowledge about these disciplines to be most crucial for successful management of modern libraries, especially on the pretentious publishing market and on the market of information suppliers. Within the technological and economic environment, the cooperation is the only logical solution, which benefits the producers of information services and products as well as libraries. The following text finds that libraries will achieve long-term success and will be proactive in developing partnerships only by using relationship marketing. This relatively new approach offers libraries new ways for successful and long-term management of alliances between partners.

  20. Important macro and microelements in chickpea and lentil

    International Nuclear Information System (INIS)

    Ahmad, M.; Hussain, M.; Shafique, M.

    2002-01-01

    Important macro and microelements in different genotypes of chickpea and lentil were determined. Maximum concentrations (mg/100g) of Na, K, Ca, Mg, P, Fe, Zn, Mn and Cu were observed in chickpea genotypes C-727 (24.23), Pb-91 (1686.9), CM-98 (87.02), Pb-91 (228.29), Pb-91 (181.13), Paidar-91 (6.78), CM-89 (3.34), Paidar-91 (1.60) and CM-72 (1.29) and lentil genotypes TCL-85-1 (34.43), 46-3-3-1 (1250.3), 583-2 (85.0), 46-3-3-1 (200.59), Precoz (329.1), 583-2 (6.95), TCL-85-1 (4.40), 46-3-3-1 (1.37) and 79-1 (0.73). K, Mg, Mn and Cu were higher in chickpea, Na and P contents were higher in lentil whereas Ca, Fe and Zn contents were comparable in both the pulses. Coefficient of variability (CV) in different elements varied from 4.76% (Mn) to 15.09 % (Na) in chickpea and 7.66% (Na) to 21.39% (P) in lentil. Correlations between protein content and different minerals in chickpea and lentil were not significant. Field fortification of staples for minerals versus post-harvest addition is discussed. (author)

  1. Macro- and Micro-Political Vernaculizations of Rights

    Science.gov (United States)

    Bloomer, Fiona

    2017-01-01

    Abstract How abortion is dealt with in law and policy is shaped through the multiple political and societal discourses on the issue within a particular society. Debate on abortion is constantly in flux, with progressive and regressive movements witnessed globally. This paper examines the translation of human rights norms into discourses on abortion in Northern Ireland, a region where abortion is highly restricted, with extensive contemporary public debate into potential liberalization of abortion law. This paper emanates from research examining political debates on abortion in Northern Ireland and contrasts findings with recent civil society developments, identifying competing narratives of human rights with regard to abortion at the macro- and micro-political level. The paper identifies the complexities of using human rights as a lobbying tool, and questions the utility of rights-based arguments in furthering abortion law reform. The paper concludes that a legalistic rights-based approach may have limited efficacy in creating a more nuanced debate and perspective on abortion in Northern Ireland but that it has particular resonance in arguing for limited reform in extreme cases. PMID:28630550

  2. MACRO ECONOMICS FACTORS AND BANK LENDING BEHAVIOUR IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Rofikoh Rokhim

    2014-10-01

    Full Text Available 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, saving rate and GDP growth were found not meaningfully contributed to change investment lending distribution, but they significantly influenced the other lending distribution. Lastly, reserve requirement and exchange rate did not significantly influence all lending type.Keywords: Loan, interest rate, growth, GDP.JEL Classification Numbers: G21, E43, E51AbstrakStudi ini meneliti faktor ekonomi makro yang mempengaruhi distribusi pinjaman dan mengamati perbandingan masing-masing faktor berdasarkan jenis pinjaman yaitu pinjaman investasi, modal kerja dan konsumsi. Dengan menggunakan data dari bank-bank komersial di Indonesia antara 2003-2011, dengan menggunakan analisis data panel, ditemukan bahwa likuiditas perbankan dan tingkat inflasi berpengaruh negatif signifikan, sedangkan jumlah bank berpengaruh positif dan kuat untuk mendorong distribusi pinjaman pada semua jenis pinjaman. Selain itu, tingkat tabungan dan pertumbuhan PDB ditemukan tidak bermakna dalam kontribusinya untuk mempengaruhi distribusi kredit investasi, tetapi secara signifikan mempengaruhi distribusi pinjaman lainnya. Terakhir, GWM dan nilai tukar tidak signifikan mempengaruhi semua tiga kategori jenis pinjaman. Keywords: Loan, interest rate, growth, GDPJEL Classification Numbers: G21, E43, E51

  3. Spatial Language Learning

    Science.gov (United States)

    Fu, Zhengling

    2016-01-01

    Spatial language constitutes part of the basic fabric of language. Although languages may have the same number of terms to cover a set of spatial relations, they do not always do so in the same way. Spatial languages differ across languages quite radically, thus providing a real semantic challenge for second language learners. The essay first…

  4. Language and the Law.

    Science.gov (United States)

    Gibbons, John

    1999-01-01

    Discusses the language of law and its general interest to the field of applied linguistics. Specific focus is on legal language, the problems and remedies of legal communication (e.g., language and disadvantage before the law, improving legal communication) the legislation of language (e.g., language rights, language crimes), and forensic…

  5. Macro-Finance Determinants of the Long-Run Stock-Bond Correlation

    DEFF Research Database (Denmark)

    Asgharian, Hossein; Christiansen, Charlotte; Hou, Ai Jun

    itself. Macro-finance variables and the lagged realized correlation are simultaneously significant in forecasting the long-run stock-bond correlation. The behavior of the long-run stock-bond correlation is very different when estimated taking the macro-finance variables into account. Supporting......We investigate the long-run stock-bond correlation using a novel model that combines the dynamic conditional correlation model with the mixed-data sampling approach. The long-run correlation is affected by both macro-finance variables (historical and forecasts) and the lagged realized correlation...

  6. Immunopositivity for histone macroH2A1 isoforms marks steatosis-associated hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Francesca Rappa

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common cancers worldwide. Prevention and risk reduction are important and the identification of specific biomarkers for early diagnosis of HCC represents an active field of research. Increasing evidence indicates that fat accumulation in the liver, defined as hepatosteatosis, is an independent and strong risk factor for developing an HCC. MacroH2A1, a histone protein generally associated with the repressed regions of chromosomes, is involved in hepatic lipid metabolism and is present in two alternative spliced isoforms, macroH2A1.1 and macroH2A1.2. These isoforms have been shown to predict lung and colon cancer recurrence but to our knowledge, their role in fatty-liver associated HCC has not been investigated previously.We examined macroH2A1.1 and macroH2A1.2 protein expression levels in the liver of two murine models of fat-associated HCC, the high fat diet/diethylnistrosamine (DEN and the phosphatase and tensin homolog (PTEN liver specific knock-out (KO mouse, and in human liver samples of subjects with steatosis or HCC, using immunoblotting and immunohistochemistry.Protein levels for both macroH2A1 isoforms were massively upregulated in HCC, whereas macroH2A1.2 was specifically upregulated in steatosis. In addition, examination of human liver samples showed a significant difference (p<0.01 in number of positive nuclei in HCC (100% of tumor cells positive for either macroH2A1.1 or macroH2A1.2, when compared to steatosis (<2% of hepatocytes positive for either isoform. The steatotic areas flanking the tumors were highly immunopositive for macroH2A1.1 and macroH2A1.2.These data obtained in mice and humans suggest that both macroH2A1 isoforms may play a role in HCC pathogenesis and moreover may be considered as novel diagnostic markers for human HCC.

  7. Macro-Finance Determinants of the Long-Run Stock-Bond Correlation

    DEFF Research Database (Denmark)

    Asgharian, Hossein; Christiansen, Charlotte; Hou, Ai Jun

    2016-01-01

    We investigate long-run stock–bond correlation using a model that combines the dynamic conditional correlation model with the mixed-data sampling approach and allows long-run correlation to be affected by macro-finance factors (historical and forecasts). We use macro-finance factors related...... to inflation and interest rates, illiquidity, state of the economy, and market uncertainty. Macro-finance factors, particularly their forecasts, are good at forecasting long-run stock–bond correlation. Supporting the flight-to-quality phenomenon, long-run correlation tends to be small and negative when...

  8. Modeling air concentration over macro roughness conditions by Artificial Intelligence techniques

    Science.gov (United States)

    Roshni, T.; Pagliara, S.

    2018-05-01

    Aeration is improved in rivers by the turbulence created in the flow over macro and intermediate roughness conditions. Macro and intermediate roughness flow conditions are generated by flows over block ramps or rock chutes. The measurements are taken in uniform flow region. Efficacy of soft computing methods in modeling hydraulic parameters are not common so far. In this study, modeling efficiencies of MPMR model and FFNN model are found for estimating the air concentration over block ramps under macro roughness conditions. The experimental data are used for training and testing phases. Potential capability of MPMR and FFNN model in estimating air concentration are proved through this study.

  9. Language as a whole - A new framework for linguistic knowledge integration. Comment on "Approaching human language with complex networks" by Cong and Liu

    Science.gov (United States)

    Chen, Xinying

    2014-12-01

    Researchers have been talking about the language system theoretically for many years [1]. A well accepted assumption is that language is a complex adaptive system [2] which is hierarchical [3] and contains multiple levels along the meaning-form dimension [4]. Over the last decade or so, driven by the availability of digital language data and the popularity of statistical approach, many researchers interested in theoretical questions have started to try to quantitatively describe microscopic linguistic features in a certain level of a language system by using authentic language data. Despite the fruitful findings, one question remains unclear. That is, how does a whole language system look like? For answering this question, network approach, an analysis method emphasizes the macro features of structures, has been introduced into linguistic studies [5]. By analyzing the static and dynamic linguistics networks constructed from authentic language data, many macro and micro linguistic features, such as lexical, syntactic or semantic features have been discovered and successfully applied in linguistic typographical studies so that the huge potential of linguistic networks research has revealed [6].

  10. Language learning interventions | Kilfoil | Journal for Language ...

    African Journals Online (AJOL)

    The results for that intervention show that the hypothesis was correct and students need more time and structure if they are to improve their language competence sufficiently. Keywords: language learning interventions, English for specific purposes, language competence, fossilization. Journal for Language Teaching Vol.

  11. Benthic macro and meiofauna of seagrass (Thalassia hemprichii) bed at Minicoy, Lakshadweep

    Digital Repository Service at National Institute of Oceanography (India)

    Ansari, Z.A.

    Macrofauna, comprising 9 groups, was dominated by polychaete worms, while meiofauna, comprising 10 groups, was dominated by nematodes Densities of both macro and meiofauna were higher near the shore where biomass of Thalassia hemprichii was maximum...

  12. Design for manufacturability of macro and micro products: a case study of heat exchanger design

    DEFF Research Database (Denmark)

    Omidvarnia, F.; Weng Feng, L.; Hansen, H. N.

    2018-01-01

    In this paper, a novel methodology in designing a micro heat exchanger is proposed by modifying a conventional design methodology for macro products with the considerations of differences between design of a micro and a macro product. The methodology starts with the identification of differences...... for fabricating micro heat exchangers are ranked based on the defined criteria. Following the design methodology, primary design ideas for micro heat exchangers are generated according to the heat transfer principles for macro heat exchangers. Taking micro design considerations into account, the designs from next...... iteration are created. Finally, the performances of the designs for micro heat exchangers are compared with their macro counterparts. The most appropriate designs for micro heat exchangers are finalized. The micro specific design guidelines obtained by the designer through evaluating the modeling results...

  13. Response of tropical peat swamp forest tree species seedlings to macro nutrients

    Directory of Open Access Journals (Sweden)

    Tri Wira Yuwati

    2015-10-01

    Full Text Available Abstract Efforts of restoration of degraded tropical peat swamp forest were facing constraints due to the low available nutrient level of peat. The transplanted peat swamp forest species seedlings experienced low survival rate and poor growth performance. This study aimed to demonstrate the response of ten tropical peat swamp forest species seedlings whether climax and pioneer species to macro-nutrients addition in the nursery. The growth performance of climax and pioneer tropical peat swamp species seedlings was recorded following addition of macro nutrients of Nitrogen (N, Phosphorus(P, Potassium(K and Dolomitic limestone (CaMg. The result showed that Alstonia spatulata and Parartocarpus venenosus showed positive growth response following macro nutrients addition. This study concluded that tropical peat swamp pioneer species has lower necessity for macro-nutrients addition than tropical peat swamp climax species.

  14. Soft sediment dwelling macro-invertebrates of Rajapur Bay, central west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Harkantra, S.N.; Parulekar, A.H.

    Thirtyfour species of soft sediment dwelling macro-invertebrates were recorded in Rajapur Bay at the proposed effluent discharge location of nuclear power plant. The fauna mainly composed of polychaetes (42.52%), molluscs (39.03%), crustaceans (7...

  15. Global Conflicts and the Macro-Regional Modernities: Interview with Marek Hrubec

    Czech Academy of Sciences Publication Activity Database

    Hrubec, Marek; Solík, M.

    2015-01-01

    Roč. 6, č. 1 (2015), s. 83-98 ISSN 1338-130X Institutional support: RVO:67985955 Keywords : global conflicts * injustice * recognition * macro-regions * modernities * critical theory * intercultural Subject RIV: AJ - Letters, Mass- media , Audiovision

  16. Interaction of micro and macro elements with manure on barley feed ...

    African Journals Online (AJOL)

    ajl yemi

    2011-11-28

    Nov 28, 2011 ... on barley feed yield and soil nutrient content in Sistan region ... In order to study the effect of interaction of 'micro' and 'macro' ... different proportions of manure and chemical fertilizer treatment were: 100% manure (F1), 100%.

  17. Development of an automated desktop procedure for defining macro-reaches for river longitudinal profiles

    CSIR Research Space (South Africa)

    Dollar, LH

    2006-07-01

    Full Text Available This paper presents an automated desktop procedure for delineating river longitudinal profiles into macro-reaches for use in Ecological Reserve assessments and to aid freshwater ecosystem conservation planning. The procedure was developed for use...

  18. First results from the MACRO experiment at the Gran Sasso Laboratory

    International Nuclear Information System (INIS)

    Giacomelli, G.; Bellotti, R.; Cafagna, F.; Calicchio, M.; De Cataldo, G.; De Marzo, C.; Erriquez, E.; Favuzzi, C.; Giglietto, N.; Nappi, E.; Spinelli, P.; Cechini, S.; Fabbri, M.; Mandrioli, G.; Matteuzzi, P.; Pal, B.; Patrizii, L.; Predieri, F.; Sanzani, G.L.; Serra, P.; Spurio, M.; Sini, G.P.; Togo, V.; Ahlen, S.P.; Ficenec, D.; Hazen, E.; Klein, S.; Levin, D.; Marin, A.; Stone, J.L.; Sulak, L.R.; Worstell, W.; Barish, B.; Coutu, S.; Hong, J.T.; Liu, G.; Peck, C.; Solie, D.; Steele, J.; Lane, C.; Steinberg, R.; Battistoni, G.; Bilokon, H.; Bloise, C.; Campana, P.; Chiarella, V.; Forti, C.; Grillo, A.; Iarocci, E.; Marini, A.; Patera, V.; Reynoldson, J.; Ronga, F.; Satta, L.; Spinetti, M.; Valente, V.; Bower, C.; Heinz, R.; Mufson, S.; Petrakis, J.; Monacelli, P.; Reale, A.; Bernardini, P.; Mancarella, G.; Barbarino, G.C.; Fiore, M.; Baldini, A.; Bemporad, C.; Flaminio, V.; Giannini, G.; Grassi, M.; Pazzi, R.; Auriemma, G.; De Vincenzi, M.; Iori, M.; Lamanna, E.; Lipari, P.; Martellotti, G.; Petrera, S.; Petrillo, L.; Rosa, G.; Sciubba, A.; Severi, M.; Green, P.; Webb, R.; Bisi, V.; Giubellino, P.; Marzari-Chiesa, A.; Masera, M.; Monteno, M.; Ramello, L.

    1991-01-01

    The first physics results obtained with the MACRO detector in the underground Gran Sasso Laboratory are reported. Results were also obtained in conjunction with the EAS-TOP detector located on top of the Gran Sasso mountain. (orig.)

  19. On the relationship between micro and macro correlations in nuclear measurement uncertainties

    International Nuclear Information System (INIS)

    Smith, D.L.

    1987-01-01

    Consideration is given to the propagation of micro correlations between the component experimental errors (corresponding to diverse attributes of the measurement process) through to the macro correlations between the total errors in the final derived experimental values. Whenever certain micro correlations cannot be precisely specified, the macro correlations must also be uncertain. However, on the basis of fundamental principles from mathematical statistics, it is shown that these uncertainties in the macro correlations can be substantially smaller than the individual uncertainties for specific micro correlations, provided that the number of distinct attributes contributing to the total experimental error is reasonably large. Furthermore, the resulting macro correlations are shown to be approximately normally distributed regardless of teh distributions assumed for the micro correlations. Examples are provided to demonstrate these concepts and to illustrate their relevance to experimental nuclear research. (orig.)

  20. The relationship between venture capital investment and macro economic variables via statistical computation method

    Science.gov (United States)

    Aygunes, Gunes

    2017-07-01

    The objective of this paper is to survey and determine the macroeconomic factors affecting the level of venture capital (VC) investments in a country. The literary depends on venture capitalists' quality and countries' venture capital investments. The aim of this paper is to give relationship between venture capital investment and macro economic variables via statistical computation method. We investigate the countries and macro economic variables. By using statistical computation method, we derive correlation between venture capital investments and macro economic variables. According to method of logistic regression model (logit regression or logit model), macro economic variables are correlated with each other in three group. Venture capitalists regard correlations as a indicator. Finally, we give correlation matrix of our results.

  1. WinBUGSio: A SAS Macro for the Remote Execution of WinBUGS

    Directory of Open Access Journals (Sweden)

    Michael K. Smith

    2007-09-01

    Full Text Available This is a macro which facilitates remote execution of WinBUGS from within SAS. The macro pre-processes data for WinBUGS, writes the WinBUGS batch-script, executes this script and reads in output statistics from the WinBUGS log-file back into SAS native format. The user specifies the input and output file names and directory path as well as the statistics to be monitored in WinBUGS. The code works best for a model that has already been set up and checked for convergence diagnostics within WinBUGS. An obvious extension of the use of this macro is for running simulations where the input and output files all have the same name but all that differs between simulation iterations is the input dataset. The functionality and syntax of the macro call are described in this paper and illustrated using a simple linear regression model.

  2. Threats to the Sustainability of the Outsourced Call Center Industry in the Philippines: Implications for Language Policy

    Science.gov (United States)

    Friginal, Eric

    2009-01-01

    This study overviews current threats to the sustainability of the outsourced call center industry in the Philippines and discusses implications for macro and micro language policies given the use of English in this cross-cultural interactional context. This study also summarizes the present state of outsourced call centers in the Philippines, and…

  3. Emergent/quantum gravity: macro/micro structures of spacetime

    International Nuclear Information System (INIS)

    Hu, B L

    2009-01-01

    Emergent gravity views spacetime as an entity emergent from a more complete theory of interacting fundamental constituents valid at much finer resolution or higher energies, usually assumed to be above the Planck energy. In this view general relativity is an effective theory valid only at long wavelengths and low energies. We describe the tasks of emergent gravity from any ('top-down') candidate theory for the microscopic structure of spacetime (quantum gravity), namely, identifying the conditions and processes or mechanisms whereby the familiar macroscopic spacetime described by general relativity and matter content described by quantum field theory both emerge with high probability and reasonable robustness. We point out that this task may not be so easy as commonly conjured (as implied in the 'theory of everything') because there are emergent phenomena which cannot simply be deduced from a given micro-theory. Going in the opposite direction ('bottom-up') is the task of quantum gravity, i.e., finding a theory for the microscopic structure of spacetime, which, in this new view, cannot come from quantizing the metric or connection forms because they are the collective variables which are meaningful only for the macroscopic theory (valid below the Planck energy). This task looks very difficult or almost impossible because it entails reconstructing lost information. We point out that the situation may not be so hopeless if we ask the right questions and have the proper tools for what we want to look for. We suggest pathways to move 'up' (in energy) from the given macroscopic conditions of classical gravity and quantum field theory to the domain closer to the micro-macro interface where spacetime emerged and places to look for clues or tell-tale signs at low energy where one could infer indirectly some salient features of the micro-structure of spacetime.

  4. Active control of structures using macro-fiber composite (MFC)

    Energy Technology Data Exchange (ETDEWEB)

    Kovalovs, A; Barkanov, E; Gluhihs, S [Institute of Materials and Structures, Riga Technical University, 16/20 Azenes Str., Riga, LV-1048 (Latvia)

    2007-12-15

    This paper presents the use of macro-fiber composites (MFC) for vibration reduces of structures. The MFC consist of polyimid films with IDE-electrodes that are glued on the top and the bottom of rectangular piezoceramic fibers. The interdigitated electrodes deliver the electric field required to activate the piezoelectric effect in the fibers and allows to invoke the stronger longitudinal piezoelectric effect along the length of the fibers. When this actuator embedded in a surface or attached to flexible structures, the MFC actuator provides distributed solid-state deflection and vibration control. The major advantages of the piezoelectric fibre composite actuators are their high performance, flexibility, and durability when compared with the traditional piezoceramic (PZT) actuators. In addition, the ability of MFC devices to couple the electrical and mechanical fields is larger than in monolithic PZT. In this study, we showed the experimental results that an MFC could be used as actuator to find modal parameters and reduce vibration for structures such as an aluminium beam and metal music plate. Two MFC actuators were attached to the surfaces of test subjects. First MFC actuator used to supply a signal as exciter of vibration and second MFC show his application for reduction of vibration in the range of resonance frequencies. Experimental results of aluminium beam with MFC actuators compared with finite element model which modelled in ANSYS software. The applied voltage is modelled as a thermal load according to thermal analogy for MFC. The experimental and numerical results presented in this paper confirm the potential of MFC for use in the vibration control of structures.

  5. ERICA: intake of macro and micronutrients of Brazilian adolescents

    Directory of Open Access Journals (Sweden)

    Amanda de Moura Souza

    2016-02-01

    Full Text Available ABSTRACT OBJECTIVE To describe food and macronutrient intake profile and estimate the prevalence of inadequate micronutrient intake of Brazilian adolescents. METHODS Data from 71,791 adolescents aged from 12 to 17 years were evaluated in the 2013-2014 Brazilian Study of Cardiovascular Risks in Adolescents (ERICA. Food intake was estimated using 24-hour dietary recall (24-HDR. A second 24-HDR was collected in a subsample of the adolescents to estimate within-person variability and calculate the usual individual intake. The prevalence of food/food group intake reported by the adolescents was also estimated. For sodium, the prevalence of inadequate intake was estimated based on the Tolerable Upper Intake Level (UL. The Estimated Average Requirement (EAR method used as cutoff was applied to estimate the prevalence of inadequate nutrient intake. All the analyses were stratified according to sex, age group and Brazilian macro-regions. All statistical analyses accounted for the sample weight and the complex sampling design. RESULTS Rice, beans and other legume, juice and fruit drinks, breads and meat were the most consumed foods among the adolescents. The average energy intake ranged from 2,036 kcal (girls aged from 12 to 13 years to 2,582 kcal (boy aged from14 to 17 years. Saturated fat and free sugar intake were above the maximum limit recommended ( 50.0%. Sodium intake was above the UL for more than 80.0% of the adolescents. CONCLUSIONS The diets of Brazilian adolescents were characterized by the intake of traditional Brazilian food, such as rice and beans, as well as by high intake of sugar through sweetened beverages and processed foods. This food pattern was associated with an excessive intake of sodium, saturated fatty acids and free sugar.

  6. Educating Assessors: Preparing Librarians with Micro and Macro Skills

    Directory of Open Access Journals (Sweden)

    Rachel Applegate

    2016-04-01

    Full Text Available Abstract Objective – To examine the fit between libraries’ needs for evaluation skills, and library education and professional development opportunities. Many library position descriptions and many areas of library science education focus on professional skills and activities, such as delivering information literacy, designing programs, and managing resources. Only some positions, some parts of positions, and some areas of education specifically address assessment/evaluation skills. The growth of the Library Assessment Conference, the establishment of the ARL-ASSESS listserv, and other evidence indicates that assessment skills are increasingly important. Method – Four bodies of evidence were examined for the prevalence of assessment needs and assessment education: the American Library Association core competencies; job ads from large public and academic libraries; professional development courses and sessions offered by American Library Association (ALA divisions and state library associations; and course requirements contained in ALA-accredited Masters of Library Science (MLS programs. Results – While one-third of job postings made some mention of evaluation responsibilities, less than 10% of conference or continuing education offerings addressed assessment skills. In addition, management as a topic is a widespread requirement in MLS programs (78%, while research (58% and assessment (15% far less common. Conclusions – Overall, there seems to be more need for assessment/evaluation skills than there are structured offerings to educate people in developing those skills. In addition, roles are changing: some of the most professional-level activities of graduate-degreed librarians involve planning, education, and assessment. MLS students need to understand that these macro skills are essential to leadership, and current librarians need opportunities to add to their skill sets.

  7. Macro-Invertebrate Decline in Surface Water Polluted with Imidacloprid

    Science.gov (United States)

    Van Dijk, Tessa C.; Van Staalduinen, Marja A.; Van der Sluijs, Jeroen P.

    2013-01-01

    Imidacloprid is one of the most widely used insecticides in the world. Its concentration in surface water exceeds the water quality norms in many parts of the Netherlands. Several studies have demonstrated harmful effects of this neonicotinoid to a wide range of non-target species. Therefore we expected that surface water pollution with imidacloprid would negatively impact aquatic ecosystems. Availability of extensive monitoring data on the abundance of aquatic macro-invertebrate species, and on imidacloprid concentrations in surface water in the Netherlands enabled us to test this hypothesis. Our regression analysis showed a significant negative relationship (Pmacro-invertebrate abundance and imidacloprid concentration for all species pooled. A significant negative relationship was also found for the orders Amphipoda, Basommatophora, Diptera, Ephemeroptera and Isopoda, and for several species separately. The order Odonata had a negative relationship very close to the significance threshold of 0.05 (P = 0.051). However, in accordance with previous research, a positive relationship was found for the order Actinedida. We used the monitoring field data to test whether the existing three water quality norms for imidacloprid in the Netherlands are protective in real conditions. Our data show that macrofauna abundance drops sharply between 13 and 67 ng l−1. For aquatic ecosystem protection, two of the norms are not protective at all while the strictest norm of 13 ng l−1 (MTR) seems somewhat protective. In addition to the existing experimental evidence on the negative effects of imidacloprid on invertebrate life, our study, based on data from large-scale field monitoring during multiple years, shows that serious concern about the far-reaching consequences of the abundant use of imidacloprid for aquatic ecosystems is justified. PMID:23650513

  8. Active control of structures using macro-fiber composite (MFC)

    International Nuclear Information System (INIS)

    Kovalovs, A; Barkanov, E; Gluhihs, S

    2007-01-01

    This paper presents the use of macro-fiber composites (MFC) for vibration reduces of structures. The MFC consist of polyimid films with IDE-electrodes that are glued on the top and the bottom of rectangular piezoceramic fibers. The interdigitated electrodes deliver the electric field required to activate the piezoelectric effect in the fibers and allows to invoke the stronger longitudinal piezoelectric effect along the length of the fibers. When this actuator embedded in a surface or attached to flexible structures, the MFC actuator provides distributed solid-state deflection and vibration control. The major advantages of the piezoelectric fibre composite actuators are their high performance, flexibility, and durability when compared with the traditional piezoceramic (PZT) actuators. In addition, the ability of MFC devices to couple the electrical and mechanical fields is larger than in monolithic PZT. In this study, we showed the experimental results that an MFC could be used as actuator to find modal parameters and reduce vibration for structures such as an aluminium beam and metal music plate. Two MFC actuators were attached to the surfaces of test subjects. First MFC actuator used to supply a signal as exciter of vibration and second MFC show his application for reduction of vibration in the range of resonance frequencies. Experimental results of aluminium beam with MFC actuators compared with finite element model which modelled in ANSYS software. The applied voltage is modelled as a thermal load according to thermal analogy for MFC. The experimental and numerical results presented in this paper confirm the potential of MFC for use in the vibration control of structures

  9. Macro-scale turbulence modelling for flows in porous media

    International Nuclear Information System (INIS)

    Pinson, F.

    2006-03-01

    - This work deals with the macroscopic modeling of turbulence in porous media. It concerns heat exchangers, nuclear reactors as well as urban flows, etc. The objective of this study is to describe in an homogenized way, by the mean of a spatial average operator, turbulent flows in a solid matrix. In addition to this first operator, the use of a statistical average operator permits to handle the pseudo-aleatory character of turbulence. The successive application of both operators allows us to derive the balance equations of the kind of flows under study. Two major issues are then highlighted, the modeling of dispersion induced by the solid matrix and the turbulence modeling at a macroscopic scale (Reynolds tensor and turbulent dispersion). To this aim, we lean on the local modeling of turbulence and more precisely on the k - ε RANS models. The methodology of dispersion study, derived thanks to the volume averaging theory, is extended to turbulent flows. Its application includes the simulation, at a microscopic scale, of turbulent flows within a representative elementary volume of the porous media. Applied to channel flows, this analysis shows that even within the turbulent regime, dispersion remains one of the dominating phenomena within the macro-scale modeling framework. A two-scale analysis of the flow allows us to understand the dominating role of the drag force in the kinetic energy transfers between scales. Transfers between the mean part and the turbulent part of the flow are formally derived. This description significantly improves our understanding of the issue of macroscopic modeling of turbulence and leads us to define the sub-filter production and the wake dissipation. A f - f - w >f model is derived. It is based on three balance equations for the turbulent kinetic energy, the viscous dissipation and the wake dissipation. Furthermore, a dynamical predictor for the friction coefficient is proposed. This model is then successfully applied to the study of

  10. MACRO1: a code to test a methodology for analyzing nuclear-waste management systems

    International Nuclear Information System (INIS)

    Edwards, L.L.

    1979-01-01

    The code is primarily a manager of probabilistic data and deterministic mathematical models. The user determines the desired aggregation of the available models into a composite model of a physical system. MACRO1 then propagates the finite probability distributions of the inputs to the model to finite probability distributions over the outputs. MACRO1 has been applied to a sample analysis of a nuclear-waste repository, and its results compared satisfactorily with previously obtained Monte Carlo statistics

  11. Search for GUT magnetic monopoles and nuclearites 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; De Marzo, C; De Mitri, I; De Vincenzi, M; Dekhissi, H; Derkaoui, J; 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; Katsavounidis, E; Katsavounidis, I; Kearns, E; Kim, H; Kumar, A; Kyriazopoulou, S; Lamanna, E; Lane, C; Larocci, E; Levin, D S; Lipari, P; Longley, N P; Longo, M J; Loparco, F; Maarou, 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; 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; 10.1016/S1350-4487(03)00140-9

    2003-01-01

    We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles and nuclearites. Several searches were performed with different subdetectors, i.e. scintillation counters, limited streamer tubes and nuclear track detectors. No magnetic monopole or nuclearite candidates were found. The MACRO upper limit to the local flux of GUT magnetic monopoles is at the level of 1.4*10/sup -16/ cm/sup -2/s/sup -1/sr/sup -1/.

  12. Examination of Inequalities in Hungary by Microsimulation in Consistency with Macro Data

    OpenAIRE

    Cserháti, Ilona; Keresztély, Tibor; Takács, Tibor

    2016-01-01

    Effective decision making uses various databases including both micro and macro level datasets. In many cases it is a big challenge to ensure the consistency of the two levels. Different types of problems can occur and several methods can be used to solve them. The paper concentrates on the input alignment of the households’ income for microsimulation, which means refers to improving the elements of a micro data survey (EU-SILC) by using macro data from administrative sources. We use a combin...

  13. Interactions between leaf macro, micronutrients and soil properties in pistachio (Pistacia vera L.) orchards

    OpenAIRE

    Koukoulakis, Prodromos; Chatzissavvidis, Christos; Papadopoulos, Aristotelis; Pontikis, Dimitrios

    2013-01-01

    The interactions between: (i) leaf dry matter macronutrients, micronutrients and soil chemical properties, (ii) leaf macro- and micronutrients, (iii) soil macro- and micronutrients and (iv) soil chemical properties, and soil micro- and macronutrients in 50 pistachio orchards were investigated in leaves and soils by means of regression analysis. Most of the soils were deficient in plant-available P, Zn, Mn, Fe, and B, while they were excessively supplied with Cu. Leaf analysis showed that most...

  14. Practice to Policy: Clinical psychologists' experiences of macro-level work

    OpenAIRE

    Browne, N.

    2017-01-01

    Many clinical psychologists are venturing beyond their traditional therapeutic roles to undertake macro-level work, engaging with social change, policy and public health. However, no research has systematically examined clinical psychologists’ roles in policy work and the implications for the profession. Part 1 of the thesis is a literature review of one area of macro-level policy aimed at improving the social determinants of mental health. It reviews nine intervention studies of housing impr...

  15. Detection of macro-ecological patterns in South American hummingbirds is affected by spatial scale

    DEFF Research Database (Denmark)

    Rahbek, Carsten; Graves, Gary R.

    2000-01-01

    Scale is widely recognized as a fundamental conceptual problem in biology, but the question of whether species-richness patterns vary with scale is often ignored in macro-ecological analyses, despite the increasing application of such data in international conservation programmes. We tested for s...... peaks, decreasing the power of statistical tests to discriminate the causal agents of regional richness gradients. Ideally, the scale of analysis should be varied systematically to provide the optimal resolution of macro-ecological pattern....

  16. Language sampling

    DEFF Research Database (Denmark)

    Rijkhoff, Jan; Bakker, Dik

    1998-01-01

    This article has two aims: [1] to present a revised version of the sampling method that was originally proposed in 1993 by Rijkhoff, Bakker, Hengeveld and Kahrel, and [2] to discuss a number of other approaches to language sampling in the light of our own method. We will also demonstrate how our...... sampling method is used with different genetic classifications (Voegelin & Voegelin 1977, Ruhlen 1987, Grimes ed. 1997) and argue that —on the whole— our sampling technique compares favourably with other methods, especially in the case of exploratory research....

  17. Improvement of aquaponic performance through micro- and macro-nutrient addition.

    Science.gov (United States)

    Ru, Dongyun; Liu, Jikai; Hu, Zhen; Zou, Yina; Jiang, Liping; Cheng, Xiaodian; Lv, Zhenting

    2017-07-01

    Aquaponics is one of the "zero waste" industry in the twenty-first century, and is considered to be one of the major trends for the future development of agriculture. However, the low nitrogen utilization efficiency (NUE) restricted its widely application. To date, many attempts have been conducted to improve its NUE. In the present study, effect of micro- and macro-nutrient addition on performance of tilapia-pak choi aquaponics was investigated. Results showed that the addition of micro- and macro-nutrients improved the growth of plant directly and facilitated fish physiology indirectly, which subsequently increased NUE of aquaponics from 40.42 to 50.64%. In addition, remarkable lower total phosphorus concentration was obtained in aquaponics with micro- and macro-nutrient addition, which was attributed to the formation of struvite. Most of the added micro-nutrients were enriched in plant root, while macro-nutrients mainly existed in water. Moreover, no enrichment of micro- and macro-nutrients in aquaponic products (i.e., fish and plant leaves) was observed, indicating that it had no influence on food safety. The findings here reported manifest that appropriate addition of micro- and macro-nutrients to aquaponics is necessary, and would improve its economic feasibility.

  18. Multidisciplinary acute care research organization (MACRO): if you build it, they will come.

    Science.gov (United States)

    Early, Barbara J; Huang, David T; Callaway, Clifton W; Zenati, Mazen; Angus, Derek C; Gunn, Scott R; Yealy, Donald M; Unikel, Daniel; Billiar, Timothy R; Peitzman, Andrew B; Sperry, Jason L

    2013-07-01

    Clinical research will increasingly play a core role in the evolution and growth of acute care surgery program development across the country. What constitutes an efficient and effective clinical research infrastructure in the current fiscal and academic environment remains obscure. We sought to characterize the effects of implementation of a multidisciplinary acute care research organization (MACRO) at a busy tertiary referral university setting. In 2008, to minimize redundancy and cost as well as to maximize existing resources promoting acute care research, MACRO was created, unifying clinical research infrastructure among the Departments of Critical Care Medicine, Emergency Medicine, and Surgery. During the periods 2008 to 2012, we performed a retrospective analysis and determined volume of clinical studies, patient enrollment for both observational and interventional trials, and staff growth since MACRO's origination and characterized changes over time. From 2008 to 2011, the volume of patients enrolled in clinical studies, which MACRO facilitates has significantly increased more than 300%. The percentage of interventional/observational trials has remained stable during the same period (50-60%). Staff has increased from 6 coordinators to 10, with an additional 15 research associates allowing 24/7 service. With this significant growth, MACRO has become financially self-sufficient, and additional outside departments now seek MACRO's services. Appropriate organization of acute care clinical research infrastructure minimizes redundancy and can promote sustainable, efficient growth in the current academic environment. Further studies are required to determine if similar models can be successful at other acute care surgery programs.

  19. Soil dehydrogenase activity of natural macro aggregates in a toposequence of forest soil

    Directory of Open Access Journals (Sweden)

    Maira Kussainova

    2013-01-01

    Full Text Available The main objective of this study was to determine changes in soil dehydrogenase activity in natural macro aggregates development along a slope in forest soils. This study was carried out in Kocadag, Samsun, Turkey. Four landscape positions i.e., summit, shoulder backslope and footslope, were selected. For each landseape position, soil macro aggregates were separated into six aggregate size classes using a dry sieving method and then dehydrogenase activity was analyzed. In this research, topography influenced the macroaggregate size and dehydrogenase activity within the aggregates. At all landscape positions, the contents of macro aggregates (especially > 6.3 mm and 2.00–4.75 mm in all soil samples were higher than other macro aggregate contents. In footslope position, the soils had generally the higher dehydrogenase activity than the other positions at all landscape positions. In all positions, except for shoulder, dehydrogenase activity was greater macro aggregates of <1 mm than in the other macro aggregate size.

  20. Critical Thinking Skills to Literary Works: A Method of Teaching Language through Literature

    Directory of Open Access Journals (Sweden)

    Fithriyah Inda Nur Abida

    2016-05-01

    Full Text Available Teaching a language has become a challenging task for the teachers to train and to teach language for their students. In present time, the ability to master a language is vital for a language is a powerful means of  communicating. Most of us will not focus on the language present in the literature part because our mind sets only towards the grammar. This has made both the teacher and students to ignore the literature part and made them to focus only on grammatical part to learn language. The urge behind using literary works in the teaching a language is to argue that the current attempts to implant literary works to the teaching of a language definitely develop students’ critical thinking in such a way that help them to easily master a particular language. Learning literary works in a classroom not only make the students learn about a story but also study how the language are structured and how its structured bring a great difference in meaning. Through a literary works student sees the language of real-life contexts. They learn the feelings, ideas, and experiences of linguistics components that give a realistic touch and help them to learn a language in a comprehensive way. It is also found that using literary works in the teaching learning process can improve student’s ability both in micro-linguistics and macro-linguistics.

  1. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial

    DEFF Research Database (Denmark)

    Burnett, Alan K; Hills, Robert K; Milligan, Donald

    2011-01-01

    PURPOSE: Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously...... established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients. PATIENTS AND METHODS: In this open-label trial, 1,113 patients, predominantly younger...... in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit...

  2. A radiolabeled antibody targeting CD123+ leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

    Directory of Open Access Journals (Sweden)

    Jeffrey V. Leyton

    2015-01-01

    Full Text Available Radioimmunotherapy (RIT with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS peptides and labeled with the Auger electron-emitter, 111In (111In-NLS-CSL360 was studied in the prevalent NOD/SCID mouse AML engraftment assay. Significant decreases in CD123+ leukemic cells and impairment of leukemic stem cell self-renewal were achieved with high doses of RIT. However, NOD/SCID mice were very radiosensitive to these doses. At low non-toxic treatment doses, 111In-NLS-CSL360 demonstrated a trend towards improved survival associated with decreased spleen/body weight ratio, an indicator of leukemia burden, and almost complete eradication of leukemia from the bone marrow in some mice.

  3. Language training

    CERN Multimedia

    2015-01-01

    If one of your New Year’s resolutions is to learn a language, there is no excuse any more.    You can attend one of our English or French courses and you can practise the language with a tandem partner!   General & Professional French courses The next General & Professional French course will start on 26 January. These collective courses aim to bring participants who have at least level A1 to higher levels (up to C2). Each level consists of a combination of face-to-face sessions (40 hours) with personal work (20 hours) following a specially designed programme. A final progress test takes place at the end of the term. Please note that it is mandatory to take the placement test. Please sign up here. French courses for beginners The aim of this course is to give some basic skills to beginners in order to communicate in simple everyday situations in both social and professional life. These courses can start at any time during the year, as soon as a group of beg...

  4. Language Training

    CERN Multimedia

    HR Department

    Permanence A "permanence" for language Training has been set up. If anyone has a question or requires information on any aspect of English or French training please come to our office 5 4-016 at the following times. Lucette Fournier - French courses Monday 13.30 - 15.30 Tuesday\t10.30 - 12.30 Tessa Osborne - English courses Wednesday\t12.00 - 14.00 Thursday\t11.00 - 13.00   New courses Specific English and French courses - Exam preparation/ We are now offering specific courses in English and French leading to a recognised external examination (e.g. Cambridge, DELF, DALF). If you are interested in following one of these courses and have at least an upper intermediate level of English or French, please enrol through the following link:  English courses French courses Or contact: Tessa Osborne 72957 (English courses) Lucette Fournier 73483 (French courses) Language Training Nathalie Dumeaux Tel. 78144 nathalie.dumeaux@cern.ch

  5. Language Training

    CERN Multimedia

    HR Department

    2009-01-01

    PermanenceA "permanence" for language Training has been set up. If anyone has a question or requires information on any aspect of English or French training please come to our office 5 4-016 at the following times. Lucette Fournier French courses Monday 13.30 - 15.30 Tuesday\t10.30 - 12.30 Tessa Osborne English courses Wednesday\t12.00 - 14.00 Thursday\t11.00 - 13.00 New courses Specific English and French courses - Exam preparation/ We are now offering specific courses in English and French leading to a recognised external examination (e.g. Cambridge, DELF and BULATS). If you are interested in following one of these courses and have at least an upper intermediate level of English or French, please enrol through the following link: http://English courses http://French courses Or contact: Tessa Osborne 72957 (English courses) Lucette Fournier 73483 (French courses) Language Training Nathalie Dumeaux Tel. 78144 mailto:nathalie.dumeaux@cern.ch

  6. LANGUAGE TRAINING

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch FRENCH TRAINING General and Professional French Courses The next session will take place from 26 January to 02 April 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz: Tel. 73127. Writing Professional Documents in French The next session will take place from 26 January to 02 April 2004. This course is designed for people wi...

  7. LANGUAGE TRAINING

    CERN Multimedia

    2004-01-01

    If you wish to participate in one of the following courses, please discuss with your supervisor and apply electronically directly from the course description pages that can be found on the Web at: http://www.cern.ch/Training/ or fill in an "application for training" form available from your Divisional Secretariat or from your DTO (Divisional Training Officer). Applications will be accepted in the order of their receipt. LANGUAGE TRAINING Françoise Benz tel. 73127 language.training@cern.ch FRENCH TRAINING General and Professional French Courses The next session will take place from 26 January to 02 April 2004. These courses are open to all persons working on the Cern site, and to their spouses. For registration and further information on the courses, please consult our Web pages: http://cern.ch/Training or contact Mrs. Benz : Tel. 73127. Writing Professional Documents in French The next session will take place from 26 January to 02 April 2004. This course is designed for peop...

  8. Capitalizing on Speaking Skill of EFL Learners for the Language Literacy

    Directory of Open Access Journals (Sweden)

    Fauzia Hasan Siddiqui

    2014-03-01

    Full Text Available This study aims at grabbing the attention of EFL /ESL teachers, trainers, and administrators towards the importance of teaching speaking skill to enhance overall language proficiency of EFL learners. Comprehensive research done in the field of applied linguistics and English Language Teaching (ELT establishes a positive correlation of speaking skill with the overall language proficiency. Despite this obvious significance of speaking skill in language learning process, it has not gained sufficient attention in the ELT or the assessments in Oman.  Relying on the available literature on the importance of the speaking skill and its effective role in enhancing other language macro skills (listening, reading, and writing, this exploratory research analyzes the currents status of speaking skill in ELT and assessments at the General Foundation Programme (GFP in Oman. As many GFP’s have IELTS (International English Language Testing System  exam as their programme exit examination, the study begins with measuring the correlation of speaking skill grades with other macro skill in order to accentuate the positive impact of speaking skill on other language skills. Secondly, it presents the statistics of time devoted to teaching and weights that speaking skill hold in the GFP in Oman. Finally, the study suggests the ways to optimize speaking skill opportunities to create successful literacy experience among adult EFL learners.

  9. Foreign Language Teachers' Language Proficiency and Their Language Teaching Practice

    Science.gov (United States)

    Richards, Heather; Conway, Clare; Roskvist, Annelies; Harvey, Sharon

    2013-01-01

    Teachers' subject knowledge is recognized as an essential component of effective teaching. In the foreign language context, teachers' subject knowledge includes language proficiency. In New Zealand high schools, foreign languages (e.g. Chinese, French, German, Japanese and Spanish) have recently been offered to learners earlier in their schooling,…

  10. Technology in Language Use, Language Teaching, and Language Learning

    Science.gov (United States)

    Chun, Dorothy; Smith, Bryan; Kern, Richard

    2016-01-01

    This article offers a capacious view of technology to suggest broad principles relating technology and language use, language teaching, and language learning. The first part of the article considers some of the ways that technological media influence contexts and forms of expression and communication. In the second part, a set of heuristic…

  11. BIBLIOGRAPHY ON LANGUAGE DEVELOPMENT.

    Science.gov (United States)

    Harvard Univ., Cambridge, MA. Graduate School of Education.

    THIS BIBLIOGRAPHY LISTS MATERIAL ON VARIOUS ASPECTS OF LANGUAGE DEVELOPMENT. APPROXIMATELY 65 UNANNOTATED REFERENCES ARE PROVIDED TO DOCUMENTS DATING FROM 1958 TO 1966. JOURNALS, BOOKS, AND REPORT MATERIALS ARE LISTED. SUBJECT AREAS INCLUDED ARE THE NATURE OF LANGUAGE, LINGUISTICS, LANGUAGE LEARNING, LANGUAGE SKILLS, LANGUAGE PATTERNS, AND…

  12. Inference in `poor` languages

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, S.

    1996-10-01

    Languages with a solvable implication problem but without complete and consistent systems of inference rules (`poor` languages) are considered. The problem of existence of finite complete and consistent inference rule system for a ``poor`` language is stated independently of the language or rules syntax. Several properties of the problem arc proved. An application of results to the language of join dependencies is given.

  13. Let There Be Languages!

    Science.gov (United States)

    Gunnarsson, Petur

    1992-01-01

    Examines the resilience of small languages in the face of larger ones. Highlights include the concept of one dominant language, such as Esperanto; the threat of television to small visual-language societies; the power of visual media; man's relationship to language; and the resilience of language. (LRW)

  14. Language as Pure Potential

    Science.gov (United States)

    Park, Joseph Sung-Yul

    2016-01-01

    Language occupies a crucial position in neoliberalism, due to the reimagination of language as commodified skill. This paper studies the role of language ideology in this transformation by identifying a particular ideology that facilitates this process, namely the ideology which views language as pure potential. Neoliberalism treats language as a…

  15. Linguistics in Language Education

    Science.gov (United States)

    Kumar, Rajesh; Yunus, Reva

    2014-01-01

    This article looks at the contribution of insights from theoretical linguistics to an understanding of language acquisition and the nature of language in terms of their potential benefit to language education. We examine the ideas of innateness and universal language faculty, as well as multilingualism and the language-society relationship. Modern…

  16. Language Teachers' Target Language Project: Language for Specific Purposes of Language Teaching

    Science.gov (United States)

    Korenev, Alexey; Westbrook, Carolyn; Merry, Yvonne; Ershova, Tatiana

    2016-01-01

    The Language Teachers' Target Language project (LTTL) aims to describe language teachers' target language use domain (Bachman & Palmer 2010) and to develop a language test for future teachers of English. The team comprises four researchers from Moscow State University (MSU) and Southampton Solent University.

  17. Foreign Language Attrition.

    Science.gov (United States)

    de Bot, Kees; Weltens, Bert

    1995-01-01

    Reviews recent research on language maintenance and language loss, focusing on the loss of a second language in a first language environment, the linguistic aspects of loss, and relearning a "lost" language. An annotated bibliography discusses nine important works in the field. (43 references) (MDM)

  18. A Case of AML Characterized by a Novel t(4;15(q31;q22 Translocation That Confers a Growth-Stimulatory Response to Retinoid-Based Therapy

    Directory of Open Access Journals (Sweden)

    Justin M. Watts

    2017-07-01

    Full Text Available Here we report the case of a 30-year-old woman with relapsed acute myeloid leukemia (AML who was treated with all-trans retinoic acid (ATRA as part of investigational therapy (NCT02273102. The patient died from rapid disease progression following eight days of continuous treatment with ATRA. Karyotype analysis and RNA-Seq revealed the presence of a novel t(4;15(q31;q22 reciprocal translocation involving the TMEM154 and RASGRF1 genes. Analysis of primary cells from the patient revealed the expression of TMEM154-RASGRF1 mRNA and the resulting fusion protein, but no expression of the reciprocal RASGRF1-TMEM154 fusion. Consistent with the response of the patient to ATRA therapy, we observed a rapid proliferation of t(4;15 primary cells following ATRA treatment ex vivo. Preliminary characterization of the retinoid response of t(4;15 AML revealed that in stark contrast to non-t(4;15 AML, these cells proliferate in response to specific agonists of RARα and RARγ. Furthermore, we observed an increase in the levels of nuclear RARγ upon ATRA treatment. In summary, the identification of the novel t(4;15(q31;q22 reciprocal translocation opens new avenues in the study of retinoid resistance and provides potential for a new biomarker for therapy of AML.

  19. Different impact of intermediate and unfavourable cytogenetics at the time of diagnosis on outcome of de novo AML after allo-SCT: a long-term retrospective analysis from a single institution.

    Science.gov (United States)

    Nahi, H; Remberger, M; Machaczka, M; Ungerstedt, J; Mattson, J; Ringden, O; Le-Blanc, Katarina; Ljungman, P; Hägglund, H

    2012-12-01

    Karyotype of myeloblasts at the time of AML diagnosis has been shown to be prognostic significant for pre-remission outcome and outcome after allo-SCT, but the latter requires further studies. We conducted a retrospective analysis of the impact of intermediate and unfavourable cytogenetics at the time of primary diagnosis on outcome after allo-SCT in de novo AML. The study included 169 patients who underwent allo-SCT at Karolinska University Hospital between 1980 and 2010. Intermediate and unfavourable cytogenetics were found in 129 (76%) and 40 patients (24%), respectively. Myeloablative and reduced-intensity conditioning were given to 120 (71%) and 49 (29%) patients, respectively. Allo-SCT was performed in CR1 in 122 patients (72%). TRM was 16% in both cytogenetics groups. Relapse occurred in 29% patients with intermediate and in 45% patients with unfavourable cytogenetics (P=0.01). The probabilities of 5-year OS for patients with intermediate and unfavourable cytogenetics were 60 and 43%, respectively (P=0.02). Multivariate analysis revealed intermediate cytogenetics, chronic GVHD, and recipient CMV-negative serostatus as variables associated with favourable OS. Our study showed that outcome after allo-SCT in de novo AML differs depending on cytogenetic risk-group; however its position in post-remission therapy of eligible AML patients is not threatened.

  20. A Jehovah’s Witness with Acute Myeloid Leukemia Successfully Treated with an Epigenetic Drug, Azacitidine: A Clue for Development of Anti-AML Therapy Requiring Minimum Blood Transfusions

    Directory of Open Access Journals (Sweden)

    Yumi Yamamoto

    2014-01-01

    Full Text Available Therapy for acute leukemia in Jehovah’s Witnesses patients is very challenging because of their refusal to accept blood transfusions, a fundamental supportive therapy for this disease. These patients are often denied treatment for fear of treatment-related death. We present the first Jehovah’s Witness patient with acute myeloid leukemia (AML treated successfully with azacitidine. After achieving complete remission (CR with one course of azacitidine therapy, the patient received conventional postremission chemotherapy and remained in CR. In the case of patients who accept blood transfusions, there are reports indicating the treatment of AML patients with azacitidine. In these reports, azacitidine therapy was less toxic, including hematoxicity, compared with conventional chemotherapy. The CR rate in azacitidine-treated patients was inadequate; however, some characteristics could be useful in predicting azacitidine responders. The present case is useful for treating Jehovah’s Witnesses patients with AML and provides a clue for anti-AML therapy requiring minimum blood transfusions.

  1. Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: A collaborative study by the International-Berlin- Frankfurt-Münster AML-study group

    NARCIS (Netherlands)

    E.A. Coenen (Eva); C.M. Zwaan (Christian Michel); D. Reinhardt (Dirk); C.J. Harrison (Christine); O.A. Haas (Oskar); V. de Haas (Valerie); V. Mihál (Vladimir); B. de Moerloose (Barbara); M. Jeison (Marta); J.E. Rubnitz (Jeffrey); D. Tomizawa (Daisuke); D. Johnston (Donna); T.A. Alonzo (Todd); H. Hasle (Henrik); A. Auvrignon (Anne); M.N. Dworzak (Michael); A. Pession (Andrea); V.H.J. van der Velden (Vincent); J. Swansbury (John); K.-F. Wong (Kit-Fai); N. Terui (Nobuhiko); S. Savasan (Sureyya); M. Winstanley (Mark); G. Vaitkeviciene (Goda); M. Zimmermann (Martin); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2013-01-01

    textabstractIn pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical

  2. Language variety, language hierarchy, and language choice in the international university

    DEFF Research Database (Denmark)

    Haberland, Hartmut; Mortensen, Janus

    2012-01-01

    Introduction to thematic issue on Language variety, language hierarchy, and language choice in the international university......Introduction to thematic issue on Language variety, language hierarchy, and language choice in the international university...

  3. A special purpose simulation language for nuclear power plants

    International Nuclear Information System (INIS)

    Saphier, D.

    1980-01-01

    A special purpose block-oriented simulation language, 'The Dynamic Simulator for Nuclear Power Plants' (DSNP), was developed at Argonne National Laboratory. The dominant feature of DSNP is the ability to transform a power plant flowchart or block diagram directly into a simulation program. The user is required to recognize the symbolic DSNP statements for the appropriate physical component, and list these statements in a logical sequence according to the flow of physical properties in the simulated power plant. At present most of the component models in DSNP are of the lumped parameter type. Although DSNP is a special purpose simulation language, it also has all the features of a general purpose simulation language, and in particular a powerful macro processor. The use of DSNP is demonstrated by a sample problem simulating a reactor startup accident. (Auth.)

  4. Controlling Particle Morphologies at Fluid Interfaces: Macro- and Micro- approaches

    Science.gov (United States)

    Beesabathuni, Shilpa Naidu

    The controlled generation of varying shaped particles is important for many applications: consumer goods, biomedical diagnostics, food processing, adsorbents and pharmaceuticals which can benefit from the availability of geometrically complex and chemically inhomogeneous particles. This thesis presents two approaches to spherical and non-spherical particle synthesis using macro and microfluidics. In the first approach, a droplet microfluidic technique is explored to fabricate spherical conducting polymer, polyaniline, particles with precise control over morphology and functionality. Microfluidics has recently emerged as an important alternate to the synthesis of complex particles. The conducting polymer, polyaniline, is widely used and known for its stability, high conductivity, and favorable redox properties. In this approach, monodisperse micron-sized polyaniline spherical particles were synthesized using two-phase droplet microfluidics from Aniline and Ammonium persulfate oxidative polymerization in an oil-based continuous phase. The morphology of the polymerized particles is porous in nature which can be used for encapsulation as well as controlled release applications. Encapsulation of an enzyme, glucose oxidase, was also performed using the technique to synthesize microspheres for glucose sensing. The polymer microspheres were characterized using SEM, UV-Vis and EDX to understand the relationship between their microstructure and stability. In the second approach, molten drop impact in a cooling aqueous medium to generate non-spherical particles was explored. Viscoelastic wax based materials are widely used in many applications and their performance and application depends on the particle morphology and size. The deformation of millimeter size molten wax drops as they impacted an immiscible liquid interface was investigated. Spherical molten wax drops impinged on a cooling water bath, then deformed and as a result of solidification were arrested into various

  5. The third population boom and corresponding macro-policies.

    Science.gov (United States)

    Tian, X

    1990-01-01

    China's birth peak between 1962-1973, and the expected 3rd peak beginning in 1986 has and will create a need for better, stable family planning measures; economic planning between 1990 and 2020 needs to accommodate the working population which in 2010 is expected to be 71.4% of the population (956 million); and a macro-strategic policy needs to be developed of the elderly who may constitute 17.44% of the population. The aging trend in China's working age population is expected to rise so rapidly that in 48 years, between 1982 and 2040, the over 65 population will quadruple ( a process in developed countries usually taking 80 years), thus creating a significant impact on a society with a low level of economic development. It is suggested that along with the growth in the national economy should come a state-provided welfare and retirement system, with reforms necessary to generate the additional income for elderly support; it is important that the cultural pattern of family care of the elderly remain intact. Assisting the able elderly in earning income in the service sector is encouraged. China's population has historically undergone 2 peak growth periods, between 1685 and 1830 with a 1% growth rate and between 1949-89 with an annual growth rate of 1.8%. The 2nd period is marked by 2 smaller peaks, one between 1953- 1957 with a growth rate of 2.38% and 1962-73 with a growth rate of 2.56%. A decline after 1974 changed to another upward cycle in 1986 with an increase to a 1.43 % growth rate expected to continue to 1996. The 1st peak between 1953-57 has already affected population control and the job market, and the fecund population is of concern because of the absolute size of the population, and because the planned limit for population growth of 1.2 billion by the year 2000 may be exceeded; and the projected rates, which have been increasing as expected, mean a population of 1.5 billion by 2050.

  6. Effecting Organizational Change at the Macro Level of Professions

    Science.gov (United States)

    Green, Robert Anthony

    Much has been written in academic and popular publications about organizational change. Topics have ranged from case studies to anecdotal stories of how leaders can change an organization. There is little written on changing the culture and vision of a profession at the macro level. This dissertation shows that one key to effecting change within a profession is to educate those at the entrant level and thereby effect change with the profession. Over time, these new entrants to the profession will rise to senior positions and be able to effect greater change through the hiring, training, and mentoring processes inherent in the professions and the organizations for which they work. One way to effect change in these entrants is through education in college and professional schools. This study is specifically focused on effecting change in the interdisciplinary field of engineering and public policy. Public policy involves countless infrastructure issues at all levels of government. Engineers are well-versed in dealing with the technical issues of infrastructure but their voice is often lacking at the policy level. Similarly, political scientists are well-versed in policy but are often lacking in a thorough understanding of the technical aspects of the policy. Through an introductory course in engineering and public policy, undergraduate students from the seemingly disparate fields of engineering and political science were placed in a common classroom and through lectures, writings, presentations, and guided discussions their attitudes on key areas were changed. Areas studied were professional interest, legitimacy, deference, the public policy process, and education outside of a specific field. Through the process of education, changes in each of these areas was possible. Further, the movement was towards making students in each discipline more open to the input, opinions, and attitudes of others, and specifically in shifting engineers toward a more positive view of

  7. Concomitant macro and microvascular complications in diabetic nephropathy

    International Nuclear Information System (INIS)

    Alwakeel, Jamal S; AlSuwaida, Abdulkareem; Isnani, Arthur C; AlHarbi, Ali; Alam Awatif

    2009-01-01

    To determine the prevalence of concomitant microvascular and macro vascular complications of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 dia-betic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 + -11.4 years, mean duration of diabetes was 15.4 + -7.5 years, mean age at the onset of nephropathy was 61.5 + - 12.4 years, and mean duration of nephropathy was 3.9 + - 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative retinopathy (11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Deterioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing complications were significant after the onset of nephropathy; ACS (1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggressive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate

  8. Concomitant macro and microvascular complications in diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Alwakeel, Jamal S; AlSuwaida, Abdulkareem [Div. of Nephrology, Dept. of Medicine, King Khalid Univ., Hospital, Riyadh (Saudi Arabia); Isnani, Arthur C [Dept. of Family and Community Medicine, King Khalid Univ. Hospital, Riyadh (Saudi Arabia); AlHarbi, Ali [Coll. of Medicine and Research Center, King Khalid Univ. Hospital, Riyadh (Saudi Arabia); Awatif, Alam [Div. of Nephrology, Dept. of Medicine, Security Forces Hospital, Riyadh (Saudi Arabia)

    2009-07-01

    To determine the prevalence of concomitant microvascular and macro vascular complications of diabetic nephropathy we retrospectively reviewed the medical records of all 1,952 type 2 dia-betic patients followed-up at Security Forces Hospital, Riyadh, Saudi Arabia from January 1989 to December 2004. There were 626 (32.1%) patients (294 (47%) were males) who developed diabetic nephropathy. Their mean age was 66.9 + -11.4 years, mean duration of diabetes was 15.4 + -7.5 years, mean age at the onset of nephropathy was 61.5 + - 12.4 years, and mean duration of nephropathy was 3.9 + - 3.8 years. Concomitant diabetic complications included cataract (38.2%), acute coronary syndrome (36.1%), peripheral neuropathy (24.9%), myocardial infarction (24.1%), background retinopathy (22.4%), stroke (17.6%), proliferative retinopathy (11.7%), foot infection (7.3%), limb amputation (3.7%) and blindness (3%). Hypertension was documented in 577 (92.2%) patients, dyslipidemia in 266 (42.5%) and mortality from all causes in 86 (13.7%). There were 148 (23.6%) patients with one complication, 81 (12.9%) with two, 83 (13.3%) with three, and 61 (9.7%) with four or more. Deterioration of glomerular filtration rate was observed in 464 (74%) patients and doubling of serum creatinine in 250 (39.9%), while 95 (15.2%) developed end-stage renal disease (ESRD) at the end of study and 79 (12.6%) required dialysis. Complications were significantly more prevalent among males with greater number reaching ESRD level than females (P< 0.05). Relative risks of developing complications were significant after the onset of nephropathy; ACS (1.41), MI (1.49), stroke (1.48), diabetic foot (1.6), amputation (1.58) and death (1.93). We conclude that complications of diabetes are aggressive and progressive including high prevalence of diabetic nephropathy. Careful monitoring and proper institution of management protocols should be implemented to identify diabetic patients at high risk for complications and mitigate

  9. EFL Writing Apprehension: The Macro or the Micro?

    Directory of Open Access Journals (Sweden)

    Mohammad Alnufaie

    2013-06-01

    Full Text Available This study was part of a doctoral project to explore the writing apprehension levels of 121 second-year undergraduate Saudi student writers who were studying English as a foreign language and for specific purposes in a Saudi industrial college.The study draws on Dörnyei’s (1994 framework of L2 motivation levels and their micro-motivational conditions in L2 learning situations, and addresses EFL writing apprehension in strategy-related conditions. For data collection, aWriting Strategy Apprehension Scale (WSAS was developed and adapted from a test designed by John Daly and Michael Miller (1975 and from the Second Language Writing Anxiety Inventory (SLWAI designed by Cheng (2004.The participants were classified into three levels of apprehension (apprehensive strategy users, average apprehensive strategy users, and low apprehensive strategy users. The results showwhile the majority of the participants (57.9% were average in their stress and apprehension levels towards writing strategies, almost a third of them (31.4% were highly apprehensive. In addition, the most stressful strategies were those that indicate the lack of generating ideas, the care about accuracy, and the follow of teacher’s expectations.

  10. Use of recombinant granulocyte-macrophage colony-stimulating factor during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia (AML) : Final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer (EORTC-LCG) and the Dutch Belgian Hemato-Oncology Cooperative Group (HOVON)

    NARCIS (Netherlands)

    Lowenberg, B; Suciu, S; Archimbaud, E; Ossenkoppele, G; Verhoef, GEG; Vellenga, E; Wijermans, P; Berneman, Z; Dekker, AW; Stryckmans, P; Jehn, U; Muus, P; Sonneveld, P; Dardenne, M; Zittoun, R

    1997-01-01

    We conducted a prospective randomized multicenter clinical trial comparing the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to intensive chemotherapy in patients of 61 years and older with untreated newly diagnosed acute myeloid leukemia (AML). Patients were

  11. Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region

    International Nuclear Information System (INIS)

    Sakamoto, K; Imamura, T; Yano, M; Yoshida, H; Fujiki, A; Hirashima, Y; Hosoi, H

    2014-01-01

    All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML–RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPε and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML

  12. Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123"+/CD131"− phenotype of leukemia stem cells

    International Nuclear Information System (INIS)

    Gao, Catherine; Leyton, Jeffrey V.; Schimmer, Aaron D.; Minden, Mark; Reilly, Raymond M.

    2016-01-01

    Chimeric IgG_1 monoclonal antibody CSL360 recognizes the CD123"+/CD131"− phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates incorporating nuclear translocation sequence (NLS) peptides bound specifically to Raji cells transfected with CD123 and exhibited a K_D of 11 nmols/L in a competition receptor-binding assay using CD123-transfected CHO cells. "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and transported to the nucleus of human AML-5 myeloid leukemia cells. The clonogenic survival of AML-5 cells was reduced by "1"1"1In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control "1"1"1In-DTPA-chIgG_1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free "1"1"1In acetate did not decrease cell survival. These results are promising for further evaluation of "1"1"1In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation. - Highlights: • "1"1"1In-DTPA-NLS-CSL360 the CD123"+/CD131"− phenotype of leukemic stem cells (LSC). • "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and imported into the nucleus of AML-5 leukemia cells. • "1"1"1In-DTPA-NLS-CSL360 reduced the clonogenic survival of AML-5 leukemia cells by 4-fold.

  13. Plant litter functional diversity effects on litter mass loss depend on the macro-detritivore community.

    Science.gov (United States)

    Patoine, Guillaume; Thakur, Madhav P; Friese, Julia; Nock, Charles; Hönig, Lydia; Haase, Josephine; Scherer-Lorenzen, Michael; Eisenhauer, Nico

    2017-11-01

    A better understanding of the mechanisms driving litter diversity effects on decomposition is needed to predict how biodiversity losses affect this crucial ecosystem process. In a microcosm study, we investigated the effects of litter functional diversity and two major groups of soil macro-detritivores on the mass loss of tree leaf litter mixtures. Furthermore, we tested the effects of litter trait community means and dissimilarity on litter mass loss for seven traits relevant to decomposition. We expected macro-detritivore effects on litter mass loss to be most pronounced in litter mixtures of high functional diversity. We used 24 leaf mixtures differing in functional diversity, which were composed of litter from four species from a pool of 16 common European tree species. Earthworms, isopods, or a combination of both were added to each litter combination for two months. Litter mass loss was significantly higher in the presence of earthworms than in that of isopods, whereas no synergistic effects of macro-detritivore mixtures were found. The effect of functional diversity of the litter material was highest in the presence of both macro-detritivore groups, supporting the notion that litter diversity effects are most pronounced in the presence of different detritivore species. Species-specific litter mass loss was explained by nutrient content, secondary compound concentration, and structural components. Moreover, dissimilarity in N concentrations increased litter mass loss, probably because detritivores having access to nutritionally diverse food sources. Furthermore, strong competition between the two macro-detritivores for soil surface litter resulted in a decrease of survival of both macro-detritivores. These results show that the effects of litter functional diversity on decomposition are contingent upon the macro-detritivore community and composition. We conclude that the temporal dynamics of litter trait diversity effects and their interaction with

  14. Health Literacy - Multiple Languages

    Science.gov (United States)

    ... Here: Home → Multiple Languages → All Health Topics → Health Literacy URL of this page: https://medlineplus.gov/languages/ ... W XYZ List of All Topics All Health Literacy - Multiple Languages To use the sharing features on ...

  15. Cosmetic Dentistry - Multiple Languages

    Science.gov (United States)

    ... Here: Home → Multiple Languages → All Health Topics → Cosmetic Dentistry URL of this page: https://medlineplus.gov/languages/ ... W XYZ List of All Topics All Cosmetic Dentistry - Multiple Languages To use the sharing features on ...

  16. Atrial Fibrillation - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Atrial Fibrillation URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Atrial Fibrillation - Multiple Languages To use the sharing features on ...

  17. Journal for Language Teaching

    African Journals Online (AJOL)

    PROMOTING ACCESS TO AFRICAN RESEARCH ... Journal for Language Teaching = Ijenali Yekufundzisa Lulwimi = Tydskrif vir Taalonderrig ... SAALT was founded in 1964 for the benefit of language teaching and language teachers and ...

  18. Zika Virus - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Zika Virus URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Zika Virus - Multiple Languages To use the sharing features on ...

  19. Elder Abuse - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Elder Abuse URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Elder Abuse - Multiple Languages To use the sharing features on ...

  20. Herbal Medicine - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Herbal Medicine URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Herbal Medicine - Multiple Languages To use the sharing features on ...

  1. Introduction to formal languages

    CERN Document Server

    Révész, György E

    1991-01-01

    Covers all areas, including operations on languages, context-sensitive languages, automata, decidability, syntax analysis, derivation languages, and more. Numerous worked examples, problem exercises, and elegant mathematical proofs. 1983 edition.

  2. Domestic Violence - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Domestic Violence URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Domestic Violence - Multiple Languages To use the sharing features on ...

  3. Diabetic Foot - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Diabetic Foot URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Diabetic Foot - Multiple Languages To use the sharing features on ...

  4. Child Abuse - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Child Abuse URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Child Abuse - Multiple Languages To use the sharing features on ...

  5. A Natural Language Architecture

    OpenAIRE

    Sodiya, Adesina Simon

    2007-01-01

    Natural languages are the latest generation of programming languages, which require processing real human natural expressions. Over the years, several groups or researchers have trying to develop widely accepted natural language languages based on artificial intelligence (AI). But no true natural language has been developed. The goal of this work is to design a natural language preprocessing architecture that identifies and accepts programming instructions or sentences in their natural forms ...

  6. The Effects of Exurbanization on Bird and Macro invertebrate Communities in Deciduous Forests on the Cumberland Plateau, Tennessee

    International Nuclear Information System (INIS)

    Casey, J.M.; Wilson, M.E.; Haskell, D.G.; Hollingshead, N.

    2009-01-01

    To investigate the potential causes of changes to bird communities in exurban areas, we examined the relationship between bird and macro invertebrate communities in exurbanized forest. We randomly located sampling points across a gradient of exurbanization. We used point counts to quantify bird communities and sweep netting, soil cores, pitfalls, and frass collectors to quantify macro invertebrates. Bird communities had higher richness and abundance in exurban areas compared to undeveloped forests, and lost some species of conservation concern but gained others. The macro invertebrate community was slightly more abundant in exurban areas, with a slight shift in taxonomic composition. The abundance of macro invertebrates in soil cores (but not pitfalls) predicted the abundance of ground-foraging birds. The abundance of macro invertebrates in sweep nets was not associated with the abundance of aerial insectivore birds. Exurbanization therefore appears to change bird and macro invertebrate communities, but to a lesser extent than agricultural forest fragmentation or intensive urbanization.

  7. Language Assessment Literacy: Implications for Language Teachers

    Science.gov (United States)

    Giraldo, Frank

    2018-01-01

    Recently, the applied linguistics field has examined the knowledge, skills, and principles needed for assessment, defined as language assessment literacy. Two major issues in language assessment literacy have been addressed but not fully resolved--what exactly language assessment literacy is and how it differs among stakeholders (e.g., students…

  8. Discussion: Imagining the Languaged Worker's Language

    Science.gov (United States)

    Urciuoli, Bonnie

    2016-01-01

    What people perceive as "a language"--a named entity--is abstracted from practices and notions about those practices. People take for granted that language is somehow a "thing," an objectively distinct and bounded entity. How languages come to be thus imagined indexes the conditions under which they are imagined. The articles…

  9. Language and Language Policy in Singapore.

    Science.gov (United States)

    Baxter, William H., III

    1985-01-01

    Singapore's language policy must balance the wishes of the various ethnic groups, the political situation in the regions, and the needs of economic development. Malay, Mandarin Chinese, English, and Tamil are all recognized as official languages. Malay has special symbolic status as the national language. (RM)

  10. Macro- and Micronutrients of Human Milk Composition: Are They Related to Maternal Diet? A Comprehensive Systematic Review.

    Science.gov (United States)

    Keikha, Mojtaba; Bahreynian, Maryam; Saleki, Mohammad; Kelishadi, Roya

    2017-11-01

    This study aims at systematically reviewing the observational and interventional studies on the association of maternal macro- and micronutrient intake with breast milk content. We systematically searched the Medline via PubMed, Scopus, and ISI Web of Knowledge till October 2016 with the following search strategy: ("human milk" OR "breast milk" OR "breast milk composition" OR "human breast milk composition" OR "composition breast milk" OR "mother milk" OR "human breast milk") AND ("maternal diet" OR "maternal nutrition"). We also searched Google scholar for increasing the sensitivity of our search. The search was not limited to title and abstract due to the possibility that the desired outcome might have been considered a secondary aim. We excluded conference papers, editorials, letters, commentary, short survey, and notes. The search was refined to English language, and we did not consider any time limitation. To increase the sensitivity and to select more studies, the reference list of the published studies was checked as well. This review included 59 observational and 43 interventional studies on maternal diet related to breast milk composition. Different studies determined the associations and effects of some maternal dietary intake of micro and macronutrients and its reflection in human milk. Maternal dietary intake, particularly fatty acids, and some micronutrients, including fat soluble vitamins, vitamin B 1 , and vitamin C, was related to their content in breast milk composition.

  11. [MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

    Science.gov (United States)

    Liu, Ren-Hu; Meng, Jin-Ling

    2003-05-01

    MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor.

  12. Macro-habitat preferences by the African manatee and crocodiles – ecological and conservation implications

    Directory of Open Access Journals (Sweden)

    L. Luiselli

    2012-07-01

    Full Text Available African manatees (Trichechus senegalensis and crocodiles are threatened species in parts of their range. In West Africa, crocodiles may constitute the main predators for manatees apart from humans. Here, we explore the macro-habitat selection of manatees and two species of crocodiles (West African crocodiles Crocodylus suchus and dwarf crocodile Osteolaemus tetraspis in the Niger Delta (Nigeria, testing the hypotheses that (i manatees may avoid crocodiles in order to minimize risks of predation, and (ii the two crocodile species do compete. The study was carried out between 1994 and 2010 with a suite of different field techniques. We observed that the main macro-habitat types were freshwater rivers and coastal lagoons for manatees, mangroves for West African crocodiles, and rivers and creeks for dwarf crocodiles, with (i the three species differing significantly in terms of their macro-habitat type selection, and (ii significant seasonal influence on habitat selection of each species. Null models for niche overlap showed a significantly lower overlap in macro-habitat type use between manatee and crocodiles, whereas the two crocodiles were relatively similar. Null model analyses did not indicate any competitive interactions between crocodiles. On the other hand, manatees avoided macro-habitats where crocodiles, and especially West African crocodiles, are abundant.

  13. Macro-Elements and Trace Elements in Cereal Grains Cultivated in Latvia

    Directory of Open Access Journals (Sweden)

    Jākobsone Ida

    2015-09-01

    Full Text Available Cereal-based foods have great importance in the compensation of micro- and trace element deficiency, because 50% of the foods produced worldwide are made up of cereal grains. The aim of the research was to determine the concentration of macro-elements and trace elements in different cereals cultivated in Latvia. Various cereals were used in the research: rye (n = 45, barley (n = 54, spring wheat (n = 27, winter wheat (n = 53, triticale (n = 45 and oats (n = 42. Thirteen macro- and trace elements (Cd, Pb, Ni, Cr, Al, Cu, K, Na, Mn, Fe, Zn, Mg, Ca were determined in cereal grain samples (n = 266. Macro-elements and trace elements varied significantly (p < 0.01 or p < 0.001. The highest concentrations of macro- and trace elements were found in oats and the lowest in rye. The obtained data will expand the opportunity for food and nutrition scientists to evaluate content of the examined elements in grain products, and dietary consumption (bioavailability of the examined macro-elements and trace elements.

  14. Development of Hollow Steel Ball Macro-Encapsulated PCM for Thermal Energy Storage Concrete.

    Science.gov (United States)

    Dong, Zhijun; Cui, Hongzhi; Tang, Waiching; Chen, Dazhu; Wen, Haibo

    2016-01-19

    The application of thermal energy storage with phase change materials (PCMs) for energy efficiency of buildings grew rapidly in the last few years. In this research, octadecane paraffin was served as a PCM, and a structural concrete with the function of indoor temperature control was developed by using a macro-encapsulated PCM hollow steel ball (HSB). The macro-encapsulated PCM-HSB was prepared by incorporation of octadecane into HSBs through vacuum impregnation. Test results showed that the maximum percentage of octadecane carried by HSBs was 80.3% by mass. The macro-encapsulated PCM-HSB has a latent heat storage capacity as high as 200.5 J/g. The compressive strength of concrete with macro-encapsulated PCM-HSB at 28 days ranged from 22 to 40 MPa. The indoor thermal performance test revealed that concrete with macro-encapsulated octadecane-HSB was capable of reducing the peak indoor air temperature and the fluctuation of indoor temperature. It can be very effective in transferring the heating and cooling loads away from the peak demand times.

  15. Impact of heavy metals on macro-invertebrate fauna of the thaddo stream

    International Nuclear Information System (INIS)

    Nazneen, S.; Begum, F.; Sharmeen, R.; Ahmed, Z.

    2003-01-01

    Impact of some heavy metals like zinc, lead, copper, chromium and cadmium were studied at four spots on the macro-invertebrate fauna of the Thaddo stream, a tributary of Malir River. This was in correlation with an earlier study on the physico-chemical aspects of water which showed a severe pollution in this stream. Present data for the qualitative and quantitative analyses of macro-invertebrates and the ranges of heavy metals (Zn 0.5-3.5, Pb 0.90-1.42, Cu 0.35-0.93, Cr 0.0-0.08 and Cd 0.003-0.01 ppm) in the water samples also indicate high level of pollution in the stream. Macro-invertebrate fauna comprises only of aquatic insects which include larvae of Chironomus spp., adults of the Notonectus sp., and nymphs of Gomphus sp. (dragon fly) belonging to the order Diptera , Hemiptera and Odonata, respectively. Quantitatively Notonectus sp. predominated and followed by Chironomus larvae. The maximum concentrations of all heavy metals were recorded at spot 3. A general trend of increase was observed from up stream to down stream regions particularly in the level of zinc. However, a reverse trend was observed in the abundance of macro-invertebrates with a great reduction at spot 4. The statistical analysis of the data generally indicates a negative correlation between the values of the studied heavy metals and the abundance of macro-invertebrates throughout this study. (author)

  16. [A global view of population health in Colombia: role of social macro-determinants].

    Science.gov (United States)

    Idrovo, Alvaro J; Ruiz-Rodríguez, Myriam

    2007-09-01

    The social environment is an important determinant of population and individual health. However, its impact is often not considered in national health policies and generally its attributes are considered as constants. For this reason, contemporary health policies place greater emphasis on individual risk factors. Colombias position in the world ranking is described with respect to several social macro-determinants of health, previously characterized as components of class/welfare regime model. The exploratory study included all countries with comparable data including the following: (1) economic development [gross domestic product per capita adjusted for purchasing power parity], (2) income inequality [Gini coefficient], (3) social capital corruption perceptions index and generalized trust, and (4) political regime index of freedom. First, correlations between these macro-determinants were estimated, and second, the relationship between them and life expectancy at birth was explored. Finally, the position of Colombia in global context was determined. Important correlations occurred among the macro-determinants. Colombia tended to have intermediate to low positions in the global context in all macro-determinants, with the exception of gross domestic product per capita adjusted for purchasing power parity. The macro-determinant of population health with the highest potential of effecting improvement in health conditions is to modify income inequality.

  17. Development of Hollow Steel Ball Macro-Encapsulated PCM for Thermal Energy Storage Concrete

    Directory of Open Access Journals (Sweden)

    Zhijun Dong

    2016-01-01

    Full Text Available The application of thermal energy storage with phase change materials (PCMs for energy efficiency of buildings grew rapidly in the last few years. In this research, octadecane paraffin was served as a PCM, and a structural concrete with the function of indoor temperature control was developed by using a macro-encapsulated PCM hollow steel ball (HSB. The macro-encapsulated PCM-HSB was prepared by incorporation of octadecane into HSBs through vacuum impregnation. Test results showed that the maximum percentage of octadecane carried by HSBs was 80.3% by mass. The macro-encapsulated PCM-HSB has a latent heat storage capacity as high as 200.5 J/g. The compressive strength of concrete with macro-encapsulated PCM-HSB at 28 days ranged from 22 to 40 MPa. The indoor thermal performance test revealed that concrete with macro-encapsulated octadecane-HSB was capable of reducing the peak indoor air temperature and the fluctuation of indoor temperature. It can be very effective in transferring the heating and cooling loads away from the peak demand times.

  18. MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.

    Science.gov (United States)

    Posavec Marjanović, Melanija; Hurtado-Bagès, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Hélène; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M; Ahel, Ivan; Ladurner, Andreas G; Yanes, Oscar; Bouvet, Philippe; Suelves, Mònica; Teperino, Raffaele; Pospisilik, J Andrew; Buschbeck, Marcus

    2017-11-01

    Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD + -derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD + consumption. The resultant accumulation of the NAD + precursor NMN allows for maintenance of mitochondrial NAD + pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD + consumption and establishing a buffer of NAD + precursors in differentiated cells.

  19. Expression, purification and crystallization of the SARS-CoV macro domain

    International Nuclear Information System (INIS)

    Malet, Hélène; Dalle, Karen; Brémond, Nicolas; Tocque, Fabienne; Blangy, Stéphanie; Campanacci, Valérie; Coutard, Bruno; Grisel, Sacha; Lichière, Julie; Lantez, Violaine; Cambillau, Christian; Canard, Bruno; Egloff, Marie-Pierre

    2006-01-01

    The SARS-CoV macro domain was expressed, purified and crystallized. Selenomethionine-labelled crystals diffracted to 1.8 Å resolution. Macro domains or X domains are found as modules of multidomain proteins, but can also constitute a protein on their own. Recently, biochemical and structural studies of cellular macro domains have been performed, showing that they are active as ADP-ribose-1′′-phosphatases. Macro domains are also present in a number of positive-stranded RNA viruses, but their precise function in viral replication is still unknown. The major human pathogen severe acute respiratory syndrome coronavirus (SARS-CoV) encodes 16 non-structural proteins (nsps), one of which (nsp3) encompasses a macro domain. The SARS-CoV nsp3 gene region corresponding to amino acids 182–355 has been cloned, expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P2 1 , with unit-cell parameters a = 37.5, b = 55.6, c = 108.9 Å, β = 91.4°, and the asymmetric unit contains either two or three molecules. Both native and selenomethionine-labelled crystals diffract to 1.8 Å

  20. Healthy public policy in poor countries: tackling macro-economic policies.

    Science.gov (United States)

    Mohindra, K S

    2007-06-01

    Large segments of the population in poor countries continue to suffer from a high level of unmet health needs, requiring macro-level, broad-based interventions. Healthy public policy, a key health promotion strategy, aims to put health on the agenda of policy makers across sectors and levels of government. Macro-economic policy in developing countries has thus far not adequately captured the attention of health promotion researchers. This paper argues that healthy public policy should not only be an objective in rich countries, but also in poor countries. This paper takes up this issue by reviewing the main macro-economic aid programs offered by international financial institutions as a response to economic crises and unmanageable debt burdens. Although health promotion researchers were largely absent during a key debate on structural adjustment programs and health during the 1980s and 1990s, the international macro-economic policy tool currently in play offers a new opportunity to participate in assessing these policies, ensuring new forms of macro-economic policy interventions do not simply reproduce patterns of (neoliberal) economics-dominated development policy.