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Sample records for bcr sequential extraction

  1. Assessment of the BCR sequential extraction procedure for thallium fractionation using synthetic mineral mixtures

    Czech Academy of Sciences Publication Activity Database

    Vaněk, A.; Grygar, Tomáš; Chrastný, V.; Tejnecký, V.; Drahota, Petr; Komárek, M.

    2010-01-01

    Roč. 176, 1-3 (2010), s. 913-918 ISSN 0304-3894 Institutional research plan: CEZ:AV0Z4032918; CEZ:AV0Z30130516 Keywords : Metal * Sequential extraction * Goethite * Ferrihydrite * Birnessite * Illite Subject RIV: DD - Geochemistry Impact factor: 3.723, year: 2010

  2. Voltammetric behaviour at gold electrodes immersed in the BCR sequential extraction scheme media Application of underpotential deposition-stripping voltammetry to determination of copper in soil extracts

    Energy Technology Data Exchange (ETDEWEB)

    Beni, Valerio; Newton, Hazel V.; Arrigan, Damien W.M.; Hill, Martin; Lane, William A.; Mathewson, Alan

    2004-01-30

    The development of mercury-free electroanalytical systems for in-field analysis of pollutants requires a foundation on the electrochemical behaviour of the chosen electrode material in the target sample matrices. In this work, the behaviour of gold working electrodes in the media employed in the BCR sequential extraction protocol, for the fractionation of metals in solid environmental matrices, is reported. All three of the BCR sequential extraction media are redox active, on the basis of acidity and oxygen content as well as the inherent reducing or oxidising nature of some of the reagents employed: 0.11 M acetic acid, 0.1 M hydroxylammonium chloride (adjusted to pH 2) and 1 M ammonium acetate (adjusted to pH 2) with added trace hydrogen peroxide. The available potential ranges together with the demonstrated detection of target metals in these media are presented. Stripping voltammetry of copper or lead in the BCR extract media solutions reveal a multi-peak behaviour due to the stripping of both bulk metal and underpotential metal deposits. A procedure based on underpotential deposition-stripping voltammetry (UPD-SV) was evaluated for application to determination of copper in 0.11 M acetic acid soil extracts. A preliminary screening step in which different deposition times are applied to the sample enables a deposition time commensurate with UPD-SV to be selected so that no bulk deposition or stripping occurs thus simplifying the shape and features of the resulting voltammograms. Choice of the suitable deposition time is then followed by standards addition calibration. The method was validated by the analysis of a number of BCR 0.11 M acetic acid soil extracts. Good agreement was obtained been the UPD-SV method and atomic spectroscopic results.

  3. Speciation of heavy metals in street dust samples from Sakarya I. Organized industrial district using the BCR sequential extraction procedure by ICP-OES

    Directory of Open Access Journals (Sweden)

    N. Ozcan

    2013-05-01

    Full Text Available This paper focuses on the concentrations of heavy metals (Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn in 20 dust samples collected from the streets of the Organized Industrial District in Sakarya, Turkey using sequential extraction procedure were determined by ICP-OES. The three-step BCR sequential extraction procedure was used in order to evaluate mobility, availability and persistence of heavy elements in street dust samples. Three operationally defined fractions isolated using the BCR procedure was: acid extractable, reducible, and oxidizable. The mobility sequence based on the sum of the BCR sequential extraction stages: Cd (82.3% > Mn (80.0% > Zn (78.8% > Cu (70.2% > Ni (65.9% > Pb (63.8% > Cr (47.3% > Co (32.6%. Validation of the analytical results was checked by analysis of the BCR-701 certified reference material. The concentrations of metals in the street dust samples have been shown a decrease after the each extraction stage.

  4. Arsenic Mobility and Availability in Sediments by Application of BCR Sequential Extractions Method

    International Nuclear Information System (INIS)

    Larios, R.; Fernandez, R.; Rucandio, M. I.

    2011-01-01

    Arsenic is a metalloid found in nature, both naturally and due to anthropogenic activities. Among them, mining works are an important source of arsenic release to the environment. Asturias is a region where important mercury mines were exploited, and in them arsenic occurs in para genesis with mercury minerals. The toxicity and mobility of this element depends on the chemical species it is found. Fractionation studies are required to analyze the mobility of this metalloid in soils and sediments. Among them, the proposed by the Bureau Community of Reference (BCR) is one of the most employed. This method attempts to divide up, by operationally defined stages, the amount of this element associated with carbonates (fraction 1), iron and manganese oxy hydroxides (fraction 2), organic matter and sulphides (fraction 3), and finally as the amount associated residual fraction to primary and secondary minerals, that is, from the most labile fractions to the most refractory ones. Fractionation of arsenic in sediments from two mines in Asturias were studied, La Soterrana and Los Rueldos. Sediments from La Soterrana showed high levels of arsenic in the non-residual phases, indicating that the majority of arsenic has an anthropogenic origin. By contrast, in sediments from Los Rueldos most of the arsenic is concentrated in the residual phase, indicating that this element remains bound to very refractory primary minerals, as is also demonstrated by the strong correlation of arsenic fractionation and the fractionation of elements present in refractory minerals, such as iron, aluminum and titanium. (Author) 51 refs.

  5. Fractionation of metals in street sediment samples by using the BCR sequential extraction procedure and multivariate statistical elucidation of the data

    International Nuclear Information System (INIS)

    Kartal, Senol; Aydin, Zeki; Tokalioglu, Serife

    2006-01-01

    The concentrations of metals (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, and Zn) in street sediment samples were determined by flame atomic absorption spectrometry (FAAS) using the modified BCR (the European Community Bureau of Reference) sequential extraction procedure. According to the BCR protocol for extracting the metals from the relevant target phases, 1.0 g of specimen of the sample was treated with 0.11 M acetic acid (exchangeable and bound to carbonates), 0.5 M hydroxylamine hydrochloride (bound to iron- and manganese-oxides), and 8.8 M hydrogen peroxide plus 1 M ammonium acetate (bound to sulphides and organics), sequentially. The residue was treated with aqua regia solution for recovery studies, although this step is not part of the BCR procedure. The mobility sequence based on the sum of the BCR sequential extraction stages was: Cd ∼ Zn (∼90%) > Pb (∼84%) > Cu (∼75%) > Mn (∼70%) > Co (∼57%) > Ni (∼43%) > Cr (∼40%) > Fe (∼17%). Enrichment factors as the criteria for examining the impact of the anthropogenic emission sources of heavy metals were calculated, and it was observed that the highest enriched elements were Cd, Pb, and Zn in the dust samples, average 190, 111, and 20, respectively. Correlation analysis (CA) and principal component analysis (PCA) were applied to the data matrix to evaluate the analytical results and to identify the possible pollution sources of metals. PCA revealed that the sampling area was mainly influenced from three pollution sources, namely; traffic, industrial, and natural sources. The results show that chemical sequential extraction is a precious operational tool. Validation of the analytical results was checked by both recovery studies and analysis of the standard reference material (NIST SRM 2711 Montana Soil)

  6. Use of the modified BCR three-step sequential extraction procedure for the study of trace element dynamics in contaminated soils

    International Nuclear Information System (INIS)

    Pueyo, M.; Mateu, J.; Rigol, A.; Vidal, M.; Lopez-Sanchez, J.F.; Rauret, G.

    2008-01-01

    The modified BCR three-step sequential extraction procedure was used to examine the temporal dynamics of trace elements in soils contaminated by an accidental spill from an opencast mine in south-west Spain. Soils were mainly contaminated with pyritic sludge and acidic wastewater, whereas some soils were affected only by acidic wastewater. The distributions obtained for both some major (Ca, Fe and Mn) and trace elements (As, Cd, Cu, Pb and Zn) in the sludge and soil samples taken at different times after the accident, 1-3 months and 21 months, were compared. Sequential extractions were useful in identifying different sources of contamination, and in obtaining additional information on the solubility of secondary minerals formed by pyrite oxidation. Thus, the effectiveness of the BCR procedure has proved to be a useful tool for predicting short- and long-term mobility of trace elements, even in complex environmental scenarios. - The modified BCR three-step sequential extraction procedure has proved a useful prediction tool for short- and long-term mobility of trace elements in contaminated soils

  7. Use of the modified BCR three-step sequential extraction procedure for the study of trace element dynamics in contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Pueyo, M.; Mateu, J.; Rigol, A.; Vidal, M. [Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques 1-11, E-08028 Barcelona (Spain); Lopez-Sanchez, J.F. [Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques 1-11, E-08028 Barcelona (Spain)], E-mail: fermin.lopez@ub.edu; Rauret, G. [Departament de Quimica Analitica, Universitat de Barcelona, Marti i Franques 1-11, E-08028 Barcelona (Spain)

    2008-03-15

    The modified BCR three-step sequential extraction procedure was used to examine the temporal dynamics of trace elements in soils contaminated by an accidental spill from an opencast mine in south-west Spain. Soils were mainly contaminated with pyritic sludge and acidic wastewater, whereas some soils were affected only by acidic wastewater. The distributions obtained for both some major (Ca, Fe and Mn) and trace elements (As, Cd, Cu, Pb and Zn) in the sludge and soil samples taken at different times after the accident, 1-3 months and 21 months, were compared. Sequential extractions were useful in identifying different sources of contamination, and in obtaining additional information on the solubility of secondary minerals formed by pyrite oxidation. Thus, the effectiveness of the BCR procedure has proved to be a useful tool for predicting short- and long-term mobility of trace elements, even in complex environmental scenarios. - The modified BCR three-step sequential extraction procedure has proved a useful prediction tool for short- and long-term mobility of trace elements in contaminated soils.

  8. Chemometric evaluation for the relation of BCR sequential extraction method and in vitro gastro-intestinal method for the assessment of metal bioavailability in contaminated soils in Turkey.

    Science.gov (United States)

    Karadaş, Cennet; Kara, Derya

    2012-05-01

    A chemometric evaluation has been done to classify metal ions in soils and to determine whether or not the gastric and intestinal phases of a physiologically based extraction test bear any relation to any of the phases of the four-stage Community Bureau of Reference (BCR) extraction protocol. Nine trace analytes (As, Ba, Cd, Cr, Cu, Mn, Ni, Pb and Zn) were determined in extracts obtained from the BCR sequential extraction procedure as well as from in vitro gastro-intestinal experiments. The results showed that high As, Pb, Zn and Cd concentrations were found in these soils. Principal component analysis (PCA) and linear discriminant analysis were used as classification techniques. Stepwise multiple linear regression analysis was applied to the data set to determine how the bioaccessibility of a metal is linked to the operationally defined fractions of metal speciation in soil. This analysis showed that the metal concentrations in the intestinal and gastric extracts are mainly dependent on the concentrations found in BCR phases 1 and 2 for each metal ion except for Cr, which was mainly dependent on the concentrations found in BCR phase 3. From the chemometric technique of correlation analysis, it was concluded that the metals extracted using BCR phases 1 and 2 are more likely to be bioaccessible, i.e. are also extracted by gastric and intestinal digestion solutions. When the correlation and PCA results were interpreted together, it indicated that the bioaccessiblity of Zn, Pb, Mn and Cd were higher than As, Ba, Cr, Ni and Cu for these soils.

  9. Fractionation And Environmental Risk Of Trace Metals In Surface Sediment Of The East China Sea By Modified BCR Sequential Extraction Method

    Directory of Open Access Journals (Sweden)

    Roy Andreas

    2016-05-01

    Full Text Available Geochemical fractionation of Cadmium (Cd, Lead (Pb, Cobalt (Co, Zink (Zn, Iron (Fe and Manganese (Mn in sediment of the East China Sea were determined using four-stages of modified BCR sequential extraction method combination with ICP-MS. The total concentration of trace metals in sediment samples were in the following order: Fe >Mn>Pb> Zn > Co > Cd. Cd is present mainly in acid soluble fraction. Pb and Mn are in the group with presenting of easy reducible fraction and acid soluble fraction. Fe and Co were found in a group with mainly in residual fraction, while Zn was distributed in all four fractions. The highest contamination factors were found for Cd and Mn while the lowest were found for Fe and Co in almost station. The result showed low risk for Fe and Co in all station, Pb (except S2 and S3, Zn at S3,S6 and S7, and Mn at S1. A medium risk is indicated for Pb at S2 and S3, Zn at S1 and S5, and Mn at S2 and S6. A high risk showed for Zn at S2 and S4, and Mn at S4 and S5, while Cd at almost station (except S4 was very high risk.

  10. Speciation of heavy metals Cu, Ni and Zn by modified BCR sequential extraction procedure in sediments from Banten Bay, Banten Province, Indonesia

    Science.gov (United States)

    Lestari; Budiyanto, F.; Hindarti, D.

    2018-02-01

    Banten Bay is categorized as a marine area that is busy with marine tourism activities, settlements and also industries. One potential impact of the condition is the occurrence of pollution from both industrial and domestic sources, erosion and sedimentation in the coastal environment. Samples were collected from 25 representative stations in April 2016. Chemical speciation of three heavy metals (Cu, Ni, and Zn) was studied using a modified sequential extraction procedure proposed by the European Standard, Measurements and Testing (SM&T) program, formerly the Community Bureau of Reference (BCR). The aims of this study are to determine geochemical speciation of 4 bounds of metal: acid-soluble, reducible, oxidizable and residual, and to assess their impacts in the sediments of Banten Bay, Indonesia. The result shows that the percentage of Copper (45.90-83.75%), Nickel (18.28-65.66%), and Zinc (30.45-79.51%) were mostly accumulated in residual fraction of the total concentrations. The Risk Assessment Code (RAC) reveals that about 0-7.07% of Copper and 1.11-24.35 % of Zinc at sites exist in exchangeable fraction and therefore, they are in low risk category. While 7.34-34.90 of Ni at sites exists in exchangeable fraction and therefore, it is in medium risk category to aquatic environment.

  11. Multivariate Analyses and Evaluation of Heavy Metals by Chemometric BCR Sequential Extraction Method in Surface Sediments from Lingdingyang Bay, South China

    Directory of Open Access Journals (Sweden)

    Linglong Cao

    2015-04-01

    Full Text Available Sediments in estuary areas are recognized as the ultimate reservoirs for numerous contaminants, e.g., toxic metals. Multivariate analyses by chemometric evaluation were performed to classify metal ions (Cu, Zn, As, Cr, Pb, Ni and Cd in superficial sediments from Lingdingyang Bay and to determine whether or not there were potential contamination risks based on the BCR sequential extraction scheme. The results revealed that Cd was mainly in acid-soluble form with an average of 75.99% of its total contents and thus of high potential availability, indicating significant anthropogenic sources, while Cr, As, Ni were enriched in the residual fraction which could be considered as the safest ingredients to the environment. According to the proportion of secondary to primary phases (KRSP, Cd had the highest bioavailable fraction and represented high or very high risk, followed by Pb and Cu with medium risks in most of samples. The combined evaluation of the Pollution Load Index (PLI and the mean Effect Range Median Quotient (mERM-Q highlighted that the greatest potential environmental risk area was in the northwest of Lingdingyang Bay. Almost all of the sediments had a 21% probability of toxicity. Additionally, Principal Component Analysis (PCA revealed that the survey region was significantly affected by two main sources of anthropogenic contributions: PC1 showed increased loadings of variables in acid-soluble and reducible fractions that were consistent with the input from industrial wastes (such as manufacturing, metallurgy, chemical industry and domestic sewages; PC2 was characterized by increased loadings of variables in residual fraction that could be attributed to leaching and weathering of parent rocks. The results obtained demonstrated the need for appropriate remediation measures to alleviate soil pollution problem due to the more aggregation of potentially risky metals. Therefore, it is of crucial significance to implement the targeted

  12. Application of a modified BCR sequential extraction (three-step) procedure for the determination of extractable trace metal contents in a sewage sludge amended soil reference material (CRM 483), complemented by a three-year stability study of acetic acid and EDTA extractable metal content.

    Science.gov (United States)

    Rauret, G; López-Sánchez, J F; Sahuquillo, A; Barahona, E; Lachica, M; Ure, A M; Davidson, C M; Gomez, A; Lück, D; Bacon, J; Yli-Halla, M; Muntau, H; Quevauviller, P

    2000-06-01

    This paper provides additional data on a sewage sludge amended soil certified reference material, CRM 483, which was certified in 1997 for its EDTA and acetic acid extractable contents of some trace metals, following standardised extraction procedures. The additional work aimed to test the long-term stability of the material and the applicability of an improved version of the BCR three-step sequential extraction procedure on the sewage sludge amended soil (CRM 483). The paper demonstrates the CRM 483 long-term stability for EDTA and acetic acid extractable contents of Cd, Cr, Cu, Ni, Pb and Zn and gives the results (obtained in the framework of an interlaboratory study) for the extractable contents of the same elements in the CRM 483, following the BCR three-step sequential extraction scheme. The aqua regia extractable contents following the ISO 11466 Standard are also given. The data are given as indicative (not certified) values.

  13. Arsenic Mobility and Availability in Sediments by Application of BCR Sequential Extractions Method; Movilidad y Disponibilidad de Arsenico en Sedimentos Mediante la Aplicacion del Metodo de Extracciones Secuenciales BCR

    Energy Technology Data Exchange (ETDEWEB)

    Larios, R.; Fernandez, R.; Rucandio, M. I.

    2011-05-13

    Arsenic is a metalloid found in nature, both naturally and due to anthropogenic activities. Among them, mining works are an important source of arsenic release to the environment. Asturias is a region where important mercury mines were exploited, and in them arsenic occurs in para genesis with mercury minerals. The toxicity and mobility of this element depends on the chemical species it is found. Fractionation studies are required to analyze the mobility of this metalloid in soils and sediments. Among them, the proposed by the Bureau Community of Reference (BCR) is one of the most employed. This method attempts to divide up, by operationally defined stages, the amount of this element associated with carbonates (fraction 1), iron and manganese oxy hydroxides (fraction 2), organic matter and sulphides (fraction 3), and finally as the amount associated residual fraction to primary and secondary minerals, that is, from the most labile fractions to the most refractory ones. Fractionation of arsenic in sediments from two mines in Asturias were studied, La Soterrana and Los Rueldos. Sediments from La Soterrana showed high levels of arsenic in the non-residual phases, indicating that the majority of arsenic has an anthropogenic origin. By contrast, in sediments from Los Rueldos most of the arsenic is concentrated in the residual phase, indicating that this element remains bound to very refractory primary minerals, as is also demonstrated by the strong correlation of arsenic fractionation and the fractionation of elements present in refractory minerals, such as iron, aluminum and titanium. (Author) 51 refs.

  14. Investigations of Cu, Pb and Zn partitioning by sequential extraction in harbour sediments after electrodialytic remediation

    DEFF Research Database (Denmark)

    Kirkelund, Gunvor Marie; Ottosen, Lisbeth M.; Villumsen, Arne

    2010-01-01

    remediation time. A three step sequential extraction scheme (BCR), with an extra residual step, was used to evaluate the heavy metal distribution in the sediments before and after electrodialytic remediation. Cu was mainly associated with the oxidisable phase of the sediment, both before and after remediation...

  15. Speciation of heavy metals in untreated sewage sludge by using microwave assisted sequential extraction procedure.

    Science.gov (United States)

    Jamali, Muhammad K; Kazi, Tasneem G; Arain, Muhammad B; Afridi, Hassan I; Jalbani, Nusrat; Kandhro, Ghulam A; Shah, Abdul Q; Baig, Jameel A

    2009-04-30

    A fast microwave assisted extraction procedure was developed and optimized for their eventual exploitation in the three-stage sequential extraction procedure proposed by modified BCR protocol (the community Bureau of Reference now the European Union "Measurement and Testing Programme"). The effects of the microwave treatment on the extraction of Cd, Cr, Cu, Ni, Pb and Zn from untreated sewage sludge collected from Hyderabad city (Pakistan) were compared with those obtained from sequential BCR extraction procedure. In sequential BCR method, each extraction step takes 16 h, where as with the use of compromised microwave conditions, extraction steps could be completed in about 120 s, for each step, respectively. Extractable Cd, Cr, Pb and Ni obtained by both comparable methodologies were measured by electrothermal atomic absorption spectrometry (ETAAS), while for Cu and Zn flame atomic absorption spectrometry (FAAS) was used. The validations of both extraction techniques were compared by the analysis of certified reference material of soil amended with sewage sludge (BCR 483). The results of the partitioning study of untreated waste water sewage sludge, indicate that more easily mobilized forms (step 1) were predominant for Cd, Ni and Zn (28.3, 28.4 and 43.7%), in contrast, the largest amount of Cd and Pb (66.4 and 72.8%) was associated with the iron/manganese oxide while Cr and Ni (71.2 and 38.7%) in organic matter/sulphide fractions. The overall metal recoveries in steps 1-3 (excluding residual step) were 95.3-104% of those obtained with the sequential BCR protocol. The accuracy of the proposed microwave extraction method (expressed as %R.S.D.) was lower than 10% for all metals.

  16. Comparison of three sequential extraction protocols for the fractionation of potentially toxic metals in coastal sediments.

    Science.gov (United States)

    Oyeyiola, Aderonke Oluwabukola; Olayinka, Kehinde O; Alo, Babajide I

    2011-01-01

    In the determination of the best sequential extraction procedures (SEP) for the speciation of metals in sediment samples from the Lagos lagoon system, three sequential extraction procedures were compared for the fractionation of Cd, Cr, Cu, Pb, and Zn. The SEP compared included a modified Tessier's procedure carried out in five steps, while the two other procedures were the three-step original Community Bureau of Reference (BCR) and the modified BCR techniques (four steps). Quantification of the metal concentration was achieved with a flame atomic absorption spectrophotometer. The results obtained by the three methods were compared, and the modified BCR and Tessier SEP were found to extract more Cu, Cr, Pb, and Zn in the reducible phase and therefore a decrease in the oxidizable phase than the original BCR SEP. The most mobile elements were found to be Cd, Pb, and Zn. These are of environmental concern, as these potentially toxic metals could be easily released into the aquatic environment with consequent ingestion by aquatic organisms, thereby entering the food chain. The mass balance (percent recovery) was found to be between 85% and 115% in most cases. Prior to the comparison, the analytical performance of the laboratory was tested using a secondary reference material, GLAURM, using the three-step modified BCR procedure. The results showed high reliability of the analytical performance of the laboratory for all the metals considered.

  17. Effect of Thai saraphi flower extracts on WT1 and BCR/ABL protein ...

    African Journals Online (AJOL)

    In this study, the cytotoxic effects of crude ethanolic and fractional extracts including hexane, ethyl acetate, and methanol fractions from M. siamensis flowers were investigated in order to determine their effect on WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. Materials and Methods: The ...

  18. Sequential injection system incorporating a micro extraction column for automatic fractionation of metal ions in solid samples

    DEFF Research Database (Denmark)

    Chomchoei, Roongrat; Miró, Manuel; Hansen, Elo Harald

    2005-01-01

    to conventional batch methods, this fully automated approach furthermore offers the potentials of a variety of operational extraction protocols. Employing the three-step sequential extraction BCR scheme to a certified homogeneous soil reference material (NIST, SRM 2710), this communication investigates four...

  19. Sequential extraction applied to Peruibe black mud, SP, Brazil

    International Nuclear Information System (INIS)

    Torrecilha, Jefferson Koyaishi

    2014-01-01

    The Peruibe Black mud is used in therapeutic treatments such as psoriasis, peripheral dermatitis, acne and seborrhoea, as well as in the treatment of myalgia, arthritis, rheumatism and non-articular processes. Likewise other medicinal clays, it may not be free from possible adverse health effects due to possible hazardous minerals leading to respiratory system occurrences and other effects, caused by the presence of toxic elements. Once used for therapeutic purposes, any given material should be fully characterized and thus samples of Peruibe black mud were analyzed to determine physical and chemical properties: moisture content, organic matter and loss on ignition; pH, particle size, cation exchange capacity and swelling index. The elemental composition was determined by Neutron Activation Analysis, Atomic Absorption Graphite Furnace and X-ray fluorescence; the mineralogical composition was determined by X-ray diffraction. Another tool widely used to evaluate the behavior of trace elements, in various environmental matrices, is the sequential extraction. Thus, a sequential extraction procedure was applied to fractionate the mud in specific geochemical forms and verify how and how much of the elements may be contained in it. Considering the several sequential extraction procedures, BCR-701 method (Community Bureau of Reference) was used since it is considered the most reproducible among them. A simple extraction with an artificial sweat was, also, applied in order to verify which components are potentially available for absorption by the patient skin during the topical treatment. The results indicated that the mud is basically composed by a silty-clay material, rich in organic matter and with good cation exchange capacity. There were no significant variations in mineralogy and elemental composition of both, in natura and mature mud forms. The analysis by sequential extraction and by simple extraction indicated that the elements possibly available in larger

  20. Evaluation of uranium and arsenic retention by soil from a low level radioactive waste management site using sequential extraction

    International Nuclear Information System (INIS)

    Evans, G.J.; Dhoum, R.T.

    1998-01-01

    The European Communities Bureau of Reference (BCR) and Chunguo sequential extraction procedures were employed to evaluate the retention of U and As by a soil contaminated with low level radioactive waste. Modifications were made to both procedures to optimize the measurement of soil and extractant samples using epithermal neutron activation analysis. Based on the BCR procedure, approximately 20% of the U appeared to be bound to the carbonate fraction, 10% to the mineral oxide fraction and 20% to the organic fraction. In the case of As, the majority was strongly bound in the residue fraction. The results obtained with the Chunguo procedure supported these conclusions to some extent, in that the majority of the U and As was found to be strongly bound to the soil in a manner consistent with its presence in the residue fraction. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  1. Comparison of sequential and single extraction in order to estimate environmental impact of metals from fly ash

    Directory of Open Access Journals (Sweden)

    Tasić Aleksandra M.

    2016-01-01

    Full Text Available The aim of this paper was to simulate leaching of metals from fly ash in different environmental conditions using ultrasound and microwave-assisted extraction techniques. Single-agent extraction and sequential extraction procedures were used to determine the levels of different metals leaching. The concentration of metals (Al, Fe, Mn, Cd, Co, Cr, Ni, Pb, Cu, As, Be in fly ash extracts were measured by Inductively Coupled Plasma-Atomic Emission Spectrometry. Single-agent extractions of metals were conducted during sonication times of 10, 20, 30, 40 and 50 min. Single-agent extraction with deionized water was also undertaken by exposing samples to microwave radiation at the temperature of 50°C. The sequential extraction was undertaken according to the BCR procedure which was modified and applied to study the partitioning of metals in coal fly ash. The microwave-assisted sequential extraction was performed at different extraction temperatures: 50, 100 and 150°C. The partitioning of metals between the individual fractions was investigated and discussed. The efficiency of the extraction process for each step was examined. In addition, the results of the microwave-assisted sequential extraction are compared to the results obtained by standard ASTM method. The mobility of most elements contained in fly ash is markedly pH sensitive. [Projekat Ministarstva nauke Republike Srbije, br. 172030, br. 176006 i br. III43009

  2. Comparison of three-stage sequential extraction and toxicity characteristic leaching tests to evaluate metal mobility in mining wastes

    International Nuclear Information System (INIS)

    Margui, E.; Salvado, V.; Queralt, I.; Hidalgo, M.

    2004-01-01

    Abandoned mining sites contain residues from ore processing operations that are characterised by high concentrations of heavy metals. The form in which a metal exists strongly influences its mobility and, thus, the effects on the environment. Operational methods of speciation analysis, such as the use of sequential extraction procedures, are commonly applied. In this work, the modified three-stage sequential extraction procedure proposed by the BCR (now the Standards, Measurements and Testing Programme) was applied for the fractionation of Ni, Zn, Pb and Cd in mining wastes from old Pb-Zn mining areas located in the Val d'Aran (NE Spain) and Cartagena (SE Spain). Analyses of the extracts were performed by inductively coupled plasma atomic emission spectrometry and electrothermal atomic absorption spectrometry. The procedure was evaluated by using a certified reference material, BCR-701. The results of the partitioning study indicate that more easily mobilised forms (acid exchangeable) were predominant for Cd and Zn, particularly in the sample from Cartagena. In contrast, the largest amount of lead was associated with the iron and manganese oxide fractions. On the other hand, the applicability of lixiviation tests commonly used to evaluate the leaching of toxic species from landfill disposal (US-EPA Toxicity Characteristic Leaching Procedure and DIN 38414-S4) to mining wastes was also investigated and the obtained results compared with the information on metal mobility derivable from the application of the three-stage sequential extraction procedure

  3. Two approaches for sequential extraction of radionuclides in soils: batch and column methods

    International Nuclear Information System (INIS)

    Vidal, M.; Rauret, G.

    1993-01-01

    A three-step sequential extraction designed by Community Bureau of Reference (BCR) is applied to two types of soil (sandy and sandy-loam) which had been previously contaminated with a radionuclide aerosol containing 134 Cs, 85 Sr and 110m Ag. This scheme is applied using both batch and column methods. The radionuclide distribution obtained with this scheme depends both on the method and on soil type. Compared with the batch method, column extraction is an inadvisable method. Kinetic aspects seem to be important, especially in the first and third fractions. The radionuclide distribution shows that radiostrontium has high mobility, radiocaesium is highly retained by clay minerals whereas Fe/Mn oxides and organic matter have an important role in radiosilver retention. (Author)

  4. Arsenic fractionation in agricultural soil using an automated three-step sequential extraction method coupled to hydride generation-atomic fluorescence spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Rosas-Castor, J.M. [Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Químicas, Cd. Universitaria, San Nicolás de los Garza, Nuevo León, C.P. 66451 Nuevo León (Mexico); Group of Analytical Chemistry, Automation and Environment, University of Balearic Islands, Cra. Valldemossa km 7.5, 07122 Palma de Mallorca (Spain); Portugal, L.; Ferrer, L. [Group of Analytical Chemistry, Automation and Environment, University of Balearic Islands, Cra. Valldemossa km 7.5, 07122 Palma de Mallorca (Spain); Guzmán-Mar, J.L.; Hernández-Ramírez, A. [Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Químicas, Cd. Universitaria, San Nicolás de los Garza, Nuevo León, C.P. 66451 Nuevo León (Mexico); Cerdà, V. [Group of Analytical Chemistry, Automation and Environment, University of Balearic Islands, Cra. Valldemossa km 7.5, 07122 Palma de Mallorca (Spain); Hinojosa-Reyes, L., E-mail: laura.hinojosary@uanl.edu.mx [Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Químicas, Cd. Universitaria, San Nicolás de los Garza, Nuevo León, C.P. 66451 Nuevo León (Mexico)

    2015-05-18

    Highlights: • A fully automated flow-based modified-BCR extraction method was developed to evaluate the extractable As of soil. • The MSFIA–HG-AFS system included an UV photo-oxidation step for organic species degradation. • The accuracy and precision of the proposed method were found satisfactory. • The time analysis can be reduced up to eight times by using the proposed flow-based BCR method. • The labile As (F1 + F2) was <50% of total As in soil samples from As-contaminated-mining zones. - Abstract: A fully automated modified three-step BCR flow-through sequential extraction method was developed for the fractionation of the arsenic (As) content from agricultural soil based on a multi-syringe flow injection analysis (MSFIA) system coupled to hydride generation-atomic fluorescence spectrometry (HG-AFS). Critical parameters that affect the performance of the automated system were optimized by exploiting a multivariate approach using a Doehlert design. The validation of the flow-based modified-BCR method was carried out by comparison with the conventional BCR method. Thus, the total As content was determined in the following three fractions: fraction 1 (F1), the acid-soluble or interchangeable fraction; fraction 2 (F2), the reducible fraction; and fraction 3 (F3), the oxidizable fraction. The limits of detection (LOD) were 4.0, 3.4, and 23.6 μg L{sup −1} for F1, F2, and F3, respectively. A wide working concentration range was obtained for the analysis of each fraction, i.e., 0.013–0.800, 0.011–0.900 and 0.079–1.400 mg L{sup −1} for F1, F2, and F3, respectively. The precision of the automated MSFIA–HG-AFS system, expressed as the relative standard deviation (RSD), was evaluated for a 200 μg L{sup −1} As standard solution, and RSD values between 5 and 8% were achieved for the three BCR fractions. The new modified three-step BCR flow-based sequential extraction method was satisfactorily applied for arsenic fractionation in real agricultural

  5. Ranking and similarity of conventional, microwave and ultrasound element sequential extraction methods.

    Science.gov (United States)

    Relić, Dubravka; Héberger, Károly; Sakan, Sanja; Škrbić, Biljana; Popović, Aleksandar; Đorđević, Dragana

    2018-05-01

    This study aims to compare three extraction techniques of four sequential element extraction steps from soil and sediment samples that were taken from the location of the Pančevo petrochemical industry (Serbia). Elements were extracted using three different techniques: conventional, microwave and ultrasound extraction. A novel procedure - sum of the ranking differences (SRD) - was able to rank the techniques and elements, to see whether this method is a suitable tool to reveal the similarities and dissimilarities in element extraction techniques, provided that a proper ranking reference is available. The concentrations of the following elements Al, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Si, Sn, Sr, V and Zn were determined through ICP OES. The different efficiencies and recovery values of element concentrations using each of the three extraction techniques were examined by the CRM BCR-701. By using SRD, we obtained a better separation between the different extraction techniques and steps when we rank their differences among the samples while lower separation was obtained according to analysed elements. Appling this method for ordering the elements could be useful for three purposes: (i) to find possible associations among the elements; (ii) to find possible elements that have outlier concentrations or (iii) detect differences in geochemical origin or behaviour of elements. Cross-validation of the SRD values in combination with cluster and principal component analysis revealed the same groups of extraction steps and techniques. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Determination of heavy metals and their speciation in street dusts by inductively coupled plasma-optical emission spectrometry after a Community Bureau of Reference sequential extraction procedure.

    Science.gov (United States)

    Altundag, Huseyin; Imamoglu, Mustafa; Doganci, Secil; Baysal, Erkan; Albayrak, Sinem; Tuzen, Mustafa

    2013-01-01

    Sequential selective extraction techniques are commonly used to fractionate the solid-phase forms of metals in soils. This procedure provides measurements of extractable metals from media, such as acetic acid (0.11 M), hydroxyl ammonium chloride (0.1 M), hydrogen peroxide (8.8 M) plus ammonium acetate (1 M), and aqua regia stages of the sequential extraction procedure. In this work, the extractable Pb, Cu, Mn, Sr, Ni, V, Fe, Zn, and Cr were evaluated in street dust samples from Sakarya, Turkey, between May and October 2009 using the three-step sequential extraction procedure described by the Community Bureau of Reference (BCR, now the Standards, Measurements, and Testing Programme) of the European Union. The sampling sites were divided into 10 categories; a total of 50 street dusts were analyzed. The determination of multielements in the samples was performed by inductively coupled plasma-optical emission spectrometry. Validation of the proposed method was performed using BCR 701 certified reference material. The results showed good agreement between the obtained and the certified values for the metals analyzed.

  7. SEQUENTIAL ELECTRODIALYTIC EXTRACTION OF PHOSPHORUS COMPOUNDS

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention relates to an apparatus for electrodialytic extraction of phosphorus from a particulate material in suspension and to a method for electrodialytic phosphorus recovery, which uses the apparatus. The method may be applied for wastewater treatment, and/or treatment of particulate...... material rich in phosphorus. The present invention provides an apparatus for electrodialytic extraction of phosphorus from a particulate material comprising acidic and/or alkaline soluble phosphorus compounds, in suspension, comprising: • a first electrodialytic cell comprising a first anolyte compartment...

  8. Fractionation of potentially toxic elements in urban soils from five European cities by means of a harmonised sequential extraction procedure

    International Nuclear Information System (INIS)

    Davidson, Christine M.; Urquhart, Graham J.; Ajmone-Marsan, Franco; Biasioli, Mattia; Costa Duarte, Armando da; Diaz-Barrientos, Encarnacion; Grcman, Helena; Hossack, Iain; Hursthouse, Andrew S.; Madrid, Luis; Rodrigues, Sonia; Zupan, Marko

    2006-01-01

    The revised (four-step) BCR sequential extraction procedure has been applied to fractionate the chromium, copper, iron, manganese, nickel, lead and zinc contents in urban soil samples from public-access areas in five European cities. A preliminary inter-laboratory comparison was conducted and showed that data obtained by different laboratories participating in the study were sufficiently harmonious for comparisons to be made between cities and land types (e.g. parks, roadside, riverbanks, etc.). Analyte recoveries by sequential extraction, with respect to direct aqua regia digestion, were generally acceptable (100 ± 15%). Iron, nickel and, at most sites, chromium were found mainly in association with the residual phase of the soil matrix. Copper was present in the reducible, oxidisable and residual fractions, whilst zinc was found in all four sequential extracts. Manganese was strongly associated with reducible material as, in some cities, was lead. This is of concern because high lead concentrations were present in some soils (>500 mg kg -1 ) and the potential exists for remobilisation under reducing conditions. As would be expected, extractable metal contents were generally highest in older, more heavily industrialised cities. Copper, lead and zinc showed marked (and often correlated) variations in concentrations between sites within the same city whereas manganese and, especially, iron, did not. No overall relationships were, however, found between analyte concentrations and land use, nor between analyte partitioning and land use

  9. Sequential Dimensionality Reduction for Extracting Localized Features

    OpenAIRE

    Casalino, Gabriella; Gillis, Nicolas

    2015-01-01

    Linear dimensionality reduction techniques are powerful tools for image analysis as they allow the identification of important features in a data set. In particular, nonnegative matrix factorization (NMF) has become very popular as it is able to extract sparse, localized and easily interpretable features by imposing an additive combination of nonnegative basis elements. Nonnegative matrix underapproximation (NMU) is a closely related technique that has the advantage to identify features seque...

  10. Sequential extraction applied to Peruibe black mud, SP, Brazil; Extracao sequencial aplicada a lama negra de Peruibe

    Energy Technology Data Exchange (ETDEWEB)

    Torrecilha, Jefferson Koyaishi

    2014-07-01

    The Peruibe Black mud is used in therapeutic treatments such as psoriasis, peripheral dermatitis, acne and seborrhoea, as well as in the treatment of myalgia, arthritis, rheumatism and non-articular processes. Likewise other medicinal clays, it may not be free from possible adverse health effects due to possible hazardous minerals leading to respiratory system occurrences and other effects, caused by the presence of toxic elements. Once used for therapeutic purposes, any given material should be fully characterized and thus samples of Peruibe black mud were analyzed to determine physical and chemical properties: moisture content, organic matter and loss on ignition; pH, particle size, cation exchange capacity and swelling index. The elemental composition was determined by Neutron Activation Analysis, Atomic Absorption Graphite Furnace and X-ray fluorescence; the mineralogical composition was determined by X-ray diffraction. Another tool widely used to evaluate the behavior of trace elements, in various environmental matrices, is the sequential extraction. Thus, a sequential extraction procedure was applied to fractionate the mud in specific geochemical forms and verify how and how much of the elements may be contained in it. Considering the several sequential extraction procedures, BCR-701 method (Community Bureau of Reference) was used since it is considered the most reproducible among them. A simple extraction with an artificial sweat was, also, applied in order to verify which components are potentially available for absorption by the patient skin during the topical treatment. The results indicated that the mud is basically composed by a silty-clay material, rich in organic matter and with good cation exchange capacity. There were no significant variations in mineralogy and elemental composition of both, in natura and mature mud forms. The analysis by sequential extraction and by simple extraction indicated that the elements possibly available in larger

  11. Use of sequential extraction to assess metal partitioning in soils

    International Nuclear Information System (INIS)

    Kaasalainen, Marika; Yli-Halla, Markku

    2003-01-01

    The state of heavy metal pollution and the mobility of Cd, Cu, Ni, Cr, Pb and Zn were studied in three texturally different agricultural soil profiles near a Cu-Ni smelter in Harjavalta, Finland. The pseudo-total concentrations were determined by an aqua regia procedure. Metals were also determined after division into four fractions by sequential extraction with (1) acetic acid (exchangeable and specifically adsorbed metals), (2) a reducing agent (bound to Fe/Mn hydroxides), (3) an oxidizing agent (bound to soil organic matter) and (4) aqua regia (bound to mineral structures). Fallout from the smelter has increased the concentrations of Cd, Cu and Ni in the topsoil, where 75-90% of Cd, 49-72% of Cu and 22-52% of Ni occurred in the first two fractions. Slight Pb and Zn pollution was evident as well. High proportions of mobile Cd, Cu and Ni also deeper in the sandy soil, closest to the smelter, indicated some downward movement of metals. The hydroxide-bound fraction of Pb dominated in almost all soils and horizons, while Ni, Cr and Zn mostly occurred in mineral structures. Aqua regia extraction is usefully supplemented with sequential extraction, particularly in less polluted soils and in soils that exhibit substantial textural differences within the profiles. - Sequential extraction is most useful with soils with low metal pollutant levels

  12. Determination of Cd, Pb, Zn and Cu in Sediment Compartments by Sequential Extraction and Isotope Dilution Inductively Coupled Plasma Mass Spectrometry (ID-ICP-MS

    Directory of Open Access Journals (Sweden)

    Gardolinski Paulo C. F. C.

    2002-01-01

    Full Text Available Trace concentrations of Cd, Cu, Pb and Zn in four different sediment fractions extracted in sequence were determined by isotope dilution inductively coupled mass spectrometry (IDICPMS. The metals from each fraction were extracted following the sequential extraction procedure recommended by the Bureau Commun de Référence (BCR of the Commission of the European Communities. As an alternative to external calibration, the elements were quantified by spiking the extracted solutions with 112Cd, 63Cu, 208Pb and 66Zn and application of isotope dilution. The proposed approach was applied to a sample collected from a lake and two standard reference materials, NIST2704 river sediment from the National Institute of Standards & Technology and the BCR-277 estuarine sediment. Detection limits, for each extracted solution, varied from 0.31 to 0.53 mug L¹ for Cd, 0.92 to 2.9 mug L¹ for Cu, 0.22 to 1.1 mug L¹ for Pb and 1.3 to 7.6 mug L¹ for Zn. The sum of the metals concentration in the different fractions was compatible with 95% confidence level found amounts obtained with complete digestion of the samples and with the certified values of the standard reference materials.

  13. Phenolic Content and Antioxidant Activity of Hibiscus cannabinus L. Seed Extracts after Sequential Solvent Extraction

    Directory of Open Access Journals (Sweden)

    Shahid Iqbal

    2012-10-01

    Full Text Available A sequential solvent extraction scheme was employed for the extraction of antioxidant compounds from kenaf (Hibiscus cannabinus L. seeds. Yield of extracts varied widely among the solvents and was the highest for hexane extract (16.6% based on dry weight basis, while water extract exhibited the highest total phenolic content (18.78 mg GAE/g extract, total flavonoid content (2.49 mg RE/g extract, and antioxidant activities (p < 0.05. DPPH and hydroxyl radical scavenging, β-carotene bleaching, metal chelating activity, ferric thiocyanate and thiobarbituric acid reactive substances assays were employed to comprehensively assess the antioxidant potential of different solvent extracts prepared sequentially. Besides water, methanolic extract also exhibited high retardation towards the formation of hydroperoxides and thiobarbituric acid reactive substances in the total antioxidant activity tests (p < 0.05. As conclusion, water and methanol extracts of kenaf seed may potentially serve as new sources of antioxidants for food and nutraceutical applications.

  14. Metal fractionation of atmospheric aerosols via sequential chemical extraction: a review

    Energy Technology Data Exchange (ETDEWEB)

    Smichowski, Patricia; Gomez, Dario [Unidad de Actividad Quimica, Comision Nacional de Energia Atomica, San Martin (Argentina); Polla, Griselda [Unidad de Actividad Fisica, Comision Nacional de Energia Atomica, San Martin (Argentina)

    2005-01-01

    This review surveys schemes used to sequentially chemically fractionate metals and metalloids present in airborne particulate matter. It focuses mainly on sequential chemical fractionation schemes published over the last 15 years. These schemes have been classified into five main categories: (1) based on Tessier's procedure, (2) based on Chester's procedure, (3) based on Zatka's procedure, (4) based on BCR procedure, and (5) other procedures. The operational characteristics as well as the state of the art in metal fractionation of airborne particulate matter, fly ashes and workroom aerosols, in terms of applications, optimizations and innovations, are also described. Many references to other works in this area are provided. (orig.)

  15. Sequential extraction of heavy metals during composting of sewage sludge.

    Science.gov (United States)

    Amir, Soumia; Hafidi, Mohamed; Merlina, Georges; Revel, Jean-Claude

    2005-05-01

    The major limitation of soil application of sewage sludge compost is the total heavy metal contents and their bioavailability to the soil-plant system. This study was conducted to determine the heavy metal speciation and the influence of changing the physico-chemical properties of the medium in the course of composting on the concentrations, bioavailability or chemical forms of Cu, Zn, Pb and Ni in sewage sludge. Principal physical and chemical properties and FTIR spectroscopical characterization of sludge compost during treatment show the stability and maturity of end product. The total metal contents in the final compost were much lower than the limit values of composts to be used as good soil fertilizer. Furthermore, it was observed by using a sequential extraction procedure in sludge compost at different steps of treatment, that a large proportion of the heavy metals were associated to the residual fraction (70-80%) and more resistant fractions to extraction X-NaOH, X-EDTA, X-HNO3 (12-29%). Less than 2% of metals bound to bioavailable fractions X-(KNO3+H2O). Heavy metal distribution and bioavailability show some changes during composting depending on the metal itself and the physico-chemical properties of the medium. Bioavailable fractions of all elements tend to decrease except Ni-H2O. Zn and mainly Cu present more affinity to organic and carbonate fractions. In contrast, Pb is usually preferentially bound to sulfide forms X-HNO3. Nickel shows a significant decrease of organic form. Significant degrees of correlation were found between heavy metal fractions and changes of some selected variables (e.g. pH, ash, organic matter, humic substance) during the course of composting. Mobile fractions of metals are poorly predictable from the total content. The R2 value was significantly increased by the inclusion of other variables such as the amount of organic matter (OM) and pH.

  16. Evaluation of the mobility and pollution index of selected essential/toxic metals in paddy soil by sequential extraction method.

    Science.gov (United States)

    Hasan, Maria; Kausar, Dilshad; Akhter, Gulraiz; Shah, Munir H

    2018-01-01

    Comparative distribution and mobility of selected essential and toxic metals in the paddy soil from district Sargodha, Pakistan was evaluated by the modified Community Bureau of Reference (mBCR) sequential extraction procedure. Most of the soil samples showed slightly alkaline nature while the soil texture was predominantly silty loam in nature. The metal contents were quantified in the exchangeable, reducible, oxidisable and residual fractions of the soil by flame atomic absorption spectrophotometry and the metal data were subjected to the statistical analyses in order to evaluate the mutual relationships among the metals in each fraction. Among the metals, Ca, Sr and Mn were found to be more mobile in the soil. A number of significant correlations between different metal pairs were noted in various fractions. Contamination factor, geoaccumulation index and enrichment factor revealed extremely severe enrichment/contamination for Cd; moderate to significant enrichment/contamination for Ni, Zn, Co and Pb while Cr, Sr, Cu and Mn revealed minimal to moderate contamination and accumulation in the soil. Multivariate cluster analysis showed significant anthropogenic intrusions of the metals in various fractions. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Utilizing a sequential injection system furnished with an extraction microcolumn as a novel approach for executing sequential extractions of metal species in solid samples

    DEFF Research Database (Denmark)

    Chomchoei, R.; Hansen, Elo Harald; Shiowatana, J.

    2007-01-01

    This communication presents a novel approach to perform sequential extraction of elements in solid samples by using a sequential injection (SI) system incorporating a specially designed extraction microcolumn. Based on the operation of the syringe pump, different modes of extraction are potentially...... that the system entails many advantages such as being fully automated, and besides being characterised by rapidity, ease of operation and robustness, it is less prone to risks of contamination and personal errors as encountered in traditional batch systems. Moreover, improvement of the precision and accuracy...... of the chemical fractionation of metal in solids as compared with previous reports are obtained. The system ensures that extraction is performed at designated pH values. Variation of sample weight to column volume ratios do not affect the amounts of extractable metals, nor do extraction flow rates ranging from 50...

  18. Fractionation of plutonium in environmental and bio-shielding concrete samples using dynamic sequential extraction

    DEFF Research Database (Denmark)

    Qiao, Jixin; Hou, Xiaolin

    2010-01-01

    Fractionation of plutonium isotopes (238Pu, 239,240Pu) in environmental samples (i.e. soil and sediment) and bio-shielding concrete from decommissioning of nuclear reactor were carried out by dynamic sequential extraction using an on-line sequential injection (SI) system combined with a specially...... to the treatment and disposal of nuclear waste from decommissioning....

  19. Estimating the extractability of potentially toxic metals in urban soils: A comparison of several extracting solutions

    International Nuclear Information System (INIS)

    Madrid, F.; Reinoso, R.; Florido, M.C.; Diaz Barrientos, E.; Ajmone-Marsan, F.; Davidson, C.M.; Madrid, L.

    2007-01-01

    Metals released by the extraction with aqua regia, EDTA, dilute HCl and sequential extraction (SE) by the BCR protocol were studied in urban soils of Sevilla, Torino, and Glasgow. By multivariate analysis, the amounts of Cu, Pb and Zn liberated by any method were statistically associated with one another, whereas other metals were not. The mean amounts of all metals extracted by HCl and by SE were well correlated, but SE was clearly underestimated by HCl. Individual data for Cu, Pb and Zn by both methods were correlated only if each city was considered separately. Other metals gave poorer relationships. Similar conclusions were reached comparing EDTA and HCl, with much lower values for EDTA. Dilute HCl extraction cannot thus be recommended for general use as alternative to BCR SE in urban soils. - Dilute HCl extraction is tested as an alternative to the BCR sequential extraction in urban soils

  20. Estimating the extractability of potentially toxic metals in urban soils: A comparison of several extracting solutions

    Energy Technology Data Exchange (ETDEWEB)

    Madrid, F. [Instituto de Recursos Naturales y Agrobiologia de Sevilla (CSIC), Apartado 1052, 41080 Sevilla (Spain); Reinoso, R. [Instituto de Recursos Naturales y Agrobiologia de Sevilla (CSIC), Apartado 1052, 41080 Sevilla (Spain); Florido, M.C. [Departamento de Cristalografia, Mineralogia y Quimica Agricola, Universidad de Sevilla, Avda. Reina Mercedes, s/n, 41012 Sevilla (Spain); Diaz Barrientos, E. [Instituto de Recursos Naturales y Agrobiologia de Sevilla (CSIC), Apartado 1052, 41080 Sevilla (Spain); Ajmone-Marsan, F. [DI.VA.P.R.A., Chimica Agraria, Universita di Torino, Via Leonardo da Vinci, 44, 10095 Grugliasco, Torino (Italy); Davidson, C.M. [Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland (United Kingdom); Madrid, L. [Instituto de Recursos Naturales y Agrobiologia de Sevilla (CSIC), Apartado 1052, 41080 Sevilla (Spain)]. E-mail: madrid@irnase.csic.es

    2007-06-15

    Metals released by the extraction with aqua regia, EDTA, dilute HCl and sequential extraction (SE) by the BCR protocol were studied in urban soils of Sevilla, Torino, and Glasgow. By multivariate analysis, the amounts of Cu, Pb and Zn liberated by any method were statistically associated with one another, whereas other metals were not. The mean amounts of all metals extracted by HCl and by SE were well correlated, but SE was clearly underestimated by HCl. Individual data for Cu, Pb and Zn by both methods were correlated only if each city was considered separately. Other metals gave poorer relationships. Similar conclusions were reached comparing EDTA and HCl, with much lower values for EDTA. Dilute HCl extraction cannot thus be recommended for general use as alternative to BCR SE in urban soils. - Dilute HCl extraction is tested as an alternative to the BCR sequential extraction in urban soils.

  1. Evaluation of a sequential extraction process used for determining mercury binding mechanisms to coal combustion byproducts.

    Science.gov (United States)

    Noel, James D; Biswas, Pratim; Giammar, Daniel E

    2007-07-01

    Leaching of mercury from coal combustion byproducts is a concern because of the toxicity of mercury. Leachability of mercury can be assessed by using sequential extraction procedures. Sequential extraction procedures are commonly used to determine the speciation and mobility of trace metals in solid samples and are designed to differentiate among metals bound by different mechanisms and to different solid phases. This study evaluated the selectivity and effectiveness of a sequential extraction process used to determine mercury binding mechanisms to various materials. A six-step sequential extraction process was applied to laboratory-synthesized materials with known mercury concentrations and binding mechanisms. These materials were calcite, hematite, goethite, and titanium dioxide. Fly ash from a full-scale power plant was also investigated. The concentrations of mercury were measured using inductively coupled plasma (ICP) mass spectrometry, whereas the major elements were measured by ICP atomic emission spectrometry. The materials were characterized by X-ray powder diffraction and scanning electron microscopy with energy dispersive spectroscopy. The sequential extraction procedure provided information about the solid phases with which mercury was associated in the solid sample. The procedure effectively extracted mercury from the target phases. The procedure was generally selective in extracting mercury. However, some steps in the procedure extracted mercury from nontarget phases, and others resulted in mercury redistribution. Iron from hematite and goethite was only leached in the reducible and residual extraction steps. Some mercury associated with goethite was extracted in the ion exchangeable step, whereas mercury associated with hematite was extracted almost entirely in the residual step. Calcium in calcite and mercury associated with calcite were primarily removed in the acid-soluble extraction step. Titanium in titanium dioxide and mercury adsorbed onto

  2. Selenium Speciation Assessed by X-Ray Absorption Spectroscopy of Sequentially Extracted Anaerobic Biofilms

    NARCIS (Netherlands)

    Lenz, M.; Hullebusch, van E.D.; Farges, F.; Nikitenko, S.; Borca, C.N.; Grolimund, D.; Lens, P.N.L.

    2008-01-01

    Wet chemical methods such as sequential extraction procedures are commonly used to assess selenium fractionation in anoxic environments, allowing an estimation of the mobility and bioavailability of selenium. However, the interpretation can be biased by unselective extraction of targeted species and

  3. Phenanthrene sorption to sequentially extracted soil humic acids and humins.

    Science.gov (United States)

    Kang, Seunghun; Xing, Baoshan

    2005-01-01

    Humic substances strongly influence the environmental fate of hydrophobic organic chemicals in soils and sediments. In this study, the sorption of phenanthrene by humic acids (HAs) and humins was examined. HAs were obtained from progressively extracting a soil, eight times with 0.1 M Na4P207 and two times with 0.1 M NaOH solution, and then the residue was separated into two humin fractions by their organic carbon contents. The chemical and structural heterogeneity of the HAs and humins were characterized by elemental analysis, ultraviolet-visible spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy, and solid-state 13C NMR. There were significant chemical and structural differences among the HA fractions and humins; the later extracted HAs had relatively high aliphatic carbons content. All sorption data were fitted to a Freundlich equation, S = K(F)C(N), where S and C are the sorbed and solution-phase concentrations, respectively, and K(F) and N are constants. All of the phenanthrene sorptions were nonlinear, and the nonlinearity decreased with further extractions from 0.90 (first extracted HA) to 0.96 (ninth HA) and was the lowest (0.88) for the higher organic carbon content humin. Phenanthrene sorption coefficient by HAs significantly increased with progressive extractions, being the highest for the humins. For HAs isotherms, a positive trend was observed between the sorption coefficient and the aliphaticity, but a negative relation was shown between the nonlinearity and the aliphaticity and between the sorption capacity and polarity of HAs. Phenanthrene sorption was greatly affected by chemical structure and composition of humic substances, even from a same soil. In addition, polarity of humic substances seems to mainly regulate the magnitude of phenanthrene sorption rather than structure.

  4. The respective effects of soil heavy metal fractions by sequential extraction procedure and soil properties on the accumulation of heavy metals in rice grains and brassicas.

    Science.gov (United States)

    Xiao, Ling; Guan, Dongsheng; Peart, M R; Chen, Yujuan; Li, Qiqi

    2017-01-01

    This study was carried out to examine heavy metal accumulation in rice grains and brassicas and to identify the different controls, such as soil properties and soil heavy metal fractions obtained by the Community Bureau of Reference (BCR) sequential extraction, in their accumulation. In Guangdong Province, South China, rice grain and brassica samples, along with their rhizospheric soil, were collected from fields on the basis of distance downstream from electroplating factories, whose wastewater was used for irrigation. The results showed that long-term irrigation using the electroplating effluent has not only enriched the rhizospheric soil with Cd, Cr, Cu, and Zn but has also increased their mobility and bioavailability. The average concentrations of Cd and Cr in rice grains and brassicas from closest to the electroplating factories were significantly higher than those from the control areas. Results from hybrid redundancy analysis (hRDA) and redundancy analysis (RDA) showed that the BCR fractions of soil heavy metals could explain 29.0 and 46.5 % of total eigenvalue for heavy metal concentrations in rice grains and brassicas, respectively, while soil properties could only explain 11.1 and 33.4 %, respectively. This indicated that heavy metal fractions exerted more control upon their concentrations in rice grains and brassicas than soil properties. In terms of metal interaction, an increase of residual Zn in paddy soil or a decrease of acid soluble Cd in the brassica soil could enhance the accumulation of Cd, Cu, Cr, and Pb in both rice grains and brassicas, respectively, while the reducible or oxidizable Cd in soil could enhance the plants' accumulation of Cr and Pb. The RDA showed an inhibition effect of sand content and CFO on the accumulation of heavy metals in rice grains and brassicas. Moreover, multiple stepwise linear regression could offer prediction for Cd, Cu, Cr, and Zn concentrations in the two crops by soil heavy metal fractions and soil properties.

  5. Sequential chemical extraction for a phosphogypsum environmental impact evaluation

    Science.gov (United States)

    Gennari, R. F.; Garcia, I.; Medina, N. H.; Silveira, M. A. G.

    2013-05-01

    Phosphogypsum (PG) is gypsum generated during phosphoric acid production. PG is stocked in large stacks or accumulated in lakes; it contains heavy metals and naturally occurring radioactive elements. The metal contamination may affect the functionality, sustainability and biodiversity of ecosystems. In this work, PG samples were analyzed by Plasma Spectrometry. Total metal content and in the extractable fraction of chemical elements were determined. For K, Ni, Zn, Cr, Cd, Ba, Pb and U, the results obtained are lower than those obtained in a Idaho plant are including and also lower than those found in the soil, indicating this PG sample analyzed probably will not cause any additional metal neither natural radiation contamination.

  6. Development of a procedure for the sequential extraction of substances binding trace elements in plant biomass

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, D.; Pavlík, Milan; Vašíčková, Soňa; Száková, J.; Vokáč, Karel; Balík, J.; Tlustoš, P.

    2005-01-01

    Roč. 381, - (2005), s. 863-872 ISSN 1618-2642 Institutional research plan: CEZ:AV0Z4055905 Keywords : organic compounds binding trace elements * spinach plant * sequential extraction Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.695, year: 2005

  7. Sequential extraction protocol for organic matter from soils and sediments using high resolution mass spectrometry.

    Science.gov (United States)

    Tfaily, Malak M; Chu, Rosalie K; Toyoda, Jason; Tolić, Nikola; Robinson, Errol W; Paša-Tolić, Ljiljana; Hess, Nancy J

    2017-06-15

    A vast number of organic compounds are present in soil organic matter (SOM) and play an important role in the terrestrial carbon cycle, facilitate interactions between organisms, and represent a sink for atmospheric CO 2 . The diversity of different SOM compounds and their molecular characteristics is a function of the organic source material and biogeochemical history. By understanding how SOM composition changes with sources and the processes by which it is biogeochemically altered in different terrestrial ecosystems, it may be possible to predict nutrient and carbon cycling, response to system perturbations, and impact of climate change will have on SOM composition. In this study, a sequential chemical extraction procedure was developed to reveal the diversity of organic matter (OM) in different ecosystems and was compared to the previously published protocol using parallel solvent extraction (PSE). We compared six extraction methods using three sample types, peat soil, spruce forest soil and river sediment, so as to select the best method for extracting a representative fraction of organic matter from soils and sediments from a wide range of ecosystems. We estimated the extraction yield of dissolved organic carbon (DOC) by total organic carbon analysis, and measured the composition of extracted OM using high resolution mass spectrometry. This study showed that OM composition depends primarily on soil and sediment characteristics. Two sequential extraction protocols, progressing from polar to non-polar solvents, were found to provide the highest number and diversity of organic compounds extracted from the soil and sediments. Water (H 2 O) is the first solvent used for both protocols followed by either co-extraction with methanol-chloroform (MeOH-CHCl 3 ) mixture, or acetonitrile (ACN) and CHCl 3 sequentially. The sequential extraction protocol developed in this study offers improved sensitivity, and requires less sample compared to the PSE workflow where a new

  8. Sequential extraction protocol for organic matter from soils and sediments using high resolution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Tfaily, Malak M.; Chu, Rosalie K.; Toyoda, Jason; Toli?, Nikola; Robinson, Errol W.; Pa?a-Toli?, Ljiljana; Hess, Nancy J.

    2017-03-31

    A vast number of organic compounds are present in soil organic matter (SOM) and play an important role in the terrestrial carbon cycle, facilitate interactions between organisms, and represent a sink for atmospheric CO2. The diversity of different SOM compounds and their molecular characteristics is a function of the organic source material and biogeochemical history. By understanding how SOM composition changes with sources and the processes by which it is biogeochemically altered in different terrestrial ecosystems, it may be possible to predict nutrient and carbon cycling, response to system perturbations, and impact of climate change will have on SOM composition. In this study, a sequential chemical extraction procedure was developed to reveal the diversity of organic matter (OM) in different ecosystems and was compared to the previously published protocol using parallel solvent extraction (PSE). We compared six extraction methods using three sample types, peat soil, spruce forest soil and river sediment, so as to select the best method for extracting a representative fraction of organic matter from soils and sediments from a wide range of ecosystems. We estimated the extraction yield of dissolved organic carbon (DOC) by total organic carbon analysis, and measured the composition of extracted OM using high resolution mass spectrometry. This study showed that OM composition depends primarily on soil and sediment characteristics. Two sequential extraction protocols, progressing from polar to non-polar solvents, were found to provide the highest number and diversity of organic compounds extracted from the soil and sediments. Water (H2O) is the first solvent used for both protocols followed by either co-extraction with methanol-chloroform (MeOH-CHCl3) mixture, or acetonitrile (ACN) and CHCl3 sequentially. The sequential extraction protocol developed in this study offers improved sensitivity, and requires less sample compared to the PSE workflow where a new sample

  9. Modified sequential extraction for biochar and petroleum coke: Metal release potential and its environmental implications.

    Science.gov (United States)

    von Gunten, Konstantin; Alam, Md Samrat; Hubmann, Magdalena; Ok, Yong Sik; Konhauser, Kurt O; Alessi, Daniel S

    2017-07-01

    A modified Community Bureau of Reference (CBR) sequential extraction method was tested to assess the composition of untreated pyrogenic carbon (biochar) and oil sands petroleum coke. Wood biochar samples were found to contain lower concentrations of metals, but had higher fractions of easily mobilized alkaline earth and transition metals. Sewage sludge biochar was determined to be less recalcitrant and had higher total metal concentrations, with most of the metals found in the more resilient extraction fractions (oxidizable, residual). Petroleum coke was the most stable material, with a similar metal distribution pattern as the sewage sludge biochar. The applied sequential extraction method represents a suitable technique to recover metals from these materials, and is a valuable tool in understanding the metal retaining and leaching capability of various biochar types and carbonaceous petroleum coke samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Distributions and concentrations of thallium in Korean soils determined by single and sequential extraction procedures.

    Science.gov (United States)

    Lee, Jin-Ho; Kim, Dong-Jin; Ahn, Byung-Koo

    2015-06-01

    The objectives of this study were to investigate the distribution of thallium in soils collected near suspected areas such as cement plants, active and closed mines, and smelters and to examine the extraction of thallium in the soils using 19 single chemical and sequential chemical extraction procedures. Thallium concentrations in soils near cement plants were distributed between 1.20 and 12.91 mg kg(-1). However, soils near mines and smelters contained relatively low thallium concentrations ranging from 0.18 to 1.09 mg kg(-1). Thallium extractability with 19 single chemical extractants from selected soils near cement plants ranged from 0.10% to 8.20% of the total thallium concentration. In particular, 1.0 M NH4Cl, 1.0 M (NH4)2SO4, and 1.0 M CH3COONH4 extracted more thallium than other extractants. Sequential fractionation results of thallium from different soils such as industrially and artificially contaminated soils varied with the soil properties, especially soil pH and the duration of thallium contamination.

  11. Sequential injection analysis with chemiluminescence detection for rapid monitoring of commercial Calendula officinalis extractions.

    Science.gov (United States)

    Hughes, Rachel R; Scown, David; Lenehan, Claire E

    2015-01-01

    Plant extracts containing high levels of antioxidants are desirable due to their reported health benefits. Most techniques capable of determining the antioxidant activity of plant extracts are unsuitable for rapid at-line analysis as they require extensive sample preparation and/or long analysis times. Therefore, analytical techniques capable of real-time or pseudo real-time at-line monitoring of plant extractions, and determination of extraction endpoints, would be useful to manufacturers of antioxidant-rich plant extracts. To develop a reliable method for the rapid at-line extraction monitoring of antioxidants in plant extracts. Calendula officinalis extracts were prepared from dried flowers and analysed for antioxidant activity using sequential injection analysis (SIA) with chemiluminescence (CL) detection. The intensity of CL emission from the reaction of acidic potassium permanganate with antioxidants within the extract was used as the analytical signal. The SIA-CL method was applied to monitor the extraction of C. officinalis over the course of a batch extraction to determine the extraction endpoint. Results were compared with those from ultra high performance liquid chromatography (UHPLC). Pseudo real-time, at-line monitoring showed the level of antioxidants in a batch extract of Calendula officinalis plateaued after 100 min of extraction. These results correlated well with those of an offline UHPLC study. SIA-CL was found to be a suitable method for pseudo real-time monitoring of plant extractions and determination of extraction endpoints with respect to antioxidant concentrations. The method was applied at-line in the manufacturing industry. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Evaluation of degree of readsorption of radionuclides during sequential extraction in soil: comparison between batch and dynamic extraction systems

    DEFF Research Database (Denmark)

    Petersen, Roongrat; Hansen, Elo Harald; Hou, Xiaolin

    developed in our laboratory for heavy metal fractionation has shown the reduction of readsorption problem in comparison with the batch techniques. Moreover, the system shows many advantages over the batch system such as speed of extraction, simple procedure, fully automatic, less risk of contamination......Sequential extraction techniques have been widely used to fractionate metals in solid samples (soils, sediments, solid wastes, etc.) due to their leachability. The results are useful for obtaining information about bioavailability, potential mobility and transport of element in natural environments....... However, the techniques have an important problem with redistribution as a result of readsorption of dissolved analytes onto the remaining solids phases during extraction. Many authors have demonstrated the readsorption problem and inaccuracy from it. In our previous work, a dynamic extraction system...

  13. Sequential extraction for the speciation of some heavy metals in soils

    International Nuclear Information System (INIS)

    Zemberyova, M.; Zwaik, A.A.H.; Farkasovska, I.

    1998-01-01

    The five step sequential extraction for speciation of copper and nickel originally designed for sediments has been applied to soil samples. The extractant solutions were: 1 mol/l ammonium acetate, 1 mol/l hydroxylammonium chloride in 25% acetic acid (1:1), 0.1 mol/l hydrochlorid acid, 0.5 mol/l sodium hydroxide and 8 mol/l nitric acid. The residue was decomposed by HF and HNO 3 . Using this procedure the metal fraction bound to the organic matter can be distinguished. The concentrations of analytes were determined in the soil extracts by FAAS and ETAAS. Accuracy was assessed by comparing the sum of the contents of copper and nickel in soil extracts with the total certified values of CRMs of soils. The overall recovery values for nickel was 84-105% and for copper 105-114%. (author)

  14. Selenium speciation in phosphate mine soils and evaluation of a sequential extraction procedure using XAFS

    Energy Technology Data Exchange (ETDEWEB)

    Favorito, Jessica E.; Luxton, Todd P.; Eick, Matthew J.; Grossl, Paul R. (VP); (Utah SU); (EPA)

    2017-10-01

    Selenium is a trace element found in western US soils, where ingestion of Se-accumulating plants has resulted in livestock fatalities. Therefore, a reliable understanding of Se speciation and bioavailability is critical for effective mitigation. Sequential extraction procedures (SEP) are often employed to examine Se phases and speciation in contaminated soils but may be limited by experimental conditions. We examined the validity of a SEP using X-ray absorption spectroscopy (XAS) for both whole and a sequence of extracted soils. The sequence included removal of soluble, PO4-extractable, carbonate, amorphous Fe-oxide, crystalline Fe-oxide, organic, and residual Se forms. For whole soils, XANES analyses indicated Se(0) and Se(-II) predominated, with lower amounts of Se(IV) present, related to carbonates and Fe-oxides. Oxidized Se species were more elevated and residual/elemental Se was lower than previous SEP results from ICP-AES suggested. For soils from the SEP sequence, XANES results indicated only partial recovery of carbonate, Fe-oxide and organic Se. This suggests Se was incompletely removed during designated extractions, possibly due to lack of mineral solubilization or reagent specificity. Selenium fractions associated with Fe-oxides were reduced in amount or removed after using hydroxylamine HCl for most soils examined. XANES results indicate partial dissolution of solid-phases may occur during extraction processes. This study demonstrates why precautions should be taken to improve the validity of SEPs. Mineralogical and chemical characterizations should be completed prior to SEP implementation to identify extractable phases or mineral components that may influence extraction effectiveness. Sequential extraction procedures can be appropriately tailored for reliable quantification of speciation in contaminated soils.

  15. Beryllium solubility in occupational airborne particles: Sequential extraction procedure and workplace application.

    Science.gov (United States)

    Rousset, Davy; Durand, Thibaut

    2016-01-01

    Modification of an existing sequential extraction procedure for inorganic beryllium species in the particulate matter of emissions and in working areas is described. The speciation protocol was adapted to carry out beryllium extraction in closed-face cassette sampler to take wall deposits into account. This four-step sequential extraction procedure aims to separate beryllium salts, metal, and oxides from airborne particles for individual quantification. Characterization of the beryllium species according to their solubility in air samples may provide information relative to toxicity, which is potentially related to the different beryllium chemical forms. Beryllium salts (BeF(2), BeSO(4)), metallic beryllium (Bemet), and beryllium oxide (BeO) were first individually tested, and then tested in mixtures. Cassettes were spiked with these species and recovery rates were calculated. Quantitative analyses with matched matrix were performed using inductively coupled plasma mass spectrometry (ICP-MS). Method Detection Limits (MDLs) were calculated for the four matrices used in the different extraction steps. In all cases, the MDL was below 4.2 ng/sample. This method is appropriate for assessing occupational exposure to beryllium as the lowest recommended threshold limit values are 0.01 µg.m(-3) in France([) (1) (]) and 0.05 µg.m(-3) in the USA.([ 2 ]) The protocol was then tested on samples from French factories where occupational beryllium exposure was suspected. Beryllium solubility was variable between factories and among the same workplace between different tasks.

  16. Pumpkin (Cucurbita maxima) seed proteins: sequential extraction processing and fraction characterization.

    Science.gov (United States)

    Rezig, Leila; Chibani, Farhat; Chouaibi, Moncef; Dalgalarrondo, Michèle; Hessini, Kamel; Guéguen, Jacques; Hamdi, Salem

    2013-08-14

    Seed proteins extracted from Tunisian pumpkin seeds ( Cucurbita maxima ) were investigated for their solubility properties and sequentially extracted according to the Osborne procedure. The solubility of pumpkin proteins from seed flour was greatly influenced by pH changes and ionic strength, with higher values in the alkaline pH regions. It also depends on the seed defatting solvent. Protein solubility was decreased by using chloroform/methanol (CM) for lipid extraction instead of pentane (P). On the basis of differential solubility fractionation and depending on the defatting method, the alkali extract (AE) was the major fraction (42.1 (P), 22.3% (CM)) compared to the salt extract (8.6 (P), 7.5% (CM)). In salt, alkali, and isopropanol extracts, all essential amino acids with the exceptions of threonine and lysine met the minimum requirements for preschool children (FAO/WHO/UNU). The denaturation temperatures were 96.6 and 93.4 °C for salt and alkali extracts, respectively. Pumpkin protein extracts with unique protein profiles and higher denaturation temperatures could impart novel characteristics when used as food ingredients.

  17. Non-cellulosic heteropolysaccharides from sugarcane bagasse - sequential extraction with pressurized hot water and alkaline peroxide at different temperatures.

    Science.gov (United States)

    Banerjee, Protibha Nath; Pranovich, Andrey; Dax, Daniel; Willför, Stefan

    2014-03-01

    The xylan-rich hemicellulose components of sugarcane bagasse were sequentially extracted with pressurized hot-water extraction (PHWE) and alkaline peroxide. The hemicelluloses were found to contain mainly arabinoxylans with varying substitutions confirmed by different chemical and spectroscopic methods. The arabinoxylans obtained from PHWE were found to be more branched compared to those obtained after alkaline extraction. Sequential extraction could be useful for the isolation of hemicelluloses with different degree of branching, molar mass, and functional groups from sugarcane bagasse, which can be of high potential use for various industrial applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Preparative yield and properties of humic acids obtained by sequential alkaline extractions

    Science.gov (United States)

    Kholodov, V. A.; Yaroslavtseva, N. V.; Konstantinov, A. I.; Perminova, I. V.

    2015-10-01

    The preparative yield, composition, and structure of humic acids obtained by sequential alkaline extractions from two soils (a soddy-podzolic soil under forest and a typical chernozem in treatment with permanent black fallow of a long-term experiment since 1964) have been studied. The preparative yield of humic acids from the first extraction is 0.40 and 0.94% for the soddy-podzolic soil (Retisols) and the chernozem, respectively. The preparative yield from the second extraction is lower by several times, and the yield from the third extraction is lower by an order of magnitude. The study of the obtained preparations by elemental analysis, gel-permeation chromatography, and 13C NMR spectroscopy has shown insignificant changes in the elemental, molecular-weight, and structural-group composition of humic acids among the extractions. It has been supposed that this is related to the soil features: typical climatic factors for the formation of soil subtype in the case of soddy-podzolic soil and the land use in the long-term experiment in the case of typical chernozem. It has been concluded that that a single extraction is sufficient for the separation of humic acids and the preparation of a representative sample.

  19. Instant controlled pressure drop technology and ultrasound assisted extraction for sequential extraction of essential oil and antioxidants.

    Science.gov (United States)

    Allaf, Tamara; Tomao, Valérie; Ruiz, Karine; Chemat, Farid

    2013-01-01

    The instant controlled pressure drop (DIC) technology enabled both the extraction of essential oil and the expansion of the matrix itself which improved solvent extraction. The sequential use of DIC and Ultrasound Assisted Extraction (UAE) triggered complementary actions materialized by supplementary effects. We visualized these combination impacts by comparing them to standard techniques: Hydrodistillation (HD) and Solvent Extraction (SE). First, the extraction of orange peel Essential Oils (EO) was achieved by HD during 4h and DIC process (after optimization) during 2 min; EO yields was 1.97 mg/g dry material (dm) with HD compared to 16.57 mg/g d m with DIC. Second, the solid residue was recovered to extract antioxidant compounds (naringin and hesperidin) by SE and UAE. Scanning electron microscope showed that after HD the recovered solid shriveled as opposite to DIC treatment which expanded the product structure. HPLC analyses showed that the best kinetics and yields of naringin and hesperidin extraction was when DIC and UAE are combined. Indeed, after 1h of extraction, DIC treated orange peels with UAE were 0.825 ± 1.6 × 10(-2)g/g of dry material (dm) for hesperidin and 6.45 × 10(-2) ± 2.3 × 10(-4)g/g d m for naringin compared to 0.64 ± 2.7 × 10(-2)g/g of dry material (dm) and 5.7 × 10(-2) ± 1.6 × 10(-3)g/g d m, respectively with SE. By combining DIC to UAE, it was possible to enhance kinetics and yields of antioxidant extraction. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Allium Roseum L. Extract Exerts Potent Suppressive Activities on Chronic Myeloid Leukemia K562 Cell Viability Through the Inhibition of BCR-ABL, PI3K/Akt, and ERK1/2Pathways and the Abrogation of VEGF Secretion.

    Science.gov (United States)

    Souid, Soumaya; Najjaa, Hanen; Riahi-Chebbi, Ichrak; Haoues, Meriam; Neffati, Mohamed; Arnault, Ingrid; Auger, Jacques; Karoui, Habib; Essafi, Makram; Essafi-Benkhadir, Khadija

    2017-01-01

    Use of plant extracts, alone or combined to the current chemotherapy as chemosensitizers, has emerged as a promising strategy to overcome tumor drug resistance. Here, we investigated the anticancer activity of Allium roseum L. extracts, a wild edible species in North Africa, on human Chronic Myeloid Leukemia (CML) K562 cells. The dehydrated aqueous extract (DAE) disturbed the cell cycle progression and induced the apoptosis of K562 cells. Chemical analysis of DAE showed a diversity of organosulfur compounds S-alk(en)yl-cysteine sulfoxides (RCSO) and high amount of allicin, suggesting that such molecule may be behind its antitumor effect. DAE was efficient in inhibiting K562 cell viability. DAE inhibitory effect was associated with the dephosphorylation of the BCR-ABL kinase and interfered with ERK 1/2 , Akt, and STAT5 pathways. Furthermore, we found that DAE-induced inactivation of Akt kinase led to the activation of its target FOXO3 transcription factor, enhancing the expression of FOXO3-regulated proapoptotic effectors, Bim and Bax, and cell cycle inhibitor p27. Finally, we found that DAE reduced the secretion of vascular endothelial growth factor. Overall, our data suggest that A. roseum extract has great potential as a nontoxic cheap and effective alternative to conventional chemotherapy.

  1. Assessment of a sequential extraction protocol by examining solution chemistry and mineralogical evolution

    Science.gov (United States)

    Maubec, Nicolas; Pauwels, Hélène; Noël, Hervé; Bourrat, Xavier

    2015-04-01

    Knowledge of the behavior of heavy metals, such as copper and zinc in sediments, is a key factor to improve the management of rivers. The mobility of these metals, which may be harmful to the environment, depends directly on their concentration and speciation , which in turn depend on physico-chemical parameters such as mineralogy of the sediment fraction, pH, redox potential, salinity etc ... (Anderson et al., 2000; Sterckeman et al., 2004; Van Oort et al., 2008). Several methods based on chemical extractions are currently applied to assess the behavior of heavy metals in soils and sediments. Among them, sequential extraction procedure is widely used in soil and sediment science and provides details about the origin, biological and physicochemical availability, mobilization and transports of trace metals elements. It is based on the use of a series of extracting reagents to extract selectively heavy metals according to their association within the solid phase (Cornu and Clozel, 2000) including the following different fraction : exchangeable, bound to carbonates, associated to oxides (reducible fraction), linked to organic matter and sulfides (oxidizable fraction) as well as silicate minerals so called residual fraction (Hickey and Kittrick, 1984; Tessier et al., 1979). Consequently sequential extraction method is expected to simulate a lot of potential natural and anthropogenic modifications of environmental conditions (Arey et al., 1999; Brannon and Patrick, 1987; Hickey and Kittrick, 1984; La Force et al., 1999; Tessier et al., 1979). For three decades, a large number of protocols has been proposed, characterized by specific reagents and experimental conditions (concentrations, number of steps, extraction orders and solid/solution ratio) (Das et al., 1995; Gomez Ariza et al., 2000; Quevauviller et al., 1994; Rauret, 1998; Tack and Verloo, 1995), but it appeared that several of them suffer from a lack of selectivity of applied reagents: besides target ones, some

  2. Selectivity assessment of an arsenic sequential extraction procedure for evaluating mobility in mine wastes

    International Nuclear Information System (INIS)

    Drahota, Petr; Grösslová, Zuzana; Kindlová, Helena

    2014-01-01

    Highlights: • Extraction efficiency and selectivity of phosphate and oxalate were tested. • Pure As-bearing mineral phases and mine wastes were used. • The reagents were found to be specific and selective for most major forms of As. • An optimized sequential extraction scheme for mine wastes has been developed. • It has been tested over a model mineral mixtures and natural mine waste materials. - Abstract: An optimized sequential extraction (SE) scheme for mine waste materials has been developed and tested for As partitioning over a range of pure As-bearing mineral phases, their model mixtures, and natural mine waste materials. This optimized SE procedure employs five extraction steps: (1) nitrogen-purged deionized water, 10 h; (2) 0.01 M NH 4 H 2 PO 4 , 16 h; (3) 0.2 M NH 4 -oxalate in the dark, pH3, 2 h; (4) 0.2 M NH 4 -oxalate, pH3/80 °C, 4 h; (5) KClO 3 /HCl/HNO 3 digestion. Selectivity and specificity tests on natural mine wastes and major pure As-bearing mineral phases showed that these As fractions appear to be primarily associated with: (1) readily soluble; (2) adsorbed; (3) amorphous and poorly-crystalline arsenates, oxides and hydroxosulfates of Fe; (4) well-crystalline arsenates, oxides, and hydroxosulfates of Fe; as well as (5) sulfides and arsenides. The specificity and selectivity of extractants, and the reproducibility of the optimized SE procedure were further verified by artificial model mineral mixtures and different natural mine waste materials. Partitioning data for extraction steps 3, 4, and 5 showed good agreement with those calculated in the model mineral mixtures (<15% difference), as well as that expected in different natural mine waste materials. The sum of the As recovered in the different extractant pools was not significantly different (89–112%) than the results for acid digestion. This suggests that the optimized SE scheme can reliably be employed for As partitioning in mine waste materials

  3. Relationship between Cadmium Fractions Obtained by Sequential Extraction of Soil and the Soil Properties in Contaminated and Uncontaminated Paddy Soils

    OpenAIRE

    Honma, Toshimitsu; Ohba, Hirotomo; Makino, Tomoyuki; Ohyama, Takuji

    2015-01-01

    The method for the sequential extraction of cadmium from soil was adapted to investigate the relationship between different chemical forms of cadmium in soils and the soil properties of Cd-contaminated and uncontaminated paddy soils. Air-dried soil samples from each field site were sequentially fractionated into five forms: exchangeable Cd, inorganically bound Cd, organically bound Cd, oxide-occluded fraction, and residual Cd. The average and range of soil properties such as pH, total C, tota...

  4. Testing sequential extraction methods for the analysis of multiple stable isotope systems from a bone sample

    Science.gov (United States)

    Sahlstedt, Elina; Arppe, Laura

    2017-04-01

    Stable isotope composition of bones, analysed either from the mineral phase (hydroxyapatite) or from the organic phase (mainly collagen) carry important climatological and ecological information and are therefore widely used in paleontological and archaeological research. For the analysis of the stable isotope compositions, both of the phases, hydroxyapatite and collagen, have their more or less well established separation and analytical techniques. Recent development in IRMS and wet chemical extraction methods have facilitated the analysis of very small bone fractions (500 μg or less starting material) for PO43-O isotope composition. However, the uniqueness and (pre-) historical value of each archaeological and paleontological finding lead to preciously little material available for stable isotope analyses, encouraging further development of microanalytical methods for the use of stable isotope analyses. Here we present the first results in developing extraction methods for combining collagen C- and N-isotope analyses to PO43-O-isotope analyses from a single bone sample fraction. We tested sequential extraction starting with dilute acid demineralization and collection of both collagen and PO43-fractions, followed by further purification step by H2O2 (PO43-fraction). First results show that bone sample separates as small as 2 mg may be analysed for their δ15N, δ13C and δ18OPO4 values. The method may be incorporated in detailed investigation of sequentially developing skeletal material such as teeth, potentially allowing for the investigation of interannual variability in climatological/environmental signals or investigation of the early life history of an individual.

  5. Fractionation of heavy metals in liquefied chromated copper arsenate (CCA)-treated wood sludge using a modified BCR-sequential extraction procedure

    Science.gov (United States)

    Hui Pan; Chung-Yun Hse; Robert Gambrell; Todd F. Shupe

    2009-01-01

    Chromated copper arsenate (CCA)-treated wood was liquefied with polyethylene glycol/glycerin and sulfuric acid. After liquefaction, most CCA metals (98% As, 92% Cr, and 83% Cu) were removed from liquefied CCA-treated wood by precipitation with calcium hydroxide. The original CCA-treated wood and liquefied CCA-treated wood sludge were fractionated by a modified...

  6. Sequential healing at implants installed immediately into extraction sockets. An experimental study in dogs.

    Science.gov (United States)

    Mainetti, Tomaso; Lang, Niklaus P; Bengazi, Franco; Favero, Vittorio; Soto Cantero, Luis; Botticelli, Daniele

    2016-01-01

    To compare the sequential healing at implants installed in a healed alveolar bony ridge or immediately after tooth extraction without functional load. In the mandible of 12 dogs, the mesial roots of the first molars were endodontically treated, the tooth hemisected, and the distal roots extracted. After 3 months, the mesial roots of the fourth premolars were endodontically treated, the tooth hemisected, and the distal roots extracted in one side of the mandible. Implants were placed immediately into extraction sockets (IPIES) of the fourth premolar and in the healed sites in the molar regions. Healing abutments were placed, and the flaps were sutured to allow a non-submerged healing. The time of surgery and of sacrifices were planned in such a way to obtain biopsies representing the healing after 1 and 2 weeks and 1 and 3 months, respectively. Ground sections were prepared for histological evaluation of tissues components on the implant surface and the coronal termination level of osseointegration (M-B). New bone apposition on the implant surface was slightly higher at the healed compared to the IPIES sites, being 7.4% and 4.1% after 1 week, and 67.3% and 65.3% after 3 months, respectively. Old bone was progressively resorbed, from 27.0% and 21.9% after 1 week, to 2.5% and 2.0% after 3 months, at healed and IPIES sites, respectively. M-B was 1.4 mm and 2.6 mm after 1 week, 1.2 mm and 1.2 mm after 3 months, at healed and IPIES sites, respectively. Similar patterns of sequential osseointegration were found at implants installed in healed alveolar bone or in alveolar sockets immediately after tooth extraction. The coronal termination level of osseointegration, that was different after 1 week, was found similar at the 3-month observation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Sequential microwave superheated water extraction of mannans from spent coffee grounds.

    Science.gov (United States)

    Passos, Cláudia P; Moreira, Ana S P; Domingues, M Rosário M; Evtuguin, Dmitry V; Coimbra, Manuel A

    2014-03-15

    The feasibility of using sequential microwave superheated water extraction (MAE) for the recovery of mannans from spent coffee grounds (SCG) was studied. Due to the high contents of mannose still present in the SCG residue left after two consecutive MAE, the unextracted material was re-suspended in water and submitted to a third microwave irradiation (MAE3) at 200 °C for 3 min. With MAE3, mannose recovery achieved 48%, increasing to 56% by MAE4, and reaching a maximum of 69% with MAE5. Glycosidic-linkage analysis showed that in MAE3 mainly galactomannans were recovered, while debranched galactomannans were recovered with MAE4 and MAE5. With increasing the number of extractions, the average degree of polymerization of the mannans decreased, as observed by size-exclusion chromatography and by methylation analysis. Scanning electron microscopy images showed a decrease on cell walls thickness. After final MAE5, the remaining un-extracted insoluble material, representing 22% of the initial SCG, was composed mainly by cellulose (84%). Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Evaluation of dissipation gradients of polycyclic aromatic hydrocarbons in rice rhizosphere utilizing a sequential extraction procedure

    International Nuclear Information System (INIS)

    Ma Bin; Wang Jiaojiao; Xu Minmin; He Yan; Wang Haizhen; Wu Laosheng; Xu Jianming

    2012-01-01

    The aim of this study was to evaluate the spatial dissipation gradient of PAHs, including phenanthrene, pyrene, and benzo[a]pyrene, with various bioavailability represented with sequential extraction. Dissipation rates of PAHs in the rhizosphere were greater than those in the bulk soil. The n-butanol extracted fraction showed a general trend of dissipation during phytoremediation. Moreover, the formation of bound PAH residues was inhibited in the rhizosphere. While concerning the PAH toxicity, the reduction rates of PAH toxicity were significantly greater than total soil PAH concentrations. Microbial biomass was the highest at four mm away from the root surface. However, the PAH dissipation rates were the highest at one mm and two mm away from the root surface in high and low PAH treatments, respectively. These results suggest that rhizoremediation with rice is a useful approach to reduce the toxicity of PAHs in soil. - Highlights: ► Dissipation gradients were different in soils spiked with different PAHs concentrations. ► Butanol extracted fraction indicated the remediation in rhizosphere. ► Toxicity of PAHs was more efficiently reduced than total concentration. ► Promotion of PAHs degraders was not synchronized with microbial biomass. - Stimulation of PAH degradation in rice rhizosphere was not simultaneous with microbial biomass.

  9. Sequential healing of open extraction sockets. An experimental study in monkeys.

    Science.gov (United States)

    Scala, Alessandro; Lang, Niklaus P; Schweikert, Michael T; de Oliveira, José Américo; Rangel-Garcia, Idelmo; Botticelli, Daniele

    2014-03-01

    To describe the sequential healing of open extraction sockets at which no attempts to obtain a primary closure of the coronal access to the alveolus have been made. The third mandibular premolar was extracted bilaterally in 12 monkeys, and no sutures were applied to close the wound. The healing after 4, 10, 20, 30, 90 and 180 days was morphometrically studied. After 4 days of healing, a blood clot mainly occupied the extraction sockets, with the presence of an inflammatory cells' infiltrate. A void was confined in the central zones of the coronal and middle regions, in continuity with the entrance of the alveoli. At 10 days, the alveolus was occupied by a provisional matrix, with new bone formation lining the socket bony walls. At 20 days, the amount of woven bone was sensibly increasing. At 30 days, the alveolar socket was mainly occupied by mineralized immature bone at different stages of healing. At 90 and 180 days, the amount of mineralized bone decreased and substituted by trabecular bone and bone marrow. Bundle bone decreased from 95.5% at 4 days to 7.6% at 180 days, of the whole length of the inner alveolar surface. Modeling processes start from the lateral and apical walls of the alveolus, leading to the closure of the socket with newly formed bone within a month from extraction. Remodeling processes will follow the previous stages, resulting in trabecular and bone marrow formation and in a corticalization of the socket access. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  10. BCR-ABL1: Test

    Science.gov (United States)

    ... Thompson, E. (Revised 2009 July). Modalities of Cancer Therapy. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec11/ch149/ch149b.html?qt=bcr-abl&alt=sh through ... 15). Current Status of Therapy for Chronic Myeloid Leukemia: A Review of Drug ...

  11. Fractionation study in bioleached metallurgy wastes using six-step sequential extraction.

    Science.gov (United States)

    Krasnodebska-Ostrega, Beata; Pałdyna, Joanna; Kowalska, Joanna; Jedynak, Łukasz; Golimowski, Jerzy

    2009-08-15

    The stored metallurgy wastes contain residues from ore processing operations that are characterized by relatively high concentrations of heavy metals. The bioleaching process makes use of bacteria to recover elements from industrial wastes and to decrease potential risk of environmental contamination. Wastes were treated by solutions containing bacteria. In this work, the optimized six-stage sequential extraction procedure was applied for the fractionation of Ni, Cr, Fe, Mn, Cu and Zn in iron-nickel metallurgy wastes deposited in Southern Poland (Szklary). Fractionation and total concentrations of elements in wastes before and after various bioleaching treatments were studied. Analyses of the extracts were performed by ICP-MS and FAAS. To achieve the most effective bioleaching of Zn, Cr, Ni, Cu, Mn, Fe the usage of both autotrophic and heterotrophic bacteria in sequence, combined with flushing of the residue after bioleaching is required. 80-100% of total metal concentrations were mobilized after the proposed treatment. Wastes treated according to this procedure could be deposited without any risk of environmental contamination and additionally the metals could be recovered for industrial purposes.

  12. COMPARISON OF Sr ISOTOPIC RATIOS FROM TWO SOILS NEAR RAVENNA (ITALY USING AQUA REGIA AND TWO-STEP SEQUENTIAL EXTRACTS

    Directory of Open Access Journals (Sweden)

    Francesca Castorina

    2010-08-01

    Full Text Available The Sr-isotope ratios of several samples from a natural and an agricultural soil from Ravenna were determined using aqua regia and the two-step sequential extraction. Results indicate that the two-step extraction can provide the researcher with wider and more precise information on Sr sources, thus being a more suitable methodology for achieving scientific goals than the aqua regia extraction. Lastly, the extracts of hydrochloric acid and aqua regia display similar ranges of δ87Sr, indicating that the two procedures provide comparable information on Sr sources.

  13. Evaluation of Heavy Metals Concentration and Sequential Extraction in Zahedan Compost

    Directory of Open Access Journals (Sweden)

    Safoora Javan

    2016-03-01

    Full Text Available Background: Producing compost out of municipal solid wastes and organic materials is one of the main ways to recycle organic materials which plays an important role in waste management. Compost can also bring some toxic substances such as heavy metals into the soil and food chain and these substances have negative effects on the living things. Methods: This research is a cross-sectional descriptive study which was carried out during two seasons of spring and summer on Zahedan vermicompost factory. There were 100 samples in the research and the rate of mobility of heavy metals of lead, cadmium, and nickel was measured through five-step sequential extraction method. Then the hazard of the metals was assessed too. Results: The results show that the highest rate of mobility is related to chromium and then cadmium and lead. Moreover, the risk assessment of heavy metals estimates the average risk of all three metals for the living things in the environment. Conclusion: Heavy metals of lead and cadmium and nickel in Zahedan compost are less than the standard that is set for Iran. 

  14. Arsenic release from arsenopyrite weathering: Insights from sequential extraction and microscopic studies

    International Nuclear Information System (INIS)

    Basu, Ankan; Schreiber, Madeline E.

    2013-01-01

    Highlights: ► We studied arsenopyrite weathering reactions in rocks and sediments at mine site. ► Arsenopyrite oxidizes to scorodite, which dissolves incongruently to Fe hydroxide. ► Weathering of arsenopyrite to Fe hydroxide releases As to water. ► Dominant As reservoir in sediment is Fe hydroxide. -- Abstract: At a former As mine site, arsenopyrite oxidation has resulted in formation of scorodite and As-bearing iron hydroxide, both in host rock and mine tailings. Electron microprobe analysis documents that arsenopyrite weathers along two pathways: one that involves formation of sulfur, and one that does not. In both pathways, arsenopyrite oxidizes to form scorodite, which dissolves incongruently to form As-bearing iron hydroxides. From a mass balance perspective, arsenopyrite oxidation to scorodite conserves As, but as scorodite dissolves incongruently to iron hydroxides, As is released to solution, resulting in elevated As concentrations in the headwater stream adjacent to the site. The As-bearing iron hydroxide is the dominant solid phase reservoir of As in mine tailings and stream sediment, as suggested by sequential extraction. This As-bearing iron hydroxide is stable under the aerobic and pH 4–6 conditions at the site; however, changes in biogeochemical conditions resulting from sediment burial or future remedial efforts, which could promote As release from this reservoir due to reductive dissolution, should be avoided

  15. Sequential extraction and availability of copper in Cu fungicide-amended vineyard soils from Southern Brazil

    International Nuclear Information System (INIS)

    Correa Nogueirol, Roberta; Ferracciu Alleoni, Luis Reynaldo; Ribeiro Nachtigall, Gilmar; Wellington de Melo, George

    2010-01-01

    The continuous use of cupric fungicides in vineyards, mainly copper sulfate (as a component of the bordeaux mixture), has increased Cu concentration in soils to levels near or even above the maximum established by the Commission of Soil Chemistry and Fertility of the States of Santa Catarina and Rio Grande do Sul, Brazil. Besides the total content, the fractions of the element along the soil profile must be known, because the total content of Cu in the soil is not sufficient to express its environmental impact. The objective of this study was to evaluate the variation of Cu contentes along the soil profile and its speciation and partitioning in 29 soil samples from vineyards in the state of Rio Grande do Sul, Brazil. Samples were collected in areas cropped with vineyards older than 15 years that had been frequently treated with the bordeaux mixture. These samples were from Nitosols, Acrisols, Cambisols and Leptosols and were analysed by sequential extractions and several chemical extractors. Soils had diverse chemical and physical attributes: clay content in the plowed layer (0-0.2 m) ranged from 120 to 610 g kg -1 , pH ranged from 5.3 to 7.3 and organic carbon contents varied from 2.9 to 51 g dm -3 . Among the 29 samples, 16 had the total Cu above the maximum limit allowed by the European Community regulations (140 mg kg -1 ). The average amount of Cu bonded to the oxide fraction accounted for 49.5% of the total Cu.

  16. Sequential extraction and availability of copper in Cu fungicide-amended vineyard soils from Southern Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Correa Nogueirol, Roberta [University of Sao Paulo (ESALQ/USP), C.P. 9, Piracicaba 13418-900, SP (Brazil); Ferracciu Alleoni, Luis Reynaldo, E-mail: alleoni@esalq.usp.br [Department of Soil Science, ESALQ/USP. C.P. 9, Piracicaba 13418-900, SP (Brazil); Ribeiro Nachtigall, Gilmar; Wellington de Melo, George [National Research Center of Grapes and Wine - Embrapa Uva e Vinho, C.P. 130, Bento Goncalves 95700-000, RS (Brazil)

    2010-09-15

    The continuous use of cupric fungicides in vineyards, mainly copper sulfate (as a component of the bordeaux mixture), has increased Cu concentration in soils to levels near or even above the maximum established by the Commission of Soil Chemistry and Fertility of the States of Santa Catarina and Rio Grande do Sul, Brazil. Besides the total content, the fractions of the element along the soil profile must be known, because the total content of Cu in the soil is not sufficient to express its environmental impact. The objective of this study was to evaluate the variation of Cu contentes along the soil profile and its speciation and partitioning in 29 soil samples from vineyards in the state of Rio Grande do Sul, Brazil. Samples were collected in areas cropped with vineyards older than 15 years that had been frequently treated with the bordeaux mixture. These samples were from Nitosols, Acrisols, Cambisols and Leptosols and were analysed by sequential extractions and several chemical extractors. Soils had diverse chemical and physical attributes: clay content in the plowed layer (0-0.2 m) ranged from 120 to 610 g kg{sup -1}, pH ranged from 5.3 to 7.3 and organic carbon contents varied from 2.9 to 51 g dm{sup -3}. Among the 29 samples, 16 had the total Cu above the maximum limit allowed by the European Community regulations (140 mg kg{sup -1}). The average amount of Cu bonded to the oxide fraction accounted for 49.5% of the total Cu.

  17. Sequential microwave-assisted extraction of oil from layer poultry feeds and GC-MS quantification of the fatty acids

    International Nuclear Information System (INIS)

    Mahesar, S.A.; Sherazi, S.T.H.; Bhanger, M.I.; Abro, K.; Kandhro, A.A.

    2010-01-01

    The present study reports the effect of sequential microwave-assisted extraction (SeMAE) on fatty acids composition (FAC) of layer poultry feed oil as compared to conventional Soxhlet extraction (SE) method. The FAC of extracted oil was determined by gas chromatography - mass spectrometry (GC-MS). There was no significant difference found in the amount of total extracted oil and FAC by SeMAE and SE. However, slightly greater content of trans fat in the samples revealed that SE lead to the formation of a little higher level of trans fat as compare to SeMAE. Therefore, the SeMAE could be used as a remarkable substitute to conventional SE for extraction of oil from the poultry feeds due to its faster speed, lesser solvent consumption, more environmental friendly. (author)

  18. Sequential Microwave-Assisted Extraction of Oil from Layer Poultry Feeds and GC-MS Quantification of the Fatty Acids

    Directory of Open Access Journals (Sweden)

    S. A. Mahesar

    2010-06-01

    Full Text Available The present study reports the effect of sequential microwave-assisted extraction (SeMAE on fatty acids composition (FAC of layer poultry feed oil as compared to conventional Soxhlet extraction (SE method. The FAC of extracted oil was determined by gas chromatography–mass spectrometry (GC-MS. There was no significant difference found in the amount of total extracted oil and FAC by SeMAE and SE. However, slightly greater content of trans fat in the samples revealed that SE lead to the formation of a little higher level of trans fat as compare to SeMAE. Therefore, the SeMAE could be used as a remarkable substitute to conventional SE for extraction of oil from the poultry feeds due to its faster speed, lesser solvent consumption, more environmental friendly.

  19. AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

    Energy Technology Data Exchange (ETDEWEB)

    O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian; Eide, Christopher A.; Rivera, Victor M.; Wang, Frank; Adrian, Lauren T.; Zhou, Tianjun; Huang, Wei-Sheng; Xu, Qihong; Metcalf, III, Chester A.; Tyner, Jeffrey W.; Loriaux, Marc M.; Corbin, Amie S.; Wardwell, Scott; Ning, Yaoyu; Keats, Jeffrey A.; Wang, Yihan; Sundaramoorthi, Raji; Thomas, Mathew; Zhou, Dong; Snodgrass, Joseph; Commodore, Lois; Sawyer, Tomi K.; Dalgarno, David C.; Deininger, Michael W.N.; Druker, Brian J.; Clackson, Tim; (OHSU- Cancer Instit.); (ARIAD)

    2010-09-07

    Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABL{sup T315I} mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABL{sup T315I}-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML.

  20. Sequential Extraction as Novel Approach to Compare 12 Medicinal Plants From Kenya Regarding Their Potential to Release Chromium, Manganese, Copper, and Zinc.

    Science.gov (United States)

    Mogwasi, R; Zor, S; Kariuki, D K; Getenga, M Z; Nischwitz, V

    2018-04-01

    This study is focusing on a novel approach to screen a large number of medicinal plants from Kenya regarding their contents and availability of selected metals potentially relevant for treatment of diabetes patients. For this purpose, total levels of zinc, chromium, manganese, and copper were determined by flame atomic absorption spectrometry and inductively coupled plasma mass spectrometry as well as BCR sequential extraction to fractionate the elemental species in anti-diabetic medicinal plants collected from five natural locations in two sub counties in Nyamira County, Kenya. Solanum mauense had the highest zinc level of 123.0 ± 3.1 mg/kg while Warburgia ugandensis had the lowest level of 13.9 ± 0.4 mg/kg. The highest level of copper was in Bidens pilosa (29.0 ± 0.6 mg/kg) while the lowest was in Aloe vera (3.0 ± 0.1 mg/kg). Croton macrostachyus had the highest manganese level of 1630 ± 40 mg/kg while Clerodendrum myricoides had the lowest (80.2 ± 1.2 mg/kg). The highest level of chromium was in Solanum mauense (3.20 ± 0.06 mg/kg) while the lowest (0.04 ± 0.01 mg/kg) were in Clerodendrum myricoides and Warburgia ugandesis among the medicinal plants from Nyamira and Borabu, respectively. The levels of the elements were statistically different from that of other elements while the level of a given element was not statistically different in the medicinal plants from the different sub counties. Sequential extraction was performed to determine the solubility and thus estimate the bioavailability of the four investigated essential and potentially therapeutically relevant metals. The results showed that the easily bioavailable fraction (EBF) of chromium, manganese, zinc, and copper ranged from 6.7 to 13.8%, 4.1 to 10%, 2.4 to 10.2%, and 3.2 to 12.0% while the potentially bioavailable fraction (PBF) ranged from 50.1 to 67.6%, 32.2 to 48.7%, 23.0 to 41.1%, and 34.6 to 53.1%, respectively. Bidens pilosa, Croton macrostachyus, Ultrica dioica

  1. Sequential Combination of Microwave- and Ultrasound-Assisted Extraction of Total Flavonoids from Osmanthus fragrans Lour. Flowers

    Directory of Open Access Journals (Sweden)

    Jianfeng Yu

    2017-12-01

    Full Text Available Microwave-assisted and ultrasound-assisted extraction assays were used to isolate total flavonoids (TF from Osmanthus fragrans flowers. The effects of the solid-liquid ratio, ethanol concentration, microwave power, microwave extraction time, ultrasonic power and ultrasonic extraction time on the yield of TF were studied. A sequential combination of microwave- and ultrasound-assisted extraction (SC-MUAE methods was developed, which was subsequently optimized by Box-Behnken design-response surface methodology (BBD-RSM. The interaction effects of the ethanol concentration (40–60%, microwave extraction time (5–7 min, ultrasonic extraction time (8–12 min and ultrasonic power (210–430 W on the yield of TF were investigated. The optimum operating parameters for the extraction of TF were determined to be as follows: ethanol concentration (48.15%, microwave extraction time (6.43 min, ultrasonic extraction time (10.09 min and ultrasonic power (370.9 W. Under these conditions, the extraction yield of TF was 7.86 mg/g.

  2. Volatile profile characterisation of Chilean sparkling wines produced by traditional and Charmat methods via sequential stir bar sorptive extraction.

    Science.gov (United States)

    Ubeda, C; Callejón, R M; Troncoso, A M; Peña-Neira, A; Morales, M L

    2016-09-15

    The volatile compositions of Charmat and traditional Chilean sparkling wines were studied for the first time. For this purpose, EG-Silicone and PDMS polymeric phases were compared and, afterwards, the most adequate was selected. The best extraction method turned out to be a sequential extraction in the headspace and by immersion using two PDMS twisters. A total of 130 compounds were determined. In traditional Chilean sparkling wines, ethyl esters were significantly higher, while acetic esters and ketones were predominant in the Charmat wines. PCA and LDA confirmed the differences in the volatile profiles between the production methods (traditional vs. Charmat). Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Development of an automated sequential injection on-line solvent extraction-back extraction procedure as demonstrated for the determination of cadmium with detection by electrothermal atomic absorption spectrometry

    DEFF Research Database (Denmark)

    Wang, Jianhua; Hansen, Elo Harald

    2002-01-01

    An automated sequential injection (SI) on-line solvent extraction-back extraction separation/preconcentration procedure is described. Demonstrated for the assay of cadmium by electrothermal atomic absorption spectrometry (ETAAS), the analyte is initially complexed with ammonium pyrrolidinedithioc......An automated sequential injection (SI) on-line solvent extraction-back extraction separation/preconcentration procedure is described. Demonstrated for the assay of cadmium by electrothermal atomic absorption spectrometry (ETAAS), the analyte is initially complexed with ammonium...

  4. Sequential Application of Soil Vapor Extraction and Bioremediation Processes for the Remediation of Ethylbenzene-Contaminated Soils

    DEFF Research Database (Denmark)

    Soares, António Carlos Alves; Pinho, Maria Teresa; Albergaria, José Tomás

    2012-01-01

    Soil vapor extraction (SVE) is an efficient, well-known and widely applied soil remediation technology. However, under certain conditions it cannot achieve the defined cleanup goals, requiring further treatment, for example, through bioremediation (BR). The sequential application...... of these technologies is presented as a valid option but is not yet entirely studied. This work presents the study of the remediation of ethylbenzene (EB)-contaminated soils, with different soil water and natural organic matter (NOMC) contents, using sequential SVE and BR. The obtained results allow the conclusion that......: (1) SVE was sufficient to reach the cleanup goals in 63% of the experiments (all the soils with NOMC below 4%), (2) higher NOMCs led to longer SVE remediation times, (3) BR showed to be a possible and cost-effective option when EB concentrations were lower than 335 mg kgsoil −1, and (4...

  5. A sequential extraction procedure to determine Ra and U isotopes by alpha-particle spectrometry in selective leachates

    International Nuclear Information System (INIS)

    Aguado, J.L.; Bolivar, J.P.; San-Miguel, E.G.; Garcia-Tenorio, R.

    2003-01-01

    A radiochemical sequential extraction procedure has been developed in our laboratory to determine 226 Ra and 234,238 U by alpha spectrometry in environmental samples. This method has been validated for both radionuclides by comparing in selected samples the values obtained through its application with the results obtained by applying alternative procedures. Recoveries obtained, counting periods applied and background levels found in the alpha spectra give suitable detection limits to allow the Ra and U determination in operational forms defined in riverbed contaminated sediments. Results obtained in these speciation studies show that 226 Ra and 234,238 U contamination tend to be associated to precipitated forms of the sediments. (author)

  6. Determination of Lead(II), Copper(II), Zinc(II), Cobalt(II), Cadmium(II), Iron(III), Mercury(II) using sequential injection extractions.

    Science.gov (United States)

    van Staden, J F; Taljaard, R E

    2004-12-15

    Sequential injection analysis is still dominated by single component analysis. In this proposed robust, economical simple instrumental system seven different metal ions are determined simultaneously using thin-film sequential injection extraction (SIE) with multivariate calibration and multiwavelength detection. Dithizone, in ethanol, is used as extractant and the metal dithizonates' spectra are generated by a diode array spectrophotometer between 300 and 700nm. The SI thin-film extraction using water miscible with ethanol works due to the hydrophobic interaction of ethanol with the Teflon wall to create a thin film. A sample frequency of 27 samples per hour was obtained with a sample carry-over of less than 1%. The results of the proposed sequential injection extraction system compare favourably with the results obtained by using standard atomic absorption spectrometry (AAS) methods on conventional extraction samples.

  7. Anticancer Properties and Phenolic Contents of Sequentially Prepared Extracts from Different Parts of Selected Medicinal Plants Indigenous to Malaysia

    Directory of Open Access Journals (Sweden)

    Hadiza Altine Adamu

    2012-05-01

    Full Text Available Different parts of four edible medicinal plants (Casearia capitellata, Baccaurea motleyana, Phyllanthus pulcher and Strobilanthus crispus, indigenous to Malaysia, were extracted in different solvents, sequentially. The obtained 28 extracts were evaluated for their in vitro anticancer properties, using the MTS assay, on four human cancer cell lines: colon (HT-29, breast (MCF-7, prostate (DU-145 and lung (H460 cancers. The best anticancer activity was observed for the ethyl acetate (EA extract of Casearia capitellata leaves on MCF-7 cell lines with IC50 2.0 μg/mL and its methanolic (MeOH extract showed an outstanding activity against lung cancer cell lines. Dichloromethane (DCM extract of Phyllanthus pulcher aerial parts showed the highest anticancer activity against DU-145 cell lines, while significant activity was exhibited by DCM extract of Phyllanthus pulcher roots on colon cancer cell lines with IC50 value of 8.1 μg/mL. Total phenolic content (TPC ranged over 1–40 mg gallic acid equivalents (GAE/g. For all the samples, highest yields of phenolics were obtained for MeOH extracts. Among all the extracts analyzed, the MeOH extracts of Strobilanthus crispus leaves exhibited the highest TPC than other samples (p < 0.05. This study shows that the nature of phenol determines its anticaner activity and not the number of phenols present.

  8. Sequential extraction of heavy metals in river sediments of an abandoned pyrite mining area: pollution detection and affinity series.

    Science.gov (United States)

    Pagnanelli, F; Moscardini, E; Giuliano, V; Toro, L

    2004-11-01

    In this paper heavy metal pollution at an abandoned Italian pyrite mine has been investigated by comparing total concentrations and speciation of heavy metals (Fe, Cu, Mn, Zn, Pb and As) in a red mud sample and a river sediment. Acid digestions show that all the investigated heavy metals present larger concentrations in the sediment than in the tailing. A modified Tessier's procedure has been used to discriminate heavy metal bound to organic fraction from those originally present in the mineral sulphide matrix and to detect a possible trend of metal mobilisation from red mud to river sediment. Sequential extractions on bulk and size fractionated samples denote that sediment samples present larger percent concentrations of the investigated heavy metals in the first extractive steps (I-IV) especially in lower dimension size fractionated samples suggesting that heavy metals in the sediment are significantly bound by superficial adsorption mechanisms. Copyright 2004 Elsevier Ltd.

  9. Distribution of Zinc and Cadmium in Tissues of Giant Reed (Arundo Donax L.: Sequential Extraction - Radiometric Study

    Directory of Open Access Journals (Sweden)

    Richveisová Barbora Micháleková

    2014-06-01

    Full Text Available Heavy metals are taken up by the vascular plant root system from water solutions in cationic forms. Subsequently, during both short and long distance transport to other plant tissues, cation forms are incorporated to many bioorganic compounds differing in stability, ionic character and physico-chemical properties such as solubility in lipid structures and mobility across cell membrane systems. Many sequential and single step extraction methods have been elaborated for characterization of the role of individual components of plant cells components in transport and detoxication of heavy metals. In our study, dry biomass of giant reed (Arundo donax L. grown in hydroponic media spiked with 65ZnCl2 and 109CdCl2 was treated with dithizone solutions as complexing ligand in order to convert free Zn2+ and Cd2+ ions to corresponding dithizonates. Treatment with dithizone showed that up to 67 % of the total plant Cd and 56 % of the total plant Zn were transformed to dithizonate complexes extracted with chloroform. Extraction of biomass with Folch reagent showed that up to 48 % of the total root cadmium and up to 18 % of the total shoot cadmium is bound in lipid fraction. Zinc was not found in lipid fraction of root and shoot. Derivatization of the dried root and shoot lipid fraction by dithizone showed that two third of Cd in root and practically all Cd in shoot lipid fraction could be transformed to Cd-dithizonate. Methods of biomass treating with complexing ligands and a method of sequential extraction procedures with non-polar organic solvents and radiotracer methodology seem to be useful methods for the study of metal speciation and distribution in vascular plants

  10. Rapid Determination of Plutonium Isotopes in Environmental Samples Using Sequential Injection Extraction Chromatography and Detection by Inductively Coupled Plasma Mass Spectrometry

    DEFF Research Database (Denmark)

    Qiao, Jixin; Hou, Xiaolin; Roos, Per

    2009-01-01

    This article presents an automated method for the rapid determination of 239Pu and 240Pu in various environmental samples. The analytical method involves the in-line separation of Pu isotopes using extraction chromatography (TEVA) implemented in a sequential injection (SI) network followed...... of the in-line extraction chromatographic run was...

  11. Evaluation of sequential solvent and thermal extraction followed by analytical pyrolysis for chemical characterization of carbonaceous particulate matter.

    Science.gov (United States)

    Beránek, Josef; Kozliak, Evguenii; Kubátová, Alena

    2013-03-01

    A stepwise analytical protocol is presented for recognition of uncharacterized organic chemical entities comprising carbonaceous air particulate matter (PM). In this method, thermal treatment of PM samples starts with thermal extraction (TE) using temperatures below 300 °C to evolve volatile low molecular weight (LMW) chemicals followed by pyrolysis (Py) of non-volatile high molecular weight (HMW) compounds to yield signature patterns of their decomposition products. Both volatile species and pyrolyzed products are characterized using gas chromatography (GC) with a mass spectrometric (MS) detection. The efficacy of sequential TE (at 200 and 300 °C) and Py (at 400, 500, 600, 700, 800, 900 and 1000 °C) was demonstrated on a defined mixture of LMW species and non-volatile polystyrene, a model HMW compound. When a solid matrix, in a form of silica or graphite particles, was introduced to this system, we determined that a solvent extraction (SE) applied prior to a sequential TE/Py-GC/MS sample analysis was an essential step to eliminate the analyte-matrix interactions, which hindered the vaporization of LMW compounds from a solid matrix resulting in a poor TE/Py separation. This SE/TE/Py-GC/MS method was then successfully applied to PM samples representing real-world PM matrices to discover several novel features of PM composition. HMW species were observed in both water-soluble (extracts) and unextractable (solid residues after an exhaustive solvent extraction) fractions of wood smoke and urban PM. The species evolving upon pyrolysis were associated with the corresponding precursor polymers, such as oxidized fragments of lignin, polysaccharides and lipids, in wood smoke PM and non-volatile anthropogenic hydrocarbons in urban PM. The proposed sequential SE/TE/Py-GC/MS protocol is capable of revealing otherwise unobserved chemical components while providing useful information on their interactions within a complex and poorly characterized PM matrix. Signature SE

  12. Improving enzymatic hydrolysis efficiency of wheat straw through sequential autohydrolysis and alkaline post-extraction.

    Science.gov (United States)

    Wu, Xinxing; Huang, Chen; Zhai, Shengcheng; Liang, Chen; Huang, Caoxing; Lai, Chenhuan; Yong, Qiang

    2018-03-01

    In this work, a two-step pretreatment process of wheat straw was established by combining autohydrolysis pretreatment and alkaline post-extraction. The results showed that employing alkaline post-extraction to autohydrolyzed wheat straw could significantly improve its enzymatic hydrolysis efficiency from 36.0% to 83.7%. Alkaline post-extraction lead to the changes of the structure characteristics of autohydrolyzed wheat straw. Associations between enzymatic hydrolysis efficiency and structure characteristics were also studied. The results showed that the factors of structure characteristics such as delignification, xylan removal yield, crystallinity, accessibility and hydrophobicity are positively related to enzymatic hydrolysis efficiency within a certain range for alkaline post-extracted wheat straw. The results demonstrated that autohydrolysis coupled with alkaline post-extraction is an effective and promising method to gain fermentable sugars from biomass. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Sequential extraction procedures to ascertain the role of organic matter in the fate of iodine in soils

    International Nuclear Information System (INIS)

    Gavalda, D.; Colle, C.

    2004-01-01

    In the assessment of the radiological impact on man of radioactive substances the fate of the long-lived 129 I in soils is of special interest. In order to predict the behaviour of iodine in the environment the knowledge of soil parameters which are responsible for its sorption is necessary. Sequential extraction techniques were performed to investigate the degree of binding of iodine with soil components and more specifically with the different constituents of soil organic matter (humic acid, fulvic acid, humin) which are liable to change with time. A speciation scheme was especially developed to study the role of organic matter in iodine retention and complexation. In the first steps, several mineral fractions of iodine were extracted: water soluble (H 2 O), exchangeable (1M MgCl 2 ), carbonate bound (0.01N HCl), bound to Fe-Mn oxides (0.5 M NH 4 OH,HCl adjusted to pH=2 with HNO 3 ). After these preliminary steps, the extraction of organic matter was carried out with neutral pyrophosphate (Na 2 H 2 P 2 O 7 / K 4 P 2 O 7 1/1 0.1M pH=7) to determine iodine bound to organo-mineral complexes and sodium hydroxide (0.5 M NaOH) to quantify iodine bound to humic substances. For these extracts, the distribution of iodine between humic and fulvic acids was studied. Iodine bound to residual and insoluble organic matter (humin) was extracted with H 2 O 2 30% adjusted to pH=2 with HNO 3 . In the last step, iodine bound to the residual soil was extracted by wet digestion (H 2 SO 4 ). In this scheme, all the traditional organic reagents (acetate, acetic acid,..) were removed and replaced by mineral reagents to allow the monitoring of organic carbon in the soil extracts. (author)

  14. Environmentally friendly microwave-assisted sequential extraction method followed by ICP-OES and ion-chromatographic analysis for rapid determination of sulphur forms in coal samples.

    Science.gov (United States)

    Mketo, Nomvano; Nomngongo, Philiswa N; Ngila, J Catherine

    2018-05-15

    A rapid three-step sequential extraction method was developed under microwave radiation followed by inductively coupled plasma-optical emission spectroscopic (ICP-OES) and ion-chromatographic (IC) analysis for the determination of sulphur forms in coal samples. The experimental conditions of the proposed microwave-assisted sequential extraction (MW-ASE) procedure were optimized by using multivariate mathematical tools. Pareto charts generated from 2 3 full factorial design showed that, extraction time has insignificant effect on the extraction of sulphur species, therefore, all the sequential extraction steps were performed for 5 min. The optimum values according to the central composite designs and counter plots of the response surface methodology were 200 °C (microwave temperature) and 0.1 g (coal amount) for all the investigated extracting reagents (H 2 O, HCl and HNO 3 ). When the optimum conditions of the proposed MW-ASE procedure were applied in coal CRMs, SARM 18 showed more organic sulphur (72%) and the other two coal CRMs (SARMs 19 and 20) were dominated by sulphide sulphur species (52-58%). The sum of the sulphur forms from the sequential extraction steps have shown consistent agreement (95-96%) with certified total sulphur values on the coal CRM certificates. This correlation, in addition to the good precision (1.7%) achieved by the proposed procedure, suggests that the sequential extraction method is reliable, accurate and reproducible. To safe-guard the destruction of pyritic and organic sulphur forms in extraction step 1, water was used instead of HCl. Additionally, the notorious acidic mixture (HCl/HNO 3 /HF) was replaced by greener reagent (H 2 O 2 ) in the last extraction step. Therefore, the proposed MW-ASE method can be applied in routine laboratories for the determination of sulphur forms in coal and coal related matrices. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Sequential high pressure extractions applied to recover piceatannol and scirpusin B from passion fruit bagasse.

    Science.gov (United States)

    Viganó, Juliane; Aguiar, Ana C; Moraes, Damila R; Jara, José L P; Eberlin, Marcos N; Cazarin, Cinthia B B; Maróstica, Mário R; Martínez, Julian

    2016-07-01

    Passion fruit seeds are currently discarded on the pulp processing but are known for their high piceatannol and scirpusin B contents. Using pressurized liquid extraction (PLE), these highly valuable phenolic compounds were efficiently extracted from defatted passion fruit bagasse (DPFB). PLE was performed using mixtures of ethanol and water (50 to 100% ethanol, w/w) as solvent, temperatures from 50 to 70°C and pressure at 10MPa. The extraction methods were compared in terms of the global yield, total phenolic content (TPC), piceatannol content and the antioxidant capacity of the extracts. The DPFB extracts were also compared with those from non-defatted passion fruit bagasse (nDPFB). Identification and quantification of piceatannol were performed using UHPLC-MS/MS. The results showed that high TPC and piceatannol content were achieved for the extracts obtained from DPFB through PLE at 70°C and using 50 and 75% ethanol as the solvent. The best PLE conditions for TPC (70°C, 75% ethanol) resulted in 55.237mgGAE/g dried and defatted bagasse, whereas PLE at 70°C and 50% ethanol achieved 18.590mg of piceatannol/g dried and defatted bagasse, and such yields were significantly higher than those obtained using conventional extraction techniques. The antioxidant capacity assays showed high correlation with the TPC (r>0.886) and piceatannol (r>0.772). The passion fruit bagasse has therefore proved to be a rich source of piceatannol and PLE showed high efficiency to recover phenolic compounds from defatted passion fruit bagasse. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Exploiting Sequential Injection on-line Solvent Extraction/Back Extraction with Detection by ETAAS or ICPMS

    DEFF Research Database (Denmark)

    Wang, Jianhua; Hansen, Elo Harald

    presents an on-line SI-solvent extraction/back extraction procedure used in connection with detection by either ETAAS or ICPMS. Incorporating two newly designed dual-conical gravitational phase separators, its performance is demonstrated for the determination of various metals in reference materials.......Electrothermal atomic absorption spectrometry (ETAAS) and inductively coupled plasma mass spectrometry (ICPMS) are highly sensitive techniques for trace metal analyses. Nevertheless, separation/preconcentration procedures are often called for in order to overcome their inherent low matrix...... tolerances. With detection by ETAAS, separation/preconcentration by solvent extraction has enjoyed much use. However, this approach is not necessarily the optimal one since introduction of organic eluates directly into the graphite tube might lead to deteriorated reproducibility and lower sensitivity...

  17. Exploiting sequential injection on-line solvent extraction/back extraction with detection by ETAAS and ICPMS

    DEFF Research Database (Denmark)

    Wang, Jianhua; Hansen, Elo Harald

    presents an on-line SI-solvent extraction/back extraction procedure used in connection with detection by either ETAAS or ICPMS. Incorporating two newly designed dual-conical gravitational phase separators, its performance is demonstrated for the determination of various metals in reference materials.......Electrothermal atomic absorption spectrometry (ETAAS) and inductively coupled plasma mass spectrometry (ICPMS) are highly sensitive techniques for trace metal analyses. Nevertheless, separation/preconcentration procedures are often called for in order to overcome their inherent low matrix tolerance....... With detection by ETAAS, separation/preconcentration by solvent extraction has enjoyed much use. However, this approach is not necessarily the optimal one since introduction of organic eluates directly into the graphite tube might lead to deteriorated reproducibility and lower sensitivity. And for ICPMS...

  18. Recovery of Cobalt as Cobalt Oxalate from Cobalt Tailings Using Moderately Thermophilic Bioleaching Technology and Selective Sequential Extraction

    Directory of Open Access Journals (Sweden)

    Guobao Chen

    2016-07-01

    Full Text Available Cobalt is a very important metal which is widely applied in various critical areas, however, it is difficult to recover cobalt from minerals since there is a lack of independent cobalt deposits in nature. This work is to provide a complete process to recover cobalt from cobalt tailings using the moderately thermophilic bioleaching technology and selective sequential extraction. It is found that 96.51% Co and 26.32% Cu were extracted after bioleaching for four days at 10% pulp density. The mean compositions of the leach solutions contain 0.98 g·L−1 of Co, 6.52 g·L−1 of Cu, and 24.57 g·L−1 of Fe (III. The copper ion was then recovered by a solvent extraction process and the ferric ions were selectively removed by applying a goethite deironization process. The technological conditions of the above purification procedures were deliberately discussed. Over 98.6% of copper and 99.9% of ferric ions were eliminated from the leaching liquor. Cobalt was finally produced as cobalt oxalate and its overall recovery during the whole process was greater than 95%. The present bioleaching process of cobalt is worth using for reference to deal with low-grade cobalt ores.

  19. Sequential Extraction of Cu, Cd, Pb and Zn from Soil Around ...

    African Journals Online (AJOL)

    The presence of heavy metals in soil around industrial wastes dump sites restricts their use for agricultural purpose. This study attempts to extract Cu, Cd, Pb and Zn from soils around some selected industrial wastes dump sites in Kaduna. Four dump sites were identified namely Kudenda, Kakuri, Gonigora and Dirkaniya.

  20. BCR-ABL1 transcript types showed distinct laboratory characteristics in patients with chronic myeloid leukemia.

    Science.gov (United States)

    Vasconcelos, A P; Azevedo, I F; Melo, F C B C; Neves, W B; Azevedo, A C A C; Melo, R A M

    2017-04-20

    In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent. Samples were collected for RNA extraction and analyzed by reverse transcription-polymerase chain reaction (PCR), according to the international protocol BIOMED-1. The LeukemiaNet 2013 criteria were used to establish the molecular response. The frequency distribution of the BCR-ABL1 transcripts was e14a2 (64%), e13a2 (34%), and double positives (2%). The results showed a statistically significant association of the e14a2 transcript type with thrombocytosis (P = 0.0005) and the e13a2 with higher leukocyte count (P = 0.0491). In a subgroup of 44 patients, the molecular response to treatment with Imatinib was assessed by quantitative PCR at 3 months (BCR-ABL1 ≤ 10%), 6 months (BCR-ABL1 ≤ 1%), or 12 months (BCR-ABL1 ≤ 0.1%). Although patients with the transcript e14a2 showed higher frequency of good responses than patients with the transcript e13a2, this difference was not statistically significant. In agreement with published data, our results showed association of the BCR-ABL1 transcript e14a2 with thrombocytosis and the BCR-ABL1 transcript e13a2 with higher leukocytosis in patients with chronic myeloid leukemia.

  1. Sequential extraction procedures to ascertain the role of organic matter in the fate of iodine in soils

    Energy Technology Data Exchange (ETDEWEB)

    Gavalda, D.; Colle, C. [CEA Cadarache (DEI/SECRE/LRE), Laboratory of Radioecology and Ecotoxicology, Institute for Radioprotection and Nuclear Safety, 13 - Saint-Paul-lez-Durance (France)

    2004-07-01

    In the assessment of the radiological impact on man of radioactive substances the fate of the long-lived {sup 129}I in soils is of special interest. In order to predict the behaviour of iodine in the environment the knowledge of soil parameters which are responsible for its sorption is necessary. Sequential extraction techniques were performed to investigate the degree of binding of iodine with soil components and more specifically with the different constituents of soil organic matter (humic acid, fulvic acid, humin) which are liable to change with time. A speciation scheme was especially developed to study the role of organic matter in iodine retention and complexation. In the first steps, several mineral fractions of iodine were extracted: water soluble (H{sub 2}O), exchangeable (1M MgCl{sub 2} ), carbonate bound (0.01N HCl), bound to Fe-Mn oxides (0.5 M NH{sub 4}OH,HCl adjusted to pH=2 with HNO{sub 3}). After these preliminary steps, the extraction of organic matter was carried out with neutral pyrophosphate (Na{sub 2}H{sub 2}P{sub 2}O{sub 7}/ K{sub 4}P{sub 2}O{sub 7} 1/1 0.1M pH=7) to determine iodine bound to organo-mineral complexes and sodium hydroxide (0.5 M NaOH) to quantify iodine bound to humic substances. For these extracts, the distribution of iodine between humic and fulvic acids was studied. Iodine bound to residual and insoluble organic matter (humin) was extracted with H{sub 2}O{sub 2} 30% adjusted to pH=2 with HNO{sub 3}. In the last step, iodine bound to the residual soil was extracted by wet digestion (H{sub 2}SO{sub 4}). In this scheme, all the traditional organic reagents (acetate, acetic acid,..) were removed and replaced by mineral reagents to allow the monitoring of organic carbon in the soil extracts. (author)

  2. Sequential Extractions and Toxicity Potential of Trace Metals Absorbed into Airborne Particles in an Urban Atmosphere of Southwestern Nigeria

    Directory of Open Access Journals (Sweden)

    Emmanuel Gbenga Olumayede

    2018-01-01

    Full Text Available The paper investigates the hypothesis that biotoxicities of trace metals depend not only on the concentration as expressed by the total amount, but also on their geochemical fractions and bioavailability. Airborne particles were collected using SKC Air Check XR 5000 high volume Sampler at a human breathing height of 1.5–2.0 meters, during the dry season months from November 2014 to March 2015 at different locations in Akure (7°10′N and 5°15′E. The geochemical-based sequential extractions were performed on the particles using a series of increasingly stringent solutions selected to extract metals (Cd, Cu, Cr, Ni, Pb, Zn, and Mn into four operational geochemical phases—exchangeable, reducible, organic, and residual—and then quantified using an Atomic Absorption Spectrophotometer. The results showed metals concentration of order Pb > Cr > Cd > Zn > Ni > Cu > Mn. However, most metals in the samples exist in nonmobile fractions: exchangeable (6.43–16.2%, reducible (32.58–47.39%, organic (4.73–9.88%, and residual (18.28–27.53%. The pollution indices show ingestion as the leading route of metal exposure, with noncarcinogenic (HQ and cancer risk (HI for humans in the area being higher than 1.0 × 10−4, indicating a health threat.

  3. Comparison of first pass bolus AIFs extracted from sequential 18F-FDG PET and DSC-MRI of mice

    International Nuclear Information System (INIS)

    Evans, Eleanor; Sawiak, Stephen J.; Ward, Alexander O.; Buonincontri, Guido; Hawkes, Robert C.; Adrian Carpenter, T.

    2014-01-01

    Accurate kinetic modelling of in vivo physiological function using positron emission tomography (PET) requires determination of the tracer time–activity curve in plasma, known as the arterial input function (AIF). The AIF is usually determined by invasive blood sampling methods, which are prohibitive in murine studies due to low total blood volumes. Extracting AIFs from PET images is also challenging due to large partial volume effects (PVE). We hypothesise that in combined PET with magnetic resonance imaging (PET/MR), a co-injected bolus of MR contrast agent and PET ligand can be tracked using fast MR acquisitions. This protocol would allow extraction of a MR AIF from MR contrast agent concentration–time curves, at higher spatial and temporal resolution than an image-derived PET AIF. A conversion factor could then be applied to the MR AIF for use in PET kinetic analysis. This work has compared AIFs obtained from sequential DSC-MRI and PET with separate injections of gadolinium contrast agent and 18 F-FDG respectively to ascertain the technique′s validity. An automated voxel selection algorithm was employed to improve MR AIF reproducibility. We found that MR and PET AIFs displayed similar character in the first pass, confirmed by gamma variate fits (p<0.02). MR AIFs displayed reduced PVE compared to PET AIFs, indicating their potential use in PET/MR studies

  4. Sequential extraction of heavy metals in river sediments of an abandoned pyrite mining area: pollution detection and affinity series

    Energy Technology Data Exchange (ETDEWEB)

    Pagnanelli, F. [Department of Chemistry, University of Rome ' ' La Sapienza' ' , P.le A. Moro, 5, 00185 Rome (Italy)]. E-mail: francesca.pagnanelli@uniroma1.it; Moscardini, E. [Department of Chemistry, University of Rome ' ' La Sapienza' ' , P.le A. Moro, 5, 00185 Rome (Italy); Giuliano, V. [Institute of Environmental Geology and Geoengineering (CNR), Via Bolognola, 7, 00138 Rome (Italy); Toro, L. [Department of Chemistry, University of Rome ' ' La Sapienza' ' , P.le A. Moro, 5, 00185 Rome (Italy)

    2004-11-01

    In this paper heavy metal pollution at an abandoned Italian pyrite mine has been investigated by comparing total concentrations and speciation of heavy metals (Fe, Cu, Mn, Zn, Pb and As) in a red mud sample and a river sediment. Acid digestions show that all the investigated heavy metals present larger concentrations in the sediment than in the tailing. A modified Tessier's procedure has been used to discriminate heavy metal bound to organic fraction from those originally present in the mineral sulphide matrix and to detect a possible trend of metal mobilisation from red mud to river sediment. Sequential extractions on bulk and size fractionated samples denote that sediment samples present larger percent concentrations of the investigated heavy metals in the first extractive steps (I-IV) especially in lower dimension size fractionated samples suggesting that heavy metals in the sediment are significantly bound by superficial adsorption mechanisms. - Capsule: A modified Tessier's procedure, discriminating organic and sulphide bound metals, was used to detect pollutant mobilisation from red mud to river sediment in an abandoned pyrite mine.

  5. Sequential solvent extraction for the modes of occurrence of selenium in coals of different ranks from the Huaibei Coalfield, China

    Directory of Open Access Journals (Sweden)

    Wang Lei

    2007-12-01

    Full Text Available Abstract Forms of selenium in bituminous coal, anthracite, and cokeite (natural coke from Huaibei Coalfield, Anhui, China, have been determined by sequential solvent extraction. The selenium content in bulk samples is 4.0, 2.4, and 2.0 μg/g in bituminous coal, anthracite, and cokeite, respectively. The six forms of selenium determined by six-step solvent extraction are water-leachable, ion-exchangeable, organic matter-associated, carbonate-associated, silicate-associated, and sulfide-associated. The predominant forms of selenium in bituminous coal are organic matter-associated (39.0%, sulfide-associated (21.1%, and silicate bound (31.8%; these three forms account for 92% of the total. The organic matter bound-selenium decrease dramatically from bituminous coal (39.0% to anthracite (11.6% and to cokeite (0%, indicating that organic matter bound selenium is converted to other forms during metamorphism of the coal, most likely sulfide-form. The sulfide-associated form increased remarkably from bituminous coal (21.1% to anthracite (50.4% and cokeite (54.5%, indicating the formation of selenium sulfide, possibly in pyrite during the transformation of bituminous coal to anthracite and cokeite. The silicate-associated selenium in bituminous coal (31.8% is much higher than that in anthracite (16.4% and cokeite (15.8%, indicating that silicate-associated selenium is partly converted to sulfide during metamorphism.

  6. Extraction, texture analysis and polysaccharide epitope mapping data of sequential extracts of strawberry, apple, tomato and aubergine fruit parenchyma

    Directory of Open Access Journals (Sweden)

    Valérie Cornuault

    2018-04-01

    Full Text Available The data included in this article are related to the research article entitled “Disentangling pectic homogalacturonan and rhamnogalacturonan-I polysaccharides: evidence for sub-populations in fruit parenchyma systems” (Cornuault et al., 2018 [1]. Cell wall properties are an important contributor to fruit texture. These datasets compile textural and immunochemical analysis of polysaccharides of four economically important fruit crops: tomato, strawberry, aubergine and apple with contrasting textures and related taxonomical origins. Cell wall components and their extractability were assessed using characterized monoclonal antibodies. In addition, textural data obtained for the four parenchyma systems show variations in the mechanical properties. The two datasets are a basis to relate cell wall composition and organization to the mechanical properties of the fruit parenchyma tissues. Keywords: Pectic polysaccharides, Fruits, Cell wall, Texture, Monoclonal antibodies, Solanaceae, Rosaceae, Tomato, Aubergine, Apple, Strawberry

  7. Speciation of 210Po and 210Pb in air particulates determined by sequential extraction

    International Nuclear Information System (INIS)

    Al-Masri, M.S.; Al-Karfan, K.; Khalili, H.; Hassan, M.

    2006-01-01

    Speciation of 210 Po and 210 Pb in air particulates of two Syrian phosphate sites with different climate conditions has been studied. The sites are the mines and Tartous port at the Mediterranean Sea. Air filters were collected during September 2000 until February 2002 and extracted chemically using different selective fluids in an attempt to identify the different forms of these two radionuclides. The results have shown that the inorganic and insoluble 21 Po and 21 Pb (attached to silica and soluble in mineral acids) portion was found to be high in both sites and reached a maximum value of 94% and 77% in the mine site and Tartous port site, respectively. In addition, only 24% of 21 Pb in air particulates was found to be associated with organic materials probably produced from the incomplete burning of fuel vehicle and similar activities. Moreover, the 210 Po/ 21- Pb activity ratio in air particulates was higher than that in all samples at both sites and varied between 3.85 in November 2000 at Tartous port site and 20 in April 2001 at the mine area. These activity ratios were also higher than the natural levels. The 210 Po/ 210 Pb activity ratio was also determined in each portion resulting from the selective extraction and found to be higher than that in most samples. The sources of 210 Po excess in these portions are discussed. Soil suspension, which is common in the dry climate dominant in the area, sea water spray and heating of phosphate ores were considered; polonium is more volatile than the lead compounds at even moderate temperature. Furthermore, variations in the chemical forms of 210 Po and 210 Pb during the year were also investigated. However, the results of this study can also be utilized for dose assessment to phosphate industry workers

  8. Phenolic compounds and antioxidant activity of Pecan [Carya illinoinensis (Wangenh. C. Koch] kernel cake extracts obtained by sequential extraction

    Directory of Open Access Journals (Sweden)

    Block, Jane Mara

    2009-12-01

    Full Text Available The total phenolic and condensed tannin contents of different Pecan kernel cake extracts (ether, acetone, alcohol and distilled water were estimated and their antioxidant activities were evaluated through ABTS, DPPH and ß-carotene/linoleic acid systems. Color variations of the Pecan kernel cake were determined through an instrumental analysis using the CIE Lab system. Significantly higher levels (p El contenido de taninos condensado y fenoles totales de diferentes extractos de tortas de almendra de pecana (éter, acetona, alcohol y agua destilada fueron estimados y sus actividades antioxidantes fueron evaluadas mediantes los métodos con ABTS, DPPH y el sistema ß-caroteno/ácido linoleico. Las variaciones de color de la torta de almendra de pecana fueron determinadas mediante análisis instrumental usando el sistema CIE Lab. Los contenidos de fenoles totales, taninos condensados y actividad antioxidante, medida mediante los métodos con ABTS Y DPPH (30 min y 24 h, fueron significativamente más altos (p < 0.05 con el extracto de acetona (16.4 mg GAE/g; 31.2 mg CE/g; 235.3 μmol TEAC/g and 68.6 and 100.3 mg TEAC/g, respectivamente. El porcentaje de inhibición de la oxidación en el sistema ß-caroteno/ ácido linoleico vario desde 37.9 a 93.1% con el extracto de acetona a 300 ppm, mostrando resultados significativamente superiores. Las muestras con una mayor tendencia a tonos rojos presento los niveles más altos de taninos condensados.

  9. Strontium distribution and origins in a natural clayey formation (Callovian-Oxfordian, Paris Basin, France): a new sequential extraction procedure

    International Nuclear Information System (INIS)

    Lerouge, C.; Gaucher, E.C.; Tournassat, C.; Negrel, P.; Crouzet, C.; Guerrot, C.; Gautier, A.; Michel, P.; Vinsot, A.; Buschaert, S.

    2010-01-01

    Document available in extended abstract form only. Strontium is a minor element in the Callovian-Oxfordian clayey formation of Bure (ANDRA Underground Research laboratory, France) and may be interesting as a natural analogue of cationic radionuclides. The objective of our study was to better understand the chemical behaviour of this element since the sediment deposition. Previous mineralogical work showed that main strontium-bearing minerals in the clay-stones, in addition to clay minerals, are celestite, carbonates and accessory micas and K-feldspars. In order to establish the strontium distribution and determine its origins across the clayey formation and establish a strontium diffusion profile, a four step sequential extraction procedure combined with strontium isotopes was developed and adapted to the mineralogy of the Bure clay-stones. The four-steps sequential extraction developed and applied to sixteen samples of Callovian-Oxfordian clay-stones showed that the exchangeable fraction (27 to 48% of the total strontium) and the carbonate fraction (38-47% of the total strontium) are the two main fractions carrying the strontium, the detrital fraction being secondary (< 15%). Celestite is the major strontium-carrier mineral that can perturb the results of the sequential extraction but not significantly modify the distribution of strontium at the scale of the formation. The celestite was studied on micronic to centi-metric crystals, separated by hand-picking on core samples. The development of this sequential extraction procedure for the Callovian-Oxfordian formation shows the importance of the first cobalt hexamine trichloride step to extract the exchangeable strontium adsorbed on clay minerals and block the exchangeable sites with cobalt for the following steps, allowing a good separation of exchangeable fraction and carbonates. However the reagent/solid ratio of 20 seems to be less adapted to carbonate-rich samples. The good separation between exchangeable

  10. Development of a rapid method for the sequential extraction and subsequent quantification of fatty acids and sugars from avocado mesocarp tissue.

    Science.gov (United States)

    Meyer, Marjolaine D; Terry, Leon A

    2008-08-27

    Methods devised for oil extraction from avocado (Persea americana Mill.) mesocarp (e.g., Soxhlet) are usually lengthy and require operation at high temperature. Moreover, methods for extracting sugars from avocado tissue (e.g., 80% ethanol, v/v) do not allow for lipids to be easily measured from the same sample. This study describes a new simple method that enabled sequential extraction and subsequent quantification of both fatty acids and sugars from the same avocado mesocarp tissue sample. Freeze-dried mesocarp samples of avocado cv. Hass fruit of different ripening stages were extracted by homogenization with hexane and the oil extracts quantified for fatty acid composition by GC. The resulting filter residues were readily usable for sugar extraction with methanol (62.5%, v/v). For comparison, oil was also extracted using the standard Soxhlet technique and the resulting thimble residue extracted for sugars as before. An additional experiment was carried out whereby filter residues were also extracted using ethanol. Average oil yield using the Soxhlet technique was significantly (P oil extracts following both methods were very similar. Oil recovery improved with increasing ripeness of the fruit with minor differences observed in the fatty acid composition during postharvest ripening. After lipid removal, methanolic extraction was superior in recovering sucrose and perseitol as compared to 80% ethanol (v/v), whereas mannoheptulose recovery was not affected by solvent used. The method presented has the benefits of shorter extraction time, lower extraction temperature, and reduced amount of solvent and can be used for sequential extraction of fatty acids and sugars from the same sample.

  11. Sequential Total Variation Denoising for the Extraction of Fetal ECG from Single-Channel Maternal Abdominal ECG.

    Science.gov (United States)

    Lee, Kwang Jin; Lee, Boreom

    2016-07-01

    Fetal heart rate (FHR) is an important determinant of fetal health. Cardiotocography (CTG) is widely used for measuring the FHR in the clinical field. However, fetal movement and blood flow through the maternal blood vessels can critically influence Doppler ultrasound signals. Moreover, CTG is not suitable for long-term monitoring. Therefore, researchers have been developing algorithms to estimate the FHR using electrocardiograms (ECGs) from the abdomen of pregnant women. However, separating the weak fetal ECG signal from the abdominal ECG signal is a challenging problem. In this paper, we propose a method for estimating the FHR using sequential total variation denoising and compare its performance with that of other single-channel fetal ECG extraction methods via simulation using the Fetal ECG Synthetic Database (FECGSYNDB). Moreover, we used real data from PhysioNet fetal ECG databases for the evaluation of the algorithm performance. The R-peak detection rate is calculated to evaluate the performance of our algorithm. Our approach could not only separate the fetal ECG signals from the abdominal ECG signals but also accurately estimate the FHR.

  12. Sequential Total Variation Denoising for the Extraction of Fetal ECG from Single-Channel Maternal Abdominal ECG

    Directory of Open Access Journals (Sweden)

    Kwang Jin Lee

    2016-07-01

    Full Text Available Fetal heart rate (FHR is an important determinant of fetal health. Cardiotocography (CTG is widely used for measuring the FHR in the clinical field. However, fetal movement and blood flow through the maternal blood vessels can critically influence Doppler ultrasound signals. Moreover, CTG is not suitable for long-term monitoring. Therefore, researchers have been developing algorithms to estimate the FHR using electrocardiograms (ECGs from the abdomen of pregnant women. However, separating the weak fetal ECG signal from the abdominal ECG signal is a challenging problem. In this paper, we propose a method for estimating the FHR using sequential total variation denoising and compare its performance with that of other single-channel fetal ECG extraction methods via simulation using the Fetal ECG Synthetic Database (FECGSYNDB. Moreover, we used real data from PhysioNet fetal ECG databases for the evaluation of the algorithm performance. The R-peak detection rate is calculated to evaluate the performance of our algorithm. Our approach could not only separate the fetal ECG signals from the abdominal ECG signals but also accurately estimate the FHR.

  13. Sequential Total Variation Denoising for the Extraction of Fetal ECG from Single-Channel Maternal Abdominal ECG

    Science.gov (United States)

    Lee, Kwang Jin; Lee, Boreom

    2016-01-01

    Fetal heart rate (FHR) is an important determinant of fetal health. Cardiotocography (CTG) is widely used for measuring the FHR in the clinical field. However, fetal movement and blood flow through the maternal blood vessels can critically influence Doppler ultrasound signals. Moreover, CTG is not suitable for long-term monitoring. Therefore, researchers have been developing algorithms to estimate the FHR using electrocardiograms (ECGs) from the abdomen of pregnant women. However, separating the weak fetal ECG signal from the abdominal ECG signal is a challenging problem. In this paper, we propose a method for estimating the FHR using sequential total variation denoising and compare its performance with that of other single-channel fetal ECG extraction methods via simulation using the Fetal ECG Synthetic Database (FECGSYNDB). Moreover, we used real data from PhysioNet fetal ECG databases for the evaluation of the algorithm performance. The R-peak detection rate is calculated to evaluate the performance of our algorithm. Our approach could not only separate the fetal ECG signals from the abdominal ECG signals but also accurately estimate the FHR. PMID:27376296

  14. Evaluation of Mobility, Bioavailability and Toxicity of Pb and Cd in Contaminated Soil Using TCLP, BCR and Earthworms

    Science.gov (United States)

    Kede, Maria Luiza F. M.; Correia, Fabio V.; Conceição, Paulo F.; Salles Junior, Sidney F.; Marques, Marcia; Moreira, Josino C.; Pérez, Daniel V.

    2014-01-01

    The objective of the present study was to investigate the reduction of mobility, availability and toxicity found in soil contaminated with lead (Pb) and cadmium (Cd) from Santo Amaro Municipality, Bahia, Brazil using two combined methods, commonly tested separately according to the literature: metal mobilization with phosphates and phytoextraction. The strategy applied was the treatment with two sources of phosphates (separately and mixed) followed by phytoremediation with vetiver grass (Vetiveria zizanioides (L.)). The treatments applied (in triplicates) were: T1—potassium dihydrogen phosphate (KH2PO4); T2—reactive natural phosphate fertilizer (NRP) and; T3—a mixture 1:1 of KH2PO4 and NRP. After this step, untreated and treated soils were planted with vetiver grass. The extraction procedures and assays applied to contaminated soil before and after the treatments included metal mobility test (TCLP); sequential extraction with BCR method; toxicity assays with Eisenia andrei. The soil-to-plant transfer factors (TF) for Pb and Cd were estimated in all cases. All treatments with phosphates followed by phytoremediation reduced the mobility and availability of Pb and Cd, being KH2PO4 (T1) plus phytoremediation the most effective one. Soil toxicity however, remained high after all treatments. PMID:25386955

  15. On-line coupling of Micro-Extraction by Packed Sorbent with Sequential Injection Chromatography system for direct extraction and determination of betaxolol in human urine.

    Science.gov (United States)

    Šrámková, Ivana; Chocholouš, Petr; Sklenářová, Hana; Šatínský, Dalibor

    2015-10-01

    A novel approach for automation of Micro-Extraction by Packed Sorbent (MEPS), a solid phase extraction technique, is presented, enabling precise and repeatable liquid handling due to the employment of sequential injection technique. The developed system was used for human urine sample clean-up and pre-concentration of betaxolol before its separation and determination. A commercial MEPS C-18 cartridge was integrated into an SIChrom™ system. The chromatographic separation was performed on a monolithic High Resolution C18 (50×4.6 mm) column which was coupled on-line in the system with Micro-Extraction using an additional selection valve. A mixture of acetonitrile and aqueous solution of 0.5% triethylamine with acetic acid, pH adjusted to 4.5 in ratio 30:70 was used as a mobile phase for elution of betaxolol from MEPS directly onto the monolithic column where the separation took place. Betaxolol was quantified by a fluorescence detector at wavelengths λ(ex)=220 nm and λ(em)=305 nm. The linear calibration range of 5-400 ng mL(-1), with limit of detection 1.5 ng mL(-1) and limit of quantification 5 ng mL(-1) and correlation r=0.9998 for both the standard and urine matrix calibration were achieved. The system recovery was 105±5%; 100±4%; 108±1% for three concentration levels of betaxolol in 10 times diluted urine - 5, 20 and 200 ng mL(-1), respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. On-line dynamic fractionation and automatic determination of inorganic phosphorous in environmental solid substrates exploiting sequential injection microcolumn extraction and flow injection analysi

    DEFF Research Database (Denmark)

    Buanuam, Janya; Miró, Manuel; Hansen, Elo Harald

    2006-01-01

    associations for phosphorus, that is, exchangeable, Al- and Fe-bound and Ca-bound fractions, were elucidated by accommodation in the flow manifold of the 3 steps of the Hietjles-Litjkema (HL) scheme involving the use of 1.0 M NH4Cl, 0.1 M NaOH and 0.5 M HCl, respectively, as sequential leaching reagents....... The precise timing and versatility of SI for tailoring various operational extraction modes were utilised for investigating the extractability and extent of phosphorous re-distribution for variable partitioning times. Automatic spectrophotometric determination of soluble reactive phosphorous in soil extracts...

  17. Comprehensive Profiling of Phytohormones in Honey by Sequential Liquid-Liquid Extraction Coupled with Liquid Chromatography-Mass Spectrometry.

    Science.gov (United States)

    Wang, Qing; Cai, Wen-Jing; Yu, Lei; Ding, Jun; Feng, Yu-Qi

    2017-01-25

    Honey exhibits various nutritional and medicinal functions, which are highly related to the active components; thus, the exploration of new compounds in honey is of great importance. Because honey is a byproduct of flower nectar, which is rich in phytohormones, the existence of phytohormones in honey is anticipated. In this research, a method for comprehensive profiling of 49 phytohormones in honey was developed by sequential liquid-liquid extraction (LLE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Good linearities for 49 phytohormones were obtained with correlation coefficients (R) larger than 0.9913. The limits of detection (LODs) were in the range of 0.2-628.2 pg/mL. Satisfied reproducibility and reliability were achieved by evaluation of the intra- and interday precisions with relative standard deviations (RSDs) less than 15.8% and relative recoveries ranging from 80.4 to 123.7%. The method was further applied to analyze the phytohormones in 14 monofloral raw honey samples and 3 commercial honey samples. The existence of 34 phytohormones was confirmed, including 14 cytokinins (CKs), 8 gibberellins (GAs), 5 brassinosteroids (BRs), indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), abscisic acid (ABA), salicylic acid (SA), jasmonic acid (JA), jasmonoyl-leucine (JA-Leu), and jasmonoyl-phenylalanine (JA-Phe). In addition, the content and species of phytohormones varies in different kinds of honey. The study is beneficial to fully illustrate the phytohormone profile of honey and contributive to elucidate the mechanism of its nutritional and medicinal functions.

  18. Development of on-line single-drop micro-extraction sequential injection system for electrothermal atomic absorption spectrometric determination of trace metals

    International Nuclear Information System (INIS)

    Anthemidis, Aristidis N.; Adam, Ibrahim S.I.

    2009-01-01

    A novel automatic sequential injection (SI) single-drop micro-extraction (SDME) system is proposed as versatile approach for on-line metal preconcentration and/or separation. Coupled to electrothermal atomic absorption spectrometry (ETAAS) the potentials of this SI scheme are demonstrated for trace cadmium determination in water samples. A non-charged complex of cadmium with ammonium diethyldithiophosphate (DDPA) was produced and extracted on-line into a 60 μL micro-drop of di-isobutyl ketone (DIBK). The extraction procedure was performed into a newly designed flow-through extraction cell coupled on a sequential injection manifold. As the complex Cd(II)-DDPA flowed continuously around the micro-droplet, the analyte was extracting into the solvent micro-drop. All the critical parameters were optimized and offered good performance characteristics and high preconcentration ratios. For 600 s micro-extraction time, the enhancement factor was 10 and the sampling frequency was 6 h -1 . The detection limit was 0.01 μg L -1 and the precision (RSD at 0.1 μg L -1 of cadmium) was 3.9%. The proposed method was evaluated by analyzing certified reference material

  19. Combining Sequential Extractions and X-ray Absorption Spectroscopy for Quantitative and Qualitative Zinc Speciation in Soil

    Science.gov (United States)

    Bauer, Tatiana; Minkina, Tatiana; Batukaev, Abdulmalik; Nevidomskaya, Dina; Burachevskaya, Marina; Tsitsuashvili, Viktoriya; Urazgildieva, Kamilya

    2017-04-01

    The combined use of X-ray absorption spectrometry and extractive fractionation is an effective approach for studying the interaction of metal ions with soil compounds and identifying the phases-carriers of metals in soil and their stable fixation. These studies were carried out using the technique of X-ray absorption spectroscopy and chemical extractive fractionation. In a model experiment the samples taken in Calcic Chernozem were artificially contaminated with higher portion of Zn(NO3)2 (2000 mg/kg). The metal were incubated in soil samples for 2 year. The samples of soil mineral and organic phases (calcite, kaolinite, bentonite, humic acids) were saturated with Zn2+ from a solution of nitrate salts of metal. The total content of Zn in soil and soil various phases was determined using the X-ray fluorescence method. Extended X-ray absorption fine structure (EXAFS) Zn was measured at the Structural Materials Science beamline of the Kurchatov Center for Synchrotron Radiation. Sequential fractionation of Zn in soil conducted by Tessier method (Tessier et al., 1979) which determining 5 fractions of metals in soil: exchangeable, bound to Fe-Mn oxide, bound to carbonate, bound to the organic matter, and bound to silicate (residual). This methodology has so far more than 4000 citations (Web of Science), which demonstrates the popularity of this approach. Much Zn compounds are contained in uncontaminated soils in stable primary and secondary silicates inherited from the parental rocks (67% of the total concentrations in all fractions), which is a regional trait of soils in the fore-Caucasian plain. Extracted fractionation of metal compounds in soil samples, artificially contaminated with Zn salts, indicates the priority holding of Zn2+ ions by silicates, carbonates and Fe-Mn oxides. The Zn content significantly increases in the exchangeable fraction. Atomic structure study of the soil various phases saturated with Zn2+ ion by using (XANES) X-ray absorption spectroscopy

  20. Exploring Manganese Fractionation Using a Sequential Extraction Method to Evaluate Welders' Gas Metal Arc Welding Exposures during Heavy Equipment Manufacturing.

    Science.gov (United States)

    Hanley, Kevin W; Andrews, Ronnee; Bertke, Steven; Ashley, Kevin

    2017-01-01

    The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume at three factories where heavy equipment was manufactured. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. One hundred nine worker-days were monitored for either total or respirable Mn during gas metal arc welding. The samples were analyzed using an experimental method to separate different Mn fractions based on selective chemical solubility. The full-shift total particle size Mn time-weighted average (TWA) breathing zone concentrations ranged 0.38-26 for soluble Mn in a mild ammonium acetate solution; 3.2-170 for Mn0,2+ in acetic acid; 3.1-290 for Mn3+,4+ in hydroxylamine-hydrochloride; and non-detectable (ND)-130 µg m-3 for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all the total particulate Mn TWA fractions yielded results that ranged from 6.9 to 610 µg m-3. The range of respirable size Mn TWA concentrations were 0.33-21 for soluble Mn; 15-140 for Mn0,2+; 14-170 for Mn3+,4+; 5.3-230 for insoluble Mn; and 36-530 µg m-3 for Mn (sum of fractions). Total particulate TWA GM concentrations of the Mn (sum) were 53 (GSD = 2.5), 150 (GSD = 1.7), and 120 (GSD = 1.8) µg m-3 for the three separate factories. Although all of the workers' exposures were measured below the OSHA regulatory permissible exposure limit and NIOSH recommended exposure limit for Mn, 70 welders' exposures exceeded the ACGIH Threshold Limit Values® for total Mn (100 µg m-3) and 29 exceeded the recently adopted respirable Mn TLV (20 µg m-3). This study shows that a welding fume exposure control and management program is warranted for Mn, which includes improved exhaust ventilation and may necessitate the use of respiratory protection, especially for welding parts that impede air circulation. Published by Oxford University Press on behalf of

  1. Extraction Of Bioactive Compounds From Cob And Pericarp Of Purple Corn (zea Mays L.) By Sequential Extraction In Fixed Bed Extractor Using Supercritical Co2, Ethanol, And Water As Solvents

    OpenAIRE

    Monroy; Yaneth M.; Rodrigues; Rodney A. F.; Sartoratto; Adilson; Cabral; Fernando A.

    2016-01-01

    Purple corn (Zea mays L.) is traditionally used in Peru in the preparation of desserts and juices. Purple corn cob and kernel extracts have intense color and are rich in anthocyanins and phenolic compounds. Purple corn cob, whole grain, ground grain, and pericarp extracts were obtained by supercritical fluid technology in a fixed bed at 50 degrees C and 400 bar in a sequential extraction process using supercritical carbon dioxide (scCO(2)) as a solvent in the first step, ethanol in a second s...

  2. Real time on-chip sequential adaptive principal component analysis for data feature extraction and image compression

    Science.gov (United States)

    Duong, T. A.

    2004-01-01

    In this paper, we present a new, simple, and optimized hardware architecture sequential learning technique for adaptive Principle Component Analysis (PCA) which will help optimize the hardware implementation in VLSI and to overcome the difficulties of the traditional gradient descent in learning convergence and hardware implementation.

  3. Mobility of arsenic, cadmium and zinc in a multi-element contaminated soil profile assessed by in-situ soil pore water sampling, column leaching and sequential extraction.

    Science.gov (United States)

    Beesley, Luke; Moreno-Jiménez, Eduardo; Clemente, Rafael; Lepp, Nicholas; Dickinson, Nicholas

    2010-01-01

    Three methods for predicting element mobility in soils have been applied to an iron-rich soil, contaminated with arsenic, cadmium and zinc. Soils were collected from 0 to 30 cm, 30 to 70 cm and 70 to 100 cm depths in the field and soil pore water was collected at different depths from an adjacent 100 cm deep trench. Sequential extraction and a column leaching test in the laboratory were compared to element concentrations in pore water sampled directly from the field. Arsenic showed low extractability, low leachability and occurred at low concentrations in pore water samples. Cadmium and zinc were more labile and present in higher concentrations in pore water, increasing with soil depth. Pore water sampling gave the best indication of short term element mobility when field conditions were taken into account, but further extraction and leaching procedures produced a fuller picture of element dynamics, revealing highly labile Cd deep in the soil profile.

  4. Disruption of Bcr-Abl coiled coil oligomerization by design.

    Science.gov (United States)

    Dixon, Andrew S; Pendley, Scott S; Bruno, Benjamin J; Woessner, David W; Shimpi, Adrian A; Cheatham, Thomas E; Lim, Carol S

    2011-08-05

    Oligomerization is an important regulatory mechanism for many proteins, including oncoproteins and other pathogenic proteins. The oncoprotein Bcr-Abl relies on oligomerization via its coiled coil domain for its kinase activity, suggesting that a designed coiled coil domain with enhanced binding to Bcr-Abl and reduced self-oligomerization would be therapeutically useful. Key mutations in the coiled coil domain of Bcr-Abl were identified that reduce homo-oligomerization through intermolecular charge-charge repulsion yet increase interaction with the Bcr-Abl coiled coil through additional salt bridges, resulting in an enhanced ability to disrupt the oligomeric state of Bcr-Abl. The mutations were modeled computationally to optimize the design. Assays performed in vitro confirmed the validity and functionality of the optimal mutations, which were found to exhibit reduced homo-oligomerization and increased binding to the Bcr-Abl coiled coil domain. Introduction of the mutant coiled coil into K562 cells resulted in decreased phosphorylation of Bcr-Abl, reduced cell proliferation, and increased caspase-3/7 activity and DNA segmentation. Importantly, the mutant coiled coil domain was more efficacious than the wild type in all experiments performed. The improved inhibition of Bcr-Abl through oligomeric disruption resulting from this modified coiled coil domain represents a viable alternative to small molecule inhibitors for therapeutic intervention.

  5. Rapid and simultaneous determination of neptunium and plutonium isotopes in environmental samples by extraction chromatography using sequential injection analysis and ICP-MS

    DEFF Research Database (Denmark)

    Qiao, Jixin; Hou, Xiaolin; Roos, Per

    2010-01-01

    This paper reports an automated analytical method for rapid and simultaneous determination of plutonium isotopes (239Pu and 240Pu) and neptunium (237Np) in environmental samples. An extraction chromatographic column packed with TrisKem TEVA® resin was incorporated in a sequential injection (SI...... procedures were investigated and compared for the adjustment of oxidation states of plutonium and neptunium to Pu(IV) and Np(IV), respectively. A two-step protocol using sulfite and concentrated nitric acid as redox reagents was proven to be the most effective method. The analytical results for both...

  6. Induction of autophagy by Imatinib sequesters Bcr-Abl in autophagosomes and down-regulates Bcr-Abl protein.

    LENUS (Irish Health Repository)

    Elzinga, Baukje M

    2013-06-01

    Chronic Myeloid Leukemia (CML) is a disease of hematopoietic stem cells which harbor the chimeric gene Bcr-Abl. Expression levels of this constitutively active tyrosine kinase are critical for response to tyrosine kinase inhibitor treatment and also disease progression, yet the regulation of protein stability is poorly understood. We have previously demonstrated that imatinib can induce autophagy in Bcr-Abl expressing cells. Autophagy has been associated with the clearance of large macromolecular signaling complexes and abnormal proteins, however, the contribution of autophagy to the turnover of Bcr-Abl protein in imatinib treated cells is unknown. In this study, we show that following imatinib treatment, Bcr-Abl is sequestered into vesicular structures that co-localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1\\/ATG7). Pharmacological inhibition of autophagy also reduced Bcr-Abl\\/LC3 co-localization in both K562 and CML patient cells. Bcr-Abl protein expression was reduced with imatinib treatment. Inhibition of both autophagy and proteasome activity in imatinib treated cells was required to restore Bcr-Abl protein levels to those of untreated cells. This ability to down-regulate Bcr-Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of imatinib.

  7. Mapping of four distinct BCR-related loci to chromosome region 22q11: order of BCR loci relative to chronic myelogenous leukemia and acute lymphoblastic leukemia breakpoints

    Energy Technology Data Exchange (ETDEWEB)

    Croce, C.M.; Huebner, K.; Isobe, M.; Fainstain, E.; Lifshitz, B.; Shtivelman, E.; Canaani, E.

    1987-10-01

    A probe derived from the 3' region of the BCR gene (breakpoint cluster region gene) detects four distinct loci in the human genome. One of the loci corresponds to the complete BCR gene, whereas the other contain a 3' segment of the gene. After HindIII cleavage of human DNA, these four loci are detected as 23-, 19-, 13-, and 9-kikobase-pair fragments, designated BCR4, BCR3, BCR2, and BCR1, respectively, with BCR1 deriving from the original complete BCR gene. All four BCR loci segregate 100% concordantly with human chromosome 22 in a rodent-human somatic cell hybrid panel and are located at chromosome region 22q11.2 by chromosomal in situ hybridization. The BCR2 and BCR4 loci are amplified in leukemia cell line K562 cells, indicating that they fall within the amplification unit that includes immunoglobulin lambda light chain locus (IGL) and ABL locus on the K562 Philadelphia chromosome (Ph/sup 1/). Similarly, in mouse-human hybrids retaining a Ph/sup 1/ chromosome derived from an acute lymphoblastic leukemia-in the absence of the 9q/sup +/ and 22, only BCR2 and BCR4 loci are retained. Thus, the order of loci on chromosome 22 is centromere ..-->.. BCR2, BCR4, and IGL ..-->.. BCR1 ..-->.. BCR3 ..-->.. SIS, possibly eliminating BCR2 and BCR4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph/sup 1/ chromosome.

  8. Trace metal distribution in the Arosa estuary (N.W. Spain): The application of a recently developed sequential extraction procedure for metal partitioning

    Energy Technology Data Exchange (ETDEWEB)

    Santamaria-Fernandez, Rebeca [School of Earth, Ocean and Environmental Sciences, University of Plymouth, Plymouth, PL4 8AA (United Kingdom); Cave, Mark R. [British Geological Survey, Keyworth, Nottingham, NG12 5GG (United Kingdom); Hill, Steve J. [School of Earth, Ocean and Environmental Sciences, University of Plymouth, Plymouth, PL4 8AA (United Kingdom)]. E-mail: SJHill@plymouth.ac.uk

    2006-01-31

    A study of the trace metal distribution in sediment samples from the Galician coast (Spain) has been performed. A multielement extraction method optimised via experimental design has been employed. The method uses centrifugation to pass the extractant solution at varying pH, through the sediment sample. The sequential leaches were collected and analysed by ICP-AES. Chemometric approaches were utilised to identify the composition of the physico-chemical components in order to characterise the sample. The samples collected at different sites could be classified according to their differences in metal bio-availability and important information regarding element distribution within the physico-chemical components is given. The method has proved to be a quick and reliable way to evaluate sediment samples for environmental geochemistry analysis. In addition, this approach has potential as fast screening method for the bio-availability of metals in the environment.

  9. Automated Online Solid-Phase Extraction Coupled with Sequential Injection-HPLC-EC System for the Determination of Sulfonamides in Shrimp

    Directory of Open Access Journals (Sweden)

    Pimkwan Chantarateepra

    2012-01-01

    Full Text Available The use of fully automated online solid-phase extraction (SPE coupled with sequential injection analysis, high-performance liquid chromatography (HPLC, and electrochemical detection (EC for the separation and determination of sulfonamides has been developed. A homemade microcolumn SPE system coupled with sequential injection analysis (SIA was used to automate the sample cleanup and extraction of sulfonamides. The optimal flow rate of sample loading and elution was found to be 10 μL/s, and optimal elution time of zone was 20–24 s. Under the optimal conditions, a linear relationship between peak area and sulfonamide concentrations was obtained in the range of 0.01–8.0 μg mL−1. Detection limits for seven sulfonamides were between 1.2 ng mL−1 and 11.2 ng mL−1. The proposed method has been applied for the determination of sulfonamides in shrimp. Recoveries in the range of 84–107% and relative standard deviations (RSDs below 6.5% for intraday and 13% for inter-day were received for three concentration levels of spiking. The results showed that the present method was simple, rapid, accurate and highly sensitive for the determination of sulfonamides.

  10. A kinetic study of trace element leachability from abandoned-mine-polluted soil treated with SS-MSW compost and red mud. Comparison with results from sequential extraction

    Energy Technology Data Exchange (ETDEWEB)

    Brunori, C.; Cremisini, C.; D' Annibale, L.; Massanisso, P.; Pinto, V. [ENEA-C.R., Roma (Italy)

    2005-04-01

    The effect of adding treated red mud, a by-product of alumina production, to soil polluted by an abandoned mine and characterised by high concentrations of heavy metals, relatively low reaction grade, and low organic carbon content, was investigated. Also studied was addition of both red mud and compost (produced from source-separated municipal solid waste) - the synergistic action of red mud and compost could be exploited to achieve both metal trapping and an increase in organic carbon content. Leaching batch tests were performed on four different systems: soil, soil and treated red mud, soil and compost, soil and compost plus treated red mud. Dilute sulfuric acid and EDTA solution (liquid/solid ratio 10:1) were used in the tests - sulfuric acid to ''mimic'' acid rain and EDTA in accordance with general methods for estimating ''plant-available'' metals. Sequential extraction was also applied to the same samples. The use of relatively non-specific extractant reagents in the leaching tests led to a kinetic approach (already proposed in literature), because measurements of trace elements extracted at equilibrium cannot be related to their speciation. Comparison of information obtainable by the kinetic approach to evaluation of data from leaching tests with results from sequential extraction enabled evaluation whether the ''kinetic fractionation method'', a relatively rapid and simple procedure, furnishes adequate information about the mobility and bioavailability of trace elements. Especially interesting results were obtained for Mn, Zn, and Ni, present in large amounts in the soil studied - their leachability was significantly reduced by addition of red mud and compost, suggesting interesting perspectives in soil-remediation activity. (orig.)

  11. A kinetic study of trace element leachability from abandoned-mine-polluted soil treated with SS-MSW compost and red mud. Comparison with results from sequential extraction.

    Science.gov (United States)

    Brunori, C; Cremisini, C; D'Annibale, L; Massanisso, P; Pinto, V

    2005-04-01

    The effect of adding treated red mud, a by-product of alumina production, to soil polluted by an abandoned mine and characterised by high concentrations of heavy metals, relatively low reaction grade, and low organic carbon content, was investigated. Also studied was addition of both red mud and compost (produced from source-separated municipal solid waste)--the synergistic action of red mud and compost could be exploited to achieve both metal trapping and an increase in organic carbon content. Leaching batch tests were performed on four different systems: soil, soil and treated red mud, soil and compost, soil and compost plus treated red mud. Dilute sulfuric acid and EDTA solution (liquid/solid ratio 10:1) were used in the tests--sulfuric acid to "mimic" acid rain and EDTA in accordance with general methods for estimating "plant-available" metals. Sequential extraction was also applied to the same samples. The use of relatively non-specific extractant reagents in the leaching tests led to a kinetic approach (already proposed in literature), because measurements of trace elements extracted at equilibrium cannot be related to their speciation. Comparison of information obtainable by the kinetic approach to evaluation of data from leaching tests with results from sequential extraction enabled evaluation whether the "kinetic fractionation method", a relatively rapid and simple procedure, furnishes adequate information about the mobility and bioavailability of trace elements. Especially interesting results were obtained for Mn, Zn, and Ni, present in large amounts in the soil studied--their leachability was significantly reduced by addition of red mud and compost, suggesting interesting perspectives in soil-remediation activity.

  12. On-line liquid phase micro-extraction based on drop-in-plug sequential injection lab-at-valve platform for metal determination

    International Nuclear Information System (INIS)

    Mitani, Constantina; Anthemidis, Aristidis N.

    2013-01-01

    Highlights: ► Drop-in-plug micro-extraction based on SI-LAV platform for metal preconcentration. ► Automatic liquid phase micro-extraction coupled with FAAS. ► Organic solvents with density higher than water are used. ► Lead determination in environmental water and urine samples. -- Abstract: A novel automatic on-line liquid phase micro-extraction method based on drop-in-plug sequential injection lab-at-valve (LAV) platform was proposed for metal preconcentration and determination. A flow-through micro-extraction chamber mounted at the selection valve was adopted without the need of sophisticated lab-on-valve components. Coupled to flame atomic absorption spectrometry (FAAS), the potential of this lab-at-valve scheme is demonstrated for trace lead determination in environmental and biological water samples. A hydrophobic complex of lead with ammonium pyrrolidine dithiocarbamate (APDC) was formed on-line and subsequently extracted into an 80 μL plug of chloroform. The extraction procedure was performed by forming micro-droplets of aqueous phase into the plug of the extractant. All critical parameters that affect the efficiency of the system were studied and optimized. The proposed method offered good performance characteristics and high preconcentration ratios. For 10 mL sample consumption an enhancement factor of 125 was obtained. The detection limit was 1.8 μg L −1 and the precision expressed as relative standard deviation (RSD) at 50.0 μg L −1 of lead was 2.9%. The proposed method was evaluated by analyzing certified reference materials and applied for lead determination in natural waters and urine samples

  13. Assessment of metal bioavailability in the vineyard soil-grapevine system using different extraction methods.

    Science.gov (United States)

    Vázquez Vázquez, Francisco A; Pérez Cid, Benita; Río Segade, Susana

    2016-10-01

    This study was focused on the assessment of single and sequential extraction methods to predict the bioavailability of metals in the vineyard soil-grapevine system. The modified BCR sequential extraction method and two single-step extraction methods based on the use of EDTA and acetic acid were applied to differently amended vineyard soils. The variety effect was studied on the uptake of metals by leaves and grapes. Most of the elements studied (Ca, Mg, Cu, Fe, Mn, Zn and Pb) were weakly mobilized from vineyard soils, with the exception of Cu and Mn. The determination of total metal content in leaves and grapes showed a different accumulation pattern in the two parts of the vine. A significant relationship was observed, for all the elements studied except for Fe, between the content bioavailable in the soil and the accumulated in both leaves and grapes (R=0.602-0.775, p<0.01). Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. A multisyringe flow-through sequential extraction system for on-line monitoring of orthophosphate in soils and sediments

    DEFF Research Database (Denmark)

    Buanuam, Janya; Miró, Manuel; Hansen, Elo Harald

    2007-01-01

    of extracted organic phosphorus and condensed inorganic phosphates within the time frame of the assay. The potential of the novel system for accommodation of the harmonized protocol from the Standards, Measurement and Testing (SMT) Program of the Commission of the European Communities for inorganic phosphorus.......5 mol l-1 HCl as extractants according to the Hietjles-Lijklema (HL) scheme for fractionation of phosphorus associated with different geological phases, and on-line processing of the extracts via the Molybdenum Blue (MB) reaction by exploiting multisyringe flow injection as the interface between...... of the operational times from days to hours, highly temporal resolution of the leaching process, and the capability for immediate decision for stopping or proceeding with the ongoing extraction. Very importantly, accurate determination of the various orthophosphate pools is ensured by minimization of the hydrolysis...

  15. Neuroprotective Effect of Total and Sequential Extract of Scrophularia striata Boiss. in Rat Cerebellar Granule Neurons Following Glutamate- Induced Neurotoxicity: An In-vitro Study

    Science.gov (United States)

    Salavati, Parvin; Ramezani, Mina; Monsef-Esfahani, Hamid R; Hajiagha, Reza; Parsa, Maliheh; Tavajohi, Shoreh; Ostad, Seyed Nasser

    2013-01-01

    Neuroprotective effect of the extract from aerial parts of Scrophularia striata Boiss (Scrophulariaceae) was investigated against glutamate-induced neurotoxicity on cultured rat pups Cerebellar Granule Neurons (CGNs). CGNs from 8 days old Sprague-Dawley rat were prepared and cultured. The experiments were performed after 8 days in culture. The plant was collected from the northeastern part (Ruin region) of Iran and air-dried at room temperature. The total extract was prepared with maceration of prepared powder in ethanol 80% for three times. Sequential extracts were obtained using dried and powdered aerial parts with increasingly polar solvents: petroleum ether, chloroform, ethyl acetate and methanol 80% solution. Cultured cells were exposed to 125 μM of glutamate for 12 h following a 24 h of incubation with test fractions at concentration of 10 mcg/mL. Morphological assay was performed using invert light microscope after fixation and staining with haematoxylin. Neuronal viability was measured using MTT assay. Statistical analysis was done using SPSS software. One way analysis of variance (ANOVA) was performed by Tukey post-hoc test. Values were considered statistically significant when p-value ≤ 0.05. Results of this study showed a significant neuroprotective activity of high polarity methanolic fraction of aerial parts of Scrophularia striata against glutamate-induced neurotoxicity in a dosedependent manner. Treatment with 10 mcg/mL of the fractions showed the best result. PMID:24250613

  16. A sequential approach to control gas for the extraction of multi-gassy coal seams from traditional gas well drainage to mining-induced stress relief

    International Nuclear Information System (INIS)

    Kong, Shengli; Cheng, Yuanping; Ren, Ting; Liu, Hongyong

    2014-01-01

    Highlights: • The gas reservoirs characteristics are measured and analyzed. • A sequential approach to control gas of multi-gassy coal seams is proposed. • The design of gas drainage wells has been improved. • The utilization ways of different concentrations of gas production are shown. - Abstract: As coal resources become exhausted in shallow mines, mining operations will inevitably progress from shallow depth to deep and gassy seams due to increased demands for more coal products. However, during the extraction process of deeper and gassier coal seams, new challenges to current gas control methods have emerged, these include the conflict between the coal mine safety and the economic benefits, the difficulties in reservoirs improvement, as well as the imbalance between pre-gas drainage, roadway development and coal mining. To solve these problems, a sequential approach is introduced in this paper. Three fundamental principles are proposed: the mining-induced stress relief effect of the first-mined coalbed should be sufficient to improve the permeability of the others; the coal resource of the first-mined seams must be abundant to guarantee the economic benefits; the arrangement of the vertical wells must fit the underground mining panel. Tunlan coal mine is taken as a typical example to demonstrate the effectiveness of this approach. The approach of integrating surface coalbed methane (CBM) exploitation with underground gas control technologies brings three major benefits: the improvement of underground coal mining safety, the implementation of CBM extraction, and the reduction of greenhouse gas emissions. This practice could be used as a valuable example for other coal mines having similar geological conditions

  17. Sequential extraction results in improved proteome profiling of medicinal plant Pinellia ternata tubers, which contain large amounts of high-abundance proteins.

    Directory of Open Access Journals (Sweden)

    Xiaolin Wu

    Full Text Available Pinellia ternata tuber is one of the well-known Chinese traditional medicines. In order to understand the pharmacological properties of tuber proteins, it is necessary to perform proteome analysis of P. ternata tubers. However, a few high-abundance proteins (HAPs, mainly mannose-binding lectin (agglutinin, exist in aggregates of various sizes in the tubers and seriously interfere with proteome profiling by two-dimensional electrophoresis (2-DE. Therefore, selective depletion of these HAPs is a prerequisite for enhanced proteome analysis of P. ternata tubers. Based on differential protein solubility, we developed a novel protocol involving two sequential extractions for depletion of some HAPs and prefractionation of tuber proteins prior to 2-DE. The first extraction using 10% acetic acid selectively extracted acid-soluble HAPs and the second extraction using the SDS-containing buffer extracted remaining acid-insoluble proteins. After application of the protocol, 2-DE profiles of P. ternata tuber proteins were greatly improved and more protein spots were detected, especially low-abundance proteins. Moreover, the subunit composition of P. ternata lectin was analyzed by electrophoresis. Native lectin consists of two hydrogen-bonded subunits (11 kDa and 25 kDa and the 11 kDa subunit was a glycoprotein. Subsequently, major HAPs in the tubers were analyzed by mass spectrometry, with nine protein spots being identified as lectin isoforms. The methodology was easy to perform and required no specialized apparatus. It would be useful for proteome analysis of other tuber plants of Araceae.

  18. Dynamic flow-through sequential extraction for assessment of fractional transformation and inter-element associations of arsenic in stabilized soil and sludge

    International Nuclear Information System (INIS)

    Buanuam, Janya; Wennrich, Rainer

    2010-01-01

    A dynamic flow-through extraction system was applied for the first time to ascertain the fractional transformation and inter-element associations of arsenic in stabilized environmental solids, as exemplified by the partitioning of soil and sludge stabilized with three additives, namely MnO 2 , Ca(OH) 2 and FeSO 4 . The extraction system used not only gave fractionation data, but also the extraction profiles (extractograms) which were used for investigation of the breaking down of phases, kinetic releasing of As and elemental association between As and inorganic additives. Five geochemical fractions of As were elucidated by accommodation in the flow manifold of a modified Wenzel's sequential extraction scheme, well established for fractionation of arsenic. The results revealed that MnO 2 and FeSO 4 have a slight effect on As phase transformation for soil and sludge samples amended for one week whereas the addition of Ca(OH) 2 increases As mobility due to the desorption of As from the solid Fe-oxides phase. The significant change in fractional transformation after 8 weeks of incubation can be seen in MnO 2 -treated soil. There was an increase of 17% in the non-mobilizable As fraction in MnO 2 -treated soil. From extractograms, arsenic in untreated soil was found to be rapidly leached and concurrently released with Fe. This may be evidence that the release of As is dependent on the dissolution of amorphous Fe oxides. In MnO 2 -treated soil, a strong affinity was observed between Mn and As in the amorphous Fe/Al oxides fraction, and this plays an important role in slowing down the kinetics of As releasing.

  19. Comparison of first pass bolus AIFs extracted from sequential {sup 18}F-FDG PET and DSC-MRI of mice

    Energy Technology Data Exchange (ETDEWEB)

    Evans, Eleanor, E-mail: ee244@cam.ac.uk [Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ (United Kingdom); Sawiak, Stephen J. [Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ (United Kingdom); Behavioural and Clinical Neuroscience Institute, Department of Experimental Psychology, University of Cambridge, Cambridge, CB2 3EB (United Kingdom); Ward, Alexander O.; Buonincontri, Guido; Hawkes, Robert C.; Adrian Carpenter, T. [Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ (United Kingdom)

    2014-01-11

    Accurate kinetic modelling of in vivo physiological function using positron emission tomography (PET) requires determination of the tracer time–activity curve in plasma, known as the arterial input function (AIF). The AIF is usually determined by invasive blood sampling methods, which are prohibitive in murine studies due to low total blood volumes. Extracting AIFs from PET images is also challenging due to large partial volume effects (PVE). We hypothesise that in combined PET with magnetic resonance imaging (PET/MR), a co-injected bolus of MR contrast agent and PET ligand can be tracked using fast MR acquisitions. This protocol would allow extraction of a MR AIF from MR contrast agent concentration–time curves, at higher spatial and temporal resolution than an image-derived PET AIF. A conversion factor could then be applied to the MR AIF for use in PET kinetic analysis. This work has compared AIFs obtained from sequential DSC-MRI and PET with separate injections of gadolinium contrast agent and {sup 18}F-FDG respectively to ascertain the technique′s validity. An automated voxel selection algorithm was employed to improve MR AIF reproducibility. We found that MR and PET AIFs displayed similar character in the first pass, confirmed by gamma variate fits (p<0.02). MR AIFs displayed reduced PVE compared to PET AIFs, indicating their potential use in PET/MR studies.

  20. Iodine speciation in coastal and inland bathing waters and seaweeds extracts using a sequential injection standard addition flow-batch method.

    Science.gov (United States)

    Santos, Inês C; Mesquita, Raquel B R; Bordalo, Adriano A; Rangel, António O S S

    2015-02-01

    The present work describes the development of a sequential injection standard addition method for iodine speciation in bathing waters and seaweeds extracts without prior sample treatment. Iodine speciation was obtained by assessing the iodide and iodate content, the two inorganic forms of iodine in waters. For the determination of iodide, an iodide ion selective electrode (ISE) was used. The indirect determination of iodate was based on the spectrophotometric determination of nitrite (Griess reaction). For the iodate measurement, a mixing chamber was employed (flow batch approach) to explore the inherent efficient mixing, essential for the indirect determination of iodate. The application of the standard addition method enabled detection limits of 0.14 µM for iodide and 0.02 µM for iodate, together with the direct introduction of the target water samples, coastal and inland bathing waters. The results obtained were in agreement with those obtained by ICP-MS and a colorimetric reference procedure. Recovery tests also confirmed the accuracy of the developed method which was effectively applied to bathing waters and seaweed extracts. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Sequential analysis

    CERN Document Server

    Wald, Abraham

    2013-01-01

    In 1943, while in charge of Columbia University's Statistical Research Group, Abraham Wald devised Sequential Design, an innovative statistical inference system. Because the decision to terminate an experiment is not predetermined, sequential analysis can arrive at a decision much sooner and with substantially fewer observations than equally reliable test procedures based on a predetermined number of observations. The system's immense value was immediately recognized, and its use was restricted to wartime research and procedures. In 1945, it was released to the public and has since revolutio

  2. CD-200 induces apoptosis and inhibits Bcr-Abl signaling in imatinib-resistant chronic myeloid leukemia with T315I mutation.

    Science.gov (United States)

    Fang, Zhenghuan; Jung, Kyung Hee; Yan, Hong Hua; Kim, Soo Jung; Son, Mi Kwon; Rumman, Marufa; Lee, Hyunseung; Kim, Ki Woon; Yoo, Hye-Dong; Hong, Soon-Sun

    2015-07-01

    Chronic myeloid leukemia (CML) is characterized by a constitutively active Bcr-Abl tyrosine kinase. Although Imatinib has been proven to be an effective drug against CML, its resistance has been observed with disease relapse due to T315I predominant point mutation. Liriodendron tulipifera L., one of the fastest growing hardwood tree species, exerts antioxidant activity and anti-inflammatory effects. However, its anticancer effect has been minimally reported. In this study, we extracted CD-200 from Liriodendron tulipifera L. and investigated its effect on cell survival or apoptosis in CML cells with Bcr-Abl/T315I (BaF3/T315I) as well as wild-type Bcr-Abl (BaF3/WT). CD-200 inhibited cell proliferation in the BaF3/WT cells, and also in the BaF3/T315I cells with Imatinib resistance. Moreover, it strongly inhibited Bcr-Abl signaling pathways in a dose-dependent manner. Also, it significantly increased the sub-G1 phase and the expression of cleaved PARP and caspase-3, as well as the TUNEL-positive apoptotic cells. In addition, we observed that CD-200 induced apoptosis with a loss of mitochondrial membrane potential by decreasing the expression of Mcl-1 and survivin. Furthermore, CD-200 showed a significant inhibition in tumor growth, compared to Imatinib in BaF3/T315I mouse xenograft models. Taken together, our study demonstrates that CD-200 exhibits apoptosis induction and anti-proliferative effect by blocking the Bcr-Abl signaling pathways in the Bcr-Abl/T315I with resistance to Imatinib. We suggest that CD-200 may be a natural product to target Bcr-Abl and overcome Imatinib resistance in CML patients.

  3. Understanding the remobilization of copper, zinc, cadmium and lead due to ageing through sequential extraction and isotopic exchangeability.

    Science.gov (United States)

    Kumar, Manish

    2016-06-01

    Artificial infiltration facilities (AIFs) are useful to control urban runoff and regulate combined sewer overflows. Over the years, AIFs accumulate significant amounts of soakaway sediments and organic matter. The prolonged retention of soakaway sediments in AIFs is likely to cause metal remobilization due to ageing processes. The measurement of the individual consequence of ageing demands homogeneity in physical and chemical profiles of samples. This leads to assessment of metal remobilization in a single soil core through solid-phase extractions and isotopic exchangeability (E value). Depth-wise variation in the physicochemical properties and metal content of the underlying soil (below 1 m of AIFs) was created through 2 weeks of continuous leaching with artificial road runoff (ARR). Ten samples obtained from a 50-cm core by sectioning it at 5-cm intervals were subsequently incubated for 18 months. The results suggest that degradation of organic matter and changes in functional groups due to ageing govern metal remobilization. In general, the top segment showed significant alteration due to ageing. Post incubation, Zn increased dramatically in contrast to subdued Cu and Pb levels in exchangeable fractions with concomitant rise in organic-bound fractions. Isotopic exchangeability of Cd and Zn showed pronounced effect of ageing, although the effect of ageing was distinct in chemical partitioning and isotopic exchangeability of metals; a comparative study of short-term versus long-term incubation will benefit assessment of initial dynamics and final equilibrium. Consequently, the outcome from this work is a viable tool in risk prediction related to soakaway sediment accumulation in AIF.

  4. Study on demetalization of sewage sludge by sequential extraction before liquefaction for the production of cleaner bio-oil and bio-char.

    Science.gov (United States)

    Leng, Lijian; Yuan, Xingzhong; Shao, Jianguang; Huang, Huajun; Wang, Hou; Li, Hui; Chen, Xiaohong; Zeng, Guangming

    2016-01-01

    Demetalization of sewage sludge (SS) by sequential extraction before liquefaction was implemented to produce cleaner bio-char and bio-oil. Demetalization steps 1 and 2 did not cause much organic matter loss on SS, and thus the bio-oil and bio-char yields and the compositions of bio-oils were also not affected significantly. However, the demetalization procedures resulted in the production of cleaner bio-chars and bio-oils. The total concentrations and the acid soluble/exchangeable fraction (F1 fraction, the most toxic heavy metal fraction) of heavy metals (Cu, Cr, Pb, Zn, and Cd) in these products were significantly reduced and the environmental risks of these products were also relived considerably compared with those produced from raw SS, respectively. Additionally, these bio-oils had less heavy fractions. Demetalization processes with removal of F1 and F2 fractions of heavy metals would benefit the production of cleaner bio-char and bio-oil by liquefaction of heavy metal abundant biomass like SS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Automated magnetic sorbent extraction based on octadecylsilane functionalized maghemite magnetic particles in a sequential injection system coupled with electrothermal atomic absorption spectrometry for metal determination.

    Science.gov (United States)

    Giakisikli, Georgia; Anthemidis, Aristidis N

    2013-06-15

    A new automatic sequential injection (SI) system for on-line magnetic sorbent extraction coupled with electrothermal atomic absorption spectrometry (ETAAS) has been successfully developed for metal determination. In this work, we reported effective on-line immobilization of magnetic silica particles into a microcolumn by the external force of two strong neodymium iron boron (NdFeB) magnets across it, avoiding the use of frits. Octadecylsilane functionalized maghemite magnetic particles were used as sorbent material. The potentials of the system were demonstrated for trace cadmium determination in water samples. The method was based on the on-line complex formation with diethyldithiocarbamate (DDTC), retention of Cd-DDTC on the surface of the MPs and elution with isobutyl methyl ketone (IBMK). The formation mechanism of the magnetic solid phase packed column and all critical parameters (chemical, flow, graphite furnace) influencing the performance of the system were optimized and offered good analytical characteristics. For 5 mL sample volume, a detection limit of 3 ng L(-1), a relative standard deviation of 3.9% at 50 ng L(-1) level (n=11) and a linear range of 9-350 ng L(-1) were obtained. The column remained stable for more than 600 cycles keeping the cost down in routine analysis. The proposed method was evaluated by analyzing certified reference materials and natural waters. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Evaluation of the distribution patterns of Pb, Cu and Cd from MSWI fly ash during thermal treatment by sequential extraction procedure.

    Science.gov (United States)

    Chou, Jing-Dong; Wey, Ming-Yen; Chang, Shih-Hsien

    2009-03-15

    Municipal solid waste incinerator (MSWI) fly ash was frequently classified as hazardous materials as the metals' concentration of toxicity characteristic leaching procedure (TCLP) exceeded regulations. Many studies have focused on reducing the concentration of TCLP using thermal treatment and increasing the application of thermally treated slag. However, the metal patterns in MSWI fly ash with or without thermal treatment have seldom been addressed. The main objective of this study was evaluation of the distribution patterns of Pb, Cu and Cd from MSWI fly ash during thermal treatment by sequential extraction procedure. The experimental parameters included the form of pretreatment, the proportion of bottom ash (bottom ash/fly ash, B/F=0, 0.1 and 1) and the retention time. The results indicated that (1) In comparison to raw fly ash, the distribution patterns of Pb, Cu and Cd become stable in thermally treated slag. (2) Washing pretreatment caused the Pb pattern to become stable, while the influence on Cu and Cd were not significant. (3) The distribution patterns of Pb, Cu, and Cd became more stable as the retention time increased. (4) Adding bottom ash could make the distribution patterns of Pb and Cd more stable.

  7. Sequential extractions for the study of radiocesium and radiostrontium dynamics in mineral and organic soils from Western Europe and Chernobyl areas

    Energy Technology Data Exchange (ETDEWEB)

    Rigol, A.; Roig, M.; Vidal, M.; Rauret, G. [Univ. de Barcelona (Spain). Dept. Quimica Analitica

    1999-03-15

    To study radiostrontium (RSr) and radiocesium (RCs) aging in soils, three sequential extraction schemes were used on Mediterranean loamy and loam-sandy soils, podsols and peaty podsols from the area near Chernobyl, and peats from Western Europe. Aging was quantified by changes in radionuclide distribution. Two factors were thought to affect radionuclide distribution: time elapsed since contamination and drying-wetting cycles. Changes in radionuclide distribution were of low significance in Mediterranean loamy and loam-sandy soils in the short term, even after drying-wetting cycles. In the short term, podsols and peaty podsols showed a decrease in the RSr exchangeable fraction in the laboratory samples, whereas samples taken 6 years after contamination did not show any further decrease. For RCs in podsols and peaty-podsols, the application of drying-wetting cycles for 9 months led to observe a 2--3-fold decrease in the exchangeable fraction, whereas time alone did not lead to any change. No RCs aging was observed in peats with a low or almost negligible content of mineral matter, low base saturation and low interception potential for RCs, even after drying-wetting cycles. Finally, changes in the radionuclide exchangeable fraction over time in these soils corresponded to changes in transfer factors over a similar period.

  8. Ultrasonographic observation of the breast in early postmenopausal women during therapy with Cimicifuga foetida extract and sequential therapy with estrogen and progestin.

    Science.gov (United States)

    Gaowa, Sharen; Sun, Ai-Jun; Jiang, Ying; He, Fa-Wei; Zheng, Ting-Ping; Wang, Ya-Ping

    2015-04-20

    It is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women. This was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment. In comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check. In early postmenopausal patients, C. foetida extract therapy and estrogen and progesterone therapy at low doses did not increase the incidence of malignant breast tumors.

  9. Toxic trace element assessment for soils/sediments deposited during Hurricanes Katrina and Rita from southern Louisiana, USA: a sequential extraction analysis.

    Science.gov (United States)

    Shi, Honglan; Witt, Emitt C; Shu, Shi; Su, Tingzhi; Wang, Jianmin; Adams, Craig

    2010-07-01

    Analysis of soil/sediment samples collected in the southern Louisiana, USA, region three weeks after Hurricanes Katrina and Rita passed was performed using sequential extraction procedures to determine the origin, mode of occurrence, biological availability, mobilization, and transport of trace elements in the environment. Five fractions: exchangeable, bound to carbonates, bound to iron (Fe)-manganese (Mn) oxides, bound to organic matter, and residual, were subsequently extracted. The toxic trace elements Pb, As, V, Cr, Cu, and Cd were analyzed in each fraction, together with Fe in 51 soil/sediment samples. Results indicated that Pb and As were at relatively high concentrations in many of the soil/sediment samples. Because the forms in which Pb and As are present tend to be highly mobile under naturally occurring environmental conditions, these two compounds pose an increased health concern.Vanadium and Cr were mostly associated with the crystal line nonmobile residual fraction. A large portion of the Cu was associated with organic matter and residual fraction. Cadmium concentrations were low in all soil/sediment samples analyzed and most of this element tended to be associated with the mobile fractions. An average of 21% of the Fe was found in the Fe-Mn oxide fraction, indicating that a substantial part of the Fe was in an oxidized form. The significance of the overall finding of the present study indicated that the high concentrations and high availabilities of the potentially toxic trace elements As and Pb may impact the environment and human health in southern Louisiana and, in particular, the New Orleans area. Copyright (c) 2010 SETAC.

  10. Chemical sequential extraction of heavy metals and sulphur in bottom ash and in fly ash from a pulp and paper mill complex.

    Science.gov (United States)

    Nurmesniemi, Hannu; Pöykiö, Risto; Kuokkanen, Toivo; Rämö, Jaakko

    2008-08-01

    A five-stage sequential extraction procedure was used to determine the distribution of 11 metals (Cd, Cr, Cu, Mo, Pb, Zn, As, Co, V, Ni, Ba), and sulphur (S) in bottom ash and in fly ash from a fluidized bed co-combustion (i.e. wood and peat) boiler of Stora Enso Oyj Oulu Mill at Oulu, Northern Finland, into the following fractions: (1) water-soluble fraction (H2O); (2) exchangeable fraction (CH3COOH); (3) easily reduced fraction (NH2OH-HCl); (4) oxidizable fraction (H2O2 + CH3COONH4); and (5) residual fraction (HF + HNO3 + HCl). Although metals were extractable in all fractions, the highest concentrations of most of the metals occurred in the residual fraction. From the environmental point of view, this fraction is the non-mobile fraction and is potentially the least harmful. The Ca concentrations of 29.3 g kg(-1) (dry weight) in bottom ash and of 68.5 g kg(-1) (dry weight) in fly ash were correspondingly approximately 18 and 43 times higher than the average value of 1.6 g kg(-1) (dry weight) in arable land in Central Finland. The ashes were strongly alkaline pH (approximately 12) and had a liming effects of 9.3% (bottom ash) and 13% (fly ash) expressed as Ca equivalents (dry weight). The elevated Ca concentrations indicate that the ashes are potential agents for soil remediation and for improving soil fertility. The pH and liming effect values indicate that the ashes also have a pH buffering capacity. From the environmental point of view, it is notable that the heavy metal concentrations in both types of ash were lower than the Finnish criteria for ash utilization.

  11. Sulfur K-edge XANES and acid volatile sulfide analyses of changes in chemical speciation of S and Fe during sequential extraction of trace metals in anoxic sludge from biogas reactors.

    Science.gov (United States)

    Shakeri Yekta, Sepehr; Gustavsson, Jenny; Svensson, Bo H; Skyllberg, Ulf

    2012-01-30

    The effect of sequential extraction of trace metals on sulfur (S) speciation in anoxic sludge samples from two lab-scale biogas reactors augmented with Fe was investigated. Analyses of sulfur K-edge X-ray absorption near edge structure (S XANES) spectroscopy and acid volatile sulfide (AVS) were conducted on the residues from each step of the sequential extraction. The S speciation in sludge samples after AVS analysis was also determined by S XANES. Sulfur was mainly present as FeS (≈ 60% of total S) and reduced organic S (≈ 30% of total S), such as organic sulfide and thiol groups, in the anoxic solid phase. Sulfur XANES and AVS analyses showed that during first step of the extraction procedure (the removal of exchangeable cations), a part of the FeS fraction corresponding to 20% of total S was transformed to zero-valent S, whereas Fe was not released into the solution during this transformation. After the last extraction step (organic/sulfide fraction) a secondary Fe phase was formed. The change in chemical speciation of S and Fe occurring during sequential extraction procedure suggests indirect effects on trace metals associated to the FeS fraction that may lead to incorrect results. Furthermore, by S XANES it was verified that the AVS analysis effectively removed the FeS fraction. The present results identified critical limitations for the application of sequential extraction for trace metal speciation analysis outside the framework for which the methods were developed. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Development of a simple extraction cell with bi-directional continuous flow coupled on-line to ICP-MS for assessment of elemental associations in solid samples

    DEFF Research Database (Denmark)

    Buanuam, Janya; Tiptanasup, Kasipa; Shiowatana, Juwadee

    2006-01-01

    A continuous-flow system comprising a novel, custom-built extraction module and hyphenated with inductively coupled plasma-mass spectrometric (ICP-MS) detection is proposed for assessing metal mobilities and geochemical associations in soil compartments as based on using the three step BCR (now...... the Measurements and Testing Programme of the European Commission) sequential extraction scheme. Employing a peristaltic pump as liquid driver, alternate directional flows of the extractants are used to overcome compression of the solid particles within the extraction unit to ensure a steady partitioning flow rate...... and thus to maintain constant operationally defined extraction conditions. The proposed flow set-up is proven to allow for trouble-free handling of soil samples up to 1 g and flow rates ≤ 10 mL min–1. The miniaturized extraction system was coupled to ICP-MS through a flow injection interface in order...

  13. Extração seqüencial de cobre, ferro e zinco em ervas medicinais Sequential extraction of copper, iron and zinc in medicinal plants

    Directory of Open Access Journals (Sweden)

    Édira Castello Branco de Andrade

    2005-12-01

    initially for the pharmacists, indicates the ratio of the nutrient that is absorbed and used by the organism. This way, the determination of the total content of the metal ingested by the organism does not make possible to trace a profile of the efficiency of its absorption. Techniques of chemical speciation, as the sequential extraction, can assist in the evaluation of the bioavailability of minerals. Samples of medicinal grass of two lots were analyzed in relation to the total content of copper, iron and zinc for spectroscopy of atomic absorption in the flame, and the sequential extraction was applied. F, Dixon and t-student tests were used. One observed that, in average, the samples presented copper, iron and zinc total content of respectively 1.37 mg%, 5.13 mg% and 2.96 mg%. When comparing these values with the content of these metals in foods of vegetal origin, it can be verified that the analyzed medicinal grass can be considered a good source of metals. It was still observed that the metals have copper, iron and zinc can be found in the samples under at least four distinct chemical species and that extractors I and Iv were more efficient. Techniques of chemical speciation that can identify the compounds obtained from different extractors can assist in the evaluation of their bioavailability, as well as in the absorption processes.

  14. Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Wagner, Sebastian A; Beli, Petra

    2015-01-01

    B-cell receptor (BCR) signaling is essential for the development and function of B cells; however, the spectrum of proteins involved in BCR signaling is not fully known. Here we used quantitative mass spectrometry-based proteomics to monitor the dynamics of BCR signaling complexes (signalosomes......) and to investigate the dynamics of downstream phosphorylation and ubiquitylation signaling. We identify most of the previously known components of BCR signaling, as well as many proteins that have not yet been implicated in this system. BCR activation leads to rapid tyrosine phosphorylation and ubiquitylation...... of the receptor-proximal signaling components, many of which are co-regulated by both the modifications. We illustrate the power of multilayered proteomic analyses for discovering novel BCR signaling components by demonstrating that BCR-induced phosphorylation of RAB7A at S72 prevents its association...

  15. BCR and its mutants, the reciprocal t(9;22-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

    Directory of Open Access Journals (Sweden)

    Puccetti Elena

    2006-11-01

    Full Text Available Abstract Background The reciprocal (9;22 translocation fuses the bcr (breakpoint cluster region gene on chromosome 22 to the abl (Abelson-leukemia-virus gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+ the derivative 9+ encodes either the p40(ABL/BCR fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96(ABL/BCR fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. Methods We investigated the effects of BCR and ABL/BCRs i. on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii. on the actin cytoskeleton by direct immunofluorescence; and iii on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. Results Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. Conclusion Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22 ABL/BCR fusion proteins in comparison to their physiological counterpart BCR.

  16. BCR and its mutants, the reciprocal t(9;22)-associated ABL/BCR fusion proteins, differentially regulate the cytoskeleton and cell motility

    International Nuclear Information System (INIS)

    Zheng, Xiaomin; Güller, Saskia; Beissert, Tim; Puccetti, Elena; Ruthardt, Martin

    2006-01-01

    The reciprocal (9;22) translocation fuses the bcr (breakpoint cluster region) gene on chromosome 22 to the abl (Abelson-leukemia-virus) gene on chromosome 9. Depending on the breakpoint on chromosome 22 (the Philadelphia chromosome – Ph+) the derivative 9+ encodes either the p40 (ABL/BCR) fusion transcript, detectable in about 65% patients suffering from chronic myeloid leukemia, or the p96 (ABL/BCR) fusion transcript, detectable in 100% of Ph+ acute lymphatic leukemia patients. The ABL/BCRs are N-terminally truncated BCR mutants. The fact that BCR contains Rho-GEF and Rac-GAP functions strongly suggest an important role in cytoskeleton modeling by regulating the activity of Rho-like GTPases, such as Rho, Rac and cdc42. We, therefore, compared the function of the ABL/BCR proteins with that of wild-type BCR. We investigated the effects of BCR and ABL/BCRs i.) on the activation status of Rho, Rac and cdc42 in GTPase-activation assays; ii.) on the actin cytoskeleton by direct immunofluorescence; and iii) on cell motility by studying migration into a three-dimensional stroma spheroid model, adhesion on an endothelial cell layer under shear stress in a flow chamber model, and chemotaxis and endothelial transmigration in a transwell model with an SDF-1α gradient. Here we show that both ABL/BCRs lost fundamental functional features of BCR regarding the regulation of small Rho-like GTPases with negative consequences on cell motility, in particular on the capacity to adhere to endothelial cells. Our data presented here describe for the first time an analysis of the biological function of the reciprocal t(9;22) ABL/BCR fusion proteins in comparison to their physiological counterpart BCR

  17. Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative, BCR-positive patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    A. Hagemeijer (Anne); A. Buijs (Arjan); E.M.E. Smit (Elisabeth); L.A.J. Janssen (Bart); G.J.M. Creemers (Geert-Jan); D. van der Plas (D.); G.C. Grosveld (Gerard)

    1993-01-01

    textabstractLeukemic cells from two patients with Philadelphia-negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M-BCR region and formation of BCR-ABL fusion mRNA with b2a2

  18. BCR-ABL fusion genes are inducible by X-irradiation in vitro

    International Nuclear Information System (INIS)

    Ito, Takashi; Seyama, Toshio; Mizuno, Terumi; Hayashi, Tomonori; Nakamura, Nori; Akiyama, Mitoshi; Dohi, Kiyohiko.

    1992-01-01

    The Philadelphia chromosome consists of a reciprocal translocation between the ABL oncogene at chromosome 9q34 and the BCR gene at chromosome 22q resulting in the expression of chimeric BCR-ABL mRNAs specific to chronic myelogenous leukemia (CML). The presence of the fusion genes can be detected with high specificity and sensitivity by means of reverse transcription and polymerase chain reaction. Using this assay, it was possible to detect BCR-ABL fusion genes induced among HL60 cells after 100 Gy of X-irradiation in vitro. A total of five fusion gene transcripts were obtained. These fusion genes contained not only CML-specific BCR-ABL rearrangements, but also other forms of BCR-ABL fusions. These latter genes had junctions of BCR exon 4/ABL exon 2 intervened by a segment of DNA of unknown origin, BCR exon 5/ABL exon 2, and BCR exon 4/ABL exon 2. The results appear to be the first evidence for the induction of the BCR-ABL fusion gene by X-irradiation. In terms of leukemogenesis, it is suggested that only those cells bearing certain CML-related BCR-ABL fusion genes are positively selected by virtue of a growth advantage in vivo. (author)

  19. Vertical Geochemical Variations and Speciation Studies of As, Fe, Mn, Zn, and Cu in the Sediments of the Central Gangetic Basin: Sequential Extraction and Statistical Approach

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    2018-01-01

    Full Text Available A geochemical and speciation study of As, Fe, Mn, Zn, and Cu was performed using sequential extraction and statistical approaches in the core sediments taken at two locations—Rigni Chhapra and Chaube Chhapra—of the central Gangetic basin (India. A gradual increase in the grain size (varying from clay to coarse sands was observed in both the core profiles up to 30.5 m depth. The concentrations of analyzed elements ranged as follows: 6.9–14.2 mg/kg for As, 13,849–31,088 mg/kg for Fe, 267–711 mg/kg for Mn, 45–164 mg/kg for Cu for Rigni Chhapra while for Chaube Chhapra the range was 7.5–13.2 mg/kg for As, 10,936–37,052 mg/kg for Fe, 267–1052 mg/kg for Mn, 60–198 mg/kg for Zn and 60–108 mg/kg for Cu. Significant amounts (53–95% of all the fractionated elemental concentrations were bound within the crystal structure of the minerals as a residual fraction. The reducible fraction was the second most dominant fraction for As (7% and 8%, Fe (3%, Mn (20% and 26%, and Cu (7% and 6% respectively for both the cores. It may be released when aquifers subjected to changing redox conditions. The acid soluble fraction was of most interest because it could quickly mobilize into the water system which formed the third most dominating among all three fractions. Four color code of sediments showed an association with total As concentration and did not show a relation with any fraction of all elements analyzed. The core sediment was observed enriched with As and other elements (Cu, Fe, Mn, and Zn. However, it fell under uncontaminated to moderately contaminate which might exhibit a low risk in prevailing natural conditions. X-ray diffraction analyses indicated the availability of siderite and magnetite minerals in the core sediments in a section of dark grey with micaceous medium sand with organic matter (black.

  20. Manganese Fractionation Using a Sequential Extraction Method to Evaluate Welders' Shielded Metal Arc Welding Exposures During Construction Projects in Oil Refineries.

    Science.gov (United States)

    Hanley, Kevin W; Andrews, Ronnee; Bertke, Steven; Ashley, Kevin

    2015-01-01

    The National Institute for Occupational Safety and Health has conducted an occupational exposure assessment study of manganese (Mn) in welding fume of construction workers rebuilding tanks, piping, and process equipment at two oil refineries. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Seventy-two worker-days were monitored for either total or respirable Mn during stick welding and associated activities both within and outside of confined spaces. The samples were analyzed using an experimental method to separate different Mn fractions by valence states based on selective chemical solubility. The full-shift total particulate Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.013-29 for soluble Mn in a mild ammonium acetate solution; from 0.26-250 for Mn(0,2+) in acetic acid; from non-detectable (ND) - 350 for Mn(3+,4+) in hydroxylamine-hydrochloride; and from ND - 39 micrograms per cubic meter (μg/m(3)) for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all Mn fractions in total particulate TWA ranged from 0.52-470 μg/m(3). The range of respirable particulate Mn TWA concentrations were from 0.20-28 for soluble Mn; from 1.4-270 for Mn(0,2+); from 0.49-150 for Mn(3+,4+); from ND - 100 for insoluble Mn; and from 2.0-490 μg/m(3) for Mn (sum of fractions). For all jobs combined, total particulate TWA GM concentrations of the Mn(sum) were 99 (GSD = 3.35) and 8.7 (GSD = 3.54) μg/m(3) for workers inside and outside of confined spaces; respirable Mn also showed much higher levels for welders within confined spaces. Regardless of particle size and confined space work status, Mn(0,2+) fraction was the most abundant followed by Mn(3+,4+) fraction, typically >50% and ∼30-40% of Mn(sum), respectively. Eighteen welders' exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 μg/m(3)) and 25 exceeded the recently adopted respirable

  1. Manganese fractionation using a sequential extraction method to evaluate welders’ shielded metal arc welding exposures during construction projects in oil refineries

    Science.gov (United States)

    Hanley, Kevin W.; Andrews, Ronnee; Bertke, Steven; Ashley, Kevin

    2015-01-01

    The National Institute for Occupational Safety and Health (NIOSH) has conducted an occupational exposure assessment study of manganese (Mn) in welding fume of construction workers rebuilding tanks, piping, and process equipment at two oil refineries. The objective of this study was to evaluate exposures to different Mn fractions using a sequential extraction procedure. Seventy-two worker-days were monitored for either total or respirable Mn during stick welding and associated activities both within and outside of confined spaces. The samples were analyzed using an experimental method to separate different Mn fractions by valence states based on selective chemical solubility. The full-shift total particulate Mn time-weighted average (TWA) breathing zone concentrations ranged from 0.013 – 29 for soluble Mn in a mild ammonium acetate solution; from 0.26 – 250 for Mn0,2+ in acetic acid; from non-detectable (ND) – 350 for Mn3+,4+ in hydroxylamine-hydrochloride; and from ND – 39 micrograms per cubic meter (μg/m3) for insoluble Mn fractions in hydrochloric and nitric acid. The summation of all Mn fractions in total particulate TWA ranged from 0.52 to 470 μg/m3. The range of respirable particulate Mn TWA concentrations were from 0.20 – 28 for soluble Mn; from 1.4 – 270 for Mn0,2+; from 0.49 – 150 for Mn3+,4+; from ND – 100 for insoluble Mn; and from 2.0 – 490 μg/m3 for Mn (sum of fractions). For all jobs combined, total particulate TWA GM concentrations of the Mn(sum) were 99 (GSD=3.35) and 8.7 (GSD=3.54) μg/m3 for workers inside and outside of confined spaces; respirable Mn also showed much higher levels for welders within confined spaces. Regardless of particle size and confined space work status, Mn0,2+ fraction was the most abundant followed by Mn3+,4+ fraction, typically >50% and ~30-40% of Mn(sum), respectively. Eighteen welders’ exposures exceeded the ACGIH Threshold Limit Values for total Mn (100 μg/m3) and 25 exceeded the recently adopted

  2. Allosteric inhibition enhances the efficacy of ABL kinase inhibitors to target unmutated BCR-ABL and BCR-ABL-T315I

    Directory of Open Access Journals (Sweden)

    Mian Afsar

    2012-09-01

    Full Text Available Abstract Background Chronic myelogenous leukemia (CML and Philadelphia chromosome-positive (Ph+ acute lymphatic leukemia (Ph + ALL are caused by the t(9;22, which fuses BCR to ABL resulting in deregulated ABL-tyrosine kinase activity. The constitutively activated BCR/ABL-kinase “escapes” the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. The ABL-kinase inhibitors (AKIs Imatinib, Nilotinib or Dasatinib, which target the ATP-binding site, are effective in Ph + leukemia. Another molecular therapy approach targeting BCR/ABL restores allosteric inhibition. Given the fact that all AKIs fail to inhibit BCR/ABL harboring the ‘gatekeeper’ mutation T315I, we investigated the effects of AKIs in combination with the allosteric inhibitor GNF2 in Ph + leukemia. Methods The efficacy of this approach on the leukemogenic potential of BCR/ABL was studied in Ba/F3 cells, primary murine bone marrow cells, and untransformed Rat-1 fibroblasts expressing BCR/ABL or BCR/ABL-T315I as well as in patient-derived long-term cultures (PDLTC from Ph + ALL-patients. Results Here, we show that GNF-2 increased the effects of AKIs on unmutated BCR/ABL. Interestingly, the combination of Dasatinib and GNF-2 overcame resistance of BCR/ABL-T315I in all models used in a synergistic manner. Conclusions Our observations establish a new approach for the molecular targeting of BCR/ABL and its resistant mutants using a combination of AKIs and allosteric inhibitors.

  3. Protein Kinase CK2: A Targetable BCR-ABL Partner in Philadelphia Positive Leukemias

    Directory of Open Access Journals (Sweden)

    Alessandro Morotti

    2015-01-01

    Full Text Available BCR-ABL-mediated leukemias, either Chronic Myeloid Leukemia (CML or Philadelphia positive Acute Lymphoblastic Leukemia (ALL, are the paradigm of targeted molecular therapy of cancer due to the impressive clinical responses obtained with BCR-ABL specific tyrosine kinase inhibitors (TKIs. However, BCR-ABL TKIs do not allow completely eradicating both CML and ALL. Furthermore, ALL therapy is associated with much worse responses to TKIs than those observed in CML. The identification of additional pathways that mediate BCR-ABL leukemogenesis is indeed mandatory to achieve synthetic lethality together with TKI. Here, we review the role of BCR-ABL/protein kinase CK2 interaction in BCR-ABL leukemias, with potentially relevant implications for therapy.

  4. Measurement of BCR-ABL1 by RT-qPCR in chronic myeloid leukaemia: findings from an International EQA Programme.

    Science.gov (United States)

    Scott, Stuart; Travis, Debbie; Whitby, Liam; Bainbridge, John; Cross, Nicholas C P; Barnett, David

    2017-05-01

    Sequential measurement of BCR-ABL1 mRNA levels by reverse transcription quantitative polymerase chain reaction (RT-qPCR) is embedded in the management of patients with chronic myeloid leukaemia (CML), and has played an important role in the remarkable improvement in patient outcomes seen in this disease. As a provider of external quality assessment (EQA) in this area, UK NEQAS for Leucocyte Immunophenotyping (UKNEQAS LI) has a unique perspective on the changing face of BCR-ABL1 testing in CML. To assess the impact of technical standardisation and the development of the International Scale (IS) upon the accuracy of BCR-ABL1 testing, we reviewed EQA trial data from 2007 to 2015. Comparison of participant results identified considerable variability at both high and low levels of disease, including therapeutically important decision points; however, results converted to the IS showed less variability compared to unconverted data sets. We also found that different methods of converting to the IS produce consistently different median results within UKNEQAS LI IS data sets. This data suggests that whilst the development of the IS has improved the comparability of results between centres, there is still the need for further improvement in the processes of converting raw results to the IS in order to fully realise the benefits of molecular monitoring of CML. © 2017 John Wiley & Sons Ltd.

  5. What do results of common sequential fractionation and single-step extractions tell us about P binding with Fe and Al compounds in non-calcareous sediments?

    Czech Academy of Sciences Publication Activity Database

    Jan, Jiří; Borovec, Jakub; Kopáček, Jiří; Hejzlar, Josef

    2013-01-01

    Roč. 47, č. 2 (2013), s. 547-557 ISSN 0043-1354 R&D Projects: GA ČR(CZ) GA206/09/1764; GA MZe(CZ) QH81012; GA MZe(CZ) QI102A265 Institutional support: RVO:60077344 Keywords : sequential fractionation * ascorbate and oxalate extration * non-calcareous sediments Subject RIV: DA - Hydrology ; Limnology Impact factor: 5.323, year: 2013

  6. MYC protein dysregulation is driven by BCR-PI3K signalling in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Wang, Wei-Ge; Liu, Ze-Bing; Jiang, Xiang-Nan; Lee, Jimmy; Zhou, Xiao-Yan; Li, Xiao-Qiu

    2017-11-01

    MYC overexpression is a common feature of diffuse large B-cell lymphoma (DLBCL) and is associated with poor prognosis in patients with this neoplasm. We aimed to investigate the underlying mechanisms of MYC dysregulation, as they have not been fully determined. We immunohistochemically evaluated the correlation between B-cell receptor (BCR)-phosphoinositide 3-kinase (PI3K) pathway activity and MYC level in 108 cases of de-novo DLBCL, 25 of which featured loss of BCR, and investigated the effects of BCR-PI3K signalling on MYC level and phosphorylation in DLBCL cell lines. The expression levels of phospho-SYK and phospho-AKT correlated with MYC expression in BCR-positive DLBCL. MYC expression was significantly lower in BCR-negative tumour tissues than in BCR-positive tumour tissues. Upon BCR stimulation, the BCR-positive cell lines showed active BCR-PI3K signalling and decreased MYC phosphorylation at T58, leading to an increased overall level of MYC. Conversely, inhibition of BCR-PI3K signalling increased MYC phosphorylation and thus resulted in a decreased overall level of MYC. No effects were observed in the BCR-negative cell lines. Overexpression of MYC in DLBCL can be driven by the BCR-PI3K signalling pathway via dephosphorylation at T58, and BCR inhibitors may exert their functions by down-regulation of MYC. © 2017 John Wiley & Sons Ltd.

  7. Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells

    NARCIS (Netherlands)

    Avalos, Ana M.; Bilate, Angelina M.; Witte, Martin D.; Tai, Albert K.; He, Jiang; Frushicheva, Maria P.; Thill, Peter D.; Meyer-Wentrup, Friederike; Theile, Christopher S.; Chakraborty, Arup K.; Zhuang, Xiaowei; Ploegh, Hidde L.

    2014-01-01

    Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR.

  8. Sequential chemical extraction of heavy metals in a study of the chemical alteration of mine tailings at Ticapampa (Huaraz, Peru); Extraccion quimica secuencial de metales pesados en el estudio de alteracion quimica de relaves de mina en Ticapampa (Huaraz, Peru)

    Energy Technology Data Exchange (ETDEWEB)

    Jara Facundo, M. A.

    2011-07-01

    The upper reaches of the Rio Santa (Huaraz, Peru) are highly affected by the mining activities of generally small and very small mining companies located in two specific areas, Cordillera Blanca, and Cordillera Negra, with the largest mining claims located in the districts of Recuay and Ticapampa. To assess the mobility and bioavailability of heavy metals in the abandoned tailings pond belonging to the Alianza mining company in the district of Ticapampa, and to identify the fractions to which they are associated we applied a sequential chemical extraction. The results were compared with studies into their mineralogical characterization, a quantitative chemical analysis and a determination of potential acidity and potential neutralization by the ABA (acid-base accounting) method applied to samples of tailings. The sequential extraction procedure confirmed the mode of general alteration observed in the area through mineralogical studies: a relatively easy mobility of Pb, and Cd, and considerable immobility with regard to Ag, Cr and Co, as well as an intermediate mobility of Cu, Zn, and As. Significant cadmium and lead contents found in the most mobile fractions of the tailings may represent an environmental threat, bearing in mind the toxic nature of these elements. Despite the low mobility of arsenic, the total quantities of this element are so high that the waters of the Rio Santa are being affected. (Author) 22 refs.

  9. Minimal sequential Hausdorff spaces

    Directory of Open Access Journals (Sweden)

    Bhamini M. P. Nayar

    2004-01-01

    Full Text Available A sequential space (X,T is called minimal sequential if no sequential topology on X is strictly weaker than T. This paper begins the study of minimal sequential Hausdorff spaces. Characterizations of minimal sequential Hausdorff spaces are obtained using filter bases, sequences, and functions satisfying certain graph conditions. Relationships between this class of spaces and other classes of spaces, for example, minimal Hausdorff spaces, countably compact spaces, H-closed spaces, SQ-closed spaces, and subspaces of minimal sequential spaces, are investigated. While the property of being sequential is not (in general preserved by products, some information is provided on the question of when the product of minimal sequential spaces is minimal sequential.

  10. Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia.

    Science.gov (United States)

    Boer, Judith M; Steeghs, Elisabeth M P; Marchante, João R M; Boeree, Aurélie; Beaudoin, James J; Beverloo, H Berna; Kuiper, Roland P; Escherich, Gabriele; van der Velden, Vincent H J; van der Schoot, C Ellen; de Groot-Kruseman, Hester A; Pieters, Rob; den Boer, Monique L

    2017-01-17

    Approximately 15% of pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by gene expression similar to that of BCR-ABL1-positive disease and unfavorable prognosis. This BCR-ABL1-like subtype shows a high frequency of B-cell development gene aberrations and tyrosine kinase-activating lesions. To evaluate the clinical significance of tyrosine kinase gene fusions in children with BCP-ALL, we studied the frequency of recently identified tyrosine kinase fusions, associated genetic features, and prognosis in a representative Dutch/German cohort. We identified 14 tyrosine kinase fusions among 77 BCR-ABL1-like cases (18%) and none among 76 non-BCR-ABL1-like B-other cases. Novel exon fusions were identified for RCSD1-ABL2 and TERF2-JAK2. JAK2 mutation was mutually exclusive with tyrosine kinase fusions and only occurred in cases with high CRLF2 expression. The non/late response rate and levels of minimal residual disease in the fusion-positive BCR-ABL1-like group were higher than in the non-BCR-ABL1-like B-others (pfusion-negative BCR-ABL1-like group. The 8-year cumulative incidence of relapse in the fusion-positive BCR-ABL1-like group (35%) was comparable with that in the fusion-negative BCR-ABL1-like group (35%), and worse than in the non-BCR-ABL1-like B-other group (17%, p=0.07). IKZF1 deletions, predominantly other than the dominant-negative isoform and full deletion, co-occurred with tyrosine kinase fusions. This study shows that tyrosine kinase fusion-positive cases are a high-risk subtype of BCP-ALL, which warrants further studies with specific kinase inhibitors to improve outcome.

  11. Anaerobic Biochemical Reactor (BCR) Treatment Of Mining-Influenced Water (MIW) - Investigation Of Metal Removal Efficiency and Ecotoxicity

    Science.gov (United States)

    BCR have been successful at removing a high percentage of metals from MIW, while BCR effluent toxicity has not been examined previously in the field. This study examined 4 active pilot BCR systems for removal of metals and toxicity. Removal efficiency for Al, As, Cd, Cu, Ni, Pb...

  12. BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features.

    Science.gov (United States)

    Neuendorff, Nina Rosa; Burmeister, Thomas; Dörken, Bernd; Westermann, Jörg

    2016-08-01

    BCR-ABL-positive acute myeloid leukemia (AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. Since a clear distinction between de novo BCR-ABL+ AML and chronic myeloid leukemia (CML) blast crisis is challenging in many cases, the existence of de novo BCR-ABL+ AML has been a matter of debate for a long time. However, there is increasing evidence suggesting that BCR-ABL+ AML is in fact a distinct subgroup of AML. In this study, we analyzed all published cases since 1975 as well as cases from our institution in order to present common clinical and molecular features of this rare disease. Our analysis shows that BCR-ABL predominantly occurs in AML-NOS, CBF leukemia, and AML with myelodysplasia-related changes. The most common BCR-ABL transcripts (p190 and p210) are nearly equally distributed. Based on the analysis of published data, we provide a clinical algorithm for the initial differential diagnosis of BCR-ABL+ AML. The prognosis of BCR-ABL+ AML seems to depend on the cytogenetic and/or molecular background rather than on BCR-ABL itself. A therapy with tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, or nilotinib is reasonable, but-due to a lack of systematic clinical data-their use cannot be routinely recommended in first-line therapy. Beyond first-line treatment of AML, the use of TKI remains an individual decision, both in combination with intensive chemotherapy and/or as a bridge to allogeneic stem cell transplantation. In each single case, potential benefits have to be weighed against potential risks.

  13. Regulation of hTERT by BCR-ABL at multiple levels in K562 cells

    International Nuclear Information System (INIS)

    Chai, Juin Hsien; Zhang, Yong; Tan, Wei Han; Chng, Wee Joo; Li, Baojie; Wang, Xueying

    2011-01-01

    The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that BCR-ABL is the specific target of Gleevec in CML treatment, we investigated the regulation of the catalytic component of telomerase, hTERT, by BCR-ABL at multiple levels in K562 cells. Molecular techniques such as over expression, knockdown, real-time PCR, immunoprecipitation, western blotting, reporter assay, confocal microscopy, telomerase assays and microarray were used to suggest that hTERT expression and activity is modulated by BCR-ABL at multiple levels. Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells (BCR-ABL negative cells). We also demonstrated that the transcription factor STAT5a plays a critical role in hTERT gene regulation in K562 cells. Knockdown of STAT5a, but not STAT5b, resulted in a marked downregulation of hTERT mRNA level, TA and hTERT protein level in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec. Our data reveal that BCR-ABL can regulate TA at multiple levels, including transcription, post-translational level, and proper localization. Thus, suppression of cell growth and induction of apoptosis by Gleevec treatment may be partially due to TA inhibition. Additionally, we have identified STAT5a as critical mediator of the hTERT gene expression in BCR-ABL positive CML cells, suggesting that targeting STAT5a may be a promising therapeutic strategy for BCR-ABL positive CML patients

  14. Biosensing of BCR/ABL fusion gene using an intensity-interrogation surface plasmon resonance imaging system

    Science.gov (United States)

    Wu, Jiangling; Huang, Yu; Bian, Xintong; Li, DanDan; Cheng, Quan; Ding, Shijia

    2016-10-01

    In this work, a custom-made intensity-interrogation surface plasmon resonance imaging (SPRi) system has been developed to directly detect a specific sequence of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). The variation in the reflected light intensity detected from the sensor chip composed of gold islands array is proportional to the change of refractive index due to the selective hybridization of surface-bound DNA probes with target ssDNA. SPRi measurements were performed with different concentrations of synthetic target DNA sequence. The calibration curve of synthetic target sequence shows a good relationship between the concentration of synthetic target and the change of reflected light intensity. The detection limit of this SPRi measurement could approach 10.29 nM. By comparing SPRi images, the target ssDNA and non-complementary DNA sequence are able to be distinguished. This SPRi system has been applied for assay of BCR/ABL fusion gene extracted from real samples. This nucleic acid-based SPRi biosensor therefore offers an alternative high-effective, high-throughput label-free tool for DNA detection in biomedical research and molecular diagnosis.

  15. The Bcr-Abl kinase inhibitor INNO-406 induces autophagy and different modes of cell death execution in Bcr-Abl-positive leukemias.

    Science.gov (United States)

    Kamitsuji, Y; Kuroda, J; Kimura, S; Toyokuni, S; Watanabe, K; Ashihara, E; Tanaka, H; Yui, Y; Watanabe, M; Matsubara, H; Mizushima, Y; Hiraumi, Y; Kawata, E; Yoshikawa, T; Maekawa, T; Nakahata, T; Adachi, S

    2008-11-01

    Bcr-Abl tyrosine kinase (TK) inhibitors are promising therapeutic agents for Bcr-Abl-positive (Bcr-Abl(+)) leukemias. Although they are known to promote caspase-mediated apoptosis, it remains unclear whether caspase-independent cell death-inducing mechanisms are also triggered. Here we demonstrated that INNO-406, a second-generation Bcr-Abl TK inhibitor, induces programmed cell death (PCD) in chronic myelogenous leukemia (CML) cell lines through both caspase-mediated and caspase-independent pathways. The latter pathways include caspase-independent apoptosis (CIA) and necrosis-like cell death (CIND), and the cell lines varied regarding which mechanism was elicited upon INNO-406 treatment. We also observed that the propensity toward CIA or CIND in cells was strongly associated with cellular dependency on apoptosome-mediated caspase activity. Cells that undergo CIND have a high apoptosome activity potential whereas cells that undergo CIA tend to have a lower potential. Moreover, we found that INNO-406 promotes autophagy. When autophagy was inhibited with chloroquine or gene knockdown of beclin1 by shRNA, INNO-406-induced cell death was enhanced, which indicates that the autophagic response of the tumor cells is protective. These findings suggest new insights into the biology and therapy of Bcr-Abl(+) leukemias.

  16. Immersed single-drop microextraction interfaced with sequential injection analysis for determination of Cr(VI) in natural waters by electrothermal-atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Pena, Francisco; Lavilla, Isela; Bendicho, Carlos

    2008-01-01

    Single-drop microextraction (SDME) and sequential injection analysis have been hyphenated for ultratrace metal determination by Electrothermal-Atomic Absorption Spectrometry (ETAAS). The novel method was targeted on extraction of the Cr(VI)-APDC chelate and encompasses the potential of SDME as a miniaturized and virtually solvent-free preconcentration technique, the ability of sequential injection analysis to handle samples and the versatility of furnace autosamplers for introducing microliter samples in ETAAS. The variables influencing the microextraction of Cr(VI) onto an organic solvent drop, i.e., type of organic solvent, microextraction time, stirring rate of the sample solution, drop volume, immersion depth of the drop, salting-out effect, temperature of the sample, concentration of the complexing agent and pH of the sample solution were fully investigated. For a 5 and 20 min microextraction time, the preconcentration factors were 20 and 70, respectively. The detection limit was 0.02 μg/L of Cr(VI) and the repeatability expressed as relative standard deviation was 7%. The SDME-SIA-ETAAS technique was validated against BCR CRM 544 (lyophilized solution) and applied to ultrasensitive determination of Cr(VI) in natural waters

  17. Inhibition of BCR/ABL protein expression by miR-203 sensitizes for imatinib mesylate.

    Directory of Open Access Journals (Sweden)

    Yajuan Li

    Full Text Available Selective inhibition of BCR/ABL expression by RNA interference has been demonstrated as an effective strategy in CML treatment and a reversal to imatinib resistance. microRNAs (miRNAs are small regulatory RNAs involved in post-transcriptional gene regulation. miR-203 is supposed to directly regulate ABL and BCR/ABL expression, however, the role of miR-203 in imatinib-resistant cells is not clear. Here, we report that overexpression of miR-203 in BaF3-BCR/ABL cells with T315I mutant inhibited cell growth and colony formation ability. Furthermore, miR-203 increased sensitivity to imatinib in BaF3-BCR/ABL(T315I cells, thereby antagonizing the main mechanism of resistance to imatinib.

  18. A BCR-ABL Kinase Activity-Independent Signaling Pathway in Chronic Myelogenous Leukemia

    National Research Council Canada - National Science Library

    Li, Shaoguang

    2008-01-01

    .... We identified Src kinases as key molecules in this BCR- ABL kinase activity-independent pathway and they are essential for leukemic cells to survive imatinib treatment and for CML transition to lymphoid blast crisis...

  19. Lack of bcr and abr promotes hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Min Yu

    Full Text Available Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined.Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr-/- and abr-/- macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia.Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

  20. Molecular detection of BCR/ABL fusion gene in Saudi acute lymphoblastic leukemia patients.

    Science.gov (United States)

    El-Sissy, Azza; El-Mashari, May; Bassuni, Wafaa; El-Swaayed, Aziza

    2006-06-01

    Molecular cytogenetics is becoming one of the most useful tools targeting some genes which are generally considered to lead to leukemic transformation (as well as for numerical abnormalities). A fraction of acute lymphoblastic leukemia (ALL) cases carry the translocation t(9;22) (q34;q11.2) which juxtaposes the ABL proto-oncogene to the BCR gene generating a chimeric gene, BCR/ABL. This aberration is more frequent in adult ALL (20%-40%) than in pediatric ALL (<5%), and predicts poor clinical outcome. AIM OF OUR WORK: Is to study BCR/ABL fusion gene in ALL cases using fluorescent in situ hybridization. Twenty newly diagnosed ALL patients, 16 adult and 4 paediatric cases, were included in the study, 11 cases (55%) were of precursor B phenotype, 8 cases (40%) belonged to T lineage, while one case was biphenotypic expressing mainly precursor B cell markers tether with CD13, CD33, CD117, Detection of BCR/ABL fusion gene was done using interphase FISH technique and was confirmed molecularly using the RT-PCR technique. BCR/ABL fusion gene was negative in all the examined cases, yet abnormality involving 9q34, ABL gene, either by addition or deletion was detected in three cases (15%). Two of these cases were associated with BCR gene extra copies (three and four copies, respectively). This may reflect the frequency of association of ABL gene and BCR gene abnormality in our cases, and that absence of fusion gene BCR/ABL does not exclude their role in the leukomogenic process, yet a larger study is required to confirm and detect the prevalence of these gene disturbances in ALL and their association.

  1. Sequential diffusion of ammonium and nitrate from soil extracts to a polytetrafluoroethylene trap for 15N determination

    DEFF Research Database (Denmark)

    Sørensen, P.; Jensen, E.S.

    1991-01-01

    A novel diffusion method was used for preparation of NH4+- and NO3--N samples from soil extracts for N-15 determination. Ammonium, and nitrate following reduction to ammonia, are allowed to diffuse to an acid-wetted glass filter enclosed in polytetrafluoroethylene tape. The method was evaluated w......-degrees-C). Owing to the presence of inorganic nitrogen impurities in the potassium chloride, the N-15 enrichments should be corrected for the blank nitrogen content....

  2. BCR-ABL promotes the frequency of mutagenic single-strand annealing DNA repair

    Science.gov (United States)

    Fernandes, Margret S.; Reddy, Mamatha M.; Gonneville, Jeffrey R.; DeRoo, Scott C.; Podar, Klaus; Griffin, James D.; Weinstock, David M.

    2009-01-01

    Intracellular oxidative stress in cells transformed by the BCR-ABL oncogene is associated with increased DNA double-strand breaks. Imprecise repair of these breaks can result in the accumulation of mutations, leading to therapy-related drug resistance and disease progression. Using several BCR-ABL model systems, we found that BCR-ABL specifically promotes the repair of double-strand breaks through single-strand annealing (SSA), a mutagenic pathway that involves sequence repeats. Moreover, our results suggest that mutagenic SSA repair can be regulated through the interplay between BCR-ABL and extrinsic growth factors. Increased SSA activity required Y177 in BCR-ABL, as well as a functional PI3K and Ras pathway downstream of this site. Furthermore, our data hint at a common pathway for DSB repair whereby BCR-ABL, Tel-ABL, Tel-PDGFR, FLT3-ITD, and Jak2V617F all increase mutagenic repair. This increase in SSA may not be sufficiently suppressed by tyrosine kinase inhibitors in the stromal microenvironment. Therefore, drugs that target growth factor receptor signaling represent potential therapeutic agents to combat tyrosine kinase-induced genomic instability. PMID:19571320

  3. In-situ determination of metallic variation and multi-association in single particles by combining synchrotron microprobe, sequential chemical extraction and multivariate statistical analysis.

    Science.gov (United States)

    Zhu, Yu-Min; Zhang, Hua; Fan, Shi-Suo; Wang, Si-Jia; Xia, Yi; Shao, Li-Ming; He, Pin-Jing

    2014-07-15

    Due to the heterogeneity of metal distribution, it is challenging to identify the speciation, source and fate of metals in solid samples at micro scales. To overcome these challenges single particles of air pollution control residues were detected in situ by synchrotron microprobe after each step of chemical extraction and analyzed by multivariate statistical analysis. Results showed that Pb, Cu and Zn co-existed as acid soluble fractions during chemical extraction, regardless of their individual distribution as chlorides or oxides in the raw particles. Besides the forms of Fe2O3, MnO2 and FeCr2O4, Fe, Mn, Cr and Ni were closely associated with each other, mainly as reducible fractions. In addition, the two groups of metals had interrelations with the Si-containing insoluble matrix. The binding could not be directly detected by micro-X-ray diffraction (μ-XRD) and XRD, suggesting their partial existence as amorphous forms or in the solid solution. The combined method on single particles can effectively determine metallic multi-associations and various extraction behaviors that could not be identified by XRD, μ-XRD or X-ray absorption spectroscopy. The results are useful for further source identification and migration tracing of heavy metals. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. The bcr1 DNA repeat element is specific to the Bacillus cereus group and exhibits mobile element characteristics.

    Science.gov (United States)

    Økstad, Ole Andreas; Tourasse, Nicolas J; Stabell, Fredrik B; Sundfaer, Cathrine K; Egge-Jacobsen, Wolfgang; Risøen, Per Arne; Read, Timothy D; Kolstø, Anne-Brit

    2004-11-01

    Bacillus cereus strains ATCC 10987 and ATCC 14579 harbor an approximately 155-bp repeated element, bcr1, which is conserved in B. cereus, B. anthracis, B. thuringiensis, and B. mycoides but not in B. subtilis and B. licheniformis. In this study, we show by Southern blot hybridizations that bcr1 is present in all 54 B. cereus group strains tested but absent in 11 Bacillus strains outside the group, suggesting that bcr1 may be specific and ubiquitous to the B. cereus group. By comparative analysis of the complete genome sequences of B. cereus ATCC 10987, B. cereus ATCC 14579, and B. anthracis Ames, we show that bcr1 is exclusively present in the chromosome but absent from large plasmids carried by these strains and that the numbers of full-length bcr1 repeats for these strains are 79, 54, and 12, respectively. Numerous copies of partial bcr1 elements are also present in the three genomes (91, 128, and 53, respectively). Furthermore, the genomic localization of bcr1 is not conserved between strains with respect to chromosomal position or organization of gene neighbors, as only six full-length bcr1 loci are common to at least two of the three strains. However, the intergenic sequence surrounding a specific bcr1 repeat in one of the three strains is generally strongly conserved in the other two, even in loci where bcr1 is found exclusively in one strain. This finding indicates that bcr1 either has evolved by differential deletion from a very high number of repeats in a common ancestor to the B. cereus group or is moving around the chromosome. The identification of bcr1 repeats interrupting genes in B. cereus ATCC 10987 and ATCC 14579 and the presence of a flanking TTTAT motif in each end show that bcr1 exhibits features characteristic of a mobile element.

  5. Phosphogypsum analysis: total content and extractable element concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Gennari, Roseli F.; Medina, Nilberto H., E-mail: rgennari@dfn.if.usp.br, E-mail: medina@if.usp.br [Departamento de Fisica Nuclear, Instituto de Fisica (USP), Sao Paulo, SP (Brazil); Garcia, Isabella; Silveira, Marcilei A.G., E-mail: shila@if.usp.br [Centro Universitario da FEI. Sao Bernardo do Campo, SP (Brazil)

    2011-07-01

    Phosphogypsum stand for the chemical origin gypsum generated in fertilizers production, in which phosphate rock is attacked by sulfuric acid resulting in phosphoric acid (H{sub 3}PO{sub 4}) and phosphate fertilizers. Phosphogypsum is not a commercial product and it is stocked in large open areas or accumulated in lakes inducing to a major environmental problem due to the presence of toxic and radioactive elements. The increasing world agricultural demand is the real responsible for the severity of this environmental problem. Nevertheless, there are some possibilities for the application of this reject material, such as civil construction, waste water treatment, and in cultivated lands, etc. In the agriculture the phosphogypsum is commonly used as a nutrient source due to its large amounts of phosphorus, calcium and sulfur. However, there are still some environmental questions related to the use of this by-product since phosphogypsum is classified as TENORM (Technologically Enhanced Naturally Occurring Radioactive Material), which is a solid waste containing heavy metals and naturally occurring radioactive elements from the rock matrix. In this work, Plasma Mass Spectrometry (ICP-MS) was used to study phosphogypsum samples. Several acid solutions for samples digestion were evaluated in order to be feasible the chemical analysis. BCR sequential extractions were also performed. The results showed analyte concentrations are highly dependent on the acid solution used. The BCR guidelines could not be applied as used for soil, since the phosphogypsum solubility is different. So, it would be necessary to use different mass aliquots in the extractions, to be feasible an environmental evaluation. (author)

  6. [TEC promoter mediates P210(bcr/abl) gene expression in BaF3 cells].

    Science.gov (United States)

    Zhu, Yu-Feng; Wang, Yuan-Zhan; Meng, Fan-Yi

    2012-06-01

    P210(bcr/abl) transgene mouse is a good model to research the chronic myelogenous leukemia (CML), but the P210(bcr/abl) gene has a lethal effect on embryogenesis if driven by the constitutive promoter. So, the use of promoter which induces the special expression in hematopoietic tissue is the key to construct CML transgenic mice. This study was purposed to investigate the TEC promoter mediated P210(bcr/abl) gene expression in BaF3 cells. The CMVie promotes of IRES2-eGFP vector was replaced with the -364-+22 domain of TEC promoter cloned from mouse genome, and the P210(bcr/abl) gene was inserted into the EcoR I site of TEC-IRES2-eGFP vector. Then, the constructed vector was transfected into the BaF3 cells and 293 cells respectively. The expression levels of eGFP gene and P210(bcr/abl) gene in BaF3 and 293 cells were detected. The results showed that with fluorescent microscopy and flow cytometry, the eGFP gene was found to be expressed in the BaF3 cells, the expression rate was 7.10%, 23.35%, 64.61% at 6, 24, 72 h respectively after transfection, but the fluorescence was not seen in 293 cells. A 372 bp fragment of BCR/ABL mRNA was amplified by RT-PCR in BaF3 cells, but not in 293 cells. It is concluded that the -364-+22 domain of TEC promoter can mediate high-effective and specific expression of related genes in hematopoietic tissue, which can be used to construct P210(bcr/abl) transgene mice model.

  7. Unique amplification of BCR-ABL1 gene fusion in a case of T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Koka, Rima; Bade, Najeebah A; Sausville, Edward A; Ning, Yi; Zou, Ying

    2017-01-01

    ABL1 gene translocations can be seen in precursor T-acute lymphoblastic leukemia (T-ALL). The typical translocation partner is the NUP214 gene. BCR-ABL translocations are relatively rare in this entity. Furthermore, while there have been unique patterns of amplification noted among the NUP214-ABL fusion genes, there have been few such reports among cases with BCR-ABL fusion genes. Here we report a unique case of a 44-year old patient with T-ALL in which the blasts demonstrated a derivative chromosome 9 involving a 9;22 translocation and a dicentric Philadelphia chromosome 22 with a homogeneously staining region at the interface of the 9;22 translocation, leading to BCR-ABL1 gene amplification. Fluorescence in-situ hybridization (FISH) showed abnormal BCR/ABL1 fusions with the BCR-ABL1 gene amplification in 48% of the interphase cells analyzed. The translocation was confirmed by SNP array. We present a novel derivative chromosome 9 that shows BCR-ABL gene fusion along with a dicentric Philadelphia chromosome 22 with BCR-ABL1 gene amplification. This is a unique pattern of BCR-ABL fusion which has never been described in T-ALL. It is significant that the patient responded to standard treatment with the CALGB 10403 protocol and supplementation with a tyrosine kinase inhibitor. Identification of additional patients with this pattern of BCR-ABL fusion will allow for enhanced risk assessment and prognostication.

  8. Biofilm formation and genetic variability of BCR1 gene in the Candida parapsilosis complex.

    Science.gov (United States)

    Treviño-Rangel, Rogelio de J; Rodríguez-Sánchez, Irám P; Rosas-Taraco, Adrián G; Hernández-Bello, Romel; González, José G; González, Gloria M

    2015-01-01

    Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis are cryptic species that belong to the C. parapsilosis complex, which has been increasingly associated to fungemia in various geographic regions, principally due to the capability of these yeasts to form biofilms on indwelling medical devices. BCR1 is one of the most studied genes related to Candida spp. biofilms. To evaluate the biofilm forming capability of a subset of 65 clinical isolates of the C. parapsilosis complex using two conventional approaches, and to look for an association between the biofilm forming phenotype and genetic variants of a fragment of BCR1. The biofilm determination was carried out by crystal violet staining and tetrazolium reduction assay. On the other hand, a segment of BCR1 gene was sequenced by Sanger methodology. C. parapsilosis sensu stricto was statistically associated with a low biofilm production phenotype, while C. orthopsilosis was significantly associated with both phenotypes (high and low biofilm producers). According to the BCR1 sequence analysis, genetic variability was detected in C. orthopsilosis and C. metapsilosis without a particular biofilm formation phenotype association. Under the adopted experimental design, C. parapsilosis sensu stricto was associated with the low biofilm phenotype and C. orthopsilosis with both phenotypes (high and low biofilm producers). On the other hand, an association between a biofilm forming phenotype and a particular genetic variant of the analyzed BCR1 fragment was not found. Copyright © 2014 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  9. [Generation and identification of P210(T315I-BCR/ABL) transgenic mice].

    Science.gov (United States)

    Zhu, Yufeng; Wang, Yuanzhan; Meng, Fanyi

    2015-03-01

    To construct the P210(T315I-BCR/ABL) transgenic mice model. The transgenic vector in which the P210(T315I-BCR/ABL) gene and eGFP gene was derived by APN/CD13 promoter was constructed and microinjected into the single-cell fertilized eggs of C57 mice. Transgene integration was conformed by PCR genotyping and P210(T315I-BCR/ABL) expression levels was evaluated by RT-PCR. The CML phenotype was confirmed by blood routine examination, Wright's staining for peripheral blood and bone marrow smears, HE staining for organs of transgenic mice. Three transgenic mice lines with high expression of P210(T315I-BCR/ABL) gene and eGFP gene was selected. Compared with the wild type mice, the levels of WBC, platelet and neutrophil granulocyte of transgenic mice began to increase gradually at 2 months, and increase to 23.9×10⁹/L, 4 136×10⁹/L, and 74.6% respectively at 6 months. The remarkable hyperplasia of granulocytes was seen in the peripheral blood and bone marrow smears with splenomegaly infiltrated by leukemic cells. The P210(T315I-BCR/ABL) transgenic mice was constructed and provided a model to explore the mechanism of T315I CML and screen out the drug for T315 CML patient.

  10. Targeting the SH2-Kinase Interface in Bcr-Abl Inhibits Leukemogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Grebien, Florian; Hantschel, Oliver; Wojcik, John; Kaupe, Ines; Kovacic, Boris; Wyrzucki, Arkadiusz M.; Gish, Gerald D.; Cerny-Reiterer, Sabine; Koide, Akiko; Beug, Hartmut; Pawson, Tony; Valent, Peter; Koide, Shohei; Superti-Furga, Giulio (AAS); (Mount Sinai Hospital); (Med U. Vienna); (UC); (IMP-CNRS)

    2012-10-25

    Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of the SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention.

  11. Comparative study of the fate and mobility of metals discharged in mining and urban effluents using sequential extractions on suspended solids.

    Science.gov (United States)

    Gagnon, Christian; Turcotte, Patrice; Vigneault, Bernard

    2009-12-01

    The fate, bioavailability and environmental impacts of metals discharged in municipal and mining wastewater discharge will depend to a large extent on chemical speciation and distribution. Previous studies on metal bioaccumulation have shown that total metal concentrations are not a good predictor of bioavailability in the dispersion plumes of municipal effluents. The objective of this study was to determine the solid phase speciation of metals in surface waters receiving urban and mining effluents in order to assess their fate and relative mobility in the receiving environment. Suspended particulate matter was sampled using sediment traps at several sites downstream of effluent outfall plumes as well as at reference upstream sites. Particulate metal in operationally defined fractions--exchangeable/carbonates, reducible, oxidisable and residual--were determined in suspended particulate matter with a series of selective chemical extractions. Metal enrichment in suspended particles was generally observed in both mining and urban effluent discharges. When compared to its receiving environment, the mining effluent appeared to release more particulate metals (Cu, Fe, Zn) in the most reactive fractions (i.e. exchangeable/carbonates + reducible forms, 23-43%), while other released metals, such as Cd and Mn, were predominantly in the least reactive forms (i.e., oxidisable + residual, 73-97%). In contrast, the reactivity of all particulate metals, with the exception of Mn, from the urban effluent was much higher, with up to 65, 42, 30 and 43% for Cd, Cu, Fe and Zn, respectively, in the two most reactive fractions. As expected in effluent dispersion plumes, parameters such as the organic carbon, Fe oxide and carbonate contents have specific effects on the partitioning of several trace metals, particularly Cd, Cu and Zn. Our results indicated that the relative distributions of metals among geochemical fractions varied in the effluent receiving waters where organic carbon and

  12. Sequential charged particle reaction

    International Nuclear Information System (INIS)

    Hori, Jun-ichi; Ochiai, Kentaro; Sato, Satoshi; Yamauchi, Michinori; Nishitani, Takeo

    2004-01-01

    The effective cross sections for producing the sequential reaction products in F82H, pure vanadium and LiF with respect to the 14.9-MeV neutron were obtained and compared with the estimation ones. Since the sequential reactions depend on the secondary charged particles behavior, the effective cross sections are corresponding to the target nuclei and the material composition. The effective cross sections were also estimated by using the EAF-libraries and compared with the experimental ones. There were large discrepancies between estimated and experimental values. Additionally, we showed the contribution of the sequential reaction on the induced activity and dose rate in the boundary region with water. From the present study, it has been clarified that the sequential reactions are of great importance to evaluate the dose rates around the surface of cooling pipe and the activated corrosion products. (author)

  13. Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Groffen John

    2007-10-01

    Full Text Available Abstract Background Ph-positive leukemias are caused by the aberrant fusion of the BCR and ABL genes. Nilotinib is a selective Bcr/Abl tyrosine kinase inhibitor related to imatinib, which is widely used to treat chronic myelogenous leukemia. Because Ph-positive acute lymphoblastic leukemia only responds transiently to imatinib therapy, we have used mouse models to test the efficacy of nilotinib against lymphoblastic leukemia caused by the P190 form of Bcr/Abl. Results After transplant of 10,000 highly malignant leukemic cells into compatible recipients, untreated mice succumbed to leukemia within 21 days, whereas mice treated with 75 mg/kg nilotinib survived significantly longer. We examined cells from mice that developed leukemia while under treatment for Bcr/Abl kinase domain point mutations but these were not detected. In addition, culture of such cells ex vivo showed that they were as sensitive as the parental cell line to nilotinib but that the presence of stromal support allowed resistant cells to grow out. Nilotinib also exhibited impressive anti-leukemia activity in P190 Bcr/Abl transgenic mice that had developed overt leukemia/lymphoma masses and that otherwise would have been expected to die within 7 days. Visible lymphoma masses disappeared within six days of treatment and leukemic cell numbers in peripheral blood were significantly reduced. Treated mice survived more than 30 days. Conclusion These results show that nilotinib has very impressive anti-leukemia activity but that lymphoblastic leukemia cells can become unresponsive to it both in vitro and in vivo through mechanisms that appear to be Bcr/Abl independent.

  14. Interphase FISH for BCR-ABL1 rearrangement on neutrophils: A decisive tool to discriminate a lymphoid blast crisis of chronic myeloid leukemia from a de novo BCR-ABL1 positive acute lymphoblastic leukemia.

    Science.gov (United States)

    Balducci, Estelle; Loosveld, Marie; Rahal, Ilhem; Boudjarane, John; Alazard, Emilie; Missirian, Chantal; Lafage-Pochitaloff, Marina; Michel, Gérard; Zattara, Hélène

    2018-02-01

    Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML. This case illustrates the major interest of interphase FISH for BCR-ABL1 rearrangement on blood neutrophils as a decisive method to discriminate a lymphoid blast crisis of CML from a de novo BCR-ABL1 positive ALL. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona

    2011-01-01

    T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow......) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors....

  16. Evaluation of alternate lines of Fe for sequential multi-element determination of Cu, Fe, Mn and Zn in soil extracts by high-resolution continuum source flame atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Luiz Raposo, Jorge; Ruella de Oliveira, Silvana; Caldas, Naise Mary; Neto, Jose Anchieta Gomes

    2008-01-01

    The usefulness of the secondary line at 252.744 nm and the approach of side pixel registration were evaluated for the development of a method for sequential multi-element determination of Cu, Fe, Mn and Zn in soil extracts by high-resolution continuum source flame atomic absorption spectrometry (HR-CS FAAS). The influence of side pixel registration on the sensitivity and linearity was investigated by measuring at wings (248.325, 248.323, 248.321, 248.329, and 248.332 nm) of the main line for Fe at 248.327 nm. For the secondary line at 252.744 nm or side pixel registration at 248.325 nm, main lines for Cu (324.754 nm), Mn (279.482 nm) and Zn (213.875 nm), sample flow-rate of 5.0 mL min -1 and calibration by matrix matching, analytical curves in the 0.2-1.0 mg L -1 Cu, 1.0-20.0 mg L -1 Fe, 0.2-2.0 mg L -1 Mn, 0.1-1.0 mg L -1 Zn ranges were obtained with linear correlations better than 0.998. The proposed method was applied to seven soil samples and two soil reference materials (IAC 277; IAC 280). Results were in agreement at a 95% confidence level (paired t-test) with reference values. Recoveries of analytes added to soil extracts containing 0.15 and 0.30 mg L -1 Cu, 7.0 and 14 mg L -1 Fe, 0.60 and 1.20 mg L -1 Mn, 0.07 and 0.15 mg L -1 Zn, varied within the 94-99, 92-98, 93-101, and 93-103% intervals, respectively. The relative standard deviations (n = 12) were 2.7% (Cu), 1.4% (Fe - 252.744 nm), 5.7% (Fe - 248.325 nm), 3.2% (Mn) and 2.8% (Zn) for an extract containing 0.35 mg L -1 Cu, 14 mg L -1 Fe, 1.1 mg L -1 Mn and 0.12 mg L -1 Zn. Detection limits were 5.4 μg L -1 Cu, 55 μg L -1 Fe (252.744 nm), 147 μg L -1 Fe (248.325 nm), 3.0 μg L -1 Mn and 4.2 μg L -1 Zn

  17. Finding False Paths in Sequential Circuits

    Science.gov (United States)

    Matrosova, A. Yu.; Andreeva, V. V.; Chernyshov, S. V.; Rozhkova, S. V.; Kudin, D. V.

    2018-02-01

    Method of finding false paths in sequential circuits is developed. In contrast with heuristic approaches currently used abroad, the precise method based on applying operations on Reduced Ordered Binary Decision Diagrams (ROBDDs) extracted from the combinational part of a sequential controlling logic circuit is suggested. The method allows finding false paths when transfer sequence length is not more than the given value and obviates the necessity of investigation of combinational circuit equivalents of the given lengths. The possibilities of using of the developed method for more complicated circuits are discussed.

  18. Sistema de extração seqüencial da solução na macro e microporosidade do solo System of sequential extraction of solution in macro and microporosity of soil

    Directory of Open Access Journals (Sweden)

    Thomas V. Gloaguen

    2009-10-01

    Full Text Available Existem várias técnicas de extração da solução no solo; entretanto, a proporção entre a água gravitacional e as retidas por forças capilares é geralmente desconhecida. Neste estudo se propôs desenvolver um sistema de extração seqüencial da solução no solo a fim de caracterizar a sua composição química em função da porosidade do solo. Construíram-se colunas com terra fina secada ao ar de um Cambissolo de textura argilo-siltosa. As colunas foram saturadas por 24 h com água destilada, logo após, a solução no solo foi coletada aplicando-se sucessivamente na base das colunas um vácuo de: 0; -13,3; -26,7; -40,0; -53,3; -66,6 kPa. Mediram-se o volume, o pH, a condutividade elétrica e as concentrações de Na+, K+ e NO3-. Houve boa correlação entre o vácuo aplicado e o potencial mátrico do solo medido por tensiometria (não linear, r² = 0,998, validando o método proposto da extração seqüencial de solução. O estudo evidenciou importantes variações da composição química da solução nas diferentes porosidades do solo, com concentração iônica menor na macroporosidade, exceto para K+, demonstrando a necessidade de se uniformizar a metodologia de amostragem da solução do solo para evitar estimação incorreta da concentração de solutos no solo.Various methodologies for soil solution sampling are available, but the proportion between gravitational and capilar water is usually unknown. In this study, a sequential extraction system of soil water for determining its chemical composition as a function of the soil porosity is presented. Soil columns were filled by air-dried clay-loam Ultisol. The columns were saturated with distilled water for 24 h, and then the soil solution was sampled at the base of the column by applying the suction equivalent to 0, 13.3, 26.7, 40.0, 53.3 and 66.6 kPa. Volume, pH, electrical conductivity, Na+, K+ and NO3- were measured in the solution. The high correlation (non linear; r

  19. Chronic myeloid leukemia may be associated with several bcr-abl transcripts including the acute lymphoid leukemia-type 7 kb transcript

    NARCIS (Netherlands)

    Selleri, L.; von Lindern, M.; Hermans, A.; Meijer, D.; Torelli, G.; Grosveld, G.

    1990-01-01

    In the majority of Philadelphia (Ph)-positive chronic myeloid leukemia (CML) patients, the c-abl gene is fused to the bcr gene, resulting in the transcription of an 8.5 kb chimeric bcr-abl mRNA, which is translated into a p210bcr-abl fusion protein. In about 50% of the Ph-positive acute lymphoid

  20. Sequential inductive learning

    Energy Technology Data Exchange (ETDEWEB)

    Gratch, J. [Univ. of Southern California, Marina del Rey, CA (United States)

    1996-12-31

    This article advocates a new model for inductive learning. Called sequential induction, it helps bridge classical fixed-sample learning techniques (which are efficient but difficult to formally characterize), and worst-case approaches (which provide strong statistical guarantees but are too inefficient for practical use). Learning proceeds as a sequence of decisions which are informed by training data. By analyzing induction at the level of these decisions, and by utilizing the only enough data to make each decision, sequential induction provides statistical guarantees but with substantially less data than worst-case methods require. The sequential inductive model is also useful as a method for determining a sufficient sample size for inductive learning and as such, is relevant to learning problems where the preponderance of data or the cost of gathering data precludes the use of traditional methods.

  1. Development of a fully automated sequential injection solid-phase extraction procedure coupled to liquid chromatography to determine free 2-hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid in human urine

    International Nuclear Information System (INIS)

    Leon, Zacarias; Chisvert, Alberto; Balaguer, Angel; Salvador, Amparo

    2010-01-01

    2-Hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid, commonly known as benzophenone-3 (BZ3) and benzophenone-4 (BZ4), respectively, are substances widely used as UV filters in cosmetic products in order to absorb UV radiation and protect human skin from direct exposure to the deleterious wavelengths of sunlight. As with other UV filters, there is evidence of their percutaneous absorption. This work describes an analytical method developed to determine trace levels of free BZ3 and BZ4 in human urine. The methodology is based on a solid-phase extraction (SPE) procedure for clean-up and pre-concentration, followed by the monitoring of the UV filters by liquid chromatography-ultraviolet spectrophotometry detection (LC-UV). In order to improve not only the sensitivity and selectivity, but also the precision of the method, the principle of sequential injection analysis was used to automate the SPE process and to transfer the eluates from the SPE to the LC system. The application of a six-channel valve as an interface for the switching arrangements successfully allowed the on-line connection of SPE sample processing with LC analysis. The SPE process for BZ3 and BZ4 was performed using octadecyl (C18) and diethylaminopropyl (DEA) modified silica microcolumns, respectively, in which the analytes were retained and eluted selectively. Due to the matrix effects, the determination was based on standard addition quantification and was fully validated. The relative standard deviations of the results were 13% and 6% for BZ3 and BZ4, respectively, whereas the limits of detection were 60 and 30 ng mL -1 , respectively. The method was satisfactorily applied to determine BZ3 and BZ4 in urine from volunteers that had applied a sunscreen cosmetic containing both UV filters.

  2. Development of a fully automated sequential injection solid-phase extraction procedure coupled to liquid chromatography to determine free 2-hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid in human urine

    Energy Technology Data Exchange (ETDEWEB)

    Leon, Zacarias; Chisvert, Alberto; Balaguer, Angel [Departamento de Quimica Analitica, Facultad de Quimica, Universitat de Valencia, Doctor Moliner 50, 46100 Burjassot, Valencia (Spain); Salvador, Amparo, E-mail: amparo.salvador@uv.es [Departamento de Quimica Analitica, Facultad de Quimica, Universitat de Valencia, Doctor Moliner 50, 46100 Burjassot, Valencia (Spain)

    2010-04-07

    2-Hydroxy-4-methoxybenzophenone and 2-hydroxy-4-methoxybenzophenone-5-sulphonic acid, commonly known as benzophenone-3 (BZ3) and benzophenone-4 (BZ4), respectively, are substances widely used as UV filters in cosmetic products in order to absorb UV radiation and protect human skin from direct exposure to the deleterious wavelengths of sunlight. As with other UV filters, there is evidence of their percutaneous absorption. This work describes an analytical method developed to determine trace levels of free BZ3 and BZ4 in human urine. The methodology is based on a solid-phase extraction (SPE) procedure for clean-up and pre-concentration, followed by the monitoring of the UV filters by liquid chromatography-ultraviolet spectrophotometry detection (LC-UV). In order to improve not only the sensitivity and selectivity, but also the precision of the method, the principle of sequential injection analysis was used to automate the SPE process and to transfer the eluates from the SPE to the LC system. The application of a six-channel valve as an interface for the switching arrangements successfully allowed the on-line connection of SPE sample processing with LC analysis. The SPE process for BZ3 and BZ4 was performed using octadecyl (C18) and diethylaminopropyl (DEA) modified silica microcolumns, respectively, in which the analytes were retained and eluted selectively. Due to the matrix effects, the determination was based on standard addition quantification and was fully validated. The relative standard deviations of the results were 13% and 6% for BZ3 and BZ4, respectively, whereas the limits of detection were 60 and 30 ng mL{sup -1}, respectively. The method was satisfactorily applied to determine BZ3 and BZ4 in urine from volunteers that had applied a sunscreen cosmetic containing both UV filters.

  3. Conserved and divergent roles of Bcr1 and CFEM proteins in Candida parapsilosis and Candida albicans.

    Directory of Open Access Journals (Sweden)

    Chen Ding

    Full Text Available Candida parapsilosis is a pathogenic fungus that is major cause of hospital-acquired infection, predominantly due to growth as biofilms on indwelling medical devices. It is related to Candida albicans, which remains the most common cause of candidiasis disease in humans. The transcription factor Bcr1 is an important regulator of biofilm formation in vitro in both C. parapsilosis and C. albicans. We show here that C. parapsilosis Bcr1 is required for in vivo biofilm development in a rat catheter model, like C. albicans. By comparing the transcription profiles of a bcr1 deletion in both species we found that regulation of expression of the CFEM family is conserved. In C. albicans, three of the five CFEM cell wall proteins (Rbt5, Pga7 and Csa1 are associated with both biofilm formation and acquisition of iron from heme, which is an important virulence characteristic. In C. parapsilosis, the CFEM family has undergone an expansion to 7 members. Expression of three genes (CFEM2, CFEM3, and CFEM6 is dependent on Bcr1, and is induced in low iron conditions. All three are involved in the acquisition of iron from heme. However, deletion of the three CFEM genes has no effect on biofilm formation in C. parapsilosis. Our data suggest that the role of the CFEM family in iron acquisition is conserved between C. albicans and C. parapsilosis, but their role in biofilm formation is not.

  4. bcr-abl oncogene activation in Philadelphia chromosome-positive acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Hermans, A.; Gow, J.; Selleri, L.; von Lindern, M.; Hagemeijer, A.; Wiedemann, L. M.; Grosveld, G.

    1988-01-01

    Tumor-specific alterations in oncogenes are thought to play a central role in the development of cancer. An example is the consistent fusion of the bcr gene to the c-abl oncogene on the Ph chromosome in CML. The Ph chromosome can also be observed in ALL. About 50% of Ph+ ALL cases, in contrast to

  5. Determination of cortisol in two BCR reference sera by isotope dilution gas chromatography-mass spectrometry

    NARCIS (Netherlands)

    Derks; H.J.G.M.; Freudenthal; J.; Heiningen; A.van; Gramberg; L.G.; Klaasen; R.

    1984-01-01

    In dit rapport wordt een analytische methode voor de juiste en preciese bepaling van cortisol in humaan serum en zijn toepassing bij de certificatie van twee gevriesdroogde referentiesera van de BCR beschreven. De methode is gebaseerd op isotoopverdunnings gaschromatografie-massaspectrometrie

  6. Quantification of BCR-ABL transcripts in peripheral blood cells and ...

    African Journals Online (AJOL)

    Purpose: To investigate the feasibility of using peripheral blood plasma samples as surrogates for blood cell sampling for quantification of breakpoint cluster region-Abelson oncogene (BCR-ABL) transcript levels to monitor treatment responses in chronic myeloid leukemia (CML) patients. Methods: Peripheral blood samples ...

  7. Sequential stochastic optimization

    CERN Document Server

    Cairoli, Renzo

    1996-01-01

    Sequential Stochastic Optimization provides mathematicians and applied researchers with a well-developed framework in which stochastic optimization problems can be formulated and solved. Offering much material that is either new or has never before appeared in book form, it lucidly presents a unified theory of optimal stopping and optimal sequential control of stochastic processes. This book has been carefully organized so that little prior knowledge of the subject is assumed; its only prerequisites are a standard graduate course in probability theory and some familiarity with discrete-paramet

  8. Plowshare sequential device test

    Energy Technology Data Exchange (ETDEWEB)

    Ballou, L. B.

    1971-08-02

    For over a year we have been advocating the development of a hardened or ruggedized version of Diamond which will be suitable for sequential detonation of multiple explosives in one emplacement hole. A Plowshare-sponsored device development test, named `Yacht` is proposed for execution in Area 15 at the Nevada Test Site [NTS] in late September 1972. The test is designed to evaluate the ability of a ruggedized Diamond-type explosive assembly to withstand the effects of an adjacent nuclear detonation in the same emplacement hole and then be sequentially fired. The objectives and experimental plan for this concept is provided.

  9. Differentiation status of primary chronic myeloid leukemia cells affects sensitivity to BCR-ABL1 inhibitors.

    Science.gov (United States)

    Pietarinen, Paavo O; Eide, Christopher A; Ayuda-Durán, Pilar; Potdar, Swapnil; Kuusanmäki, Heikki; Andersson, Emma I; Mpindi, John P; Pemovska, Tea; Kontro, Mika; Heckman, Caroline A; Kallioniemi, Olli; Wennerberg, Krister; Hjorth-Hansen, Henrik; Druker, Brian J; Enserink, Jorrit M; Tyner, Jeffrey W; Mustjoki, Satu; Porkka, Kimmo

    2017-04-04

    Tyrosine kinase inhibitors (TKI) are the mainstay treatment of BCR-ABL1-positive leukemia and virtually all patients with chronic myeloid leukemia in chronic phase (CP CML) respond to TKI therapy. However, there is limited information on the cellular mechanisms of response and particularly on the effect of cell differentiation state to TKI sensitivity in vivo and ex vivo/in vitro. We used multiple, independent high-throughput drug sensitivity and resistance testing platforms that collectively evaluated 295 oncology compounds to characterize ex vivo drug response profiles of primary cells freshly collected from newly-diagnosed patients with BCR-ABL1-positive leukemia (n = 40) and healthy controls (n = 12). In contrast to the highly TKI-sensitive cells from blast phase CML and Philadelphia chromosome-positive acute lymphoblastic leukemia, primary CP CML cells were insensitive to TKI therapy ex vivo. Despite maintaining potent BCR-ABL1 inhibitory activity, ex vivo viability of cells was unaffected by TKIs. These findings were validated in two independent patient cohorts and analysis platforms. All CP CML patients under study responded to TKI therapy in vivo. When CP CML cells were sorted based on CD34 expression, the CD34-positive progenitor cells showed good sensitivity to TKIs, whereas the more mature CD34-negative cells were markedly less sensitive. Thus in CP CML, TKIs predominantly target the progenitor cell population while the differentiated leukemic cells (mostly cells from granulocytic series) are insensitive to BCR-ABL1 inhibition. These findings have implications for drug discovery in CP CML and indicate a fundamental biological difference between CP CML and advanced forms of BCR-ABL1-positive leukemia.

  10. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  11. A BCR/ABL-hIL-2 DNA Vaccine Enhances the Immune Responses in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Yanan Qin

    2013-01-01

    Full Text Available The use of a DNA vaccine encoding the BCR/ABL fusion gene is thought to be a promising approach for patients with chronic myeloid leukemia (CML to eradicate minimal residual disease after treatment with chemotherapy or targeted therapy. In this study, our strategy employs genetic technology to create a DNA vaccine encoding the BCR/ABL fusion and human interleukin-2 (hIL-2 genes. The successfully constructed plasmids BCR/ABL-pIRES-hIL-2, BCR/ABL-pIRES, and pIRES-hIL-2 were delivered intramuscularly to BALB/c mice at 14-day intervals for three cycles. The transcription and expression of the BCR/ABL and hIL-2 genes were found in the injected muscle tissues. The interferon-γ (IFN-γ serum levels were increased, and the splenic CD4+/CD8+ T cell ratio was significantly decreased in the BCR/ABL-pIRES-hIL-2-injected mice. Furthermore, specific antibodies against K562 cells could be detected by indirect immunofluorescence. These results indicate that a DNA vaccine containing BCR/ABL and hIL-2 together may elicit increased in vivo humoral and cellular immune responses in BALB/c mice.

  12. BCL6 modulates tonic BCR signaling in diffuse large B-cell lymphomas by repressing the SYK phosphatase, PTPROt.

    Science.gov (United States)

    Juszczynski, Przemyslaw; Chen, Linfeng; O'Donnell, Evan; Polo, Jose M; Ranuncolo, Stella M; Dalla-Favera, Riccardo; Melnick, Ari; Shipp, Margaret A

    2009-12-17

    Tonic B-cell receptor (BCR) signaling is a key survival pathway during normal B-cell ontogenesis and in a subset of diffuse large B-cell lymphomas (DLBCLs). We previously demonstrated that BCR-dependent DLBCL cell lines and primary tumors underwent apoptosis after treatment with an ATP-competitive inhibitor of the BCR-associated spleen tyrosine kinase (SYK). These "BCR-type" tumors also have more abundant expression of the transcriptional repressor, BCL6, and increased sensitivity to BCL6 inhibition. Herein, we evaluated potential connections between BCL6-mediated transcriptional repression and SYK-dependent BCR signaling. In transcriptionally profiled normal B-cell subsets (naive, germinal center, and memory B cells) and in primary DLBCLs, there were reciprocal patterns of expression of BCL6 and the SYK tyrosine phosphatase PTPROt. BCL6 repressed PTPROt transcription via a direct interaction with functional BCL6 binding sites in the PTPROt promoter. Enforced expression of BCL6 in normal naive B cells and RNAi-mediated depletion of BCL6 in germinal center B cells directly modulated PTPROt expression. In "BCR-type" DLBCLs, BCL6 depletion increased PTPROt expression and decreased phosphorylation of SYK and the downstream adaptor protein BLNK. Because BCL6 augments BCR signaling and BCL6 and SYK are both promising therapeutic targets in many DLBCLs, combined inhibition of these functionally related pathways warrants further study.

  13. Inhibitors of BCR signalling interrupt the survival signal mediated by the micro-environment in mantle cell lymphoma.

    Science.gov (United States)

    Bernard, Sophie; Danglade, Damien; Gardano, Laura; Laguillier, Christelle; Lazarian, Gregory; Roger, Claudine; Thieblemont, Catherine; Marzec, Jacek; Gribben, John; Cymbalista, Florence; Varin-Blank, Nadine; Ledoux, Dominique; Baran-Marszak, Fanny

    2015-06-15

    Several studies provide evidences for mantle cell lymphoma (MCL) cell survival relying on B-cell receptor (BCR)-mediated signalling pathways, whereas the nature of this activation is unknown. Significant progress in MCL treatment is achieved through therapies targeting BCR-associated kinases, i.e., Ibrutinib and Fostamatinib, inhibitors of BTK and SYK, respectively. Our study addresses survival signals emanating from the BCR or the tumour environment and how inhibiting BCR signalling effectors might impact these survival signals. We found that BTK was constitutively activated and that SYK phosphorylation was highly increased and sustained upon BCR activation of primary MCL cells. Moreover, MCL cells from leukaemic patients secreted high amount of IL-1β, IL-6, IL-8 and CCL5. Activation of the BCR induced (i) cell survival, (ii) STAT3 activation and (iii) increased autocrine secretion of IL-1β, IL-6, IL-8, CCL5, IL-10, TNFα and VEGF. Specific inhibition of BTK by Ibrutinib or SYK by Fostamatinib (R406) reversed these protective effects and decreased both basal and BCR-induced autocrine cytokine secretions associated with STAT3 phosphorylation. Interestingly, targeting BTK and SYK prevented and inhibited BCR-induced MCL cell adhesion to human bone marrow stromal cells (HMSCs) in short- and long-term co-culture. We demonstrated that BCR-induced survival relies on autocrine secretion of IL-1β, TNFα and CCL5 that might facilitate adhesion of MCL cells to HMSC. Treatment with Ibrutinib or Fostamatinib blocked the chemotactic signal thus increasing apoptosis. © 2014 UICC.

  14. Ph1 chromosomes and bcr gene rearrangements in chronic myelocytic leukemia patients developed from atomic bomb survivors

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Takechi, Miho; Shigeta, Chiharu; Sakatani, Keiko; Oguma, Nobuo; Kamada, Nanao; Takimoto, Yasuo; Kuramoto, Atsushi

    1989-01-01

    This study compared findings of chronic myelocytic leukemia (CML) in A-bomb survivors (n=8) developing CML within 10 years after the bombing and in non-exposed CML patients (n=14). Both Ph 1 chromosomes and bcr rearrangement were observed in all patients in both exposed and non-exposed groups. There was no significant difference in distribution sites of bcr rearrangement between the groups. These results suggest that bcr-abl chimera mRNA and chimera protein associated with Ph 1 chromosomes have an important role in the development of CML among A-bomb survivors, as well as among non-exposed patients. (N.K.)

  15. A sequential tree approach for incremental sequential pattern mining

    Indian Academy of Sciences (India)

    Data mining; STISPM; sequential tree; incremental mining; backward tracking. Abstract. ''Sequential pattern mining'' is a prominent and significant method to explore the knowledge and innovation from the large database. Common sequential pattern mining algorithms handle static databases.Pragmatically, looking into the ...

  16. Speciation of heavy metals in street dust samples from Sakarya I ...

    African Journals Online (AJOL)

    , Pb and Zn) in 20 dust samples collected from the streets of the Organized Industrial District in Sakarya, Turkey using sequential extraction procedure were determined by ICP-OES. The three-step BCR sequential extraction procedure was ...

  17. Expression of p190 BCR-ABL fusion gene in a patient with chronic myeloid leukemia Expressão do rearranjo gênico BCR-ABL com ponto de quebra na região menor do gene BCR em um paciente com leucemia mielóide crônica

    Directory of Open Access Journals (Sweden)

    P. V. B. Carvalho

    2003-01-01

    Full Text Available A minority of chronic myeloid leukemia cases have breakpoints in the minor cluster region (m-bcr of the BCR-ABL gene. We report on a patient with Ph-positive and m-bcr breakpoint at diagnosis. She was treated with hydroxyurea and interferon-alpha. Two years later, she developed a lymphoid blast crisis and died shortly after. We discuss herein the different forms of the BCR-ABL oncogene, its products, and the possible influence of them on the clinical outcome of patients with the disease.A leucemia mielóide crônica (LMC é uma doença mieloproliferativa clonal e caracteriza-se pela presença da translocação cromossômica entre os braços longos dos cromossomos 9 e 22, o denominado cromossomo Ph. Esta translocação determina a fusão dos genes BCR e ABL. Os diferentes pontos de quebra no gene BCR determinam a síntese de proteínas com diferentes pesos moleculares pelo gene BCR-ABL. Nós relatamos o caso de uma paciente portadora de LMC com ponto de quebra cromossômico na região menor do gene BCR. Foi tratada com hidroxiuréia e interferon alfa. Dois anos após o diagnóstico desenvolveu crise blástica linfóide e evoluiu rapidamente para o óbito. Nós discutimos nesta apresentação as diferentes formas do gene BCR-ABL e seus produtos e a possível influência dos mesmos na evolução clínica dos pacientes com a doença.

  18. Sequential measurements of conjugate observables

    Energy Technology Data Exchange (ETDEWEB)

    Carmeli, Claudio [Dipartimento di Fisica, Universita di Genova, Via Dodecaneso 33, 16146 Genova (Italy); Heinosaari, Teiko [Department of Physics and Astronomy, Turku Centre for Quantum Physics, University of Turku, 20014 Turku (Finland); Toigo, Alessandro, E-mail: claudio.carmeli@gmail.com, E-mail: teiko.heinosaari@utu.fi, E-mail: alessandro.toigo@polimi.it [Dipartimento di Matematica ' Francesco Brioschi' , Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2011-07-15

    We present a unified treatment of sequential measurements of two conjugate observables. Our approach is to derive a mathematical structure theorem for all the relevant covariant instruments. As a consequence of this result, we show that every Weyl-Heisenberg covariant observable can be implemented as a sequential measurement of two conjugate observables. This method is applicable both in finite- and infinite-dimensional Hilbert spaces, therefore covering sequential spin component measurements as well as position-momentum sequential measurements.

  19. Chronic Myeloid Leukemia 2011: Successes, challenges, and strategies – Proceedings of the 5th Annual BCR-ABL1 positive and BCR-ABL1 negative myeloproliferative neoplasms workshop

    Science.gov (United States)

    Mughal, Tariq I; Radich, Jerald P; Van Etten, Richard A.; Quintás-Cardama, Alfonso; Skorski, Tomasz; Ravandi, Farhad; DeAngelo, Daniel J.; Gambacorti-Passerini, Carlo; Martinelli, Giovanni; Tefferi, Ayalew

    2012-01-01

    This report is based on the presentations and discussions at the 5th annual BCR-ABL1 positive and BCR-ABL1 negative myeloproliferative neoplasms (MPN) workshop, which took place immediately following the 52nd American Society of Hematology (ASH) meeting in Orlando, Florida on December 7th-8th, 2011. Relevant data which was presented at the ASH meeting as well as all other recent publications were presented and discussed at the workshop. This report covers front-line therapies of BCR-ABL1-positive leukemias, in addition to addressing some topical biological, pre-clinical and clinical issues, such as new insights into genomic instability and resistance to tyrosine kinase inhibitors (TKIs), risk stratification and optimizing molecular monitoring. A report pertaining to the new therapies and other pertinent preclinical and clinical issues in the BCR-ABL1 negative MPNs is published separately. PMID:21850662

  20. Forced Sequence Sequential Decoding

    DEFF Research Database (Denmark)

    Jensen, Ole Riis

    is possible as low as Eb/No=0.6 dB, which is about 1.7 dB below the signal-to-noise ratio that marks the cut-off rate for the convolutional code. This is possible since the iteration process provides the sequential decoders with side information that allows a smaller average load and minimizes the probability...

  1. ON012380: A Non-ATP Competitive Inhibitor of BCR-ABL for the Therapy of Imatinib-Resistant CMLs

    National Research Council Canada - National Science Library

    Reddy, E. P

    2007-01-01

    Because it is now apparent that a significant proportion of patients chronically treated with imatinib develop resistance due to the acquisition of mutations in the kinase domain of BCR-ABL our aim...

  2. Unleashing the Guardian: The Targetable BCR-ABL/HAUSP/PML/PTEN Network in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Morotti, Alessandro; Torti, Davide; Carra, Giovanna; Panuzzo, Cristina; Crivellaro, Sabrina; Taulli, Riccardo; Fava, Carmen; Guerrasio, Angelo; Saglio, Giuseppe

    2017-01-01

    The complete eradication of Chronic Myeloid Leukemia is still challenging even in the era of highly selective and potent BCR-ABL tyrosine kinase inhibitors (TKIs). The 'Achilles heel' of TKI-based CML therapy is the inability of TKI to effectively target CML stem cells. Several pathways have been described to induce TKI insensitiveness in quiescent CML stem cells. In this review, we will describe the BCR-ABL/HAUSP/PML/PTEN network, whose signaling mediators converge to regulate the function of the tumor suppressor PTEN. We will also highlight the pharmacological strategies to modulate PTEN functions in order to sustain CML stem cell eradication. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Sequential Analysis of Metals in Municipal Dumpsite Composts of ...

    African Journals Online (AJOL)

    ... Ni) in Municipal dumpsite compost were determined by the sequential extraction method. Chemical parameters such as pH, conductivity, and organic carbon contents of the samples were also determined. Analysis of the extracts was carried out by atomic absorption spectrophotometer machine (Buck Scientific VPG 210).

  4. Susceptibility of Ph-positive all to TKI therapy associated with Bcr-Abl rearrangement patterns: a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Yu Jing

    Full Text Available BACKGROUND: Tyrosine kinase inhibitors (TKIs have demonstrated success in the treatment of acute lymphoblastic leukemia (ALL in patients that express BCR-ABL rearrangements (Philadelphia chromosome [Ph]. The current study aimed to assess the efficacy of TKIs and prognostic factors in the treatment of adults with Ph+-ALL. METHODS: In this multicenter retrospective study, the relationship between Ph+-ALL and treatment outcomes among Chinese patients receiving TKI-containing induction/consolidation chemotherapy was examined. A total of 86 Ph+-ALL patients were included and followed for 3.85 (0.43-9.30 years. Overall survival (OS and event-free survival (EFS were analyzed. RESULTS: A total of 86 Ph+-ALL patients (40 females and 46 males; median age: 34.0 years were enrolled, including those with BCR/ABL transcripts 190 (n = 52, 210 (n = 25, and 230 (n = 2; BCR/ABL isoform determination was not available for 7 patients. Mortality was influenced by variable BCR/ABL transcripts and TKI administration, and BCR/ABL transcripts, hematopoietic stem cell transplantation (HSCT, and TKI administration were associated with the occurrence of events. The OS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKI administration (P = 0.008, the EFS rate in the TKI administration group during steady state was significantly higher compared with those patients who did not receive TKIs (P = 0.012, and also higher than those with TKI salvage administration (P = 0.004. BCR/ABL transcripts 210 showed preferable OS and EFS compared with BCR/ABL transcripts 190 and 230 (P<0.05 for each. CONCLUSIONS: The susceptibility of Ph+-ALL to TKI associated with the patterns of BCR-ABL rearrangement is demonstrated for the first time, thus adding another risk-stratifying molecular prognostic tool for the management of patients with Ph+-ALL.

  5. Detection of BCR-ABL Fusion mRNA Using Reverse Transcriptase Loop-mediated Isothermal Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Dugan, L C; Hall, S; Kohlgruber, A; Urbin, S; Torres, C; Wilson, P

    2011-12-08

    RT-PCR is commonly used for the detection of Bcr-Abl fusion transcripts in patients diagnosed with chronic myelogenous leukemia, CML. Two fusion transcripts predominate in CML, Br-Abl e13a2 and e14a2. They have developed reverse transcriptase isothermal loop-mediated amplification (RT-LAMP) assays to detect these two fusion transcripts along with the normal Bcr transcript.

  6. An asymptomatic 61-year-old man with BCR-ABL-positive bone marrow following autologous transplantation for multiple myeloma

    Science.gov (United States)

    Roper, Nitin; Deangelo, Daniel; Kuo, Frank; Cin, Paola dal; Ghobrial, Irene; Aster, Jon C.

    2010-01-01

    A 61-year-old man treated with an autologous transplant for multiple myeloma was incidentally found to have a high level of BCR-ABL fusion gene-positive cells in his bone marrow. We describe the clinical decision-making process that led us to initiate therapy with imatinib, despite the absence of any clinical evidence of chronic myelogenous leukemia or other BCR-ABL associated hematologic malignancy. PMID:20730794

  7. A critical role of CDKN3 in Bcr-Abl-mediated tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Qinghuang Chen

    Full Text Available CDKN3 (cyclin-dependent kinase inhibitor 3, a dual specificity protein phosphatase, dephosphorylates cyclin-dependent kinases (CDKs and thus functions as a key negative regulator of cell cycle progression. Deregulation or mutations of CDNK3 have been implicated in various cancers. However, the role of CDKN3 in Bcr-Abl-mediated chronic myelogenous leukemia (CML remains unknown. Here we found that CDKN3 acts as a tumor suppressor in Bcr-Abl-mediated leukemogenesis. Overexpression of CDKN3 sensitized the K562 leukemic cells to imanitib-induced apoptosis and dramatically inhibited K562 xenografted tumor growth in nude mouse model. Ectopic expression of CDKN3 significantly reduced the efficiency of Bcr-Abl-mediated transformation of FDCP1 cells to growth factor independence. In contrast, depletion of CDKN3 expression conferred resistance to imatinib-induced apoptosis in the leukemic cells and accelerated the growth of xenograph leukemia in mice. In addition, we found that CDKN3 mutant (CDKN3-C140S devoid of the phosphatase activity failed to affect the K562 leukemic cell survival and xenografted tumor growth, suggesting that the phosphatase of CDKN3 was required for its tumor suppressor function. Furthermore, we observed that overexpression of CDKN3 reduced the leukemic cell survival by dephosphorylating CDK2, thereby inhibiting CDK2-dependent XIAP expression. Moreover, overexpression of CDKN3 delayed G1/S transition in K562 leukemic cells. Our results highlight the importance of CDKN3 in Bcr-Abl-mediated leukemogenesis, and provide new insights into diagnostics and therapeutics of the leukemia.

  8. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Directory of Open Access Journals (Sweden)

    Shweta Jain

    Full Text Available Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID, signifying class switch recombination (CSR. Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

  9. Heterogeneity of genomic fusion of BCR and ABL in Philadelphia chromosome-positive acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Rubin, C.M.; Carrino, J.J.; Dickler, M.N.; Leibowitz, D.; Smith, S.D.; Westbrook, C.A.

    1988-01-01

    Philadelphia chromosome-positive acute lymphoblastic leukemia occurs in two molecular forms, those with and those without rearrangement of the breakpoint cluster region on chromosome 22. The molecular abnormality in the former group is similar to that found in chronic myelogenous leukemia. To characterize the abnormality in the breakpoint cluster region-unrearranged form, the authors have mapped a 9; 22 translocation from the Philadelphia chromosome-positive acute lymphoblastic leukemia cell line SUP-B13 by using pulsed-field gel electrophoresis and have cloned the DNA at the translocation junctions. They demonstrate a BCR-ABL fusion gene on the Philadelphia chromosome. The exons from ABL are the same. Analysis of leukemic cells from four other patients with breakpoint cluster region-unrearranged Philadelphia chromosome-positive acute lymphoblastic leukemia revealed a rearrangement on chromosome 22 close to the breakpoint in SUP-B13 in only one patient. These data indicate that breakpoints do not cluster tightly in this region but are scattered, possibly in a large intron. Given the large size of BCR and the heterogeneity in breakpoint location, detection of BCR rearrangement by standard Southern blot analysis is difficult. Pulsed-field gel electrophoresis should allow detection at the DNA level in every patient and thus will permit clinical correlation of the breakpoint location with prognosis

  10. Autophagy induction by Bcr-Abl-expressing cells facilitates their recovery from a targeted or nontargeted treatment.

    LENUS (Irish Health Repository)

    Crowley, Lisa C

    2012-01-31

    Although Imatinib has transformed the treatment of chronic myeloid leukemia (CML), it is not curative due to the persistence of resistant cells that can regenerate the disease. We have examined how Bcr-Abl-expressing cells respond to two mechanistically different therapeutic agents, etoposide and Imatinib. We also examined Bcr-Abl expression at low and high levels as elevated expression has been associated with treatment failure. Cells expressing low levels of Bcr-Abl undergo apoptosis in response to the DNA-targeting agent (etoposide), whereas high-Bcr-Abl-expressing cells primarily induce autophagy. Autophagic populations engage a delayed nonapoptotic death; however, sufficient cells evade this and repopulate following the withdrawal of the drug. Non-Bcr-Abl-expressing 32D or Ba\\/F3 cells induce both apoptosis and autophagy in response to etoposide and can recover. Imatinib treatment induces both apoptosis and autophagy in all Bcr-Abl-expressing cells and populations rapidly recover. Inhibition of autophagy with ATG7 and Beclin1 siRNA significantly reduced the recovery of Imatinib-treated K562 cells, indicating the importance of autophagy for the recovery of treated cells. Combination regimes incorporating agents that disrupt Imatinib-induced autophagy would remain primarily targeted and may improve response to the treatment in CML.

  11. Hypoxia-Like Signatures Induced by BCR-ABL Potentially Alter the Glutamine Uptake for Maintaining Oxidative Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Pallavi Sontakke

    Full Text Available The Warburg effect is probably the most prominent metabolic feature of cancer cells, although little is known about the underlying mechanisms and consequences. Here, we set out to study these features in detail in a number of leukemia backgrounds. The transcriptomes of human CB CD34+ cells transduced with various oncogenes, including BCR-ABL, MLL-AF9, FLT3-ITD, NUP98-HOXA9, STAT5A and KRASG12V were analyzed in detail. Our data indicate that in particular BCR-ABL, KRASG12V and STAT5 could impose hypoxic signaling under normoxic conditions. This coincided with an upregulation of glucose importers SLC2A1/3, hexokinases and HIF1 and 2. NMR-based metabolic profiling was performed in CB CD34+ cells transduced with BCR-ABL versus controls, both cultured under normoxia and hypoxia. Lactate and pyruvate levels were increased in BCR-ABL-expressing cells even under normoxia, coinciding with enhanced glutaminolysis which occurred in an HIF1/2-dependent manner. Expression of the glutamine importer SLC1A5 was increased in BCR-ABL+ cells, coinciding with an increased susceptibility to the glutaminase inhibitor BPTES. Oxygen consumption rates also decreased upon BPTES treatment, indicating a glutamine dependency for oxidative phosphorylation. The current study suggests that BCR-ABL-positive cancer cells make use of enhanced glutamine metabolism to maintain TCA cell cycle activity in glycolytic cells.

  12. Synthetic Aperture Sequential Beamforming

    DEFF Research Database (Denmark)

    Kortbek, Jacob; Jensen, Jørgen Arendt; Gammelmark, Kim Løkke

    2008-01-01

    A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective...... is stored. The second stage applies the focused image lines from the first stage as input data. The SASB method has been investigated using simulations in Field II and by off-line processing of data acquired with a commercial scanner. The performance of SASB with a static image object is compared with DRF...

  13. Sequential auctions and price anomalies

    Directory of Open Access Journals (Sweden)

    Trifunović Dejan

    2014-01-01

    Full Text Available In sequential auctions objects are sold one by one in separate auctions. These sequential auctions might be organized as sequential first-price, second-price, or English auctions. We will derive equilibrium bidding strategies for these auctions. Theoretical models suggest that prices in sequential auctions with private values or with randomly assigned heterogeneous objects should have no trend. However, empirical research contradicts this result and prices exhibit a declining or increasing trend, which is called declining and increasing price anomaly. We will present a review of these empirical results, as well as different theoretical explanations for these anomalies.

  14. A sequential tree approach for incremental sequential pattern mining

    Indian Academy of Sciences (India)

    ''Sequential pattern mining'' is a prominent and significant method to explore the knowledge and innovation from the large database. Common sequential pattern mining algorithms handle static databases.Pragmatically, looking into the functional and actual execution, the database grows exponentially thereby leading to ...

  15. Disruption of Survivin in K562 cells elevates telomerase activity and protects cells against apoptosis induced by the Bcr-abl kinase inhibitor STI571

    OpenAIRE

    Wang, Zhanxiang; Pelus, Louis M.

    2008-01-01

    The Bcr-abl kinase inhibitor STI571 produces clinical responses in most patients with Chronic Myeloid Leukemia (CML); however, development of resistance limits utility. One strategy to overcome STI571 resistance is to decrease the level/activity of Bcr-abl. We reported that disruption of the anti-apoptotic protein Survivin promoted STI571-induced apoptosis in Bcr-abl+ K562 cells, through caspase-dependent Bcr-abl degradation. To investigate the utility of Survivin disruption in drug-resistant...

  16. SGX393 inhibits the CML mutant Bcr-Abl[superscript T315I] and preempts in vitro resistance when combined with nilotinib or dasatinib

    Energy Technology Data Exchange (ETDEWEB)

    O' Hare, Thomas; Eide, Christopher A.; Tyner, Jeffrey W.; Corbin, Amie S.; Wong, Matthew J.; Buchanan, Sean; Holme, Kevin; Jessen, Katayoun A.; Tang, Crystal; Lewis, Hal A.; Romero, Richard D.; Burley, Stephen K.; Deininger, Michael W. (OHSU- Cancer Instit.); (SGX)

    2010-01-12

    Imatinib inhibits Bcr-Abl, the oncogenic tyrosine kinase that causes chronic myeloid leukemia. The second-line inhibitors nilotinib and dasatinib are effective in patients with imatinib resistance resulting from Bcr-Abl kinase domain mutations. Bcr-Abl{sup T315I}, however, is resistant to all Abl kinase inhibitors in clinical use and is emerging as the most frequent cause of salvage therapy failure. SGX393 is a potent inhibitor of native and T315I-mutant Bcr-Abl kinase that blocks the growth of leukemia cell lines and primary hematopoietic cells expressing Bcr-Abl{sup T315I}, with minimal toxicity against Bcr-Abl-negative cell lines or normal bone marrow. A screen for Bcr-Abl mutants emerging in the presence of SGX393 revealed concentration-dependent reduction in the number and range of mutations. Combining SGX393 with nilotinib or dasatinib preempted emergence of resistant subclones, including Bcr-Abl{sup T315I}. These findings suggest that combination of a T315I inhibitor with the current clinically used inhibitors may be useful for reduction of Bcr-Abl mutants in Philadelphia chromosome-positive leukemia.

  17. The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib

    Science.gov (United States)

    Yeung, David T. O.; Yeoman, Alexandra L.; Altamura, Haley K.; Jamison, Bronte A.; Field, Chani R.; Hodgson, J. Graeme; Lustgarten, Stephanie; Rivera, Victor M.; Hughes, Timothy P.; Branford, Susan

    2016-01-01

    The third-generation tyrosine kinase inhibitor (TKI) ponatinib shows activity against all common BCR-ABL1 single mutants, including the highly resistant BCR-ABL1-T315I mutant, improving outcome for patients with refractory chronic myeloid leukemia (CML). However, responses are variable, and causal baseline factors have not been well-studied. The type and number of low-level BCR-ABL1 mutations present after imatinib resistance has prognostic significance for subsequent treatment with nilotinib or dasatinib as second-line therapy. We therefore investigated the impact of low-level mutations detected by sensitive mass-spectrometry before ponatinib initiation (baseline) on treatment response in 363 TKI-resistant patients enrolled in the PONATINIB for Chronic Myeloid Leukemia Evaluation and Ph+ Acute Lymphoblastic Leukemia trial, including 231 patients in chronic phase (CP-CML). Low-level mutations were detected in 53 patients (15%, including low-level T315I in 14 patients); most, however, did not undergo clonal expansion during ponatinib treatment and, moreover, no specific individual mutations were associated with inferior outcome. We demonstrate however, that the number of mutations detectable by mass spectrometry after TKI resistance is associated with response to ponatinib treatment and could be used to refine the therapeutic approach. Although CP-CML patients with T315I (63/231, 27%) had superior responses overall, those with multiple mutations detectable by mass spectrometry (20, 32%) had substantially inferior responses compared with those with T315I as the sole mutation detected (43, 68%). In contrast, for CP-CML patients without T315I, the inferior responses previously observed with nilotinib/dasatinib therapy for imatinib-resistant patients with multiple mutations were not seen with ponatinib treatment, suggesting that ponatinib may prove to be particularly advantageous for patients with multiple mutations detectable by mass spectrometry after TKI resistance

  18. Loss of the xeroderma pigmentosum group B protein binding site impairs p210 BCR/ABL1 leukemogenic activity

    International Nuclear Information System (INIS)

    Pannucci, N L; Li, D; Sahay, S; Thomas, E K; Chen, R; Tala, I; Hu, T; Ciccarelli, B T; Megjugorac, N J; Adams III, H C; Rodriguez, P L; Fitzpatrick, E R; Lagunoff, D; Williams, D A; Whitehead, I P

    2013-01-01

    Previous studies have demonstrated that p210 BCR/ABL1 interacts directly with the xeroderma pigmentosum group B (XPB) protein, and that XPB is phosphorylated on tyrosine in cells that express p210 BCR/ABL1. In the current study, we have constructed a p210 BCR/ABL1 mutant that can no longer bind to XPB. The mutant has normal kinase activity and interacts with GRB2, but can no longer phosphorylate XPB. Loss of XPB binding is associated with reduced expression of c-MYC and reduced transforming potential in ex-vivo clonogenicity assays, but does not affect nucleotide excision repair in lymphoid or myeloid cells. When examined in a bone marrow transplantation (BMT) model for chronic myelogenous leukemia, mice that express the mutant exhibit attenuated myeloproliferation and lymphoproliferation when compared with mice that express unmodified p210 BCR/ABL1. Thus, the mutant-transplanted mice show predominantly neutrophilic expansion and altered progenitor expansion, and have significantly extended lifespans. This was confirmed in a BMT model for B-cell acute lymphoblastic leukemia, wherein the majority of the mutant-transplanted mice remain disease free. These results suggest that the interaction between p210 BCR/ABL1 and XPB can contribute to disease progression by influencing the lineage commitment of lymphoid and myeloid progenitors

  19. Transferred BCR/ABL DNA from K562 extracellular vesicles causes chronic myeloid leukemia in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Jin Cai

    Full Text Available Our previous study showed that besides mRNAs and microRNAs, there are DNA fragments within extracellular vesicles (EVs. The BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia (CML, could be transferred from K562 EVs to neutrophils and decrease their phagocytic activity in vitro. Our present study provides evidence that BCR/ABL DNAs transferred from EVs have pathophysiological significance in vivo. Two months after injection of K562 EVs into the tail vein of Sprague-Dawley (SD rats, they showed some characteristics of CML, e.g., feeble, febrile, and thin, with splenomegaly and neutrophilia but with reduced neutrophil phagocytic activity. These findings were also observed in immunodeficient NOD/SCID mice treated with K562 EVs; BCR/ABL mRNA and protein were found in their neutrophils. The administration of actinomycin D, an inhibitor of de novo mRNA synthesis, prevented the abnormalities caused by K562 EVs in NOD/SCID mice related to CML, including neutrophilia and bone marrow hyperplasia. As a specific inhibitor of tyrosine kinases, imatinib blocked the activity of tyrosine kinases and the expression of phospho-Crkl, induced by the de novo BCR/ABL protein caused by K562 EVs bearing BCR/ABL DNA. Our current study shows the pathophysiological significance of transferred tumor gene from EVs in vivo, which may represent an important mechanism for tumorigenesis, tumor progression, and metastasis.

  20. Guidelines for molecular monitoring of BCR-ABL1 in chronic myeloid leukemia patients by RT-qPCR

    Directory of Open Access Journals (Sweden)

    Irene Larripa

    2017-02-01

    Full Text Available Current clinical guidelines for managing chronic myeloid leukemia include molecular monitoring of BCR-ABL1 transcript quantitative reverse-transcription PCR. Despite the proven prognostic significance of molecular response, it is not widely appreciated that quantitative reverse-transcription PCR potentially produces highly variable data, which may affect the validity of results, making comparability between different laboratories difficult. Therefore, standardized reporting of BCR-ABL1 measurements is needed for optimal clinical management. An approach to achieve comparable BCR-ABL1 values is the use of an international reporting scale. Conversion to the international scale is achieved by the application of laboratory specific conversion factor that is obtained by using validated secondary reference calibrators. Moreover, with the aim to mitigate the interlaboratory imprecision of quantitative BCR-ABL1 measurements and to facilitate local laboratory results interpretation and reporting, we decide to prepare laboratory guidelines that will further facilitate interlaboratory comparative studies and independent quality-assessment programs, which are of paramount importance for worldwide standardization of BCR-ABL1 monitoring results, in particular for those most isolated laboratories, with not easy access to commercial kits or sample interchange programs

  1. Sequential Methods and Their Applications

    CERN Document Server

    Mukhopadhyay, Nitis

    2008-01-01

    Illustrates the efficiency of sequential methodologies when dealing with contemporary statistical challenges in many areas. This book explores fixed sample size, sequential probability ratio, and nonparametric tests. It also presents multistage estimation methods for fixed-width confidence interval as well as minimum and bounded risk problems.

  2. Hepatobiliary sequential scintiscanning

    International Nuclear Information System (INIS)

    Eissner, D.

    1985-01-01

    The main criteria for interpreting hepatobiliary sequential scintiscanning (HBSS) data are given to be the following: (1) In young infants - without previous parenteral feeding - a normal up to a slightly increased activity uptake in the liver, accompanied by lack of activity excretion into the intestine (which requires a 24 - hour scan for detection) is a clear indication of bile duct atresia. However, the same findings can be obtained on very young newborn (up to one week of age) in case of a hepatitis with defined cholestasis. (2) In case of a comparably high activity uptake in the liver together with activity excretion into the intestine, which may be detectable in due time or after a delay (24-hour scan required), bile duct atresia can be excluded, the diagnosis being hepatitis. In general, hepatitis will cause a stronger liver cell damage, which excludes the criterion of activity excretion into the intestine. Similar findings can be obtained on infants with bile duct atresia with previous parenteral feeding. This is why the interpretation of HBSS data can only be effectively carried out in close cooperation with the pediatrician, and on the basis of profound knowledge of the overall clinical state of the infant. (orig.) [de

  3. Sequential Design of Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Anderson-Cook, Christine Michaela [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-06-30

    A sequential design of experiments strategy is being developed and implemented that allows for adaptive learning based on incoming results as the experiment is being run. The plan is to incorporate these strategies for the NCCC and TCM experimental campaigns to be run in the coming months. This strategy for experimentation has the advantages of allowing new data collected during the experiment to inform future experimental runs based on their projected utility for a particular goal. For example, the current effort for the MEA capture system at NCCC plans to focus on maximally improving the quality of prediction of CO2 capture efficiency as measured by the width of the confidence interval for the underlying response surface that is modeled as a function of 1) Flue Gas Flowrate [1000-3000] kg/hr; 2) CO2 weight fraction [0.125-0.175]; 3) Lean solvent loading [0.1-0.3], and; 4) Lean solvent flowrate [3000-12000] kg/hr.

  4. Adaptive sequential controller

    Energy Technology Data Exchange (ETDEWEB)

    El-Sharkawi, Mohamed A. (Renton, WA); Xing, Jian (Seattle, WA); Butler, Nicholas G. (Newberg, OR); Rodriguez, Alonso (Pasadena, CA)

    1994-01-01

    An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

  5. Adaptive sequential controller

    Science.gov (United States)

    El-Sharkawi, Mohamed A.; Xing, Jian; Butler, Nicholas G.; Rodriguez, Alonso

    1994-01-01

    An adaptive sequential controller (50/50') for controlling a circuit breaker (52) or other switching device to substantially eliminate transients on a distribution line caused by closing and opening the circuit breaker. The device adaptively compensates for changes in the response time of the circuit breaker due to aging and environmental effects. A potential transformer (70) provides a reference signal corresponding to the zero crossing of the voltage waveform, and a phase shift comparator circuit (96) compares the reference signal to the time at which any transient was produced when the circuit breaker closed, producing a signal indicative of the adaptive adjustment that should be made. Similarly, in controlling the opening of the circuit breaker, a current transformer (88) provides a reference signal that is compared against the time at which any transient is detected when the circuit breaker last opened. An adaptive adjustment circuit (102) produces a compensation time that is appropriately modified to account for changes in the circuit breaker response, including the effect of ambient conditions and aging. When next opened or closed, the circuit breaker is activated at an appropriately compensated time, so that it closes when the voltage crosses zero and opens when the current crosses zero, minimizing any transients on the distribution line. Phase angle can be used to control the opening of the circuit breaker relative to the reference signal provided by the potential transformer.

  6. [Early monitoring of BCR-ABL transcript levels and cytogenetic in assessing the prognosis of chronic myeloid leukemia].

    Science.gov (United States)

    Huang, Qin; Zhang, Xiao-yan; Li, Yan; Wang, Xiao-min

    2013-10-15

    To explore the prognostic significance of early monitoring of BCR-ABL transcript levels and cytogenetic evaluations for chronic myeloid leukemia in chronic phase (CML-CP). From July 2007 to May 2012, 56 CML-CP patients received oral imatinib 400 mg/d. The BCR-ABL transcript levels were monitored and cytogenetic examinations performed after 3 and 6 months respectively. The median follow-up time was 48 months. The 3-month BCR-ABL transcript levels ≤ 10% of patients 5-year overall survival (OS) and progression-free survival (PFS) were better than BCR-ABL transcript levels >10% of patients (OS: 100% vs 84.6%, P = 0.011; PFS: 94.6% vs 67.7%, P = 0.045); cytogenetics: Ph(+) ≤ 35 % of patients 5-year OS and PFS better than Ph(+) > 35% of patients (OS: 100% vs 76.2%, P = 0.001; PFS: 95.2% vs 38.1%, P = 0.001); the 6-month BCR-ABL transcripts level ≤ 1% of patients 5-year OS and PFS also better than BCR-ABL transcript levels> 1% of patients (OS: 100% vs 71.4%, P = 0.000; PFS: 95.2% vs 47.6%, P = 0.001); Ph(+) = 0% and Ph(+)> 0% patients, 5-year OS and PFS were significantly different (OS: 100% vs 68.6%, P = 0.000; PFS: 95.3% vs 45.7%, P = 0.000). Early molecular biology and cytogenetics monitoring have some significance in the prognostic assessment of CML-CP. And individualized treatment strategies should be based upon the monitoring results in conjunctions with comprehensive judgments.

  7. Improved FRET Biosensor for the Measurement of BCR-ABL Activity in Chronic Myeloid Leukemia Cells.

    Science.gov (United States)

    Horiguchi, Mika; Fujioka, Mari; Kondo, Takeshi; Fujioka, Yoichiro; Li, Xinxin; Horiuchi, Kosui; O Satoh, Aya; Nepal, Prabha; Nishide, Shinya; Nanbo, Asuka; Teshima, Takanori; Ohba, Yusuke

    2017-02-02

    Although the co-development of companion diagnostics with molecular targeted drugs is desirable, truly efficient diagnostics are limited to diseases in which chromosomal translocations or overt mutations are clearly correlated with drug efficacy. Moreover, even for such diseases, few methods are available to predict whether drug administration is effective for each individual patient whose disease is expected to respond to the drug(s). We have previously developed a biosensor based on the principle of Förster resonance energy transfer to measure the activity of the tyrosine kinase BCR-ABL and its response to drug treatment in patient-derived chronic myeloid leukemia cells. The biosensor harbors CrkL, one of the major substrates of BCR-ABL, and is therefore named Pickles after phosphorylation indicator of CrkL en substrate. The efficacy of this technique as a clinical test has been demonstrated, but the number of cells available for analysis is limited in a case-dependent manner, owing to the cleavage of the biosensor in patient-derived leukemia cells. Here, we describe an improved biosensor with an amino acid substitution and a nuclear export signal being introduced. Of the two predicted cleavage positions in CrkL, the mutations inhibited one cleavage completely and the other cleavage partially, thus collectively increasing the number of cells available for drug evaluation. This improved version of the biosensor holds promise in the future development of companion diagnostics to predict responses to tyrosine kinase inhibitors in patients with chronic myeloid leukemia.

  8. DMPD: Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1during B-cell development. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14962188 Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokin...ng) (.svg) (.html) (.csml) Show Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin...-1during B-cell development. PubmedID 14962188 Title Mechanisms of selection medi

  9. Direct transcriptional regulation of Bim by FoxO3a mediates STI571-induced apoptosis in Bcr-Abl-expressing cells

    NARCIS (Netherlands)

    Essafi, A.; Mattos, S.F. de; Hassen, Y.A.M.; Soeiro, I.; Mufti, G.J.; Thomas, N.S.B.; Medema, R.H.; Lam, E.W.-F.

    2005-01-01

    In this study, we have used the human BV173 and the mouse BaF3/Bcr-Abl-expressing cell lines as model systems to investigate the molecular mechanisms whereby STI571 and FoxO3a regulate Bim expression and apoptosis. FoxO3a lies downstream of Bcr-Abl signalling and is constitutively

  10. Mining Frequent Max and Closed Sequential Patterns

    OpenAIRE

    Afshar, Ramin

    2002-01-01

    Although frequent sequential pattern mining has an important role in many data mining tasks, however, it often generates a large number of sequential patterns, which reduces its efficiency and effectiveness. For many applications mining all the frequent sequential patterns is not necessary, and mining frequent Max, or Closed sequential patterns will provide the same amount of information. Comparing to frequent sequential pattern mining, frequent Max, or Closed sequential pattern mining g...

  11. Expression of p210 BCR/ABl increases hematopoietic progenitor cell radiosensitivity

    International Nuclear Information System (INIS)

    Santucci, M.A.; Anklesaria, P.; Das, I.J.; Sakakeeny, M.A.; FitzGerald, T.J.; Greenberger, J.S.; Laneuville, P.

    1993-01-01

    The cytogenetic finding of the Ph1+ chromosome and its molecular biologic marker bcr/abl gene rearrangement in cells from patients with chronic myeloid leukemia are associated with a proliferative advantage of the Ph1+ clone in vivo. Although the transition to the acute terminal phase or blastic crisis is often associated with additional cytogenetic abnormalities, the molecular events which correlate the initial cytogenetic lesion with the terminal phase are poorly understood. Defective cellular DNA repair capacity is often associated with chromosomal instability, increased mutation frequency, and biologic alterations. The authors tested whether the protein product of the bcr/abl translocation (p210) could alter DNA repair after gamma-irradiation of murine cell lines expressing the bcr/abl cDNA. The 32D cl 3 parent, 32D cl 3 pYN (containing the control vector plasmid) and each of two sources of 32D cl 3 cells expressing p210 cDNA (32D-PC1 cell line and 32D-LG7 subclone) showed a D 0 of 1.62, 1.57, 1.16, and 1.27 Gy, respectively. Thus, expression of the p210 product induced a significant increase in radiosensitivity at the clinically relevant radiation therapy dose-rate. The increased radiosensitivity of p210-expressing cells persisted if cells were held before plating in a density-inhibited state for 8 hr after gamma-irradiation, indicating little effect on the repair of potentially lethal gamma-irradiation damage. The IL-3 dependent parent 32D cl 3 cells demonstrated programmed cell death in the absence of growth factor or following gamma-irradiation to 200 cGy. Expression of p210 cDNA in the 32D-PC1 and 32D-LG7 subclones abrogated IL-3 requirement of these cell lines and inhibited gamma-irradiation induced programmed cell death. These data suggest a role for p210 in amplifying gamma-irradiation DNA damage or broadly inhibiting DNA repair, conditions that may stimulate further cytogenetic alterations in hematopoietic cells. 43 refs., 3 figs., 1 tab

  12. Effects of austenitization temperature on the microstructure of 15BCr30 and PL22 boron steels

    Directory of Open Access Journals (Sweden)

    C. A. Suski

    2013-01-01

    Full Text Available This paper studies boron precipitation and segregation at austenitic grain boundaries for low carbon boron steels types: PL22 and 15BCr30. The following parameters were evaluated: percentage of martensite/bainite, size and nucleation sites of austenitic grains and precipitates sizes. Three austenitization temperatures were studied (870, 1050 and 1200 °C. The highest martensite percentage occurred for 1050 °C. Iron-borocarbides were detected at grain boundaries for all tested temperatures. At 870 °C the coarse iron-borocarbides are due to non-solubility and coalescence. The highest martensite percentage at 1050 °C is caused by the discrete precipitation of iron-borocarbides at austenitic grains boundaries. The discrete precipitation was due to the low non-equilibrium segregation of boron at grain boundaries. The low non-equilibrium segregation and the small grain size at 1050 °C reduce the total boron concentration at grain boundaries.

  13. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona

    2011-01-01

    T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow......-up was 52 months from mutation detection and 26 months from transplantation. At transplantation, 51.5% of patients with chronic myeloid leukemia were in the chronic phase and 4.5% were in advanced phases. Median overall survival after transplantation was 10.3 months (range 5.7 months to not reached [ie......, still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome-positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic...

  14. Cytoprotective effect of imatinib mesylate in non-BCR-ABL-expressing cells along with autophagosome formation

    Energy Technology Data Exchange (ETDEWEB)

    Ohtomo, Tadashi [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Miyazawa, Keisuke, E-mail: miyazawa@tokyo-med.ac.jp [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Naito, Munekazu [Department of Anatomy, Tokyo Medical University, Tokyo (Japan); Moriya, Shota [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan); Kuroda, Masahiko [Department of Molecular Pathology, Tokyo Medical University, Tokyo (Japan); Itoh, Masahiro [Department of Anatomy, Tokyo Medical University, Tokyo (Japan); Tomoda, Akio [Department of Biochemistry, Tokyo Medical University, Tokyo (Japan)

    2010-01-01

    Treatment with imatinib mesylate (IM) results in an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis. Electron microscopy revealed an increase of autophagosomes in response to IM. IM attenuated the cytotoxic effect of cytosine arabinoside, as well as inhibiting cell death with serum-deprived culture. Cytoprotection with autophagosome formation by IM was observed in various leukemia and cancer cell lines as well as normal murine embryonic fibroblasts (MEFs). Complete inhibition of autophagy by knockdown of atg5 in the Tet-off atg5{sup -/-} MEF system attenuated the cytoprotective effect of IM, indicating that the effect is partially dependent on autophagy. However, cytoprotection by IM was not mediated through suppression of ROS production via mitophagy, ER stress via ribophagy, or proapoptotic function of ABL kinase. Although the target tyrosine kinase(s) of IM remains unclear, our data provide novel therapeutic possibilities of using IM for cytoprotection.

  15. BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

    Science.gov (United States)

    Cuellar, Sandra; Vozniak, Michael; Rhodes, Jill; Forcello, Nicholas; Olszta, Daniel

    2017-01-01

    The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

  16. Deregulated expression of Cdc6 as BCR/ABL-dependent survival factor in chronic myeloid leukemia cells.

    Science.gov (United States)

    Zhang, Jia-Hua; He, Yan-Li; Zhu, Rui; Du, Wen; Xiao, Jun-Hua

    2017-06-01

    Chronic myeloid leukemia is characterized by the presence of the reciprocal translocation t(9;22) and the BCR/ABL oncogene. The BCR/ABL oncogene activates multiple signaling pathways and involves the dysregulation of oncogenes during the progression of chronic myeloid leukemia. The cell division cycle protein 6, an essential regulator of DNA replication, is elevated in some human cancer cells. However, the expression of cell division cycle protein 6 in chronic myeloid leukemia and the underlying regulatory mechanism remain to be elucidated. In this study, our data showed that cell division cycle protein 6 expression was significantly upregulated in primary chronic myeloid leukemia cells and the chronic myeloid leukemia cell line K562 cells, as compared to the normal bone marrow mononuclear cells. BCR/ABL kinase inhibitor STI571 or BCR/ABL small interfering RNA could significantly downregulate cell division cycle protein 6 messenger RNA expression in K562 cells. Moreover, phosphoinositide 3-kinase/AKT pathway inhibitor LY294002 and Janus kinase/signal transducer and activator of transcription pathway inhibitor AG490 could downregulate cell division cycle protein 6 expression in K562 cells, but not RAS/mitogen-activated protein kinase pathway inhibitor PD98059 had such effect. Cell division cycle protein 6 gene silencing by small interfering RNA effectively resulted in decrease of proliferation, increase of apoptosis, and arrest of cell cycle in K562 cells. These findings have demonstrated that cell division cycle protein 6 overexpression may contribute to the high proliferation and low apoptosis in chronic myeloid leukemia cells and can be regulated by BCR/ABL signal transduction through downstream phosphoinositide 3-kinase/Akt and Janus kinase/signal transducer and activator of transcription pathways, suggesting cell division cycle protein 6 as a potential therapeutic target in chronic myeloid leukemia.

  17. Detection of BCR-ABL and E2A-PBX1 fusion genes by RT-PCR in acute lymphoblastic leukaemia with failed or normal cytogenetics.

    Science.gov (United States)

    Devaraj, P E; Foroni, L; Kitra-Roussos, V; Secker-Walker, L M

    1995-02-01

    To evaluate the use of molecular analysis as a complement to karyotypic analysis in the detection of specific chromosomal abnormalities, the occurrence of t(1;19)(q23;p13) and t(9;22)(q34;q11) was investigated by RT-PCR in 43 diagnostic acute lymphoblastic leukaemia cases in whom cytogenetic investigations had failed (32 cases) or showed only a normal karyotype (> or = 20 normal metaphases, 11 cases). One child (aged 14 years) and five adults (aged 18-60 years) were BCR-ABL positive on first round for M-BCR-ABL (one case) or m-BCR-ABL (one case), or on nested PCR for m-BCR-ABL (three cases). Co-expression of M-BCR-ABL (first-round PCR) and m-BCR-ABL (nested PCR was seen in one case. One m-BCR-ABL-positive case also expressed the E2A-PBX1 fusion transcript. Patients positive for the transcript(s) were older, had higher white blood cell counts and a significantly poorer event-free survival (P < 0.001) than those negative for the transcript.

  18. New mutations detected by denaturing high performance liquid chromatography during screening of exon 6 bcr-abl mutations in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.

    Science.gov (United States)

    Mascarenhas, Cintia C; Cunha, Anderson F; Miranda, Eliana C; Zulli, Roberto; Silveira, Rosana A; Costa, Fernando F; Pagnano, Katia B B; De Souza, Carmino A

    2009-07-01

    Point mutations within the ABL kinase domain are the most frequent mechanism for reactivation of kinase activity of the BCR-ABL gene and have been associated with clinical resistance to tyrosine kinase (TK) inhibitors in patients with CML, conferring a poor prognosis. T315I (Treonine-->Isoleucine) is a mutation in the exon 6 of BCR-ABL gene that makes the protein resistant to kinase inhibitors currently used for treating CML. Denaturing High-performance liquid chromatography (D-HPLC) allows for high throughput mutation screening. In this study, we screened mutations in exon 6 of the BCR-ABL gene in patients presenting failure or sub optimal response according to Leukemia Net criteria and correlated the presence of mutations with clinical outcome. Genomic DNA was extracted from peripheral blood samples from 93 patients with CML (5 intolerant and 88 resistant). The PCR product was analysed by D-HPLC, and the patients samples with abnormal D-HLPC profiles were submitted to automated sequencing, using specific primers. Overall survival (OS) was calculated from the date of mutation analysis, for the whole group and for both groups (mutation versus no mutation). We screened mutations in exon 6 of the BCR-ABL gene in 93 CML TKI - resistant patients. Twenty-three out of 93 samples (25%) showed an abnormal elution profile. Automated sequencing confirmed the presence of a nucleotide change in 19 out of 23 cases: one polymorphism, T315T, seven known point mutations: T315I, F317L, V339L, M351T, E355G and F359V and three novel mutations: C305R, D325D and I360S. OS for the whole group was 80% in a median observation time of 30 months. OS for patients without the mutation was 87% and with the mutation was 56%, in a median observation time of 37 and 10 months, respectively (p < 0.0001, RR = 68). D-HPLC is a practical and sensitive method for routine clinical monitoring for emergence of kinase domain mutations and may be useful for optimising therapy in CML. The screening of

  19. Blocking for Sequential Political Experiments.

    Science.gov (United States)

    Moore, Ryan T; Moore, Sally A

    2013-10-01

    In typical political experiments, researchers randomize a set of households, precincts, or individuals to treatments all at once, and characteristics of all units are known at the time of randomization. However, in many other experiments, subjects "trickle in" to be randomized to treatment conditions, usually via complete randomization. To take advantage of the rich background data that researchers often have (but underutilize) in these experiments, we develop methods that use continuous covariates to assign treatments sequentially. We build on biased coin and minimization procedures for discrete covariates and demonstrate that our methods outperform complete randomization, producing better covariate balance in simulated data. We then describe how we selected and deployed a sequential blocking method in a clinical trial and demonstrate the advantages of our having done so. Further, we show how that method would have performed in two larger sequential political trials. Finally, we compare causal effect estimates from differences in means, augmented inverse propensity weighted estimators, and randomization test inversion.

  20. Sequential logic analysis and synthesis

    CERN Document Server

    Cavanagh, Joseph

    2007-01-01

    Until now, there was no single resource for actual digital system design. Using both basic and advanced concepts, Sequential Logic: Analysis and Synthesis offers a thorough exposition of the analysis and synthesis of both synchronous and asynchronous sequential machines. With 25 years of experience in designing computing equipment, the author stresses the practical design of state machines. He clearly delineates each step of the structured and rigorous design principles that can be applied to practical applications. The book begins by reviewing the analysis of combinatorial logic and Boolean a

  1. Pristimerin induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation by blocking NF-κB signaling and depleting Bcr-Abl

    Science.gov (United States)

    2010-01-01

    Background Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. Bcr-Abl-T315I is the notorious point mutation that causes resistance to imatinib and the second generation tyrosine kinase inhibitors, leading to poor prognosis. CML blasts have constitutive p65 (RelA NF-κB) transcriptional activity, and NF-κB may be a potential target for molecular therapies in CML that may also be effective against CML cells with Bcr-Abl-T315I. Results In this report, we discovered that pristimerin, a quinonemethide triterpenoid isolated from Celastraceae and Hippocrateaceae, inhibited growth and induced apoptosis in CML cells, including the cells harboring Bcr-Abl-T315I mutation. Additionally, pristimerin inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Pristimerin blocked the TNFα-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Pristimerin inhibited two steps in NF-κB signaling: TAK1→IKK and IKK→IκBα. Pristimerin potently inhibited two pairs of CML cell lines (KBM5 versus KBM5-T315I, 32D-Bcr-Abl versus 32D-Bcr-Abl-T315I) and primary cells from a CML patient with acquired resistance to imatinib. The mRNA and protein levels of Bcr-Abl in imatinib-sensitive (KBM5) or imatinib-resistant (KBM5-T315I) CML cells were reduced after pristimerin treatment. Further, inactivation of Bcr-Abl by imatinib pretreatment did not abrogate the TNFα-induced NF-κB activation while silencing p65 by siRNA did not affect the levels of Bcr-Abl, both results together indicating that NF-κB inactivation and Bcr-Abl inhibition may be parallel independent pathways. Conclusion To our knowledge, this is the first report to show that pristimerin is effective in vitro and in vivo against CML cells, including those with the T315I mutation. The mechanisms may involve inhibition of NF-κB and Bcr-Abl. We concluded that pristimerin could be a lead compound for further drug development to

  2. Frequency of the ETV6-RUNX1, BCR-ABL1, TCF3-PBX1, and MLL-AFF1 fusion genes in Guatemalan pediatric acute lymphoblastic leukemia patients and their ethnic associations.

    Science.gov (United States)

    Carranza, Claudia; Granados, Lilian; Morales, Oneida; Jo, Wendy; Villagran, Swuanny; Tinti, Damaris; Villegas, Mauricio; Antillón, Federico; Torselli, Silvana; Silva, Gabriel

    2013-06-01

    Fusion genes involved in acute lymphoblastic leukemia (ALL) occur mostly due to genetic and environmental factors, and only a limited number of studies have reported any ethnic influence. This study assesses whether an ethnic influence has an effect on the frequency of any of the four fusion genes: BCR-ABL1, ETV6-RUNX1, TCF3-PBX1, and MLL-AFF1 found in ALL. To study this ethnic influence, mononuclear cells were obtained from bone marrow samples from 143 patients with ALL. We performed RNA extraction and reverse transcription, then assessed the quality of the cDNA by amplifying the ABL1 control gene, and finally evaluated the presence of the four transcripts by multiplex polymerase chain reaction. We found 10 patients who had the BCR-ABL1 fusion gene (7%); 3 patients (2%) were TCF3-PBX1 positive; and 6 patients (4.5%) were ETV6-RUNX1 positive. The incidence of this last fusion gene is quite low when compared to the values reported in most countries. The low incidence of the ETV6-RUNX1 fusion gene found in Guatemala matches the incidence rates that have been reported in Spain and Indian Romani. Since it is known that an ethnic resemblance exists among these three populations, as shown by ancestral marker studies, the ALL data suggests an ethnic influence on the occurrence and frequency of this particular fusion gene. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage

    DEFF Research Database (Denmark)

    Järås, Marcus; Johnels, Petra; Agerstam, Helena

    2009-01-01

    OBJECTIVE: The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. MATERIALS AND METHODS: We investigated...... and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. RESULTS: Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells...... and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under...

  4. Sequential determination of important ecotoxic radionuclides in nuclear waste samples

    International Nuclear Information System (INIS)

    Bilohuscin, J.

    2016-01-01

    In the dissertation thesis we focused on the development and optimization of a sequential determination method for radionuclides 93 Zr, 94 Nb, 99 Tc and 126 Sn, employing extraction chromatography sorbents TEVA (R) Resin and Anion Exchange Resin, supplied by Eichrom Industries. Prior to the attestation of sequential separation of these proposed radionuclides from radioactive waste samples, a unique sequential procedure of 90 Sr, 239 Pu, 241 Am separation from urine matrices was tried, using molecular recognition sorbents of AnaLig (R) series and extraction chromatography sorbent DGA (R) Resin. On these experiments, four various sorbents were continually used for separation, including PreFilter Resin sorbent, which removes interfering organic materials present in raw urine. After the acquisition of positive results of this sequential procedure followed experiments with a 126 Sn separation using TEVA (R) Resin and Anion Exchange Resin sorbents. Radiochemical recoveries obtained from samples of radioactive evaporate concentrates and sludge showed high efficiency of the separation, while values of 126 Sn were under the minimum detectable activities MDA. Activity of 126 Sn was determined after ingrowth of daughter nuclide 126m Sb on HPGe gamma detector, with minimal contamination of gamma interfering radionuclides with decontamination factors (D f ) higher then 1400 for 60 Co and 47000 for 137 Cs. Based on the acquired experiments and results of these separation procedures, a complex method of sequential separation of 93 Zr, 94 Nb, 99 Tc and 126 Sn was proposed, which included optimization steps similar to those used in previous parts of the dissertation work. Application of the sequential separation method for sorbents TEVA (R) Resin and Anion Exchange Resin on real samples of radioactive wastes provided satisfactory results and an economical, time sparing, efficient method. (author)

  5. Human visual system automatically encodes sequential regularities of discrete events.

    Science.gov (United States)

    Kimura, Motohiro; Schröger, Erich; Czigler, István; Ohira, Hideki

    2010-06-01

    For our adaptive behavior in a dynamically changing environment, an essential task of the brain is to automatically encode sequential regularities inherent in the environment into a memory representation. Recent studies in neuroscience have suggested that sequential regularities embedded in discrete sensory events are automatically encoded into a memory representation at the level of the sensory system. This notion is largely supported by evidence from investigations using auditory mismatch negativity (auditory MMN), an event-related brain potential (ERP) correlate of an automatic memory-mismatch process in the auditory sensory system. However, it is still largely unclear whether or not this notion can be generalized to other sensory modalities. The purpose of the present study was to investigate the contribution of the visual sensory system to the automatic encoding of sequential regularities using visual mismatch negativity (visual MMN), an ERP correlate of an automatic memory-mismatch process in the visual sensory system. To this end, we conducted a sequential analysis of visual MMN in an oddball sequence consisting of infrequent deviant and frequent standard stimuli, and tested whether the underlying memory representation of visual MMN generation contains only a sensory memory trace of standard stimuli (trace-mismatch hypothesis) or whether it also contains sequential regularities extracted from the repetitive standard sequence (regularity-violation hypothesis). The results showed that visual MMN was elicited by first deviant (deviant stimuli following at least one standard stimulus), second deviant (deviant stimuli immediately following first deviant), and first standard (standard stimuli immediately following first deviant), but not by second standard (standard stimuli immediately following first standard). These results are consistent with the regularity-violation hypothesis, suggesting that the visual sensory system automatically encodes sequential

  6. Feasibility Study of the Use of Thiosulfate as Extractant Agent in the Electrokinetic Remediation of a Soil Contaminated by Mercury from Almadén

    DEFF Research Database (Denmark)

    Subires-Muñoz, José Diego; García-Rubio, Ana; Vereda-Alonso, Carlos

    2010-01-01

    Natural soils are rather complex, making the predictability of the behavior of some remediation techniques very complicated. In this paper, the remediation of a Hg contaminated soil close to Almadén using a thiosulfate solution as extractant agent is studied. In addition, the use of the BCR...... extraction procedure before and after the remediation was performed. Once again, a clear relationship between the remediation and the extraction results are observed, giving further support to the idea that BCR can be used as a reasonable tool for feasibility studies of EKR among other remediation techniques....

  7. Effect of humic acid on the underpotential deposition-stripping voltammetry of copper in acetic acid soil extract solutions at mercaptoacetic acid-modified gold electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Herzog, Gregoire; Beni, Valerio; Dillon, Patrick H.; Barry, Thomas; Arrigan, Damien W.M

    2004-05-24

    Electrochemical measurements were undertaken for the investigation of the underpotential deposition-stripping process of copper at bare and modified gold electrodes in 0.11 M acetic acid, the first fraction of the European Union's Bureau Communautaire de References (BCR) sequential extraction procedure for fractionating metals within soils and sediments. Gold electrodes modified with mercaptoacetic acid showed higher sensitivity for the detection of copper than bare gold electrodes, both in the absence and in the presence of humic acid in acetic acid solutions, using the underpotential deposition-stripping voltammetry (UPD-SV) method. In the presence of 50 mg l{sup -1} of humic acid, the mercaptoacetic acid modified electrode proved to be 1.5 times more sensitive than the bare gold electrode. The mercaptoacetic acid monolayer formed on the gold surface provided efficient protection against the adsorption of humic acid onto the gold electrode surface. Variation of the humic acid concentration in the solution showed little effect on the copper stripping signal at the modified electrode. UPD-SV at the modified electrode was applied to the analysis of soil extract samples. Linear correlation of the electrochemical results with atomic spectroscopic results yielded the straight-line equation y ({mu}g l{sup -1}) = 1.10x - 44 (ppb) (R=0.992, n=6), indicating good agreement between the two methods.

  8. Attack Trees with Sequential Conjunction

    NARCIS (Netherlands)

    Jhawar, Ravi; Kordy, Barbara; Mauw, Sjouke; Radomirović, Sasa; Trujillo-Rasua, Rolando

    2015-01-01

    We provide the first formal foundation of SAND attack trees which are a popular extension of the well-known attack trees. The SAND at- tack tree formalism increases the expressivity of attack trees by intro- ducing the sequential conjunctive operator SAND. This operator enables the modeling of

  9. Coexistence of p190 BCR/ABL Transcript and CALR 52-bp Deletion in Chronic Myeloid Leukemia Blast Crisis: A Case Report.

    Science.gov (United States)

    Seghatoleslami, Mohammad; Ketabchi, Neda; Ordo, Alireza; Asl, Javad Mohammadi; Golchin, Neda; Saki, Najmaldin

    2016-01-01

    We introduce a 78-year-old woman presented with thrombocytosis and high blast count who had a history of splenectomy. Her cytogenetic analysis revealed aberrant chromosomal rearrangements in different clonal populations harboring 46XX karyotype with t(9;22) (q34;q11). RT-PCR assay detected the e1a2 BCR-ABL translocation resulting from rearrangement of the minor breakpoint cluster region (m-bcr) in BCR gene. Subsequent evaluation of the disease showed calreticulin (CALR) 52-bp deletion as well as the absence of JAK2 (V617F) heterozygous mutation in granulocyte population of peripheral blood using allele-specific PCR and bi-directional DNA sequencing. To our knowledge, this is the first case of a patient initially diagnosed as p190 BCR-ABL transcript positive CML in blast crisis characterized by a 52-bp deletion in CALR gene.

  10. Coexistence of P190 BCR/ABL transcript and CALR 52-bp deletion in chronic myeloid leukemia blast crisis: a case report

    Directory of Open Access Journals (Sweden)

    najmaldin saki

    2016-01-01

    Full Text Available We present a case of a 78-year-old woman presented with thrombocytosis and high blast count, who had a history of splenectomy. Her cytogenetic analysis revealed aberrant chromosomal rearrangements in different clonal populations harboring 46XX karyotype with t(9;22(q34;q11. RT-PCR assay detected the e1a2 BCR-ABL translocation resulting from a rearrangement of the minor breakpoint cluster region (m-bcr in the BCR gene. Subsequent evaluations of the disease showed calreticulin (CALR 52-bp deletion as well as the absence of JAK2V617F heterozygous mutation in granulocyte population of peripheral blood using allele-specific PCR and bi-directional DNA sequencing. To our knowledge, this is the first case of a patient initially diagnosed as p190 BCR-ABL transcript positive CML in blastic crisis characterized with a 52-bp deletion in CALR gene.

  11. Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase: ENEST1st sub-analysis.

    Science.gov (United States)

    Hochhaus, Andreas; Mahon, Franҫois-Xavier; le Coutre, Philipp; Petrov, Ljubomir; Janssen, Jeroen J W M; Cross, Nicholas C P; Rea, Delphine; Castagnetti, Fausto; Hellmann, Andrzej; Rosti, Gianantonio; Gattermann, Norbert; Coronel, Maria Liz Paciello; Gutierrez, Maria Asuncion Echeveste; Garcia-Gutierrez, Valentin; Vincenzi, Beatrice; Dezzani, Luca; Giles, Francis J

    2017-07-01

    The ENEST1st sub-analysis presents data based on Philadelphia chromosome (Ph) status, i.e., Ph+ and Ph-/BCR-ABL1 + chronic myeloid leukemia. Patients received nilotinib 300 mg twice daily, up to 24 months. At screening, 983 patients were identified as Ph+ and 30 patients as Ph-/BCR-ABL + based on cytogenetic and RT-PCR assessment; 76 patients had unknown karyotype (excluded from this sub-analysis). In the Ph-/BCR-ABL1 + subgroup, no additional chromosomal aberrations were reported. In the Ph+ subgroup, 952 patients had safety and molecular assessments. In the Ph-/BCR-ABL1 + subgroup, 30 patients had safety assessments and 28 were followed up for molecular assessments. At 18 months, the molecular response (MR) 4 rate [MR 4 ; BCR-ABL1 ≤0.01% on International Scale (IS)] was similar in the Ph-/BCR-ABL1+ (39.3%) and Ph+ subgroups (38.1%). By 24 months, the cumulative rates of major molecular response (BCR-ABL1 IS ≤0.1%;), MR 4 , and MR 4.5 (BCR-ABL1 IS ≤0.0032%) were 85.7, 60.7, and 50.0%, respectively, in the Ph-/BCR-ABL1 + subgroup, and 80.3, 54.7, and 38.3%, respectively, in the Ph+ subgroup. In both Ph-/BCR-ABL1 + and Ph+ subgroups, rash (20 and 22%), pruritus (16.7 and 16.7%), nasopharyngitis (13.3 and 10.4%), fatigue (10 and 14.2%), headache (10 and 15.8%), and nausea (6.7 vs 11.4%) were frequent non-hematologic adverse events, whereas hypophosphatemia (23.3 and 6.8%), anemia (10 and 6.5%), and thrombocytopenia (3.3 and 10.2%) were the common hematologic/biochemical laboratory events. Based on similar molecular response and safety results in both subgroups, we conclude that Ph-/BCR-ABL1 + patients benefit from nilotinib in the same way as Ph+ patients.

  12. Association of HLA Class I and Class II genes with bcr-abl transcripts in leukemia patients with t(9;22) (q34;q11)

    International Nuclear Information System (INIS)

    Mundhada, Shailendra; Luthra, Rajyalakshmi; Cano, Pedro

    2004-01-01

    Based on the site of breakpoint in t(9;22) (q34;q11), bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. Significant negative associations (p < 0.05) were observed with HLA-A*02 (b2a2, e1a2), -A*68 (b2a2, b3a2, e1a2), -B*14 (b2a2, b3a2, e1a2), -B*15 (b2a2, b3a2), -B*40 (b2a2), -DQB1*0303 (b2a2, b3a2), -DQB1*0603 (b2a2), -DRB1*0401 (e1a2), -DRB1*0701 (b3a2), and -DRB1*1101 (b2a2). The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22) (q34;q11)-positive leukemia

  13. c-Myb and its target Bmi1 are required for p190BCR/ABL leukemogenesis in mouse and human cells.

    Science.gov (United States)

    Waldron, T; De Dominici, M; Soliera, A R; Audia, A; Iacobucci, I; Lonetti, A; Martinelli, G; Zhang, Y; Martinez, R; Hyslop, T; Bender, T P; Calabretta, B

    2012-04-01

    Expression of c-Myb is required for normal hematopoiesis and for proliferation of myeloid leukemia blasts and a subset of T-cell leukemia, but its role in B-cell leukemogenesis is unknown. We tested the role of c-Myb in p190(BCR/ABL)-dependent B-cell leukemia in mice transplanted with p190(BCR/ABL)-transduced marrow cells with a c-Myb allele (Myb(f/d)) and in double transgenic p190(BCR/ABL)/Myb(w/d) mice. In both models, loss of a c-Myb allele caused a less aggressive B-cell leukemia. In p190(BCR/ABL)-expressing human B-cell leukemia lines, knockdown of c-Myb expression suppressed proliferation and colony formation. Compared with c-Myb(w/f) cells, expression of Bmi1, a regulator of stem cell proliferation and maintenance, was decreased in pre-B cells from Myb(w/d) p190(BCR/ABL) transgenic mice. Ectopic expression of a mutant c-Myb or Bmi1 enhanced the proliferation and colony formation of Myb(w/d) p190(BCR/ABL) B-cells; by contrast, Bmi1 downregulation inhibited colony formation of p190(BCR/ABL)-expressing murine B cells and human B-cell leukemia lines. Moreover, c-Myb interacted with a segment of the human Bmi1 promoter and enhanced its activity. In blasts from 19 Ph(1) adult acute lymphoblastic leukemia patients, levels of c-Myb and Bmi1 showed a positive correlation. Together, these findings support the existence of a c-Myb-Bmi1 transcription-regulatory pathway required for p190(BCR/ABL) leukemogenesis.

  14. Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges.

    Science.gov (United States)

    Noens, Lucien; Hensen, Marja; Kucmin-Bemelmans, Izabela; Lofgren, Christina; Gilloteau, Isabelle; Vrijens, Bernard

    2014-03-01

    BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2(nd) generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation.

  15. Structural Mechanism of the Pan-BCR-ABL Inhibitor Ponatinib (AP24534): Lessons for Overcoming Kinase Inhibitor Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tianjun; Commodore, Lois; Huang, Wei-Sheng; Wang, Yihan; Thomas, Mathew; Keats, Jeff; Xu, Qihong; Rivera, Victor M.; Shakespeare, William C.; Clackson, Tim; Dalgarno, David C.; Zhu, Xiaotian (ARIAD)

    2012-01-20

    The BCR-ABL inhibitor imatinib has revolutionized the treatment of chronic myeloid leukemia. However, drug resistance caused by kinase domain mutations has necessitated the development of new mutation-resistant inhibitors, most recently against the T315I gatekeeper residue mutation. Ponatinib (AP24534) inhibits both native and mutant BCR-ABL, including T315I, acting as a pan-BCR-ABL inhibitor. Here, we undertook a combined crystallographic and structure-activity relationship analysis on ponatinib to understand this unique profile. While the ethynyl linker is a key inhibitor functionality that interacts with the gatekeeper, virtually all other components of ponatinib play an essential role in its T315I inhibitory activity. The extensive network of optimized molecular contacts found in the DFG-out binding mode leads to high potency and renders binding less susceptible to disruption by single point mutations. The inhibitory mechanism exemplified by ponatinib may have broad relevance to designing inhibitors against other kinases with mutated gatekeeper residues.

  16. Localization of preferential sites of rearrangement within the BCR gene in Philadelphia chromosome-positive acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Denny, C.T.; Shah, N.P.; Ogden, S.; Willman, C.; McConnell, T.; Crist, W.; Carroll, A.; Witte, O.N.

    1989-01-01

    The Philadelphia chromosome associated with acute lymphoblastic leukemia (ALL) has been linked to a hybrid BCR/ABL protein product that differs from that found in chronic myelogenous leukemia. This implies that the molecular structures of the two chromosomal translocations also differ. Localization of translocation breakpoints in Philadelphia chromosome-positive ALL has been impeded due to the only partial characterization of the BCR locus. The authors have isolated the entire 130-kilobase BCR genomic locus from a human cosmid library. They have demonstrated that these breakpoints are all located at the 3' end of the intron around an unusual restriction fragment length polymorphism caused by deletion of a 1-kilobase fragment containing Alu family reiterated sequences. This clustering is unexpected in light of previous theories of rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia that would have predicted a random dispersion of breakpoints in the first intron in Philadelphia chromosome-positive ALL. The proximity of the translocation breakpoints to this constitutive deletion may indicate shared mechanisms of rearrangement or that such polymorphisms mark areas of the genome prone to recombination

  17. Characterization of a novel variant BCR-ABL1 fusion transcript in a patient with chronic myeloid leukemia: Implications for molecular monitoring.

    Science.gov (United States)

    Crampe, Mireille; Haslam, Karl; Kelly, Johanna; Conneally, Eibhlin; Langabeer, Stephen E

    2017-06-01

    Molecular monitoring of BCR-ABL1 transcript levels using quantitative polymerase chain reaction is an essential part of the modern management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Establishing the diagnostic BCR-ABL1 fusion transcript is necessary in order to select appropriate primers and probes for such monitoring. A case is described in which quantitative polymerase chain reaction failed to detect the presence of BCR-ABL1 fusion transcript in a Philadelphia chromosome-positive chronic myeloid leukemia patient. Further investigation demonstrated a novel in-frame BCR-ABL1 fusion transcript with a breakpoint in BCR exon 13 and insertion of a sequence of ABL1 intron 1, therefore enabling subsequent molecular monitoring. This case highlights the requirement for characterization of the BCR-ABL1 transcript type at chronic myeloid leukemia diagnosis. Issues concerning standardized methodological approaches and interpretation of transcript levels in such rare cases are discussed. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  18. Arabinose and ferulic acid rich pectic polysaccharides extracted from sugar beet pulp.

    NARCIS (Netherlands)

    Oosterveld, A.; Beldman, G.; Schols, H.A.; Voragen, A.G.J.

    1996-01-01

    Arabinose and ferulic acid rich polysaccharides were extracted from sugar beet pulp using two extraction methods: a sequential extraction with H2O (2 times), NaOH/EDTA (2 times), and 4 M NaOH (2 times; method A) and a sequential extraction in which the NaOH/EDTA extraction was replaced by an

  19. Random sequential adsorption of cubes.

    Science.gov (United States)

    Cieśla, Michał; Kubala, Piotr

    2018-01-14

    Random packings built of cubes are studied numerically using a random sequential adsorption algorithm. To compare the obtained results with previous reports, three different models of cube orientation sampling were used. Also, three different cube-cube intersection algorithms were tested to find the most efficient one. The study focuses on the mean saturated packing fraction as well as kinetics of packing growth. Microstructural properties of packings were analyzed using density autocorrelation function.

  20. Time-sequential changes of differentially expressed miRNAs during the process of anterior lumbar interbody fusion using equine bone protein extract, rhBMP-2 and autograft

    Science.gov (United States)

    Chen, Da-Fu; Zhou, Zhi-Yu; Dai, Xue-Jun; Gao, Man-Man; Huang, Bao-Ding; Liang, Tang-Zhao; Shi, Rui; Zou, Li-Jin; Li, Hai-Sheng; Bünger, Cody; Tian, Wei; Zou, Xue-Nong

    2014-03-01

    The precise mechanism of bone regeneration in different bone graft substitutes has been well studied in recent researches. However, miRNAs regulation of the bone formation has been always mysterious. We developed the anterior lumbar interbody fusion (ALIF) model in pigs using equine bone protein extract (BPE), recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS), and autograft as bone graft substitute, respectively. The miRNA and gene expression profiles of different bone graft materials were examined using microarray technology and data analysis, including self-organizing maps, KEGG pathway and Biological process GO analyses. We then jointly analyzed miRNA and mRNA profiles of the bone fusion tissue at different time points respectively. Results showed that miRNAs, including let-7, miR-129, miR-21, miR-133, miR-140, miR-146, miR-184, and miR-224, were involved in the regulation of the immune and inflammation response, which provided suitable inflammatory microenvironment for bone formation. At late stage, several miRNAs directly regulate SMAD4, Estrogen receptor 1 and 5-hydroxytryptamine (serotonin) receptor 2C for bone formation. It can be concluded that miRNAs play important roles in balancing the inflammation and bone formation.

  1. Differential regulation of the Rac1 GTPase-activating protein (GAP) BCR during oxygen/glucose deprivation in hippocampal and cortical neurons.

    Science.gov (United States)

    Smith, Katharine R; Rajgor, Dipen; Hanley, Jonathan G

    2017-12-08

    Brain ischemia causes oxygen and glucose deprivation (OGD) in neurons, triggering a cascade of events leading to synaptic accumulation of glutamate. Excessive activation of glutamate receptors causes excitotoxicity and delayed cell death in vulnerable neurons. Following global cerebral ischemia, hippocampal CA1 pyramidal neurons are more vulnerable to injury than their cortical counterparts, but the mechanisms that underlie this difference are unclear. Signaling via Rho-family small GTPases, their upstream guanine nucleotide exchange factors, and GTPase-activating proteins (GAPs) is differentially dysregulated in response to OGD/ischemia in hippocampal and cortical neurons. Increased Rac1 activity caused by OGD/ischemia contributes to neuronal death in hippocampal neurons via diverse effects on NADPH oxidase activity and dendritic spine morphology. The Rac1 guanine nucleotide exchange factor Tiam1 mediates an OGD-induced increase in Rac1 activity in hippocampal neurons; however, the identity of an antagonistic GAP remains elusive. Here we show that the Rac1 GAP breakpoint cluster region (BCR) associates with NMDA receptors (NMDARs) along with Tiam1 and that this protein complex is more abundant in hippocampal compared with cortical neurons. Although total BCR is similar in the two neuronal types, BCR is more active in hippocampal compared with cortical neurons. OGD causes an NMDAR- and Ca 2+ -permeable AMPAR-dependent deactivation of BCR in hippocampal but not cortical neurons. BCR knockdown occludes OGD-induced Rac1 activation in hippocampal neurons. Furthermore, disrupting the Tiam1-NMDAR interaction with a fragment of Tiam1 blocks OGD-induced Tiam1 activation but has no effect on the deactivation of BCR. This work identifies BCR as a critical player in Rac1 regulation during OGD in hippocampal neurons. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. A novelBCR-ABL1fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case.

    Science.gov (United States)

    Zhou, Fen; Jin, Runming; Hu, Yu; Mei, Heng

    2017-01-01

    Chronic myelogenous leukemia (CML) is a pluripotent hematopoietic stem cell disorder caused by the fusion of the BCR and ABL1 genes. Quantitative RT-PCR (qRT-PCR) is a routinely performed screening technique to identify BCR-ABL1 fusion genes, but a limitation of this method is its inability to recognize novel fusions that have not been previously characterized. Next-generation sequencing (NGS) is an effective and sensitive detection method for the determination of novel BCR-ABL1 fusion genes as well as previously characterized ones. The oncoprotein tyrosine kinase BCR-ABL1 is a constitutively active kinase involved in the activation of a number of signaling pathways, and it has been the therapeutic target for tyrosine kinase inhibitors (TKIs) such as imatinib. Reports have presented opposing viewpoints about the effect of the disrupted Src homology 3 (SH3) domain on TKI efficacy. We here report that using NGS we identified a novel BCR-ABL1 fusion gene with breakpoints in the BCR intron 14 and the ABL1 intron 2, leading to partial deletion of its SH3 domain. In the present case, the patient received targeted therapy with the TKI imatinib at 400 mg/day and no adverse reaction was reported. The patient eventually entered remission with decreased proliferation of karyocytes and granulocytes. We also identified mutations in genes, including TP53 , FLT3 , ASXL1 , SETBP1 , CEBPA and CBL, that seemed to have an influence on the outcome of TKI therapy targeting the BCR-ABL1 protein. Together with previously reported results, it is clear that the genetic heterogeneity of CML patients significantly affects the presentation of the disease and its progression and therefore should inform the design of the therapeutic strategy.

  3. Bach2 regulates aberrant activation of B cell in systemic lupus erythematosus and can be negatively regulated by BCR-ABL/PI3K.

    Science.gov (United States)

    Zhu, Zhengwei; Yang, Chao; Wen, Leilei; Liu, Lu; Zuo, Xianbo; Zhou, Fusheng; Gao, Jinping; Zheng, Xiaodong; Shi, Yinjuan; Zhu, Caihong; Liang, Bo; Yin, Xianyong; Wang, Wenjun; Cheng, Hui; Shen, Songke; Tang, Xianfa; Tang, Huayang; Sun, Liangdan; Zhang, Anping; Yang, Sen; Cui, Yong; Zhang, Xuejun; Sheng, Yujun

    2018-04-01

    This study was aimed to explore the effect of Bach2 on B cells in systemic lupus erythematosus (SLE), as well as the underlying mechanisms. Expression of Bach2, phosphorylated-Bach2 (p-Bach2), Akt, p-Akt and BCR-ABL (p210) in B cells isolated from SLE patients and the healthy persons were assessed by Western blot. Immunofluorescence staining was performed to assess the localization of Bach2 in B cells. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IgG produced by B cells. Cell counting kit-8 (CCK-8) and Annexin-V FITC/PI double staining assay were adopted to evaluate cell proliferation and apoptosis in B cells, respectively. Compared to the healthy controls, Bach2, p-Akt and p210 were significantly decreased, while nuclear translocation of Bach2, IgG, CD40 and CD86 obviously up-regulated in B cells from SLE patients. Bach2 significantly inhibited the proliferation, promoted apoptosis of B cells from SLE patients, whereas BCR-ABL dramatically reversed cell changes induced by Bach2. Besides, BCR-ABL also inhibited nuclear translocation of Bach2 in B cells from SLE patients. Further, LY294002 treatment had no effect on decreased expression of Bach2 induced by BCR-ABL, but significantly eliminated BCR-ABL-induced phosphorylation of Bach2 and restored reduced nuclear translocation of Bach2 induced by BCR-ABL in B cells from SLE. Bach2 may play a suppressive role in B cells from SLE, and BCR-ABL may inhibit the nuclear translocation of Bach2 via serine phosphorylation through the PI3K pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Random sequential adsorption on fractals.

    Science.gov (United States)

    Ciesla, Michal; Barbasz, Jakub

    2012-07-28

    Irreversible adsorption of spheres on flat collectors having dimension d fractals (1 < d < 2), and on general Cantor set (d < 1). Adsorption process is modeled numerically using random sequential adsorption (RSA) algorithm. The paper concentrates on measurement of fundamental properties of coverages, i.e., maximal random coverage ratio and density autocorrelation function, as well as RSA kinetics. Obtained results allow to improve phenomenological relation between maximal random coverage ratio and collector dimension. Moreover, simulations show that, in general, most of known dimensional properties of adsorbed monolayers are valid for non-integer dimensions.

  5. Identification of novel tyrosine kinase inhibitors for drug resistant T315I mutant BCR-ABL: a virtual screening and molecular dynamics simulations study

    Science.gov (United States)

    Banavath, Hemanth Naick; Sharma, Om Prakash; Kumar, Muthuvel Suresh; Baskaran, R.

    2014-11-01

    BCR-ABL tyrosine kinase plays a major role in the pathogenesis of chronic myeloid leukemia (CML) and is a proven target for drug development. Currently available drugs in the market are effective against CML; however, side-effects and drug-resistant mutations in BCR-ABL limit their full potential. Using high throughput virtual screening approach, we have screened several small molecule databases and docked against wild-type and drug resistant T315I mutant BCR-ABL. Drugs that are currently available, such as imatinib and ponatinib, were also docked against BCR-ABL protein to set a cutoff value for our screening. Selected lead compounds were further evaluated for chemical reactivity employing density functional theory approach, all selected ligands shows HLG value > 0.09900 and the binding free energy between protein-ligand complex interactions obtained was rescored using MM-GBSA. The selected compounds showed least ΔG score -71.53 KJ/mol to maximum -126.71 KJ/mol in both wild type and drug resistant T315I mutant BCR-ABL. Following which, the stability of the docking complexes were evaluated by molecular dynamics simulation (MD) using GROMACS4.5.5. Results uncovered seven lead molecules, designated with Drug-Bank and PubChem ids as DB07107, DB06977, ST013616, DB04200, ST007180 ST019342, and DB01172, which shows docking scores higher than imatinib and ponatinib.

  6. Frequency of p190 and p210 BCR-ABL rearrangements and survival in Brazilian adult patients with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ilana de França Azevedo

    2014-10-01

    Full Text Available Objective: This study investigated the occurrence of the p190 and p210 break point clusterregion-Abelson (BCR-ABL rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival. Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR using specific primers was employed to identify molecular rearrangements. Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%. The most common immunophenotype was B lineage (76%. BCR-ABL rearrangements was detected in 14 (34% patients with the following distribution: p190 (28%, p210 (50% and double positive (22%. Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44% and positive BCR-ABL (28%. Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia.

  7. Total uncertainty budget calculation for the determination of mercury in incineration ash (BCR 176R) by atomic fluorescence spectrometry.

    Science.gov (United States)

    Tirez, Kristof; Beutels, Filip; Brusten, Wilfried; Noten, Bart; De Brucker, Nicole

    2002-11-01

    The mercury mass fraction has been determined by atomic fluorescence spectrometry (AFS) in the framework of the project "Certification of a reference material (trace elements in fly ash) in replacement of BCR CRM 176". Calculation of the uncertainty budget, as described in this manuscript, emphasizes a practical and realistic approach to estimation of uncertainty components on the basis of statistical assumptions. GUM Workbench software was used, and resulted in a mercury mass fraction of 1.58+/-0.11 mg kg(-1) (with coverage factor k=2.2, 95% probability) related to dry mass, submitted in the certification exercise. The calculated total uncertainty budget applies to analogous samples analyzed by this procedure.

  8. Fluorescence in situ hybridization patterns of BCR/ABL1 fusion in chronic myelogenous leukemia at diagnosis

    Directory of Open Access Journals (Sweden)

    Poonam P Jain

    2012-01-01

    Full Text Available Background : Chronic myelogenous leukemia (CML is characterised by the t(9;22(q34;q11.2 which results in the formation of the BCR/ABL1 fusion gene. Occasionally, the t(9;22 may be associated with submicroscopic deletions of chromosomes 9 and/or 22 which appear to be associated with a worse prognosis. Three or four-way variant t(9;22 may also occur. All these changes as well as gain of the Philadelphia chromosome which represents disease progression can be detected by fluorescence in situ hybridization (FISH analysis. FISH analysis at presentation is used to determine the number of cells with BCR/ABL1 fusion and establish whether the patterns are typical or atypical. Response to therapy can then be monitored by serial testing. Patients and Methods : The study group consisted of all patients diagnosed or suspected to have CML who had interphase FISH analysis at presentation on peripheral blood/bone marrow using a commercially available BCR/ABL1 dual colour, dual fusion probe. The study was performed at a tertiary hospital in India between 2004 and 2010. Results: There were 1076 diagnostic samples which were positive for BCR/ABL1 fusion. Typical dual fusion signals (two fusions, one red and one green, 2F1R1G were seen in 801 cases (74 %. Atypical signal patterns were seen in 275 cases (26%. These were: 1F1R2G (4%, 1F2R1G (2.5% and 1F1R1G (11% representing deletions of the derivative 9 involving chromosome 9 sequences, chromosome 22 sequences, or both respectively; 3F1R1G (6.5% usually representing gain of an additional Philadelphia chromosome and 1F2R2G (1% representing a three- or four-way variant translocation. More than one signal pattern was seen in 1%. Conclusions: Our findings were similar to the literature with respect to the distribution of signal patterns except that we had a lower number of patients with variant translocations. While each signal pattern is typically associated with a particular abnormality, there can be more than one

  9. Screening und Charakterisierung von Peptidliganden für den BCR-ABL mRNA Translokationsbereich

    OpenAIRE

    Bäumler, Jörg

    2006-01-01

    Die reziproke Translokation t(9;22) ist in 95% der chronischen myeloischen Leukämie vorhanden. Bei der Translokation entsteht ein Fusionsprotein BCR-ABL, welches ausreichend für die Entstehung von Leukämien ist. 30% aller akuten lymphatischen Leukämien sind ebenfalls positiv für diese Translokation. Durch die Translokation entsteht am Translokationsbruchpunkt eine einzigartige RNA-Sequenz, welche als Ziel für eine RNA-Liganden Suche dienen kann. Ziel dieser Arbeit war es, Peptidliganden zu fi...

  10. The Bacterial Sequential Markov Coalescent.

    Science.gov (United States)

    De Maio, Nicola; Wilson, Daniel J

    2017-05-01

    Bacteria can exchange and acquire new genetic material from other organisms directly and via the environment. This process, known as bacterial recombination, has a strong impact on the evolution of bacteria, for example, leading to the spread of antibiotic resistance across clades and species, and to the avoidance of clonal interference. Recombination hinders phylogenetic and transmission inference because it creates patterns of substitutions (homoplasies) inconsistent with the hypothesis of a single evolutionary tree. Bacterial recombination is typically modeled as statistically akin to gene conversion in eukaryotes, i.e. , using the coalescent with gene conversion (CGC). However, this model can be very computationally demanding as it needs to account for the correlations of evolutionary histories of even distant loci. So, with the increasing popularity of whole genome sequencing, the need has emerged for a faster approach to model and simulate bacterial genome evolution. We present a new model that approximates the coalescent with gene conversion: the bacterial sequential Markov coalescent (BSMC). Our approach is based on a similar idea to the sequential Markov coalescent (SMC)-an approximation of the coalescent with crossover recombination. However, bacterial recombination poses hurdles to a sequential Markov approximation, as it leads to strong correlations and linkage disequilibrium across very distant sites in the genome. Our BSMC overcomes these difficulties, and shows a considerable reduction in computational demand compared to the exact CGC, and very similar patterns in simulated data. We implemented our BSMC model within new simulation software FastSimBac. In addition to the decreased computational demand compared to previous bacterial genome evolution simulators, FastSimBac provides more general options for evolutionary scenarios, allowing population structure with migration, speciation, population size changes, and recombination hotspots. FastSimBac is

  11. Solubility of manure phosphorus characterized by selective and sequential extractions

    Science.gov (United States)

    The increasing awareness of the severity of the problem of phosphorus (P) derived from agricultural production moving off-farm and threatening water quality has led to the search for methods to characterize the forms and potential solubilities of phosphorus in food animal manures and manure products...

  12. Immediate Sequential Bilateral Cataract Surgery

    DEFF Research Database (Denmark)

    Kessel, Line; Andresen, Jens; Erngaard, Ditte

    2015-01-01

    The aim of the present systematic review was to examine the benefits and harms associated with immediate sequential bilateral cataract surgery (ISBCS) with specific emphasis on the rate of complications, postoperative anisometropia, and subjective visual function in order to formulate evidence......-based national Danish guidelines for cataract surgery. A systematic literature review in PubMed, Embase, and Cochrane central databases identified three randomized controlled trials that compared outcome in patients randomized to ISBCS or bilateral cataract surgery on two different dates. Meta-analyses were...... performed using the Cochrane Review Manager software. The quality of the evidence was assessed using the GRADE method (Grading of Recommendation, Assessment, Development, and Evaluation). We did not find any difference in the risk of complications or visual outcome in patients randomized to ISBCS or surgery...

  13. The Role of Mitochondrial DNA Damage and Repair in the Resistance of BCR/ABL-Expressing Cells to Tyrosine Kinase Inhibitors

    Directory of Open Access Journals (Sweden)

    Janusz Blasiak

    2013-08-01

    Full Text Available Chronic myeloid leukemia (CML is a hematological malignancy that arises from the transformation of stem hematopoietic cells by the fusion oncogene BCR/ABL and subsequent clonal expansion of BCR/ABL-positive progenitor leukemic cells. The BCR/ABL protein displays a constitutively increased tyrosine kinase activity that alters many regulatory pathways, leading to uncontrolled growth, impaired differentiation and increased resistance to apoptosis featured by leukemic cells. Current CML therapy is based on tyrosine kinase inhibitors (TKIs, primarily imatinib, which induce apoptosis in leukemic cells. However, some patients show primary resistance to TKIs while others develop it in the course of therapy. In both cases, resistance may be underlined by perturbations in apoptotic signaling in leukemic cells. As mitochondria may play an important role in such signaling, alteration in mitochondrial metabolism may change resistance to pro-apoptotic action of TKIs in BCR/ABL-positive cells. Because BCR/ABL may induce reactive oxygen species and unfaithful DNA repair, it may affect the stability of mitochondrial DNA, influencing mitochondrial apoptotic signaling and in this way change the sensitivity of CML cells to TKIs. Moreover, cancer cells, including BCR/ABL-positive cells, show an increased level of glucose metabolism, resulting from the shift from oxidative phosphorylation to glycolysis to supply ATP for extensive proliferation. Enhanced level of glycolysis may be associated with TKI resistance and requires change in the expression of several genes regulated mostly by hypoxia-inducible factor-1α, HIF-1α. Such regulation may be associated with the impaired mitochondrial respiratory system in CML cells. In summary, mitochondria and mitochondria-associated molecules and pathways may be attractive targets to overcome TKI resistance in CML.

  14. The role of mitochondrial DNA damage and repair in the resistance of BCR/ABL-expressing cells to tyrosine kinase inhibitors.

    Science.gov (United States)

    Glowacki, Sylwester; Synowiec, Ewelina; Blasiak, Janusz

    2013-08-07

    Chronic myeloid leukemia (CML) is a hematological malignancy that arises from the transformation of stem hematopoietic cells by the fusion oncogene BCR/ABL and subsequent clonal expansion of BCR/ABL-positive progenitor leukemic cells. The BCR/ABL protein displays a constitutively increased tyrosine kinase activity that alters many regulatory pathways, leading to uncontrolled growth, impaired differentiation and increased resistance to apoptosis featured by leukemic cells. Current CML therapy is based on tyrosine kinase inhibitors (TKIs), primarily imatinib, which induce apoptosis in leukemic cells. However, some patients show primary resistance to TKIs while others develop it in the course of therapy. In both cases, resistance may be underlined by perturbations in apoptotic signaling in leukemic cells. As mitochondria may play an important role in such signaling, alteration in mitochondrial metabolism may change resistance to pro-apoptotic action of TKIs in BCR/ABL-positive cells. Because BCR/ABL may induce reactive oxygen species and unfaithful DNA repair, it may affect the stability of mitochondrial DNA, influencing mitochondrial apoptotic signaling and in this way change the sensitivity of CML cells to TKIs. Moreover, cancer cells, including BCR/ABL-positive cells, show an increased level of glucose metabolism, resulting from the shift from oxidative phosphorylation to glycolysis to supply ATP for extensive proliferation. Enhanced level of glycolysis may be associated with TKI resistance and requires change in the expression of several genes regulated mostly by hypoxia-inducible factor-1α, HIF-1α. Such regulation may be associated with the impaired mitochondrial respiratory system in CML cells. In summary, mitochondria and mitochondria-associated molecules and pathways may be attractive targets to overcome TKI resistance in CML.

  15. Detection of a rare BCR-ABL tyrosine kinase fusion protein in H929 multiple myeloma cells using immunoprecipitation (IP)-tandem mass spectrometry (MS/MS).

    Science.gov (United States)

    Breitkopf, Susanne B; Yuan, Min; Pihan, German A; Asara, John M

    2012-10-02

    Hypothesis directed proteomics offers higher throughput over global analyses. We show that immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) in H929 multiple myeloma (MM) cancer cells led to the discovery of a rare and unexpected BCR-ABL fusion, informing a therapeutic intervention using imatinib (Gleevec). BCR-ABL is the driving mutation in chronic myeloid leukemia (CML) and is uncommon to other cancers. Three different IP-MS experiments central to cell signaling pathways were sufficient to discover a BCR-ABL fusion in H929 cells: phosphotyrosine (pY) peptide IP, p85 regulatory subunit of phosphoinositide-3-kinase (PI3K) IP, and the GRB2 adaptor IP. The pY peptides inform tyrosine kinase activity, p85 IP informs the activating adaptors and receptor tyrosine kinases (RTKs) involved in AKT activation and GRB2 IP identifies RTKs and adaptors leading to ERK activation. Integration of the bait-prey data from the three separate experiments identified the BCR-ABL protein complex, which was confirmed by biochemistry, cytogenetic methods, and DNA sequencing revealed the e14a2 fusion transcript. The tyrosine phosphatase SHP2 and the GAB2 adaptor protein, important for MAPK signaling, were common to all three IP-MS experiments. The comparative treatment of tyrosine kinase inhibitor (TKI) drugs revealed only imatinib, the standard of care in CML, was inhibitory to BCR-ABL leading to down-regulation of pERK and pS6K and inhibiting cell proliferation. These data suggest a model for directed proteomics from patient tumor samples for selecting the appropriate TKI drug(s) based on IP and LC-MS/MS. The data also suggest that MM patients, in addition to CML patients, may benefit from BCR-ABL diagnostic screening.

  16. Combining the ABL1 kinase inhibitor ponatinib and the histone deacetylase inhibitor vorinostat: a potential treatment for BCR-ABL-positive leukemia.

    Science.gov (United States)

    Okabe, Seiichi; Tauchi, Tetsuzo; Kimura, Shinya; Maekawa, Taira; Kitahara, Toshihiko; Tanaka, Yoko; Ohyashiki, Kazuma

    2014-01-01

    Resistance to imatinib (Gleevec®) in cancer cells is frequently because of acquired point mutations in the kinase domain of BCR-ABL. Ponatinib, also known as AP24534, is an oral multi-targeted tyrosine kinase inhibitor (TKI), and it has been investigated in a pivotal phase 2 clinical trial. The histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) has been evaluated for its significant clinical activity in hematological malignancies. Thus, treatments combining ABL TKIs with additional drugs may be a promising strategy in the treatment of leukemia. In the current study, we analyzed the efficacy of ponatinib and vorinostat treatment by using BCR-ABL-positive cell lines. Treatment with ponatinib for 72 h inhibited cell growth and induced apoptosis in K562 cells in a dose-dependent manner. We found that ponatinib potently inhibited the growth of Ba/F3 cells ectopically expressing BCR-ABL T315I mutation. Upon BCR-ABL phosphorylation, Crk-L was decreased, and poly (ADP-ribose) polymerase (PARP) was activated in a dose-dependent manner. Combined treatment of Ba/F3 T315I mutant cells with vorinostat and ponatinib resulted in significantly increased cytotoxicity. Additionally, the intracellular signaling of ponatinib and vorinostat was examined. Caspase 3 and PARP activation increased after combination treatment with ponatinib and vorinostat. Moreover, an increase in the phosphorylation levels of γH2A.X was observed. Previously established ponatinib-resistant Ba/F3 cells were also resistant to imatinib, nilotinib, and dasatinib. We investigated the difference in the efficacy of ponatinib and vorinostat by using ponatinib-resistant Ba/F3 cells. Combined treatment of ponatinib-resistant cells with ponatinib and vorinostat caused a significant increase in cytotoxicity. Thus, combined administration of ponatinib and vorinostat may be a powerful strategy against BCR-ABL mutant cells and could enhance the cytotoxic effects of ponatinib in those BCR

  17. Susceptibility of Aedes aegypti pupae to neem seed kernal extracts ...

    African Journals Online (AJOL)

    Azadirachta indica) seed kernel extracts (NSKE) on Aedes aegypti. The neem seed kernel powder was sequentially extracted with hexane, benzene, ethyl acetate, acetone, DMSO, 2-propanol, ethanol, methanol and dstiledwater.

  18. Bcr-aBL1 kinase domain mutation analysis in chronic myeloid leukaemia patients with suboptimal response to tyrosine kinase inhibitors

    Directory of Open Access Journals (Sweden)

    Tadej Pajič

    2012-12-01

    Conclusions: It seems that the BCR-ABl1 mutations are rare in patients who do not achieve a MMR by 18 months or more or who have lost MMR. The T315I mutation detected in one patient in our cohort of CML patients indicates that the BCR-ABL1 mutation analysis could be recommended in these cases. The silent mutation detected did not lead to amino acid change, however, it is listed in major single nucleotide polymorphisms databases (SNP, rs2227985. The role of the SNP in the resistance to TKIs is not clear.

  19. A case of acute myeloid leukemia with e6a2 BCR-ABL fusion transcript acquired after progressing from chronic myelomonocytic leukemia

    OpenAIRE

    Jinjuan Yao; Dan Douer; Lu Wang; Maria E. Arcila; Khedoudja Nafa; April Chiu

    2017-01-01

    Philadelphia (Ph) chromosome is a cytogenetic hallmark of chronic myeloid leukemia (CML). Most patients with CML harbor either the e13a2 or e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. We report a patient with chronic myelomonocytic leukemia (CMML), initially Ph chromosome negative at presentation, with rapid disease progression to acute myeloid leukemia (AML) and appearance of Ph chromosome and BCR-ABL e6a2, a very uncommon fusion trans...

  20. MEK inhibition potentiates the antitumor effect of Arsenic Trioxide in Bcr-Abl+ Imatinib-resistant Chronic Myeloid Leukemia cells: preclinical in vitro and in vivo study

    OpenAIRE

    Mazzera, Laura

    2014-01-01

    La Leucemia Mieloide Cronica (LMC) è una malattia caratterizzata dalla presenza di una specifica anormalità cromosomica, il cromosoma Philadelphia, codificante per una proteina di fusione di peso molecolare 210 Kd (p210) chiamata Bcr-Abl, che è una tirosin-chinasi sempre attiva. Il farmaco d’elezione per il trattamento di questa patologia è il tirosin-chinasi inibitore (TKI) Imatinib (Gleevec) che riduce l'attività di Bcr-Abl. L’utilizzo dell’Imatinib in clinica è però limitato dall’insorgenz...

  1. Coexistence of p210BCR-ABLand CBFβ-MYH11 fusion genes in myeloid leukemia: A report of 4 cases.

    Science.gov (United States)

    Wang, Yuan-Yuan; Ding, Wen-Jing; Jiang, Feng; Chen, Zi-Xing; Cen, Jian-Nong; Qi, Xiao-Fei; Liang, Jian-Ying; Liu, Dan-Dan; Pan, Jin-Lan; Chen, Su-Ning

    2017-11-01

    Numerous acquired molecular and cytogenetic abnormalities are strongly associated with hematological malignancies. The breakpoint cluster region-ABL proto-oncogene 1 ( BCR-ABL ) rearrangement leads to a p210 chimeric protein in typical chronic myeloid leukemia (CML), whereas 17-25% of patients with acute lymphocytic leukemia and 0.9-3% patients with de novo acute myeloid leukemia (AML) carry a p190 BCR-ABL fusion protein. Cases of patients with AML/CML carrying two specific primary molecular changes, BCR-ABL and core binding factor-β-myosin heavy chain 11 ( CBFβ-MYH11 ) fusion genes have been rarely reported. The present study aimed to understand the nature and mechanism of this particular type of leukemia through case reports and literature review. A total of four patients who were diagnosed as AML/CML with BCR-ABL and CBFβ-MYH11 fusion genes in the First Affiliated Hospital of Soochow University (Suzhou, China) between January 2004 and December 2012 were examined. Morphological analysis of bone marrow cells, flow cytometry, quantitative polymerase chain reaction of p 210BCR-ABL and CBFβ-MYH11 transcripts as well as cytogenetic and fluorescence in situ hybridization analyses were performed. A total of 4 patients who exhibited fusion of p 210BCR-ABL and CBFβ-MYH11 were identified. A single patient (case 1) was first diagnosed CML-acute phase (AP), which progressed rapidly to CML-blast crisis (BC), and three patients (cases 2, 3 and 4) were diagnosed with AML with bone marrow eosinophilia at first presentation with no evidence of previous onset of CML. All cases achieved remission following conventional chemotherapy/hematological stem cell transplantation combined with the inhibitor of tyrosine kinase (TKI) maintenance therapy. The patients with CML carrying and expressing BCR-ABL and CBFβ-MYH11 fusion genes appeared more likely to rapidly progress to AP or BC. Therefore, the product of the CBFβ-MYH11 fusion gene may serve an important role in the

  2. Evaluation of the accessibility of CCA metals in liquefied CCA-treated wood sludge for recovery and reuse

    Science.gov (United States)

    Hui Pan; Todd F. Shupe; Chung-Yun Hse

    2009-01-01

    CCA-treated wood was liquefied with polyethylene glycol/glycerin and sulfuric acid. The heavy metals were precipitated by Ca(OH)2 from liquefied CCA-treated wood. The original CCA-treated wood and precipitated wood sludge were fractionated by a modified BCR (Community Bureau of Reference) sequential extraction procedure. The purpose of the BCR...

  3. Trial Sequential Methods for Meta-Analysis

    Science.gov (United States)

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  4. Sequential association rules in atonal music

    NARCIS (Netherlands)

    Honingh, A.; Weyde, T.; Conklin, D.; Chew, E.; Childs, A.; Chuan, C.-H.

    2009-01-01

    This paper describes a preliminary study on the structure of atonal music. In the same way as sequential association rules of chords can be found in tonal music, sequential association rules of pitch class set categories can be found in atonal music. It has been noted before that certain pitch class

  5. Multi-agent sequential hypothesis testing

    KAUST Repository

    Kim, Kwang-Ki K.

    2014-12-15

    This paper considers multi-agent sequential hypothesis testing and presents a framework for strategic learning in sequential games with explicit consideration of both temporal and spatial coordination. The associated Bayes risk functions explicitly incorporate costs of taking private/public measurements, costs of time-difference and disagreement in actions of agents, and costs of false declaration/choices in the sequential hypothesis testing. The corresponding sequential decision processes have well-defined value functions with respect to (a) the belief states for the case of conditional independent private noisy measurements that are also assumed to be independent identically distributed over time, and (b) the information states for the case of correlated private noisy measurements. A sequential investment game of strategic coordination and delay is also discussed as an application of the proposed strategic learning rules.

  6. Preliminary validation of a sequential fractionation method to study phosphorus chemistry in a calcareous soil.

    Science.gov (United States)

    Audette, Yuki; O'Halloran, Ivan P; Evans, Les J; Voroney, R Paul

    2016-06-01

    A sequential fractionation method proposed by Jiang and Gu (1989) distinguished three types of calcium phosphates (Ca-P) according to their different plant availabilities. Three extractants, NaHCO3, NH4Ac, and H2SO4 were used to extract Ca2-P, Ca8-P, and Ca10-P types, respectively, from soil. This sequential fractionation method was tested and modified for analyzing the P chemistry of a calcareous soil. The solubility test and the model diagrams of the stability of the major Ca-P minerals showed that NaHCO3 was able to extract brushite (Ca2-P type), and NH4Ac extracted brushite and β-tricalcium P (Ca8-P type) as well as hydroxyapatite (Ca10-P type). Therefore the P forms targeted by extraction with NH4Ac should include both Ca8-and Ca10-P types. The sum of the P extracted by all extractants in the sequential fractionation method in the calcareous soil was in agreement with the total P measured by the perchloric acid digestion method. A proportion of organic P measured by the sequential fractionation method was in agreement with the result from solution (31)P NMR spectroscopy. This study showed that the modified sequential fractionation method and its target P forms would be useful for quantifying and characterizing inorganic and organic P in a calcareous soil, even though it should be used in combination with other techniques, such as solution (31)P NMR spectroscopy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Human visual system automatically represents large-scale sequential regularities.

    Science.gov (United States)

    Kimura, Motohiro; Widmann, Andreas; Schröger, Erich

    2010-03-04

    Our brain recordings reveal that large-scale sequential regularities defined across non-adjacent stimuli can be automatically represented in visual sensory memory. To show that, we adopted an auditory paradigm developed by Sussman, E., Ritter, W., and Vaughan, H. G. Jr. (1998). Predictability of stimulus deviance and the mismatch negativity. NeuroReport, 9, 4167-4170, Sussman, E., and Gumenyuk, V. (2005). Organization of sequential sounds in auditory memory. NeuroReport, 16, 1519-1523 to the visual domain by presenting task-irrelevant infrequent luminance-deviant stimuli (D, 20%) inserted among task-irrelevant frequent stimuli being of standard luminance (S, 80%) in randomized (randomized condition, SSSDSSSSSDSSSSD...) and fixed manners (fixed condition, SSSSDSSSSDSSSSD...). Comparing the visual mismatch negativity (visual MMN), an event-related brain potential (ERP) index of memory-mismatch processes in human visual sensory system, revealed that visual MMN elicited by deviant stimuli was reduced in the fixed compared to the randomized condition. Thus, the large-scale sequential regularity being present in the fixed condition (SSSSD) must have been represented in visual sensory memory. Interestingly, this effect did not occur in conditions with stimulus-onset asynchronies (SOAs) of 480 and 800 ms but was confined to the 160-ms SOA condition supporting the hypothesis that large-scale regularity extraction was based on perceptual grouping of the five successive stimuli defining the regularity. 2010 Elsevier B.V. All rights reserved.

  8. Simulation and sequential dynamical systems

    Energy Technology Data Exchange (ETDEWEB)

    Mortveit, H.S.; Reidys, C.M.

    1999-06-01

    Computer simulations have a generic structure. Motivated by this the authors present a new class of discrete dynamical systems that captures this structure in a mathematically precise way. This class of systems consists of (1) a loopfree graph {Upsilon} with vertex set {l_brace}1,2,{hor_ellipsis},n{r_brace} where each vertex has a binary state, (2) a vertex labeled set of functions (F{sub i,{Upsilon}}:F{sub 2}{sup n} {yields} F{sub 2}{sup n}){sub i} and (3) a permutation {pi} {element_of} S{sub n}. The function F{sub i,{Upsilon}} updates the state of vertex i as a function of the states of vertex i and its {Upsilon}-neighbors and leaves the states of all other vertices fixed. The permutation {pi} represents the update ordering, i.e., the order in which the functions F{sub i,{Upsilon}} are applied. By composing the functions F{sub i,{Upsilon}} in the order given by {pi} one obtains the dynamical system (equation given in paper), which the authors refer to as a sequential dynamical system, or SDS for short. The authors will present bounds for the number of functionally different systems and for the number of nonisomorphic digraphs {Gamma}[F{sub {Upsilon}},{pi}] that can be obtained by varying the update order and applications of these to specific graphs and graph classes.

  9. Sequential provisional implant prosthodontics therapy.

    Science.gov (United States)

    Zinner, Ira D; Markovits, Stanley; Jansen, Curtis E; Reid, Patrick E; Schnader, Yale E; Shapiro, Herbert J

    2012-01-01

    The fabrication and long-term use of first- and second-stage provisional implant prostheses is critical to create a favorable prognosis for function and esthetics of a fixed-implant supported prosthesis. The fixed metal and acrylic resin cemented first-stage prosthesis, as reviewed in Part I, is needed for prevention of adjacent and opposing tooth movement, pressure on the implant site as well as protection to avoid micromovement of the freshly placed implant body. The second-stage prosthesis, reviewed in Part II, should be used following implant uncovering and abutment installation. The patient wears this provisional prosthesis until maturation of the bone and healing of soft tissues. The second-stage provisional prosthesis is also a fail-safe mechanism for possible early implant failures and also can be used with late failures and/or for the necessity to repair the definitive prosthesis. In addition, the screw-retained provisional prosthesis is used if and when an implant requires removal or other implants are to be placed as in a sequential approach. The creation and use of both first- and second-stage provisional prostheses involve a restorative dentist, dental technician, surgeon, and patient to work as a team. If the dentist alone cannot do diagnosis and treatment planning, surgery, and laboratory techniques, he or she needs help by employing the expertise of a surgeon and a laboratory technician. This team approach is essential for optimum results.

  10. Multilevel sequential Monte Carlo samplers

    KAUST Repository

    Beskos, Alexandros

    2016-08-29

    In this article we consider the approximation of expectations w.r.t. probability distributions associated to the solution of partial differential equations (PDEs); this scenario appears routinely in Bayesian inverse problems. In practice, one often has to solve the associated PDE numerically, using, for instance finite element methods which depend on the step-size level . hL. In addition, the expectation cannot be computed analytically and one often resorts to Monte Carlo methods. In the context of this problem, it is known that the introduction of the multilevel Monte Carlo (MLMC) method can reduce the amount of computational effort to estimate expectations, for a given level of error. This is achieved via a telescoping identity associated to a Monte Carlo approximation of a sequence of probability distributions with discretization levels . ∞>h0>h1⋯>hL. In many practical problems of interest, one cannot achieve an i.i.d. sampling of the associated sequence and a sequential Monte Carlo (SMC) version of the MLMC method is introduced to deal with this problem. It is shown that under appropriate assumptions, the attractive property of a reduction of the amount of computational effort to estimate expectations, for a given level of error, can be maintained within the SMC context. That is, relative to exact sampling and Monte Carlo for the distribution at the finest level . hL. The approach is numerically illustrated on a Bayesian inverse problem. © 2016 Elsevier B.V.

  11. Frequency of the minor BCR-ABL (e1;a2 transcript oncogene in a Mexican population with adult acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    I. Olarte-Carrillo

    2015-07-01

    Conclusion: Prevalence of BCR-ABL expression by RT-PCR has not previously been reported in Mexico. Our laboratory found a higher prevalence than that reported in Latin-American series, but lower than that reported for the European population.

  12. Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia

    Directory of Open Access Journals (Sweden)

    Sarah L. McCarron

    2013-01-01

    Full Text Available A minority of chronic myeloid leukaemia (CML patients express variant transcripts of which the e19a2 BCR-ABL1 fusion is the most common. Instances of tyrosine kinase inhibitor (TKI resistance in e19a2 BCR-ABL1 CML patients have rarely been reported. A case of e19a2 BCR-ABL1 CML is described in whom imatinib resistance, associated with a Q252H ABL1 kinase domain mutation, became apparent soon after initiation of TKI therapy. The patient rapidly transformed to myeloid blast crisis (BC with considerable bone marrow fibrosis and no significant molecular response to a second generation TKI. The clinical course was complicated by comorbidities with the patient rapidly succumbing to advanced disease. This scenario of Q252H-associated TKI resistance with rapid BC transformation has not been previously documented in e19a2 BCR-ABL1 CML. This case highlights the considerable challenges remaining in the management of TKI-resistant BC CML, particularly in the elderly patient.

  13. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni

    2009-01-01

    The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP...

  14. The BCR-ABLT315I mutation compromises survival in chronic phase chronic myelogenous leukemia patients resistant to tyrosine kinase inhibitors, in a matched pair analysis

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Ibrahim, Amr R; Soverini, Simona

    2013-01-01

    The BCR-ABL T315I mutation confers resistance to currently licensed tyrosine kinase inhibitors in chronic myelogenous leukemia. However, the impact of this mutation on survival in early stages of disease, in chronic phase, has never been detailed. Using matched pair analysis, a cohort of 64...

  15. Photodynamic treatment (ALA-PDT) suppresses the expression of the oncogenic Bcr-Abl kinase and affects the cytoskeleton organization in K562 cells

    Czech Academy of Sciences Publication Activity Database

    Pluskalová, M.; Pešlová, G.; Grebeňová, D.; Halada, Petr; Hrkal, Z.

    2006-01-01

    Roč. 83, - (2006), s. 205-212 ISSN 1011-1344 R&D Projects: GA MZd NL7681 Institutional research plan: CEZ:AV0Z50200510 Keywords : k562 * bcr -abl * photodynamic treatment Subject RIV: EE - Microbiology, Virology Impact factor: 1.909, year: 2006

  16. BCR CDR3 length distributions differ between blood and spleen and between old and young patients, and TCR distributions can be used to detect myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Pickman, Yishai; Mehr, Ramit; Dunn-Walters, Deborah

    2013-01-01

    Complementarity-determining region 3 (CDR3) is the most hyper-variable region in B cell receptor (BCR) and T cell receptor (TCR) genes, and the most critical structure in antigen recognition and thereby in determining the fates of developing and responding lymphocytes. There are millions of different TCR Vβ chain or BCR heavy chain CDR3 sequences in human blood. Even now, when high-throughput sequencing becomes widely used, CDR3 length distributions (also called spectratypes) are still a much quicker and cheaper method of assessing repertoire diversity. However, distribution complexity and the large amount of information per sample (e.g. 32 distributions of the TCRα chain, and 24 of TCRβ) calls for the use of machine learning tools for full exploration. We have examined the ability of supervised machine learning, which uses computational models to find hidden patterns in predefined biological groups, to analyze CDR3 length distributions from various sources, and distinguish between experimental groups. We found that (a) splenic BCR CDR3 length distributions are characterized by low standard deviations and few local maxima, compared to peripheral blood distributions; (b) healthy elderly people's BCR CDR3 length distributions can be distinguished from those of the young; and (c) a machine learning model based on TCR CDR3 distribution features can detect myelodysplastic syndrome with approximately 93% accuracy. Overall, we demonstrate that using supervised machine learning methods can contribute to our understanding of lymphocyte repertoire diversity. (paper)

  17. BCR-ABL transcripts are early predictors for hematological relapse in chronic myeloid leukemia after hematopoietic cell transplantation with reduced intensity conditioning

    NARCIS (Netherlands)

    Lange, T; Deininger, M; Brand, R; Hegenbart, U; Al-Ali, H; Krahl, R; Poenisch, W; Uharek, L; Leiblein, S; Gentilini, C; Petersdorf, E; Storb, RF; Niederwieser, D

    Kinetics of BCR-ABL transcript elimination and its prognostic implications on relapse were analyzed in patients with chronic myeloid leukemia (CML) after reduced intensity hematopoietic cell transplantation (HCT). In all, 19 CML patients were conditioned with 2Gy total-body irradiation in

  18. Sr and Pb isotopic composition of five USGS glasses (BHVO-2G, BIR-1G, BCR-2G, TB-1G, NKT-1G)

    NARCIS (Netherlands)

    Elburg, M.A.; Vroon, P.Z.; van der Wagt, R.A.C.A.; Tchalikian, A.

    2005-01-01

    Sr isotopic compositions and Rb/Sr ratios of three USGS glasses (BHVO-2G, BIR-1G, BCR-2G) are identical to those of the original USGS reference materials. NKT-1G and TB-1G give values of 0.70351 and 0.70558, respectively. Pb isotopic ratios were measured by the standard-sample bracketing technique

  19. [Construction of Eukaryotic Expression Vector of siRNA Specific for BCR/ABL Fusion Gene and Its Effects on K562 Cells].

    Science.gov (United States)

    Li, Ming; Wang, Bao-Lin; Wang, Li-Na; Xi, Ya-Ming

    2016-12-01

    To construct eukaryotic expression vector of siRNA specific for BCR/ABL and to investigate the effect of recombinant plasmid on BCR/ABL and P210 protein expression in K562 cells. siRNA(small interfering RNA)was designed according to the Tuschl's principle of Ai-based medicine, and was converted into cDNA coding expression of shRNA(small hairpin RNAs)of siRNA for BCR/ABL fusion gene. The cDNA was synthesized and inserted into plasmid pTER. The pTER117 and pTER363 of recombinant plasmid being eukaryotic expression vector was controlled by the H1 promoter of RNA polymerase III, and identified by the restriction map and the sequence analysis. The recombinant plasmid did not only have the screening resisting antibiotics, its expression but also are induced by tetracycline (tet). After steadily transfection into K562 cells by Lipofectamine, their positive mono-cell clones being resistant to Zeocin were isolated. TaqMan real-time quantitative RT-PCR (RQ-PCR) and Western blot respectively detected expression of BCR/ABL mRNA and P210 protein. Trypaum blue dying was used to analyze the proliferation of K562 cells. Cell apoptosis was observed by flow cytometer. the recombinant plasmid was steadily transfected into K562 cells by Lipofectamine 2000, Their positive mono-cell clones being resistant to Zeocin were isolated. The proliferation of K562 cells were remarkably inhibited by the recombinant plasmid induced gene expression by tetracycline. Tetracycline induced its expression for 48 h and 72 h. pTER117, pTER363 decreased the mRNA level of BCR/ABL 90%, 82% and 91.5%, 84%, respectively, P210 protein were almost measured in K562 cells. FCM analysis showed that the recombinant plasmid induced apoptosis in K562 cells, the apoptosis rate were respectively 34.4%, 58.1% in K562 cells treated by pTER117 for 48 h and 72 h, apoptosis rate were 31.8%, 54.6% by pTER363, but the control groups did not show these effects on K562 cells. The siRNA eukaryotic expression vector against BCR

  20. Sensitive detection of pre-existing BCR-ABL kinase domain mutations in CD34+ cells of newly diagnosed chronic-phase chronic myeloid leukemia patients is associated with imatinib resistance: implications in the post-imatinib era.

    Directory of Open Access Journals (Sweden)

    Zafar Iqbal

    Full Text Available BACKGROUND: BCR-ABL kinase domain mutations are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CML patients. Recent studies indicate the presence of pre-existing BCR-ABL mutations in a higher percentage of CML patients when CD34+ stem/progenitor cells are investigated using sensitive techniques, and these mutations are associated with imatinib resistance and disease progression. However, such studies were limited to smaller number of patients. METHODS: We investigated BCR-ABL kinase domain mutations in CD34+ cells from 100 chronic-phase CML patients by multiplex allele-specific PCR and sequencing at diagnosis. Mutations were re-investigated upon manifestation of imatinib resistance using allele-specific PCR and direct sequencing of BCR-ABL kinase domain. RESULTS: Pre-existing BCR-ABL mutations were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48, all patients with pre-existing BCR-ABL mutations exhibited imatinib resistance. Of the 68 patients without pre-existing BCR-ABL mutations, 24 developed imatinib resistance; allele-specific PCR and BCR-ABL kinase domain sequencing detected mutations in 22 of these patients. All 32 patients with pre-existing BCR-ABL mutations had the same mutations after manifestation of imatinib-resistance. In imatinib-resistant patients without pre-existing BCR-ABL mutations, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients except T315I and Y253F mutations responded to imatinib dose escalation. CONCLUSION: Pre-existing BCR-ABL mutations can be detected in a substantial number of chronic-phase CML patients by sensitive allele-specific PCR technique using CD34+ cells. These mutations are associated with imatinib resistance if affecting drug binding directly or indirectly. After the recent approval of nilotinib, dasatinib, bosutinib and ponatinib for treatment of chronic myeloid

  1. Group separation of rare earth elements by liquid-liquid extraction for the neutron activation analysis of silicate rocks

    International Nuclear Information System (INIS)

    Wyttenbach, A.; Bajo, S.; Tobler, L.

    1983-01-01

    Rare earth elements are isolated as a group from neutron activated rock samples by a new radiochemical procedure based on extraction with thenoyltrifluoracetone/phenanthroline in CHCl 3 . The procedure consists of three extraction steps, obviates the use of inactive carriers and gives practically quantitative chemical yields, thereby avoiding fractionation of the individual rare earths. Details of the dissolution, chemical separations. and counting procedure are given together with an analysis of BCR-1. (author)

  2. Identification of Genes Upregulated by the Transcription Factor Bcr1 That Are Involved in Impermeability, Impenetrability, and Drug Resistance of Candida albicans a/α Biofilms

    Science.gov (United States)

    Srikantha, Thyagarajan; Daniels, Karla J.; Pujol, Claude; Kim, Elena

    2013-01-01

    Candida albicans forms two types of biofilm, depending upon the configuration of the mating type locus. Although architecturally similar, a/α biofilms are impermeable, impenetrable, and drug resistant, whereas a/a and α/α biofilms lack these traits. The difference appears to be the result of an alternative matrix. Overexpression in a/a cells of BCR1, a master regulator of the a/α matrix, conferred impermeability, impenetrability, and drug resistance to a/a biofilms. Deletion of BCR1 in a/α cells resulted in the loss of these a/α-specific biofilm traits. Using BCR1 overexpression in a/a cells, we screened 107 genes of interest and identified 8 that were upregulated by Bcr1. When each was overexpressed in a/a biofilms, the three a/α traits were partially conferred, and when each was deleted in a/α cells, the traits were partially lost. Five of the eight genes have been implicated in iron homeostasis, and six encode proteins that are either in the wall or plasma membrane or secreted. All six possess sites for O-linked and N-linked glycosylation that, like glycosylphosphatidylinositol (GPI) anchors, can cross-link to the wall and matrix, suggesting that they may exert a structural role in conferring impermeability, impenetrability, and drug resistance, in addition to their physiological functions. The fact that in a screen of 107 genes, all 8 of the Bcr1-upregulated genes identified play a role in impermeability, impenetrability, and drug resistance suggests that the formation of the a/α matrix is highly complex and involves a larger number of genes than the initial ones identified here. PMID:23563485

  3. [Construction of genetically modified dendritic cell vaccine expressing bcr/abl fusion gene and inducing specific cytotoxic T lymphocytes to kill K562 cells in vitro].

    Science.gov (United States)

    Wang, Wen-Wen; Huang, Ren-Wei; Hu, Yuan; Li, Xu-Dong; Wang, Dong-Ning; He, Yi; Liu, Jia-Jun

    2009-06-01

    Specific immunological effect mediated by T lymphocytes plays an important role in treating chronic myelocytic leukemia (CML). Dendritic cells (DCs)-based immunotherapy has become popular in treating tumors. This study was to construct DC vaccines by transducing with replication-defective recombinant adenoviruses expressing bcr/abl fusion gene of CML, observe the lethal effects of specific cytotoxic T lymphocytes (CTLs) triggered by genetically modified DC vaccines expressing bcr/abl fusion gene against K562 cells in vitro. DNA fragment of bcr/abl fusion gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) to construct a recombinant adenovirus vector and produce recombinant adenoviruses. DCs were induced from peripheral blood monocytes in vitro, and transfected with recombinant adenoviruses or pulsed with peptide to induce specific CTLs. The lethal effect of CTLs against leukemic K562 cells in vitro was observed. We successfully constructed the replication-defective recombinant adenoviral vector expressing bcr/abl fusion gene. The recombinant adenoviruses we produced had a high virus titer of 2.0 x 10(10) pfu/mL. Transfection efficiency of DCs in vitro was 50%-60%. DC vaccines expressing bcr/abl fusion gene were successfully prepared and used to induce specific CTLs. With effector:target cell ratios of 40:1 and 20:1, the killing rates of K562 cells by CTLs were (47.6+/-4.7)% and (47.5+/-1.6)% in genetically modified DCs group, (25.8+/-4.4)% and (24.6+/-6.3)% in peptide-pulsed DCs group, and were (5.7+/-1.3)% and (4.5+/-1.6)% in control DCs group. The differences between every two groups were significant (all Pfusion gene has a stronger contribution than peptide-pulsed DCs in triggering specific CTLs against K562 cells.

  4. PLK1 inhibitors synergistically potentiate HDAC inhibitor lethality in imatinib mesylate-sensitive or -resistant BCR/ABL+ leukemia cells in vitro and in vivo.

    Science.gov (United States)

    Dasmahapatra, Girija; Patel, Hiral; Nguyen, Tri; Attkisson, Elisa; Grant, Steven

    2013-01-15

    To determine whether Polo-like kinase 1 (PLK1) inhibitors (e.g., BI2536) and histone deacetylase (HDAC) inhibitors (e.g., vorinostat) interact synergistically in the BCR/ABL(+) leukemia cells sensitive or resistant to imatinib mesylate (IM) in vitro and in vivo. K562 and LAMA84 cells sensitive or resistant to imatinib mesylate and primary CML cells were exposed to BI2536 and vorinostat. Effects on cell viability and signaling pathways were determined using flow cytometry, Western blotting, and gene transfection. K562 and BV173/E255K animal models were used to test in vivo efficacy. Cotreatment with BI2536 and vorinostat synergistically induced cell death in parental or imatinib mesylate-resistant BCR/ABL(+) cells and primary CD34(+) bone marrow cells but was minimally toxic to normal cells. BI2536/vorinostat cotreatment triggered pronounced mitochondrial dysfunction, inhibition of p-BCR/ABL, caspase activation, PARP cleavage, reactive oxygen species (ROS) generation, and DNA damage (manifest by increased expression of γH2A.X, p-ATM, p-ATR), events attenuated by the antioxidant TBAP. PLK1 short hairpin RNA (shRNA) knockdown significantly increased HDACI lethality, whereas HDAC1-3 shRNA knockdown reciprocally increased BI2536-induced apoptosis. Genetic interruption of the DNA damage linker H1.2 partially but significantly reduced PLK1/HDAC inhibitor-mediated cell death, suggesting a functional role for DNA damage in lethality. Finally, BI2536/vorinostat cotreatment dramatically reduced tumor growth in both subcutaneous and systemic BCR/ABL(+) leukemia xenograft models and significantly enhanced animal survival. These findings suggest that concomitant PLK1 and HDAC inhibition is active against imatinib mesylate-sensitive or refractory CML and ALL cells both in vitro and in vivo and that this strategy warrants further evaluation in the setting of BCR/ABL(+) leukemias. ©2012 AACR.

  5. Stationary Anonymous Sequential Games with Undiscounted Rewards.

    Science.gov (United States)

    Więcek, Piotr; Altman, Eitan

    Stationary anonymous sequential games with undiscounted rewards are a special class of games that combine features from both population games (infinitely many players) with stochastic games. We extend the theory for these games to the cases of total expected reward as well as to the expected average reward. We show that in the anonymous sequential game equilibria correspond to the limits of those of related finite population games as the number of players grows to infinity. We provide examples to illustrate our results.

  6. Quantification of BCR-ABL transcripts in peripheral blood cells and ...

    African Journals Online (AJOL)

    The disease status of CML patients was categorized according to the European Leukemia Net [10]. RNA extraction procedure,. Peripheral blood samples of study subjects were collected in ethylenediaminetetraacetate (EDTA) tubes. Plasma was separated from blood cells by centrifugation at 1200 x g for 10 minutes. RNA.

  7. Conventional and fluorescence in situ hybridization analysis of three-way complex BCR-ABL rearrangement in a chronic myeloid leukemia patient

    Directory of Open Access Journals (Sweden)

    Ganguly Bani

    2007-01-01

    Full Text Available Chromosomal analysis was carried out in bone marrow sample of an 11-year-old girl suspected of myeloproliferative disorder. Conventional G-banding study detected a complex three-way translocation involving 7, 9 and 22, which has resulted in the formation of a variant Philadelphia chromosome causing rearrangement of abl and bcr genes in 87% cells. Fluorescence in situ hybridization (FISH confirmed the fusion of bcr-abl oncogene. Thus the bone marrow karyotype was observed as 46,XX (13% / 46,XX,t(7;9;22(q11;q34;q11 (87%. Hyperdiploidy was present in two cells. In this study, both conventional cytogenetic and FISH diagnosis proved to be significant to identify the variant nature of the Philadelphia chromosome and hyperdiploid condition for introduction of a suitable treatment regimen and estimation of life expectancy of the young girl.

  8. BCR-ABL1-positive chronic myeloid leukemia emerging in a patient with secondary myelofibrosis harboring the JAK2-V617F mutation.

    Science.gov (United States)

    Amemiya, Ayae; Ito, Yoshikazu; Ishibashi, Yasunori; Saito, Yuu; Katagiri, Seiichiro; Suguro, Tamiko; Asano, Michiyo; Yoshizawa, Seiichiro; Akahane, Daigo; Tanaka, Yuko; Fujimoto, Hiroaki; Okabe, Seiichi; Gotoh, Moritaka; Tauchi, Tetsuzo; Ohyashiki, Kazuma

    2017-01-01

    A 53-year-old woman with a 27-year history of myeloproliferative neoplasms came to our hospital because of a marked white blood cell count increase and progressive anemia. Clinical examination demonstrated positivity for BCR-ABL1 and JAK2-V617F mutations. She was given a diagnosis of chronic myeloid leukemia. Using the international scale, a molecular response (MR) 4.5 was achieved after treatment with dasatinib, despite the persistence of marked splenomegaly. The pathological findings of myelofibrosis were demonstrated by bone marrow biopsy. After stopping dasatinib administration for 4 years and 5 months, treatment with ruxolitinib was started. Five months later, the size of her spleen was reduced. We speculated that translocation of BCR-ABL1 might have occurred in a sub-clone of the JAK2-V617F mutated tumor clone.

  9. A novel BCR-ABL transcript e2a2 in a chronic myelogenous leukaemia patient with a duplicated Ph-chromosome and monosomy 7.

    Science.gov (United States)

    Leibundgut, E O; Jotterand, M; Rigamonti, V; Parlier, V; Mühlematter, D; Tobler, A; Solenthaler, M

    1999-09-01

    A novel BCR-ABL transcript was detected by multiplex RT-PCR in a patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukaemia (CML) in accelerated phase. Sequencing of the aberrant transcript revealed an in-frame e2a2 fusion that included a 9 basepairs insertion. Cytogenetic analysis showed t(9;22), an additional Ph chromosome and monosomy 7. The clinical course was dismal: therapy was poorly tolerated, and the patient died in blast crisis 10 months after diagnosis. These data support the association of additional Ph and monosomy 7 with poor prognosis and suggest that the novel e2a2 BCR-ABL transcript may be related to an aggressive clinical course.

  10. A stacked sequential learning method for investigator name recognition from web-based medical articles

    Science.gov (United States)

    Zhang, Xiaoli; Zou, Jie; Le, Daniel X.; Thoma, George

    2010-01-01

    "Investigator Names" is a newly required field in MEDLINE citations. It consists of personal names listed as members of corporate organizations in an article. Extracting investigator names automatically is necessary because of the increasing volume of articles reporting collaborative biomedical research in which a large number of investigators participate. In this paper, we present an SVM-based stacked sequential learning method in a novel application - recognizing named entities such as the first and last names of investigators from online medical journal articles. Stacked sequential learning is a meta-learning algorithm which can boost any base learner. It exploits contextual information by adding the predicted labels of the surrounding tokens as features. We apply this method to tag words in text paragraphs containing investigator names, and demonstrate that stacked sequential learning improves the performance of a nonsequential base learner such as an SVM classifier.

  11. Sequential decoding of intramuscular EMG signals via estimation of a Markov model.

    Science.gov (United States)

    Monsifrot, Jonathan; Le Carpentier, Eric; Aoustin, Yannick; Farina, Dario

    2014-09-01

    This paper addresses the sequential decoding of intramuscular single-channel electromyographic (EMG) signals to extract the activity of individual motor neurons. A hidden Markov model is derived from the physiological generation of the EMG signal. The EMG signal is described as a sum of several action potentials (wavelet) trains, embedded in noise. For each train, the time interval between wavelets is modeled by a process that parameters are linked to the muscular activity. The parameters of this process are estimated sequentially by a Bayes filter, along with the firing instants. The method was tested on some simulated signals and an experimental one, from which the rates of detection and classification of action potentials were above 95% with respect to the reference decomposition. The method works sequentially in time, and is the first to address the problem of intramuscular EMG decomposition online. It has potential applications for man-machine interfacing based on motor neuron activities.

  12. Passive Baited Sequential Filth Fly Trap.

    Science.gov (United States)

    Aldridge, Robert L; Britch, Seth C; Snelling, Melissa; Gutierez, Arturo; White, Gregory; Linthicum, Kenneth J

    2015-09-01

    Filth fly control measures may be optimized with a better understanding of fly population dynamics measured throughout the day. We describe the modification of a commercial motorized sequential mosquito trap to accept liquid odorous bait and leverage a classic inverted-cone design to passively confine flies in 8 modified collection bottles corresponding to 8 intervals. Efficacy trials in a hot-arid desert environment indicate no significant difference (P  =  0.896) between the modified sequential trap and a Rid-Max® fly trap.

  13. Asynchronous Operators of Sequential Logic Venjunction & Sequention

    CERN Document Server

    Vasyukevich, Vadim

    2011-01-01

    This book is dedicated to new mathematical instruments assigned for logical modeling of the memory of digital devices. The case in point is logic-dynamical operation named venjunction and venjunctive function as well as sequention and sequentional function. Venjunction and sequention operate within the framework of sequential logic. In a form of the corresponding equations, they organically fit analytical expressions of Boolean algebra. Thus, a sort of symbiosis is formed using elements of asynchronous sequential logic on the one hand and combinational logic on the other hand. So, asynchronous

  14. Double sequential defibrillation for refractory ventricular fibrillation.

    Science.gov (United States)

    El Tawil, Chady; Mrad, Sandra; Khishfe, Basem F

    2017-12-01

    A 54-year-old suffered from an out-of-hospital cardiac arrest. Compressions were started within minutes and the patient was in refractory ventricular fibrillation despite multiple asynchronized shocks and maximal doses of antiarrhythmic agents. Double sequential defibrillation was attempted with successful Return Of Spontaneous Circulation (ROSC) after a total of 61min of cardiac arrest. The patient was discharged home neurologically intact. Double sequential defibrillation could be a simple effective approach to patients with refractory ventricular fibrillation. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Conversion from Excel into Aleph sequential

    OpenAIRE

    Renaville, François; Thirion, Paul

    2009-01-01

    Libraries must sometimes load records that are not available to them in a bibliographic format standard (Marc21, Unimarc...): integration of the book database of an academic research center, list of new e-journals bought by the library... This can make the conversion procedure of the data to the Aleph sequential format quite hard. Sometimes the records are only available in Excel. This poster explains how to convert easily in a few steps an Excel file into Aleph sequential in order to load re...

  16. Heavy metals extraction from anaerobically digested sludge

    NARCIS (Netherlands)

    Marchioretto, M.M.; Bruning, H.; Loan, N.T.P.; Rulkens, W.H.

    2002-01-01

    This paper reports on the chemical extraction efficiency in the removal of heavy metals from sludge from an activated-sludge system, which receives as influent both industrial and municipal wastewater. Utilizing a series of chemical extractants in a sequential order comprised the first phase of the

  17. Philadelphia-positive acute lymphoblastic leukemia patients already harbor BCR-ABL kinase domain mutations at low levels at the time of diagnosis

    Science.gov (United States)

    Soverini, Simona; Vitale, Antonella; Poerio, Angela; Gnani, Alessandra; Colarossi, Sabrina; Iacobucci, Ilaria; Cimino, Giuseppe; Elia, Loredana; Lonetti, Annalisa; Vignetti, Marco; Paolini, Stefania; Meloni, Giovanna; di Maio, Valeria; Papayannidis, Cristina; Amabile, Marilina; Guarini, Anna; Baccarani, Michele; Martinelli, Giovanni; Foà, Robin

    2011-01-01

    Background In patients with Philadelphia-positive acute lymphoblastic leukemia, resistance to treatment with tyrosine kinase inhibitors is frequent and most often associated with the development of point mutations in the BCR-ABL kinase domain. We aimed to assess: (i) in how many patients BCR-ABL kinase domain mutations are already detectable at relatively low levels at the time of diagnosis, and (ii) whether mutation detection correlates with subsequent response to therapy. Design and Methods We retrospectively analyzed samples collected at diagnosis from 15 patients with Philadelphia-positive acute lymphoblastic leukemia who subsequently received tyrosine kinase inhibitor therapy (dasatinib) by cloning the BCR-ABL kinase domain in a bacterial vector and sequencing 200 independent clones per sample. Results Mutations at relatively low levels (2–4 clones out of 200) could be detected in all patients – eight who relapsed and seven who achieved persistent remission. Each patient had evidence of two to eight different mutations, the majority of which have never been reported in association with resistance to tyrosine kinase inhibitors. In two patients out of six who relapsed because of a mutation, the mutation (a T315I) was already detectable in a few clones at the time of diagnosis. On the other hand, a patient who was found to harbor an F317L mutation is in persistent remission on dasatinib. Conclusions Our results suggest that the BCR-ABL kinase domain is prone to randomly accumulate point mutations in Philadelphia-positive acute lymphoblastic leukemia, although the presence of these mutations in a relatively small leukemic subclone does not always preclude a primary response to tyrosine kinase inhibitors. PMID:21193419

  18. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Seymour, J F; Kim, D W; Rubin, E

    2014-01-01

    leukemia (ALL) with the T315I mutation. Adults with Ph+ chronic phase (CP)-, accelerated phase (AP)- or blast phase (BP)-CML, or ALL and documented BCR-ABL T315I mutation were treated with a 5-day continuous infusion of MK-0457 administered every 14 days at 40 mg/m(2)/h, 32 mg/m(2)/h or 24 mg/m(2)/h. Fifty...

  19. Contribution of nuclear analysis methods to the certification of BCR reference materials for non-metals in non-ferrous metals

    International Nuclear Information System (INIS)

    Pauwels, J.

    1979-01-01

    A number of reference materials for oxygen in different non-ferrous metals have been certified by BCR in the frame of a multidisciplinary Community project. The contribution of nuclear analysis methods is illustrated by several examples concerning the optimization of sample preparation techniques, the analysis of low and high oxygen non-ferrous metals and the extension of the program to other non-metals, especially nitrogen and carbon. (author)

  20. UV Differentially Induces Oxidative Stress, DNA Damage and Apoptosis in BCR-ABL1-Positive Cells Sensitive and Resistant to Imatinib

    Science.gov (United States)

    Synowiec, Ewelina; Hoser, Grazyna; Wojcik, Katarzyna; Pawlowska, Elzbieta; Skorski, Tomasz; Błasiak, Janusz

    2015-01-01

    Chronic myeloid leukemia (CML) cells express the active BCR-ABL1 protein, which has been targeted by imatinib in CML therapy, but resistance to this drug is an emerging problem. BCR-ABL1 induces endogenous oxidative stress promoting genomic instability and imatinib resistance. In the present work, we investigated the extent of oxidative stress, DNA damage, apoptosis and expression of apoptosis-related genes in BCR-ABL1 cells sensitive and resistant to imatinib. The resistance resulted either from the Y253H mutation in the BCR-ABL1 gene or incubation in increasing concentrations of imatinib (AR). UV irradiation at a dose rate of 0.12 J/(m2·s) induced more DNA damage detected by the T4 pyrimidine dimers glycosylase and hOGG1, recognizing oxidative modifications to DNA bases in imatinib-resistant than -sensitive cells. The resistant cells displayed also higher susceptibility to UV-induced apoptosis. These cells had lower native mitochondrial membrane potential than imatinib-sensitive cells, but UV-irradiation reversed that relationship. We observed a significant lowering of the expression of the succinate dehydrogenase (SDHB) gene, encoding a component of the complex II of the mitochondrial respiratory chain, which is involved in apoptosis sensing. Although detailed mechanism of imatinib resistance in AR cells in unknown, we detected the presence of the Y253H mutation in a fraction of these cells. In conclusion, imatinib-resistant cells may display a different extent of genome instability than their imatinib-sensitive counterparts, which may follow their different reactions to both endogenous and exogenous DNA-damaging factors, including DNA repair and apoptosis. PMID:26251899

  1. Frequency and clinical impact of ETV6/RUNX1, AF4-MLL, and BCR/ABL fusion genes on features of acute lymphoblastic leukemia at presentation.

    Science.gov (United States)

    Ajuba, I C; Madu, A J; Okocha, C; Ibegbulam, O G; Okpala, I; Nna, O E

    2016-01-01

    Variations in disease presentation and outcome of leukemia treatment has been associated with the presence of certain mutant genes. Three major translocations (ETV6-RUNX1, BCR-ABL, and AF4-MLL) in acute lymphoblastic leukemia (ALL) have been shown to affect treatment outcome. This study is aimed at assessing the relationship between these translocations and the presence of other indicators of disease severity (white cell count, hemoglobin concentration, platelet count, and hematocrit) in ALL. Forty chemotherapy naïve patients aged between 9 months and 54 years had their marrow samples analyzed for the prevalent mutations. Their clinical and laboratory details on presentation were also obtained. Abnormal genes detected were BCR/ABL1 major transcript in 5 (12.5%), ETV6/RUNX1 in 2 (5.0%), MLL/AF4 none and none of the patients had more than one fusion gene. There was no relationship between the presence of these fusion genes and the clinical and laboratory features of ALL. An association exists between the fusion genes and ethnic origin of the patients (P = 0.005). There is no significant association between the abnormal fusion genes detected and some laboratory features of prognostic importance, which include total white blood cell count (P = 0.416) and FAB subtype (P = 0.576). Presence of fusion the genes BCR/ABL1, ETV6/RUNX1, and MLL/AF4 does not have any impact on the clinical and laboratory features of ALL at presentation.

  2. A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells.

    Science.gov (United States)

    Rix, U; Remsing Rix, L L; Terker, A S; Fernbach, N V; Hantschel, O; Planyavsky, M; Breitwieser, F P; Herrmann, H; Colinge, J; Bennett, K L; Augustin, M; Till, J H; Heinrich, M C; Valent, P; Superti-Furga, G

    2010-01-01

    Resistance to the BCR-ABL tyrosine kinase inhibitor imatinib poses a pressing challenge in treating chronic myeloid leukemia (CML). This resistance is often caused by point mutations in the ABL kinase domain or by overexpression of LYN. The second-generation BCR-ABL inhibitor INNO-406 is known to inhibit most BCR-ABL mutants and LYN efficiently. Knowledge of its full target spectrum would provide the molecular basis for potential side effects or suggest novel therapeutic applications and possible combination therapies. We have performed an unbiased chemical proteomics native target profile of INNO-406 in CML cells combined with functional assays using 272 recombinant kinases thereby identifying several new INNO-406 targets. These include the kinases ZAK, DDR1/2 and various ephrin receptors. The oxidoreductase NQO2, inhibited by both imatinib and nilotinib, is not a relevant target of INNO-406. Overall, INNO-406 has an improved activity over imatinib but a slightly broader target profile than both imatinib and nilotinib. In contrast to dasatinib and bosutinib, INNO-406 does not inhibit all SRC kinases and most TEC family kinases and is therefore expected to elicit fewer side effects. Altogether, these properties may make INNO-406 a valuable component in the drug arsenal against CML.

  3. BCR-ABL, ETV6-RUNX1 and E2A-PBX1: prevalence of the most common acute lymphoblastic leukemia fusion genes in Mexican patients.

    Science.gov (United States)

    Jiménez-Morales, S; Miranda-Peralta, E; Saldaña-Alvarez, Y; Perez-Vera, P; Paredes-Aguilera, R; Rivera-Luna, R; Velázquez-Cruz, R; Ramírez-Bello, J; Carnevale, A; Orozco, L

    2008-10-01

    This study was conducted to determine the frequency of the most common fusion genes in Mexican pediatric patients with acute lymphoblastic leukemia (ALL). Molecular analysis using RT-PCR was carried out in 53-blood samples: 52 patients with de novo ALL and one with relapsed ALL. The ETV6-RUNX1 fusion was found in 7 cases (13.5%), BCR-ABL fusion was detected in 2 cases (3.8%), and 6 patients (11.5%) expressed the chimeric gene E2A-PBX1. The prevalence of E2A-PBX1 is one of the highest that has been described thus far in childhood ALL. Furthermore, we detected both the BCR-ABL, and E2A-PBX1 fusion in the relapsed patient. With regards to the immunophenotype, ETV6-RUNX1 was expressed in both pre-B and T-cell cases, while the presence of E2A-PBX1 and BCR-ABL was associated with the pre-B ALL phenotype. The prevalence of E2A-PBX1 in Mexican pediatric cases supports the existence of ethnic differences in the frequency of molecular markers of ALL.

  4. Coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites for the detection of BCR/ABL fusion gene

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xueping [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Wang, Li [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Department of Medical Laboratory, Chongqing Emergency Medical Center (Chongqing The Fourth Hospital), Chongqing, 400016 (China); Sheng, Shangchun [The No.2 Peoples' Hospital of Yibin, Sichuan, 644000 (China); Wang, Teng; Yang, Juan [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Xie, Guoming, E-mail: guomingxie@cqmu.edu.cn [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China); Feng, Wenli, E-mail: fengwlcqmu@sina.com [Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016 (China)

    2015-08-19

    This article described a novel method by coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites (GS/PANI/AuNPs) for highly sensitive and specific detection of BCR/ABL fusion gene (bcr/abl) in chronic myeloid leukemia (CML). DNA circuit known as catalyzed hairpin assembly (CHA) is enzyme-free and can be simply operated to achieve exponential amplification, which has been widely employed in biosensing. However, application of CHA has been hindered by the need of specially redesigned sequences for each single-stranded DNA input. Herein, a transducer hairpin (HP) was designed to obtain a universal DNA circuit with favorable signal-to-background ratio. To further improve signal amplification, GS/PANI/AuNPs with excellent conductivity and enlarged effective area were introduced into this DNA circuit. Consequently, by combining the advantages of CHA and GS/PANI/AuNPs, bcr/abl could be detected in a linear range from 10 pM to 20 nM with a detection limit of 1.05 pM. Moreover, this protocol showed excellent specificity, good stability and was successfully applied for the detection of real sample, which demonstrated its great potential in clinical application. - Highlights: • A transducer hairpin was designed to improve the versatility of DNA circuit. • GS/PANI/AuNPs were introduced to the DNA circuit for further signal amplification. • The established biosensor displayed high sensitivity and good specificity.

  5. Low expression of miR-196b enhances the expression of BCR-ABL1 and HOXA9 oncogenes in chronic myeloid leukemogenesis.

    Directory of Open Access Journals (Sweden)

    Yue Liu

    Full Text Available MicroRNAs (miRNAs can function as tumor suppressors or oncogene promoters during tumor development. In this study, low levels of expression of miR-196b were detected in patients with chronic myeloid leukemia. Bisulfite genomic sequencing PCR and methylation-specific PCR were used to examine the methylation status of the CpG islands in the miR-196b promoter in K562 cells, patients with leukemia and healthy individuals. The CpG islands showed more methylation in patients with chronic myeloid leukemia compared with healthy individuals (P<0.05, which indicated that low expression of miR-196b may be associated with an increase in the methylation of CpG islands. The dual-luciferase reporter assay system demonstrated that BCR-ABL1 and HOXA9 are the target genes of miR-196b, which was consistent with predictions from bioinformatics software analyses. Further examination of cell function indicated that miR-196b acts to reduce BCR-ABL1 and HOXA9 protein levels, decrease cell proliferation rate and retard the cell cycle. A low level of expression of miR-196b can cause up-regulation of BCR-ABL1 and HOXA9 expression, which leads to the development of chronic myeloid leukemia. MiR-196b may represent an effective target for chronic myeloid leukemia therapy.

  6. Design and analytic validation of BCR-ABL1 quantitative reverse transcription polymerase chain reaction assay for monitoring minimal residual disease.

    Science.gov (United States)

    Jennings, Lawrence J; Smith, Frederick A; Halling, Kevin C; Persons, Diane L; Kamel-Reid, Suzanne

    2012-01-01

    Monitoring minimal residual disease by quantitative reverse transcription polymerase chain reaction has proven clinically useful, but as yet there are no Food and Drug Administration-approved tests. Guidelines have been published that provide important information on validation of such tests; however, no practical examples have previously been published. To provide an example of the design and validation of a quantitative reverse transcription polymerase chain reaction test. To describe the approach used by an individual laboratory for development and validation of a laboratory-developed quantitative reverse transcription polymerase chain reaction test for BCR-ABL1 fusion transcripts. Elements of design and analytic validation of a laboratory-developed quantitative molecular test are discussed using quantitative detection of BCR-ABL1 fusion transcripts as an example. Validation of laboratory-developed quantitative molecular tests requires careful planning and execution to adequately address all required analytic performance parameters. How these are addressed depends on the potential for technical errors and confidence required for a given test result. We demonstrate how one laboratory validated and clinically implemented a quantitative BCR-ABL1 assay that can be used for the management of patients with chronic myelogenous leukemia.

  7. PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation.

    Science.gov (United States)

    Mian, A A; Rafiei, A; Haberbosch, I; Zeifman, A; Titov, I; Stroylov, V; Metodieva, A; Stroganov, O; Novikov, F; Brill, B; Chilov, G; Hoelzer, D; Ottmann, O G; Ruthardt, M

    2015-05-01

    Targeting BCR/ABL with tyrosine kinase inhibitors (TKIs) is a proven concept for the treatment of Philadelphia chromosome-positive (Ph+) leukemias. Resistance attributable to either kinase mutations in BCR/ABL or nonmutational mechanisms remains the major clinical challenge. With the exception of ponatinib, all approved TKIs are unable to inhibit the 'gatekeeper' mutation T315I. However, a broad spectrum of kinase inhibition increases the off-target effects of TKIs and may be responsible for cardiovascular issues of ponatinib. Thus, there is a need for more selective options for the treatment of resistant Ph+ leukemias. PF-114 is a novel TKI developed with the specifications of (i) targeting T315I and other resistance mutations in BCR/ABL; (ii) achieving a high selectivity to improve safety; and (iii) overcoming nonmutational resistance in Ph+ leukemias. PF-114 inhibited BCR/ABL and clinically important mutants including T315I at nanomolar concentrations. It suppressed primary Ph+ acute lymphatic leukemia-derived long-term cultures that either displayed nonmutational resistance or harbor the T315I. In BCR/ABL- or BCR/ABL-T315I-driven murine leukemia as well as in xenograft models of primary Ph+ leukemia harboring the T315I, PF-114 significantly prolonged survival to a similar extent as ponatinib. Our work supports clinical evaluation of PF-114 for the treatment of resistant Ph+ leukemia.

  8. Characteristics and outcome of chronic myeloid leukemia patients with E255K/V BCR-ABL kinase domain mutations.

    Science.gov (United States)

    Naqvi, Kiran; Cortes, Jorge E; Luthra, Raja; O'Brien, Susan; Wierda, William; Borthakur, Gautam; Kadia, Tapan; Garcia-Manero, Guillermo; Ravandi, Farhad; Rios, Mary Beth; Dellasala, Sara; Pierce, Sherry; Jabbour, Elias; Patel, Keyur; Kantarjian, Hagop

    2018-02-20

    Kinase domain (KD) mutations of ABL1 represent the most common resistance mechanism to tyrosine kinase inhibitors (TKI) in CML. Besides T315I, mutations in codon 255 are highly resistant mutations in vitro to all TKI. We aimed to study the incidence, prognosis, and response to treatment in patients with E255K/V. We evaluated 976 patients by sequencing of BCR-ABL1 fusion transcript for ABL1 KD mutations. We identified KD mutations in 381 (39%) patients, including E255K/V in 48 (13% of all mutations). At mutation detection, 14 patients (29%) were in chronic phase (CP), 12 (25%) in accelerated phase (AP), and 22 (46%) in blast phase (BP). 9/14 CP patients responded to treatment (best response complete hematologic response-CHR-4; complete cytogenetic response-CCyR-1; major molecular response-MMR-4); only 4/12 AP patients (CHR 3; MMR 1) and 7/22 BP patients responded (CCyR 2; MMR 2; partial cytogenetic response-PCyR-3). After a median follow-up of 65 months from mutation detection, 36 patients (75%) died: 9/14 (64%) in CP, 9/12 (75%) in AP, and 18/22 (82%) in BP (p = 0.003); median overall survival was 12 months. Patients with E255K/V mutation have a poor prognosis, regardless of the stage of the disease at detection.

  9. Dehydrocostus Lactone Suppresses Proliferation of Human Chronic Myeloid Leukemia Cells Through Bcr/Abl-JAK/STAT Signaling Pathways.

    Science.gov (United States)

    Cai, Hong; Qin, Xiaosong; Yang, Chunhui

    2017-10-01

    This study evaluates the anticancer effects of dehydrocostus lactone, a plant-derived sesquiterpene lactone, on human chronic myeloid leukemia cells. Dehydrocostus lactone significantly inhibits cell proliferation by inducing cells to undergo cell cycle arrest, apoptosis, and differentiation. Dehydrocostus lactone suppresses the expression of cyclin B1, cyclin A, cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin-dependent kinase 1 (CDK1) and increases p21 expression, resulting in S-G2/M phase arrest in K562 cells. Dehydrocostus lactone also induces apoptosis by increasing the generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential (MMP), and modulating the protein levels of Bcl-2 family members. We also found that dehydrocostus lactone significantly inhibits the phosphorylation expression of Bcr/Abl, STAT5, JAK2, and STAT3 and downstream molecules including p-CrkL, Mcl-1, Bcl-XL, and Bcl-2 proteins in K562 cells. At a low concentration, dehydrocostus lactone significantly increased CD11b and CD14 expression on the surface of K562 cells, and induced cells to differentiate into monocytes or mature macrophages. Taken together, this study provides new insight into the molecular mechanisms of dehydrocostus lactone actions that may contribute to the chemoprevention of chronic myeloid leukemia. J. Cell. Biochem. 118: 3381-3390, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Eyewitness confidence in simultaneous and sequential lineups: a criterion shift account for sequential mistaken identification overconfidence.

    Science.gov (United States)

    Dobolyi, David G; Dodson, Chad S

    2013-12-01

    Confidence judgments for eyewitness identifications play an integral role in determining guilt during legal proceedings. Past research has shown that confidence in positive identifications is strongly associated with accuracy. Using a standard lineup recognition paradigm, we investigated accuracy using signal detection and ROC analyses, along with the tendency to choose a face with both simultaneous and sequential lineups. We replicated past findings of reduced rates of choosing with sequential as compared to simultaneous lineups, but notably found an accuracy advantage in favor of simultaneous lineups. Moreover, our analysis of the confidence-accuracy relationship revealed two key findings. First, we observed a sequential mistaken identification overconfidence effect: despite an overall reduction in false alarms, confidence for false alarms that did occur was higher with sequential lineups than with simultaneous lineups, with no differences in confidence for correct identifications. This sequential mistaken identification overconfidence effect is an expected byproduct of the use of a more conservative identification criterion with sequential than with simultaneous lineups. Second, we found a steady drop in confidence for mistaken identifications (i.e., foil identifications and false alarms) from the first to the last face in sequential lineups, whereas confidence in and accuracy of correct identifications remained relatively stable. Overall, we observed that sequential lineups are both less accurate and produce higher confidence false identifications than do simultaneous lineups. Given the increasing prominence of sequential lineups in our legal system, our data argue for increased scrutiny and possibly a wholesale reevaluation of this lineup format. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  11. Weak Sequential Composition in Process Algebras

    NARCIS (Netherlands)

    Rensink, Arend; Jonsson, B.; Parrow, J.; Wehrheim, H.

    1994-01-01

    n this paper we study a special operator for sequential composition, which is defined relative to a dependency relation over the actions of a given system. The idea is that actions which are not dependent (intuitively because they share no common resources) do not have to wait for one another to

  12. Sequential Bayesian technique: An alternative approach for ...

    Indian Academy of Sciences (India)

    This paper proposes a sequential Bayesian approach similar to Kalman filter for estimating reliability growth or decay of software. The main advantage of proposed method is that it shows the variation of the parameter over a time, as new failure data become available. The usefulness of the method is demonstrated with ...

  13. Sequential Bayesian technique: An alternative approach for ...

    Indian Academy of Sciences (India)

    MS received 8 October 2007; revised 15 July 2008. Abstract. This paper proposes a sequential Bayesian approach similar to Kalman filter for estimating reliability growth or decay of software. The main advantage of proposed method is that it shows the variation of the parameter over a time, as new failure data become ...

  14. Fareed Zakaria's Democratic Sequentialism and Nigeria's ...

    African Journals Online (AJOL)

    This essay will attempt to analyse the prospects for political and economic liberalisation and ultimately democracy in Nigeria by examining Fareed Zakaria's prescription of democratic sequentialism i.e, liberalism before democracy. Zakaria's argument was that due to cultural variation, different societies will require different ...

  15. Early Astronomical Sequential Photography, 1873-1923

    Science.gov (United States)

    Bonifácio, Vitor

    2011-11-01

    In 1873 Jules Janssen conceived the first automatic sequential photographic apparatus to observe the eagerly anticipated 1874 transit of Venus. This device, the 'photographic revolver', is commonly considered today as the earliest cinema precursor. In the following years, in order to study the variability or the motion of celestial objects, several instruments, either manually or automatically actuated, were devised to obtain as many photographs as possible of astronomical events in a short time interval. In this paper we strive to identify from the available documents the attempts made between 1873 and 1923, and discuss the motivations behind them and the results obtained. During the time period studied astronomical sequential photography was employed to determine the time of the instants of contact in transits and occultations, and to study total solar eclipses. The technique was seldom used but apparently the modern film camera invention played no role on this situation. Astronomical sequential photographs were obtained both before and after 1895. We conclude that the development of astronomical sequential photography was constrained by the reduced number of subjects to which the technique could be applied.

  16. Sensitivity Analysis in Sequential Decision Models.

    Science.gov (United States)

    Chen, Qiushi; Ayer, Turgay; Chhatwal, Jagpreet

    2017-02-01

    Sequential decision problems are frequently encountered in medical decision making, which are commonly solved using Markov decision processes (MDPs). Modeling guidelines recommend conducting sensitivity analyses in decision-analytic models to assess the robustness of the model results against the uncertainty in model parameters. However, standard methods of conducting sensitivity analyses cannot be directly applied to sequential decision problems because this would require evaluating all possible decision sequences, typically in the order of trillions, which is not practically feasible. As a result, most MDP-based modeling studies do not examine confidence in their recommended policies. In this study, we provide an approach to estimate uncertainty and confidence in the results of sequential decision models. First, we provide a probabilistic univariate method to identify the most sensitive parameters in MDPs. Second, we present a probabilistic multivariate approach to estimate the overall confidence in the recommended optimal policy considering joint uncertainty in the model parameters. We provide a graphical representation, which we call a policy acceptability curve, to summarize the confidence in the optimal policy by incorporating stakeholders' willingness to accept the base case policy. For a cost-effectiveness analysis, we provide an approach to construct a cost-effectiveness acceptability frontier, which shows the most cost-effective policy as well as the confidence in that for a given willingness to pay threshold. We demonstrate our approach using a simple MDP case study. We developed a method to conduct sensitivity analysis in sequential decision models, which could increase the credibility of these models among stakeholders.

  17. S.M.P. SEQUENTIAL MATHEMATICS PROGRAM.

    Science.gov (United States)

    CICIARELLI, V; LEONARD, JOSEPH

    A SEQUENTIAL MATHEMATICS PROGRAM BEGINNING WITH THE BASIC FUNDAMENTALS ON THE FOURTH GRADE LEVEL IS PRESENTED. INCLUDED ARE AN UNDERSTANDING OF OUR NUMBER SYSTEM, AND THE BASIC OPERATIONS OF WORKING WITH WHOLE NUMBERS--ADDITION, SUBTRACTION, MULTIPLICATION, AND DIVISION. COMMON FRACTIONS ARE TAUGHT IN THE FIFTH, SIXTH, AND SEVENTH GRADES. A…

  18. The curse of sequentiality in routing games

    NARCIS (Netherlands)

    Correa, José; de Jong, Jasper; de Keijzer, Bart; Uetz, Marc Jochen; Markakis, Evangelos; Schäfer, Guido

    2015-01-01

    In the "The curse of simultaneity", Paes Leme at al. show that there are interesting classes of games for which sequential decision making and corresponding subgame perfect equilibria avoid worst case Nash equilibria, resulting in substantial improvements for the price of anarchy. This is called the

  19. A framework for sequential multiblock component methods

    NARCIS (Netherlands)

    Smilde, A.K.; Westerhuis, J.A.; Jong, S.de

    2003-01-01

    Multiblock or multiset methods are starting to be used in chemistry and biology to study complex data sets. In chemometrics, sequential multiblock methods are popular; that is, methods that calculate one component at a time and use deflation for finding the next component. In this paper a framework

  20. STABILIZED SEQUENTIAL QUADRATIC PROGRAMMING: A SURVEY

    Directory of Open Access Journals (Sweden)

    Damián Fernández

    2014-12-01

    Full Text Available We review the motivation for, the current state-of-the-art in convergence results, and some open questions concerning the stabilized version of the sequential quadratic programming algorithm for constrained optimization. We also discuss the tools required for its local convergence analysis, globalization challenges, and extentions of the method to the more general variational problems.

  1. Adult Word Recognition and Visual Sequential Memory

    Science.gov (United States)

    Holmes, V. M.

    2012-01-01

    Two experiments were conducted investigating the role of visual sequential memory skill in the word recognition efficiency of undergraduate university students. Word recognition was assessed in a lexical decision task using regularly and strangely spelt words, and nonwords that were either standard orthographically legal strings or items made from…

  2. Interpretability degrees of finitely axiomatized sequential theories

    NARCIS (Netherlands)

    Visser, Albert

    In this paper we show that the degrees of interpretability of finitely axiomatized extensions-in-the-same-language of a finitely axiomatized sequential theory-like Elementary Arithmetic EA, IΣ1, or the Gödel-Bernays theory of sets and classes GB-have suprema. This partially answers a question posed

  3. Interpretability Degrees of Finitely Axiomatized Sequential Theories

    NARCIS (Netherlands)

    Visser, Albert

    2012-01-01

    In this paper we show that the degrees of interpretability of finitely axiomatized extensions-in-the-same-language of a finitely axiomatized sequential theory —like Elementary Arithmetic EA, IΣ1, or the Gödel-Bernays theory of sets and classes GB— have suprema. This partially answers a question

  4. Sequential auctions for full truckload allocation

    NARCIS (Netherlands)

    Mes, Martijn R.K.

    2008-01-01

    In this thesis we examine the use of sequential auctions for the dynamic allocation of transportation jobs. For all players, buyers and sellers, we develop strategies and examine their performance both in terms of individual benefits and with respect to the global logistical performance (resource

  5. Phosphorus Concentrations in Sequentially Fractionated Soil Samples as Affected by Digestion Methods

    Science.gov (United States)

    do Nascimento, Carlos A. C.; Pagliari, Paulo H.; Schmitt, Djalma; He, Zhongqi; Waldrip, Heidi

    2015-01-01

    Sequential fractionation has helped improving our understanding of the lability and bioavailability of P in soil. Nevertheless, there have been no reports on how manipulation of the different fractions prior to analyses affects the total P (TP) concentrations measured. This study investigated the effects of sample digestion, filtration, and acidification on the TP concentrations determined by ICP-OES in 20 soil samples. Total P in extracts were either determined without digestion by ICP-OES, or ICP-OES following block digestion, or autoclave digestion. The effects of sample filtration, and acidification on undigested alkaline extracts prior to ICP-OES were also evaluated. Results showed that, TP concentrations were greatest in the block-digested extracts, though the variability introduced by the block-digestion was the highest. Acidification of NaHCO3 extracts resulted in lower TP concentrations, while acidification of NaOH randomly increased or decreased TP concentrations. The precision observed with ICP-OES of undigested extracts suggests this should be the preferred method for TP determination in sequentially extracted samples. Thus, observations reported in this work would be helpful in appropriate sample handling for P determination, thereby improving the precision of P determination. The results are also useful for literature data comparison and discussion when there are differences in sample treatments. PMID:26647644

  6. Antimalaria activity of ethanolic extracts of leaves of Terminalia ...

    African Journals Online (AJOL)

    The leaves of Terminalia catappa were air dried, grounded and soaked with ethanol. The extracts obtained (47.23g, TC1) was fractionated sequentially using aqueous methanol with petroleum ether, chloroform and ethyl acetate respectively. The residue of ethanol extract (marc) was extracted with 5M HCl, basified and ...

  7. Rationalizing Boundedly Rational Choice : Sequential Rationalizability and Rational Shortlist Methods

    OpenAIRE

    Manzini, Paola; Mariotti, Marco

    2004-01-01

    A sequentially rationalizable choice function is a choice function which can be obtained by applying sequentially a fixed set of asymmetric binary relations (rationales). A Rational ShortlistMethod (RSM) is a choice function which is sequentially rationalizable by two rationales. These concepts translate into economic language some human choice heuristics studied in psychology. We provide a full characterization of RSMs and study some properties of sequential rationalizability. These properti...

  8. Sequential shrink photolithography for plastic microlens arrays

    Science.gov (United States)

    Dyer, David; Shreim, Samir; Jayadev, Shreshta; Lew, Valerie; Botvinick, Elliot; Khine, Michelle

    2011-01-01

    Endeavoring to push the boundaries of microfabrication with shrinkable polymers, we have developed a sequential shrink photolithography process. We demonstrate the utility of this approach by rapidly fabricating plastic microlens arrays. First, we create a mask out of the children’s toy Shrinky Dinks by simply printing dots using a standard desktop printer. Upon retraction of this pre-stressed thermoplastic sheet, the dots shrink to a fraction of their original size, which we then lithographically transfer onto photoresist-coated commodity shrink wrap film. This shrink film reduces in area by 95% when briefly heated, creating smooth convex photoresist bumps down to 30 µm. Taken together, this sequential shrink process provides a complete process to create microlenses, with an almost 99% reduction in area from the original pattern size. Finally, with a lithography molding step, we emboss these bumps into optical grade plastics such as cyclic olefin copolymer for functional microlens arrays. PMID:21863126

  9. Robust Sequential Analysis for Special Capacities

    OpenAIRE

    高橋, 一

    1985-01-01

    Huber type robustness will be considered for some extensions of Wald's Sequential Probability Ratio Test, including Wald's three decision problem and the Kiefer-Weiss formulation. The results of Huber (1965, 1968), Huber and Strassen (1973), Rieder (1977) and Osterreicher (1978) will be extended to derive a least favorable tuple in the multiple decision problem. And then the asymptotically least favorable KieferWeiss procedure together with its asymptotic relative efficiency for the s-contami...

  10. Sleep memory processing: the sequential hypothesis

    OpenAIRE

    Giuditta, Antonio

    2014-01-01

    According to the sequential hypothesis (SH) memories acquired during wakefulness are processed during sleep in two serial steps respectively occurring during slow wave sleep (SWS) and rapid eye movement (REM) sleep. During SWS memories to be retained are distinguished from irrelevant or competing traces that undergo downgrading or elimination. Processed memories are stored again during REM sleep which integrates them with preexisting memories. The hypothesis received support from a wealth of ...

  11. Sequential neural models with stochastic layers

    DEFF Research Database (Denmark)

    Fraccaro, Marco; Sønderby, Søren Kaae; Paquet, Ulrich

    2016-01-01

    How can we efficiently propagate uncertainty in a latent state representation with recurrent neural networks? This paper introduces stochastic recurrent neural networks which glue a deterministic recurrent neural network and a state space model together to form a stochastic and sequential neural...... generative model. The clear separation of deterministic and stochastic layers allows a structured variational inference network to track the factorization of the model's posterior distribution. By retaining both the nonlinear recursive structure of a recurrent neural network and averaging over...

  12. On Locally Most Powerful Sequential Rank Tests

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan

    2017-01-01

    Roč. 36, č. 1 (2017), s. 111-125 ISSN 0747-4946 R&D Projects: GA ČR GA17-07384S Grant - others:Nadační fond na podporu vědy(CZ) Neuron Institutional support: RVO:67985807 Keywords : nonparametric tests * sequential ranks * stopping variable Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.339, year: 2016

  13. Sequential pattern recognition by maximum conditional informativity

    Czech Academy of Sciences Publication Activity Database

    Grim, Jiří

    2014-01-01

    Roč. 45, č. 1 (2014), s. 39-45 ISSN 0167-8655 R&D Projects: GA ČR(CZ) GA14-02652S; GA ČR(CZ) GA14-10911S Keywords : Multivariate statistics * Statistical pattern recognition * Sequential decision making * Product mixtures * EM algorithm * Shannon information Subject RIV: IN - Informatics, Computer Science Impact factor: 1.551, year: 2014 http://library.utia.cas.cz/separaty/2014/RO/grim-0428565.pdf

  14. Sequential tests for near-real-time accounting

    International Nuclear Information System (INIS)

    Cobb, D.D.

    1981-01-01

    Statistical hypothesis testing is used in the analysis of nuclear materials accounting data for evidence of diversion. Sequential hypothesis testing is particularly well suited for analyzing data that arise sequentially in time from near-real-time accounting systems. The properties of selected sequential tests adapted for this application are described. 10 figures, 12 tables

  15. Sequential Injection Method for Rapid and Simultaneous Determination of 236U, 237Np, and Pu Isotopes in Seawater

    DEFF Research Database (Denmark)

    Qiao, Jixin; Hou, Xiaolin; Steier, Peter

    2013-01-01

    An automated analytical method implemented in a novel dual-column tandem sequential injection (SI) system was developed for simultaneous determination of 236U, 237Np, 239Pu, and 240Pu in seawater samples. A combination of TEVA and UTEVA extraction chromatography was exploited to separate and purify...

  16. Attomolar electrochemical detection of the BCR/ABL fusion gene based on an amplifying self-signal metal nanoparticle-conducting polymer hybrid composite.

    Science.gov (United States)

    Avelino, Karen Y P S; Frias, Isaac A M; Lucena-Silva, Norma; Gomes, Renan G; de Melo, Celso P; Oliveira, Maria D L; Andrade, César A S

    2016-12-01

    In the last ten years, conjugated polymers started to be used in the immobilization of nucleic acids via non-covalent interactions. In the present study, we describe the construction and use of an electrochemical DNA biosensor based on a nanostructured polyaniline-gold composite, specifically developed for the detection of the BCR/ABL chimeric oncogene. This chromosome translocation is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). The working principle of the biosensor rests on measuring the conductivity resulting from the non-covalent interactions between the hybrid nanocomposite and the DNA probe. The nanostructured platform exhibits a large surface area that enhances the conductivity. Positive cases, which result from the hybridization between DNA probe and targeted gene, induce changes in the amperometric current and in the charge transfer resistance (R CT ) responses. Atomic force microscopy (AFM) images showed changes in the genosensor surface after exposure to cDNA sample of patient with leukemia, evidencing the hybridization process. This new hybrid sensing-platform displayed high specificity and selectivity, and its detection limit is estimated to be as low as 69.4 aM. The biosensor showed excellent analytical performance for the detection of the BCR/ABL oncogene in clinical samples of patients with leukemia. Hence, this electrochemical sensor appears as a simple and attractive tool for the molecular diagnosis of the BCR/ABL oncogene even in early-stage cases of leukemia and for the monitoring of minimum levels of residual disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Automated sequential injection-microcolumn approach with on-line flame atomic absorption spectrometric detection for implementing metal fractionation schemes of homogeneous and non-homogeneous solid samples of environmental interest

    DEFF Research Database (Denmark)

    Chomchoei, Roongrat; Miró, Manuel; Hansen, Elo Harald

    2005-01-01

    An automated sequential injection (SI) system incorporating a dual-conical microcolumn is proposed as a versatile approach for the accommodation of both single and sequential extraction schemes for metal fractionation of solid samples of environmental concern. Coupled to flame atomic absorption...

  18. Nuclear topography and expression of the BCR/ABL fusion gene and its protein level influenced by cell differentiation and RNA interference

    Czech Academy of Sciences Publication Activity Database

    Bártová, Eva; Harničarová, Andrea; Pacherník, Jiří; Kozubek, Stanislav

    2005-01-01

    Roč. 29, č. 8 (2005), s. 901-913 ISSN 0145-2126 R&D Projects: GA AV ČR(CZ) 1QS500040508; GA ČR(CZ) GA202/04/0907; GA MZd NC6987; GA AV ČR(CZ) IAA5004306; GA MŠk(CZ) LC535 Institutional research plan: CEZ:AV0Z50040507 Keywords : BCR /ABL fusion gene * chromatin arrangement * gene expression Subject RIV: BO - Biophysics Impact factor: 2.372, year: 2005

  19. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F+ HEL Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Axel Weber

    2015-03-01

    Full Text Available Signal transducers and activators of transcription (Stats play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML and Jak2(V617F in other myeloproliferative diseases (MPD. We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL

  20. CFD simulation of hemodynamics in sequential and individual coronary bypass grafts based on multislice CT scan datasets.

    Science.gov (United States)

    Hajati, Omid; Zarrabi, Khalil; Karimi, Reza; Hajati, Azadeh

    2012-01-01

    There is still controversy over the differences in the patency rates of the sequential and individual coronary artery bypass grafting (CABG) techniques. The purpose of this paper was to non-invasively evaluate hemodynamic parameters using complete 3D computational fluid dynamics (CFD) simulations of the sequential and the individual methods based on the patient-specific data extracted from computed tomography (CT) angiography. For CFD analysis, the geometric model of coronary arteries was reconstructed using an ECG-gated 64-detector row CT. Modeling the sequential and individual bypass grafting, this study simulates the flow from the aorta to the occluded posterior descending artery (PDA) and the posterior left ventricle (PLV) vessel with six coronary branches based on the physiologically measured inlet flow as the boundary condition. The maximum calculated wall shear stress (WSS) in the sequential and the individual models were estimated to be 35.1 N/m(2) and 36.5 N/m(2), respectively. Compared to the individual bypass method, the sequential graft has shown a higher velocity at the proximal segment and lower spatial wall shear stress gradient (SWSSG) due to the flow splitting caused by the side-to-side anastomosis. Simulated results combined with its surgical benefits including the requirement of shorter vein length and fewer anastomoses advocate the sequential method as a more favorable CABG method.

  1. A sequential nonparametric pattern classification algorithm based on the Wald SPRT. [Sequential Probability Ratio Test

    Science.gov (United States)

    Poage, J. L.

    1975-01-01

    A sequential nonparametric pattern classification procedure is presented. The method presented is an estimated version of the Wald sequential probability ratio test (SPRT). This method utilizes density function estimates, and the density estimate used is discussed, including a proof of convergence in probability of the estimate to the true density function. The classification procedure proposed makes use of the theory of order statistics, and estimates of the probabilities of misclassification are given. The procedure was tested on discriminating between two classes of Gaussian samples and on discriminating between two kinds of electroencephalogram (EEG) responses.

  2. Sequential tool use in great apes.

    Directory of Open Access Journals (Sweden)

    Gema Martin-Ordas

    Full Text Available Sequential tool use is defined as using a tool to obtain another non-food object which subsequently itself will serve as a tool to act upon a further (subgoal. Previous studies have shown that birds and great apes succeed in such tasks. However, the inclusion of a training phase for each of the sequential steps and the low cost associated with retrieving the longest tools limits the scope of the conclusions. The goal of the experiments presented here was, first to replicate a previous study on sequential tool use conducted on New Caledonian crows and, second, extend this work by increasing the cost of retrieving a tool in order to test tool selectivity of apes. In Experiment 1, we presented chimpanzees, orangutans and bonobos with an out-of-reach reward, two tools that were available but too short to reach the food and four out-of-reach tools differing in functionality. Similar to crows, apes spontaneously used up to 3 tools in sequence to get the reward and also showed a strong preference for the longest out-of reach tool independently of the distance of the food. In Experiment 2, we increased the cost of reaching for the longest out-of reach tool. Now apes used up to 5 tools in sequence to get the reward and became more selective in their choice of the longest tool as the costs of its retrieval increased. The findings of the studies presented here contribute to the growing body of comparative research on tool use.

  3. Reaction probability for sequential separatrix crossings

    International Nuclear Information System (INIS)

    Cary, J.R.; Skodje, R.T.

    1988-01-01

    The change of the crossing parameter (essentially the phase) between sequential slow separatrix crossings is calculated for Hamiltonian systems with one degree of freedom. Combined with the previous separatrix crossing analysis, these results reduce the dynamics of adiabatic systems with separatrices to a map. This map determines whether a trajectory leaving a given separatrix lobe is ultimately captured by the other lobe. Averaging these results over initial phase yields the reaction probability, which does not asymptote to the fully phase-mixed result even for arbitrarily long times between separatrix crossings

  4. A sequential/parallel track selector

    CERN Document Server

    Bertolino, F; Bressani, Tullio; Chiavassa, E; Costa, S; Dellacasa, G; Gallio, M; Musso, A

    1980-01-01

    A medium speed ( approximately 1 mu s) hardware pre-analyzer for the selection of events detected in four planes of drift chambers in the magnetic field of the Omicron Spectrometer at the CERN SC is described. Specific geometrical criteria determine patterns of hits in the four planes of vertical wires that have to be recognized and that are stored as patterns of '1's in random access memories. Pairs of good hits are found sequentially, then the RAMs are used as look-up tables. (6 refs).

  5. THE DEVELOPMENT OF SPECIAL SEQUENTIALLY-TIMED

    Directory of Open Access Journals (Sweden)

    Stanislav LICHOROBIEC

    2016-06-01

    Full Text Available This article documents the development of the noninvasive use of explosives during the destruction of ice mass in river flows. The system of special sequentially-timed charges utilizes the increase in efficiency of cutting charges by covering them with bags filled with water, while simultaneously increasing the effect of the entire system of timed charges. Timing, spatial combinations during placement, and the linking of these charges results in the loosening of ice barriers on a frozen waterway, while at the same time regulating the size of the ice fragments. The developed charges will increase the operability and safety of IRS units.

  6. Pass-transistor asynchronous sequential circuits

    Science.gov (United States)

    Whitaker, Sterling R.; Maki, Gary K.

    1989-01-01

    Design methods for asynchronous sequential pass-transistor circuits, which result in circuits that are hazard- and critical-race-free and which have added degrees of freedom for the input signals, are discussed. The design procedures are straightforward and easy to implement. Two single-transition-time state assignment methods are presented, and hardware bounds for each are established. A surprising result is that the hardware realizations for each next state variable and output variable is identical for a given flow table. Thus, a state machine with N states and M outputs can be constructed using a single layout replicated N + M times.

  7. From sequential to parallel programming with patterns

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    To increase in both performance and efficiency, our programming models need to adapt to better exploit modern processors. The classic idioms and patterns for programming such as loops, branches or recursion are the pillars of almost every code and are well known among all programmers. These patterns all have in common that they are sequential in nature. Embracing parallel programming patterns, which allow us to program for multi- and many-core hardware in a natural way, greatly simplifies the task of designing a program that scales and performs on modern hardware, independently of the used programming language, and in a generic way.

  8. Decoding restricted participation in sequential electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Knaut, Andreas; Paschmann, Martin

    2017-06-15

    Restricted participation in sequential markets may cause high price volatility and welfare losses. In this paper we therefore analyze the drivers of restricted participation in the German intraday auction which is a short-term electricity market with quarter-hourly products. Applying a fundamental electricity market model with 15-minute temporal resolution, we identify the lack of sub-hourly market coupling being the most relevant driver of restricted participation. We derive a proxy for price volatility and find that full market coupling may trigger quarter-hourly price volatility to decrease by a factor close to four.

  9. Boundary conditions in random sequential adsorption

    Science.gov (United States)

    Cieśla, Michał; Ziff, Robert M.

    2018-04-01

    The influence of different boundary conditions on the density of random packings of disks is studied. Packings are generated using the random sequential adsorption algorithm with three different types of boundary conditions: periodic, open, and wall. It is found that the finite size effects are smallest for periodic boundary conditions, as expected. On the other hand, in the case of open and wall boundaries it is possible to introduce an effective packing size and a constant correction term to significantly improve the packing densities.

  10. On Locally Most Powerful Sequential Rank Tests

    Czech Academy of Sciences Publication Activity Database

    Kalina, Jan

    2017-01-01

    Roč. 36, č. 1 (2017), s. 111-125 ISSN 0747-4946 R&D Projects: GA ČR GA17-07384S Grant - others:Nadační fond na podporu vědy(CZ) Neuron Institutional support: RVO:67985556 Keywords : nonparametric tests * sequential ranks * stopping variable Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.339, year: 2016 http://library.utia.cas.cz/separaty/2017/SI/kalina-0474065.pdf

  11. Chemical and sequential analysis of some metals in sediments from the North Coast of the Gulf of Mexico

    International Nuclear Information System (INIS)

    Trinidad Martinez; Brenda Estanol; Miguel Angel Zuniga

    2016-01-01

    Sediments collected from the North Coast of the Gulf of Mexico got carefully mixed, dried, and finally subjected to physical and chemical analysis. Metal concentration was determined by energy dispersive X-ray fluorescence (EDXRF). Sequential chemical analysis was performed by modified TESSIER technique. Results and statistical analysis (α = 0.05) show concentrations of most elements (excepting Mn, Ca, Ga, As and Pb) in the range of those of the earth crust's values, which set a sampling zone base line. Sequential extraction shows the potential risk of mobilization of metals sequestered in particulate phases by oxidation of anoxic sediments or intense organic matter degradation. (author)

  12. 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.

  13. SÍNTESES E PROPRIEDADES DE FÁRMACOS INIBIDORES DA TIROSINA QUINASE BCR-ABL, UTILIZADOS NO TRATAMENTO DA LEUCEMIA MIELOIDE CRÔNICA

    Directory of Open Access Journals (Sweden)

    Liviane D. de Azevedo

    Full Text Available The chronic myeloid leukemia (CML is characterized by presence of the Philadelphia chromosome (Ph, originated from the translocation between chromosomes 9 and 22. This chromosome generates an abnormal protein tyrosine kinase which is responsible for tumor cell proliferation. The emergence of tyrosine kinase inhibitors (TKIs has transformed the treatment of CML and imatinib being the first representative of this class. Although treatment with imatinib has reached surprising results, approximately 30% of patients exhibited resistance, especially in later stages of the disease. This fact stimulated the development of novel BCR-ABL enzyme inhibitors drugs classified as tyrosine kinase inhibitors (TKIs of second and third generations. The TKIs have different chemical functions in their structure, and the knowledge of synthetic methods for preparation of these compounds can be a powerful tool for the development of new derivatives. The five approved BCR-ABL Tyrosine Kinase inhibitors (TKI used in Chronic Myeloid Leukemia (CML are reviewed aiming the main synthetic routes, highlighting the advantages and disadvantages associated with them.

  14. Accurate determination of arsenic in arsenobetaine standard solutions of BCR-626 and NMIJ CRM 7901-a by neutron activation analysis coupled with internal standard method.

    Science.gov (United States)

    Miura, Tsutomu; Chiba, Koichi; Kuroiwa, Takayoshi; Narukawa, Tomohiro; Hioki, Akiharu; Matsue, Hideaki

    2010-09-15

    Neutron activation analysis (NAA) coupled with an internal standard method was applied for the determination of As in the certified reference material (CRM) of arsenobetaine (AB) standard solutions to verify their certified values. Gold was used as an internal standard to compensate for the difference of the neutron exposure in an irradiation capsule and to improve the sample-to-sample repeatability. Application of the internal standard method significantly improved linearity of the calibration curve up to 1 microg of As, too. The analytical reliability of the proposed method was evaluated by k(0)-standardization NAA. The analytical results of As in AB standard solutions of BCR-626 and NMIJ CRM 7901-a were (499+/-55)mgkg(-1) (k=2) and (10.16+/-0.15)mgkg(-1) (k=2), respectively. These values were found to be 15-20% higher than the certified values. The between-bottle variation of BCR-626 was much larger than the expanded uncertainty of the certified value, although that of NMIJ CRM 7901-a was almost negligible. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  15. Sequential evidence accumulation in decision making

    Directory of Open Access Journals (Sweden)

    Daniel Hausmann

    2008-03-01

    Full Text Available Judgments and decisions under uncertainty are frequently linked to a prior sequential search for relevant information. In such cases, the subject has to decide when to stop the search for information. Evidence accumulation models from social and cognitive psychology assume an active and sequential information search until enough evidence has been accumulated to pass a decision threshold. In line with such theories, we conceptualize the evidence threshold as the ``desired level of confidence'' (DLC of a person. This model is tested against a fixed stopping rule (one-reason decision making and against the class of multi-attribute information integrating models. A series of experiments using an information board for horse race betting demonstrates an advantage of the proposed model by measuring the individual DLC of each subject and confirming its correctness in two separate stages. In addition to a better understanding of the stopping rule (within the narrow framework of simple heuristics, the results indicate that individual aspiration levels might be a relevant factor when modelling decision making by task analysis of statistical environments.

  16. Unsupervised Sequential Outlier Detection With Deep Architectures.

    Science.gov (United States)

    Lu, Weining; Cheng, Yu; Xiao, Cao; Chang, Shiyu; Huang, Shuai; Liang, Bin; Huang, Thomas

    2017-09-01

    Unsupervised outlier detection is a vital task and has high impact on a wide variety of applications domains, such as image analysis and video surveillance. It also gains long-standing attentions and has been extensively studied in multiple research areas. Detecting and taking action on outliers as quickly as possible are imperative in order to protect network and related stakeholders or to maintain the reliability of critical systems. However, outlier detection is difficult due to the one class nature and challenges in feature construction. Sequential anomaly detection is even harder with more challenges from temporal correlation in data, as well as the presence of noise and high dimensionality. In this paper, we introduce a novel deep structured framework to solve the challenging sequential outlier detection problem. We use autoencoder models to capture the intrinsic difference between outliers and normal instances and integrate the models to recurrent neural networks that allow the learning to make use of previous context as well as make the learners more robust to warp along the time axis. Furthermore, we propose to use a layerwise training procedure, which significantly simplifies the training procedure and hence helps achieve efficient and scalable training. In addition, we investigate a fine-tuning step to update all parameters set by incorporating the temporal correlation in the sequence. We further apply our proposed models to conduct systematic experiments on five real-world benchmark data sets. Experimental results demonstrate the effectiveness of our model, compared with other state-of-the-art approaches.

  17. Continuous sequential boundaries for vaccine safety surveillance.

    Science.gov (United States)

    Li, Rongxia; Stewart, Brock; Weintraub, Eric; McNeil, Michael M

    2014-08-30

    Various recently developed sequential methods have been used to detect signals for post-marketing surveillance in drug and vaccine safety. Among these, the maximized sequential probability ratio test (MaxSPRT) has been used to detect elevated risks of adverse events following vaccination using large healthcare databases. However, a limitation of MaxSPRT is that it only provides a time-invariant flat boundary. In this study, we propose the use of time-varying boundaries for controlling how type I error is distributed throughout the surveillance period. This is especially useful in two scenarios: (i) when we desire generally larger sample sizes before a signal is generated, for example, when early adopters are not representative of the larger population; and (ii) when it is desired for a signal to be generated as early as possible, for example, when the adverse event is considered rare but serious. We consider four specific time-varying boundaries (which we call critical value functions), and we study their statistical power and average time to signal detection. The methodology we present here can be viewed as a generalization or flexible extension of MaxSPRT. Published 2014. This article is a US Government work and is in the public domain in the USA.

  18. Noncommutative Biology: Sequential Regulation of Complex Networks.

    Directory of Open Access Journals (Sweden)

    William Letsou

    2016-08-01

    Full Text Available Single-cell variability in gene expression is important for generating distinct cell types, but it is unclear how cells use the same set of regulatory molecules to specifically control similarly regulated genes. While combinatorial binding of transcription factors at promoters has been proposed as a solution for cell-type specific gene expression, we found that such models resulted in substantial information bottlenecks. We sought to understand the consequences of adopting sequential logic wherein the time-ordering of factors informs the final outcome. We showed that with noncommutative control, it is possible to independently control targets that would otherwise be activated simultaneously using combinatorial logic. Consequently, sequential logic overcomes the information bottleneck inherent in complex networks. We derived scaling laws for two noncommutative models of regulation, motivated by phosphorylation/neural networks and chromosome folding, respectively, and showed that they scale super-exponentially in the number of regulators. We also showed that specificity in control is robust to the loss of a regulator. Lastly, we connected these theoretical results to real biological networks that demonstrate specificity in the context of promiscuity. These results show that achieving a desired outcome often necessitates roundabout steps.

  19. Dating phylogenies with sequentially sampled tips.

    Science.gov (United States)

    Stadler, Tanja; Yang, Ziheng

    2013-09-01

    We develop a Bayesian Markov chain Monte Carlo (MCMC) algorithm for estimating divergence times using sequentially sampled molecular sequences. This type of data is commonly collected during viral epidemics and is sometimes available from different species in ancient DNA studies. We derive the distribution of ages of nodes in the tree under a birth-death-sequential-sampling (BDSS) model and use it as the prior for divergence times in the dating analysis. We implement the prior in the MCMCtree program in the PAML package for divergence dating. The BDSS prior is very flexible and, with different parameters, can generate trees of very different shapes, suitable for examining the sensitivity of posterior time estimates. We apply the method to a data set of SIV/HIV-2 genes in comparison with a likelihood-based dating method, and to a data set of influenza H1 genes from different hosts in comparison with the Bayesian program BEAST. We examined the impact of tree topology on time estimates and suggest that multifurcating consensus trees should be avoided in dating analysis. We found posterior time estimates for old nodes to be sensitive to the priors on times and rates and suggest that previous Bayesian dating studies may have produced overconfident estimates.

  20. Estandarización de la TR-PCR para la detección de las fusiones génicas BCR-ABL en pacientes con leucemia Mieloide Crónica (LMC y Linfoide Aguda (LLA provenientes de HUSVP y Clíncia León XIII

    Directory of Open Access Journals (Sweden)

    Gonzálo Vásquez Palacio

    2006-04-01

    Full Text Available La translocación recíproca t(9:22(q34;q11 involucra el proto-oncogen ABL y el gen BCR, originando un gen de fusión BCR-ABL, que codifica una proteína con elevada actividad tirosina quinasa, implicada en la leucemogénesis.

  1. ECTOPIC PREGNANCY AFTER SEQUENTIAL EMBRYO TRANSFER: REVIEW OF 22 CASES

    OpenAIRE

    Nadkarni Purnima K, Nadkarni Kishore, Singh Pooja P, Singh Prabhakar , Nadkarni Aditi A , Agarwal Neha R

    2015-01-01

    Objective: To assess the prevalence of ectopic pregnancy among women who conceived with assisted reproductive technology and to see if there is increased risk after sequential embryo transfer. Methods: The ectopic pregnancy rate for ART pregnancies was calculated among women who conceived and had ectopic pregnancy after ICSI followed by Sequential embryo transfer from an ART centre. Variation in ectopic risk by patient and ART treatment factors was assessed including Sequential transfer, risk...

  2. Hypotension Risk Prediction via Sequential Contrast Patterns of ICU Blood Pressure.

    Science.gov (United States)

    Ghosh, Shameek; Feng, Mengling; Nguyen, Hung; Li, Jinyan

    2016-09-01

    Acute hypotension is a significant risk factor for in-hospital mortality at intensive care units. Prolonged hypotension can cause tissue hypoperfusion, leading to cellular dysfunction and severe injuries to multiple organs. Prompt medical interventions are thus extremely important for dealing with acute hypotensive episodes (AHE). Population level prognostic scoring systems for risk stratification of patients are suboptimal in such scenarios. However, the design of an efficient risk prediction system can significantly help in the identification of critical care patients, who are at risk of developing an AHE within a future time span. Toward this objective, a pattern mining algorithm is employed to extract informative sequential contrast patterns from hemodynamic data, for the prediction of hypotensive episodes. The hypotensive and normotensive patient groups are extracted from the MIMIC-II critical care research database, following an appropriate clinical inclusion criteria. The proposed method consists of a data preprocessing step to convert the blood pressure time series into symbolic sequences, using a symbolic aggregate approximation algorithm. Then, distinguishing subsequences are identified using the sequential contrast mining algorithm. These subsequences are used to predict the occurrence of an AHE in a future time window separated by a user-defined gap interval. Results indicate that the method performs well in terms of the prediction performance as well as in the generation of sequential patterns of clinical significance. Hence, the novelty of sequential patterns is in their usefulness as potential physiological biomarkers for building optimal patient risk stratification systems and for further clinical investigation of interesting patterns in critical care patients.

  3. Adaptive Learning in Extensive Form Games and Sequential Equilibrium

    DEFF Research Database (Denmark)

    Groes, Ebbe; Jacobsen, Hans Jørgen; Sloth, Birgitte

    1999-01-01

    This paper studies adaptive learning in extensive form games and provides conditions for convergence points of adaptive learning to be sequential equilibria. Precisely, we present a set of conditions on learning sequences such that an assessment is a sequential equilibrium if and only if there is......This paper studies adaptive learning in extensive form games and provides conditions for convergence points of adaptive learning to be sequential equilibria. Precisely, we present a set of conditions on learning sequences such that an assessment is a sequential equilibrium if and only...

  4. Sequential reconstruction of driving-forces from nonlinear nonstationary dynamics

    Science.gov (United States)

    Güntürkün, Ulaş

    2010-07-01

    This paper describes a functional analysis-based method for the estimation of driving-forces from nonlinear dynamic systems. The driving-forces account for the perturbation inputs induced by the external environment or the secular variations in the internal variables of the system. The proposed algorithm is applicable to the problems for which there is too little or no prior knowledge to build a rigorous mathematical model of the unknown dynamics. We derive the estimator conditioned on the differentiability of the unknown system’s mapping, and smoothness of the driving-force. The proposed algorithm is an adaptive sequential realization of the blind prediction error method, where the basic idea is to predict the observables, and retrieve the driving-force from the prediction error. Our realization of this idea is embodied by predicting the observables one-step into the future using a bank of echo state networks (ESN) in an online fashion, and then extracting the raw estimates from the prediction error and smoothing these estimates in two adaptive filtering stages. The adaptive nature of the algorithm enables to retrieve both slowly and rapidly varying driving-forces accurately, which are illustrated by simulations. Logistic and Moran-Ricker maps are studied in controlled experiments, exemplifying chaotic state and stochastic measurement models. The algorithm is also applied to the estimation of a driving-force from another nonlinear dynamic system that is stochastic in both state and measurement equations. The results are judged by the posterior Cramer-Rao lower bounds. The method is finally put into test on a real-world application; extracting sun’s magnetic flux from the sunspot time series.

  5. Multilevel sequential Monte-Carlo samplers

    KAUST Repository

    Jasra, Ajay

    2016-01-05

    Multilevel Monte-Carlo methods provide a powerful computational technique for reducing the computational cost of estimating expectations for a given computational effort. They are particularly relevant for computational problems when approximate distributions are determined via a resolution parameter h, with h=0 giving the theoretical exact distribution (e.g. SDEs or inverse problems with PDEs). The method provides a benefit by coupling samples from successive resolutions, and estimating differences of successive expectations. We develop a methodology that brings Sequential Monte-Carlo (SMC) algorithms within the framework of the Multilevel idea, as SMC provides a natural set-up for coupling samples over different resolutions. We prove that the new algorithm indeed preserves the benefits of the multilevel principle, even if samples at all resolutions are now correlated.

  6. Dancing Twins: Stellar Hierarchies That Formed Sequentially?

    Science.gov (United States)

    Tokovinin, Andrei

    2018-04-01

    This paper draws attention to the class of resolved triple stars with moderate ratios of inner and outer periods (possibly in a mean motion resonance) and nearly circular, mutually aligned orbits. Moreover, stars in the inner pair are twins with almost identical masses, while the mass sum of the inner pair is comparable to the mass of the outer component. Such systems could be formed either sequentially (inside-out) by disk fragmentation with subsequent accretion and migration, or by a cascade hierarchical fragmentation of a rotating cloud. Orbits of the outer and inner subsystems are computed or updated in four such hierarchies: LHS 1070 (GJ 2005, periods 77.6 and 17.25 years), HIP 9497 (80 and 14.4 years), HIP 25240 (1200 and 47.0 years), and HIP 78842 (131 and 10.5 years).

  7. Sequential scintigraphic staging of small cell carcinoma

    International Nuclear Information System (INIS)

    Bitran, J.D.; Bekerman, C.; Pinsky, S.

    1981-01-01

    Thirty patients with small cell carcinoma (SCC) of the lung were sequentially staged following a history and physical exam with liver, bran, bone, and gallium-67 citrate scans. Scintigraphic evaluation disclosed 7 of 30 patients (23%) with advanced disease, stage IIIM1. When Gallium-67 scans were used as the sole criteria for staging, they proved to be accurate and identified six of the seven patients with occult metastatic disease. Gallium-67 scans proved to be accurate in detecting thoracic and extrathoracic metastases in the 30 patients with SCC, especially within the liver and lymph node-bearing area. The diagnostic accuracy of gallium-67 fell in regions such as bone or brain. Despite the limitations of gallium-67 scanning, the authors conclude that these scans are useful in staging patients with SCC and should be the initial scans used in staging such patients

  8. Gleason-Busch theorem for sequential measurements

    Science.gov (United States)

    Flatt, Kieran; Barnett, Stephen M.; Croke, Sarah

    2017-12-01

    Gleason's theorem is a statement that, given some reasonable assumptions, the Born rule used to calculate probabilities in quantum mechanics is essentially unique [A. M. Gleason, Indiana Univ. Math. J. 6, 885 (1957), 10.1512/iumj.1957.6.56050]. We show that Gleason's theorem contains within it also the structure of sequential measurements, and along with this the state update rule. We give a small set of axioms, which are physically motivated and analogous to those in Busch's proof of Gleason's theorem [P. Busch, Phys. Rev. Lett. 91, 120403 (2003), 10.1103/PhysRevLett.91.120403], from which the familiar Kraus operator form follows. An axiomatic approach has practical relevance as well as fundamental interest, in making clear those assumptions which underlie the security of quantum communication protocols. Interestingly, the two-time formalism is seen to arise naturally in this approach.

  9. Merging particle filter for sequential data assimilation

    Directory of Open Access Journals (Sweden)

    S. Nakano

    2007-07-01

    Full Text Available A new filtering technique for sequential data assimilation, the merging particle filter (MPF, is proposed. The MPF is devised to avoid the degeneration problem, which is inevitable in the particle filter (PF, without prohibitive computational cost. In addition, it is applicable to cases in which a nonlinear relationship exists between a state and observed data where the application of the ensemble Kalman filter (EnKF is not effectual. In the MPF, the filtering procedure is performed based on sampling of a forecast ensemble as in the PF. However, unlike the PF, each member of a filtered ensemble is generated by merging multiple samples from the forecast ensemble such that the mean and covariance of the filtered distribution are approximately preserved. This merging of multiple samples allows the degeneration problem to be avoided. In the present study, the newly proposed MPF technique is introduced, and its performance is demonstrated experimentally.

  10. Sequential Therapy in Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bradford R Hirsch

    2016-04-01

    Full Text Available The treatment of metastatic renal cell carcinoma (mRCC has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network's Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future.

  11. Prosody and alignment: a sequential perspective

    Science.gov (United States)

    Szczepek Reed, Beatrice

    2010-12-01

    In their analysis of a corpus of classroom interactions in an inner city high school, Roth and Tobin describe how teachers and students accomplish interactional alignment by prosodically matching each other's turns. Prosodic matching, and specific prosodic patterns are interpreted as signs of, and contributions to successful interactional outcomes and positive emotions. Lack of prosodic matching, and other specific prosodic patterns are interpreted as features of unsuccessful interactions, and negative emotions. This forum focuses on the article's analysis of the relation between interpersonal alignment, emotion and prosody. It argues that prosodic matching, and other prosodic linking practices, play a primarily sequential role, i.e. one that displays the way in which participants place and design their turns in relation to other participants' turns. Prosodic matching, rather than being a conversational action in itself, is argued to be an interactional practice (Schegloff 1997), which is not always employed for the accomplishment of `positive', or aligning actions.

  12. Sequential Stereotype Priming: A Meta-Analysis.

    Science.gov (United States)

    Kidder, Ciara K; White, Katherine R; Hinojos, Michelle R; Sandoval, Mayra; Crites, Stephen L

    2017-08-01

    Psychological interest in stereotype measurement has spanned nearly a century, with researchers adopting implicit measures in the 1980s to complement explicit measures. One of the most frequently used implicit measures of stereotypes is the sequential priming paradigm. The current meta-analysis examines stereotype priming, focusing specifically on this paradigm. To contribute to ongoing discussions regarding methodological rigor in social psychology, one primary goal was to identify methodological moderators of the stereotype priming effect-whether priming is due to a relation between the prime and target stimuli, the prime and target response, participant task, stereotype dimension, stimulus onset asynchrony (SOA), and stimuli type. Data from 39 studies yielded 87 individual effect sizes from 5,497 participants. Analyses revealed that stereotype priming is significantly moderated by the presence of prime-response relations, participant task, stereotype dimension, target stimulus type, SOA, and prime repetition. These results carry both practical and theoretical implications for future research on stereotype priming.

  13. Discriminative predation: Simultaneous and sequential encounter experiments

    Directory of Open Access Journals (Sweden)

    C. D. BEATTY, D.W.FRANKS

    2012-08-01

    Full Text Available There are many situations in which the ability of animals to distinguish between two similar looking objects can have significant selective consequences. For example, the objects that require discrimination may be edible versus defended prey, predators versus non-predators, or mates of varying quality. Working from the premise that there are situations in which discrimination may be more or less successful, we hypothesized that individuals find it more difficult to distinguish between stimuli when they encounter them sequentially rather than simultaneously. Our study has wide biological and psychological implications from the perspective of signal perception, signal evolution, and discrimination, and could apply to any system where individuals are making relative judgments or choices between two or more stimuli or signals. While this is a general principle that might seem intuitive, it has not been experimentally tested in this context, and is often not considered in the design of models or experiments, or in the interpretation of a wide range of studies. Our study is different from previous studies in psychology in that a the level of similarity of stimuli are gradually varied to obtain selection gradients, and b we discuss the implications of our study for specific areas in ecology, such as the level of perfection of mimicry in predator-prey systems. Our experiments provide evidence that it is indeed more difficult to distinguish between stimuli – and to learn to distinguish between stimuli – when they are encountered sequentially rather than simultaneously, even if the intervening time interval is short [Current Zoology 58 (4: 649–657, 2012].

  14. Exploring the potential of sequential simulation.

    Science.gov (United States)

    Powell, Polly; Sorefan, Zinah; Hamilton, Sara; Kneebone, Roger; Bello, Fernando

    2016-04-01

    Several recent papers have highlighted the need for better integrated care to improve health care for children and families. Our team spent a year exploring the potential of 'Sequential Simulation' (SqS) as a teaching tool to address this need with young people and multidisciplinary teams. SqS allows the simulation of a series of key events or 'crunch points' that come together to represent the patient journey, and highlights the impact of individuals on this journey. The pilot SqS was based on an adolescent with asthma - a common condition that requires excellent multidisciplinary care with the patient at the centre. The SqS was designed using transportable sets and audio-visual equipment to create realism. Actors were employed to play the roles of the young person and mother and health professionals played themselves. The SqS was run at different events with varied audiences, including young people, health professionals and teachers. It was used to explore the difficulties that can arise during a patient journey, the importance of communication throughout, and to highlight the significance of each individual in the patient experience. The SqS was met with enthusiasm and felt to be an innovative and effective way of promoting better teamwork and communication. It was well received at a school asthma education event for pupils and community teams, demonstrating its varied potential. The year was the first step in the introduction of this exciting new concept that has the potential to help promote better integrated care for paediatric patients and their families. Our team spent a year exploring the potential of 'Sequential Simulation' as a teaching tool [to provide better integrated care]. © 2015 John Wiley & Sons Ltd.

  15. ANTHOCYANINS ALIPHATIC ALCOHOLS EXTRACTION FEATURES

    Directory of Open Access Journals (Sweden)

    P. N. Savvin

    2015-01-01

    Full Text Available Anthocyanins red pigments that give color a wide range of fruits, berries and flowers. In the food industry it is widely known as a dye a food additive E163. To extract from natural vegetable raw materials traditionally used ethanol or acidified water, but in same technologies it’s unacceptable. In order to expand the use of anthocyanins as colorants and antioxidants were explored extracting pigments alcohols with different structures of the carbon skeleton, and the position and number of hydroxyl groups. For the isolation anthocyanins raw materials were extracted sequentially twice with t = 60 C for 1.5 hours. The evaluation was performed using extracts of classical spectrophotometric methods and modern express chromaticity. Color black currant extracts depends on the length of the carbon skeleton and position of the hydroxyl group, with the alcohols of normal structure have higher alcohols compared to the isomeric structure of the optical density and index of the red color component. This is due to the different ability to form hydrogen bonds when allocating anthocyanins and other intermolecular interactions. During storage blackcurrant extracts are significant structural changes recoverable pigments, which leads to a significant change in color. In this variation, the stronger the higher the length of the carbon skeleton and branched molecules extractant. Extraction polyols (ethyleneglycol, glycerol are less effective than the corresponding monohydric alcohols. However these extracts saved significantly higher because of their reducing ability at interacting with polyphenolic compounds.

  16. Aloe plant extracts as alternative larvicides for mosquito control ...

    African Journals Online (AJOL)

    The larvicidal activity of extracts from Aloe turkanensis, Aloe ngongensis and Aloe fibrosa against the common malaria vector, Anopheles gambie, was determined. Ground Aloe leaves from the three plants were sequentially extracted with hexane, ethyl acetate, chloroform, acetone and methanol. Only the ethyl acetate ...

  17. In vitro insulinotropic actions of various extracts of Moringa oleifera ...

    African Journals Online (AJOL)

    This study investigated the in vitro insulin-releasing and cytotoxic effects of various extracts of Moringa oleifera leaves. Pulverized Moringa oleifera leaves were sequentially extracted with dichloromethane, acetone, ethylacetate and water. Clonal pancreatic beta cells, BRIN-BD11, were grown in an atmosphere of 5% CO2 ...

  18. Extraction mechanics in lingual orthodontics: Challenges and solutions

    Directory of Open Access Journals (Sweden)

    Tushar M Hegde

    2016-01-01

    Full Text Available The 21st century has witnessed a slow but sure incorporation of lingual orthodontic protocols into the orthodontic mainstream. Extraction mechanics with lingual orthodontic appliance poses challenges to even the most experienced clinician. This article is a case series of three cases treated by extraction mechanics in a detailed and sequential manner.

  19. Speciation chimique du plomb et du cuivre par extraction ...

    African Journals Online (AJOL)

    The methodology consisted of a sampling, extraction of lead and copper in water and sediment collected and assessment of these metals with an atomic absorption spectrophotometer flame. The Tessier sequential extraction method is used for this study. The results obtained indicate that only the copper is detected in the ...

  20. Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia = Determinação da lactate desidrogenase (LDH e do transcrito Bcr-Abl em pacientes com leucemia mielóide crônica

    Directory of Open Access Journals (Sweden)

    Roberto Iemitsu Tatakihara

    2010-07-01

    Full Text Available Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2 transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1. Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease. Leucemia mieloide crônica (LMC é uma desordem mieloproliferativa maligna que é originada de célula-tronco pluripotente caracterizada por expansão anormal, maligna de clones de células tronco da medula óssea na circulação. A grande maioria dos pacientes com LMC apresentam transcritos Bcr-Abl. Lactato desidrogenase (LDH,considerado um marcador bioquímico para crescimento tumoral, glicólise anaeróbica, e tem sido considerado um fator de pior prognóstico da LMC. Portanto, este estudo visa avaliar a concentraçãode LDH no plasma e a detecção do transcrito Bcr-Abl em 22 pacientes com LMC e 56 indivíduos saudáveis. Foram avaliados 22 pacientes com LMC e 56 doadores saudáveis. A

  1. Increased acetylation of lysine 317/320 of p53 caused by BCR-ABL protects from cytoplasmic translocation of p53 and mitochondria-dependent apoptosis in response to DNA damage

    NARCIS (Netherlands)

    Kusio-Kobialka, Monika; Wolanin, Kamila; Podszywalow-Bartnicka, Paulina; Sikora, Ewa; Skowronek, Krzysztof; McKenna, Sharon L.; Ghizzoni, Massimo; Dekker, Frank J.; Piwocka, Katarzyna

    Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cells caused by the expression of BCR-ABL. Loss of p53 has not been implicated as important for the development of CML. Mutations in p53 protein are infrequent, however they correlate with the disease progression. The absence of p53

  2. Derivation of sequential, real-time, process-control programs

    Science.gov (United States)

    Marzullo, Keith; Schneider, Fred B.; Budhiraja, Navin

    1991-01-01

    The use of weakest-precondition predicate transformers in the derivation of sequential, process-control software is discussed. Only one extension to Dijkstra's calculus for deriving ordinary sequential programs was found to be necessary: function-valued auxiliary variables. These auxiliary variables are needed for reasoning about states of a physical process that exists during program transitions.

  3. Factor screening for simulation with multiple responses : Sequential bifurcation

    NARCIS (Netherlands)

    Shi, W.; Kleijnen, J.P.C.; Liu, Z.

    2014-01-01

    The goal of factor screening is to find the really important inputs (factors) among the many inputs that may be changed in a realistic simulation experiment. A specific method is sequential bifurcation (SB), which is a sequential method that changes groups of inputs simultaneously. SB is most

  4. Factor Screening for Simulation with Multiple Responses : Sequential Bifurcation

    NARCIS (Netherlands)

    Shi, W.; Kleijnen, Jack P.C.; Liu, Zhixue

    2012-01-01

    Abstract: Factor screening searches for the really important inputs (factors) among the many inputs that are changed in a realistic simulation experiment. Sequential bifurcation (or SB) is a sequential method that changes groups of inputs simultaneously. SB is the most e¢ cient and effective method

  5. Factor Screening For Simulation With Multiple Responses : Sequential Bifurcation

    NARCIS (Netherlands)

    Shi, W.; Kleijnen, Jack P.C.; Liu, Zhixue

    2013-01-01

    Abstract: Factor screening searches for the really important inputs (factors) among the many inputs that are changed in a realistic simulation experiment. Sequential bifurcation (SB) is a sequential method that changes groups of inputs simultaneously. SB is the most efficient and effective method if

  6. A Survey of Multi-Objective Sequential Decision-Making

    NARCIS (Netherlands)

    Roijers, D.M.; Vamplew, P.; Whiteson, S.; Dazeley, R.

    2013-01-01

    Sequential decision-making problems with multiple objectives arise naturally in practice and pose unique challenges for research in decision-theoretic planning and learning, which has largely focused on single-objective settings. This article surveys algorithms designed for sequential

  7. Accounting for Heterogeneous Returns in Sequential Schooling Decisions

    NARCIS (Netherlands)

    Zamarro, G.

    2006-01-01

    This paper presents a method for estimating returns to schooling that takes into account that returns may be heterogeneous among agents and that educational decisions are made sequentially.A sequential decision model is interesting because it explicitly considers that the level of education of each

  8. The sequential price of anarchy for atomic congestion games

    NARCIS (Netherlands)

    de Jong, Jasper; Uetz, Marc Jochen; Liu, Tie-Yan; Qi, Qi; Ye, Yinyu

    2014-01-01

    In situations without central coordination, the price of anarchy relates the quality of any Nash equilibrium to the quality of a global optimum. Instead of assuming that all players choose their actions simultaneously, we consider games where players choose their actions sequentially. The sequential

  9. Applications of Bayesian decision theory to sequential mastery testing

    NARCIS (Netherlands)

    Vos, Hendrik J.

    1999-01-01

    The purpose of this paper is to formulate optimal sequential rules for mastery tests. The framework for the approach is derived from Bayesian sequential decision theory. Both a threshold and linear loss structure are considered. The binomial probability distribution is adopted as the psychometric

  10. Quantum Probability Zero-One Law for Sequential Terminal Events

    Science.gov (United States)

    Rehder, Wulf

    1980-07-01

    On the basis of the Jauch-Piron quantum probability calculus a zero-one law for sequential terminal events is proven, and the significance of certain crucial axioms in the quantum probability calculus is discussed. The result shows that the Jauch-Piron set of axioms is appropriate for the non-Boolean algebra of sequential events.

  11. The Clinical effectiveness of sequential treatment of skeletal class III ...

    African Journals Online (AJOL)

    Aim: To assess the dentofacial changes induced by the sequential treatment in the skeletal class III malocclusion with maxillary retrognathism. Study design: Controlled clinical trial assessing the effectiveness of sequential treatment of skeletal class III malocclusion. Materials and Methods: The treated group consisted of 30 ...

  12. Lag Sequential Analysis: Taking Consultation Communication Research to the Movies.

    Science.gov (United States)

    Benes, Kathryn M.; Gutkin, Terry B.; Kramer, Jack J.

    1995-01-01

    Describes lag-sequential analysis and its unique contributions to research literature, addressing communication processes in school-based consultation. For purposes of demonstrating the application and potential utility of lag-sequential analysis, article analyzes the communication behaviors of two consultants. Considers directions for future…

  13. Sequential injection spectrophotometric determination of V(V) in ...

    African Journals Online (AJOL)

    Sequential injection spectrophotometric determination of V(V) in environmental polluted waters. ES Silva, PCAG Pinto, JLFC Lima, MLMFS Saraiva. Abstract. A fast and robust sequential injection analysis (SIA) methodology for routine determination of V(V) in environmental polluted waters is presented. The determination ...

  14. Group-sequential analysis may allow for early trial termination

    DEFF Research Database (Denmark)

    Gerke, Oke; Vilstrup, Mie H; Halekoh, Ulrich

    2017-01-01

    assumed to be normally distributed, and sequential one-sided hypothesis tests on the population standard deviation of the differences against a hypothesised value of 1.5 were performed, employing an alpha spending function. The fixed-sample analysis (N = 45) was compared with the group-sequential analysis......BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG...... and the final analysis. Other partitions did not suggest early stopping after adjustment for multiple testing due to one influential outlier and our small sample size. CONCLUSIONS: Group-sequential testing may enable early stopping of a trial, allowing for potential time and resource savings. The testing...

  15. Beam geometry selection using sequential beam addition.

    Science.gov (United States)

    Popple, Richard A; Brezovich, Ivan A; Fiveash, John B

    2014-05-01

    The selection of optimal beam geometry has been of interest since the inception of conformal radiotherapy. The authors report on sequential beam addition, a simple beam geometry selection method, for intensity modulated radiation therapy. The sequential beam addition algorithm (SBA) requires definition of an objective function (score) and a set of candidate beam geometries (pool). In the first iteration, the optimal score is determined for each beam in the pool and the beam with the best score selected. In the next iteration, the optimal score is calculated for each beam remaining in the pool combined with the beam selected in the first iteration, and the best scoring beam is selected. The process is repeated until the desired number of beams is reached. The authors selected three treatment sites, breast, lung, and brain, and determined beam arrangements for up to 11 beams from a pool comprised of 25 equiangular transverse beams. For the brain, arrangements were additionally selected from a pool of 22 noncoplanar beams. Scores were determined for geometries comprised equiangular transverse beams (EQA), as well as two tangential beams for the breast case. In all cases, SBA resulted in scores superior to EQA. The breast case had the strongest dependence on beam geometry, for which only the 7-beam EQA geometry had a score better than the two tangential beams, whereas all SBA geometries with more than two beams were superior. In the lung case, EQA and SBA scores monotonically improved with increasing number of beams; however, SBA required fewer beams to achieve scores equivalent to EQA. For the brain case, SBA with a coplanar pool was equivalent to EQA, while the noncoplanar pool resulted in slightly better scores; however, the dose-volume histograms demonstrated that the differences were not clinically significant. For situations in which beam geometry has a significant effect on the objective function, SBA can identify arrangements equivalent to equiangular

  16. Beam geometry selection using sequential beam addition

    Energy Technology Data Exchange (ETDEWEB)

    Popple, Richard A., E-mail: rpopple@uabmc.edu; Brezovich, Ivan A.; Fiveash, John B. [Department of Radiation Oncology, The University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, Alabama 35294 (United States)

    2014-05-15

    Purpose: The selection of optimal beam geometry has been of interest since the inception of conformal radiotherapy. The authors report on sequential beam addition, a simple beam geometry selection method, for intensity modulated radiation therapy. Methods: The sequential beam addition algorithm (SBA) requires definition of an objective function (score) and a set of candidate beam geometries (pool). In the first iteration, the optimal score is determined for each beam in the pool and the beam with the best score selected. In the next iteration, the optimal score is calculated for each beam remaining in the pool combined with the beam selected in the first iteration, and the best scoring beam is selected. The process is repeated until the desired number of beams is reached. The authors selected three treatment sites, breast, lung, and brain, and determined beam arrangements for up to 11 beams from a pool comprised of 25 equiangular transverse beams. For the brain, arrangements were additionally selected from a pool of 22 noncoplanar beams. Scores were determined for geometries comprised equiangular transverse beams (EQA), as well as two tangential beams for the breast case. Results: In all cases, SBA resulted in scores superior to EQA. The breast case had the strongest dependence on beam geometry, for which only the 7-beam EQA geometry had a score better than the two tangential beams, whereas all SBA geometries with more than two beams were superior. In the lung case, EQA and SBA scores monotonically improved with increasing number of beams; however, SBA required fewer beams to achieve scores equivalent to EQA. For the brain case, SBA with a coplanar pool was equivalent to EQA, while the noncoplanar pool resulted in slightly better scores; however, the dose-volume histograms demonstrated that the differences were not clinically significant. Conclusions: For situations in which beam geometry has a significant effect on the objective function, SBA can identify

  17. Combined inhibition of β-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo.

    Science.gov (United States)

    Zhou, H; Mak, P Y; Mu, H; Mak, D H; Zeng, Z; Cortes, J; Liu, Q; Andreeff, M; Carter, B Z

    2017-10-01

    Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation, remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in granulocyte-macrophage progenitors, and highest among a novel CD34 + CD38 + CD123 hi Tim-3 hi subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells. A novel Wnt/β-catenin signaling modulator, C82, and nilotinib synergistically killed KBM5 T315I and TKI-resistant primary BC-CML cells with or without BCR-ABL kinase mutations even under leukemia/MSC co-culture conditions. Silencing of β-catenin by short interfering RNA restored sensitivity of primary BCR-ABL T315I/E255V BC-CML cells to nilotinib. Combining the C82 pro-drug, PRI-724, with nilotinib significantly prolonged the survival of NOD/SCID/IL2Rγ null mice injected with primary BCR-ABL T315I/E255V BC-CML cells. The combined treatment selectively targeted CML progenitors and inhibited CD44, c-Myc, survivin, p-CRKL and p-STAT5 expression. In addition, pretreating primary BC-CML cells with C82, or the combination, but not with nilotinib alone, significantly impaired their engraftment potential in NOD/SCID/IL2Rγ-null-3/GM/SF mice and significantly prolonged survival. Our data suggest potential benefit of concomitant β-catenin and Bcr-Abl inhibition to prevent or overcome Bcr-Abl kinase-dependent or -independent TKI resistance in BC-CML.

  18. Sequential error concealment for video/images by weighted template matching

    DEFF Research Database (Denmark)

    Koloda, Jan; Østergaard, Jan; Jensen, Søren Holdt

    2012-01-01

    In this paper we propose a novel spatial error concealment algorithm for video and images based on convex optimization. Block-based coding schemes in packet loss environment are considered. Missing macro blocks are sequentially reconstructed by filling them with a weighted set of templates...... extracted from the available neighbourhood. Moreover, a fast approximation of the optimization method is proposed. The technique produces high quality reconstructions that outperforms the state-of-the-art algorithms both in terms of PSNR and MS-SSIM....

  19. A rapid and efficient automated method for the sequential separation of plutonium and radiostrontium in seawater

    International Nuclear Information System (INIS)

    Hyuncheol Kim; Kun Ho Chung; Mee Jang; Mun ja Kang; Geun-Sik Choi

    2015-01-01

    A novel method for the simultaneous separation of Pu and 90 Sr in seawater is proposed that is based on precipitation and extraction chromatography with an automated radionuclide separator. Pu from seawater is co-precipitated with Fe(OH) 2 ; 90 Sr is precipitated as SrCO 3 . The precipitates are then dissolved in HNO 3 and sequentially separated using TEVA and Sr-resin columns on an automated radionuclide separator (MARS, Modular Automated Radionuclide Separator). The yield of Pu and Sr from 1 and 10 L of seawater ranged between 50 and 74 %, and between 77 and 95 %, respectively. (author)

  20. Speciation fingerprints of binary mixtures by the optimized sequential two-phase separation

    International Nuclear Information System (INIS)

    Macasek, F.

    1995-01-01

    The analysis of the separation methods suitable for chemical speciation of radionuclides and metals, and advantages of sequential (double) distribution technique were discussed. The equilibria are relatively easy to control and the method enables to minimize a matrix composition adjustment, and therefore it minimizes also the disturbance of original (native) state of elements. The technique may consist in the repeat solvent extraction of sample, or the replicate equilibration with sorbent. The common condition of applicability is a linear separation isotherm of the species, what is mostly a reasonable condition in case of trace concentrations. The equations used for simultaneous fitting were written in general form. 1 tab., 1 fig., 2 refs

  1. Social Influences in Sequential Decision Making.

    Directory of Open Access Journals (Sweden)

    Markus Schöbel

    Full Text Available People often make decisions in a social environment. The present work examines social influence on people's decisions in a sequential decision-making situation. In the first experimental study, we implemented an information cascade paradigm, illustrating that people infer information from decisions of others and use this information to make their own decisions. We followed a cognitive modeling approach to elicit the weight people give to social as compared to private individual information. The proposed social influence model shows that participants overweight their own private information relative to social information, contrary to the normative Bayesian account. In our second study, we embedded the abstract decision problem of Study 1 in a medical decision-making problem. We examined whether in a medical situation people also take others' authority into account in addition to the information that their decisions convey. The social influence model illustrates that people weight social information differentially according to the authority of other decision makers. The influence of authority was strongest when an authority's decision contrasted with private information. Both studies illustrate how the social environment provides sources of information that people integrate differently for their decisions.

  2. Social Influences in Sequential Decision Making

    Science.gov (United States)

    Schöbel, Markus; Rieskamp, Jörg; Huber, Rafael

    2016-01-01

    People often make decisions in a social environment. The present work examines social influence on people’s decisions in a sequential decision-making situation. In the first experimental study, we implemented an information cascade paradigm, illustrating that people infer information from decisions of others and use this information to make their own decisions. We followed a cognitive modeling approach to elicit the weight people give to social as compared to private individual information. The proposed social influence model shows that participants overweight their own private information relative to social information, contrary to the normative Bayesian account. In our second study, we embedded the abstract decision problem of Study 1 in a medical decision-making problem. We examined whether in a medical situation people also take others’ authority into account in addition to the information that their decisions convey. The social influence model illustrates that people weight social information differentially according to the authority of other decision makers. The influence of authority was strongest when an authority's decision contrasted with private information. Both studies illustrate how the social environment provides sources of information that people integrate differently for their decisions. PMID:26784448

  3. Phenomenology of the next sequential lepton

    International Nuclear Information System (INIS)

    Rizzo, T.G.

    1980-01-01

    We consider the phenomenology of a sequential, charged lepton in the mass range 6 --13 GeV. We find the semileptonic branching ratio of such a lepton to be approx. 13%; the dominant two-body modes are found to include the decay L → ν/sub L/F* with a branching ratio approx. 6%. In this analysis we assume that the mass of the lepton under consideration is lighter than the t quark such that decays such as L → ν/sub L/t-barq, where q= (d, s, or b) are kinematically forbidden. We also find that decays such as L → ν/sub L/B* (c-barb) can also be as large as approx. 6% depending on the mixing angles; the lifetime of such a lepton is found to be approx. 2.6 x 10 -12 M/sub L/ -5 sec, where M/sub L/ is in GeV

  4. Sleep memory processing: the sequential hypothesis.

    Science.gov (United States)

    Giuditta, Antonio

    2014-01-01

    According to the sequential hypothesis (SH) memories acquired during wakefulness are processed during sleep in two serial steps respectively occurring during slow wave sleep (SWS) and rapid eye movement (REM) sleep. During SWS memories to be retained are distinguished from irrelevant or competing traces that undergo downgrading or elimination. Processed memories are stored again during REM sleep which integrates them with preexisting memories. The hypothesis received support from a wealth of EEG, behavioral, and biochemical analyses of trained rats. Further evidence was provided by independent studies of human subjects. SH basic premises, data, and interpretations have been compared with corresponding viewpoints of the synaptic homeostatic hypothesis (SHY). Their similarities and differences are presented and discussed within the framework of sleep processing operations. SHY's emphasis on synaptic renormalization during SWS is acknowledged to underline a key sleep effect, but this cannot marginalize sleep's main role in selecting memories to be retained from downgrading traces, and in their integration with preexisting memories. In addition, SHY's synaptic renormalization raises an unsolved dilemma that clashes with the accepted memory storage mechanism exclusively based on modifications of synaptic strength. This difficulty may be bypassed by the assumption that SWS-processed memories are stored again by REM sleep in brain subnuclear quantum particles. Storing of memories in quantum particles may also occur in other vigilance states. Hints are provided on ways to subject the quantum hypothesis to experimental tests.

  5. DNA-nanostructure-assembly by sequential spotting

    Directory of Open Access Journals (Sweden)

    Breitenstein Michael

    2011-11-01

    Full Text Available Abstract Background The ability to create nanostructures with biomolecules is one of the key elements in nanobiotechnology. One of the problems is the expensive and mostly custom made equipment which is needed for their development. We intended to reduce material costs and aimed at miniaturization of the necessary tools that are essential for nanofabrication. Thus we combined the capabilities of molecular ink lithography with DNA-self-assembling capabilities to arrange DNA in an independent array which allows addressing molecules in nanoscale dimensions. Results For the construction of DNA based nanostructures a method is presented that allows an arrangement of DNA strands in such a way that they can form a grid that only depends on the spotted pattern of the anchor molecules. An atomic force microscope (AFM has been used for molecular ink lithography to generate small spots. The sequential spotting process allows the immobilization of several different functional biomolecules with a single AFM-tip. This grid which delivers specific addresses for the prepared DNA-strand serves as a two-dimensional anchor to arrange the sequence according to the pattern. Once the DNA-nanoarray has been formed, it can be functionalized by PNA (peptide nucleic acid to incorporate advanced structures. Conclusions The production of DNA-nanoarrays is a promising task for nanobiotechnology. The described method allows convenient and low cost preparation of nanoarrays. PNA can be used for complex functionalization purposes as well as a structural element.

  6. Sequential acquisition of mutations in myelodysplastic syndromes.

    Science.gov (United States)

    Makishima, Hideki

    2017-01-01

    Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, DDX41 mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic DNMT3A and TET2 mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms. In MDS, mutations of genes such as NRAS and FLT3, designated as Type-1 genes, may be significantly associated with leukemic evolution. Another type (Type-2) of genes, including RUNX1 and GATA2, are related to progression from low-risk to high-risk MDS. Overall, various driver mutations are sequentially acquired in MDS, at a specific time, in either germline cells, normal hematopoietic cells, or clonal MDS cells.

  7. Sequential decoders for large MIMO systems

    KAUST Repository

    Ali, Konpal S.

    2014-05-01

    Due to their ability to provide high data rates, multiple-input multiple-output (MIMO) systems have become increasingly popular. Decoding of these systems with acceptable error performance is computationally very demanding. In this paper, we employ the Sequential Decoder using the Fano Algorithm for large MIMO systems. A parameter called the bias is varied to attain different performance-complexity trade-offs. Low values of the bias result in excellent performance but at the expense of high complexity and vice versa for higher bias values. Numerical results are done that show moderate bias values result in a decent performance-complexity trade-off. We also attempt to bound the error by bounding the bias, using the minimum distance of a lattice. The variations in complexity with SNR have an interesting trend that shows room for considerable improvement. Our work is compared against linear decoders (LDs) aided with Element-based Lattice Reduction (ELR) and Complex Lenstra-Lenstra-Lovasz (CLLL) reduction. © 2014 IFIP.

  8. Sleep memory processing: the sequential hypothesis

    Directory of Open Access Journals (Sweden)

    Antonio eGiuditta

    2014-12-01

    Full Text Available According to the sequential hypothesis (SH memories acquired during wakefulness are processed during sleep in two serial steps respectively occurring during slow wave sleep (SWS and REM sleep. During SWS memories to be retained are distinguished from irrelevant or competing traces that undergo downgrading or elimination. Processed memories are stored again during REM sleep which integrates them with preexisting memories. The hypothesis received support from a wealth of EEG, behavioral, and biochemical analyses of trained rats. Further evidence was provided by independent studies of human subjects. SH basic premises, data, and interpretations have been compared with corresponding viewpoints of the synaptic homeostatic hypothesis (SHY. Their similarities and differences are presented and discussed within the framework of sleep processing operations. SHY’s emphasis on synaptic renormalization during SWS is acknowledged to underline a key sleep effect, but this cannot marginalize sleep’s main role in selecting memories to be retained from downgrading traces, and in their integration with preexisting memories. In addition, SHY’s synaptic renormalization raises an unsolved dilemma that clashes with the accepted memory storage mechanism exclusively based on modifications of synaptic strength. This difficulty may be bypassed by the assumption that SWS-processed memories are stored again by REM sleep in brain subnuclear quantum particles. Storing of memories in quantum particles may also occur in other vigilance states. Hints are provided on ways to subject the quantum hypothesis to experimental tests.

  9. Sequential parameter estimation for stochastic systems

    Directory of Open Access Journals (Sweden)

    G. A. Kivman

    2003-01-01

    Full Text Available The quality of the prediction of dynamical system evolution is determined by the accuracy to which initial conditions and forcing are known. Availability of future observations permits reducing the effects of errors in assessment the external model parameters by means of a filtering algorithm. Usually, uncertainties in specifying internal model parameters describing the inner system dynamics are neglected. Since they are characterized by strongly non-Gaussian distributions (parameters are positive, as a rule, traditional Kalman filtering schemes are badly suited to reducing the contribution of this type of uncertainties to the forecast errors. An extension of the Sequential Importance Resampling filter (SIR is proposed to this aim. The filter is verified against the Ensemble Kalman filter (EnKF in application to the stochastic Lorenz system. It is shown that the SIR is capable of estimating the system parameters and to predict the evolution of the system with a remarkably better accuracy than the EnKF. This highlights a severe drawback of any Kalman filtering scheme: due to utilizing only first two statistical moments in the analysis step it is unable to deal with probability density functions badly approximated by the normal distribution.

  10. Preceding movement effects on sequential aiming.

    Science.gov (United States)

    Cheng, Darian T; De Grosbois, John; Smirl, Jonathan; Heath, Matthew; Binsted, Gordon

    2011-11-01

    In this study, two experiments were devised to examine the control strategy used by individuals when performing sequential aiming movements. Of particular interest was the aiming behavior displayed when task difficulty was changed midway through a sequence of movements. In Experiment 1, target size was manipulated, as the targets were made either larger or smaller, between the 8th and 12th movement of the sequence. In Experiment 2, the amplitude between the two targets was similarly changed while the target size remained constant. Results revealed that in Experiment 1, individuals took two movements following the perturbation to target size, to re-tune their movement times in order to correspond with the new task difficulty. Conversely for Experiment 2, movement time changed immediately and in correspondence with the new target amplitude. These findings demonstrate that participants can use information from the preceding movement to prepare and guide subsequent movements--but only when target size is changed. When response amplitude changes mid-sequence, it seems individuals rely more on immediate, target-derived information. Therefore, counter to some current accounts of visual movement control, it appears that memory representations of the preceding movement can guide subsequent movements; however, this information appears selectively accessed in a context-dependent fashion.

  11. Constrained treatment planning using sequential beam selection

    International Nuclear Information System (INIS)

    Woudstra, E.; Storchi, P.R.M.

    2000-01-01

    In this paper an algorithm is described for automated treatment plan generation. The algorithm aims at delivery of the prescribed dose to the target volume without violation of constraints for target, organs at risk and the surrounding normal tissue. Pre-calculated dose distributions for all candidate orientations are used as input. Treatment beams are selected in a sequential way. A score function designed for beam selection is used for the simultaneous selection of beam orientations and weights. In order to determine the optimum choice for the orientation and the corresponding weight of each new beam, the score function is first redefined to account for the dose distribution of the previously selected beams. Addition of more beams to the plan is stopped when the target dose is reached or when no additional dose can be delivered without violating a constraint. In the latter case the score function is modified by importance factor changes to enforce better sparing of the organ with the limiting constraint and the algorithm is run again. (author)

  12. Spatiotemporal Mining of Time-Series Remote Sensing Images Based on Sequential Pattern Mining

    Science.gov (United States)

    Liu, H. C.; He, G. J.; Zhang, X. M.; Jiang, W.; Ling, S. G.

    2015-07-01

    With the continuous development of satellite techniques, it is now possible to acquire a regular series of images concerning a given geographical zone with both high accuracy and low cost. Research on how best to effectively process huge volumes of observational data obtained on different dates for a specific geographical zone, and to exploit the valuable information regarding land cover contained in these images has received increasing interest from the remote sensing community. In contrast to traditional land cover change measures using pair-wise comparisons that emphasize the compositional or configurational changes between dates, this research focuses on the analysis of the temporal sequence of land cover dynamics, which refers to the succession of land cover types for a given area over more than two observational periods. Using a time series of classified Landsat images, ranging from 2006 to 2011, a sequential pattern mining method was extended to this spatiotemporal context to extract sets of connected pixels sharing similar temporal evolutions. The resultant sequential patterns could be selected (or not) based on the range of support values. These selected patterns were used to explore the spatial compositions and temporal evolutions of land cover change within the study region. Experimental results showed that continuous patterns that represent consistent land cover over time appeared as quite homogeneous zones, which agreed with our domain knowledge. Discontinuous patterns that represent land cover change trajectories were dominated by the transition from vegetation to bare land, especially during 2009-2010. This approach quantified land cover changes in terms of the percentage area affected and mapped the spatial distribution of these changes. Sequential pattern mining has been used for string mining or itemset mining in transactions analysis. The expected novel significance of this study is the generalization of the application of the sequential pattern

  13. Distortion product otoacoustic emissions: comparison of sequential vs. simultaneous presentation of primary tones.

    Science.gov (United States)

    Kumar, U Ajith; Maruthy, Sandeep; Chandrakant, Vishwakarma

    2009-03-01

    Distortion product otoacoustic emissions are one form of evoked otoacoustic emissions. DPOAEs provide the frequency specific information about the hearing status in mid and high frequency regions. But in most screening protocols TEOAEs are preferred as it requires less time compared to DPOAE. This is because, in DPOAE each stimulus is presented one after the other and responses are analyzed. Grason and Stadler Incorporation 60 (GSI-60) offer simultaneous presentation of four sets of primary tones at a time and checks for the DPOAE. In this mode of presentation, all the pairs are presented at a time and following that response is extracted separately whereas, in sequential mode primaries are presented in orderly fashion one after the other. In this article simultaneous and sequential protocols were used to compare the Distortion product otoacoustic emission amplitude, noise floor and administration time in individuals with normal hearing and mild sensori-neural (SN) hearing loss. In simultaneous protocols four sets of primary tones (i.e. 8 tones) were presented together whereas, in sequential presentation mode one set of primary tones was presented each time. Simultaneous protocol was completed in less than half the time required for the completion of sequential protocol. Two techniques yielded similar results at frequencies above 1000 Hz only in normal hearing group. In SN hearing loss group simultaneous presentation yielded signifi cantly higher noise floors and distortion product amplitudes. This result challenges the use of simultaneous presentation technique in neonatal hearing screening programmes and on other pathologies. This discrepancy between two protocols may be due to some changes in biomechanical process in the cochlear and/or due to higher distortion/noise produced by the system during the simultaneous presentation mode.

  14. Comparison of metals extractability from Al/Fe-based drinking water treatment residuals.

    Science.gov (United States)

    Wang, Changhui; Bai, Leilei; Pei, Yuansheng; Wendling, Laura A

    2014-12-01

    Recycling of drinking water treatment residuals (WTRs) as environment amendments has attracted substantial interest due to their productive reuse concomitant with waste minimization. In the present study, the extractability of metals within six Al/Fe-hydroxide-comprised WTRs collected throughout China was investigated using fractionation, in vitro digestion and the toxicity characteristic leaching procedure (TCLP). The results suggested that the major components and structure of the WTRs investigated were similar. The WTRs were enriched in Al, Fe, Ca, and Mg, also contained varying quantities of As, Ba, Be, Cd, Co, Cr, Cu, K, Mn, Mo, Na, Ni, Pb, Sr, V, and Zn, but Ag, Hg, Sb, and Se were not detected. Most of the metals within the WTRs were largely non-extractable using the European Community Bureau of Reference (BCR) procedure, but many metals exhibited high bioaccessibility based on in vitro digestion. However, the WTRs could be classified as non-hazardous according to the TCLP assessment method used by the US Environmental Protection Agency (USEPA). Further analysis showed the communication factor, which is calculated as the ratio of total extractable metal by BCR procedure to the total metal, for most metals in the six WTRs, was similar, whereas the factor for Ba, Mn, Sr, and Zn varied substantially. Moreover, metals in the WTRs investigated had different risk assessment code. In summary, recycling of WTRs is subject to regulation based on assessment of risk due to metals prior to practical application.

  15. The sequential trauma score - a new instrument for the sequential mortality prediction in major trauma*

    Directory of Open Access Journals (Sweden)

    Huber-Wagner S

    2010-05-01

    Full Text Available Abstract Background There are several well established scores for the assessment of the prognosis of major trauma patients that all have in common that they can be calculated at the earliest during intensive care unit stay. We intended to develop a sequential trauma score (STS that allows prognosis at several early stages based on the information that is available at a particular time. Study design In a retrospective, multicenter study using data derived from the Trauma Registry of the German Trauma Society (2002-2006, we identified the most relevant prognostic factors from the patients basic data (P, prehospital phase (A, early (B1, and late (B2 trauma room phase. Univariate and logistic regression models as well as score quality criteria and the explanatory power have been calculated. Results A total of 2,354 patients with complete data were identified. From the patients basic data (P, logistic regression showed that age was a significant predictor of survival (AUCmodel p, area under the curve = 0.63. Logistic regression of the prehospital data (A showed that blood pressure, pulse rate, Glasgow coma scale (GCS, and anisocoria were significant predictors (AUCmodel A = 0.76; AUCmodel P + A = 0.82. Logistic regression of the early trauma room phase (B1 showed that peripheral oxygen saturation, GCS, anisocoria, base excess, and thromboplastin time to be significant predictors of survival (AUCmodel B1 = 0.78; AUCmodel P +A + B1 = 0.85. Multivariate analysis of the late trauma room phase (B2 detected cardiac massage, abbreviated injury score (AIS of the head ≥ 3, the maximum AIS, the need for transfusion or massive blood transfusion, to be the most important predictors (AUCmodel B2 = 0.84; AUCfinal model P + A + B1 + B2 = 0.90. The explanatory power - a tool for the assessment of the relative impact of each segment to mortality - is 25% for P, 7% for A, 17% for B1 and 51% for B2. A spreadsheet for the easy calculation of the sequential trauma

  16. Fast sequential Monte Carlo methods for counting and optimization

    CERN Document Server

    Rubinstein, Reuven Y; Vaisman, Radislav

    2013-01-01

    A comprehensive account of the theory and application of Monte Carlo methods Based on years of research in efficient Monte Carlo methods for estimation of rare-event probabilities, counting problems, and combinatorial optimization, Fast Sequential Monte Carlo Methods for Counting and Optimization is a complete illustration of fast sequential Monte Carlo techniques. The book provides an accessible overview of current work in the field of Monte Carlo methods, specifically sequential Monte Carlo techniques, for solving abstract counting and optimization problems. Written by authorities in the

  17. District heating in sequential energy supply

    International Nuclear Information System (INIS)

    Persson, Urban; Werner, Sven

    2012-01-01

    Highlights: ► European excess heat recovery and utilisation by district heat distribution. ► Heat recovery in district heating systems – a structural energy efficiency measure. ► Introduction of new theoretical concepts to express excess heat recovery. ► Fourfold potential for excess heat utilisation in EU27 compared to current levels. ► Large scale excess heat recovery – a collaborative challenge for future Europe. -- Abstract: Increased recovery of excess heat from thermal power generation and industrial processes has great potential to reduce primary energy demands in EU27. In this study, current excess heat utilisation levels by means of district heat distribution are assessed and expressed by concepts such as recovery efficiency, heat recovery rate, and heat utilisation rate. For two chosen excess heat activities, current average EU27 heat recovery levels are compared to currently best Member State practices, whereby future potentials of European excess heat recovery and utilisation are estimated. The principle of sequential energy supply is elaborated to capture the conceptual idea of excess heat recovery in district heating systems as a structural and organisational energy efficiency measure. The general conditions discussed concerning expansion of heat recovery into district heating systems include infrastructure investments in district heating networks, collaboration agreements, maintained value chains, policy support, world market energy prices, allocation of synergy benefits, and local initiatives. The main conclusion from this study is that a future fourfold increase of current EU27 excess heat utilisation by means of district heat distribution to residential and service sectors is conceived as plausible if applying best Member State practice. This estimation is higher than the threefold increase with respect to direct feasible distribution costs estimated by the same authors in a previous study. Hence, no direct barriers appear with

  18. Multiple imputation with sequential penalized regression.

    Science.gov (United States)

    Zahid, Faisal M; Heumann, Christian

    2018-01-01

    Missing data is a common issue that can cause problems in estimation and inference in biomedical, epidemiological and social research. Multiple imputation is an increasingly popular approach for handling missing data. In case of a large number of covariates with missing data, existing multiple imputation software packages may not work properly and often produce errors. We propose a multiple imputation algorithm called mispr based on sequential penalized regression models. Each variable with missing values is assumed to have a different distributional form and is imputed with its own imputation model using the ridge penalty. In the case of a large number of predictors with respect to the sample size, the use of a quadratic penalty guarantees unique estimates for the parameters and leads to better predictions than the usual Maximum Likelihood Estimation (MLE), with a good compromise between bias and variance. As a result, the proposed algorithm performs well and provides imputed values that are better even for a large number of covariates with small samples. The results are compared with the existing software packages mice, VIM and Amelia in simulation studies. The missing at random mechanism was the main assumption in the simulation study. The imputation performance of the proposed algorithm is evaluated with mean squared imputation error and mean absolute imputation error. The mean squared error ([Formula: see text]), parameter estimates with their standard errors and confidence intervals are also computed to compare the performance in the regression context. The proposed algorithm is observed to be a good competitor to the existing algorithms, with smaller mean squared imputation error, mean absolute imputation error and mean squared error. The algorithm's performance becomes considerably better than that of the existing algorithms with increasing number of covariates, especially when the number of predictors is close to or even greater than the sample size. Two

  19. “Shotgun” Versus Sequential Testing

    Science.gov (United States)

    Carr, Phyllis L; Rothberg, Michael B; Friedman, Robert H; Felsenstein, Donna; Pliskin, Joseph S

    2005-01-01

    Background Although vaginitis is a common outpatient problem, only 60% of patients can be diagnosed at the initial office visit of a primary care provider using the office procedures of pH testing, whiff tests, normal saline, and potassium hydroxide preps. Objective To determine the most cost-effective diagnostic and treatment approach for the medical management of vaginitis. Design Decision and cost-effectiveness analyses. Participants Healthy women with symptoms of vaginitis undiagnosed after an initial pelvic exam, wet mount preparations, pH, and the four criteria to diagnose bacterial vaginosis. Setting General office practice. Methods We evaluated 28 diagnostic strategies comprised of combinations of pH testing, vaginal cultures for yeast and Trichomonas vaginalis, Gram's stain for bacterial vaginosis, and DNA probes for Neisseria gonorrhoeae and Chlamydia. Data sources for the study were confined to English language literature. Measurement The outcome measures were symptom-days and costs. Results The least expensive strategy was to perform yeast culture, gonorrhoeae and Chlamydia probes at the initial visit, and Gram's stain and Trichomonas culture only when the vaginal pH exceeded 4.9 ($330, 7.30 symptom days). Other strategies cost $8 to $76 more and increased duration of symptoms by up to 1.3 days. In probabilistic sensitivity analysis, this strategy was always the most effective strategy and was also least expensive 58% of the time. Conclusions For patients with vaginitis symptoms undiagnosed by pelvic examination, wet mount preparations and related office tests, a comprehensive, pH-guided testing strategy at the initial office visit is less expensive and more effective than ordering tests sequentially. PMID:16117745

  20. Large-scale sequential quadratic programming algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Eldersveld, S.K.

    1992-09-01

    The problem addressed is the general nonlinear programming problem: finding a local minimizer for a nonlinear function subject to a mixture of nonlinear equality and inequality constraints. The methods studied are in the class of sequential quadratic programming (SQP) algorithms, which have previously proved successful for problems of moderate size. Our goal is to devise an SQP algorithm that is applicable to large-scale optimization problems, using sparse data structures and storing less curvature information but maintaining the property of superlinear convergence. The main features are: 1. The use of a quasi-Newton approximation to the reduced Hessian of the Lagrangian function. Only an estimate of the reduced Hessian matrix is required by our algorithm. The impact of not having available the full Hessian approximation is studied and alternative estimates are constructed. 2. The use of a transformation matrix Q. This allows the QP gradient to be computed easily when only the reduced Hessian approximation is maintained. 3. The use of a reduced-gradient form of the basis for the null space of the working set. This choice of basis is more practical than an orthogonal null-space basis for large-scale problems. The continuity condition for this choice is proven. 4. The use of incomplete solutions of quadratic programming subproblems. Certain iterates generated by an active-set method for the QP subproblem are used in place of the QP minimizer to define the search direction for the nonlinear problem. An implementation of the new algorithm has been obtained by modifying the code MINOS. Results and comparisons with MINOS and NPSOL are given for the new algorithm on a set of 92 test problems.

  1. On sequential dynamical systems and simulation

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, C.L.; Mortveit, H.S.; Reidys, C.M.

    1999-06-01

    The generic structure of computer simulations motivates a new class of discrete dynamical systems that captures this structure in a mathematically precise way. This class of systems consists of (1) a loopfree graph {Upsilon} with vertex set {l_brace}1,2,{hor_ellipsis},n{r_brace} where each vertex has a binary state, (2) a vertex labeled set of functions (F{sub i,{Upsilon}}:F{sub 2}{sup n} {r_arrow} F{sub 2}{sup n}){sub i} and (3) a permutation {pi} {element_of} S{sub n}. The function F{sub i,{Upsilon}} updates the state of vertex i as a function of the states of vertex i and its {Upsilon}-neighbors and leaves the states of all other vertices fixed. The permutation {pi} represents the update ordering, i.e., the order in which the functions F{sub i,{Upsilon}} are applied. By composing the functions F{sub i,{Upsilon}} in the order given by {pi} one obtains the dynamical system (equation given in paper) which the authors refer to as a sequential dynamical system, or SDS for short. The authors will present bounds for the number of functionally different systems and for the number of nonisomorphic digraphs {Gamma}[F{sub {Upsilon}},{pi}] that can be obtained by varying the update order and applications of these to specific graphs and graph classes. This will be done using both combinatorial/algebraic techniques and probabilistic techniques. Finally the authors give results on dynamical system properties for some special systems.

  2. Fermentation characteristics of polysaccharide fractions extracted from the cell walls of soya bean cotyledons

    NARCIS (Netherlands)

    Laar, van H.; Tamminga, S.; Williams, B.A.; Verstegen, M.W.A.; Schols, H.A.

    2000-01-01

    Full-fat soya beans were separated into hulls and cotyledons. After separation the cell wall fraction was extracted from the cotyledons. These purified cell walls were sequentially extracted with 0.05 M cyclohexane-trans-1,2-diamine-N,N,N ,N -tetraacetate (CDTA) 0.05 M NH4 oxalate (extract 1), 0.05

  3. Sequential ensemble-based optimal design for parameter estimation: SEQUENTIAL ENSEMBLE-BASED OPTIMAL DESIGN

    Energy Technology Data Exchange (ETDEWEB)

    Man, Jun [Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou China; Zhang, Jiangjiang [Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou China; Li, Weixuan [Pacific Northwest National Laboratory, Richland Washington USA; Zeng, Lingzao [Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou China; Wu, Laosheng [Department of Environmental Sciences, University of California, Riverside California USA

    2016-10-01

    The ensemble Kalman filter (EnKF) has been widely used in parameter estimation for hydrological models. The focus of most previous studies was to develop more efficient analysis (estimation) algorithms. On the other hand, it is intuitively understandable that a well-designed sampling (data-collection) strategy should provide more informative measurements and subsequently improve the parameter estimation. In this work, a Sequential Ensemble-based Optimal Design (SEOD) method, coupled with EnKF, information theory and sequential optimal design, is proposed to improve the performance of parameter estimation. Based on the first-order and second-order statistics, different information metrics including the Shannon entropy difference (SD), degrees of freedom for signal (DFS) and relative entropy (RE) are used to design the optimal sampling strategy, respectively. The effectiveness of the proposed method is illustrated by synthetic one-dimensional and two-dimensional unsaturated flow case studies. It is shown that the designed sampling strategies can provide more accurate parameter estimation and state prediction compared with conventional sampling strategies. Optimal sampling designs based on various information metrics perform similarly in our cases. The effect of ensemble size on the optimal design is also investigated. Overall, larger ensemble size improves the parameter estimation and convergence of optimal sampling strategy. Although the proposed method is applied to unsaturated flow problems in this study, it can be equally applied in any other hydrological problems.

  4. Characterization of plant-derived carbon and phosphorus in lakes by sequential fractionation and NMR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shasha [College of Water Sciences, Beijing Normal University, Beijing 100875 (China); State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Zhu, Yuanrong, E-mail: zhuyuanrong07@mails.ucas.ac.cn [State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Wu, Fengchang, E-mail: wufengchang@vip.skleg.cn [State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Meng, Wei [State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); He, Zhongqi [USDA-ARS Southern Regional Research Center, 1100 Robert E Lee Blvd, New Orleans, LA 70124 (United States); Giesy, John P. [State Key Laboratory of Environment Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Department of Biomedical and Veterinary Biosciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan (Canada)

    2016-10-01

    Although debris from aquatic macrophytes is one of the most important endogenous sources of organic matter (OM) and nutrients in lakes, its biogeochemical cycling and contribution to internal load of nutrients in eutrophic lakes are still poorly understood. In this study, sequential fractionation by H{sub 2}O, 0.1 M NaOH and 1.0 M HCl, combined with {sup 13}C and {sup 31}P NMR spectroscopy, was developed and used to characterize organic carbon (C) and phosphorus (P) in six aquatic plants collected from Tai Lake (Ch: Taihu), China. Organic matter, determined by total organic carbon (TOC), was unequally distributed in H{sub 2}O (21.2%), NaOH (29.9%), HCl (3.5%) and residual (45.3%) fractions. For P in debris of aquatic plants, 53.3% was extracted by H{sub 2}O, 31.9% by NaOH, and 11% by HCl, with 3.8% in residual fractions. Predominant OM components extracted by H{sub 2}O and NaOH were carbohydrates, proteins and aliphatic acids. Inorganic P (P{sub i}) was the primary form of P in H{sub 2}O fractions, whereas organic P (P{sub o}) was the primary form of P in NaOH fractions. The subsequent HCl fractions extracted fewer species of C and P. Some non-extractable carbohydrates, aromatics and metal phytate compounds remained in residual fractions. Based on sequential extraction and NMR analysis, it was proposed that those forms of C (54.7% of TOC) and P (96.2% of TP) in H{sub 2}O, NaOH and HCl fractions are potentially released to overlying water as labile components, while those in residues are stable and likely preserved in sediments of lakes. These results will be helpful in understanding internal loading of nutrients from debris of aquatic macrophytes and their recycling in lakes. - Highlights: • Sequential fractionation combined with NMR analysis was applied on aquatic plants. • Labile and stable C and P forms in aquatic plants were characterized. • 54.7% of OM and 96.2% of P in aquatic plants are potentially available. • 45.3% of OM and 3.8% of P in aquatic

  5. In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants.

    Science.gov (United States)

    Soverini, Simona; De Benedittis, Caterina; Castagnetti, Fausto; Gugliotta, Gabriele; Mancini, Manuela; Bavaro, Luana; Machova Polakova, Katerina; Linhartova, Jana; Iurlo, Alessandra; Russo, Domenico; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

    2016-08-02

    Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal

  6. Biodegradable charged polyester-based vectors (BCPVs) as an efficient non-viral transfection nanoagent for gene knockdown of the BCR-ABL hybrid oncogene in a human chronic myeloid leukemia cell line

    Science.gov (United States)

    Yang, Chengbin; Panwar, Nishtha; Wang, Yucheng; Zhang, Butian; Liu, Maixian; Toh, Huiting; Yoon, Ho Sup; Tjin, Swee Chuan; Chong, Peter Han Joo; Law, Wing-Cheung; Chen, Chih-Kuang; Yong, Ken-Tye

    2016-04-01

    First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro

  7. Sequential Learning and Recognition of Comprehensive Behavioral Patterns Based on Flow of People

    Science.gov (United States)

    Gibo, Tatsuya; Aoki, Shigeki; Miyamoto, Takao; Iwata, Motoi; Shiozaki, Akira

    Recently, surveillance cameras have been set up everywhere, for example, in streets and public places, in order to detect irregular situations. In the existing surveillance systems, as only a handful of surveillance agents watch a large number of images acquired from surveillance cameras, there is a possibility that they may miss important scenes such as accidents or abnormal incidents. Therefore, we propose a method for sequential learning and the recognition of comprehensive behavioral patterns in crowded places. First, we comprehensively extract a flow of people from input images by using optical flow. Second, we extract behavioral patterns on the basis of change-point detection of the flow of people. Finally, in order to recognize an observed behavioral pattern, we draw a comparison between the behavioral pattern and previous behavioral patterns in the database. We verify the effectiveness of our approach by placing a surveillance camera on a campus.

  8. Protein Extractability

    African Journals Online (AJOL)

    Results showed that protein extractability was dependent on pH, type of salt, salt concentrations and extraction time. Salts extracted more proteins from the moringa seed flour than water. Maximum extraction of protein was. 85.06% and 84.72% with 0.5 M CaCl and 0.75 M NaCl respectively. On varying the pH, maximum ...

  9. Extraction, fatty acid profile and antioxidant activity of sesame extract (Sesamum Indicum L.

    Directory of Open Access Journals (Sweden)

    R. H. R. Carvalho

    2012-06-01

    Full Text Available This article carried out the extraction of sesame oil by using three extraction techniques: supercritical fluid extraction (SFE, Soxhlet and sequential extraction. The SFE was performed using supercritical carbon dioxide (SC-CO2 as solvent and ethanol as cosolvent. Tests were performed at 20 MPa, 35ºC and a flow rate of 2.5 g CO2/min with a total extraction time of 210 minutes. The Soxhlet extraction was performed for 8 hours, using petroleum ether and ethanol as solvents, until the exhaustion of the oil contained in the seeds. The sequential extraction used ethyl ether, ethanol and water as solvents. The Soxhlet extraction was the most effective (58.93%, while the SFE technique obtained 26.47% as the best result. The antioxidant activity (AA was determined by the β-carotene/linoleic acid system, with good oxidation inhibition percentages (29.32-83.49% for all the extracts. The main fatty acids (FA in sesame oil were oleic and linoleic acids.

  10. Ultrasound Vector Flow Imaging: Part I: Sequential Systems

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Nikolov, Svetoslav Ivanov; Yu, Alfred C. H.

    2016-01-01

    The paper gives a review of the most important methods for blood velocity vector flow imaging (VFI) for conventional, sequential data acquisition. This includes multibeam methods, speckle tracking, transverse oscillation, color flow mapping derived vector flow imaging, directional beamforming...

  11. Sequential Low Cost Interventions Double Hand Hygiene Rates ...

    African Journals Online (AJOL)

    Sequential Low Cost Interventions Double Hand Hygiene Rates Among Medical Teams in a Resource Limited Setting. Results of a Hand Hygiene Quality Improvement Project Conducted At University Teaching Hospital of Kigali (Chuk), Kigali, Rwanda.

  12. Process tomography via sequential measurements on a single quantum system

    CSIR Research Space (South Africa)

    Bassa, H

    2015-09-01

    Full Text Available The authors utilize a discrete (sequential) measurement protocol to investigate quantum process tomography of a single two-level quantum system, with an unknown initial state, undergoing Rabi oscillations. The ignorance of the dynamical parameters...

  13. Randomized Sequential Trial of Valproic Acid in Amyotrophic Lateral Sclerosis

    NARCIS (Netherlands)

    Piepers, Sanne; Veldink, Jan H.; de Jong, Sonja W.; van der Tweel, Ingeborg; van der Pol, W.-Ludo; Uijtendaal, Esther V.; Schelhaas, H. Jurgen; Scheffer, Hans; de Visser, Marianne; de Jong, J. M. B. Vianney; Wokke, John H. J.; Groeneveld, Geert Jan; van den Berg, Leonard H.

    2009-01-01

    Objective: To determine whether valproic acid (VPA), a histone deacetylase inhibitor that showed antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclinical studies, is safe and effective in amyotrophic lateral sclerosis (ALS) using a sequential trial design. Methods:

  14. A Sequential Preparation of Organic Compounds for Senior Chemistry Classes

    Science.gov (United States)

    Merrigan, Cecilia; Crotty, Patricia

    1971-01-01

    Describes procedures suitable for student preparation of benzaldehyde, benzoic acid, and ethyl benzoate sequentially from benzyl alcohol. Preparation for benzyl chloride also given. All reagents except benzyl alcohol are common inorganic chemicals. (AL)

  15. A Survey of Multi-Objective Sequential Decision-Making

    OpenAIRE

    Roijers, D.M.; Vamplew, P.; Whiteson, S.; Dazeley, R.

    2013-01-01

    Sequential decision-making problems with multiple objectives arise naturally in practice and pose unique challenges for research in decision-theoretic planning and learning, which has largely focused on single-objective settings. This article surveys algorithms designed for sequential decision-making problems with multiple objectives. Though there is a growing body of literature on this subject, little of it makes explicit under what circumstances special methods are needed to solve multi-obj...

  16. A Trust-region-based Sequential Quadratic Programming Algorithm

    DEFF Research Database (Denmark)

    Henriksen, Lars Christian; Poulsen, Niels Kjølstad

    This technical note documents the trust-region-based sequential quadratic programming algorithm used in other works by the authors. The algorithm seeks to minimize a convex nonlinear cost function subject to linear inequalty constraints and nonlinear equality constraints.......This technical note documents the trust-region-based sequential quadratic programming algorithm used in other works by the authors. The algorithm seeks to minimize a convex nonlinear cost function subject to linear inequalty constraints and nonlinear equality constraints....

  17. Sequential weak continuity of null Lagrangians at the boundary

    Czech Academy of Sciences Publication Activity Database

    Kalamajska, A.; Kraemer, S.; Kružík, Martin

    2014-01-01

    Roč. 49, 3/4 (2014), s. 1263-1278 ISSN 0944-2669 R&D Projects: GA ČR GAP201/10/0357 Institutional support: RVO:67985556 Keywords : null Lagrangians * nonhomogeneous nonlinear mappings * sequential weak/in measure continuity Subject RIV: BA - General Mathematics Impact factor: 1.518, year: 2014 http://library.utia.cas.cz/separaty/2013/MTR/kruzik-sequential weak continuity of null lagrangians at the boundary.pdf

  18. Sequential lending with dynamic joint liability in micro-finance

    OpenAIRE

    Chowdhury, Shyamal; Roy Chowdhury, Prabal; Sengupta, Kunal

    2014-01-01

    This paper develops a theory of sequential lending in groups in micro-finance that centers on the notion of dynamic incentives, in particular the simple idea that default incentives should be relatively uniformly distributed across time. In a framework that allows project returns to accrue over time, as well as strategic default, we show that sequential lending can help resolve problems arising out of coordinated default, thus improving project efficiency vis-a-vis individual l...

  19. Learning and sleep: the sequential hypothesis.

    Science.gov (United States)

    Ambrosini, M V.; Giuditta, A

    2001-12-01

    During the last 30 years, paradoxical sleep (PS) has been generally considered as the only type of sleep involved in memory processing, mainly for the consistent increase of PS episodes in laboratory animals learning a relatively complex task, and for the retention deficits induced by post-training PS deprivation. The vicissitudes of this idea, examined in detail by several laboratories, have been critically presented in a number of review articles However, according to a more comprehensive unitary proposal (the sequential hypothesis), memory processing during sleep does require the initial participation of slow-wave sleep (SS) in addition to the subsequent involvement of PS. The evidence supporting this hypothesis, largely derived from experiments concerning rats trained for a two-way active avoidance task, is reviewed here in some detail. Recent studies of human sleep are in full agreement with this view. In the rat, the main effect of learning on post-training SS consists in the selective increment in the average duration of SS episodes initiating different types of sleep sequences. Notably, following training for a two-way active avoidance task, the occurrence of this effect in sleep sequences including transition sleep (TS), such as SS-->TS-->W and SS-->TS-->PS, appears related to the processing of memories of the novel avoidance response. Conversely, the occurrence of the same effect in sleep sequences lacking TS may reflect the processing of memories of innate responses (escapes and freezings). Memories of innate and novel responses are assumed to engage in a dynamic competitive interaction to attain control of waking behaviour. Interestingly, in baseline sleep, variables of SS-->TS-->W and SS-->TS-->PS sequences, such as the average duration of SS, TS, and PS episodes, have proved to be good indices of the capacity to learn, as shown by their strong correlations with the number of avoidances scored by rats the following day. Comparable correlations have not

  20. Sequential pattern data mining and visualization

    Science.gov (United States)

    Wong, Pak Chung [Richland, WA; Jurrus, Elizabeth R [Kennewick, WA; Cowley, Wendy E [Benton City, WA; Foote, Harlan P [Richland, WA; Thomas, James J [Richland, WA

    2009-05-26

    One or more processors (22) are operated to extract a number of different event identifiers therefrom. These processors (22) are further operable to determine a number a display locations each representative of one of the different identifiers and a corresponding time. The display locations are grouped into sets each corresponding to a different one of several event sequences (330a, 330b, 330c. 330d, 330e). An output is generated corresponding to a visualization (320) of the event sequences (330a, 330b, 330c, 330d, 330e).

  1. Branching ratios in sequential statistical multifragmentation

    International Nuclear Information System (INIS)

    Moretto, L.G.; Phair, L.; Tso, K.; Jing, K.; Wozniak, G.J.

    1995-01-01

    The energy dependence of the probability of producing n fragments follows a characteristic statistical law. Experimental intermediate-mass-fragment multiplicity distributions are shown to be binomial at all excitation energies. From these distributions a single binary event probability can be extracted that has the thermal dependence p=exp[-B/T]. Thus, it is inferred that multifragmentation is a sequence of thermal binary events. The increase of p with excitation energy implies a corresponding contraction of the time-scale and explains recently observed fragment-fragment and fragment-spectator Coulomb correlations. (authors). 22 refs., 5 figs

  2. Branching ratios in sequential statistical multifragmentation

    International Nuclear Information System (INIS)

    Moretto, L.G.; Phair, L.; Tso, K.; Jing, K.; Wozniak, G.J.

    1995-01-01

    The energy dependence of the probability of producing n fragments follows a characteristic statistical law. Experimental intermediate-mass-fragment multiplicity distributions are shown to be binomial at all excitation energies. From these distributions a single binary event probability can be extracted that has the thermal dependence p = exp[-B/T]. Thus, it is inferred that multifragmentation is a sequence of thermal binary events. The increase of p with excitation energy implies a corresponding contraction of the time-scale and explains recently observed fragment-fragment and fragment-spectator Coulomb correlations. (author). 22 refs., 5 figs

  3. ECTOPIC PREGNANCY AFTER SEQUENTIAL EMBRYO TRANSFER: REVIEW OF 22 CASES

    Directory of Open Access Journals (Sweden)

    Nadkarni Purnima K, Nadkarni Kishore, Singh Pooja P, Singh Prabhakar , Nadkarni Aditi A , Agarwal Neha R

    2015-07-01

    Full Text Available Objective: To assess the prevalence of ectopic pregnancy among women who conceived with assisted reproductive technology and to see if there is increased risk after sequential embryo transfer. Methods: The ectopic pregnancy rate for ART pregnancies was calculated among women who conceived and had ectopic pregnancy after ICSI followed by Sequential embryo transfer from an ART centre. Variation in ectopic risk by patient and ART treatment factors was assessed including Sequential transfer, risk factor for ectopic pregnancy, tubal infertility and previous ectopic pregnancy. Results: Of 1960 women, who underwent ICSI, 1047(53.41% had positive pregnancy, 22(2.1% women had an ectopic pregnancy out of which 2(9% had heterotrophic pregnancy. The mean age was 30.4±4.33. Tubal factor contributed to 31.81% cases and 27.27% had previous history of ectopic pregnancy. Sequential transfer was done in all the patients with more than one embryo transferred. There was no significant increase in the ectopic pregnancy when Sequential embryo transfer was done. Conclusion: Tubal factor infertility and history of previous ectopic pregnancy contributed to risk factor for ectopic pregnancy in our study. Sequential transfer did not increase the risk of ectopic pregnancy.

  4. CISA: combined NMR resonance connectivity information determination and sequential assignment.

    Science.gov (United States)

    Wan, Xiang; Lin, Guohui

    2007-01-01

    A nearly complete sequential resonance assignment is a key factor leading to successful protein structure determination via NMR spectroscopy. Assuming the availability of a set of NMR spectral peak lists, most of the existing assignment algorithms first use the differences between chemical shift values for common nuclei across multiple spectra to provide the evidence that some pairs of peaks should be assigned to sequentially adjacent amino acid residues in the target protein. They then use these connectivities as constraints to produce a sequential assignment. At various levels of success, these algorithms typically generate a large number of potential connectivity constraints, and it grows exponentially as the quality of spectral data decreases. A key observation used in our sequential assignment program, CISA, is that chemical shift residual signature information can be used to improve the connectivity determination, and thus to dramatically decrease the number of predicted connectivity constraints. Fewer connectivity constraints lead to less ambiguities in the sequential assignment. Extensive simulation studies on several large test datasets demonstrated that CISA is efficient and effective, compared to three most recently proposed sequential resonance assignment programs RANDOM, PACES, and MARS.

  5. Vacuum extraction

    DEFF Research Database (Denmark)

    Nielsen, Mathilde Maagaard; Oestergaard, Jeanett; Johansen, Marianne

    2012-01-01

    Objectives. To develop and validate an Objective Structured Assessment of Technical Skills (OSATS) scale for vacuum extraction. Design. Two part study design: Primarily, development of a procedure-specific checklist for vacuum extraction. Hereafter, validationof the developed OSATS scale for vacuum...... with daily work in the obstetric field were tested. Methods. The Delphi method was used for development of the scale. In a simulated vacuum extraction scenario first-year residents and obstetric chief physicians were rated using the developed OSATS scale for vacuum extraction to test construct validity...... scale for vacuum extraction is a reliable test for differentiating between competence levels in a simulated setting....

  6. Which method better evaluates the molecular response in newly diagnosed chronic phase chronic myeloid leukemia patients with imatinib treatment, BCR-ABL(IS) or log reduction from the baseline level?

    Science.gov (United States)

    Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Li, Jin-Lan; Li, Ling-Di; Zhu, Hong-Hu; Lai, Yue-Yun; Lu, Xi-Jing; Liu, Yan-Rong; Jiang, Bin; Huang, Xiao-Jun

    2013-09-01

    The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all Plog reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤ 10%(IS) and ≥ 1 log reduction at 3 months and ≤ 1%(IS) at 6 months were significantly associated with PFS (P=0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  7. Overcoming imatinib resistance using Src inhibitor CGP76030, Abl inhibitor nilotinib and Abl/Lyn inhibitor INNO-406 in newly established K562 variants with BCR-ABL gene amplification.

    Science.gov (United States)

    Morinaga, Koji; Yamauchi, Takahiro; Kimura, Shinya; Maekawa, Taira; Ueda, Takanori

    2008-06-01

    Because imatinib (IM) resistance in chronic myeloid leukemia is primarily caused by the re-establishment of Abl kinase, new inhibitors may be efficacious. We evaluated 3 new agents against 2 new K562 variants, IM-R1 and IM-R2 cells, which were developed having 7- and 27-fold greater IM resistance, respectively, than the parental K562 cells. Both variants possessed BCR-ABL gene amplification along with elevated levels of its transcript and protein. Greater BCR-ABL gene amplification was observed in IM-R2 cells than in IM-R1 cells, which was consistent with the higher mRNA and protein levels of Bcr-Abl, and ultimately correlated with the greater IM resistance in IM-R2 cells. No mutation in the Abl kinase domain was detected in either variant. Despite the absence of Lyn overexpression, the Src kinase inhibitor CGP76030 showed positive cooperability with IM in inhibiting cell growth of not only K562 cells but also these 2 variants. This might be because of the augmented inhibition of Erk1/2 phosphorylation. The new Abl kinase inhibitor nilotinib was 10-fold more potent than IM in inhibiting the growth of K562 cells. Nilotinib inhibited the growth of IM-R1 and IM-R2 cells as potently as K562 cells. The combination of nilotinib with CGP76030 showed little additivity, because the potency of nilotinib masked the efficacy of CGP76030. The new dual Abl/Lyn inhibitor INNO-406 (formerly NS-187) was slightly more potent than nilotinib in inhibiting the growth of all 3 cell lines. Because BCR-ABL gene amplification occurs in blast crisis, these inhibitors might overcome IM resistance in such patients' leukemia. (c) 2008 Wiley-Liss, Inc.

  8. Characterization of the CDR3 structure of the Vβ21 T cell clone in patients with P210(BCR-ABL)-positive chronic myeloid leukemia and B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Zha, Xianfeng; Chen, Shaohua; Yang, Lijian; Li, Bo; Chen, Yu; Yan, Xiaojuan; Li, Yangqiu

    2011-10-01

    The clonally expanded T cells identified in most cancer patients that respond to tumor-associated antigen such as P210(BCR-ABL) protein have definite, specific antitumor cytotoxicity. T cell receptor (TCR) Vβ CDR3 repertoire diversity was analyzed in patients with chronic myeloid leukemia (CML) and BCR-ABL(+) B-cell acute lymphoblastic leukemia (B-ALL) by GeneScan. A high frequency of oligoclonal expansion of the TCR Vβ21 subfamily was observed in the peripheral blood of CML and B-ALL patients. These clonally expanded Vβ21 T cells were correlated with the pathophysiologic process of CML. A conserved amino acid motif (SLxxV) was observed within the CDR3 region in only 3 patients with CML. Preferential usage of the Jβ segments was also observed in a minority of patients. The 3-dimensional structures of the CDR3 region containing the same motif or using the same Jβ segment displayed low similarity; on the contrary, the conformation of the CDR3 region containing no conserved motif in some T cell clones was highly similar. In conclusion, our findings indicate a high frequency of TCR Vβ21 subfamily expansion in p210(BCR-ABL)-positive CML and B-ALL patients. The characterization of the CDR3 structure was complex. Regrettably, at this time it was not possible to confirm that the Vβ21 T cell clones were derived from the stimulation of p210(BCR-ABL) protein. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  9. Approach for independent-matrix removal of polycyclic aromatic hydrocarbons from solid samples based on microwave-assisted Soxhlet extraction with on-line fluorescence monitoring

    Science.gov (United States)

    Garcia-Ayuso; Luque-Garcia; de Castro MD

    2000-08-01

    A flow injection interface for fluorometric monitoring of focused microwave-assisted Soxhlet extraction (FMASE) is presented. This assembly allows real-time on-line monitoring of the PAHs extracted from solid samples in each Soxhlet cycle and provides qualitative and semi-quantitative information from natural and spiked samples. Hence, the extraction kinetics can be followed and the end of the leaching step determined independently of the sample matrix, thus avoiding excessive extraction times. The research also involves the study of the multivariate effects of the FMASE parameters by a central composite design. The method was applied to a certified reference material (CRM 524, BCR, industrial soil/organics) for quality assurance/validation. The total content of each analyte was determined by HPLC-fluorometric detection, and the results obtained demonstrated that FMASE is a technique as efficient as conventional Soxhlet to extract PAHs from soils but with a drastic reduction of both extraction time and organic solvent disposal.

  10. A Bayesian Theory of Sequential Causal Learning and Abstract Transfer.

    Science.gov (United States)

    Lu, Hongjing; Rojas, Randall R; Beckers, Tom; Yuille, Alan L

    2016-03-01

    Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about abstract causal constraints? Recent empirical studies have revealed that experience with one set of causal cues can dramatically alter subsequent learning and performance with entirely different cues, suggesting that learning involves abstract transfer, and such transfer effects involve sequential presentation of distinct sets of causal cues. It has been demonstrated that pre-training (or even post-training) can modulate classic causal learning phenomena such as forward and backward blocking. To account for these effects, we propose a Bayesian theory of sequential causal learning. The theory assumes that humans are able to consider and use several alternative causal generative models, each instantiating a different causal integration rule. Model selection is used to decide which integration rule to use in a given learning environment in order to infer causal knowledge from sequential data. Detailed computer simulations demonstrate that humans rely on the abstract characteristics of outcome variables (e.g., binary vs. continuous) to select a causal integration rule, which in turn alters causal learning in a variety of blocking and overshadowing paradigms. When the nature of the outcome variable is ambiguous, humans select the model that yields the best fit with the recent environment, and then apply it to subsequent learning tasks. Based on sequential patterns of cue-outcome co-occurrence, the theory can account for a range of phenomena in sequential causal learning, including various blocking effects, primacy effects in some experimental conditions, and apparently abstract transfer of causal knowledge. Copyright © 2015

  11. INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity.

    Science.gov (United States)

    Yokota, Asumi; Kimura, Shinya; Masuda, Satohiro; Ashihara, Eishi; Kuroda, Junya; Sato, Kiyoshi; Kamitsuji, Yuri; Kawata, Eri; Deguchi, Yasuyuki; Urasaki, Yoshimasa; Terui, Yasuhito; Ruthardt, Martin; Ueda, Takanori; Hatake, Kiyohiko; Inui, Ken-ichi; Maekawa, Taira

    2007-01-01

    Central nervous system (CNS) relapse accompanying the prolonged administration of imatinib mesylate has recently become apparent as an impediment to the therapy of Philadelphia chromosome-positive (Ph+) leukemia. CNS relapse may be explained by limited penetration of imatinib mesylate into the cerebrospinal fluid because of the presence of P-glycoprotein at the blood-brain barrier. To overcome imatinib mesylate-resistance mechanisms such as bcr-abl amplification, mutations within the ABL kinase domain, and activation of Lyn, we developed a dual BCR-ABL/Lyn inhibitor, INNO-406 (formerly NS-187), which is 25 to 55 times more potent than imatinib mesylate in vitro and at least 10 times more potent in vivo. The aim of this study was to investigate the efficacy of INNO-406 in treating CNS Ph+ leukemia. We found that INNO-406, like imatinib mesylate, is a substrate for P-glycoprotein. The concentrations of INNO-406 in the CNS were about 10% of those in the plasma. However, this residual concentration was enough to inhibit the growth of Ph+ leukemic cells which expressed not only wild-type but also mutated BCR-ABL in the murine CNS. Furthermore, cyclosporine A, a P-glycoprotein inhibitor, augmented the in vivo activity of INNO-406 against CNS Ph+ leukemia. These findings indicate that INNO-406 is a promising agent for the treatment of CNS Ph+ leukemia.

  12. Expression of BCR-ABL, E2A-PBX1, and MLL-AF4 fusion transcripts in newly diagnosed children with acute lymphoblastic leukemia: a Children's Cancer Group initiative.

    Science.gov (United States)

    Gaynon, P S; Crotty, M L; Sather, H N; Bostrom, B C; Nachman, J B; Steinherz, P G; Heerema, N A; Sarquis, M; Tuel-Ahlgren, L; Uckun, F M

    1997-06-01

    We used reverse transcriptase polymerase chain reaction (RT-PCR) assays to examine primary leukemic cells in on-study diagnostic bone marrow specimens from 642 children with newly diagnosed acute lymphoblastic leukemia (ALL) for the expression of MLL-AF4, E2A-PBX1, and BCR-ABL fusion transcripts. All PCR assays were performed centrally in the Children's Cancer Group ALL Biology Reference Laboratory. MLL-AF4 transcript was found in only 0.7% of the study population which excluded infants. E2A-PBX1 transcript was found in 2.5% of the study population and 3.3% of B-precursor cases. Expression was associated with massive hepatomegaly. BCR-ABL transcript was found in 2.3% of cases and correlated with older age, induction failure, and inferior event-free survival (EFS). RT-PCR assays allow rapid identification of patients with MLL-AF4 and BCR-ABL positive ALL. These patients have a poor outcome with contemporary therapy and rapid identification facilitates timely allocation to innovative treatment programs.

  13. Establishment and characterization of A novel Philadelphia-chromosome positive chronic myeloid leukemia cell line, TCC-S, expressing P210 and P190 BCR/ABL transcripts but missing normal ABL gene.

    Science.gov (United States)

    Van, Phan Nguyen Thanh; Xinh, Phan Thi; Kano, Yasuhiko; Tokunaga, Katsushi; Sato, Yuko

    2005-03-01

    A novel Philadelphia-chromosome positive (Ph+) cell line, TCC-S, has been established from a patient with Ph+ chronic myeloid leukemia (CML) in the blastic crisis. TCC-S cells were shown to express both P210 and P190 BCR/ABL transcripts by reverse transcriptase-polymerase chain reaction (PCR), although quantitative-PCR revealed that TCC-S cells mainly expressed P210 BCR/ABL transcript. Karyotype analysis revealed several triploid clones which constantly harbored two der(9)del(9) (p12)t(9;22) (q34;qll)s and two del(9) (q21)s. The der(9)del(9) (p12)t(9;22) (q34;q11) is rarely found in other CML cell lines. Moreover, to the best of our knowledge, del(9) (q21) resulting in missing of a restrict region including normal ABL gene has not been found among CML cell lines previously described. Thus, TCC-S cells with only BCR/ABL gene and no normal ABL gene may be a useful tool for functional study of ABL in Ph+ CML.

  14. Extraction method

    International Nuclear Information System (INIS)

    Stary, J.; Kyrs, M.; Navratil, J.; Havelka, S.; Hala, J.

    1975-01-01

    Definitions of the basic terms and of relations are given and the knowledge is described of the possibilities of the extraction of elements, oxides, covalent-bound halogenides and heteropolyacids. Greatest attention is devoted to the detailed analysis of the extraction of chelates and ion associates using diverse agents. For both types of compounds detailed conditions are given of the separation and the effects of the individual factors are listed. Attention is also devoted to extractions using mixtures of organic agents, the synergic effects thereof, and to extractions in non-aqueous solvents. The effects of radiation on extraction and the main types of apparatus used for extractions carried out in the laboratory are described. (L.K.)

  15. Andrographolide downregulates the v-Src and Bcr-Abl oncoproteins and induces Hsp90 cleavage in the ROS-dependent suppression of cancer malignancy.

    Science.gov (United States)

    Liu, Sheng-Hung; Lin, Chao-Hsiung; Liang, Fong-Ping; Chen, Pei-Fen; Kuo, Cheng-Deng; Alam, Mohd Mujahid; Maiti, Barnali; Hung, Shih-Kai; Chi, Chin-Wen; Sun, Chung-Ming; Fu, Shu-Ling

    2014-01-15

    Andrographolide is a diterpenoid compound isolated from Andrographis paniculata that exhibits anticancer activity. We previously reported that andrographolide suppressed v-Src-mediated cellular transformation by promoting the degradation of Src. In the present study, we demonstrated the involvement of Hsp90 in the andrographolide-mediated inhibition of Src oncogenic activity. Using a proteomics approach, a cleavage fragment of Hsp90α was identified in andrographolide-treated cells. The concentration- and time-dependent induction of Hsp90 cleavage that accompanied the reduction in Src was validated in RK3E cells transformed with either v-Src or a human truncated c-Src variant and treated with andrographolide. In cancer cells, the induction of Hsp90 cleavage by andrographolide and its structural derivatives correlated well with decreased Src levels, the suppression of transformation, and the induction of apoptosis. Moreover, the andrographolide-induced Hsp90 cleavage, Src degradation, inhibition of transformation, and induction of apoptosis were abolished by a ROS inhibitor, N-acetyl-cysteine. Notably, Hsp90 cleavage, decreased levels of Bcr-Abl (another known Hsp90 client protein), and the induction of apoptosis were also observed in human K562 leukemia cells treated with andrographolide or its active derivatives. Together, we demonstrated a novel mechanism by which andrographolide suppressed cancer malignancy that involved inhibiting Hsp90 function and reducing the levels of Hsp90 client proteins. Our results broaden the molecular basis of andrographolide-mediated anticancer activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Acute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report

    Directory of Open Access Journals (Sweden)

    Xi Zhang

    Full Text Available ABSTRACT CONTEXT: Acute promyelocytic leukemia (APL accounts for 8% to 10% of cases of acute myeloid leukemia (AML. Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD, and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms’ tumor gene (WT1 in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR. To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest.

  17. Mouse embryonic stem cells that express a NUP98-HOXD13 fusion protein are impaired in their ability to differentiate and can be complemented by BCR-ABL.

    Science.gov (United States)

    Slape, Christopher; Chung, Yang Jo; Soloway, Paul D.; Tessarollo, Lino; Aplan, Peter D

    2007-01-01

    NUP98-HOXD13 (NHD13) fusions have been identified in patients with myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML) and chronic myeloid leukemia blast crisis (CML-BC). We generated “knock-in” mouse embryonic stem (ES) cells that express a NHD13 fusion gene from the endogenous murine NUP98 promoter, and used an in vitro differentiation system to differentiate the ES cells to haematopoietic colonies. Replating assays demonstrated that the partially differentiated NHD13 ES cells were immortal, and two of these cultures were transferred to liquid culture. These cell lines are partially differentiated immature haematopoietic cells, as determined by morphology, immunophenotype and gene expression profile. Despite these characteristics, they were unable to differentiate when exposed to high concentrations of Epo, G-CSF, or M-CSF. The cell lines are incompletely transformed, as evidenced by their dependence on IL3, and their failure to initiate tumours when injected into immunodeficient mice. We attempted genetic complementation of the NHD13 gene using IL3 independence and tumorigenicity in immunodeficient mice as markers of transformation, and found that BCR-ABL successfully transformed the cell lines. These findings support the hypothesis that expression of a NHD13 fusion gene impairs haematopoietic differentiation, and that these cell lines present a model system to study the nature of this impaired differentiation. PMID:17377591

  18. Treating Philadelphia chromosome/BCR-ABL1 positive patients with Glivec (Imatinib mesylate): 10 years' experience at Patan Hospital, Nepal.

    Science.gov (United States)

    Kayastha, Gyan K; Ranjitkar, Nora; Gurung, Radha; Kc, Raj K; Karki, Sanjit; Shrestha, Roshan; Thapa, Raj K; Rajbhandari, Piyush; Poudyal, Buddhi; Acharya, Paras; Roberts, David J; Hayes, Bruce; Zimmerman, Mark; Basnyat, Buddha; Mansfield, Aaron

    2017-06-01

    The Glivec International Patient Assistance Programme makes Glivec (Imatinib mesylate) available to Philadelphia chromosome/BCR-ABL1 positive patients with chronic myeloid leukaemia (CML) in Lower and Middle Income Countries (LMIC). We have established a large cohort of 211 CML patients who are eligible for Imatinib, in Kathmandu, Nepal. Thirty-one patients were lost to follow-up. We report on 180 CML patients with a median age of 38 years (range 9-81). Of these 180 patients, 162 underwent cytogenetic testing and 110 were investigated by reverse transcription polymerase chain reaction. One hundred and thirty-nine of the 180 patients (77·2%) had at least one optimal response. Taken together, our cohort has a 95% overall survival rate and 78% of the patients were still taking Glivec at a median time of 48·8 months (range 3-140 months). The number of patients who actually failed therapy, as defined by the LeukaemiaNet 2013 criteria, was 39 (21·7%). While our cohort has some differences with those in North America or Europe, we have shown Glivec is effective in inducing an optimal response in our patients in Nepal and that it is possible to deliver a clinical service for CML patients using tyrosine kinase inhibitors in resource-poor settings. © 2017 John Wiley & Sons Ltd.

  19. Recent developments in automated determinations of trace level concentrations of elements and on-line fractionations schemes exploiting the micro-sequential injection - lab-on-valve approach

    DEFF Research Database (Denmark)

    Hansen, Elo Harald; Miró, Manuel; Long, Xiangbao

    2006-01-01

    . In this context sequential injection (SI) and lab-on-valve (LOV) schemes have proven themselves as superb vehicles to act as front-end microanalytical methodologies, particularly when employing solid-phase extraction (SPE) procedures. In this communication, selected SPE-procedures in a bead-renewable fashion...... are presented as based on the exploitation of micro-sequential injection (μSI-LOV) using hydrophobic as well as hydrophilic bead materials. The examples given comprise the presentation of a universal approach for SPE-assays, front-end speciation of Cr(III) and Cr(VI) in a fully automated and enclosed set...

  20. Synthesizing genetic sequential logic circuit with clock pulse generator.

    Science.gov (United States)

    Chuang, Chia-Hua; Lin, Chun-Liang

    2014-05-28

    Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.