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Sample records for reduction bcr procedure

  1. Fractionation of metals by sequential extraction procedures (BCR and Tessier) in soil exposed to fire of wide temperature range

    Science.gov (United States)

    Fajkovic, Hana; Rončević, Sanda; Nemet, Ivan; Prohić, Esad; Leontić-Vazdar, Dana

    2017-04-01

    Forest fire presents serious problem, especially in Mediterranean Region. Effects of fire are numerous, from climate change and deforestation to loss of soil organic matter and changes in soil properties. One of the effects, not well documented, is possible redistribution and/or remobilisation of pollutants previously deposited in the soil, due to the new physical and chemical soil properties and changes in equilibrium conditions. For understanding and predicting possible redistribution and/or remobilisation of potential pollutants from soil, affected by fire different in temperature, several laboratory investigations were carried out. To evaluate the influence of organic matter on soil under fire, three soil samples were analysed and compared: (a) the one with added coniferous organic matter; (b) deciduous organic matter (b) and (c) soil without additional organic matter. Type of organic matter is closely related to pH of soil, as pH is influencing the mobility of some pollutants, e.g. metals. For that reason pH was also measured through all experimental steps. Each of mentioned soil samples (a, b and c) were heated at 1+3 different temperatures (25°C, 200°C, 500°C and 850°C). After heating, whereby fire effect on soil was simulated, samples were analysed by BCR protocol with the addition of a first step of sequential extraction procedure by Tessier and analysis of residual by aqua regia. Element fractionation of heavy metals by this procedure was used to determine the amounts of selected elements (Al, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb and Zn). Selected metal concentrations were determined using inductively coupled plasma atomic emission spectrometer. Further on, loss of organic matter was calculated after each heating procedure as well as the mineral composition. The mineral composition was determined using an X-ray diffraction. From obtained results, it can be concluded that temperature has an influence on concentration of elements in specific step of

  2. 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

  3. 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)

  4. Stepwise effects of the BCR sequential chemical extraction procedure on dissolution and metal release from common ferromagnesian clay minerals: A combined solution chemistry and X-ray powder diffraction study

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, P.C. [Geology Department, Middlebury College, Middlebury, Vermont 05753 (United States)], E-mail: pryan@middlebury.edu; Hillier, S. [Macaulay Institute, Aberdeen, AB15 8QH UK (United Kingdom); Wall, A.J. [Department of Geosciences, Penn State University, University Park, Pennsylvania, 16802 (United States)

    2008-12-15

    Sequential extraction procedures (SEPs) are commonly used to determine speciation of trace metals in soils and sediments. However, the non-selectivity of reagents for targeted phases has remained a lingering concern. Furthermore, potentially reactive phases such as phyllosilicate clay minerals often contain trace metals in structural sites, and their reactivity has not been quantified. Accordingly, the objective of this study is to analyze the behavior of trace metal-bearing clay minerals exposed to the revised BCR 3-step plus aqua regia SEP. Mineral quantification based on stoichiometric analysis and quantitative powder X-ray diffraction (XRD) documents progressive dissolution of chlorite (CCa-2 ripidolite) and two varieties of smectite (SapCa-2 saponite and SWa-1 nontronite) during steps 1-3 of the BCR procedure. In total, 8 ({+-} 1) % of ripidolite, 19 ({+-} 1) % of saponite, and 19 ({+-} 3) % of nontronite (% mineral mass) dissolved during extractions assumed by many researchers to release trace metals from exchange sites, carbonates, hydroxides, sulfides and organic matter. For all three reference clays, release of Ni into solution is correlated with clay dissolution. Hydrolysis of relatively weak Mg-O bonds (362 kJ/mol) during all stages, reduction of Fe(III) during hydroxylamine hydrochloride extraction and oxidation of Fe(II) during hydrogen peroxide extraction are the main reasons for clay mineral dissolution. These findings underscore the need for precise mineral quantification when using SEPs to understand the origin/partitioning of trace metals with solid phases.

  5. Otimização das condições de pré-redução do As(V em extratos do método BCR para quantificação de arsênio por HG-AAS Optimization of pre-reduction conditions of as(V in BCR extracts to quantify arsenic by HG-AAS

    Directory of Open Access Journals (Sweden)

    Eduardo Vinícius Vieira Varejão

    2009-08-01

    Full Text Available A determinação de As por espectrometria de absorção atômica com geração de hidretos (HG-AAS constitui um método simples, sensível, preciso e de baixo custo. Entretanto, essa técnica requer a pré-redução das espécies de As(V, o que se obtém através do uso de agentes redutores como o KI. Em extratos contendo agentes oxidantes, a pré-redução do As é comprometida, como acontece em extratos obtidos pela aplicação do método BCR (acrônimo francês para Community Bureau of Reference para a extração sequencial de As em sedimentos. O objetivo deste trabalho foi avaliar as condições de redução do As(V a As(III, de modo a permitir o uso da HG-AAS para a quantificação do arsênio em extratos obtidos a partir do método BCR. Foram avaliadas condições reacionais utilizando KI, L-cisteína e ácido ascórbico. Para cada uma das etapas de extração do método BCR, diferentes condições de pré-redução possibilitaram a detecção quantitativa do As presente. O uso do método BCR para a extração de arsênio em amostras de sedimentos contaminadas e a aplicação das condições de pré-redução do As(V selecionadas, seguida pela detecção por HG-AAS, forneceram percentagens de recuperação entre 91 e 99 %.The determination of As by hydride generation atomic absorption spectroscopy (HG-AAS is a simple, sensitive, precise and low-cost method. However, this technique requires the pre-reduction of the existing As(V species, which is obtained by the use of reducing agents such as KI. In extracts containing oxidizing agents, the pre-reduction of As is impaired, as it occurs in extracts obtained by the BCR (French acronym for Community Bureau of Reference method for the sequential extraction of As in sediments. The objective of this study was to evaluate the conditions for the reduction of As(V to As(III in a way that allows the use of HG-AAS for the quantification of arsenic in extracts obtained using the BCR method. Reaction

  6. Helicopter Flight Procedures for Community Noise Reduction

    Science.gov (United States)

    Greenwood, Eric

    2017-01-01

    A computationally efficient, semiempirical noise model suitable for maneuvering flight noise prediction is used to evaluate the community noise impact of practical variations on several helicopter flight procedures typical of normal operations. Turns, "quick-stops," approaches, climbs, and combinations of these maneuvers are assessed. Relatively small variations in flight procedures are shown to cause significant changes to Sound Exposure Levels over a wide area. Guidelines are developed for helicopter pilots intended to provide effective strategies for reducing the negative effects of helicopter noise on the community. Finally, direct optimization of flight trajectories is conducted to identify low noise optimal flight procedures and quantify the magnitude of community noise reductions that can be obtained through tailored helicopter flight procedures. Physically realizable optimal turns and approaches are identified that achieve global noise reductions of as much as 10 dBA Sound Exposure Level.

  7. 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.

  8. Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

    Science.gov (United States)

    Cariani, E; Capucci, M; Micheletti, M; Spalenza, F; Zanella, I; Albertini, A; Rossi, G

    2003-06-01

    Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

  9. Update on Nonsurgical Lung Volume Reduction Procedures

    Directory of Open Access Journals (Sweden)

    J. Alberto Neder

    2016-01-01

    Full Text Available There has been a surge of interest in endoscopic lung volume reduction (ELVR strategies for advanced COPD. Valve implants, coil implants, biological LVR (BioLVR, bronchial thermal vapour ablation, and airway stents are used to induce lung deflation with the ultimate goal of improving respiratory mechanics and chronic dyspnea. Patients presenting with severe air trapping (e.g., inspiratory capacity/total lung capacity (TLC 225% predicted and thoracic hyperinflation (TLC > 150% predicted have the greatest potential to derive benefit from ELVR procedures. Pre-LVRS or ELVR assessment should ideally include cardiological evaluation, high resolution CT scan, ventilation and perfusion scintigraphy, full pulmonary function tests, and cardiopulmonary exercise testing. ELVR procedures are currently available in selected Canadian research centers as part of ethically approved clinical trials. If a decision is made to offer an ELVR procedure, one-way valves are the first option in the presence of complete lobar exclusion and no significant collateral ventilation. When the fissure is not complete, when collateral ventilation is evident in heterogeneous emphysema or when emphysema is homogeneous, coil implants or BioLVR (in that order are the next logical alternatives.

  10. 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.

  11. Reduction procedures for accurate analysis of MSX surveillance experiment data

    Science.gov (United States)

    Gaposchkin, E. Mike; Lane, Mark T.; Abbot, Rick I.

    1994-01-01

    Technical challenges of the Midcourse Space Experiment (MSX) science instruments require careful characterization and calibration of these sensors for analysis of surveillance experiment data. Procedures for reduction of Resident Space Object (RSO) detections will be presented which include refinement and calibration of the metric and radiometric (and photometric) data and calculation of a precise MSX ephemeris. Examples will be given which support the reduction, and these are taken from ground-test data similar in characteristics to the MSX sensors and from the IRAS satellite RSO detections. Examples to demonstrate the calculation of a precise ephemeris will be provided from satellites in similar orbits which are equipped with S-band transponders.

  12. A procedure for seismic risk reduction in Campania Region

    Science.gov (United States)

    Zuccaro, G.; Palmieri, M.; Maggiò, F.; Cicalese, S.; Grassi, V.; Rauci, M.

    2008-07-01

    The Campania Region has set and performed a peculiar procedure in the field of seismic risk reduction. Great attention has been paid to public strategic buildings such as town halls, civil protection buildings and schools. The Ordinance 3274 promulgate in the 2004 by the Italian central authority obliged the owners of strategic buildings to perform seismic analyses within 2008 in order to check the safety of the structures and the adequacy to the use. In the procedure the Campania region, instead of the local authorities, ensure the complete drafting of seismic checks through financial resources of the Italian Government. A regional scientific technical committee has been constituted, composed of scientific experts, academics in seismic engineering. The committee has drawn up guidelines for the processing of seismic analyses. At the same time, the Region has issued a public competition to select technical seismic engineering experts to appoint seismic analysis in accordance with guidelines. The scientific committee has the option of requiring additional documents and studies in order to approve the safety checks elaborated. The Committee is supported by a technical and administrative secretariat composed of a group of expert in seismic engineering. At the moment several seismic safety checks have been completed. The results will be presented in this paper. Moreover, the policy to mitigate the seismic risk, set by Campania region, was to spend the most of the financial resources available on structural strengthening of public strategic buildings rather than in safety checks. A first set of buildings of which the response under seismic action was already known by data and studies of vulnerability previously realised, were selected for immediate retrofitting designs. Secondly, an other set of buildings were identified for structural strengthening. These were selected by using the criteria specified in the Guide Line prepared by the Scientific Committee and based on

  13. A procedure for seismic risk reduction in Campania Region

    International Nuclear Information System (INIS)

    Zuccaro, G.; Palmieri, M.; Cicalese, S.; Grassi, V.; Rauci, M.; Maggio, F.

    2008-01-01

    The Campania Region has set and performed a peculiar procedure in the field of seismic risk reduction. Great attention has been paid to public strategic buildings such as town halls, civil protection buildings and schools. The Ordinance 3274 promulgate in the 2004 by the Italian central authority obliged the owners of strategic buildings to perform seismic analyses within 2008 in order to check the safety of the structures and the adequacy to the use. In the procedure the Campania region, instead of the local authorities, ensure the complete drafting of seismic checks through financial resources of the Italian Government. A regional scientific technical committee has been constituted, composed of scientific experts, academics in seismic engineering. The committee has drawn up guidelines for the processing of seismic analyses. At the same time, the Region has issued a public competition to select technical seismic engineering experts to appoint seismic analysis in accordance with guidelines. The scientific committee has the option of requiring additional documents and studies in order to approve the safety checks elaborated. The Committee is supported by a technical and administrative secretariat composed of a group of expert in seismic engineering. At the moment several seismic safety checks have been completed. The results will be presented in this paper. Moreover, the policy to mitigate the seismic risk, set by Campania region, was to spend the most of the financial resources available on structural strengthening of public strategic buildings rather than in safety checks. A first set of buildings of which the response under seismic action was already known by data and studies of vulnerability previously realised, were selected for immediate retrofitting designs. Secondly, an other set of buildings were identified for structural strengthening. These were selected by using the criteria specified in the Guide Line prepared by the Scientific Committee and based on

  14. Evaluation of a Noise Reduction Procedure for Chest Radiography

    Science.gov (United States)

    Fukui, Ryohei; Ishii, Rie; Kodani, Kazuhiko; Kanasaki, Yoshiko; Suyama, Hisashi; Watanabe, Masanari; Nakamoto, Masaki; Fukuoka, Yasushi

    2013-01-01

    Background The aim of this study was to evaluate the usefulness of noise reduction procedure (NRP), a function in the new image processing for chest radiography. Methods A CXDI-50G Portable Digital Radiography System (Canon) was used for X-ray detection. Image noise was analyzed with a noise power spectrum (NPS) and a burger phantom was used for evaluation of density resolution. The usefulness of NRP was evaluated by chest phantom images and clinical chest radiography. We employed the Bureau of Radiological Health Method for scoring chest images while carrying out our observations. Results NPS through the use of NRP was improved compared with conventional image processing (CIP). The results in image quality showed high-density resolution through the use of NRP, so that chest radiography examination can be performed with a low dose of radiation. Scores were significantly higher than for CIP. Conclusion In this study, use of NRP led to a high evaluation in these so we are able to confirm the usefulness of NRP for clinical chest radiography. PMID:24574577

  15. Optimisation of beryllium-7 gamma analysis following BCR sequential extraction

    International Nuclear Information System (INIS)

    Taylor, A.; Blake, W.H.; Keith-Roach, M.J.

    2012-01-01

    Graphical abstract: Showing decrease in analytical uncertainty using the optimal (combined preconcentrated sample extract) method. nv (no value) where extract activities were 7 Be geochemical behaviour is required to support tracer studies. ► Sequential extraction with natural 7 Be returns high analytical uncertainties. ► Preconcentrating extracts from a large sample mass improved analytical uncertainty. ► This optimised method can be readily employed in studies using low activity samples. - Abstract: The application of cosmogenic 7 Be as a sediment tracer at the catchment-scale requires an understanding of its geochemical associations in soil to underpin the assumption of irreversible adsorption. Sequential extractions offer a readily accessible means of determining the associations of 7 Be with operationally defined soil phases. However, the subdivision of the low activity concentrations of fallout 7 Be in soils into geochemical fractions can introduce high gamma counting uncertainties. Extending analysis time significantly is not always an option for batches of samples, owing to the on-going decay of 7 Be (t 1/2 = 53.3 days). Here, three different methods of preparing and quantifying 7 Be extracted using the optimised BCR three-step scheme have been evaluated and compared with a focus on reducing analytical uncertainties. The optimal method involved carrying out the BCR extraction in triplicate, sub-sampling each set of triplicates for stable Be analysis before combining each set and coprecipitating the 7 Be with metal oxyhydroxides to produce a thin source for gamma analysis. This method was applied to BCR extractions of natural 7 Be in four agricultural soils. The approach gave good counting statistics from a 24 h analysis period (∼10% (2σ) where extract activity >40% of total activity) and generated statistically useful sequential extraction profiles. Total recoveries of 7 Be fell between 84 and 112%. The stable Be data demonstrated that the

  16. Medical and occupational dose reduction in pediatric barium meal procedures

    Science.gov (United States)

    Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Ledesma, J. A.; Legnani, A.; Bunick, A. P.; Sauzen, J.; Yagui, A.; Vosiak, P.

    2017-11-01

    Doses received in pediatric Barium Meal procedure can be rather high. It is possible to reduce dose values following the recommendations of the European Communities (EC) and the International Commission on Radiological Protection (ICRP). In the present work, the modifications of radiographic techniques made in a Brazilian hospital according to the EC and the ICRP recommendations and their influence on medical and occupational exposure are reported. The procedures of 49 patients before and 44 after the optimization were studied and air kerma-area product (PK,A) values and the effective doses were evaluated. The occupational equivalent doses were measured next to the eyes, under the thyroid shield and on each hand of both professionals who remained inside the examination room. The implemented modifications reduced by 70% and 60% the PK,A and the patient effective dose, respectively. The obtained dose values are lower than approximately 75% of the results from similar studies. The occupational annual equivalent doses for all studied organs became lower than the limits set by the ICRP. The equivalent doses in one examination were on average below than 75% of similar studies.

  17. 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

    International Nuclear Information System (INIS)

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

    1987-01-01

    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 λ light chain locus (IGL) and ABL locus on the K562 Philadelphia chromosome (Ph 1 ). Similarly, in mouse-human hybrids retaining a Ph 1 chromosome derived from an acute lymphoblastic leukemia-in the absence of the 9q + 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 1 chromosome

  18. Aspects of the licensing procedures for enrichment reduction in research reactors

    International Nuclear Information System (INIS)

    Krull, W.

    1983-01-01

    The enrichment reduction for research reactors requires a licensing procedure. For this purpose the qualification of the new fuel has to be demonstrated and changes in reactor safety have to be investigated like reactivity values, form-factors, Pu- and fission product inventory, safety margins and accidents. Calculations should be partly experimentally verified. The possible extent of the licensing procedure is discussed. (orig.) [de

  19. Optimisation of beryllium-7 gamma analysis following BCR sequential extraction

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, A. [Plymouth University, School of Geography, Earth and Environmental Sciences, 8 Kirkby Place, Plymouth PL4 8AA (United Kingdom); Blake, W.H., E-mail: wblake@plymouth.ac.uk [Plymouth University, School of Geography, Earth and Environmental Sciences, 8 Kirkby Place, Plymouth PL4 8AA (United Kingdom); Keith-Roach, M.J. [Plymouth University, School of Geography, Earth and Environmental Sciences, 8 Kirkby Place, Plymouth PL4 8AA (United Kingdom); Kemakta Konsult, Stockholm (Sweden)

    2012-03-30

    Graphical abstract: Showing decrease in analytical uncertainty using the optimal (combined preconcentrated sample extract) method. nv (no value) where extract activities were BCR three-step scheme have been evaluated and compared with a focus on reducing analytical uncertainties. The optimal method involved carrying out the BCR extraction in triplicate, sub-sampling each set of triplicates for stable Be analysis before combining each set and coprecipitating the {sup 7}Be with metal oxyhydroxides to produce a thin source for gamma analysis. This method was applied to BCR extractions of natural {sup 7}Be in four agricultural soils. The approach gave good counting statistics from a 24 h analysis period ({approx}10% (2

  20. 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.

  1. Time Savings and Surgery Task Load Reduction in Open Intraperitoneal Onlay Mesh Fixation Procedure

    Science.gov (United States)

    Roy, Sanjoy; Hammond, Jeffrey; Panish, Jessica; Shnoda, Pullen; Savidge, Sandy; Wilson, Mark

    2015-01-01

    Background. This study assessed the reduction in surgeon stress associated with savings in procedure time for mechanical fixation of an intraperitoneal onlay mesh (IPOM) compared to a traditional suture fixation in open ventral hernia repair. Study Design. Nine general surgeons performed 36 open IPOM fixation procedures in porcine model. Each surgeon conducted two mechanical (using ETHICON SECURESTRAPTM Open) and two suture fixation procedures. Fixation time was measured using a stopwatch, and related surgeon stress was assessed using the validated SURG-TLX questionnaire. T-tests were used to compare between-group differences, and a two-sided 95% confidence interval for the difference in stress levels was established using nonparametric methodology. Results. The mechanical fixation group demonstrated an 89.1% mean reduction in fixation time, as compared to the suture group (p Open demonstrated a significant reduction in fixation time and surgeon stress, which may translate into improved operating efficiency, improved performance, improved surgeon quality of life, and reduced overall costs of the procedure. PMID:26240834

  2. Time Savings and Surgery Task Load Reduction in Open Intraperitoneal Onlay Mesh Fixation Procedure

    Directory of Open Access Journals (Sweden)

    Sanjoy Roy

    2015-01-01

    Full Text Available Background. This study assessed the reduction in surgeon stress associated with savings in procedure time for mechanical fixation of an intraperitoneal onlay mesh (IPOM compared to a traditional suture fixation in open ventral hernia repair. Study Design. Nine general surgeons performed 36 open IPOM fixation procedures in porcine model. Each surgeon conducted two mechanical (using ETHICON SECURESTRAPTM Open and two suture fixation procedures. Fixation time was measured using a stopwatch, and related surgeon stress was assessed using the validated SURG-TLX questionnaire. T-tests were used to compare between-group differences, and a two-sided 95% confidence interval for the difference in stress levels was established using nonparametric methodology. Results. The mechanical fixation group demonstrated an 89.1% mean reduction in fixation time, as compared to the suture group (p<0.00001. Surgeon stress scores measured using SURG-TLX were 55.5% lower in the mechanical compared to the suture fixation group (p<0.001. Scores in five of the six sources of stress were significantly lower for mechanical fixation. Conclusions. Mechanical fixation with ETHICON SECURESTRAPTM Open demonstrated a significant reduction in fixation time and surgeon stress, which may translate into improved operating efficiency, improved performance, improved surgeon quality of life, and reduced overall costs of the procedure.

  3. Total reduction of distorted echelle spectrograms - An automatic procedure. [for computer controlled microdensitometer

    Science.gov (United States)

    Peterson, R. C.; Title, A. M.

    1975-01-01

    A total reduction procedure, notable for its use of a computer-controlled microdensitometer for semi-automatically tracing curved spectra, is applied to distorted high-dispersion echelle spectra recorded by an image tube. Microdensitometer specifications are presented and the FORTRAN, TRACEN and SPOTS programs are outlined. The intensity spectrum of the photographic or electrographic plate is plotted on a graphic display. The time requirements are discussed in detail.

  4. An Interactive Procedure to Preserve the Desired Edges during the Image Processing of Noise Reduction

    Directory of Open Access Journals (Sweden)

    Lin-Tsang Lee

    2010-01-01

    Full Text Available The paper propose a new procedure including four stages in order to preserve the desired edges during the image processing of noise reduction. A denoised image can be obtained from a noisy image at the first stage of the procedure. At the second stage, an edge map can be obtained by the Canny edge detector to find the edges of the object contours. Manual modification of an edge map at the third stage is optional to capture all the desired edges of the object contours. At the final stage, a new method called Edge Preserved Inhomogeneous Diffusion Equation (EPIDE is used to smooth the noisy images or the previously denoised image at the first stage for achieving the edge preservation. The Optical Character Recognition (OCR results in the experiments show that the proposed procedure has the best recognition result because of the capability of edge preservation.

  5. A Systematic Cycle Time Reduction Procedure for Enhancing the Competitiveness and Sustainability of a Semiconductor Manufacturer

    Directory of Open Access Journals (Sweden)

    Toly Chen

    2013-11-01

    Full Text Available Cycle time reduction plays an important role in improving the competitiveness and sustainability of a semiconductor manufacturer. However, in the past, cycle time reduction was usually unplanned owing to the lack of a systematic and quantitative procedure. To tackle this problem, a systematic procedure was established in this study for planning cycle time reduction actions to enhance the competitiveness and sustainability of a semiconductor manufacturer. First, some controllable factors that are influential to the job cycle time are identified. Subsequently, the relationship between the controllable factors and the job cycle time is fitted with a back propagation network. Based on this relationship, actions to shorten the job cycle time can be planned. The feasibility and effectiveness of an action have to be assessed before it can be taken in practice. An example containing the real data of hundreds of jobs has been used to illustrate the applicability of the proposed methodology. In addition, the financial benefits of the cycle time reduction action were analyzed, which provided the evidence that the proposed methodology enabled the sustainable development of the semiconductor manufacturer, since capital adequacy is very important in the semiconductor manufacturing industry.

  6. A vertical-energy-thresholding procedure for data reduction with multiple complex curves.

    Science.gov (United States)

    Jung, Uk; Jeong, Myong K; Lu, Jye-Chyi

    2006-10-01

    Due to the development of sensing and computer technology, measurements of many process variables are available in current manufacturing processes. It is very challenging, however, to process a large amount of information in a limited time in order to make decisions about the health of the processes and products. This paper develops a "preprocessing" procedure for multiple sets of complicated functional data in order to reduce the data size for supporting timely decision analyses. The data type studied has been used for fault detection, root-cause analysis, and quality improvement in such engineering applications as automobile and semiconductor manufacturing and nanomachining processes. The proposed vertical-energy-thresholding (VET) procedure balances the reconstruction error against data-reduction efficiency so that it is effective in capturing key patterns in the multiple data signals. The selected wavelet coefficients are treated as the "reduced-size" data in subsequent analyses for decision making. This enhances the ability of the existing statistical and machine-learning procedures to handle high-dimensional functional data. A few real-life examples demonstrate the effectiveness of our proposed procedure compared to several ad hoc techniques extended from single-curve-based data modeling and denoising procedures.

  7. Effects of Mitral Annulus Remodeling Following MitraClip Procedure on Reduction of Functional Mitral Regurgitation.

    Science.gov (United States)

    Hidalgo, Francisco; Mesa, Dolores; Ruiz, Martín; Delgado, Mónica; Rodríguez, Sara; Pardo, Laura; Pan, Manuel; López, Amador; Romero, Miguel A; Suárez de Lezo, José

    2016-11-01

    The percutaneous mitral valve repair procedure (MitraClip) appears to reduce mitral annulus diameter in patients with functional mitral regurgitation, but the relationship between this and regurgitation severity has not been demonstrated. The aim of this study was to determine the effect of mitral annulus remodeling on the reduction of mitral regurgitation in patients with functional etiology. The study included all patients with functional mitral regurgitation treated with MitraClip at our hospital until January 2015. Echocardiogram (iE33 model, Philips) was performed in all patients immediately after device positioning. Changes in the mitral annulus correlated with mitral regurgitation severity, as assessed using the effective regurgitant orifice area. The study included 23 patients (age, 65±14 years; 74% men; left ventricular ejection fraction, 31%±13%; systolic pulmonary artery pressure, 47±10 mmHg). After the procedure, the regurgitant orifice area decreased by 0.30 cm 2 ±0.04 cm 2 (P<.0005), from a baseline of 0.49 cm 2 ±0.09 cm 2 . Anteroposterior diameter decreased by 3.14 mm±1.01 mm (P<.0005) from a baseline of 28.27 mm±4.9 mm, with no changes in the intercommissural diameter (0.50 mm±0.91 mm vs 40.68 mm±4.7 mm; P=.26). A significant association was seen between anteroposterior diameter reduction and regurgitant orifice area reduction (r=.49; P=.020). In patients with functional mitral regurgitation, the MitraClip device produces an immediate reduction in the anteroposterior diameter. This remodeling may be related to the reduction in mitral regurgitation. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  8. Manual ward reduction of gastroschisis without anesthesia, a safe procedure – 8 years experience

    Directory of Open Access Journals (Sweden)

    Kamal Nain Rattan

    2017-01-01

    Full Text Available Introduction: Gastroschisis is the most common type of abdominal wall defect at birth. Various modalities of treatment have been proposed ranging from primary closure to the staged closure using prosthetic materials under general anesthesia. One of the modalities is manual ward reduction with primary repair of gastroschisis without anesthesia. We are reporting our 8 years of experience with manual ward reduction of gastroschisis with primary repair without anesthesia.Materials and methods: It is a retrospective analysis of all patients of gastroschisis who presented in our institution from January 2008 to June 2016. The data were analyzed for antenatal diagnosis, sex, day of presentation, weight of baby, associated anomalies, management by manual reduction without anesthesia and post reduction morbidity and mortality.Results: Out of a total of 68 patients, 28 were females and 40 were males. Fifty-five cases (80.8% were antenatally diagnosed. Fifty-nine patients (86.7% presented within 24 hours of birth while the rest had delayed presentation. Preterms (< 37 weeks were 18 (26.4%. Cases of simple gastroschisis were 22 while those complicated were 46. The average birth weight was 1.88 kg with the lowest weight of 1 kg who was a 27-week preterm. In 60 patients (88.2%, bedside manual reduction without anesthesia and primary closure was possible while in 8 patients it could not be done owing to delayed presentation and complications. The mortality in these patients was 40%.Conclusion: Manual reduction and primary closure of gastroschisis without anesthesia is a safe procedure. It requires no ventilator support and can be managed with antibiotics, total parenteral nutrition (TPN and continuous positive airway pressure (CPAP in the post-reduction period.

  9. New image-processing and noise-reduction software reduces radiation dose during complex endovascular procedures.

    Science.gov (United States)

    Kirkwood, Melissa L; Guild, Jeffrey B; Arbique, Gary M; Tsai, Shirling; Modrall, J Gregory; Anderson, Jon A; Rectenwald, John; Timaran, Carlos

    2016-11-01

    A new proprietary image-processing system known as AlluraClarity, developed by Philips Healthcare (Best, The Netherlands) for radiation-based interventional procedures, claims to lower radiation dose while preserving image quality using noise-reduction algorithms. This study determined whether the surgeon and patient radiation dose during complex endovascular procedures (CEPs) is decreased after the implementation of this new operating system. Radiation dose to operators, procedure type, reference air kerma, kerma area product, and patient body mass index were recorded during CEPs on two Philips Allura FD 20 fluoroscopy systems with and without Clarity. Operator dose during CEPs was measured using optically stimulable, luminescent nanoDot (Landauer Inc, Glenwood, Ill) detectors placed outside the lead apron at the left upper chest position. nanoDots were read using a microStar ii (Landauer Inc) medical dosimetry system. For the CEPs in the Clarity group, the radiation dose to surgeons was also measured by the DoseAware (Philips Healthcare) personal dosimetry system. Side-by-side measurements of DoseAware and nanoDots allowed for cross-calibration between systems. Operator effective dose was determined using a modified Niklason algorithm. To control for patient size and case complexity, the average fluoroscopy dose rate and the dose per radiographic frame were adjusted for body mass index differences and then compared between the groups with and without Clarity by procedure. Additional factors, for example, physician practice patterns, that may have affected operator dose were inferred by comparing the ratio of the operator dose to procedural kerma area product with and without Clarity. A one-sided Wilcoxon rank sum test was used to compare groups for radiation doses, reference air kermas, and operating practices for each procedure type. The analysis included 234 CEPs; 95 performed without Clarity and 139 with Clarity. Practice patterns of operators during

  10. BCR-701: A review of 10-years of sequential extraction analyses

    International Nuclear Information System (INIS)

    Sutherland, Ross A.

    2010-01-01

    A detailed quantitative analysis was performed on data presented in the literature that focused on the sequential extraction of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb) and zinc (Zn) from the certified reference material BCR-701 (lake sediment) using the three-step harmonized BCR procedure. The accuracy of data reported in the literature, including precision and different measures of trueness, was assessed relative to the certified values for BCR-701. Forty data sets were accepted following extreme outlier removal, and statistically summarized with measures of central tendency, dispersion, and distribution form. In general, literature data were similar in their measurement precision to the expert laboratories used to certify the trace element contents in BCR-701. The overall median precision for literature reported data was 10% (range 6-19%), compared to certifying laboratories of 9% (range 4-33%). One measure of literature data trueness was assessed via a confirmatory approach using a robust bootstrap method. Only 22% of the comparisons indicated significantly different (all were lower) concentrations reported in the literature compared to certified values. The question of whether the differences are practically significant for environmental studies is raised. Bias was computed as a measure of trueness, and literature data were more frequently negatively biased, indicating lower concentrations reported in the literature for the six trace elements for the three-step sequential procedure compared to the certified values. However, 95% confidence intervals about the average bias for the 18 comparisons indicated only four instances when a mean bias of 0 (i.e., measured = certified) was not incorporated-suggesting statistical difference. Finally, Z-scores incorporating a Horwitz-type function were used to assess the general trueness of laboratory data. Of the 468 laboratory Z-score values computed, 92% were considered to be satisfactory, 5% were

  11. Acceptance test procedure for K basins dose reduction project clean and coat equipment

    International Nuclear Information System (INIS)

    Creed, R.F.

    1996-01-01

    This document is the Acceptance Test Procedure (ATP) for the clean and coat equipment designed by Oceaneering Hanford, Inc. under purchase order MDK-XVC-406988 for use in the 105 K East Basin. The ATP provides the guidelines and criteria to test the equipment's ability to clean and coat the concrete perimeter, divider walls, and dummy elevator pit above the existing water level. This equipment was designed and built in support of the Spent Nuclear Fuel, Dose Reduction Project. The ATP will be performed at the 305 test facility in the 300 Area at Hanford. The test results will be documented in WHC-SD-SNF-ATR-020

  12. Comparison of Procedural Sedation for the Reduction of Dislocated Total Hip Arthroplasty

    Directory of Open Access Journals (Sweden)

    Jonathan E. dela Cruz

    2014-02-01

    Propofol averaging a significantly less recovery time than the Opiate/Benzodiazepine group (p=0.05. Conclusions: For the purpose of reducing a dislocated total hip arthroplasty under conscious sedation, Propofol appears to have fewer complications and a trend of more rapid recovery than both Etomidate and Opiate/Benzodiazepine. Etomidate does appear to have some advantages over Opiate/Benzodiazepine regarding sedation complications and recovery time; however its rate of reduction complications was similar. This preliminary data supports the use of Propofol as the first line agent for procedural sedation of dislocated total hip arthroplasty as it may lead to few complications and shorter stays in the emergency department. [West J. Emerg Med. 2014;15(1:76-80.

  13. The relationship between self-efficacy and reductions in smoking in a contingency management procedure.

    Science.gov (United States)

    Romanowich, Paul; Mintz, Jim; Lamb, R J

    2009-06-01

    Social--cognitive and behavioral theories of change disagree on what the relevant controlling variables for initiating behavior change are. Correlations between baseline smoking cessation self-efficacy and the changes in breath carbon monoxide (CO) and the reduction in breath CO and increases in smoking cessation self-efficacy from baseline were obtained from a contingency management smoking cessation procedure. A test of the difference between the cross-lag correlations suggested a nonspurious causal relationship between smoking cessation self-efficacy and changes in breath CO. Path analyses showed that decreases in breath CO (reductions in smoking) predicted later increases in smoking cessation self-efficacy. Baseline self-reports of smoking cessation self-efficacy were not significantly correlated with subsequent changes in breath CO. Rather, significant correlations were found between reductions in breath CO and later increases in smoking cessation self-efficacy. These results suggest that self-efficacy may be a cognitive response to one's own behavior, and are inconsistent with a social--cognitive view of self-efficacy's role in behavior change. Implications for the development of smoking cessation programs and health-promoting behavior changes in general are discussed.

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

    Directory of Open Access Journals (Sweden)

    Maria Luiza F. M. Kede

    2014-11-01

    Full Text Available 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.

  16. Procedures for sampling and sample reduction within quality assurance systems for solid biofuels

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    The objective of this experimental study on sampling was to determine the size and number of samples of biofuels required (taken at two sampling points in each case) and to compare two methods of sampling. The first objective of the sample-reduction exercise was to compare the reliability of various sampling methods, and the second objective was to measure the variations introduced as a result of reducing the sample size to form suitable test portions. The materials studied were sawdust, wood chips, wood pellets and bales of straw, and these were analysed for moisture, ash, particle size and chloride. The sampling procedures are described. The study was conducted in Scandinavia. The results of the study were presented in Leipzig in October 2004. The work was carried out as part of the UK's DTI Technology Programme: New and Renewable Energy.

  17. Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway.

    OpenAIRE

    Puil, L; Liu, J; Gish, G; Mbamalu, G; Bowtell, D; Pelicci, P G; Arlinghaus, R; Pawson, T

    1994-01-01

    The cytosolic 185 and 210 kDa Bcr-Abl protein tyrosine kinases play important roles in the development of Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (Ph+ ALL). p185 and p210 Bcr-Abl contain identical abl-encoded sequences juxtaposed to a variable number of bcr-derived amino acids. As the mitogenic and transforming activities of tyrosine kinases involve stimulation of the Ras pathway, we analyzed Bcr-Abl oncoproteins for interacti...

  18. Optimisation of CT procedures by dose reduction in abdominal-pelvic studies of chronic patients

    International Nuclear Information System (INIS)

    Calvo, D.; Rodriguez, A.M.; Peinado, M.A.; Fernandez, B.; Fernandez, B.M.; Jimenez, J.R.

    2006-01-01

    Full text of publication follows: Objectives: CT explorations are responsible of a significant increase of collective dose during last twenty years. However, by adapting the procedures to the specific diagnostic requirements of each kind of exploration, dose values can be decreased. This can be specially interesting for chronic patients who undergo several CT controls. The aim of this research is to contrast CT image diagnostic quality by comparing those techniques commonly used in our hospital with lower dose ones. Materials and methods: In a first phase, a study on phantom has been developed to evaluate image quality variations obtained with standard a several low dose techniques. Dose reduction was quantified as well by means of C.T.D.I. w measurements on an abdominal phantom. Both aspects were taken into account to determine a dose threshold below image quality degradation was considered unacceptable from a diagnostic point of view. Subsequently, a group of 50 chronic patients under follow -up was selected to undergo a control CT but with a low dose-technique. Image diagnostic quality was compared with that of previous controls obtained using the standard technique. Three experimented radiologist carried out this evaluation over a sample of six particular slices located at the abdomen and pelvis using an ordinal scale. Such a scale gradate the confidence level of the image for each radiologist. This evaluation was repeated one and two months later without knowledge of previous results to calculate inter and intra -observer variability. Conclusions: CT studies can be carried out with a significant dose reduction preserving their diagnostic capabilities. A quantitative evaluation will be offered at the end of the study, still running. (authors)

  19. Sustainable Reduction of Sleepiness through Salutogenic Self-Care Procedure in Lunch Breaks: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Sebastian Schnieder

    2013-01-01

    Full Text Available The aim of the study was to elucidate the immediate, intermediate, and anticipatory sleepiness reducing effects of a salutogenic self-care procedure called progressive muscle relaxation (PMR, during lunch breaks. The second exploratory aim deals with determining the onset and long-term time course of sleepiness changes. In order to evaluate the intraday range and interday change of the proposed relaxation effects, 14 call center agents were assigned to either a daily 20-minute self-administered PMR or a small talk (ST group during a period of seven months. Participants’ levels of sleepiness were analyzed in a controlled trial using anticipatory, postlunchtime, and afternoon changes of sleepiness as indicated by continuously determined objective reaction time measures (16,464 measurements and self-reports administered five times per day, once per month (490 measurements. Results indicate that, in comparison to ST, the PMR break (a induces immediate, intermediate, and anticipatory reductions in sleepiness; (b these significant effects remarkably show up after one month, and sleepiness continues to decrease for at least another five months. Although further research is required referring to the specific responsible mediating variables, our results suggest that relaxation based lunch breaks are both accepted by employees and provide a sustainable impact on sleepiness.

  20. Critical analysis of dose reduction trends with special reference to procedures involved in fluoroscopy

    International Nuclear Information System (INIS)

    Anderson, K.; Mattsson, O.

    1985-01-01

    Experiences of a half-year's use of dose-checking instrumentation in fluoroscopy are presented. Radiologists under training succeeded in lowering the patient dose surprisingly well - the diagnostic results remaining unchanged or even improving, because of higher image quality as a result of better diaphragming. Other factors involved in fluoroscopy are discussed. Present systems with heavy bulky intensifiers create problems for close patient contact and for the necessary manipulation, patient adjustment and application of compression. The examination will be simplified and facilitated by the use of a flat image system: proper adjustments need fewer fluoroscopic observations, and patient dose as well as examination time can be saved. Flat display principles will take over the function of the present old-fashioned intensifiers and monitors, either as single units or equipped with TV, video or digital processing accessories. A flat image system, the 'PET-scope', was tested and found to be very convenient for fluoroscopic procedures. The physical properties were studied thoroughly - the high intensification particularly gives these systems an advantage in dose reduction. New applications are possible with these light-weight low-dose units. Fluoroscopy represents a field where considerable contributions to the 'Quality Assurance' trend can be obtained. (author)

  1. 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...

  2. Transforming and tumorigenic activity of JAK2 by fusion to BCR: molecular mechanisms of action of a novel BCR-JAK2 tyrosine-kinase.

    Directory of Open Access Journals (Sweden)

    Álvaro Cuesta-Domínguez

    Full Text Available Chromosomal translocations in tumors frequently produce fusion genes coding for chimeric proteins with a key role in oncogenesis. Recent reports described a BCR-JAK2 fusion gene in fatal chronic and acute myeloid leukemia, but the functional behavior of the chimeric protein remains uncharacterized. We used fluorescence in situ hybridization and reverse transcription polymerase chain reaction (RT-PCR assays to describe a BCR-JAK2 fusion gene from a patient with acute lymphoblastic leukemia. The patient has been in complete remission for six years following treatment and autologous transplantation, and minimal residual disease was monitored by real-time RT-PCR. BCR-JAK2 codes for a protein containing the BCR oligomerization domain fused to the JAK2 tyrosine-kinase domain. In vitro analysis of transfected cells showed that BCR-JAK2 is located in the cytoplasm. Transduction of hematopoietic Ba/F3 cells with retroviral vectors carrying BCR-JAK2 induced IL-3-independent cell growth, constitutive activation of the chimeric protein as well as STAT5 phosphorylation and translocation to the nuclei, where Bcl-xL gene expression was elicited. Primary mouse progenitor cells transduced with BCR-JAK2 also showed increased proliferation and survival. Treatment with the JAK2 inhibitor TG101209 abrogated BCR-JAK2 and STAT5 phosphorylation, decreased Bcl-xL expression and triggered apoptosis of transformed Ba/F3 cells. Therefore, BCR-JAK2 is a novel tyrosine-kinase with transforming activity. It deregulates growth factor-dependent proliferation and cell survival, which can be abrogated by the TG101209 inhibitor. Moreover, transformed Ba/F3 cells developed tumors when injected subcutaneously into nude mice, thus proving the tumorigenic capacity of BCR-JAK2 in vivo. Together these findings suggest that adult and pediatric patients with BCR-ABL-negative leukemia and JAK2 overexpression may benefit from targeted therapies.

  3. Disrupting BCR-ABL in combination with secondary leukemia-specific pathways in CML cells leads to enhanced apoptosis and decreased proliferation.

    Science.gov (United States)

    Woessner, David W; Lim, Carol S

    2013-01-07

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by expression of the fusion gene BCR-ABL following a chromosomal translocation in the hematopoietic stem cell. Therapeutic management of CML uses tyrosine kinase inhibitors (TKIs), which block ABL-signaling and effectively kill peripheral cells with BCR-ABL. However, TKIs are not curative, and chronic use is required in order to treat CML. The primary failure for TKIs is through the development of a resistant population due to mutations in the TKI binding regions. This led us to develop the mutant coiled-coil, CC(mut2), an alternative method for BCR-ABL signaling inhibition by targeting the N-terminal oligomerization domain of BCR, necessary for ABL activation. In this article, we explore additional pathways that are important for leukemic stem cell survival in K562 cells. Using a candidate-based approach, we test the combination of CC(mut2) and inhibitors of unique secondary pathways in leukemic cells. Transformative potential was reduced following silencing of the leukemic stem cell factor Alox5 by RNA interference. Furthermore, blockade of the oncogenic protein MUC-1 by the novel peptide GO-201 yielded reductions in proliferation and increased cell death. Finally, we found that inhibiting macroautophagy using chloroquine in addition to blocking BCR-ABL signaling with the CC(mut2) was most effective in limiting cell survival and proliferation. This study has elucidated possible combination therapies for CML using novel blockade of BCR-ABL and secondary leukemia-specific pathways.

  4. Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Mohamed El Missiry

    Full Text Available In chronic myeloid leukemia (CML, early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5, and BCR-ABL1 transcript levels were measured at diagnosis (dg and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response. In our cohort, 21% of patients had no decrease in BCR-ABL1 transcript levels after 1 month and were classified as poor responders. Surprisingly, these patients had lower BCR-ABL1 transcript levels at dg compared to responders (31% vs. 48%, p = 0.0083. Poor responders also significantly more often had enlarged spleen (55% vs. 15%; p<0.01 and a higher percentage of Ph+ CD34+CD38- cells in the bone marrow (91% vs. 75%, p<0.05. The major molecular response rates were inferior in the poor responders (at 12m 18% vs. 64%, p<0.01; 18m 27% vs. 75%, p<0.01; 24m 55% vs. 87%, p<0.01. In conclusion, early treatment response analysis defines a biologically distinct patient subgroup with inferior long-term outcomes.

  5. 78 FR 10085 - Limited Reductions of Funding, Termination, and Debarment Procedures; Recompetition; Enforcement...

    Science.gov (United States)

    2013-02-13

    ... reductions of funding, expansion of non-audit based suspensions for up to ninety days, and immediate special... LEGAL SERVICES CORPORATION 45 CFR Parts 1606, 1614, 1618, and 1623 Limited Reductions of Funding... regulations regarding grants for the provision of legal assistance: (1) A new ``limited reduction of funding...

  6. 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

  7. Reduction of radiation doses in leg lengthening procedures by means of audit and computed tomography scanogram techniques

    International Nuclear Information System (INIS)

    Romanowski, C.A.J.; Sprigg, A.; Underwood, A.C.

    1994-01-01

    Children with congenital bone dysplasias may benefit from leg lengthening procedures. Such procedures, by necessity, require frequent and regular imaging. It is necessary to minimize the total radiation dose to these patients, and particularly the dose to the gonads. In the present study, the films of 13 patients who had completed leg lengthening procedures were reviewed. The number of films was assessed together with the use of appropriate gonad shielding. In a second part of the study, thermoluminescent dosemeter measurements of radiation doses to a phantom were made for both plain radiographs (with and without gonad protection) and computed tomography (CT) scanograms. The results show that audit plays an important role in assessing radiographic practice with respect to accurate placement of gonad protection and confirm that a significant dose reduction can be accomplished by careful use of this lead shielding. Dose reduction can also be achieved by using alternative radiographic techniques such as CT scanograms. (author)

  8. 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)

  9. 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.

  10. COOPERATIVE THREAT REDUCTION: DOD Has Adequate Oversight of Assistance, but Procedural Limitations Remain

    National Research Council Canada - National Science Library

    2001-01-01

    ... more than $3 billion for the Cooperative Threat Reduction (CTR) program to help Russia, Belarus, Ukraine, Kazakhstan, Uzbekistan, Moldova, and Georgia secure and eliminate weapons of mass destruction...

  11. Procedural Reform and the Reduction of Discretion: The Case of the Juvenile Court.

    Science.gov (United States)

    Sosin, Michael

    The issue of controlling discretion in large public institutions is a crucial one in modern society, and procedural legal reforms are often viewed as one tactic of control. Using due process guarantees in juvenile courts as the substantive issue, this paper tests the utility of procedural reform in reducing discretion. Results indicate that…

  12. BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgV H unmutated chronic lymphocytic leukemia (CLL) cells.

    Science.gov (United States)

    Guarini, Anna; Chiaretti, Sabina; Tavolaro, Simona; Maggio, Roberta; Peragine, Nadia; Citarella, Franca; Ricciardi, Maria Rosaria; Santangelo, Simona; Marinelli, Marilisa; De Propris, Maria Stefania; Messina, Monica; Mauro, Francesca Romana; Del Giudice, Ilaria; Foà, Robert

    2008-08-01

    Chronic lymphocytic leukemia (CLL) patients exhibit a variable clinical course. To investigate the association between clinicobiologic features and responsiveness of CLL cells to anti-IgM stimulation, we evaluated gene expression changes and modifications in cell-cycle distribution, proliferation, and apoptosis of IgV(H) mutated (M) and unmutated (UM) samples upon BCR cross-linking. Unsupervised analysis highlighted a different response profile to BCR stimulation between UM and M samples. Supervised analysis identified several genes modulated exclusively in the UM cases upon BCR cross-linking. Functional gene groups, including signal transduction, transcription, cell-cycle regulation, and cytoskeleton organization, were up-regulated upon stimulation in UM cases. Cell-cycle and proliferation analyses confirmed that IgM cross-linking induced a significant progression into the G(1) phase and a moderate increase of proliferative activity exclusively in UM patients. Moreover, we observed only a small reduction in the percentage of subG(0/1) cells, without changes in apoptosis, in UM cases; contrariwise, a significant increase of apoptotic levels was observed in stimulated cells from M cases. These results document that a differential genotypic and functional response to BCR ligation between IgV(H) M and UM cases is operational in CLL, indicating that response to antigenic stimulation plays a pivotal role in disease progression.

  13. Editor's choice--Use of disposable radiation-absorbing surgical drapes results in significant dose reduction during EVAR procedures.

    Science.gov (United States)

    Kloeze, C; Klompenhouwer, E G; Brands, P J M; van Sambeek, M R H M; Cuypers, P W M; Teijink, J A W

    2014-03-01

    Because of the increasing number of interventional endovascular procedures with fluoroscopy and the corresponding high annual dose for interventionalists, additional dose-protecting measures are desirable. The purpose of this study was to evaluate the effect of disposable radiation-absorbing surgical drapes in reducing scatter radiation exposure for interventionalists and supporting staff during an endovascular aneurysm repair (EVAR) procedure. This was a randomized control trial in which 36 EVAR procedures were randomized between execution with and without disposable radiation-absorbing surgical drapes (Radpad: Worldwide Innovations & Technologies, Inc., Kansas City, US, type 5511A). Dosimetric measurements were performed on the interventionalist (hand and chest) and theatre nurse (chest) with and without the use of the drapes to obtain the dose reduction and effect on the annual dose caused by the drapes. Use of disposable radiation-absorbing surgical drapes resulted in dose reductions of 49%, 55%, and 48%, respectively, measured on the hand and chest of the interventionalist and the chest of the theatre nurse. The use of disposable radiation-absorbing surgical drapes significantly reduces scatter radiation exposure for both the interventionalist and the supporting staff during EVAR procedures. Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  14. Safety procedures in operation of inspection and maintenance of pressure reduction and metering stations

    International Nuclear Information System (INIS)

    Villas Boas, Ademar Jose; Biesemeyer, Marco Aurelio R.

    2000-01-01

    Each local Natural Gas Distribution Company in Brazil has its own working procedures for operations of inspection and maintenance on equipment and accessories connected to the gas network. Some of these Companies developed a better elaborated and documented way of working routines, while others only work based on their operators experience. The objective of this work is to create a standard procedure for operations of inspection and maintenance of Pressure Reducing Stations and Metering Stations, mainly the ones concerned to safety aspects. This work has no intention of exhausting all aspects related to this subject but to become the first step to standardize these types of operations among Natural Gas Distribution Companies. (author)

  15. Noise pollution of air compressor and its noise reduction procedures by using an enclosure

    Directory of Open Access Journals (Sweden)

    Farhad Forouharmajd

    2012-01-01

    Conclusions: An overall noise reduction by 25 dB with the use of mineral wool as an extra liner on the inside of the enclosure, suggests that the effectiveness of the enclosure can be increased by using such absorber materials.

  16. Radiation dose reduction in fluoroscopic procedures: left varicocele embolization as a model

    Energy Technology Data Exchange (ETDEWEB)

    Verstandig, Anthony G.; Shraibman, Vladimir [Shaare Zedek Medical Center, Department of Radiology, Interventional Radiology Unit, POB 3235, Jerusalem (Israel); Shamieh, Bashar [St. Joseph Hospital, Department of Radiology, Jerusalem (Israel); Raveh, David [Shaare Zedek Medical Center, Infectious Diseases Unit, POB 3235, Jerusalem (Israel)

    2015-06-01

    To investigate the effect of a radiation reduction program on total dose, fluoroscopy dose per second corrected for body habitus and degree of collimation in left varicocele embolizations (LVE). A radiation reduction program for LVE was implemented, consisting of a technique minimizing fluoroscopy time, using low-dose presets, virtual collimation, and virtual patient positioning. Height, weight, fluoroscopy time, kerma area product (KAP) and reference air kerma (Ka,r) were recorded for 100 consecutive cases satisfying the inclusion criteria. For each patient, a device specific dose correction factor, determined using a phantom, was used to standardize the KAP to that of the cylindrical diameter of the standard man and a collimation index was derived from the KAP and Ka,r. Median fluoroscopy time was 3 minutes (mean 4.5, range 1-23.8). Median KAP was 0.54 Gy/cm{sup 2} (mean 0.82, range 0.12-6.52). There was a significant decrease in KAP/second corrected for cylindrical diameter (p < 0.001) and the collimation index (p < 0.001) over time. This study shows that a dedicated dose reduction program can achieve very low total radiation dose rates for LVE. The significant decrease in collimation index and standardized KAP per second during this study suggest a learning curve for collimation. (orig.)

  17. 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.

  18. The Pelleve procedure: an effective method for facial wrinkle reduction and skin tightening.

    Science.gov (United States)

    Stampar, Michael

    2011-05-01

    Devices using radiofrequency (RF) energy and electrical energy to deliver a controlled thermal injury to heat skin have proliferated within the nonablative skin treatment market since the introduction of Thermage in 2002. By delivering continuous monopolar RF energy, rather than pulsed heating, and repeatedly bringing the skin to therapeutic temperatures until maximal contraction is obtained, the Pelleve Procedure can give obvious cosmetic results confluently over all treated areas painlessly and with no downtime. In this article, the technique, mechanism of continuous RF heating, and apparent treatment requirements to produce these results are presented. Some controversies are also addressed. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Procedures for sampling and sample-reduction within quality assurance systems for solid biofuels

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-04-15

    The bias introduced when sampling solid biofuels from stockpiles or containers instead of from moving streams is assessed as well as the number and size of samples required to represent accurately the bulk sample, variations introduced when reducing bulk samples into samples for testing, and the usefulness of sample reduction methods. Details are given of the experimental work carried out in Sweden and Denmark using sawdust, wood chips, wood pellets, forestry residues and straw. The production of a model European Standard for quality assurance of solid biofuels is examined.

  20. 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.; Berna Beverloo, H.; 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.

    2017-01-01

    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 (p<0.01), and also higher, albeit not statistically significant, compared with the fusion-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. PMID:27894077

  1. The Oncor Geodatabase for the Columbia Estuary Ecosystem Restoration Program: Handbook of Data Reduction Procedures, Workbooks, and Exchange Templates

    Energy Technology Data Exchange (ETDEWEB)

    Sather, Nichole K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Borde, Amy B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Diefenderfer, Heida L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Serkowski, John A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Coleman, Andre M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Johnson, Gary E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-12-01

    This Handbook of Data Reduction Procedures, Workbooks, and Exchange Templates is designed to support the Oncor geodatabase for the Columbia Estuary Ecosystem Restoration Program (CEERP). The following data categories are covered: water-surface elevation and temperature, sediment accretion rate, photo points, herbaceous wetland vegetation cover, tree plots and site summaries, fish catch and density, fish size, fish diet, fish prey, and Chinook salmon genetic stock identification. The handbook is intended for use by scientists collecting monitoring and research data for the CEERP. The ultimate goal of Oncor is to provide quality, easily accessible, geospatial data for synthesis and evaluation of the collective performance of CEERP ecosystem restoration actions at a program scale.

  2. Ibrutinib inhibits pre-BCR+ B-cell acute lymphoblastic leukemia progression by targeting BTK and BLK.

    Science.gov (United States)

    Kim, Ekaterina; Hurtz, Christian; Koehrer, Stefan; Wang, Zhiqiang; Balasubramanian, Sriram; Chang, Betty Y; Müschen, Markus; Davis, R Eric; Burger, Jan A

    2017-03-02

    Targeting B-cell receptor (BCR) signaling is a successful therapeutic strategy in mature B-cell malignancies. Precursor BCR (pre-BCR) signaling, which is critical during normal B lymphopoiesis, also plays an important role in pre-BCR + B cell acute lymphoblastic leukemia (B-ALL). Here, we investigated the activity and mechanism of action of the BTK inhibitor ibrutinib in preclinical models of B-ALL. Pre-BCR + ALL cells were exquisitely sensitive to ibrutinib at therapeutically relevant drug concentrations. In pre-BCR + ALL, ibrutinib thwarted autonomous and induced pre-BCR signaling, resulting in deactivation of PI3K/Akt signaling. Ibrutinib modulated the expression of pre-BCR regulators (PTPN6, CD22, CD72, and PKCβ) and substantially reduced BCL6 levels. Ibrutinib inhibited ALL cell migration toward CXCL12 and beneath marrow stromal cells and reduced CD44 expression. CRISPR-Cas9 gene editing revealed that both BTK and B lymphocyte kinase (BLK) are relevant targets of ibrutinib in pre-BCR + ALL. Consequently, in mouse xenograft models of pre-BCR + ALL, ibrutinib treatment significantly prolonged survival. Combination treatment of ibrutinib with dexamethasone or vincristine demonstrated synergistic activity against pre-BCR + ALL. These data corroborate ibrutinib as a promising targeted agent for pre-BCR + ALL and highlight the importance of ibrutinib effects on alternative kinase targets. © 2017 by The American Society of Hematology.

  3. 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...

  4. Heterogeneity of BCR-ABL rearrangement in patients with chronic myeloid leukemia in Pakistan.

    Science.gov (United States)

    Tabassum, Najia; Saboor, Mohammad; Ghani, Rubina; Moinuddin, Moinuddin

    2014-07-01

    Breakpoint cluster region-Abelson (BCR-ABL) rearrangement or Philadelphia (Ph) chromosome in Chronic Myeloid Leukemia (CML) is derived from a reciprocal chromosomal translocation between ABL gene on chromosome 9 and BCR gene on chromosome 22. This chimeric protein has various sizes and therefore different clinical behaviour. The purpose of this study was to determine the heterogeneity of BCR-ABL rearrangement in patients with Ph(+)CML in Pakistan. The study was conducted at Civil Hospital and Baqai Institute of Hematology (BIH) Karachi. Blood samples from 25 patients with CML were collected. Multiplex reverse transcription polymerase chain reaction (RT-PCR) was performed to identify various BCR-ABL transcripts. All 25 samples showed BCR-ABL rearrangements. Out of these, 24 (96%) patients expressed p210 BCR-ABL rearrangements i.e. 60% (n=15) had b3a2 and 32% (n=8) had b2a2 rearrangements. Co-expression of b3a2 /b2a2 rearrangement and p190 (e1a3) rearrangement was also identified in two patients. It is apparent that majority of the patients had p210 BCR-ABL rearrangements. Frequency of co-expression and rare fusion transcripts was very low.

  5. Labia Majora Augmentation with De-epithelialized Labial Rim (Minora) Flaps as an Auxiliary Procedure for Labia Minora Reduction.

    Science.gov (United States)

    Karabağlı, Yakup; Kocman, Emre Atacan; Velipaşaoğlu, Melih; Kose, Aydan A; Ceylan, Sezi; Cemboluk, Ozlem; Cetin, Cengiz

    2015-06-01

    Esthetic surgery of external female genitalia remains an uncommon procedure. This article describes a novel, de-epithelialized, labial rim flap technique for labia majora augmentation using de-epithelialized labia minora tissue otherwise to be excised as an adjunct to labia minora reduction. Ten patients were included in the study. The protruding segments of the labia minora were de-epithelialized with a fine scissors or scalpel instead of being excised, and a bulky section of subcutaneous tissue was obtained. Between the outer and inner surfaces of the labia minora, a flap with a subcutaneous pedicle was created in continuity with the de-epithelialized marginal tissue. A pocket was dissected in the labium majus, and the flap was transposed into the pocket to augment the labia majora. Mean patient age was 39.9 (±13.9) years, mean operation time was 60 min, and mean follow-up period was 14.5 (±3.4) months. There were no major complications (hematoma, wound dehiscence, infection) following surgery. No patient complained of postoperative difficulty with coitus or dyspareunia. All patients were satisfied with the final appearance. Several methods for labia minora reduction have been described. Auxiliary procedures are required with labia minora reduction for better results. Nevertheless, few authors have taken into account the final esthetic appearance of the whole female external genitalia. The described technique in this study is indicated primarily for mild atrophy of the labia majora with labia minora hypertrophy; the technique resulted in perfect patient satisfaction with no major complications or postoperative coital problems. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  6. Oral glucose and breast milk as a strategy for pain reduction during the heel lance procedure in newborns.

    Science.gov (United States)

    Aguilar Cordero, María José; Mur Villar, Norma; García García, Inmaculada; Rodríguez López, María Ascensión; Rizo Baeza, María Mercedes

    2014-11-01

    This paper presents the results of a study on pain reduction in newborns that undergo painful medical procedures. This research analyzed the reactions of babies before and after the heel lance procedure, a diagnostic test performed to detect phenylketonuria. This test involved the extraction of a capillary blood sample with a heel lance, a medical procedure that is painful for neonates. The main objective of this research was to evaluate the effectiveness of a 24% oral glucose solution and breastfeeding during heal lance. An experimental study was thus conducted on a sample of 93 newborns in the San Cecilio University Hospital in Granada in 2010. The babies in the sample were divided into three groups, depending on what they ingested during the heal lance. The results obtained showed that there was an association between the difference in HR and the time before the newborn's HR returned to normal after the heel lance (r = 0.562; p = 0.000). Moreover, a positive relation was found between the absolute difference in HR and the difference in oxygen saturation (OS) (r = 0.538; p = 0.000). The OS was found to be greater in the group of newborns that received breast milk. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  7. 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

  8. 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.

  9. Molecular measurement of BCR-ABL transcript variations in chronic myeloid leukemia patients in cytogenetic remission

    Directory of Open Access Journals (Sweden)

    Costa Juliana

    2010-11-01

    Full Text Available Abstract Background The monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR has become important to assess minimal residual disease (MRD and standard of care in the treatment of chronic myeloid leukemia (CML. In this study, we performed a prospective, sequential analysis using RT-qPCR monitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP who achieved complete cytogenetic remission (CCyR and major molecular remission (MMR throughout imatinib treatment. Methods The absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive. Sequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard protocols. Results Based on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories: (A 57 (62.6% had no variation on sequential analysis; (B 30 (32.9% had a single positive variation result obtained in a single sample; and (C 4 (4.39% had variations of BCR-ABL transcripts in at least two consecutive samples. Of the 34 patients who had elevated levels of transcripts (group B and C, 19 (55.8% had a BCR-ABL/BCR ratio, 13 (38.2% patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations in Ph-negative cells were observed in five (5.5% patients, and none of whom lost CCyR. Conclusions Despite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent failure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of

  10. 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.

  11. The novel anticancer agent JNJ-26854165 is active in chronic myeloid leukemic cells with unmutated BCR/ABL and T315I mutant BCR/ABL through promoting proteosomal degradation of BCR/ABL proteins.

    Science.gov (United States)

    You, Liangshun; Liu, Hui; Huang, Jian; Xie, Wanzhuo; Wei, Jueying; Ye, Xiujin; Qian, Wenbin

    2017-01-31

    Chronic myeloid leukemia (CML) is a clonal malignant disease caused by the expression of BCR/ABL. MDM2 (human homolog of the murine double minute-2) inhibitors such as Nutlin-3 have been shown to induce apoptosis in a p53-dependent manner in CML cells and sensitize cells to Imatinib. Here, we demonstrate that JNJ-26854165, an inhibitor of MDM2, inhibits proliferation and triggers cell death in a p53-independent manner in various BCR/ABL-expressing cells, which include primary leukemic cells from patients with CML blast crisis and cells expressing the Imatinib-resistant T315I BCR/ABL mutant. The response to JNJ-26854165 is associated with the downregulation of BCR/ABL dependently of proteosome activation. Moreover, in all tested CML cells, with the exception of T315I mutation cells, combining JNJ-26854165 and tyrosine kinase inhibitor (TKI) Imatinib or PD180970 leads to a synergistic effect. In conclusion, our results suggest that JNJ-26854165, used either alone or in combination with TKIs, represents a promising novel targeted approach to overcome TKI resistance and improve patient outcome in CML.

  12. 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.

  13. 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

    International Nuclear Information System (INIS)

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

    2004-01-01

    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

  14. Clinical relevance of the breakpoint sites within the M-BCR in 50 patients from Argentina with chronic myeloid leukemia.

    Science.gov (United States)

    Giere, I A; Larripa, I B

    1996-08-01

    Fifty patients from Argentina with chronic myeloid leukemia (CML) were studied in order to characterize the breakpoint site within the major breakpoint cluster region (M-BCR) and its relationship with the duration of the chronic phase (CP). The DNA digestion with the restriction enzymes: Bgl II, BAM HI and Hind III and hybridization with the 1.2Kb Hind III-Bgl II bcr probe showed that 56% of cases had the breakpoint in 5'M-bcr region and the remaining 44% in 3'M-bcr region. The duration of chronic phase from diagnosis to the onset of the blast crisis (BC) was correlated with the location of the breakpoint within the M-bcr and no statistical differences were observed between the 5' and the 3' groups. These data indicate that the breakpoint site within the bcr gene is not a prognostic indicator of the duration of CP of the disease.

  15. SU-G-IeP3-05: Effects of Image Receptor Technology and Dose Reduction Software On Radiation Dose Estimates for Fluoroscopically-Guided Interventional (FGI) Procedures

    Energy Technology Data Exchange (ETDEWEB)

    Merritt, Z; Dave, J; Eschelman, D; Gonsalves, C [Thomas Jefferson University, Philadelphia, PA (United States)

    2016-06-15

    Purpose: To investigate the effects of image receptor technology and dose reduction software on radiation dose estimates for most frequently performed fluoroscopically-guided interventional (FGI) procedures at a tertiary health care center. Methods: IRB approval was obtained for retrospective analysis of FGI procedures performed in the interventional radiology suites between January-2011 and December-2015. This included procedures performed using image-intensifier (II) based systems which were subsequently replaced, flat-panel-detector (FPD) based systems which were later upgraded with ClarityIQ dose reduction software (Philips Healthcare) and relatively new FPD system already equipped with ClarityIQ. Post procedure, technologists entered system-reported cumulative air kerma (CAK) and kerma-area product (KAP; only KAP for II based systems) in RIS; these values were analyzed. Data pre-processing included correcting typographical errors and cross-verifying CAK and KAP. The most frequent high and low dose FGI procedures were identified and corresponding CAK and KAP values were compared. Results: Out of 27,251 procedures within this time period, most frequent high and low dose procedures were chemo/immuno-embolization (n=1967) and abscess drainage (n=1821). Mean KAP for embolization and abscess drainage procedures were 260,657, 310,304 and 94,908 mGycm{sup 2}, and 14,497, 15,040 and 6307 mGycm{sup 2} using II-, FPD- and FPD with ClarityIQ- based systems, respectively. Statistically significant differences were observed in KAP values for embolization procedures with respect to different systems but for abscess drainage procedures significant differences were only noted between systems with FPD and FPD with ClarityIQ (p<0.05). Mean CAK reduced significantly from 823 to 308 mGy and from 43 to 21 mGy for embolization and abscess drainage procedures, respectively, in transitioning to FPD systems with ClarityIQ (p<0.05). Conclusion: While transitioning from II- to FPD- based

  16. Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis.

    Science.gov (United States)

    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

    2011-10-14

    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. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. PCR detection of a Maell polymorphism in the human major breakpoint cluster region (BCR)

    Energy Technology Data Exchange (ETDEWEB)

    McClure, J.S.; Litz, C.E. (Medical School, Minneapolis, MN (United States))

    1991-09-25

    Nested primer pairs flanking the second intron of the breakpoint cluster region were constructed from the published cDNA sequence. The outer primer pair 5{prime}BCR Exon 2 (5{prime}-GTT TCA GAA GCT TCT CCC TG-3{prime}) and 3{prime}BCR Exon 3 (5{prime}-ACT CTG CTT AAA TCC AGT GG-3{prime}), amplified a fragment of genomic DNA approximately 810 bp in length. The inner primer pair, 3{prime}BCR Exon 2(5{prime}-CGC TGA CCA TCA ATA AGG AA-3{prime}) and 5{prime}BCR Exon 3 (5{prime}-AGA AAC CCA TAG AGC CCC GG-3{prime}), amplified a fragment approximately 730 bp in length. Double stranded DNA amplified with the outer primer pair was subjected to asymmetric PCR using the inner primer pair. Sequencing reactions were performed using the Sequenase dideoxy sequencing kit with S{sup 35}-dATP. Sequences in homozygotes revealed either an A or a G 85 bp 5{prime} of the BCR BamHI site. Heterozygotes demonstrated both bands at the corresponding position.

  18. 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.

  19. 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....

  20. The proto-oncogene product p120CBL and the adaptor proteins CRKL and c-CRK link c-ABL, p190BCR/ABL and p210BCR/ABL to the phosphatidylinositol-3' kinase pathway.

    Science.gov (United States)

    Sattler, M; Salgia, R; Okuda, K; Uemura, N; Durstin, M A; Pisick, E; Xu, G; Li, J L; Prasad, K V; Griffin, J D

    1996-02-15

    Chronic myelogenous leukemia (CML) and some acute lymphoblastic leukemias (ALL) are caused by the t(9;22) chromosome translocation, which produces the constitutively activated BCR/ABL tyrosine kinase. When introduced into factor dependent hematopoietic cell lines, BCR/ABL induces the tyrosine phosphorylation of many cellular proteins. One prominent BCR/ABL substrate is p120CBL, the cellular homolog of the v-Cbl oncoprotein. In an effort to understand the possible contribution of p120CBL to transformation by BCR/ABL, we looked for cellular proteins which associate with p120CBL in hematopoietic cell lines transformed by BCR/ABL. In addition to p210BCR/ABL and c-ABL, p120CBL coprecipitated with an 85 kDa phosphoprotein, which was identified as the p85 subunit of PI3K. Anti-p120CBL immunoprecipitates from BCR/ABL-transformed, but not from untransformed, cell lines contained PI3K lipid kinase activity. Interestingly, the adaptor proteins CRKL and c-CRK were also found in these complexes. In vitro binding studies indicated that the SH2 domains of CRKL and c-CRK bound directly to p120CBL, while the SH3 domains of c-CRK and CRKL bound to BCR/ABL and c-ABL. The N-terminal and the C-terminal SH2 and the SH3 domain of p85PI3K bound directly in vitro to p120CBL. The ABL-SH2, but not ABL-SH3, could also bind to p120CBL. These data suggest that BCR/ABL may induce the formation of multimeric complexes of signaling proteins which include p120CBL, PI3K, c-CRK or CRKL, c-ABL and BCR/ABL itself.

  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. Radiation-Induced Noncancer Risks in Interventional Cardiology: Optimisation of Procedures and Staff and Patient Dose Reduction

    Science.gov (United States)

    Khairuddin Md Yusof, Ahmad

    2013-01-01

    Concerns about ionizing radiation during interventional cardiology have been increased in recent years as a result of rapid growth in interventional procedure volumes and the high radiation doses associated with some procedures. Noncancer radiation risks to cardiologists and medical staff in terms of radiation-induced cataracts and skin injuries for patients appear clear potential consequences of interventional cardiology procedures, while radiation-induced potential risk of developing cardiovascular effects remains less clear. This paper provides an overview of the evidence-based reviews of concerns about noncancer risks of radiation exposure in interventional cardiology. Strategies commonly undertaken to reduce radiation doses to both medical staff and patients during interventional cardiology procedures are discussed; optimisation of interventional cardiology procedures is highlighted. PMID:24027768

  3. 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

  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. 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 ...

  7. Frequency and clinical impact of ETV6/RUNX1, AF4‑MLL, and BCR ...

    African Journals Online (AJOL)

    2015-05-12

    May 12, 2015 ... features of prognostic importance, which include total white blood cell count (P = 0.416) and FAB subtype (P = 0.576). Conclusion: Presence of fusion ... Frequency and clinical impact of ETV6/RUNX1, AF4‑MLL, and BCR/ABL fusion ... define distinct clinic‑pathological subgroups and have been used in risk ...

  8. Modulation of BCR Signaling by the Induced Dimerization of Receptor-Associated SYK

    Directory of Open Access Journals (Sweden)

    Mark L. Westbroek

    2017-12-01

    Full Text Available Clustering of the B cell antigen receptor (BCR by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, we developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, we fused SYK with E. coli dihydrofolate reductase (eDHFR, which binds the small molecule trimethoprim (TMP with high affinity and selectivity and synthesized a dimer of TMP with a flexible linker. The TMP dimer is able to induce the aggregation of eDHFR-linked SYK in live cells. The induced dimerization of SYK bound to the BCR differentially regulates the activation of downstream transcription factors, promoting the activation of Nuclear Factor of Activated T cells (NFAT without affecting the activation of NFκB. The dimerization of SYK enhances the duration but not the amplitude of calcium mobilization by enhancing the extent and duration of its interaction with the crosslinked BCR at the plasma membrane.

  9. 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 ...

  10. Landfill operation and waste management procedures in the reduction of methane and leachate pollutant emissions from municipal solid waste landfills

    Energy Technology Data Exchange (ETDEWEB)

    Jokela, J.

    2002-07-01

    The objective of the present research was to find ways of minimising emissions from municipal solid waste (MSW) landfills by means of laboratory experiments. During anaerobic incubation for 237 days, the grey waste components produced between 120 and 320 m{sup 3}CH{sub 4} tTS{sup -1} and between 0.32 and 3.5 kg NH{sub 4}-N tTS{sup -1} and the first-order rate constant of degradation ranged from 0.021 and 0.058 d{sup -1}. High amounts of COD and NH{sub 4}-N were observed in the leachate of grey waste in all the procedures tested during lysimeter experiments lasting 573 days. In the 10- year-old landfilled MSW, a high rate of methanisation was achieved with rainwater addition and leachate recirculation over 538 days, whereas initially pre-wetted grey waste and landfilled MSW were rapidly acidified, thus releasing a high amount of COD into the leachate. In batch assays, the grey waste produced a methane potential amounting to 70-85 % of the total methane potential of the grey waste plus putrescibles. In low moisture conditions, i.e. below 55%, methane production was delayed in the old landfill waste and prevented in the grey waste. In the emission potential study with five waste types, putrescibles produced 410 m{sup 3}CH{sub 4} tTS{sup -1} and 3.6 kgNH{sub 4}-N tTS{sup -1}, whereas composted putrescibles produced 41 m{sup 3}CH{sub 4} tVS{sup -1}, and 2.0 kgNH{sub 4}-N tTS{sup -1}. The remains of putrescibles probably caused the leaching potential of 2.1 kgNH{sub 4}-N tTS{sup -1} in the grey waste. Aeration for 51 days in lysimeters reduced the CH{sub 4} potential of putrescibles by more than 68 % and of the lysimeter landfilled grey waste by 50 %, indicating the potential of aeration for CH4 emission reduction. Nitrogen removal of landfill leachate was studied in the laboratory as well as on-site. Over 90 % nitrification of leachate was obtained with loading rates between 100 and 130 mgNH{sub 4}-N l{sup -1} d-1 at 25 deg C. Nitrified leachate was denitrified with a

  11. Frequency of BCR-ABL Transcript Types in Syrian CML Patients

    Directory of Open Access Journals (Sweden)

    Sulaf Farhat-Maghribi

    2016-01-01

    Full Text Available Background. In Syria, CML patients are started on tyrosine kinase inhibitors (TKIs and monitored until complete molecular response is achieved. BCR-ABL mRNA transcript type is not routinely identified, contrary to the recommendations. In this study we aimed to identify the frequency of different BCR-ABL transcripts in Syrian CML patients and highlight their significance on monitoring and treatment protocols. Methods. CML patients positive for BCR-ABL transcripts by quantitative RT-PCR were enrolled. BCR-ABL transcript types were investigated using a home-made PCR method that was adapted from published protocols and optimized. The transcript types were then confirmed using a commercially available research kit. Results. Twenty-four transcripts were found in 21 patients. The most common was b2a2, followed by b3a2, b3a3, and e1a3 present solely in 12 (57.1%, 3 (14.3%, 2 (9.5%, and 1 (4.8%, respectively. Three samples (14.3% contained dual transcripts. While b3a2 transcript was apparently associated with warning molecular response to imatinib treatment, b2a2, b3a3, and e1a3 transcripts collectively proved otherwise (P=0.047. Conclusion. It might be advisable to identify the BCR-ABL transcript type in CML patients at diagnosis, using an empirically verified method, in order to link the detected transcript with the clinical findings, possible resistance to treatment, and appropriate monitoring methods.

  12. 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.

  13. Assessing of distribution, mobility and bioavailability of exogenous Pb in agricultural soils using isotopic labeling method coupled with BCR approach.

    Science.gov (United States)

    Huang, Zhi-Yong; Xie, Hong; Cao, Ying-Lan; Cai, Chao; Zhang, Zhi

    2014-02-15

    The contamination of Pb in agricultural soils is one of the most important ecological problems, which potentially results in serious health risk on human health through food chain. Hence, the fate of exogenous Pb contaminated in agricultural soils is needed to be deeply explored. By spiking soils with the stable enriched isotopes of (206)Pb, the contamination of exogenous Pb(2+) ions in three agricultural soils sampled from the estuary areas of Jiulong River, China was simulated in the present study, and the distribution, mobility and bioavailability of exogenous Pb in the soils were investigated using the isotopic labeling method coupled with a four-stage BCR (European Community Bureau of Reference) sequential extraction procedure. Results showed that about 60-85% of exogenous Pb was found to distribute in reducible fractions, while the exogenous Pb in acid-extractable fractions was less than 1.0%. After planting, the amounts of exogenous Pb presenting in acid-extractable, reducible and oxidizable fractions in rhizospheric soils decreased by 60-66%, in which partial exogenous Pb was assimilated by plants while most of the metal might transfer downward due to daily watering and applying fertilizer. The results show that the isotopic labeling technique coupled with sequential extraction procedures enables us to explore the distribution, mobility and bioavailability of exogenous Pb contaminated in soils, which may be useful for the further soil remediation. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Inhibitory effect of PTD-OD-HA fusion protein on Bcr-Abl in K562 cells

    Directory of Open Access Journals (Sweden)

    Miao GAO

    2012-10-01

    Full Text Available Objective To study the transduction dynamics, location of PTD-OD-HA fusion protein and its interaction with Bcr-Abl oncoprotein in K562 cell lines, and explore the influence of PTD-OD-HA fusion protein on oligomerization and tyrosine kinase activity of Bcr-Abl. Methods PTD-OD-HA fusion protein was labeled with FITC and co-cultured with K562 cells. The transduction efficiency of labeled PTD-OD-HA at different doses and time intervals was observed under fluorescence microscope. The location of labeled PTD-OD-HA fusion protein in K562 cells was detected by confocal microscopy. The interaction of PTD-OD-HA fusion protein with Bcr-Abl oncoprotein was confirmed by coimmunoprecipitation. The phosphorylation of Bcr-Abl oncoprotein was detected by Western blotting. Results PTD-OD-HA fusion protein labeled with FITC was transduced into K562 cells in a dose- and time-dependent manner. PTD-OD-HA fusion protein was located in the cytoplasm of K562 cells and was consistent with the location of Bcr-Abl oncoprotein. The interaction of PTD-OD-HA fusion protein with Bcr-Abl oncoprotein was proved in K562 cells. This interaction could interrupt the homologous oligomerization of Bcr-Abl oncoprotein and reduce the phosphorylation of Bcr-Abl oncoprotein. Conclusion PTD-OD-HA fusion protein could be transduced into K562 cells efficiently, inhibit the oligomerization and reduce the phosphorylation of Bcr-Abl oncoprotein.

  15. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells

    International Nuclear Information System (INIS)

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2015-01-01

    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 cells, Stat5

  16. 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.)

  17. 24 CFR 5.236 - Procedures for termination, denial, suspension, or reduction of assistance based on information...

    Science.gov (United States)

    2010-04-01

    ... or participant based on income information obtained from a SWICA or a Federal agency. Procedures... information reveals an employer or other income source that was not disclosed by the assistance applicant or..., the PHA shall request the undisclosed employer or other income source to furnish any information...

  18. 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.

  19. Selection of the Chrome Reduction Bacteria in the Waste of Tanning Leather Industries by Ozonization Method

    International Nuclear Information System (INIS)

    Yazid, M.; Aris Bastianudin; Widdi Usada

    2007-01-01

    Selection of the chrome reduction bacteria in the waste of tanning leather industries by ozonization method has been done. The objectives of this research was to obtain isolate bacteria from the waste with chrome contain, so that expected can be used for chrome bioremediation agent for arrange to improved the waste treatment for tanning leather industries. Selection of bacteria in the waste was carried out by ozonization method with time variation 0 to 210 minutes by time interval 15 minutes. Isolation bacteria was carried out was grown on the BHI media for 24 hours at 37°C temperature. So be inoculated by streak plate method on the TBX, MC, EA, CTM and BP media. Characterization of bacteria was done by saw the colonies morphology, sel morphology and biochemical characterization. So, identification of isolate bacteria by matching profile method. The result of this research can be obtained 5 isolate bacteria BCR1, BCR2, BCR3, BCR4 and BCR5 with the different phenotypic character. From the five isolate can be selected resistance ozon isolate until 180 minutes time ozonization were BCR 2, were identified belong to the genus of Bacillus. The examination results showed that the isolate bacteria be able to reduction of the chrome concentration in the waste of tanning leather industries by 71.03 %. Efficiency. (author)

  20. Effects of adding Braun jejunojejunostomy to standard Whipple procedure on reduction of afferent loop syndrome - a randomized clinical trial.

    Science.gov (United States)

    Kakaei, Farzad; Beheshtirouy, Samad; Nejatollahi, Seyed Moahammad Reza; Rashidi, Iqbal; Asvadi, Touraj; Habibzadeh, Afshin; Oliaei-Motlagh, Mohammad

    2015-12-01

    Whipple surgery (pancreaticodeudenectomy) has a high complication rate. We aimed to evaluate whether adding Braun jejunojejunostomy (side-to-side anastomosis of afferent and efferent loops distal to the gastrojejunostomy site) to a standard Whipple procedure would reduce postoperative complications. We conducted a randomized clinical trial comparing patients who underwent standard Whipple surgery (standard group) and patients who underwent standard Whipple surgery with Braun jejunojejunostomy (Braun group). Patients were followed for 1 month after the procedure and postoperative complications were recorded. Our study included 30 patients: 15 in the Braun and 15 in the standard group. In the Braun group, 4 (26.7%) patients experienced 6 complications, whereas in the standard group, 7 (46.7%) patients experienced 11 complications (p = 0.14). Complications in the Braun group were gastrointestinal bleeding and wound infection (n = 1 each) and delayed gastric emptying and pulmonary infection (n = 2 each). Complications in the standard group were death, pancreatic anastomosis leak and biliary anastomosis leak (n = 1 each); gastrointestinal bleeding (n = 2); and afferent loop syndrome and delayed gastric emptying (n = 3 each). There was no significant difference between groups in the subtypes of complications. Our results showed that adding Braun jejunojejunostomy to standard Whipple procedure was associated with lower rates of afferent loop syndrome and delayed gastric emptying. However, more studies are needed to define the role of Braun jejunojejunostomy in this regard. IRCT2014020316473N1 (www.irct.ir).

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

    Science.gov (United States)

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

    2007-04-01

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

  3. FUSION TRANSCRIPTS OF BCR/ABL GENE IN PATIENTES WITH CHRONIC MYELOID LEUKEMIA

    OpenAIRE

    Artigas, Carmen Gloria; Melo, Angélica; Roa, Juan Carlos; Roa, Iván; Quijada, Ingrid; Vittini, Cecilia; Cabrera, María Elena; Risueño, Concepción

    2003-01-01

    La anormalidad citogenética más común en la leucemia mieloide crónica (LMC) es el cromosoma Philadelphia, producida por la t(9;22), cuya expresión molecular es el gen de fusión BCR-ABL, que codifica proteínas con actividad tirosinquinasa. Según el punto de ruptura de los genes BCR o ABL se produce una proteína de fusión de 210-kD(p210) o 190-kD(p190). La presencia de este gen de fusión en pacientes con LMC tiene implicancia diagnóstica. Con el propósito de detectar transcriptos de fusión del ...

  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. 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.

  7. 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.

  8. 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.

  9. 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.

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

    Science.gov (United States)

    Jain, Shweta; Chodisetti, Sathi Babu; Agrewala, Javed N

    2011-01-01

    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.

  11. 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

  12. Regulatory effects of sestrin 3 (SESN3 in BCR-ABL expressing cells.

    Directory of Open Access Journals (Sweden)

    Eliza Vakana

    Full Text Available Chronic myeloid leukemia (CML and Ph+ acute lymphoblastic leukemia (ALL are characterized by the presence of the BCR-ABL oncoprotein, which leads to activation of a plethora of pro-mitogenic and pro-survival pathways, including the mTOR signaling cascade. We provide evidence that in BCR-ABL expressing cells, treatment with tyrosine kinase inhibitors (TKIs results in upregulation of mRNA levels and protein expression of sestrin3 (SESN3, a unique cellular inhibitor of mTOR complex 1 (mTORC1. Such upregulation appears to be mediated by regulatory effects on mTOR, as catalytic inhibition of the mTOR kinase also induces SESN3. Catalytic mTOR inhibition also results in upregulation of SESN3 expression in cells harboring the TKI-insensitive T315I-BCR-ABL mutant, which is resistant to imatinib mesylate. Overexpression of SESN3 results in inhibitory effects on different Ph+ leukemic cell lines including KT-1-derived leukemic precursors, indicating that SESN3 mediates anti-leukemic responses in Ph+ cells. Altogether, our findings suggest the existence of a novel mechanism for the generation of antileukemic responses in CML cells, involving upregulation of SESN3 expression.

  13. Lung Volume Reduction in Chronic Obstructive Pulmonary Disease (COPD AND#8211; An Updated Review of Surgical and Endoscopic Procedures

    Directory of Open Access Journals (Sweden)

    Ramakant Dixit

    2012-08-01

    Full Text Available The conventional medical management of emphysema using bronchodilators and anti-inflammatory agents has a limited benefit in patients having advanced hyperinflation of lungs due to destruction of elastic tissue. The natural course of Chronic Obstructive Pulmonary Disease (COPD has been shown to be altered by only smoking cessation and oxygen therapy so far. The lung volume reduction surgery is viewed as another modality to change the natural history of emphysema in recent years. For patients with more generalized emphysema, resection of lung parenchyma improves elastic recoil and chest wall mechanics. An extensive literature search has demonstrated that carefully selected patients of emphysema (i.e. upper lobe predominant disease, low exercise capacity and Forced Expiratory Volume in First Second (FEV1 and DLco and #8804; 20% of predicted receive benefits in terms of symptomatic improvement and physiologic response following Lung Volume Reduction Surgery (LVRS. The resurgent interest in LVRS and National Emphysema Treatment Trial findings for emphysema have stimulated a range of innovative methods, to improve the outcome and reduce complications associated with current LVRS techniques. These novel approaches include surgical resection with compression/banding devices, endobronchial blockers, sealants, obstructing devices and valves and endobronchial bronchial bypass approaches. Experimental data and preliminary results are becoming available for some of these approaches. Most of the published studies so far have been uncontrolled and unblinded. Overall, extensive research in the near future will help to determine the potential clinical applicability of these new approaches to the treatment of emphysema symptoms. [Arch Clin Exp Surg 2012; 1(4.000: 249-257

  14. Concepts and procedures required for successful reduction of tensor magnetic gradiometer data obtained from an unexploded ordnance detection demonstration at Yuma Proving Grounds, Arizona

    Science.gov (United States)

    Bracken, Robert E.; Brown, Philip J.

    2006-01-01

    On March 12, 2003, data were gathered at Yuma Proving Grounds, in Arizona, using a Tensor Magnetic Gradiometer System (TMGS). This report shows how these data were processed and explains concepts required for successful TMGS data reduction. Important concepts discussed include extreme attitudinal sensitivity of vector measurements, low attitudinal sensitivity of gradient measurements, leakage of the common-mode field into gradient measurements, consequences of thermal drift, and effects of field curvature. Spatial-data collection procedures and a spin-calibration method are addressed. Discussions of data-reduction procedures include tracking of axial data by mathematically matching transfer functions among the axes, derivation and application of calibration coefficients, calculation of sensor-pair gradients, thermal-drift corrections, and gradient collocation. For presentation, the magnetic tensor at each data station is converted to a scalar quantity, the I2 tensor invariant, which is easily found by calculating the determinant of the tensor. At important processing junctures, the determinants for all stations in the mapped area are shown in shaded relief map-view. Final processed results are compared to a mathematical model to show the validity of the assumptions made during processing and the reasonableness of the ultimate answer obtained.

  15. National Uranium Resource Evaluation. General procedure for calibration and reduction of aerial gamma-ray measurements: specification BFEC 1250-B

    International Nuclear Information System (INIS)

    Purvance, D.; Novak, E.

    1983-12-01

    The information contained in this specification was acquired over the course of the US Department of Energy (DOE) National Uranium Resource Evaluation (NURE) program during the period 1974 through 1982. NURE was a program of the DOE Grand Junction Area Office to acquire and compile geologic and other information with which to assess the magnitude and distribution of uranium resources and to determine areas favorable for the occurrence of uranium in the United States. Bendix Field Engineering Corporation (BFEC) has been the operating contractor for the DOE Grand Junction facility. The requirements stipulated herein had been incorporated as contractual specifications for the various subcontractors engaged in the aerial gamma-ray surveys, which were a major aspect of the NURE program. Although this phase of NURE activities has been completed, there exists valuable knowledge gained from these years of experience in the calibration of gamma-ray spectrometer systems and in the reduction of calibration data. Specification BFEC 1250-B is being open-filed by the US Department of Energy at this time to make this knowledge available to those desiring to apply gamma-ray spectrometry to other geophysical problems

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

    Science.gov (United States)

    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, 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

    2009-01-01

    SUMMARY 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-ABLT315I mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and pre-clinical evaluation of AP24534, a potent, orally available multi-targeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABLT315I-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. PMID:19878872

  17. 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.

  18. SU-F-I-77: Radiation Dose in Cardiac Catheterization Procedures: Impact of a Systematic Reduction in Pulsed Fluoroscopy Frame Rate

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, C; Dixon, S [Beaumont Hospital, Royal Oak, MI (United States)

    2016-06-15

    Purpose: To evaluate whether one small systematic reduction in fluoroscopy frame rate has a significant effect on the total air kerma and/or dose area product for diagnostic and interventional cardiac catheterization procedures. Methods: The default fluoroscopy frame rate (FFR) was lowered from 15 to 10 fps in 5 Siemens™ Axiom Artis cardiac catheterization labs (CCL) on July 1, 2013. A total of 7212 consecutive diagnostic and interventional CCL procedures were divided into two study groups: 3602 procedures from 10/1/12 –6/30/13 with FFR of 15 fps; and 3610 procedures 7/1/13 – 3/31/14 at 10 fps. For each procedure, total air kerma (TAK), fluoroscopy skin dose (FSD), total/fluoroscopy dose area products (TAD, FAD), and total fluoroscopy time (FT) were recorded. Patient specific data collected for each procedure included: BSA, sex, height, weight, interventional versus diagnostic; and elective versus emergent. Results: For pre to post change in FFR, each categorical variable was compared using Pearson’s Chi-square test, Odds ratios and 95% confidence intervals. No statistically significant difference in BSA, height, weight, number of interventional versus diagnostic, elective versus emergent procedures was found between the two study groups. Decreasing the default FFR from 15 fps to 10 fps in the two study groups significantly reduced TAK from 1305 to 1061 mGy (p<0.0001), FSD from 627 to 454 mGy (p<0.0001), TAD from 8681 to 6991 uGy × m{sup 2}(p<0.0001), and FAD from 4493 to 3297 uGy × m{sup 2}(p<0.0001). No statistically significant difference in FT was noted. Clinical image quality was not analyzed, and reports of noticeable effects were minimal. From July 1, 2013 to date, the default FFR has remained 10 fps. Conclusion: Reducing the FFR from 15 to 10 fps significantly reduced total air kerma and dose area product which may decrease risk for potential radiation-induced skin injuries and improve patient outcomes.

  19. Assessing of distribution, mobility and bioavailability of exogenous Pb in agricultural soils using isotopic labeling method coupled with BCR approach

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhi-Yong, E-mail: zhyhuang@jmu.edu.cn [College of Bioengineering, Jimei University, Xiamen 361021 (China); Xie, Hong [College of Bioengineering, Jimei University, Xiamen 361021 (China); Shandong Vocational Animal Science and Veterinary College, Weifang 261061 (China); Cao, Ying-Lan [College of Bioengineering, Jimei University, Xiamen 361021 (China); Cai, Chao [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Zhang, Zhi [College of Bioengineering, Jimei University, Xiamen 361021 (China)

    2014-02-15

    Highlights: • Large amounts of exogenous Pb were found to distribute in reducible fractions. • Very few of exogenous Pb were found to distribute in acid-extractable fractions. • More than 60% of exogenous Pb in rhizosphere soils lost after planting. • Isotopic labeling method and SEP enable to explore Pb bioavailability in soil. -- Abstract: The contamination of Pb in agricultural soils is one of the most important ecological problems, which potentially results in serious health risk on human health through food chain. Hence, the fate of exogenous Pb contaminated in agricultural soils is needed to be deeply explored. By spiking soils with the stable enriched isotopes of {sup 206}Pb, the contamination of exogenous Pb{sup 2+} ions in three agricultural soils sampled from the estuary areas of Jiulong River, China was simulated in the present study, and the distribution, mobility and bioavailability of exogenous Pb in the soils were investigated using the isotopic labeling method coupled with a four-stage BCR (European Community Bureau of Reference) sequential extraction procedure. Results showed that about 60–85% of exogenous Pb was found to distribute in reducible fractions, while the exogenous Pb in acid-extractable fractions was less than 1.0%. After planting, the amounts of exogenous Pb presenting in acid-extractable, reducible and oxidizable fractions in rhizospheric soils decreased by 60–66%, in which partial exogenous Pb was assimilated by plants while most of the metal might transfer downward due to daily watering and applying fertilizer. The results show that the isotopic labeling technique coupled with sequential extraction procedures enables us to explore the distribution, mobility and bioavailability of exogenous Pb contaminated in soils, which may be useful for the further soil remediation.

  20. Assessing of distribution, mobility and bioavailability of exogenous Pb in agricultural soils using isotopic labeling method coupled with BCR approach

    International Nuclear Information System (INIS)

    Huang, Zhi-Yong; Xie, Hong; Cao, Ying-Lan; Cai, Chao; Zhang, Zhi

    2014-01-01

    Highlights: • Large amounts of exogenous Pb were found to distribute in reducible fractions. • Very few of exogenous Pb were found to distribute in acid-extractable fractions. • More than 60% of exogenous Pb in rhizosphere soils lost after planting. • Isotopic labeling method and SEP enable to explore Pb bioavailability in soil. -- Abstract: The contamination of Pb in agricultural soils is one of the most important ecological problems, which potentially results in serious health risk on human health through food chain. Hence, the fate of exogenous Pb contaminated in agricultural soils is needed to be deeply explored. By spiking soils with the stable enriched isotopes of 206 Pb, the contamination of exogenous Pb 2+ ions in three agricultural soils sampled from the estuary areas of Jiulong River, China was simulated in the present study, and the distribution, mobility and bioavailability of exogenous Pb in the soils were investigated using the isotopic labeling method coupled with a four-stage BCR (European Community Bureau of Reference) sequential extraction procedure. Results showed that about 60–85% of exogenous Pb was found to distribute in reducible fractions, while the exogenous Pb in acid-extractable fractions was less than 1.0%. After planting, the amounts of exogenous Pb presenting in acid-extractable, reducible and oxidizable fractions in rhizospheric soils decreased by 60–66%, in which partial exogenous Pb was assimilated by plants while most of the metal might transfer downward due to daily watering and applying fertilizer. The results show that the isotopic labeling technique coupled with sequential extraction procedures enables us to explore the distribution, mobility and bioavailability of exogenous Pb contaminated in soils, which may be useful for the further soil remediation

  1. The Panchromatic High-Resolution Spectroscopic Survey of Local Group Star Clusters. I. General data reduction procedures for the VLT/X-shooter UVB and VIS arm

    Science.gov (United States)

    Schönebeck, Frederik; Puzia, Thomas H.; Pasquali, Anna; Grebel, Eva K.; Kissler-Patig, Markus; Kuntschner, Harald; Lyubenova, Mariya; Perina, Sibilla

    2014-12-01

    Aims: Our dataset contains spectroscopic observations of 29 globular clusters in the Magellanic Clouds and the Milky Way performed with VLT/X-shooter over eight full nights. To derive robust results instrument and pipeline systematics have to be well understood and properly modeled. We aim at a consistent data reduction procedure with an accurate understanding of the measurement accuracy limitations. Here we present detailed data reduction procedures for the VLT/X-shooter UVB and VIS arm. These are not restricted to our particular dataset, but are generally applicable to different kinds of X-shooter data without major limitation on the astronomical object of interest. Methods: ESO's X-shooter pipeline (v1.5.0) performs well and reliably for the wavelength calibration and the associated rectification procedure, yet we find several weaknesses in the reduction cascade that are addressed with additional calibration steps, such as bad pixel interpolation, flat fielding, and slit illumination corrections. Furthermore, the instrumental PSF is analytically modeled and used to reconstruct flux losses at slit transit. This also forms the basis for an optimal extraction of point sources out of the two-dimensional pipeline product. Regular observations of spectrophotometric standard stars obtained from the X-shooter archive allow us to detect instrumental variability, which needs to be understood if a reliable absolute flux calibration is desired. Results: A cascade of additional custom calibration steps is presented that allows for an absolute flux calibration uncertainty of ≲10% under virtually every observational setup, provided that the signal-to-noise ratio is sufficiently high. The optimal extraction increases the signal-to-noise ratio typically by a factor of 1.5, while simultaneously correcting for resulting flux losses. The wavelength calibration is found to be accurate to an uncertainty level of Δλ ≃ 0.02 Å. Conclusions: We find that most of the X

  2. 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

  3. The BTK Inhibitor Ibrutinib (PCI-32765) Blocks Hairy Cell Leukaemia Survival, Proliferation and BCR Signalling: A New Therapeutic Approach

    Science.gov (United States)

    Sivina, Mariela; Kreitman, Robert J.; Arons, Evgeny; Ravandi, Farhad; Burger, Jan A.

    2014-01-01

    B cell receptor (BCR) signalling plays a critical role in the progression of several B-cell malignancies, but its role in hairy cell leukaemia (HCL) is ambiguous. Bruton tyrosine kinase (BTK), a key player in BCR signalling, migration and adhesion, can be targeted with ibrutinib, a selective, irreversible BTK inhibitor. We analysed BTK expression and function in HCL and analysed the effects of ibrutinib on HCL cells. We demonstrated uniform BTK protein expression in HCL cells. Ibrutinib significantly inhibited HCL proliferation and cell cycle progression. Accordingly, ibrutinib also reduced HCL cell survival after BCR triggering with anti-immunoglobulins (A, G, and M) and abrogated the activation of kinases downstream of the BCR (PI3K and MAPK). Ibrutinib also inhibited BCR-dependent secretion of the chemokines CCL3 and CCL4 by HCL cells. Interestingly, ibrutinib inhibited CXCL12-induced signalling, a key pathway for bone marrow homing. Collectively, our data support the clinical development of ibrutinib in patients with HCL. PMID:24697238

  4. 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

  5. Is Closed Manipulative Reduction and Percutaneous Kirschner Wiring of Supracondylar Humeral Fracture in Children as Day-Care Surgery a Safe Procedure ?

    Directory of Open Access Journals (Sweden)

    Ashok R Nayak

    2013-07-01

    Full Text Available INTRODUCTION: Supracondylar fracture of the humerus is a common injury in children. It accounts for 60% of fractures around the elbow children. If the fracture is not treated properly it may give rise to many complications like malunion, Volkmann’s ischemic contracture, nerve injury, arterial injury, skin slough, heterotopic bone formation , and stiffness of elbow. The management of displaced supracondylar fracture of the elbow is one of the most difficult of the many fractures seen in children. The purpose of the study was to evaluate the anatomical and functional results of treatment of supracondylar fractures of humerus with closed reduction and percutaneous ‘K’ wire fixation as a day care procedure and record associated complications, thus decreasing the cost of treating these fractures and hospitalization. METHODS: Fifty displaced closed extension type supracondylar fractures (Gartland’s type III of the humerus in children were treated by closed reduction and percutaneous fixation with Kirschner wires. All the patients selected for this study had been treated in a day care unit and were discharged in the same evening and followed up at 3 and 6 weeks and 3 months. Open fractures, fractures with neurovascular complications and children older than 15 yrs were excluded. The final results were evaluated by Flynn’s criteria. RESULTS: The majority (72%, of the patients had fracture displaced posteomedially, Fourty one of the fifty patients had satisfactory results. The majority of the patients were male, and the average age was 8-9 years. CONCLUSION: Percutaneous fixation of supracondylar humerus done as a day care procedure is an acceptable modality of treatment and reduces the duration of hospital stay for the patient.

  6. The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac- and Rab-dependent pathways

    OpenAIRE

    Knetsch, Menno L.W.; Schäfers, Nicole; Horstmann, Heinz; Manstein, Dietmar J.

    2001-01-01

    Dictyostelium discoideum DdRacGap1 (DRG) contains both Rho-GEF and Rho-GAP domains, a feature it shares with mammalian Bcr and Abr. To elucidate the physiological role of this multifunctional protein, we characterized the enzymatic activity of recombinant DRG fragments in vitro, created DRG-null cells, and studied the function of the protein in vivo by analysing the phenotypic changes displayed by DRG-depleted cells and DRG-null cells complemented with DRG or DRG fragments. Our results show t...

  7. Determination of persistent organohalogenated pollutants in human hair reference material (BCR 397): an interlaboratory study

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Udai [Health Canada, Product Safety Laboratory, Ottawa, Ontario (Canada); Covaci, Adrian [University of Antwerp, Toxicological Center, Wilrijk (Belgium); Ryan, John Jake [Health Canada, Bureau of Chemical Safety, Health Products and Food Branch, Ottawa, Ontario (Canada); Emond, Andre [Health Canada, Environmental Research Division, First Nations and Inuit Health Branch, Ottawa, Ontario K1A0L2 (Canada)

    2004-12-01

    A human powdered hair material (BCR 397) was tested for its content in persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). Using different methods, three laboratories (two from Canada and one from Belgium) analysed a powdered hair sample to evaluate some methodologies and to obtain consensus values for selected POPs. Measured values for all PCB congeners and p,p'-DDE were within a relative standard deviation (RSD) of 15%. These first results contribute to the accuracy and precision for POPs quantification in hair and render test results more comparable among different laboratories. (orig.)

  8. Paediatric multidetector CT optimisation training: a survey of common scanning procedures and the resultant dose reduction associated with paediatric MDCT investigations in Australia

    International Nuclear Information System (INIS)

    Wallace, Anthony; Sibelle, Kimberly; Stanley, Martin; Budd, Ray; Goergen, Stacey; Heggie, John

    2008-01-01

    The growing recognition of the increased risk of stochastic injury to paediatric patients from multidetector CT (MDCT) investigations prompted a survey sponsored by Royal Australian and New Zealand College of Radiology (RANZCR), Austin Health and Monash University to initiate a national paediatric dosimetry review for some of the most common investigations undertaken in MDCT paediatric practice. The survey forms included a data sheet requiring acquisition protocol parameters and a phantom graphic sheet requiring the marking of the inferior and superior acquisition margins. Survey forms were supplied for each of 13 common MDCT acquisitions to be tested. Response data was input into CT-Expo Version 1.5.1., a CT dosimetry calculation engine, to determine dose length product (DLP (mGy.cm)) and effective dose (ED (mSv)). Initial survey data was collected, calculated, blinded and collated into various presentations that were given at a MDCT optimisation seminar in November, 2006. All sites were re-surveyed in May 2007 and doses calculated. Initial survey data showed a range of dose efficiencies spread across the surveyed sites. A measure of the initial spread of DLP values per procedure ranged from a minimum of less than 2 for a head-trauma acquisition (372 - 520 mGy.cm) to 14 for a chest-trauma acquisition (28 - 388 mGy.cm). Results of the 2nd survey strongly indicate that the application of optimisation training to paediatric MDCT scanning can produce significant dose savings by the application of simple dose saving strategies. Many protocols demonstrated dose reductions of greater than 50% with significant reductions in both the maximum and minimum values of calculated DLP and ED. The development of a survey-training-resurvey model of MDCT optimisation has proven to be a successful strategy for paediatric MDCT dose reduction in Australia. (author)

  9. [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.

  10. Suppression of bcr-abl synthesis by siRNAs or tyrosine kinase activity by Glivec alters different oncogenes, apoptotic/antiapoptotic genes and cell proliferation factors (microarray study).

    Science.gov (United States)

    Zhelev, Zhivko; Bakalova, Rumiana; Ohba, Hideki; Ewis, Ashraf; Ishikawa, Mitsuru; Shinohara, Yasuo; Baba, Yoshinobu

    2004-07-16

    Short 21-mer double-stranded/small-interfering RNAs (ds/siRNAs) were designed to target bcr-abl mRNA in chronic myelogenous leukemia. The ds/siRNAs were transfected into bcr-abl-positive K-562 (derived from blast crisis chronic myelogenous leukemia), using lipofectamine. Penetrating of ds/siRNAs into the cells was detected by fluorescent confocal microscopy, using fluorescein-labeled ds/siRNAs. The cells were treated with mix of three siRNA sequences (3 x 60 nM) during 6 days with three repetitive transfections. The siRNA-treatment was accompanied with significant reduction of bcr-abl mRNA, p210, protein tyrosine kinase activity and cell proliferation index. Treatment of cells with Glivec (during 8 days with four repetitive doses, 180 nM single dose) resulted in analogous reduction of cell proliferation activity, stronger suppression of protein tyrosine kinase activity, and very low reduction of p210. siRNA-mix and Glivec did not affect significantly the viability of normal lymphocytes. Microarray analysis of siRNA- and Glivec-treated K-562 cells demonstrated that both pathways of bcr-abl suppression were accompanied with overexpression and suppression of many different oncogenes, apoptotic/antiapoptotic and cell proliferation factors. The following genes of interest were found to decrease in relatively equal degree in both siRNA- and Glivec-treated cells: Bcd orf1 and orf2 proto-oncogene, chromatin-specific transcription elongation factor FACT 140-kDa subunit mRNA, gene encoding splicing factor SF1, and mRNA for Tec protein tyrosine kinase. siRNA-mix and Glivec provoked overexpression of the following common genes: c-jun proto-oncogene, protein kinase C-alpha, pvt-1 oncogene homologue (myc activator), interleukin-6, 1-8D gene from interferon-inducible gene family, tumor necrosis factor receptor superfamily (10b), and STAT-induced STAT inhibitor.

  11. BCR translocation to derivative chromosome 2, a new case of chronic myeloid leukemia with complex variant translocation and Philadelphia chromosome

    International Nuclear Information System (INIS)

    Al-Achkar, W.; Wafa, A.; Al-Medani, S.

    2011-01-01

    The well-known typical fusion gene BCR/ABL can be observed in connection with a complex translocation event in only 5-8% of cases with chronic myeloid leukemia (CML). Herein we report an exceptional CML case with complex chromosomal aberrations not observed before, translocated BCR to the derivative chromosome 2 [der(2)], additional to involving a four chromosomes translocation implying chromosomal regions such as 1p32 and 2q21 besides 9q34 and 22q11.2. Which were characterized by molecular cytogenetics. (author)

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

    Directory of Open Access Journals (Sweden)

    Cano Pedro

    2004-06-01

    Full Text Available Abstract Background 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. Methods 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. Results Significant negative associations (p Conclusions 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. 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

  14. Unexpected heterogeneity of BCR-ABL fusion mRNA detected by polymerase chain reaction in Philadelphia chromosome-positive acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Hooberman, A.L.; Carrino, J.J.; Leibowitz, D.; Rowley, J.D.; Le Beau, M.M.; Arlin, Z.A.; Westbrook, C.A.

    1989-01-01

    The Philadelphia (Ph 1 ) chromosome results in a fusion of portions of the BCR gene from chromosome 22 and the ABL gene from chromosome 9, producing a chimeric BCR-ABL mRNA and protein. In lymphoblastic leukemias, there are two molecular subtypes of the Ph 1 chromosome, one with a rearrangement of the breakpoint cluster region (bcr) of the BCR gene, producing the same 8.5-kilobase BCR-ABL fusion mRNA seen in chronic myelogenous leukemia (CML), and the other, without a bcr rearrangement, producing a 7.0-kilobase BCR-ABL fusion mRNA that is seen only in acute lymphoblastic leukemia (ALL). The authors studied the molecular subtype of the Ph 1 chromosome in 11 cases of Ph 1 -positive ALL, including 2 with a previous diagnosis of CML, using a sensitive method to analyze the mRNA species based on the polymerase chain reaction (PCR). They observed unexpected heterogeneity in BCR-ABL mRNA in this population. They conclude that the PCR gives additional information about the Ph 1 chromosome gene products that cannot be obtained by genomic analysis, but that it cannot be used as the sole means of detection of this chromosomal abnormality in ALL because of the high incidence of false negative results

  15. Growth of chronic myeloid leukemia cells is inhibited by infection with Ad-SH2-HA adenovirus that disrupts Grb2-Bcr-Abl complexes.

    Science.gov (United States)

    Peng, Zhi; Luo, Hong-Wei; Yuan, Ying; Shi, Jing; Huang, Shi-Feng; Li, Chun-Li; Cao, Wei-Xi; Huang, Zong-Gan; Feng, Wen-Li

    2011-05-01

    The persistence of Bcr-Abl-positive cells in patients on imatinib therapy indicates that inhibition of the Bcr-Abl kinase activity alone might not be sufficient to eradicate the leukemia cells. Many downstream effectors of Bcr-Abl have been described, including activation of both the Grb2-SoS-Ras-MAPK and Grb2-Gab2-PI3K-Akt pathways. The Bcr-Abl-Grb2 interaction, which is mediated by the direct interaction of the Grb2 SH2 domain with the phospho-Bcr-Abl Y177, is required for activation of these signaling pathways. Therefore, disrupting their interaction represents a potential therapeutic strategy for inhibiting the oncogenic downstream signals of Bcr-Abl. Adenovirus Ad-SH2-HA expressing the Grb2 SH2 domain was constructed and applied in this study. As expected, Ad-SH2-HA efficiently infected CML cells and functioned by binding to the phospho-Bcr-Abl Y177 site, competitively disrupting the Grb2 SH2-phospho-Bcr-Abl Y177 complex. They induced potent anti-proliferation and apoptosis-inducing effects in CML cell lines. Moreover, the Ras, MAPK and Akt activities were significantly reduced in the Ad-SH2-HA treated cells. These were not observed with the point-mutated control adenovirus Ad-Sm-HA with abolished phospho-Bcr-Abl Y177 binding sites. These data indicate that, in addition to the direct targeting of Bcr-Abl, selective inhibition of its downstream signaling pathways may be a therapeutic option for CML, and the Ad-SH2-HA-mediated killing strategy could be explored as a promising anti-leukemia agent in CML.

  16. 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

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

    International Nuclear Information System (INIS)

    Ohtomo, Tadashi; Miyazawa, Keisuke; Naito, Munekazu; Moriya, Shota; Kuroda, Masahiko; Itoh, Masahiro; Tomoda, Akio

    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 -/- 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.

  18. 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.

  19. BCR/ABL downregulates DNA-PK(CS)-dependent and upregulates backup non-homologous end joining in leukemic cells.

    Science.gov (United States)

    Poplawski, Tomasz; Blasiak, Janusz

    2010-06-01

    Non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are the main mechanisms involved in the processing of DNA double strand breaks (DSBs) in humans. We showed previously that the oncogenic tyrosine kinase BCR/ABL stimulated DSBs repair by HRR. To evaluate the role of BCR/ABL in DSBs repair by NHEJ we examined the ability of leukemic BCR/ABL-expressing cell line BV173 to repair DNA damage induced by two DNA topoisomerase II inhibitors: etoposide and sobuzoxane. DNA lesions induced by sobuzoxane are repaired by a NHEJ pathway which is dependent on the catalytic subunit of protein kinase dependent on DNA (DNA-PK(CS); D-NHEJ), whereas damage evoked by etoposide are repaired by two distinct NHEJ pathways, dependent on or independent of DNA-PK(CS) (backup NHEJ, B-NHEJ). Cells incubated with STI571, a highly specific inhibitor of BCR/ABL, displayed resistance to these agents associated with an accelerated kinetics of DSBs repair, as measured by the neutral comet assay and pulsed field gel electrophoresis. However, in a functional NHEJ assay, cells preincubated with STI571 repaired DSBs induced by a restriction enzyme with a lower efficacy than without the preincubation and addition of wortmannin, a specific inhibitor of DNA-PK(CS), did not change efficacy of the NHEJ reaction. We suggest that BCR/ABL switch on B-NHEJ which is more error-prone then D-NHEJ and in such manner contribute to the increase of the genomic instability of leukemic cells.

  20. 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.

  1. Dual Drug Targeting of Mutant Bcr-Abl Induces Inactive Conformation: New Strategy for the Treatment of Chronic Myeloid Leukemia and Overcoming Monotherapy Resistance.

    Science.gov (United States)

    El Rashedy, Ahmed A; Olotu, Fisayo A; Soliman, Mahmoud E S

    2018-03-01

    Bcr-Abl is an oncogenic fusion protein which expression enhances tumorigenesis, and has been highly associated with chronic myeloid leukemia (CML). Acquired drug resistance in mutant Bcr-Abl has enhanced pathogenesis with the use of single therapy agents such as nilotinib. Moreover, allosteric targeting has been identified to consequentially inhibit Bcr-Abl activity, which led to the recent development of ABL-001 (asciminib) that selectively binds the myristoyl pocket. Experimental studies have revealed that the combination of nilotinib and ABL-001 induced a 'bent' conformation in the C-terminal helix of Bcr-Abl; a benchmark of inhibition, thereby exhibiting a greater potency in the treatment of CML, surmounting the setbacks of drug resistance, disease regression and relapse. Therefore, we report the first account of the dynamics and conformational analysis of oncogenic T334I Bcr-Abl by dual targeting. Our findings revealed that unlike in the Bcr-Abl-Nilotinib complex, dual targeting by both inhibitors induced the bent conformation in the C-terminal helix that varied with time. This was coupled with significant alteration in Bcr-Abl stability, flexibility, and compactness and an overall structural re-orientation inwards towards the hydrophobic core, which reduced the solvent-exposed residues indicative of protein folding. This study will facilitate allosteric targeting and the design of more potent allosteric inhibitors for resistive target proteins in cancer. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

  2. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl{sup +} K562 and Jak2(V617F){sup +} HEL Leukemia Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Axel [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany); Borghouts, Corina [Ganymed Pharmaceuticals AG, Mainz 55131 (Germany); Brendel, Christian [Boston Children’s Hospital, Division of Hematology/Oncology, Boston, MA 02115 (United States); Moriggl, Richard [Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna 1090 (Austria); Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd, E-mail: Groner@em.uni-frankfurt.de [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany)

    2015-03-19

    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{sup +} K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells

  3. 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

  4. Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22)(p24;q11)

    OpenAIRE

    A. N. Chamseddine; P. Etancelin; D. Penther; F. Parmentier; C. Kuadjovi; V. Camus; N. Contentin; P. Lenain; C. Bastard; H. Tilly; F. Jardin

    2015-01-01

    BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24) that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U) showing a t(9;22)(p24;q11), which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most...

  5. 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...

  6. Field Test Evaluation of Conservation Retrofits of Low-Income, Single-Family Buildings in Wisconsin: Blower-Door-Directed Infiltration Reduction Procedure, Field Test Implementation and Results; TOPICAL

    International Nuclear Information System (INIS)

    Gettings, M.B.

    2001-01-01

    A blower-door-directed infiltration retrofit procedure was field tested on 18 homes in south central Wisconsin. The procedure, developed by the Wisconsin Energy Conservation Corporation, includes recommended retrofit techniques as well as criteria for estimating the amount of cost-effective work to be performed on a house. A recommended expenditure level and target air leakage reduction, in air changes per hour at 50 Pascal (ACH50), are determined from the initial leakage rate measured. The procedure produced an average 16% reduction in air leakage rate. For the 7 houses recommended for retrofit, 89% of the targeted reductions were accomplished with 76% of the recommended expenditures. The average cost of retrofits per house was reduced by a factor of four compared with previous programs. The average payback period for recommended retrofits was 4.4 years, based on predicted energy savings computed from achieved air leakage reductions. Although exceptions occurred, the procedure's 8 ACH50 minimum initial leakage rate for advising retrofits to be performed appeared a good choice, based on cost-effective air leakage reduction. Houses with initial rates of 7 ACH50 or below consistently required substantially higher costs to achieve significant air leakage reductions. No statistically significant average annual energy savings was detected as a result of the infiltration retrofits. Average measured savings were -27 therm per year, indicating an increase in energy use, with a 90% confidence interval of 36 therm. Measured savings for individual houses varied widely in both positive and negative directions, indicating that factors not considered affected the results. Large individual confidence intervals indicate a need to increase the accuracy of such measurements as well as understand the factors which may cause such disparity. Recommendations for the procedure include more extensive training of retrofit crews, checks for minimum air exchange rates to insure air quality

  7. BCR: a service to quality assurance in analytical chemistry - some experiences and achievements with regard to reference material preparation

    Energy Technology Data Exchange (ETDEWEB)

    Griepink, B. (Commission of the European Communities, Measurements and Testing Programme (BCR), Brussels (Belgium)); Quevauviller, P. (Commission of the European Communities, Measurements and Testing Programme (BCR), Brussels (Belgium)); Maier, E.A. (Commission of the European Communities, Measurements and Testing Programme (BCR), Brussels (Belgium)); Vandendriessche, S. (Commission of the European Communities, Measurements and Testing Programme (BCR), Brussels (Belgium))

    Despite all efforts to improve the quality of results of measurements, intercomparisons demonstrate a considerable discrepancy. This fact was also shown by many of the round robins organised by the BCR (Commission of the European Communities) on inorganic, speciation, and organic determinations in various environmental matrices. It is clear that further efforts have to be made to improve the state of the art of a wide variety of analyses. This means that the demand for certified reference materials (CRMs) is and will be in constant increase. RMs are required for the validation of methods, for proficiency testing or for training purposes. The production of RMs and CRMs resembling the composition of real matrices poses difficult problems for some compounds and is a challenge for the producers. This paper presents some recent experiences and achievements of the BCR in special cases. (orig.)

  8. 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

  9. Disrupting BCR-ABL in Combination with Secondary Leukemia-Specific Pathways in CML Cells Leads to Enhanced Apoptosis and Decreased Proliferation

    OpenAIRE

    Woessner, David W.; Lim, Carol S.

    2012-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by expression of the fusion gene BCR-ABL following a chromosomal translocation in the hematopoietic stem cell.1 Therapeutic management of CML uses tyrosine kinase inhibitors (TKIs), which blocks ABL-signaling and effectively kill peripheral cells with BCR-ABL. However, TKIs are not curative, and chronic use of is required in order to treat CML. The primary failure for TKIs is through development of a resistant population d...

  10. 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.

  11. Flow Cytometric Immunobead Assay for Detection of BCR-ABL1 Fusion Proteins in Chronic Myleoid Leukemia: Comparison with FISH and PCR Techniques

    Science.gov (United States)

    Recchia, Anna Grazia; Caruso, Nadia; Bossio, Sabrina; Pellicanò, Mariavaleria; De Stefano, Laura; Franzese, Stefania; Palummo, Angela; Abbadessa, Vincenzo; Lucia, Eugenio; Gentile, Massimo; Vigna, Ernesto; Caracciolo, Clementina; Agostino, Antolino; Galimberti, Sara; Levato, Luciano; Stagno, Fabio; Molica, Stefano; Martino, Bruno; Vigneri, Paolo; Di Raimondo, Francesco; Morabito, Fortunato

    2015-01-01

    Chronic Myeloid Leukemia (CML) is characterized by a balanced translocation juxtaposing the Abelson (ABL) and breakpoint cluster region (BCR) genes. The resulting BCR-ABL1 oncogene leads to increased proliferation and survival of leukemic cells. Successful treatment of CML has been accompanied by steady improvements in our capacity to accurately and sensitively monitor therapy response. Currently, measurement of BCR-ABL1 mRNA transcript levels by real-time quantitative PCR (RQ-PCR) defines critical response endpoints. An antibody-based technique for BCR-ABL1 protein recognition could be an attractive alternative to RQ-PCR. To date, there have been no studies evaluating whether flow-cytometry based assays could be of clinical utility in evaluating residual disease in CML patients. Here we describe a flow-cytometry assay that detects the presence of BCR-ABL1 fusion proteins in CML lysates to determine the applicability, reliability, and specificity of this method for both diagnosis and monitoring of CML patients for initial response to therapy. We show that: i) CML can be properly diagnosed at onset, (ii) follow-up assessments show detectable fusion protein (i.e. relative mean fluorescent intensity, rMFI%>1) when BCR-ABL1IS transcripts are between 1–10%, and (iii) rMFI% levels predict CCyR as defined by FISH analysis. Overall, the FCBA assay is a rapid technique, fully translatable to the routine management of CML patients. PMID:26111048

  12. Flow Cytometric Immunobead Assay for Detection of BCR-ABL1 Fusion Proteins in Chronic Myleoid Leukemia: Comparison with FISH and PCR Techniques.

    Directory of Open Access Journals (Sweden)

    Anna Grazia Recchia

    Full Text Available Chronic Myeloid Leukemia (CML is characterized by a balanced translocation juxtaposing the Abelson (ABL and breakpoint cluster region (BCR genes. The resulting BCR-ABL1 oncogene leads to increased proliferation and survival of leukemic cells. Successful treatment of CML has been accompanied by steady improvements in our capacity to accurately and sensitively monitor therapy response. Currently, measurement of BCR-ABL1 mRNA transcript levels by real-time quantitative PCR (RQ-PCR defines critical response endpoints. An antibody-based technique for BCR-ABL1 protein recognition could be an attractive alternative to RQ-PCR. To date, there have been no studies evaluating whether flow-cytometry based assays could be of clinical utility in evaluating residual disease in CML patients. Here we describe a flow-cytometry assay that detects the presence of BCR-ABL1 fusion proteins in CML lysates to determine the applicability, reliability, and specificity of this method for both diagnosis and monitoring of CML patients for initial response to therapy. We show that: i CML can be properly diagnosed at onset, (ii follow-up assessments show detectable fusion protein (i.e. relative mean fluorescent intensity, rMFI%>1 when BCR-ABL1IS transcripts are between 1-10%, and (iii rMFI% levels predict CCyR as defined by FISH analysis. Overall, the FCBA assay is a rapid technique, fully translatable to the routine management of CML patients.

  13. Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface*

    Science.gov (United States)

    Wojcik, John; Lamontanara, Allan Joaquim; Grabe, Grzegorz; Koide, Akiko; Akin, Louesa; Gerig, Barbara; Hantschel, Oliver; Koide, Shohei

    2016-01-01

    Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase domains and to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher affinity monobodies with single nanomolar KD values targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in chronic myelogenous leukemia cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl. PMID:26912659

  14. Computational dissection of allosteric inhibition of the SH2 domain of Bcr-Abl kinase by the monobody inhibitor AS25.

    Science.gov (United States)

    Ji, Mingfei; Zheng, Guodong; Li, Xiaolong; Zhang, Zhongqin; Jv, Guanqun; Wang, Xiaowei; Wang, Jialin

    2017-06-01

    The deregulated breakpoint cluster region (Bcr)-Abelson tyrosine kinase (Abl) fusion protein represents an attractive pharmacological target for the treatment of chronic myeloid leukemia (CML). The high affinity of monobody AS25 was designed to target the Src homology 2 (SH2) domain of Bcr-Abl, leading to allosteric inhibition of Bcr-Abl through formation of protein-protein interactions. An I164E mutation in the SH2 domain disrupts AS25 binding to the SH2 domain of Bcr-Abl. The detailed mechanisms, however, remain to be unresolved. Here, molecular dynamics (MD) simulations and binding free energy calculations were performed to explore the conformational and energetic differences between the wild-type (WT) complexes of Bcr-Abl SH2 domain and AS25 (SH2 WT -AS25) as well as the mutated complexes (SH2 I164E -AS25). The results revealed that I164E mutation not only caused an increase in the conformational flexibility of SH2-AS25 complexes, but also weakened the binding affinity of AS25 to SH2. The comparative binding modes of SH2-AS25 complexes between WT and the I164E mutant were comprehensively analyzed to unravel the disruption of hydrophobic and hydrogen bonding interactions in the interface of the SH2-AS25 complex triggered by the I164E mutation. The results obtained may help to design the next generation of higher affinity Bcr-Abl SH2-specific peptide inhibitors.

  15. Allosteric Inhibition of Bcr-Abl Kinase by High Affinity Monobody Inhibitors Directed to the Src Homology 2 (SH2)-Kinase Interface.

    Science.gov (United States)

    Wojcik, John; Lamontanara, Allan Joaquim; Grabe, Grzegorz; Koide, Akiko; Akin, Louesa; Gerig, Barbara; Hantschel, Oliver; Koide, Shohei

    2016-04-15

    Bcr-Abl is a constitutively active kinase that causes chronic myelogenous leukemia. We have shown that a tandem fusion of two designed binding proteins, termed monobodies, directed to the interaction interface between the Src homology 2 (SH2) and kinase domains and to the phosphotyrosine-binding site of the SH2 domain, respectively, inhibits the Bcr-Abl kinase activity. Because the latter monobody inhibits processive phosphorylation by Bcr-Abl and the SH2-kinase interface is occluded in the active kinase, it remained undetermined whether targeting the SH2-kinase interface alone was sufficient for Bcr-Abl inhibition. To address this question, we generated new, higher affinity monobodies with single nanomolar KD values targeting the kinase-binding surface of SH2. Structural and mutagenesis studies revealed the molecular underpinnings of the monobody-SH2 interactions. Importantly, the new monobodies inhibited Bcr-Abl kinase activity in vitro and in cells, and they potently induced cell death in chronic myelogenous leukemia cell lines. This work provides strong evidence for the SH2-kinase interface as a pharmacologically tractable site for allosteric inhibition of Bcr-Abl. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. CALR, JAK2 and MPL mutation status in Argentinean patients with BCR-ABL1- negative myeloproliferative neoplasms.

    Science.gov (United States)

    Ojeda, Mara Jorgelina; Bragós, Irma Margarita; Calvo, Karina Lucrecia; Williams, Gladis Marcela; Carbonell, María Magdalena; Pratti, Arianna Flavia

    2018-05-01

    To establish the frequency of JAK2, MPL and CALR mutations in Argentinean patients with BCR-ABL1-negative  myeloproliferative neoplasms (MPN) and to compare their clinical and haematological features. Mutations of JAK2V617F, JAK2 exon 12, MPL W515L/K and CALR were analysed in 439 Argentinean patients with BCR-ABL1-negative MPN, including 176 polycythemia vera (PV), 214 essential thrombocythemia (ET) and 49 primary myelofibrosis (PMF). In 94.9% of PV, 85.5% ET and 85.2% PMF, we found mutations in JAK2, MPL or CALR. 74.9% carried JAK2V617F, 12.3% CALR mutations, 2.1% MPL mutations and 10.7% were triple negative. In ET, nine types of CALR mutations were identified, four of which were novel. PMF patients were limited to types 1 and 2, type 2 being more frequent. In ET, patients with CALR mutation were younger and had higher platelet counts than those with JAK2V617F and triple negative. In addition, JAK2V617F patients had high leucocyte and haemoglobin values compared with CALR-mutated and triple-negative patients. In PMF, patients with mutant CALR were associated with higher platelet counts. Our study underscores the importance of JAK2, MPL and CALR genotyping for accurate diagnosis of patients with BCR-ABL1-negative MPN.

  17. 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.

  18. Combined Targeting of BCL-2 and BCR-ABL Tyrosine Kinase Eradicates Chronic Myeloid Leukemia Stem Cells

    Science.gov (United States)

    Mak, Po Yee; Mu, Hong; Zhou, Hongsheng; Mak, Duncan H.; Schober, Wendy; Leverson, Joel D.; Zhang, Bin; Bhatia, Ravi; Huang, Xuelin; Cortes, Jorge; Kantarjian, Hagop; Konopleva, Marina

    2016-01-01

    BCR-ABL tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML), but they rarely eliminate CML stem cells. Disease relapse is common upon therapy cessation, even in patients with complete molecular responses. Furthermore, once CML progresses to blast crisis (BC), treatment outcomes are dismal. We hypothesized that concomitant targeting of BCL-2 and BCR-ABL tyrosine kinase could overcome these limitations. We demonstrate increased BCL-2 expression at the protein level in bone marrow cells, particularly in Lin−Sca-1+cKit+ cells of inducible CML in mice as determined by CyTOF mass cytometry. Further, selective inhibition of BCL-2, aided by TKI-mediated MCL-1 and BCL-XL inhibition, markedly decreased leukemic Lin−Sca-1+cKit+ cell numbers and long-term stem cell frequency, and prolonged survival in a murine CML model. Additionally, this combination effectively eradicated CD34+CD38−, CD34+CD38+, and quiescent stem/progenitor CD34+ cells from BC CML patient samples. Our results suggest that BCL-2 is a key survival factor for CML stem/progenitor cells and that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve depth of response and cure rates of chronic phase and BC CML. PMID:27605552

  19. 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

  20. 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.

  1. Reductions in Average Lengths of Stays for Surgical Procedures Between the 2008 and 2014 United States National Inpatient Samples Were Not Associated With Greater Incidences of Use of Postacute Care Facilities.

    Science.gov (United States)

    Dexter, Franklin; Epstein, Richard H

    2018-03-01

    Diagnosis-related group (DRG) based reimbursement creates incentives for reduction in hospital length of stay (LOS). Such reductions might be accomplished by lesser incidences of discharges to home. However, we previously reported that, while controlling for DRG, each 1-day decrease in hospital median LOS was associated with lesser odds of transfer to a postacute care facility (P = .0008). The result, though, was limited to elective admissions, 15 common surgical DRGs, and the 2013 US National Readmission Database. We studied the same potential relationship between decreased LOS and postacute care using different methodology and over 2 different years. The observational study was performed using summary measures from the 2008 and 2014 US National Inpatient Sample, with 3 types of categories (strata): (1) Clinical Classifications Software's classes of procedures (CCS), (2) DRGs including a major operating room procedure during hospitalization, or (3) CCS limiting patients to those with US Medicare as the primary payer. Greater reductions in the mean LOS were associated with smaller percentages of patients with disposition to postacute care. Analyzed using 72 different CCSs, 174 DRGs, or 70 CCSs limited to Medicare patients, each pairwise reduction in the mean LOS by 1 day was associated with an estimated 2.6% ± 0.4%, 2.3% ± 0.3%, or 2.4% ± 0.3% (absolute) pairwise reduction in the mean incidence of use of postacute care, respectively. These 3 results obtained using bivariate weighted least squares linear regression were all P < .0001, as were the corresponding results obtained using unweighted linear regression or the Spearman rank correlation. In the United States, reductions in hospital LOS, averaged over many surgical procedures, are not accomplished through a greater incidence of use of postacute care.

  2. 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.

  3. Reduction corporoplasty.

    Science.gov (United States)

    Hakky, Tariq S; Martinez, Daniel; Yang, Christopher; Carrion, Rafael E

    2015-01-01

    Here we present the first video demonstration of reduction corporoplasty in the management of phallic disfigurement in a 17 year old man with a history sickle cell disease and priapism. Surgical management of aneurysmal dilation of the corpora has yet to be defined in the literature. We preformed bilateral elliptical incisions over the lateral corpora as management of aneurysmal dilation of the corpora to correct phallic disfigurement. The patient tolerated the procedure well and has resolution of his corporal disfigurement. Reduction corporoplasty using bilateral lateral elliptical incisions in the management of aneurysmal dilation of the corpora is a safe an feasible operation in the management of phallic disfigurement.

  4. Medicaid program; Medicaid Management Information Systems; conditions of approval and reapproval and procedures for reduction of Federal financial participation--HCFA. Final rule.

    Science.gov (United States)

    1985-07-30

    This final rule provides the additional requirements to the conditions and procedures for initial approval and reapproval of Medicaid Management Information Systems (MMIS) that were added by section 1903(r) of the Social Security Act (as amended by section 901 of the Mental Health Systems Act of 1980, Pub. L. 96-398). These provisions are intended to improve States' MMIS, ensure efficient system operations, and make the procedures for detection of fraud, waste, and abuse more effective. In addition, this final rule specifies the procedures we follow in reducing the level of Federal financial participation in State administrative expenditures if a State fails to meet the conditions for initial operation, initial approval, or reapproval of an MMIS.

  5. Medicaid program; Medicaid Management Information Systems; conditions of approval and reapproval and procedures for reduction of federal financial participation--Health Care Financing Administration. Proposed rule.

    Science.gov (United States)

    1983-03-03

    This proposal adds to regulations new conditions and procedures for initial approval and for reapproval of Medicaid Management Information Systems (MMIS) to update the regulations to reflect additional requirements added by section 901 of the Mental Health Systems Act of 1980 (Pub. L. 96-398). The proposal specifies procedures for reducing the level of Federal financial participation in a State's administrative expenditures when a State fails to meet the conditions for initial operation, initial approval or reapproval of an MMIS. It also proposes procedures with respect to waivers of the conditions of approval and reapproval and to appeals of adverse decisions. These provisions are intended to improve States' MMIS, and to ensure efficient system operations, and to detect cases of fraud, waste, and abuse effectively.

  6. Overcoming Bcr-Abl T315I mutation by combination of GNF-2 and ATP competitors in an Abl-independent mechanism

    International Nuclear Information System (INIS)

    Khateb, Mamduh; Ruimi, Nili; Khamisie, Hazem; Najajreh, Yousef; Mian, Afsar; Metodieva, Anna; Ruthardt, Martin; Mahajna, Jamal

    2012-01-01

    Philadelphia positive leukemias are characterized by the presence of Bcr-Abl fusion protein which exhibits an abnormal kinase activity. Selective Abl kinase inhibitors have been successfully established for the treatment of Ph (+) leukemias. Despite high rates of clinical response, Ph (+) patients can develop resistance against these kinase inhibitors mainly due to point mutations within the Abl protein. Of special interest is the ‘gatekeeper’ T315I mutation, which confers complete resistance to Abl kinase inhibitors. Recently, GNF-2, Abl allosteric kinase inhibitor, was demonstrated to possess cellular activity against Bcr-Abl transformed cells. Similarly to Abl kinase inhibitors (AKIs), GNF-2 failed to inhibit activity of mutated Bcr-Abl carrying the T315I mutation. Ba/F3 cells harboring native or T315I mutated Bcr-Abl constructs were treated with GNF-2 and AKIs. We monitored the effect of GNF-2 with AKIs on the proliferation and clonigenicity of the different Ba/F3 cells. In addition, we monitored the auto-phosphorylation activity of Bcr-Abl and JAK2 in cells treated with GNF-2 and AKIs. In this study, we report a cooperation between AKIs and GNF-2 in inhibiting proliferation and clonigenicity of Ba/F3 cells carrying T315I mutated Bcr-Abl. Interestingly, cooperation was most evident between Dasatinib and GNF-2. Furthermore, we showed that GNF-2 was moderately active in inhibiting the activity of JAK2 kinase, and presence of AKIs augmented GNF-2 activity. Our data illustrated the ability of allosteric inhibitors such as GNF-2 to cooperate with AKIs to overcome T315I mutation by Bcr-Abl-independent mechanisms, providing a possibility of enhancing AKIs efficacy and overcoming resistance in Ph+ leukemia cells

  7. 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.

  8. Modeling of molecular interaction between apoptin, BCR-Abl and CrkL--an alternative approach to conventional rational drug design.

    Directory of Open Access Journals (Sweden)

    Soumya Panigrahi

    Full Text Available In this study we have calculated a 3D structure of apoptin and through modeling and docking approaches, we show its interaction with Bcr-Abl oncoprotein and its downstream signaling components, following which we confirm some of the newly-found interactions by biochemical methods. Bcr-Abl oncoprotein is aberrantly expressed in chronic myelogenous leukaemia (CML. It has several distinct functional domains in addition to the Abl kinase domain. The SH3 and SH2 domains cooperatively play important roles in autoinhibiting its kinase activity. Adapter molecules such as Grb2 and CrkL interact with proline-rich region and activate multiple Bcr-Abl downstream signaling pathways that contribute to growth and survival. Therefore, the oncogenic effect of Bcr-Abl could be inhibited by the interaction of small molecules with these domains. Apoptin is a viral protein with well-documented cancer-selective cytotoxicity. Apoptin attributes such as SH2-like sequence similarity with CrkL SH2 domain, unique SH3 domain binding sequence, presence of proline-rich segments, and its nuclear affinity render the molecule capable of interaction with Bcr-Abl. Despite almost two decades of research, the mode of apoptin's action remains elusive because 3D structure of apoptin is unavailable. We performed in silico three-dimensional modeling of apoptin, molecular docking experiments between apoptin model and the known structure of Bcr-Abl, and the 3D structures of SH2 domains of CrkL and Bcr-Abl. We also biochemically validated some of the interactions that were first predicted in silico. This structure-property relationship of apoptin may help in unlocking its cancer-selective toxic properties. Moreover, such models will guide us in developing of a new class of potent apoptin-like molecules with greater selectivity and potency.

  9. 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.

  10. Coupling between p210bcr-abl and Shc and Grb2 adaptor proteins in hematopoietic cells permits growth factor receptor-independent link to ras activation pathway.

    Science.gov (United States)

    Tauchi, T; Boswell, H S; Leibowitz, D; Broxmeyer, H E

    1994-01-01

    Enforced expression of p210bcr-abl transforms interleukin 3 (IL-3)-dependent hematopoietic cell lines to growth factor-independent proliferation. It has been demonstrated that nonreceptor tyrosine kinase oncogenes may couple to the p21ras pathway to exert their transforming effect. In particular, p210bcr-abl was recently found to effect p21ras activation in hematopoietic cells. In this context, experiments were performed to evaluate a protein signaling pathway by which p210bcr-abl might regulate p21ras. It was asked whether Shc p46/p52, a protein containing a src-homology region 2 (SH2) domain, and known to function upstream from p21ras, might form specific complexes with p210bcr-abl and thus, possibly alter p21ras activity by coupling to the guanine nucleotide exchange factor (Sos/CDC25) through the Grb2 protein-Sos complex. This latter complex has been previously demonstrated to occur ubiquitously. We found that p210bcr-abl formed a specific complex with Shc and with Grb2 in three different murine cell lines transfected with a p210bcr-abl expression vector. There appeared to be a higher order complex containing Shc, Grb2, and bcr-abl proteins. In contrast to p210bcr-abl transformed cells, in which there was constitutive tight association between Grb2 and Shc, binding between Grb2 and Shc was Steel factor (SLF)-dependent in a SLF-responsive, nontransformed parental cell line. The SLF-dependent association between Grb2 and Shc in nontransformed cells involved formation of a complex of Grb2 with c-kit receptor after SLF treatment. Thus, p210bcr-abl appears to function in a hematopoietic p21ras activation pathway to allow growth factor-independent coupling between Grb2, which exists in a complex with the guanine nucleotide exchange factor (Sos), and p21ras. Shc may not be required for Grb2-c-kit interaction, because it fails to bind strongly to c-kit.

  11. 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.

  12. Activity of the novel BCR kinase inhibitor IQS019 in preclinical models of B-cell non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    P. Balsas

    2017-03-01

    Full Text Available Abstract Background Pharmacological inhibition of B cell receptor (BCR signaling has recently emerged as an effective approach in a wide range of B lymphoid neoplasms. However, despite promising clinical activity of the first Bruton’s kinase (Btk and spleen tyrosine kinase (Syk inhibitors, a small fraction of patients tend to develop progressive disease after initial response to these agents. Methods We evaluated the antitumor activity of IQS019, a new BCR kinase inhibitor with increased affinity for Btk, Syk, and Lck/Yes novel tyrosine kinase (Lyn, in a set of 34 B lymphoid cell lines and primary cultures, including samples with acquired resistance to the first-in-class Btk inhibitor ibrutinib. Safety and efficacy of the compound were then evaluated in two xenograft mouse models of B cell lymphoma. Results IQS019 simultaneously engaged a rapid and dose-dependent de-phosphorylation of both constitutive and IgM-activated Syk, Lyn, and Btk, leading to impaired cell proliferation, reduced CXCL12-dependent cell migration, and induction of caspase-dependent apoptosis. Accordingly, B cell lymphoma-bearing mice receiving IQS019 presented a reduced tumor outgrowth characterized by a decreased mitotic index and a lower infiltration of malignant cells in the spleen, in tight correlation with downregulation of phospho-Syk, phospho-Lyn, and phospho-Btk. More interestingly, IQS019 showed improved efficacy in vitro and in vivo when compared to the first-in-class Btk inhibitor ibrutinib, and was active in cells with acquired resistance to this latest. Conclusions These results define IQS019 as a potential drug candidate for a variety of B lymphoid neoplasms, including cases with acquired resistance to current BCR-targeting therapies.

  13. The Prevalence of JAK2, MPL, and CALR Mutations in Chinese Patients With BCR-ABL1-Negative Myeloproliferative Neoplasms.

    Science.gov (United States)

    Lin, Yani; Liu, Enbin; Sun, Qi; Ma, Jiao; Li, QingHua; Cao, Zeng; Wang, Jun; Jia, Yujiao; Zhang, Hongju; Song, Zhen; Ai, Xiaofei; Shi, Lihui; Feng, Xiaofang; Li, Chenwei; Wang, Jianxiang; Ru, Kun

    2015-07-01

    To evaluate the mutation frequency of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 and the value of the combined tests in the diagnosis of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). In the current study, mutations of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 were analyzed in 929 Chinese patients with BCR-ABL1-negative MPN, including 234 cases of polycythemia vera (PV), 428 ETs, 187 PMFs, and 80 unclassifiable MPNs (MPN-Us). Our result showed that the positive rate of any of four mutations in patients with PV, ET, PMF, and MPN-U was 89.3%, 83.4%, 87.2%, and 77.5%, respectively, which significantly improved the diagnostic rate, especially in ET and PMF. Meanwhile, we also found that the patients without any of four mutations were younger than those with one or more mutations. Unexpectedly, the coexistence of JAK2 V617F and CALR exon 9 was identified in six (0.6%) patients, and JAK2 V617F and MPL exon 10 were present simultaneously in two (0.2%) patients. In addition, we also identified several novel mutation types in CALR exon 9. The combined genetic tests of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 help improve the diagnostic rate for BCR-ABL1-negative MPN. Copyright© by the American Society for Clinical Pathology.

  14. Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains.

    Science.gov (United States)

    Sha, Fern; Gencer, Emel Basak; Georgeon, Sandrine; Koide, Akiko; Yasui, Norihisa; Koide, Shohei; Hantschel, Oliver

    2013-09-10

    The dysregulated tyrosine kinase BCR-ABL causes chronic myelogenous leukemia in humans and forms a large multiprotein complex that includes the Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2). The expression of SHP2 is necessary for BCR-ABL-dependent oncogenic transformation, but the precise signaling mechanisms of SHP2 are not well understood. We have developed binding proteins, termed monobodies, for the N- and C-terminal SH2 domains of SHP2. Intracellular expression followed by interactome analysis showed that the monobodies are essentially monospecific to SHP2. Two crystal structures revealed that the monobodies occupy the phosphopeptide-binding sites of the SH2 domains and thus can serve as competitors of SH2-phosphotyrosine interactions. Surprisingly, the segments of both monobodies that bind to the peptide-binding grooves run in the opposite direction to that of canonical phosphotyrosine peptides, which may contribute to their exquisite specificity. When expressed in cells, monobodies targeting the N-SH2 domain disrupted the interaction of SHP2 with its upstream activator, the Grb2-associated binder 2 adaptor protein, suggesting decoupling of SHP2 from the BCR-ABL protein complex. Inhibition of either N-SH2 or C-SH2 was sufficient to inhibit two tyrosine phosphorylation events that are critical for SHP2 catalytic activity and to block ERK activation. In contrast, targeting the N-SH2 or C-SH2 revealed distinct roles of the two SH2 domains in downstream signaling, such as the phosphorylation of paxillin and signal transducer and activator of transcription 5. Our results delineate a hierarchy of function for the SH2 domains of SHP2 and validate monobodies as potent and specific antagonists of protein-protein interactions in cancer cells.

  15. 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...

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

    Science.gov (United States)

    2010-05-01

    imatinib resistance with a novel ABL kinase inhibitor. Science. 2004; 305(5682):399-401 3. Weisberg E, Manley PW, Breitenstein W, Bruggen J, Cowan-Jacob... Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD. Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant chronic myeloid...araldehyde (5) (10 mmol), glacial acetic acid (5 mL), and a catalytic amount (100 lL ) of benzyl amine was re- fluxed for 5–8 h. After completion of

  17. Emergency procedures

    International Nuclear Information System (INIS)

    Abd Nasir Ibrahim; Azali Muhammad; Ab Razak Hamzah; Abd Aziz Mohamed; Mohammad Pauzi Ismail

    2004-01-01

    The following subjects are discussed - Emergency Procedures: emergency equipment, emergency procedures; emergency procedure involving X-Ray equipment; emergency procedure involving radioactive sources

  18. The certification of the surface density (kg/m sub 2 ) of BCR CRM 038 ('fly ash from pulverised coal') comprised in methyl cellulose films simulating dust charged filters. BCR 128

    Energy Technology Data Exchange (ETDEWEB)

    Griepink, B; Marchandise, H; Colinet, E; Dams, R

    1988-01-01

    BCR CRM 38 ('Fly Ash') has been embedded in a stable methylcellulose foil of about 10{mu}m thickness. This has been done by making a slurry of fly ash and methylcellulose in water and spiking it with {sup 42}K as a radioactive tracer. The slurry was spread over glass plates and allowed to dry. 'Filters' of uniform size were punched out of the foil. The surface density (e.g. {mu}g/cm{sup 2}) of the fly ash was calculated for each individual 'filter' by comparing the {sup 42}K-activity of the filter with that of the initial suspension. The uncertainties in the so obtained surface density of random and of systematic origin have been estimated. The total relative uncertainty in the surface density of every element certified in BCR 38 is 4-6%. Studies of stability and homogeneity have revealed that this material is well suited for the verification of the results of non-destructive analytical techniques for dust components.

  19. 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.

  20. 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.

  1. 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

  2. Comparative study of different methodologies to detect the JAK2 V617F mutation in chronic BCR-ABL1 negative myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Alline Didone

    2016-04-01

    Full Text Available Objectives: A mutation in the JAK2 gene, V617F, has been identified in several BCR-ABL1 negative myeloproliferative neoplasms (MPN: polycythemia vera (PV, essential thrombocythemia (ET, and primary myelofibrosis (PMF. Defining the presence or absence of this mutation is an essential part of clinical diagnostic algorithms and patient management. Here, we aimed to evaluate the performance of three PCR-based assays: Amplification Refractory Mutation System (ARMS, High-Resolution Melting analysis (HRM, and Sanger direct sequencing, and compare their results with those obtained by a PCR restriction fragment polymorphism assay (PCR-RFLP. Design and methods: We used blood samples from 136 patients (PV=20; PMF=20; ET=28, and other MPN suspected cases=68. Results: Comparable results were observed among the four assays in patients with PV, PMF, and MPN suspected cases. In patients with a diagnosis of ET, the JAK2 V617F mutation was detected in 67.8% of them by the PCR-ARMS and PCR-HRM assay and in 64% of them by the conventional Sanger sequence approach. The PCR-ARMS and PCR-HRM assays were 100% concordant. With these tests, only one of the 20 patients with ET and one of the three patients with clinically suspected MPN gave different results compared with those obtained by the PCR-RFLP. Conclusions: Our results have demonstrated that the PCR-ARMS and PCR-HRM assays could detect the JAK2 V617F mutation effectively in MPN patients, but PCR-HRM assays are rapid and the most cost-effective procedures. Keywords: Myeloproliferative, JAK2 V617F, Mutation, Wild type, Screening

  3. BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Falchi, Lorenzo; Baron, Jessica M.; Orlikowski, Carrie Anne; Ferrajoli, Alessandra

    2016-01-01

    The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology and clinical experience with the use of BCR signaling inhibitors for the treatment of patients with CLL. We next focus on both the most common and the most clinically significant toxicities associated with these drugs. PMID:26977270

  4. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance

    Science.gov (United States)

    Azam, Mohammad; Nardi, Valentina; Shakespeare, William C.; Metcalf, Chester A.; Bohacek, Regine S.; Wang, Yihan; Sundaramoorthi, Raji; Sliz, Piotr; Veach, Darren R.; Bornmann, William G.; Clarkson, Bayard; Dalgarno, David C.; Sawyer, Tomi K.; Daley, George Q.

    2006-01-01

    Mutation in the ABL kinase domain is the principal mechanism of imatinib resistance in patients with chronic myelogenous leukemia. Many mutations favor active kinase conformations that preclude imatinib binding. Because the active forms of ABL and SRC resemble one another, we tested two dual SRC-ABL kinase inhibitors, AP23464 and PD166326, against 58 imatinib-resistant (IMR) BCR/ABL kinase variants. Both compounds potently inhibit most IMR variants, and in vitro drug selection demonstrates that active (AP23464) and open (PD166326) conformation-specific compounds are less susceptible to resistance than imatinib. Combinations of inhibitors suppressed essentially all resistance mutations, with the notable exception of T315I. Guided by mutagenesis studies and molecular modeling, we designed a series of AP23464 analogues to target T315I. The analogue AP23846 inhibited both native and T315I variants of BCR/ABL with submicromolar potency but showed nonspecific cellular toxicity. Our data illustrate how conformational dynamics of the ABL kinase accounts for the activity of dual SRC-ABL inhibitors against IMR-mutants and provides a rationale for combining conformation specific inhibitors to suppress resistance. PMID:16754879

  5. 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.

  6. Reduction Corporoplasty

    Directory of Open Access Journals (Sweden)

    Tariq S. Hakky

    2015-04-01

    Full Text Available Objective Here we present the first video demonstration of reduction corporoplasty in the management of phallic disfigurement in a 17 year old man with a history sickle cell disease and priapism. Introduction Surgical management of aneurysmal dilation of the corpora has yet to be defined in the literature. Materials and Methods: We preformed bilateral elliptical incisions over the lateral corpora as management of aneurysmal dilation of the corpora to correct phallic disfigurement. Results The patient tolerated the procedure well and has resolution of his corporal disfigurement. Conclusions Reduction corporoplasty using bilateral lateral elliptical incisions in the management of aneurysmal dilation of the corpora is a safe an feasible operation in the management of phallic disfigurement.

  7. 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)

  8. Evolution of BCR/ABL gene mutation in CML is time dependent and dependent on the pressure exerted by tyrosine kinase inhibitor.

    Directory of Open Access Journals (Sweden)

    Shantashri Vaidya

    Full Text Available BACKGROUND: Mutations in the ABL kinase domain and SH3-SH2 domain of the BCR/ABL gene and amplification of the Philadelphia chromosome are the two important BCR/ABL dependent mechanisms of imatinib resistance. Here, we intended to study the role played by TKI, imatinib, in selection of gene mutations and development of chromosomal abnormalities in Indian CML patients. METHODS: Direct sequencing methodology was employed to detect mutations and conventional cytogenetics was done to identify Philadelphia duplication. RESULTS: Among the different mechanisms of imatinib resistance, kinase domain mutations (39% of the BCR/ABL gene were seen to be more prevalent, followed by mutations in the SH3-SH2 domain (4% and then BCR/ABL amplification with the least frequency (1%. The median duration of occurrence of mutation was significantly shorter for patients with front line imatinib than those pre-treated with hydroxyurea. Patients with high Sokal score (p = 0.003 showed significantly higher incidence of mutations, as compared to patients with low/intermediate score. Impact of mutations on the clinical outcome in AP and BC was observed to be insignificant. Of the 94 imatinib resistant patients, only 1 patient exhibited duplication of Philadelphia chromosome, suggesting a less frequent occurrence of this abnormality in Indian CML patients. CONCLUSION: Close monitoring at regular intervals and proper analysis of the disease resistance would facilitate early detection of resistance and thus aid in the selection of the most appropriate therapy.

  9. 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.

  10. 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

  11. 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

    Science.gov (United States)

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

    2013-10-01

    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.

  12. Successful treatment with allogeneic stem cell transplantation followed by DLI and TKIs for e6a2 BCR-ABL-positive acute myeloid leukaemia

    Science.gov (United States)

    Harada, Yasuhiko; Nishiwaki, Satoshi; Sugimoto, Takumi; Onodera, Koichi; Goto, Tatsunori; Sato, Takahiko; Kamoshita, Sonoko; Kawashima, Naomi; Seto, Aika; Okuno, Shingo; Yamamoto, Satomi; Iwasaki, Toshihiro; Ozawa, Yukiyasu; Miyamura, Koichi; Akatsuka, Yoshiki; Sugiura, Isamu

    2017-01-01

    Abstract Rationale: Patients with the e6a2 BCR-ABL transcript, 1 of the atypical transcripts, have been reported to have a poor prognosis, and allogeneic stem cell transplantation (ASCT) can be considered as additional therapy. However, long-term survival after ASCT for this disease is rare. Patient concerns: This report concerns a 55-year-old female patient with e6a2 BCR-ABL-positive acute myeloid leukemia including the outcome of ASCT followed by donor lymphocyte infusion (DLI). Diagnoses: The breakpoint was confirmed by direct sequencing. Her minimal residual disease could be detected by nested reverse-transcription polymerase chain reaction using primers for the minor BCR-ABL (e1a2) transcript. Interventions: Treatment with tyrosine kinase inhibitors (TKIs) and ASCT followed by DLI. Outcomes: Despite multiple cytogenetic and molecular relapses after ASCT, she remains in molecular remission at 46 months after ASCT. Lessons: This case indicates the efficacy of the combination of the graft-versus-leukemia effect and TKIs for e6a2 BCR-ABL-positive acute leukemia. When the Philadelphia chromosome with an unusual chromosomal breakpoint is suggested, we should clarify the breakpoint because that information can aid molecular assessments and decisions to provide an additional or alternative therapy. PMID:29390324

  13. 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

  14. Does mitigation save? Reviewing cost-benefit analyses of disaster risk reduction

    OpenAIRE

    Shreve, Cheney M.; Kelman, Ilan

    2014-01-01

    The benefit-cost-ratio (BCR), used in cost-benefit analysis (CBA), is an indicator that attempts to summarize the overall value for money of a project. Disaster costs continue to rise and the demand has increased to demonstrate the economic benefit of disaster risk reduction (DRR) to policy makers. This study compiles and compares original CBA case studies reporting DRR BCRs, without restrictions as to hazard type, location, scale, or other parameters. Many results were identified supporting ...

  15. 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

  16. Participation in BCR - certifications by the Laboratory of Analytical Chemistry, Institute for Nuclear Sciences, University of Gent, Belgium

    International Nuclear Information System (INIS)

    Cornelis, R.; Dyg, S.; Dams, R.; Griepink, B.

    1990-01-01

    During the last decade the Laboratory of Analytical Chemistry assisted in the certification of 31 environmental and food reference materials issued by the BCR (Bureau of Reference Materials of the European Communities). The efforts spent can be translated into the following statistics: the 10 most frequently certified elements assisted by the Gent Laboratory are As, Cd, Co, Cu, Fe, Hg, Mn, Pb, Se and Zn. They cover 70% of the certification work. The Gent Laboratory cooperated in 74% of the latter. There are 21 more major and trace elements certified, some in a single product only. Activation analysis was the main analytical technique applied by the Gent Laboratory. In many instances radiochemical separations were involved. (orig.)

  17. Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells.

    Science.gov (United States)

    Li, Qianyin; Huang, Zhenglan; Gao, Miao; Cao, Weixi; Xiao, Qin; Luo, Hongwei; Feng, Wenli

    2017-03-02

    The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag), HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag) and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 5 (STAT5) pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells) apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI)-resistance.

  18. 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

  19. Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Qianyin Li

    2017-03-01

    Full Text Available The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML. The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag, HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK and signal transducer and activator of transcription 5 (STAT5 pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI-resistance.

  20. The certification of carbon and nitrogen in molybdenum (BCR No.23)

    International Nuclear Information System (INIS)

    Vandecasteele, C.

    1985-01-01

    The experimental procedures used for the certification of carbon and nitrogen in molybdenum (CRM 023), which has already been certified for oxygen, are presented. Samples were analysed by 5 different laboratories using photon and charged particle activation analysis. The analytical methods and the approach used to analyse the data are described. The carbon content is certified to be below 0.2 μg/g; the nitrogen content to be below 0.3 μg/g

  1. The certification of boron in primary ingot aluminium. BCR No.25

    International Nuclear Information System (INIS)

    Vandecasteele, C.; Colinet, E.

    1984-01-01

    This report sets out the experimental procedures used for the certification of boron in primary ingot aluminium, which has already been certified for carbon and oxygen. Samples were analysed by seven different laboratories using the following methods: spectrophotometry, ICP-emission spectrometry, isotope dilution mass spectrometry, spark source mass spectrometry and charged particle activation analysis. The analytical methods and the statistical approach to analyse the data are described

  2. Genetic polymorphisms of hemostatic factors and thrombotic risk in non BCR-ABL myeloproliferative neoplasms: A pilot study

    Directory of Open Access Journals (Sweden)

    Dambrauskienė R

    2017-06-01

    Full Text Available The most important complications of Philadelphianegagive (non BCR-ABL myeloproliferative neoplasms (MPNs are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs, platelet glycoproteins (GPs (Ia/IIa, Ibα, IIb/IIIa and VI, von Willebrand factor (vWF, coagulation factor VII (FVII, β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c.807C>T polymorphism was more frequently found in the group of MPN patients with arterial thrombosis compared to MPN patients who were thrombosis-free [26.5 vs. 11.5%, p = 0.049; odds ratio (OR 2.68; 95% confidence interval (95% CI 1.01-7.38]. The CT genotype of the β-fibrinogen c.-148C>T polymorphism occurred more frequently in MPN patients with arterial, and total thrombosis compared to the wild or homozygous genotype (57.7 vs. 40.0 vs. 12.5%; p = 0.027, (64.7 vs. 44.4 vs. 25%; p = 0.032, respectively. The carrier state for the c.-323P10 variant of FVII SNP (summation of P10/10 and P0/10 was more frequent in MPN patients with thrombosis compared to the wild-type genotype carriers (71.4 vs. 43.4%; p = 0.049; OR 3.26; 95% CI 1.01-11.31. The coexistence of heterozygous β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP, increased the risk of arterial thrombosis (21.1 vs. 3.7%, p = 0.008; OR 6.93; 95% CI 1.38-34.80. The TT genotype of GP Ia/IIa c.807C>T, the CT genotype of β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP could be associated with risk of thrombosis in MPN patients.

  3. Concomitant BCR-ABL1 positive chronic myelogenous leukemia emerging in a patient with MPL W515L associated primary myelofibrosis

    Directory of Open Access Journals (Sweden)

    Juan C. Gomez-Gelvez, MD

    2016-03-01

    Full Text Available Myeloproliferative neoplasms (MPNs are clonal hematopoietic stem cell disorders characterized by proliferation of one or more cell lineages in the bone marrow. At present, the main criterion in the 2008 World Health Organization classification of MPNs is the presence of an underlying genetic abnormality. These mutations are generally mutually exclusive except for rare reports in the literature. We report for the first time a detailed analysis of the clinical, histologic and cytogenetic/molecular features of a patient who initially presented with MPL W515L positive primary myelofibrosis and over the course of five years developed an MPN associated with both BCR-ABL1 and MPL W515L mutation. We discuss the diagnostic challenges and therapeutic implications of concomitant BCR-ABL1 translocation with MPL W515L mutation. Multiple genetic alterations may simultaneously coexist in patients exhibiting features of myeloproliferative disorders.

  4. 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.

  5. 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.

  6. The chimeric ubiquitin ligase SH2-U-box inhibits the growth of imatinib-sensitive and resistant CML by targeting the native and T315I-mutant BCR-ABL.

    Science.gov (United States)

    Ru, Yi; Wang, Qinhao; Liu, Xiping; Zhang, Mei; Zhong, Daixing; Ye, Mingxiang; Li, Yuanchun; Han, Hua; Yao, Libo; Li, Xia

    2016-06-22

    Chronic myeloid leukemia (CML) is characterized by constitutively active fusion protein tyrosine kinase BCR-ABL. Although the tyrosine kinase inhibitor (TKI) against BCR-ABL, imatinib, is the first-line therapy for CML, acquired resistance almost inevitably emerges. The underlying mechanism are point mutations within the BCR-ABL gene, among which T315I is notorious because it resists to almost all currently available inhibitors. Here we took use of a previously generated chimeric ubiquitin ligase, SH2-U-box, in which SH2 from the adaptor protein Grb2 acts as a binding domain for activated BCR-ABL, while U-box from CHIP functions as an E3 ubiquitin ligase domain, so as to target the ubiquitination and degradation of both native and T315I-mutant BCR-ABL. As such, SH2-U-box significantly inhibited proliferation and induced apoptosis in CML cells harboring either the wild-type or T315I-mutant BCR-ABL (K562 or K562R), with BCR-ABL-dependent signaling pathways being repressed. Moreover, SH2-U-box worked in concert with imatinib in K562 cells. Importantly, SH2-U-box-carrying lentivirus could markedly suppress the growth of K562-xenografts in nude mice or K562R-xenografts in SCID mice, as well as that of primary CML cells. Collectively, by degrading the native and T315I-mutant BCR-ABL, the chimeric ubiquitin ligase SH2-U-box may serve as a potential therapy for both imatinib-sensitive and resistant CML.

  7. 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)

  8. 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.

  9. 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.

  10. β-Catenin is required for intrinsic but not extrinsic BCR-ABL1 kinase-independent resistance to tyrosine kinase inhibitors in chronic myeloid leukemia.

    Science.gov (United States)

    Eiring, A M; Khorashad, J S; Anderson, D J; Yu, F; Redwine, H M; Mason, C C; Reynolds, K R; Clair, P M; Gantz, K C; Zhang, T Y; Pomicter, A D; Kraft, I L; Bowler, A D; Johnson, K; Partlin, M Mac; O'Hare, T; Deininger, M W

    2015-12-01

    Activation of nuclear β-catenin and expression of its transcriptional targets promotes chronic myeloid leukemia (CML) progression, tyrosine kinase inhibitor (TKI) resistance, and leukemic stem cell self-renewal. We report that nuclear β-catenin has a role in leukemia cell-intrinsic but not -extrinsic BCR-ABL1 kinase-independent TKI resistance. Upon imatinib inhibition of BCR-ABL1 kinase activity, β-catenin expression was maintained in intrinsically resistant cells grown in suspension culture and sensitive cells cultured in direct contact (DC) with bone marrow (BM) stromal cells. Thus, TKI resistance uncouples β-catenin expression from BCR-ABL1 kinase activity. In β-catenin reporter assays, intrinsically resistant cells showed increased transcriptional activity versus parental TKI-sensitive controls, and this was associated with restored expression of β-catenin target genes. In contrast, DC with BM stromal cells promoted TKI resistance, but had little effects on Lef/Tcf reporter activity and no consistent effects on cytoplasmic β-catenin levels, arguing against a role for β-catenin in extrinsic TKI resistance. N-cadherin or H-cadherin blocking antibodies abrogated DC-based resistance despite increasing Lef/Tcf reporter activity, suggesting that factors other than β-catenin contribute to extrinsic, BM-derived TKI resistance. Our data indicate that, while nuclear β-catenin enhances survival of intrinsically TKI-resistant CML progenitors, it is not required for extrinsic resistance mediated by the BM microenvironment.

  11. 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.

  12. BCR-crosslinking induces a transcription of protein phosphatase component G5PR that is required for mature B-cell survival

    International Nuclear Information System (INIS)

    Huq Ronny, Faisal Mahmudul; Igarashi, Hideya; Sakaguchi, Nobuo

    2006-01-01

    BCR-crosslinking triggers activation-induced cell death (AICD) selectively in the restricted stage of B-cell differentiation. We examined the transcription of a protein phosphatase subunit G5PR in immature and mature B-cells, because absence of this factor augmented cell sensitivity to AICD, associated with increased activation of JNK and Bim. BCR-crosslinking-induced G5pr transcription in AICD-resistant mature splenic IgM lo IgD hi B-cells but not in AICD susceptible immature IgM hi IgD lo B-cells. Thus, G5pr induction correlated with the prevention of AICD; High in mature splenic CD23 hi B-cells but low in immature B-cells of neonatal mice, sub-lethally irradiated mice, or xid mice. Lack of G5pr upregulation was associated with the prolonged activation of JNK. The G5pr cDNA transfection protected an immature B-cell line WEHI-231 from BCR-mediated AICD. The differential expression of G5PR might be responsible for the antigen-dependent selection of B-cells

  13. Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort.

    Science.gov (United States)

    Kander, Elizabeth M; Raza, Sania; Zhou, Zheng; Gao, Juehua; Zakarija, Anaadriana; McMahon, Brandon J; Stein, Brady L

    2015-11-01

    The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group. Our aim was to retrospectively evaluate whether acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or treatment history are associated with bleeding in a cohort of MPN patients. Using an electronic database, MPN patients seen between 2005 and 2013 were retrospectively identified using ICD-9 codes and billing records. A bleeding event was defined as one that was identified in the medical record and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0. Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no association of bleeding with mutational status, gender, MPN subtype, aspirin use, prior thrombosis, or platelet count at presentation. There was an association between bleeding and older age at diagnosis. aVWD was identified in six patients. In this single-center retrospective study, bleeding events were identified in 15 % of patients, and associated with older age at diagnosis. aVWD was rarely tested for in this cohort.

  14. Frequency of janus associated kinase 2 (jak2) mutation in patients of bcr-abl negative myeloproliferative neoplasms

    International Nuclear Information System (INIS)

    Sadiq, M.A.; Ahmed, S.; Ali, N.

    2013-01-01

    To determine the frequency of Janus associated kinase 2 mutation in the patients of BCR-ABL negative classical myeloproliferative neoplasms. Study Design: Cross-sectional descriptive study Place and Duration of Study: Molecular Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jul 2011 to Jul 2012. Patients and Methods: Ninety three consecutive patients of Polycythaemia vera (PV), Essential thrombocythaemia (ET) and Idiopathic myelofibrosis (IMF) diagnosed by the conventional haematological criteria were included in the study. All patients were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: Out of the 93 myeloproliferative neoplasm (MPN) patients, 33(35%) had polycythaemia vera, 36(39%) had essential thrombocythaemia and 24(26%) had idiopathic myelofibrosis. JAK2 mutation was seen in 64/93 (69%) patients including 33/33(100%) in PV, 19/36(52.6%) in ET and 12/24(50%) in IMF. Conclusion: Classical myeloproliferative neoplasms are an important group of heamatological disorder in our country. JAK2 gene mutation is seen in significant proportion of these disorders (69%). JAK2 mutation analysis can be used to differentiate between polycythemia vera and secondary polycythemia in most cases with near certainty, where it was found in 100% of the cases. (author)

  15. [JAK2 V617F and exon 12 genetic variations in Korean patients with BCR/ABL1-negative myeloproliferative neoplasms].

    Science.gov (United States)

    Kim, Jeong Tae; Cho, Yong Gon; Choi, Sam Im; Lee, Young Jin; Kim, Hye Ran; Jang, Sook Jin; Moon, Dae Soo; Park, Young Jin; Park, Geon

    2010-12-01

    JAK2 genetic variations have been described in a high proportion of patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). This study was designed to analyze the frequencies of JAK2 V617F and exon 12 variations, and their correlations with clinical characteristics of Korean patients with BCR/ABL1-negative MPN. We examined a total of 154 patients with BCR/ABL1-negative MPN that included 24, 26, 89, and 15 patients with polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), and unclassified myeloproliferative neoplasms (MPNU), respectively. We performed allele-specific PCR to detect V617F in all BCR/ABL1-negative patients, and performed direct sequencing to detect exon 12 variations in 47 V617F-negative MPN patients. JAK2 c.1641+179_183del5 variation was detected by restriction fragment length polymorphism assay in 176 healthy subjects. JAK2 V617F was detected in 91 patients (59.1%): PV (91.6%), PMF (46.2%), ET (52.8%), and MPNU (66.7%). In V617F-negative MPN patients, no mutations were found in exon 12. The c.1641+179_183del5 was detected in 68.1% of V617F-negative MPN patients and 45.4% of healthy subjects (P=0.008). JAK2 V617F was closely correlated with age and leukocytosis in BCR/ABL1-negative MPN patients (P<0.05). However, c.1641+179_183del5 was not related to age, sex, or complete blood cell count parameters in V617F-negative MPN patients and healthy subjects. The c.1641+179_183del5 was associated with an increased odds ratio for MPN (odds ratio, 2.6; 95% confidences interval, 1.3-5.1; P=0.007). Frequencies of V617F are similar to reported results. JAK2 exon 12 mutations may be rare and c.1641+179_183del5 may influence the occurrence of MPN in Korean patients with V6 17F-negative MPN.

  16. Quantization Procedures

    International Nuclear Information System (INIS)

    Cabrera, J. A.; Martin, R.

    1976-01-01

    We present in this work a review of the conventional quantization procedure, the proposed by I.E. Segal and a new quantization procedure similar to this one for use in non linear problems. We apply this quantization procedures to different potentials and we obtain the appropriate equations of motion. It is shown that for the linear case the three procedures exposed are equivalent but for the non linear cases we obtain different equations of motion and different energy spectra. (Author) 16 refs

  17. Restoring penis sensation in patients with low spinal cord lesions: the role of the remaining function of the dorsal nerve in a unilateral or bilateral TOMAX procedure.

    Science.gov (United States)

    Overgoor, Max L E; Braakhekke, Jan P; Kon, Moshe; De Jong, Tom P V M

    2015-04-01

    The recently developed TOMAX-procedure restores unilateral genital sensation, improving sexual health in men with a low spinal lesion (LSL). It connects one dorsal nerve of the penis (DNP) to the intact ipsilateral ilioinguinal nerve. We proposed bilateral neurotization for full sensation of the glans but this entails cutting both DNPs, risking patients' erection/ejaculation ability. The objective was to select patients for a bilateral TOMAX-procedure by measuring remaining DNP function, and perform the first bilateral cases. In 30 LSL patients with no penile- but normal groin sensation selected for a unilateral TOMAX-procedure the integrity of the sacral-reflex-arc and DNP function was tested pre-operatively using bilateral needle electromyography (EMG)-bulbocavernosus reflex (BCR) measurements, and an interview about reflex erections (RE) ability. In 13 spina bifida- and 17 spinal cord injury patients [median age 29.5 years (range 13-59 years), spinal lesion T12 (incomplete) to sacral], seven (23%) patients reported RE, four (57%) with intact BCR, and of nine (30%) patients with intact BCR, four reported RE (44%). Even patients with a LSL and no penile sensation can have signs of remaining DNP function, but cutting both DNPs to restore full glans sensation in a bilateral TOMAX-procedure might interfere with their RE/ejaculation. To avoid this risk, we propose a selecting-protocol for a unilateral- or bilateral procedure using RE and BCR measurements. Using this protocol, three patients were bilaterally operated with promising preliminary results. Full sensation of the glans could lead to further improvement in sexual function. © 2014 Wiley Periodicals, Inc.

  18. High frequency dielectric reference materials BCR projekt 43. Final report of phase 1

    International Nuclear Information System (INIS)

    Chantry, G.

    1980-01-01

    measurement procedures

  19. A longitudinal evaluation of performance of automated BCR-ABL1 quantitation using cartridge-based detection system.

    Science.gov (United States)

    Enjeti, Anoop; Granter, Neil; Ashraf, Asma; Fletcher, Linda; Branford, Susan; Rowlings, Philip; Dooley, Susan

    2015-10-01

    An automated cartridge-based detection system (GeneXpert; Cepheid) is being widely adopted in low throughput laboratories for monitoring BCR-ABL1 transcript in chronic myelogenous leukaemia. This Australian study evaluated the longitudinal performance specific characteristics of the automated system.The automated cartridge-based system was compared prospectively with the manual qRT-PCR-based reference method at SA Pathology, Adelaide, over a period of 2.5 years. A conversion factor determination was followed by four re-validations. Peripheral blood samples (n = 129) with international scale (IS) values within detectable range were selected for assessment. The mean bias, proportion of results within specified fold difference (2-, 3- and 5-fold), the concordance rate of major molecular remission (MMR) and concordance across a range of IS values on paired samples were evaluated.The initial conversion factor for the automated system was determined as 0.43. Except for the second re-validation, where a negative bias of 1.9-fold was detected, all other biases fell within desirable limits. A cartridge-specific conversion factor and efficiency value was introduced and the conversion factor was confirmed to be stable in subsequent re-validation cycles. Concordance with the reference method/laboratory at >0.1-≤10 IS was 78.2% and at ≤0.001 was 80%, compared to 86.8% in the >0.01-≤0.1 IS range. The overall and MMR concordance were 85.7% and 94% respectively, for samples that fell within ± 5-fold of the reference laboratory value over the entire period of study.Conversion factor and performance specific characteristics for the automated system were longitudinally stable in the clinically relevant range, following introduction by the manufacturer of lot specific efficiency values.

  20. 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...

  1. Active3 noise reduction

    International Nuclear Information System (INIS)

    Holzfuss, J.

    1996-01-01

    Noise reduction is a problem being encountered in a variety of applications, such as environmental noise cancellation, signal recovery and separation. Passive noise reduction is done with the help of absorbers. Active noise reduction includes the transmission of phase inverted signals for the cancellation. This paper is about a threefold active approach to noise reduction. It includes the separation of a combined source, which consists of both a noise and a signal part. With the help of interaction with the source by scanning it and recording its response, modeling as a nonlinear dynamical system is achieved. The analysis includes phase space analysis and global radial basis functions as tools for the prediction used in a subsequent cancellation procedure. Examples are given which include noise reduction of speech. copyright 1996 American Institute of Physics

  2. Reduction redux.

    Science.gov (United States)

    Shapiro, Lawrence

    2018-04-01

    Putnam's criticisms of the identity theory attack a straw man. Fodor's criticisms of reduction attack a straw man. Properly interpreted, Nagel offered a conception of reduction that captures everything a physicalist could want. I update Nagel, introducing the idea of overlap, and show why multiple realization poses no challenge to reduction so construed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Metallothermic reduction of molybdate

    International Nuclear Information System (INIS)

    Mukherjee, T.K.; Bose, D.K.

    1987-01-01

    This paper gives a brief account of the investigations conducted so far on metallothermic reduction of high grade molybdenite with particular emphasis on the work carried out in Bhabha Atomic Research Centre. Based on thermochemical considerations, the paper first introduces a number of metallic reductants suitable for use in metallothermic reduction of molybdenite. Aluminium, sodium and tin are found to be suitable reducing agents and very rightly they have found most applications in the research and development efforts on metallothermic reduction of molybdenite. The reduction with tin was conducted on fairly large scale both in vacuum and hydrogen atmosphere. The reaction was reported to be invariant depending mainly on the reduction temperature and a temperature of the order of 1250deg to 1300degC was required for good metal recovery. In comparison to tin, aluminothermic reduction of molybdenite was studied more extensively and it was conducted in closed bomb, vacuum and also in open atmosphere. In aluminothermic reduction, the influence of amount of reducing agent, amount of heat booster, preheating temperature and charging procedure on these metal yield was studied in detail. The reduction generally yielded massive molybdenum metal contaminated with aluminium as the major impurity element. Efforts were made to purify the reduced metal by arc melting, electron beam melting and molten salt electrorefining. 9 refs. (author)

  4. Droplet Digital PCR for BCR/ABL(P210) Detecting of CML: A High Sensitive Method of the Minimal Residual Disease& Disease Progression.

    Science.gov (United States)

    Wang, Wen-Jun; Zheng, Chao-Feng; Liu, Zhuang; Tan, Yan-Hong; Chen, Xiu-Hua; Zhao, Bin-Liang; Li, Guo-Xia; Xu, Zhi-Fang; Ren, Fang-Gang; Zhang, Yao-Fang; Chang, Jian-Mei; Wang, Hong-Wei

    2018-04-25

    The present study intended to establish a droplet digital PCR (dd-PCR) for monitoring minimal residual disease (MRD) in patients with BCR/ABL (P210)-positive CML, thereby achieving deep-level monitoring of tumor load and determining the efficacy for guided clinically individualized treatment. Using dd-PCR and RT-qPCR, two cell suspensions were obtained from K562 cells and normal peripheral blood mononuclear cells by gradient dilution and were measured at the cellular level. At peripheral blood(PB) level, 61 cases with CML-chronic phase (CML-CP) were obtained after tyrosine kinase inhibitors (TKIs) treatment and regular follow-ups. By RT-qPCR, BCR/ABL (P210) fusion gene was undetectable in PB after three successive analyses, which were performed once every three months. At the same time, dd-PCR was performed simultaneously with the last equal amount of cDNA. Ten CML patients with MR4.5 were followed up by the two methods. At the cellular level, consistency of results of dd-PCR and RT-qPCR reached R 2 ≥0.99, with conversion equation of Y=33.148X 1.222 (Y: dd-PCR results; X: RT-qPCR results). In the dd-PCR test, 11 of the 61 CML patients (18.03%) tested positive and showed statistically significant difference (PPCR 3 months earlier than by RT-qPCR. In contrast with RT-qPCR, dd-PCR is more sensitive, thus enabling accurate conversion of dd-PCR results into internationally standard RT-qPCR results by conversion equation, to achieve a deeper molecular biology-based stratification of BCR/ABL(P210) MRD. It has some reference value to monitor disease progression in clinic. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Measures and experiments to the reduction of mercury in the waste recycling plant Bonn. The gold amalgam procedure - Attempt of precipitation in the scrubber with TMT 15 - enrichment of the Dioxorb absorbent with activated charcoal; Massnahmen und Versuche zur Quecksilberminderung in der Abfallverwertungsanlage Bonn. Das Gold-Amalgamverfahren: Faellungsversuch im Waescher mit TMT 15 - Anreicherung des Dioxorb-Absorbens mit Aktivkohle

    Energy Technology Data Exchange (ETDEWEB)

    Heidrich, R. [Muellverwertungsanlage Bonn GmbH, Bonn (Germany)

    2007-07-01

    MVA Bonn GmbH (Bonn, Federal Republic of Germany) operates a plant for the thermal utilization of settlement wastes. The author of the contribution under consideration reports on measures and attempts according to the reduction of mercury in the waste processing plant Bonn. In particular, three procedures are discussed: (a) The gold amalgam procedure; (b) attempt of precipitation in the scrubber with TMT-15; (c) enrichment of the adsorbent Dioxorb with activated charcoal. The gold amalgam procedure is a reliable procedure for the reduction of the mercury content in exhaust gases. Additionally, it is a very expensive procedure. The filling material containers of all three procedures should be replaced in the next revisions gradually with new containers. The danger of an enrichment of considerable quantities of mercury on the filling material packing is large. A further possibility is the filling of the finished solution over a mist eliminator. Here the danger of the blockage plays a substantial role. A thorough and reliable lowering of the mercury emission can be achieved by means of the active charcoal containing Dioxorb.

  6. 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......), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation...

  7. 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

  8. 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.

  9. Determination of cDNA encoding BCR/ABL fusion gene in patients with chronic myelogenous leukemia using a novel FRET-based quantum dots-DNA nanosensor.

    Science.gov (United States)

    Shamsipur, Mojtaba; Nasirian, Vahid; Barati, Ali; Mansouri, Kamran; Vaisi-Raygani, Asad; Kashanian, Soheila

    2017-05-08

    In the present study, we developed a sensitive method based on fluorescence resonance energy transfer (FRET) for the determination of the BCR/ABL fusion gene, which is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). For this purpose, CdTe quantum dots (QDs) were conjugated to amino-modified 18-mer oligonucleotide ((N)DNA) to form the QDs-(N)DNA nanosensor. In the presence of methylene blue (MB) as an intercalator, the hybridization of QDs-(N)DNA with the target BCR/ABL fusion gene (complementary DNA), brings the MB (acceptor) at close proximity of the QDs (donor), leading to FRET upon photoexcitation of the QDs. The enhancement in the emission intensity of MB was used to follow up the hybridization, which was linearly proportional to concentration of the target complementary DNA in a range from 1.0 × 10 -9 to 1.25 × 10 -7  M. The detection limit of the proposed method was obtained to be 1.5 × 10 -10  M. Finally, the feasibility and selectivity of the proposed nanosensor was evaluated by the analysis of derived nucleotides from both mismatched sequences and clinical samples of patients with leukemia as real samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Silencing of BCR/ABL Chimeric Gene in Human Chronic Myelogenous Leukemia Cell Line K562 by siRNA-Nuclear Export Signal Peptide Conjugates.

    Science.gov (United States)

    Shinkai, Yasuhiro; Kashihara, Shinichi; Minematsu, Go; Fujii, Hirofumi; Naemura, Madoka; Kotake, Yojiro; Morita, Yasutaka; Ohnuki, Koichiro; Fokina, Alesya A; Stetsenko, Dmitry A; Filichev, Vyacheslav V; Fujii, Masayuki

    2017-06-01

    Herein we described the synthesis of siRNA-NES (nuclear export signal) peptide conjugates by solid phase fragment coupling and the application of them to silencing of bcr/abl chimeric gene in human chronic myelogenous leukemia cell line K562. Two types of siRNA-NES conjugates were prepared, and both sense strands at 5' ends were covalently linked to a NES peptide derived from TFIIIA and HIV-1 REV, respectively. Significant enhancement of silencing efficiency was observed for both of them. siRNA-TFIIIA NES conjugate suppressed the expression of BCR/ABL gene to 8.3% at 200 nM and 11.6% at 50 nM, and siRNA-HIV-1REV NES conjugate suppressed to 4.0% at 200 nM and 6.3% at 50 nM, whereas native siRNA suppressed to 36.3% at 200 nM and 30.2% at 50 nM. We could also show complex of siRNA-NES conjugate and designed amphiphilic peptide peptideβ7 could be taken up into cells with no cytotoxicity and showed excellent silencing efficiency. We believe that the complex siRNA-NES conjugate and peptideβ7 is a promising candidate for in vivo use and therapeutic applications.

  11. 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.

  12. 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.

  13. Interaction of the B cell-specific transcriptional coactivator OCA-B and galectin-1 and a possible role in regulating BCR-mediated B cell proliferation.

    Science.gov (United States)

    Yu, Xin; Siegel, Rachael; Roeder, Robert G

    2006-06-02

    OCA-B is a B cell-specific transcriptional coactivator for OCT factors during the activation of immunoglobulin genes. In addition, OCA-B is crucial for B cell activation and germinal center formation. However, the molecular mechanisms for OCA-B function in these processes are not clear. Our previous studies documented two OCA-B isoforms and suggested a novel mechanism for the function of the myristoylated, membrane-bound form of OCA-B/p35 as a signaling molecule. Here, we report the identification of galectin-1, and related galectins, as a novel OCA-B-interacting protein. The interaction of OCA-B and galectin-1 can be detected both in vivo and in vitro. The galectin-1 binding domain in OCA-B has been localized to the N terminus of OCA-B. In B cells lacking OCA-B expression, increased galectin-1 expression, secretion, and cell surface association are observed. Consistent with these observations, and a reported inhibitory interaction of galectin-1 with CD45, the phosphatase activity of CD45 is reduced modestly, but significantly, in OCA-B-deficient B cells. Finally, galectin-1 is shown to negatively regulate B cell proliferation and tyrosine phosphorylation upon BCR stimulation. Together, these results raise the possibility that OCA-B may regulate BCR signaling through an association with galectin-1.

  14. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.

    Science.gov (United States)

    Hughes, T P; Saglio, G; Quintás-Cardama, A; Mauro, M J; Kim, D-W; Lipton, J H; Bradley-Garelik, M B; Ukropec, J; Hochhaus, A

    2015-09-01

    BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib. Retrospective analyses were conducted to characterize mutation development in patients with newly diagnosed CML-CP treated with dasatinib (n=259) or imatinib (n=260) in DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML-CP), with 3-year minimum follow-up. Mutation screening, including patients who discontinued treatment and patients who had a clinically relevant on-treatment event (no confirmed complete cytogenetic response (cCCyR) and no major molecular response (MMR) within 12 months; fivefold increase in BCR-ABL1 with loss of MMR; loss of CCyR), yielded a small number of patients with mutations (dasatinib, n=17; imatinib, n=18). Dasatinib patients had a narrower spectrum of mutations (4 vs 12 sites for dasatinib vs imatinib), fewer phosphate-binding loop mutations (1 vs 9 mutations), fewer multiple mutations (1 vs 6 patients) and greater occurrence of T315I (11 vs 0 patients). This trial was registered at www.clinicaltrials.gov as NCT00481247.

  15. 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.

  16. Environmental procedures

    International Nuclear Information System (INIS)

    1992-01-01

    The European Bank has pledged in its Agreement to place environmental management at the forefront of its operations to promote sustainable economic development in central and eastern Europe. The Bank's environmental policy is set out in the document titled, Environmental Management: The Bank's Policy Approach. This document, Environmental Procedures, presents the procedures which the European Bank has adopted to implement this policy approach with respect to its operations. The environmental procedures aim to: ensure that throughout the project approval process, those in positions of responsibility for approving projects are aware of the environmental implications of the project, and can take these into account when making decisions; avoid potential liabilities that could undermine the success of a project for its sponsors and the Bank; ensure that environmental costs are estimated along with other costs and liabilities; and identify opportunities for environmental enhancement associated with projects. The review of environmental aspects of projects is conducted by many Bank staff members throughout the project's life. This document defines the responsibilities of the people and groups involved in implementing the environmental procedures. Annexes contain Environmental Management: The Bank's Policy Approach, examples of environmental documentation for the project file and other ancillary information

  17. 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

  18. Radiochemical procedures

    International Nuclear Information System (INIS)

    Lyon, W.S.

    1982-01-01

    The modern counting instrumentation has largely obviated the need for separation processes in the radiochemical analysis but problems in low-level radioactivity measurement, environmental-type analyses, and special situations caused in the last years a renaissance of the need for separation techniques. Most of the radiochemical procedures, based on the classic works of the Manhattan Project chemists of the 1940's, were published in the National Nuclear Energy Series (NNES). Improvements such as new solvent extraction and ion exchange separations have been added to these methods throughout the years. Recently the Los Alamos Group have reissued their collected Radiochemical Procedures containing a short summary and review of basic inorganic chemistry - 'Chemistry of the Elements on the Basis of Electronic Configuration'. (A.L.)

  19. Early Death in Two Patients with Acute Promyelocytic Leukemia Presenting the bcr3 Isoform, FLT3-ITD Mutation, and Elevated WT1 Level

    Directory of Open Access Journals (Sweden)

    Marianna Greco

    2013-01-01

    Full Text Available Despite major advances in the treatment of acute promyelocytic leukemia (APL, the problem of early death (ED remains unsolved. Alongside the currently known clinical and hematological risk factors, prognostic significance has been attributed to internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD, hypogranular variant morphology, and the bcr-3 isoform of PML-RARα. We describe premature death of two patients with the hypogranular variant of APL who presented remarkably high expression levels of Wilms' tumor gene (WT1. Our results point to WT1 as an important prognostic factor of ED that needs to be promptly evaluated in all newly diagnosed cases of APL.

  20. 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...... patients with chronic phase chronic myelogenous leukemia harboring a T315I mutation and resistant to imatinib mesylate was compared to a similar cohort of 53 chronic phase patients resistant to imatinib, but with no detectable T315I mutation, in the pre-ponatinib era. These patients were matched according...... to age at diagnosis, interval between disease diagnosis and start of imatinib treatment, and duration of imatinib therapy. Kaplan-Meier survival analyses demonstrated the significant negative impact of the presence of the T315I mutation on overall survival (since imatinib-resistance: 48.4 months for T315...

  1. 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.

  2. Procedure of trace element analysis in oyster tissues by using X-ray fluorescence

    International Nuclear Information System (INIS)

    Vo Thi Tuong Hanh; Dinh Thi Bich Lieu; Dinh Thien Lam and Nguyen Manh Hung

    2004-01-01

    The procedure of trace element analysis such as Ca, Mn, Fe, Zn, Cu, Pb in molluscs (oyster tissues) was established by using X-ray fluorescence techniques. The procedure was investigated from the sample collection, drying, ashing ratio to the analytical techniques by using Cd-109, detector Si (Li) and the peak processing MCAPLUS program was applied for this study. The procedure is based on direct comparison with certified concentrations of international standard reference SRM 1566b Oyster Tissue of National Institute of Standards and Technology, Department of commerce, United States of America for Ca, Mn, Fe, Zn, Cu and the Standard Addition Methods for Pb. The accuracy of the Standard Addition Methods was estimated by CRM281 Rye Grass of Community Bureau of Reference-BCR, European Commission. The results of 10 samples which were collected from several markets in Hanoi are shown. (author)

  3. Aesthetic procedures in office practice.

    Science.gov (United States)

    Small, Rebecca

    2009-12-01

    Since the approval of botulinum toxin, dermal fillers, and lasers for cosmetic use, minimally invasive aesthetic procedures have rapidly become the treatments of choice for age-related facial changes. In the past 10 years, aesthetic procedures have increased nearly five-fold. Of the 10.2 million aesthetic treatments performed in 2008, 83 percent were minimally invasive procedures. Botulinum toxin and dermal filler injections, laser hair reduction, chemical peels, laser skin resurfacing, microdermabrasion, and intense pulsed light photorejuvenation were the most commonly performed procedures in 2008. These procedures are effective and associated with minimal discomfort, and they have a low incidence of adverse effects and short recovery times. High patient and physician satisfaction have contributed to their growing popularity and availability in the primary care setting. As patient demand for aesthetic treatments increases, family physicians should be familiar with common minimally invasive aesthetic procedures when advising patients or incorporating aesthetic care into office practice.

  4. Optimal reduction of flexible dynamic system

    International Nuclear Information System (INIS)

    Jankovic, J.

    1994-01-01

    Dynamic system reduction is basic procedure in various problems of active control synthesis of flexible structures. In this paper is presented direct method for system reduction by explicit extraction of modes included in reduced model form. Criterion for optimal system discrete approximation in synthesis reduced dynamic model is also presented. Subjected method of system decomposition is discussed in relation to the Schur method of solving matrix algebraic Riccati equation as condition for system reduction. By using exposed method procedure of flexible system reduction in addition with corresponding example is presented. Shown procedure is powerful in problems of active control synthesis of flexible system vibrations

  5. Reduction by the Positive Allosteric Modulator of the GABAB Receptor, GS39783, of Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats Exposed to the “Sipper” Procedure

    Science.gov (United States)

    Maccioni, Paola; Flore, Paolo; Carai, Mauro A. M.; Mugnaini, Claudia; Pasquini, Serena; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

    2010-01-01

    The present study was designed to evaluate (a) alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP) rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases), and (b) the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR) 55 (RR55) for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v)-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g.) 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding) and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg) behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved) and -taking (the amount of self-administered alcohol was reduced by approximately 60%). The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats. PMID:21423431

  6. Reduction by the positive allosteric modulator of the GABAB receptor, GS39783, of alcohol self-administration in Sardinian alcohol-preferring rats exposed to the “sipper” procedure

    Directory of Open Access Journals (Sweden)

    Paola Maccioni

    2010-07-01

    Full Text Available The present study was designed to evaluate (a alcohol self-administration behavior of selectively bred, Sardinian alcohol-preferring (sP rats exposed to the so-called “sipper” procedure (characterized by the temporal separation between alcohol-seeking and -taking phases, and (b the effect of the positive allosteric modulator of the GABAB receptor, GS39783, on alcohol self-administration in sP rats exposed to this procedure. To this end, sP rats were initially trained to lever-respond under a reinforcement requirement (RR 55 (RR55 for alcohol. Achievement of RR55 resulted in the 20-min presentation of the alcohol (15%, v/v-containing sipper bottle. Once stable levels of lever-responding and alcohol consumption were reached, rats were treated with 0, 25, 50, and 100 mg/kg GS39783 (i.g. 60 min before the self-administration session. Rats displayed robust alcohol-seeking (as suggested by relatively short latencies to the first lever-response and high frequencies of lever-responding and -taking (as suggested by alcohol intakes averaging approximately 1.5 g/kg behaviors. Pretreatment with GS39783 inhibited both alcohol-seeking (the number of rats achieving RR55 and the mean RR value were virtually halved and -taking (the amount of self-administered alcohol was reduced by approximately 60%. The results of the present study suggest the power of the “sipper” procedure in triggering high levels of alcohol-seeking and -taking behavior in sP rats. Further, these results extend to this additional procedure of alcohol self-administration the capacity of GS39783 to reduce the motivational properties of alcohol and alcohol consumption in sP rats.

  7. A pilot randomised trial to assess the methods and procedures for evaluating the clinical effectiveness and cost-effectiveness of Exercise Assisted Reduction then Stop (EARS) among disadvantaged smokers.

    Science.gov (United States)

    Taylor, Adrian H; Thompson, Tom P; Greaves, Colin J; Taylor, Rod S; Green, Colin; Warren, Fiona C; Kandiyali, Rebecca; Aveyard, Paul; Ayres, Richard; Byng, Richard; Campbell, John L; Ussher, Michael H; Michie, Susan; West, Robert

    2014-01-01

    There have been few rigorous studies on the effects of behavioural support for helping smokers to reduce who do not immediately wish to quit. While reduction may not have the health benefits of quitting, it may lead smokers to want to quit. Physical activity (PA) helps to reduce cravings and withdrawal symptoms, and also reduces weight gain after quitting, but smokers may be less inclined to exercise. There is scope to develop and determine the effectiveness of interventions to support smoking reduction and increase physical activity, for those not ready to quit. To conduct a pilot randomised controlled trial (RCT) [Exercise Assisted Reduction then Stop (EARS) smoking study] to (1) design and evaluate the feasibility and acceptability of a PA and smoking-reduction counselling intervention [for disadvantaged smokers who do not wish to quit but do want to reduce their smoking (to increase the likelihood of quitting)], and (2) to inform the design of a large RCT to determine the clinical effectiveness and cost-effectiveness of the intervention. A single-centre, pragmatic, pilot trial with follow-up up to 16 weeks. A mixed methods approach assessed the acceptability and feasibility of the intervention and trial methods. Smokers were individually randomised to intervention or control arms. General practices, NHS buildings, community venues, and the Stop Smoking Service (SSS) within Plymouth, UK. Aged > 18 years, smoking ≥ 10 cigarettes per day (for ≥ 2 years) who wished to cut down. We excluded individuals who were contraindicated for moderate PA, posed a safety risk to the research team, wished to quit immediately or use Nicotine Replacement Therapy, not registered with a general practitioner, or did not converse in English. We designed a client-centred, counselling-based intervention designed to support smoking reduction and increases in PA. Support sessions were delivered by trained counsellors either face to face or by telephone. Both intervention

  8. 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

  9. 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

  10. Unfavourable results following reduction mammoplasty

    Directory of Open Access Journals (Sweden)

    Lakshmi Saleem

    2013-01-01

    Full Text Available Breast reduction is a common cosmetic surgical procedure. It aims not only at bringing down the size of the breast proportionate to the build of the individual, but also to overcome the discomfort caused by massive, ill-shaped and hanging breasts. The operative procedure has evolved from mere reduction of breast mass to enhanced aesthetic appeal with a minimum of scar load. The selection of technique needs to be individualised. Bilateral breast reduction is done most often. Haematoma, seroma, fat necrosis, skin loss, nipple loss and unsightly, painful scars can be the complications of any procedure on the breast. These may result from errors in judgement, wrong surgical plan and imprecise execution of the plan. Though a surfeit of studies are available on breast reduction, very few dwell upon its complications. The following article is a distillation of three decades of experience of the senior author (L.S. in reduction mammoplasty. An effort is made to understand the reasons for unfavourable results. To conclude, most complications can be overcome with proper selection of procedure for the given patient and with gentle tissue handling.

  11. Pretreatment procedures

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    It is frequently in the patient's best interest that radiation treatments are initiated soon after the decision to treat is made. However, it is essential to good radiation therapy that the patient's treatment course be planned and beam-modifying devices be fabricated with utmost care prior to treatment. The objectives of the treatment, along with the treatment parameters and techniques necessary to achieve these objectives, must be discussed prior to initiating planning procedures. Determination of the target volume is made by the radiation oncologist; this is based on knowledge of the history of the tumor, the patterns of spread of the disease, and on diagnostic findings during the work-up of each patient. It is then necessary to obtain several measurements of the patient and also to identify the position of the target volume and of adjacent normal organs with respect to known external skin marks before the actual treatment planning is begun. Such localization can be done through several methods. The two most commonly used methods are radiographic and computed tomography (CT), both of which are discussed in this chapter. The measurements often include contours of the patient's external surface, usually in the axial plane of the central axis of the beam, and often in multiple levels within the region to be treated. Three dimensional localization and treatment planning requires thorough understanding of geometry as well as of patient positioning and immobilization. This chapter attempts to clarify some of these complicated but essential preparations for treatment

  12. Snubber reduction

    International Nuclear Information System (INIS)

    Olson, D.E.; Singh, A.K.

    1986-01-01

    Many safety-related piping systems in nuclear power plants have been oversupported. Since snubbers make up a large percentage of the pipe supports or restraints used in a plant, a plant's snubber population is much larger than required to adequately restrain the piping. This has resulted in operating problems and unnecessary expenses for maintenance and inservice inspections (ISIs) of snubbers. This paper presents an overview of snubber reduction, including: the incentives for removing snubbers, a historical perspective on how piping became oversupported, why it is possible to remove snubbers, and the costs and benefits of doing so

  13. Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia - doi: 10.4025/actascihealthsci.v32i2.6408 Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia - doi: 10.4025/actascihealthsci.v32i2.6408

    Directory of Open Access Journals (Sweden)

    Thiago Cezar Fujita

    2010-09-01

    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.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

  14. Multiple position borehole extensometer procedure: Final draft

    International Nuclear Information System (INIS)

    1986-08-01

    The purpose of the Multiple Position Borehole Extensometer Procedure is to provide detailed information for MPBXs installed at the salt Deaf Smith County ESF. This procedure includes design of equipment, installation, instructions, instrument locations, measurement requirements, support requirements, quality assurance procedures, and data acquisition requirements. Data reduction procedures are also discussed; however, the relevance of the data is discussed elsewhere in the appropriate test plans. Sufficient detail is provided in this procedure to allow for integrating the requirements of this procedure into both the facility construction and overall underground testing programs; identifying necessary equipment for procurement; determining data acquisition requirements as input to Automatic Data Acquisition System (ADAS) design; providing step-by-step procedures for training personnel as well as for directing field operations; establishing quality assurance (QA) checkpoints and implementation methods; and defining data reduction methods and providing the anticipated accuracy of the system. 11 refs., 14 figs

  15. Radon reduction

    International Nuclear Information System (INIS)

    Hamilton, M.A.

    1990-01-01

    During a radon gas screening program, elevated levels of radon gas were detected in homes on Mackinac Island, Mich. Six homes on foundations with crawl spaces were selected for a research project aimed at reducing radon gas concentrations, which ranged from 12.9 to 82.3 pCi/l. Using isolation and ventilation techniques, and variations thereof, radon concentrations were reduced to less than 1 pCi/l. This paper reports that these reductions were achieved using 3.5 mil cross laminated or 10 mil high density polyethylene plastic as a barrier without sealing to the foundation or support piers, solid and/or perforated plastic pipe and mechanical fans. Wind turbines were found to be ineffective at reducing concentrations to acceptable levels. Homeowners themselves installed all materials

  16. 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.

  17. Ascorbate/menadione-induced oxidative stress kills cancer cells that express normal or mutated forms of the oncogenic protein Bcr-Abl. An in vitro and in vivo mechanistic study.

    Science.gov (United States)

    Beck, Raphaël; Pedrosa, Rozangela Curi; Dejeans, Nicolas; Glorieux, Christophe; Levêque, Philippe; Gallez, Bernard; Taper, Henryk; Eeckhoudt, Stéphane; Knoops, Laurent; Calderon, Pedro Buc; Verrax, Julien

    2011-10-01

    Numerous studies suggest that generation of oxidative stress could be useful in cancer treatment. In this study, we evaluated, in vitro and in vivo, the antitumor potential of oxidative stress induced by ascorbate/menadione (asc/men). This combination of a reducing agent (ascorbate) and a redox active quinone (menadione) generates redox cycling leading to formation of reactive oxygen species (ROS). Asc/men was tested in several cell types including K562 cells (a stable human-derived leukemia cell line), freshly isolated leukocytes from patients with chronic myeloid leukemia, BaF3 cells (a murine pro-B cell line) transfected with Bcr-Abl and peripheral blood leukocytes derived from healthy donors. Although these latter cells were resistant to asc/men, survival of all the other cell lines was markedly reduced, including the BaF3 cells expressing either wild-type or mutated Bcr-Abl. In a standard in vivo model of subcutaneous tumor transplantation, asc/men provoked a significant delay in the proliferation of K562 and BaF3 cells expressing the T315I mutated form of Bcr-Abl. No effect of asc/men was observed when these latter cells were injected into blood of mice most probably because of the high antioxidant potential of red blood cells, as shown by in vitro experiments. We postulate that cancer cells are more sensitive to asc/men than healthy cells because of their lack of antioxidant enzymes, mainly catalase. The mechanism underlying this cytotoxicity involves the oxidative cleavage of Hsp90 with a subsequent loss of its chaperone function thus leading to degradation of wild-type and mutated Bcr-Abl protein.

  18. 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.

  19. 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.

  20. [Development of Ph negative acute myeloid leukemia in a patient with minor-BCR/ABL positive chronic myeloid leukemia achieving a partial cytogenetic response during tyrosine kinase inhibitor treatment].

    Science.gov (United States)

    Fujii, Soichiro; Miura, Ikuo; Tanaka, Hideo

    2015-06-01

    A 78-year-old male, who had CKD and chronic heart failure, was referred to our hospital for evaluation of leukocytosis. His bone marrow contained 12% blast cells and chromosome analysis showed the Ph chromosome as well as other changes. The patient was diagnosed with the accelerated-phase CML because FISH and RT-PCR disclosed BCR/ABL fusion signals and minor BCR/ABL, respectively. Imatinib was administered, but the CML was resistant to this treatment. We gave him nilotinib employing a reduced and intermittent administration protocol because of the progression of anemia and heart failure. The patient achieved PCyR in 8 months, but, 12 months later, his WBC count increased and 83% of the cells were blasts. Because the probable diagnosis was the blast crisis of CML, we switched from nilotinib to dasatinib. However, leukocytosis worsened and he died of pneumonia. It was later revealed that he had a normal karyotype and both FISH and RT-PCR analysis of BCR/ABL were negative. His final diagnosis was Ph negative AML developing from Ph positive CML in PCyR. Since there were no dysplastic changes indicative of MDS, it was assumed that the AML was not secondary leukemia caused by the tyrosine kinase inhibitor but, rather, de novo AML.

  1. Evidence-based guidelines for the use of tyrosine kinase inhibitors in adults with Philadelphia chromosome–positive or BCR-ABL–positive acute lymphoblastic leukemia: a Canadian consensus

    Science.gov (United States)

    Couban, S.; Savoie, L.; Mourad, Y. Abou; Leber, B.; Minden, M.; Turner, R.; Palada, V.; Shehata, N.; Christofides, A.; Lachance, S.

    2014-01-01

    Adult Philadelphia chromosome–positive (Ph+) or BCR-ABL–positive (BCR-ABL+) acute lymphoblastic leukemia (all) is an acute leukemia previously associated with a high relapse rate, short disease-free survival, and poor overall survival. In adults, allogeneic hematopoietic cell transplant in first remission remains the only proven curative strategy for transplant-eligible patients. The introduction of tyrosine kinase inhibitors (tkis) in the treatment of patients with Ph+ or BCR-ABL+ all has significantly improved the depth and duration of complete remission, allowing more patients to proceed to transplantation. Although tkis are now considered a standard of care in this setting, few randomized trials have examined the optimal use of tkis in patients with Ph+ all. Questions of major importance remain, including the best way to administer these medications, the choice of tki to administer, and the schedule and the duration to use. We present the results of a systematic review of the literature with consensus recommendations based on the available evidence. PMID:24764712

  2. Four-channel asymmetric Real-Time PCR hybridization probe assay: a rapid pre-screening method for critical BCR-ABL kinase domain mutations.

    Science.gov (United States)

    Martinez-Serra, Jordi; Gutiérrez, Antonio; Marcús, Toni F; Soverini, Simona; Amat, Juan Carlos; Navarro-Palou, María; Ros, Teresa; Bex, Teresa; Ballester, Carmen; Bauça, Josep Miquel; SanFelix, Sara; Novo, Andrés; Vidal, Carmen; Santos, Carmen; Besalduch, Joan

    2012-03-01

    Within the laboratory protocols, used for the study of BCR-ABL resistance mutations in chronic myeloid leukemia patients treated with Imatinib, direct sequencing remains the reference method. Since the incidence of patients with a mutation-related loss of response is not very high, it is very useful in the routine laboratory to perform a fast pre-screening method. With this in mind, we have designed a new technique, based on a single Real-Time FRET-based PCR, followed by a study of melting peaks. This new tool, developed in a LightCycler 2.0, combines four different fluorescence channels for the simultaneous detection, in a single close tube, of critical mutations within the ABL kinase domain. Assay evaluation performed on 33 samples, previously genotyped by sequentiation, resulted in full concordance of results. This new methodology detects in a few steps the presence of critical mutations associated to Imatinib resistance. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. 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.

  4. On the Issue of Labor Relations Discontinuance by Staff Reduction

    Directory of Open Access Journals (Sweden)

    Sheveleva A. A.

    2012-11-01

    Full Text Available This article is devoted to consideration of issues related to the procedure of labor law contract termination by staff reduction. The author, analyzing the judicial practice, gives practical recommendations on the procedure of employment relationships discontinuance

  5. 5 CFR 359.602 - Agency reductions in force.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Agency reductions in force. 359.602... Appointees as a Result of Reduction in Force § 359.602 Agency reductions in force. (a) Competitive procedures... removed from the SES in any reduction in force of career appointees within the agency. Such competitive...

  6. State of the direct reduction and reduction smelting processes

    Directory of Open Access Journals (Sweden)

    Markotić A.

    2002-01-01

    Full Text Available For quite a long time efforts have been made to develop processes for producing iron i.e. steel without employing conventional procedures - from ore, coke, blast furnace, iron, electric arc furnace, converter to steel. The insufficient availability and the high price of the coking coals have forced many countries to research and adopt the non-coke-consuming reduction and metal manufacturing processes (non-coke metallurgy, direct reduction, direct processes. This paper represents a survey of the most relevant processes from this domain by the end of 2000, which display a constant increase in the modern process metallurgy.

  7. Reduction of soil erosion on forest roads

    Science.gov (United States)

    Edward R. Burroughs; John G. King

    1989-01-01

    Presents the expected reduction in surface erosion from selected treatments applied to forest road traveledways, cutslopes, fillslopes, and ditches. Estimated erosion reduction is expressed as functions of ground cover, slope gradient, and soil properties whenever possible. A procedure is provided to select rock riprap size for protection of the road ditch.

  8. 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

  9. Minimal Reducts with Grasp

    Directory of Open Access Journals (Sweden)

    Iris Iddaly Mendez Gurrola

    2011-03-01

    Full Text Available The proper detection of patient level of dementia is important to offer the suitable treatment. The diagnosis is based on certain criteria, reflected in the clinical examinations. From these examinations emerge the limitations and the degree in which each patient is in. In order to reduce the total of limitations to be evaluated, we used the rough set theory, this theory has been applied in areas of the artificial intelligence such as decision analysis, expert systems, knowledge discovery, classification with multiple attributes. In our case this theory is applied to find the minimal limitations set or reduct that generate the same classification that considering all the limitations, to fulfill this purpose we development an algorithm GRASP (Greedy Randomized Adaptive Search Procedure.

  10. Reduction of symplectic principal R-bundles

    International Nuclear Information System (INIS)

    Lacirasella, Ignazio; Marrero, Juan Carlos; Padrón, Edith

    2012-01-01

    We describe a reduction process for symplectic principal R-bundles in the presence of a momentum map. These types of structures play an important role in the geometric formulation of non-autonomous Hamiltonian systems. We apply this procedure to the standard symplectic principal R-bundle associated with a fibration π:M→R. Moreover, we show a reduction process for non-autonomous Hamiltonian systems on symplectic principal R-bundles. We apply these reduction processes to several examples. (paper)

  11. Hand-held electronic data collection and procedure environment

    International Nuclear Information System (INIS)

    Kennedy, E.; Doniz, K.

    1996-01-01

    As part of a CANDU Owners Group project, AECL has developed a hand-held electronic data collection and procedure environment. Integral to this environment is the C omputerized Procedure Engine . The development of the CPE allows operators, maintainers, and technical support staff to execute virtually any type of station procedure on a general-purpose PC-compatible hand-held computer. There are several advantages to using the computerized procedures: less paper use and handling, reduction in human error, reduction in rework in the field, an increase in procedural compliance, and immediate availability of data to download to databases and plant information systems. The paper describes: the advantages of using computerized procedures, why early forms of computerized procedures were inadequate, the features that the C omputerized Procedure Engine o ffers to the user, the streamlined life cycle of a computerized procedure, and field experience. The paper concludes that computerized procedures are ready for pilot applications at stations. (author)

  12. 23 CFR 657.21 - Procedure for reduction of funds.

    Science.gov (United States)

    2010-04-01

    ... writing a proposed determination of nonconformity, and shall notify the Governor of the State of the... show cause why it should not be found in nonconformity. If the State informs the Administrator before... Administrator shall forward the proposed determination of nonconformity to the Secretary. Upon approval of the...

  13. Reduction of doses from diagnostic X-ray procedures

    International Nuclear Information System (INIS)

    Gudden, F.; Kuhn, H.

    1992-01-01

    More recent developments in the field of receiver systems for X-rays have made it possible for doses required in X-ray examinations to be gradually reduced to no more than 5% of the radiation patients were exposed to 30 years ago. Despite this fact, the image quality standards necessary to establish even considerably improved. The author suggests to repeat series of measurements carried out in the distant past to be able to make a population-based assessment of the current risk from the effective equivalence dose in one year. In all likelihood, such a survey would prove the quivalence dose to be much lower than the degree of environmental radiation exposure. (orig./DGD) [de

  14. F-111C Flight Data Reduction and Analysis Procedures

    Science.gov (United States)

    1990-12-01

    BPHI NO 24 BTHE YES 25 BPSI NO 26 BH YES 27 LVEL NO 28 LBET NO 29 LALP YES 30 LPHI NO 31 LTHE NO 32 LPSI NO 33 LH NO 34 TABLE 2 INPUTS I Ax YES 2 Av NO...03 * 51 IJ Appendix G - A priori Data from Six Degree of Free- dom Flight Dynamic Model The six degree of freedom flight dynamic mathematical model of...Estimated Mathematical mode response - > of aircraft !Gauss- Maximum " Newton --- likelihood 4,computational cost Salgorithm function Maximum

  15. Therapeutic platelet reduction: Use in postsplenectomy thrombocytosis

    Directory of Open Access Journals (Sweden)

    Gita Negi

    2015-01-01

    Full Text Available Therapeutic platelet reduction is an effective modality for the reduction of platelet count in patients with treatment of extreme thrombocytosis resulting from a variety of primary and secondary causes of thrombocytosis, which may be associated with thrombotic or hemorrhagic complications of varying degrees. These cases when symptomatic fall into the ASFA Category II indication for therapeutic platelet apheresis procedure. Here, we report a case of postsplenectomy secondary thrombocytosis presenting with extremely high platelet counts and subsequent thrombosis in the shunt and successful treatment after therapeutic platelet reduction. The case is being presented to bring forth the fact that therapeutic platelet reduction is an easy procedure that gives quick and good results and also to bring to the attention of transfusion specialists an associated but as yet unreported procedural finding.

  16. MPT0B169, a New Antitubulin Agent, Inhibits Bcr-Abl Expression and Induces Mitochondrion-Mediated Apoptosis in Nonresistant and Imatinib-Resistant Chronic Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Shuit-Mun Wong

    Full Text Available Chronic myeloid leukemia (CML is a clonal disorder of hematopoietic stem/progenitor cells that is caused by the Bcr-Abl oncoprotein. Clinical resistance to the Bcr-Abl inhibitor imatinib is a critical problem in treating CML. This study investigated the antitumor effect and mechanism of MPT0B169, a new antitubulin agent, in K562 CML cells and their derived imatinib-resistant cells, IMR2 and IMR3. IMR2 and IMR3 cells showed complete resistance to imatinib-induced growth inhibition and apoptosis. Resistance involved ERK1/2 overactivation and MDR1 overexpression. MPT0B169 inhibited the growth of K562, IMR2, and IMR3 cells in a dose- and time-dependent manner. MPT0B169 substantially inhibited the mRNA and protein levels of Bcr-Abl, followed by its downstream pathways including Akt, ERK1/2, and STAT3 in these cells. MPT0B169 treatment resulted in a decrease in the polymer form of tubulin according to Western blot analysis. It triggered cell cycle arrest at the G2/M phase before apoptosis, which was related to the upregulation of the mitotic marker MPM2 and the cyclin B1 level, and a change in the phosphorylation of Cdk1. MPT0B169 induced apoptosis in nonresistant and imatinib-resistant cells via a mitochondrion-mediated caspase pathway. Further study showed that the agent led to a decrease in the antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 and an increase in the apoptotic protein Bax. Taken together, our results suggest that MPT0B169 might be a promising agent for overcoming imatinib resistance in CML cells.

  17. Dasatinib rapidly induces deep molecular response in chronic-phase chronic myeloid leukemia patients who achieved major molecular response with detectable levels of BCR-ABL1 transcripts by imatinib therapy.

    Science.gov (United States)

    Shiseki, Masayuki; Yoshida, Chikashi; Takezako, Naoki; Ohwada, Akira; Kumagai, Takashi; Nishiwaki, Kaichi; Horikoshi, Akira; Fukuda, Tetsuya; Takano, Hina; Kouzai, Yasuji; Tanaka, Junji; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

    2017-10-01

    With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment. In the present study, we attempted to investigate whether switching the treatment from imatinib to dasatinib can induce DMR in 16 CP-CML patients treated with imatinib for at least two years who achieved a major molecular response (MMR) with detectable levels of BCR-ABL1 transcripts. The rates of achievement of DMR at 1, 3, 6 and 12 months after switching to dasatinib treatment in the 16 patients were 44% (7/16), 56% (9/16), 63% (10/16) and 75% (12/16), respectively. The cumulative rate of achieving DMR at 12 months from initiation of dasatinib therapy was 93.8% (15/16). The proportion of natural killer cells and cytotoxic T cells in peripheral lymphocytes increased after switching to dasatinib. In contrast, the proportion of regulatory T cells decreased during treatment. The safety profile of dasatinib was consistent with previous studies. Switching to dasatinib would be a therapeutic option for CP-CML patients who achieved MMR but not DMR by imatinib, especially for patients who wish to discontinue TKI therapy.

  18. HASL procedures manual

    International Nuclear Information System (INIS)

    Harley, J.H.

    1977-08-01

    Additions and corrections to the following sections of the HASL Procedures Manual are provided: General, Sampling, Field Measurements; General Analytical Chemistry, Chemical Procedures, Data Section, and Specifications

  19. Intraoperative hydrostatic reduction of intussusception

    Directory of Open Access Journals (Sweden)

    Chatterjee Uday

    2008-01-01

    Full Text Available Aims: To find out an easier way of reduction of intussusception during open surgery to avoid unnecessary bowel injury. Materials and Methods: Under general anesthesia, before laparotomy, warm normal saline was infused into the rectum with a Foley catheter and an intravenous drip set maintaining the level of the bottle at 80 cm above the operating table. After opening the abdomen, pressure was applied on the colon filled with normal saline distal to the intussusceptum. The pressure was transmitted to the intussusceptum and the walls of the intussuscipient and caused reduction of intussusception without any injury to the intussuscipient and intussusceptum. This procedure was performed on those patients on whom laparotomy was performed as a primary procedure due to nonavailability of fluoroscopy or ultrasonography. Results: Between August 1998 and July 2005, we had six patients of mean (range age 11 months (7-17 months. In two cases, at laparotomy, the intussusceptions were found to have already reduced. Conclusions: Gentle finger pressure is necessary for reduction of intussusception. This subjective "gentleness" is dependant on experience of the surgeon and varies from person to person. Focal pressure on the intussuscipient and apex of the intussusceptum by the finger during reduction may be more damaging than the diffusely transmitted hydrostatic pressure even by a less-experienced surgeon. This will avoid the needless resection and anastomosis of the intestine on many occasions.

  20. Analytical procedures. Pt. 4

    International Nuclear Information System (INIS)

    Rackwitz, R.

    1985-01-01

    The semi-analytical procedures are summarized under the heading 'first or second-order reliability method'. The asymptotic aggravation of the theory was repeatedly hinted at. In supporting structures the probability of outage of components always is also a function of the condition of all other components. It depends moreover on the stress affecting mostly all components. This fact causes a marked reduction of the effect of redundant component arrangements in the system. It moreover requires very special formulations. Although theoretically interesting and practically important developments will leave their mark on the further progress of the theory, the statements obtained by those approaches will continue to depend on how closely the chosen physical relationships and stoachstic models can come to the scatter quantities. Sensitivity studies show that these are partly aspects of substantially higher importance with a view to decision criteria than the refinement of the (probabilistic) method. Questions of relevance and reliability of data and their adequate treatment in reliability analyses seem to rank higher in order of sequence than exaggerated demands on methodics. (orig./HP) [de

  1. Computer assisted procedure maintenance

    International Nuclear Information System (INIS)

    Bisio, R.; Hulsund, J. E.; Nilsen, S.

    2004-04-01

    The maintenance of operating procedures in a NPP is a tedious and complicated task. Through the whole life cycle of the procedures they will be dynamic, 'living' documents. Several aspects of the procedure must be considered in a revision process. Pertinent details and attributes of the procedure must be checked. An organizational structure must be created and responsibilities allotted for drafting, revising, reviewing and publishing procedures. Available powerful computer technology provides solutions within document management and computerisation of procedures. These solutions can also support the maintenance of procedures. Not all parts of the procedure life cycle are equally amenable to computerized support. This report looks at the procedure life cycle in todays NPPs and discusses the possibilities associated with introduction of computer technology to assist the maintenance of procedures. (Author)

  2. BCR-ABL1: Test

    Science.gov (United States)

    ... Gregory J. Tsongalis, PhD, HCLD, CC. Professor of Pathology, Director, Molecular Pathology, Dartmouth Hitchcock Medical Center and Geisel School of ... Reviews Besa, E. and Woermann, U. (Updated 2010 March 16). Chronic Myelogenous Leukemia. eMedicine [On-line information]. ...

  3. Finding optimal exact reducts

    KAUST Repository

    AbouEisha, Hassan M.

    2014-01-01

    The problem of attribute reduction is an important problem related to feature selection and knowledge discovery. The problem of finding reducts with minimum cardinality is NP-hard. This paper suggests a new algorithm for finding exact reducts

  4. Molecular genetic tests for JAK2V617F, Exon12_JAK2 and MPLW515K/L are highly informative in the evaluation of patients suspected to have BCR-ABL1-negative myeloproliferative neoplasms.

    Science.gov (United States)

    dos Santos, Marcos Tadeu; Mitne-Neto, Miguel; Miyashiro, Kozue; Chauffaille, Maria de Lourdes L Ferrari; Rizzatti, Edgar Gil

    2014-02-01

    Polycythaemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (MF), are the most common myeloproliferative neoplasms (MPN) in patients without the BCR-ABL1 gene rearrangement. They are caused by clonal expansion of haematopoietic stem cells and share, as a diagnostic criterion, the identification of JAK2V617F mutation. Classically, when other clinical criteria are present, a JAK2V617F negative case requires the analysis of Exon12_JAK2 for the diagnosis of PV, and of MPL515K/L mutations for the diagnosis of ET and MF. Here, we evaluated 78 samples from Brazilian patients suspected to have MPN, without stratification for PV, ET or MF. We found that 28 (35.9%) are JAK2V617F carriers; from the 50 remaining samples, one (2%) showed an Exon12_JAK2 mutation, and another (2%) was positive for MPLW515L mutation. In summary, the investigation of JAK2V617F, Exon12_JAK2 and MPLW515K/L was relevant for the diagnosis of 38.4% of patients suspected to have BCR-ABL1-negative MPN, suggesting that molecular genetic tests are useful for a quick and unequivocal diagnosis of MPN.

  5. Breast Reduction Surgery

    Science.gov (United States)

    ... considering breast reduction surgery, consult a board-certified plastic surgeon. It's important to understand what breast reduction surgery entails — including possible risks and complications — as ...

  6. Deep sedation during pneumatic reduction of intussusception.

    Science.gov (United States)

    Ilivitzki, Anat; Shtark, Luda Glozman; Arish, Karin; Engel, Ahuva

    2012-05-01

    Pneumatic reduction of intussusception under fluoroscopic guidance is a routine procedure. The unsedated child may resist the procedure, which may lengthen its duration and increase the radiation dose. We use deep sedation during the procedure to overcome these difficulties. The purpose of this study was to summarize our experience with deep sedation during fluoroscopic reduction of intussusception and assess the added value and complication rate of deep sedation. All children with intussusception who underwent pneumatic reduction in our hospital between January 2004 and June 2011 were included in this retrospective study. Anesthetists sedated the children using propofol. The fluoroscopic studies, ultrasound (US) studies and the childrens' charts were reviewed. One hundred thirty-one attempted reductions were performed in 119 children, of which 121 (92%) were successful and 10 (8%) failed. Two perforations (1.5%) occurred during attempted reduction. Average fluoroscopic time was 1.5 minutes. No complication to sedation was recorded. Deep sedation with propofol did not add any complication to the pneumatic reduction. The fluoroscopic time was short. The success rate of reduction was high,raising the possibility that sedation is beneficial, possibly by smooth muscle relaxation.

  7. Radiology residents' experience with intussusception reduction

    International Nuclear Information System (INIS)

    Bateni, Cyrus; Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L.; Li, Chin-Shang

    2011-01-01

    Residents should be exposed to adequate procedural volume to act independently upon completion of training. Informal inquiry led us to question whether residents encounter enough intussusception reductions to become comfortable with the procedure. We sought to determine radiology residents' exposure to intussusception reductions, and whether their experiences vary by region or institution. U.S. radiology residency program directors were asked to encourage their residents to complete a 12-question online survey describing characteristics of their pediatric radiology department, experiences with intussusception reduction, and confidence in their own ability to perform the procedure. Six hundred sixty-four residents responded during the study period. Of those, 308 (46.4%) had not experienced an intussusception reduction, and 228 (34%) had experienced only one or two. Twenty-two percent of fourth-year residents had never experienced an intussusception reduction, and 21% had experienced only one. Among second- through fourth-year residents, only 99 (18.3%) felt confident that they could competently reduce an intussusception (P < 0.0001), and 336 (62.2%) thought they would benefit from a computer-assisted training model simulating intussusception reduction (P < 0.0001). Radiology residents have limited opportunity to learn intussusception reduction and therefore lack confidence. Most think they would benefit from additional training with a computer-simulation model. (orig.)

  8. Recursions of Symmetry Orbits and Reduction without Reduction

    Directory of Open Access Journals (Sweden)

    Andrei A. Malykh

    2011-04-01

    Full Text Available We consider a four-dimensional PDE possessing partner symmetries mainly on the example of complex Monge-Ampère equation (CMA. We use simultaneously two pairs of symmetries related by a recursion relation, which are mutually complex conjugate for CMA. For both pairs of partner symmetries, using Lie equations, we introduce explicitly group parameters as additional variables, replacing symmetry characteristics and their complex conjugates by derivatives of the unknown with respect to group parameters. We study the resulting system of six equations in the eight-dimensional space, that includes CMA, four equations of the recursion between partner symmetries and one integrability condition of this system. We use point symmetries of this extended system for performing its symmetry reduction with respect to group parameters that facilitates solving the extended system. This procedure does not imply a reduction in the number of physical variables and hence we end up with orbits of non-invariant solutions of CMA, generated by one partner symmetry, not used in the reduction. These solutions are determined by six linear equations with constant coefficients in the five-dimensional space which are obtained by a three-dimensional Legendre transformation of the reduced extended system. We present algebraic and exponential examples of such solutions that govern Legendre-transformed Ricci-flat Kähler metrics with no Killing vectors. A similar procedure is briefly outlined for Husain equation.

  9. Computerized procedures system

    Science.gov (United States)

    Lipner, Melvin H.; Mundy, Roger A.; Franusich, Michael D.

    2010-10-12

    An online data driven computerized procedures system that guides an operator through a complex process facility's operating procedures. The system monitors plant data, processes the data and then, based upon this processing, presents the status of the current procedure step and/or substep to the operator. The system supports multiple users and a single procedure definition supports several interface formats that can be tailored to the individual user. Layered security controls access privileges and revisions are version controlled. The procedures run on a server that is platform independent of the user workstations that the server interfaces with and the user interface supports diverse procedural views.

  10. reduction mammoplasty using inferior pedicle in heavy breasts

    African Journals Online (AJOL)

    2011-09-09

    Sep 9, 2011 ... sexual relationships. Reduction mammoplasty procedure provides weight and volume reduction of the breast as well as enhancement of the aesthetic appearance of the breasts. In this study, the inferior pedicle technique was used in reduction of thirty five patients over the last four years with macromastia.

  11. Human factoring administrative procedures

    International Nuclear Information System (INIS)

    Grider, D.A.; Sturdivant, M.H.

    1991-01-01

    In nonnuclear business, administrative procedures bring to mind such mundane topics as filing correspondence and scheduling vacation time. In the nuclear industry, on the other hand, administrative procedures play a vital role in assuring the safe operation of a facility. For some time now, industry focus has been on improving technical procedures. Significant efforts are under way to produce technical procedure requires that a validated technical, regulatory, and administrative basis be developed and that the technical process be established for each procedure. Producing usable technical procedures requires that procedure presentation be engineered to the same human factors principles used in control room design. The vital safety role of administrative procedures requires that they be just as sound, just a rigorously formulated, and documented as technical procedures. Procedure programs at the Tennessee Valley Authority and at Boston Edison's Pilgrim Station demonstrate that human factors engineering techniques can be applied effectively to technical procedures. With a few modifications, those same techniques can be used to produce more effective administrative procedures. Efforts are under way at the US Department of Energy Nuclear Weapons Complex and at some utilities (Boston Edison, for instance) to apply human factors engineering to administrative procedures: The techniques being adapted include the following

  12. Procedures in diagnostic radiology

    International Nuclear Information System (INIS)

    Doyle, T.; Hare, W.S.C.; Thomson, K.; Tess, B.

    1989-01-01

    This book outlines the various procedures necessary for the successful practice of diagnostic radiology. Topics covered are: general principles, imaging of the urinary and gastrointestinal tracts, vascular radiology, arthrography, and miscellaneous diagnostic radiologic procedures

  13. Reliability of application of inspection procedures

    Energy Technology Data Exchange (ETDEWEB)

    Murgatroyd, R A

    1988-12-31

    This document deals with the reliability of application of inspection procedures. A method to ensure that the inspection of defects thanks to fracture mechanics is reliable is described. The Systematic Human Error Reduction and Prediction Analysis (SHERPA) methodology is applied to every task performed by the inspector to estimate the possibility of error. It appears that it is essential that inspection procedures should be sufficiently rigorous to avoid substantial errors, and that the selection procedures and the training period for inspectors should be optimised. (TEC). 3 refs.

  14. Reliability of application of inspection procedures

    International Nuclear Information System (INIS)

    Murgatroyd, R.A.

    1988-01-01

    This document deals with the reliability of application of inspection procedures. A method to ensure that the inspection of defects thanks to fracture mechanics is reliable is described. The Systematic Human Error Reduction and Prediction Analysis (SHERPA) methodology is applied to every task performed by the inspector to estimate the possibility of error. It appears that it is essential that inspection procedures should be sufficiently rigorous to avoid substantial errors, and that the selection procedures and the training period for inspectors should be optimised. (TEC)

  15. Infinitary Combinatory Reduction Systems: Normalising Reduction Strategies

    NARCIS (Netherlands)

    Ketema, J.; Simonsen, Jakob Grue

    2010-01-01

    We study normalising reduction strategies for infinitary Combinatory Reduction Systems (iCRSs). We prove that all fair, outermost-fair, and needed-fair strategies are normalising for orthogonal, fully-extended iCRSs. These facts properly generalise a number of results on normalising strategies in

  16. Procedural Media Representation

    OpenAIRE

    Henrysson, Anders

    2002-01-01

    We present a concept for using procedural techniques to represent media. Procedural methods allow us to represent digital media (2D images, 3D environments etc.) with very little information and to render it photo realistically. Since not all kind of content can be created procedurally, traditional media representations (bitmaps, polygons etc.) must be used as well. We have adopted an object-based media representation where an object can be represented either with a procedure or with its trad...

  17. Singular reduction of Nambu-Poisson manifolds

    Science.gov (United States)

    Das, Apurba

    The version of Marsden-Ratiu Poisson reduction theorem for Nambu-Poisson manifolds by a regular foliation have been studied by Ibáñez et al. In this paper, we show that this reduction procedure can be extended to the singular case. Under a suitable notion of Hamiltonian flow on the reduced space, we show that a set of Hamiltonians on a Nambu-Poisson manifold can also be reduced.

  18. Classification of radiological procedures

    International Nuclear Information System (INIS)

    1989-01-01

    A classification for departments in Danish hospitals which use radiological procedures. The classification codes consist of 4 digits, where the first 2 are the codes for the main groups. The first digit represents the procedure's topographical object and the second the techniques. The last 2 digits describe individual procedures. (CLS)

  19. Procedure generation and verification

    International Nuclear Information System (INIS)

    Sheely, W.F.

    1986-01-01

    The Department of Energy has used Artificial Intelligence of ''AI'' concepts to develop two powerful new computer-based techniques to enhance safety in nuclear applications. The Procedure Generation System, and the Procedure Verification System, can be adapted to other commercial applications, such as a manufacturing plant. The Procedure Generation System can create a procedure to deal with the off-normal condition. The operator can then take correct actions on the system in minimal time. The Verification System evaluates the logic of the Procedure Generator's conclusions. This evaluation uses logic techniques totally independent of the Procedure Generator. The rapid, accurate generation and verification of corrective procedures can greatly reduce the human error, possible in a complex (stressful/high stress) situation

  20. Reduction in language testing

    DEFF Research Database (Denmark)

    Dimova, Slobodanka; Jensen, Christian

    2013-01-01

    /video recorded speech samples and written reports produced by two experienced raters after testing. Our findings suggest that reduction or reduction-like pronunciation features are found in tested L2 speech, but whenever raters identify and comment on such reductions, they tend to assess reductions negatively......This study represents an initial exploration of raters' comments and actual realisations of form reductions in L2 test speech performances. Performances of three L2 speakers were selected as case studies and illustrations of how reductions are evaluated by the raters. The analysis is based on audio...

  1. Reduction of Nambu-Poisson Manifolds by Regular Distributions

    Science.gov (United States)

    Das, Apurba

    2018-03-01

    The version of Marsden-Ratiu reduction theorem for Nambu-Poisson manifolds by a regular distribution has been studied by Ibáñez et al. In this paper we show that the reduction is always ensured unless the distribution is zero. Next we extend the more general Falceto-Zambon Poisson reduction theorem for Nambu-Poisson manifolds. Finally, we define gauge transformations of Nambu-Poisson structures and show that these transformations commute with the reduction procedure.

  2. Generalized Time-Limited Balanced Reduction Method

    DEFF Research Database (Denmark)

    Shaker, Hamid Reza; Shaker, Fatemeh

    2013-01-01

    In this paper, a new method for model reduction of bilinear systems is presented. The proposed technique is from the family of gramian-based model reduction methods. The method uses time-interval generalized gramians in the reduction procedure rather than the ordinary generalized gramians...... and in such a way it improves the accuracy of the approximation within the time-interval which the method is applied. The time-interval generalized gramians are the solutions to the generalized time-interval Lyapunov equations. The conditions for these equations to be solvable are derived and an algorithm...

  3. Mercury and trace element fractionation in Almaden soils by application of different sequential extraction procedures

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, D.M.; Quejido, A.J.; Fernandez, M.; Hernandez, C.; Schmid, T.; Millan, R.; Gonzalez, M.; Aldea, M.; Martin, R.; Morante, R. [CIEMAT, Madrid (Spain)

    2005-04-01

    A comparative evaluation of the mercury distribution in a soil sample from Almaden (Spain) has been performed by applying three different sequential extraction procedures, namely, modified BCR (three steps in sequence), Di Giulio-Ryan (four steps in sequence), and a specific SEP developed at CIEMAT (six steps in sequence). There were important differences in the mercury extraction results obtained by the three procedures according to the reagents applied and the sequence of their application. These findings highlight the difficulty of setting a universal SEP to obtain information on metal fractions of different mobility for any soil sample, as well as the requirement for knowledge about the mineralogical and chemical characteristics of the samples. The specific six-step CIEMAT sequential extraction procedure was applied to a soil profile (Ap, Ah, Bt1, and Bt2 horizons). The distribution of mercury and major, minor, and trace elements in the different fractions were determined. The results indicate that mercury is mainly released with 6 M HCl. The strong association of mercury with crystalline iron oxyhydroxides, present in all the horizons of the profile, and/or the solubility of some mercury compounds in such acid can explain this fact. Minor mercury is found in the fraction assigned to oxidizable matter and in the final insoluble residue (cinnabar). (orig.)

  4. Synthesis, magnetic properties and Moessbauer spectroscopy for the pyrochlore family Bi{sub 2}BB Prime O{sub 7} with B=Cr and Fe and B Prime =Nb, Ta and Sb

    Energy Technology Data Exchange (ETDEWEB)

    Blanco, Maria C. [INFIQC (CONICET), Dpto. de Fisicoquimica, Fac. de Ciencias Quimicas, U.N.C., Cordoba (X5000HUA) (Argentina); Franco, Diego G. [INFIQC (CONICET), Dpto. de Fisicoquimica, Fac. de Ciencias Quimicas, U.N.C., Cordoba (X5000HUA) (Argentina); Centro Atomico Bariloche - CNEA, Av. E. Bustillo 9500, S.C. de Bariloche (8500), R.N. (Argentina); Jalit, Yamile; Pannunzio Miner, Elisa V. [INFIQC (CONICET), Dpto. de Fisicoquimica, Fac. de Ciencias Quimicas, U.N.C., Cordoba (X5000HUA) (Argentina); Berndt, Graciele; Paesano, Andrea [Departamento de Fisica, Universidade Estadual de Maringa, Parana (Brazil); Nieva, Gladys [Centro Atomico Bariloche - CNEA, Av. E. Bustillo 9500, S.C. de Bariloche (8500), R.N. (Argentina); Carbonio, Raul E., E-mail: carbonio@mail.fcq.unc.edu.ar [INFIQC (CONICET), Dpto. de Fisicoquimica, Fac. de Ciencias Quimicas, U.N.C., Cordoba (X5000HUA) (Argentina)

    2012-08-15

    The samples Bi{sub 2}BB Prime O{sub 7}, with B=Cr and Fe and B Prime =Nb, Ta and Sb were prepared by solid state method. The crystallographic structure was investigated on the basis of X-ray powder diffraction data. Rietveld refinements show that the crystal structure is cubic, space group Fd-3m. The Bi{sup 3+} cation on the eight-coordinate pyrochlore A-site shows displacive disorder, as a consequence of its lone pair electron configuration. There is also a considerable A-site disorder shown by Rietveld Analysis and confirmed in the case of the iron containing samples with Moessbauer spectroscopy. The magnetic measurements show paramagnetic behavior at all temperatures for the Cr oxides. The Fe pyrochlores show antiferromagnetic order around 10 K.

  5. Civil Procedure In Denmark

    DEFF Research Database (Denmark)

    Werlauff, Erik

    scientific activities conducted by the author, partly based on the author's experience as a member, through a number of years, of the Danish Standing Committee on Procedural Law (Retsplejeraadet), which on a continuous basis evaluates the need for civil procedural reforms in Denmark, and finally also based......The book contains an up-to-date survey of Danish civil procedure after the profound Danish procedural reforms in 2007. It deals with questions concerning competence and function of Danish courts, commencement and preparation of civil cases, questions of evidence and burden of proof, international...... procedural questions, including relations to the Brussels I Regulation and Denmark's participation in this Regulation via a parallel convention with the EU countries, impact on Danish civil procedure of the convention on human rights, preparation and pronouncement of judgment and verdict, questions of appeal...

  6. MCNP variance reduction overview

    International Nuclear Information System (INIS)

    Hendricks, J.S.; Booth, T.E.

    1985-01-01

    The MCNP code is rich in variance reduction features. Standard variance reduction methods found in most Monte Carlo codes are available as well as a number of methods unique to MCNP. We discuss the variance reduction features presently in MCNP as well as new ones under study for possible inclusion in future versions of the code

  7. Modern Reduction Methods

    CERN Document Server

    Andersson, Pher G

    2008-01-01

    With its comprehensive overview of modern reduction methods, this book features high quality contributions allowing readers to find reliable solutions quickly and easily. The monograph treats the reduction of carbonyles, alkenes, imines and alkynes, as well as reductive aminations and cross and heck couplings, before finishing off with sections on kinetic resolutions and hydrogenolysis. An indispensable lab companion for every chemist.

  8. Spline-procedures

    International Nuclear Information System (INIS)

    Schmidt, R.

    1976-12-01

    This report contains a short introduction to spline functions as well as a complete description of the spline procedures presently available in the HMI-library. These include polynomial splines (using either B-splines or one-sided basis representations) and natural splines, as well as their application to interpolation, quasiinterpolation, L 2 -, and Tchebycheff approximation. Special procedures are included for the case of cubic splines. Complete test examples with input and output are provided for each of the procedures. (orig.) [de

  9. Procedural sedation analgesia

    OpenAIRE

    Sheta, Saad A

    2010-01-01

    The number of noninvasive and minimally invasive procedures performed outside of the operating room has grown exponentially over the last several decades. Sedation, analgesia, or both may be needed for many of these interventional or diagnostic procedures. Individualized care is important when determining if a patient requires procedural sedation analgesia (PSA). The patient might need an anti-anxiety drug, pain medicine, immobilization, simple reassurance, or a combination of these interve...

  10. Multiple cost criteria for occupational dose reduction

    International Nuclear Information System (INIS)

    James, J.Z.

    1983-01-01

    This paper describes a simple, feasible procedure for deciding if a proposed dose reduction measure is justified under ALARA, based on engineering economic principles of project feasibility analysis. Particular attention is given to the fixing of cost criteria: the importance of melding disparate objectives into a single parameter, and the distinction between a cost criterion and a cost consideration. (author)

  11. Handbook of radiologic procedures

    International Nuclear Information System (INIS)

    Hedgcock, M.

    1986-01-01

    This book is organized around radiologic procedures with each discussed from the points of view of: indications, contraindications, materials, method of procedures and complications. Covered in this book are: emergency radiology chest radiology, bone radiology, gastrointestinal radiology, GU radiology, pediatric radiology, computerized tomography, neuroradiology, visceral and peripheral angiography, cardiovascular radiology, nuclear medicine, lymphangiography, and mammography

  12. Decision-making Procedures

    DEFF Research Database (Denmark)

    Aldashev, Gani; Kirchsteiger, Georg; Sebald, Alexander Christopher

    2009-01-01

    define procedures as mechanisms that influence the probabilities of reaching different endnodes. We show that for such procedural games a sequential psychological equilibrium always exists. Applying this approach within a principal-agent context we show that the way less attractive jobs are allocated...

  13. Maintenance procedure upgrade programs

    International Nuclear Information System (INIS)

    Campbell, J.J.; Zimmerman, C.M.

    1988-01-01

    This paper describes a systematic approach to upgrading nuclear power plant maintenance procedures. The approach consists of four phases: diagnosis, program planning, program implementation, and program evaluation. Each phase is explained as a series of steps to ensure that all factors in a procedure upgrade program are considered

  14. Actor-Network Procedures

    NARCIS (Netherlands)

    Pavlovic, Dusko; Meadows, Catherine; Ramanujam, R.; Ramaswamy, Srini

    2012-01-01

    In this paper we propose actor-networks as a formal model of computation in heterogenous networks of computers, humans and their devices, where these new procedures run; and we introduce Procedure Derivation Logic (PDL) as a framework for reasoning about security in actor-networks, as an extension

  15. Analytical procedures. Pt. 1

    International Nuclear Information System (INIS)

    Weber, G.

    1985-01-01

    In analytical procedures (Boole procedures) there is certain to be a close relationship between the safety assessment and reliability assessment of technical facilities. The paper gives an overview of the organization of models, fault trees, the probabilistic evaluation of systems, evaluation with minimum steps or minimum paths regarding statistically dependent components and of systems liable to suffer different kinds of outages. (orig.) [de

  16. Play vs. Procedures

    DEFF Research Database (Denmark)

    Hammar, Emil

    Through the theories of play by Gadamer (2004) and Henricks (2006), I will show how the relationship between play and game can be understood as dialectic and disruptive, thus challenging understandings of how the procedures of games determine player activity and vice versa. As such, I posit some...... analytical consequences for understandings of digital games as procedurally fixed (Boghost, 2006; Flannagan, 2009; Bathwaite & Sharp, 2010). That is, if digital games are argued to be procedurally fixed and if play is an appropriative and dialectic activity, then it could be argued that the latter affects...... and alters the former, and vice versa. Consequently, if the appointed procedures of a game are no longer fixed and rigid in their conveyance of meaning, qua the appropriative and dissolving nature of play, then understandings of games as conveying a fixed meaning through their procedures are inadequate...

  17. 40 CFR 76.15 - Test methods and procedures.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Test methods and procedures. 76.15 Section 76.15 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.15 Test methods and procedures. (a) The...

  18. Reduction - competitive tomorrow

    International Nuclear Information System (INIS)

    Worley, L.; Bargerstock, S.

    1995-01-01

    Inventory reduction is one of the few initiatives that represent significant cost-reduction potential that does not result in personnel reduction. Centerior Energy's Perry nuclear power plant has embarked on an aggressive program to reduce inventory while maintaining plant material availability. Material availability to the plant was above 98%, but at an unacceptable 1994 inventory book value of $47 million with inventory carrying costs calculated at 30% annually

  19. Process energy reduction

    International Nuclear Information System (INIS)

    Lowthian, W.E.

    1993-01-01

    Process Energy Reduction (PER) is a demand-side energy reduction approach which complements and often supplants other traditional energy reduction methods such as conservation and heat recovery. Because the application of PER is less obvious than the traditional methods, it takes some time to learn the steps as well as practice to become proficient in its use. However, the benefit is significant, often far outweighing the traditional energy reduction approaches. Furthermore, the method usually results in a better process having less waste and pollution along with improved yields, increased capacity, and lower operating costs

  20. Finding optimal exact reducts

    KAUST Repository

    AbouEisha, Hassan M.

    2014-01-01

    The problem of attribute reduction is an important problem related to feature selection and knowledge discovery. The problem of finding reducts with minimum cardinality is NP-hard. This paper suggests a new algorithm for finding exact reducts with minimum cardinality. This algorithm transforms the initial table to a decision table of a special kind, apply a set of simplification steps to this table, and use a dynamic programming algorithm to finish the construction of an optimal reduct. I present results of computer experiments for a collection of decision tables from UCIML Repository. For many of the experimented tables, the simplification steps solved the problem.

  1. 75 FR 78804 - Proposed Collection; Comment Request for Revenue Procedure 2003-45 and Revenue Procedure 2004-48

    Science.gov (United States)

    2010-12-16

    ... required by the Paperwork Reduction Act of 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently... Corporations, and Revenue Procedure 2004-48, Deemed Corporate Election for Late Electing S Corporations. DATES...-45, Late Election Relief for S Corporations, and Revenue Procedure 2004-48, Deemed Corporate Election...

  2. HASL procedures manual

    International Nuclear Information System (INIS)

    1980-08-01

    Addition and corrections to the following sections of the HASL Procedures Manual are provided: Table of Contents; Bibliography; Fallout Collection Methods; Wet/Dry Fallout Collection; Fluoride in Soil and Sediment; Strontium-90; Natural Series; Alpha Emitters; and Gamma Emitters

  3. EML procedures manual

    International Nuclear Information System (INIS)

    Volchok, H.L.; de Planque, G.

    1982-01-01

    This manual contains the procedures that are used currently by the Environmental Measurements Laboratory of the US Department of Energy. In addition a number of analytical methods from other laboratories have been included. These were tested for reliability at the Battelle, Pacific Northwest Laboratory under contract with the Division of Biomedical and Environmental Research of the AEC. These methods are clearly distinguished. The manual is prepared in loose leaf form to facilitate revision of the procedures and inclusion of additional procedures or data sheets. Anyone receiving the manual through EML should receive this additional material automatically. The contents are as follows: (1) general; (2) sampling; (3) field measurements; (4) general analytical chemistry; (5) chemical procedures; (6) data section; (7) specifications

  4. Cosmetic Procedure Questions

    Science.gov (United States)

    ... for Every Season How to Choose the Best Skin Care Products In This Section Dermatologic Surgery What is dermatologic ... for Every Season How to Choose the Best Skin Care Products Cosmetic Procedure Questions Want to look younger? Start ...

  5. Modified arthroscopic Brostrom procedure.

    Science.gov (United States)

    Lui, Tun Hing

    2015-09-01

    The open modified Brostrom anatomic repair technique is widely accepted as the reference standard for lateral ankle stabilization. However, there is high incidence of intra-articular pathologies associated with chronic lateral ankle instability which may not be addressed by an isolated open Brostrom procedure. Arthroscopic Brostrom procedure with suture anchor has been described for anatomic repair of chronic lateral ankle instability and management of intra-articular lesions. However, the complication rates seemed to be higher than open Brostrom procedure. Modification of the arthroscopic Brostrom procedure with the use of bone tunnel may reduce the risk of certain complications. Copyright © 2015 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  6. Assisted Medical Procedures (AMP)

    Data.gov (United States)

    National Aeronautics and Space Administration — DOCUMENTATION, DEVELOPMENT, AND PROGRESS The AMP was initially being developed as part the Advanced Integrated Clinical System (AICS)-Guided Medical Procedure System...

  7. Cosmetic Procedure Questions

    Science.gov (United States)

    ... Back Injectable Deoxycholic Acid Injectable Hyaluronic Acid Injectable Poly-l-lactic Acid Injectable Polymethylmethacrylate + Bovine Collagen Filler ... time of their procedure. 6. What are my pain management and anesthesia options? To help avoid the ...

  8. Special Blood Donation Procedures

    Science.gov (United States)

    ... Blood Products Special Blood Donation Procedures Precautions and Adverse Reactions During Blood Transfusion (See Overview of Blood Transfusion .) Plateletpheresis (platelet donation) In plateletpheresis, a donor gives only platelets rather than whole blood. Whole ...

  9. Dynamic alarm response procedures

    International Nuclear Information System (INIS)

    Martin, J.; Gordon, P.; Fitch, K.

    2006-01-01

    The Dynamic Alarm Response Procedure (DARP) system provides a robust, Web-based alternative to existing hard-copy alarm response procedures. This paperless system improves performance by eliminating time wasted looking up paper procedures by number, looking up plant process values and equipment and component status at graphical display or panels, and maintenance of the procedures. Because it is a Web-based system, it is platform independent. DARP's can be served from any Web server that supports CGI scripting, such as Apache R , IIS R , TclHTTPD, and others. DARP pages can be viewed in any Web browser that supports Javascript and Scalable Vector Graphics (SVG), such as Netscape R , Microsoft Internet Explorer R , Mozilla Firefox R , Opera R , and others. (authors)

  10. Radiochemical procedures and techniques

    International Nuclear Information System (INIS)

    Flynn, K.

    1975-04-01

    A summary is presented of the radiochemical procedures and techniques currently in use by the Chemistry Division Nuclear Chemistry Group at Argonne National Laboratory for the analysis of radioactive samples. (U.S.)

  11. Soil Sampling Operating Procedure

    Science.gov (United States)

    EPA Region 4 Science and Ecosystem Support Division (SESD) document that describes general and specific procedures, methods, and considerations when collecting soil samples for field screening or laboratory analysis.

  12. Bariatric Surgery Procedures

    Science.gov (United States)

    ... Meetings of Interest Online Education Job Board CME Policies CBN Fellowship Certificate Research Grant Program Resources All Resources Approved Procedures Patient Safety Vignettes Dr. Mason Historical Library Governing Documents Guidelines Access and Insurance Position and ...

  13. Nuclear materials management procedures

    International Nuclear Information System (INIS)

    Veevers, K.; Silver, J.M.; Quealy, K.J.; Steege, E. van der.

    1987-10-01

    This manual describes the procedures for the management of nuclear materials and associated materials at the Lucas Heights Research Laboratories. The procedures are designed to comply with Australia's nuclear non-proliferation obligations to the International Atomic Energy Agency (IAEA), bilateral agreements with other countries and ANSTO's responsibilities under the Nuclear Non-Proliferation (Safeguards) Act, 1987. The manual replaces those issued by the Australian Atomic Energy Commission in 1959, 1960 and 1969

  14. Microbial reductive dehalogenation.

    Science.gov (United States)

    Mohn, W W; Tiedje, J M

    1992-01-01

    A wide variety of compounds can be biodegraded via reductive removal of halogen substituents. This process can degrade toxic pollutants, some of which are not known to be biodegraded by any other means. Reductive dehalogenation of aromatic compounds has been found primarily in undefined, syntrophic anaerobic communities. We discuss ecological and physiological principles which appear to be important in these communities and evaluate how widely applicable these principles are. Anaerobic communities that catalyze reductive dehalogenation appear to differ in many respects. A large number of pure cultures which catalyze reductive dehalogenation of aliphatic compounds are known, in contrast to only a few organisms which catalyze reductive dehalogenation of aromatic compounds. Desulfomonile tiedjei DCB-1 is an anaerobe which dehalogenates aromatic compounds and is physiologically and morphologically unusual in a number of respects, including the ability to exploit reductive dehalogenation for energy metabolism. When possible, we use D. tiedjei as a model to understand dehalogenating organisms in the above-mentioned undefined systems. Aerobes use reductive dehalogenation for substrates which are resistant to known mechanisms of oxidative attack. Reductive dehalogenation, especially of aliphatic compounds, has recently been found in cell-free systems. These systems give us an insight into how and why microorganisms catalyze this activity. In some cases transition metal complexes serve as catalysts, whereas in other cases, particularly with aromatic substrates, the catalysts appear to be enzymes. Images PMID:1406492

  15. 12 CFR 404.10 - Fee waivers or reductions.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Fee waivers or reductions. 404.10 Section 404.10 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.10 Fee waivers or reductions. (a) General...

  16. Wing Leading Edge Concepts for Noise Reduction

    Science.gov (United States)

    Shmilovich, Arvin; Yadlin, Yoram; Pitera, David M.

    2010-01-01

    This study focuses on the development of wing leading edge concepts for noise reduction during high-lift operations, without compromising landing stall speeds, stall characteristics or cruise performance. High-lift geometries, which can be obtained by conventional mechanical systems or morphing structures have been considered. A systematic aerodynamic analysis procedure was used to arrive at several promising configurations. The aerodynamic design of new wing leading edge shapes is obtained from a robust Computational Fluid Dynamics procedure. Acoustic benefits are qualitatively established through the evaluation of the computed flow fields.

  17. Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl.

    Science.gov (United States)

    Odai, H; Sasaki, K; Iwamatsu, A; Nakamoto, T; Ueno, H; Yamagata, T; Mitani, K; Yazaki, Y; Hirai, H

    1997-04-15

    -phosphorylated and associated with Shc and Bcr-Abl. These facts suggest that pp135 is a signaling molecule that has a unique enzymatic activity and should play an important role in the signaling pathway triggered by GM-CSF and in the transformation of hematopoietic cells caused by Bcr-Abl.

  18. Procedural learning and dyslexia.

    Science.gov (United States)

    Nicolson, R I; Fawcett, A J; Brookes, R L; Needle, J

    2010-08-01

    Three major 'neural systems', specialized for different types of information processing, are the sensory, declarative, and procedural systems. It has been proposed (Trends Neurosci., 30(4), 135-141) that dyslexia may be attributable to impaired function in the procedural system together with intact declarative function. We provide a brief overview of the increasing evidence relating to the hypothesis, noting that the framework involves two main claims: first that 'neural systems' provides a productive level of description avoiding the underspecificity of cognitive descriptions and the overspecificity of brain structural accounts; and second that a distinctive feature of procedural learning is its extended time course, covering from minutes to months. In this article, we focus on the second claim. Three studies-speeded single word reading, long-term response learning, and overnight skill consolidation-are reviewed which together provide clear evidence of difficulties in procedural learning for individuals with dyslexia, even when the tasks are outside the literacy domain. The educational implications of the results are then discussed, and in particular the potential difficulties that impaired overnight procedural consolidation would entail. It is proposed that response to intervention could be better predicted if diagnostic tests on the different forms of learning were first undertaken. 2010 John Wiley & Sons, Ltd.

  19. Procedural sedation analgesia

    Directory of Open Access Journals (Sweden)

    Sheta Saad

    2010-01-01

    Full Text Available The number of noninvasive and minimally invasive procedures performed outside of the operating room has grown exponentially over the last several decades. Sedation, analgesia, or both may be needed for many of these interventional or diagnostic procedures. Individualized care is important when determining if a patient requires procedural sedation analgesia (PSA. The patient might need an anti-anxiety drug, pain medicine, immobilization, simple reassurance, or a combination of these interventions. The goals of PSA in four different multidisciplinary practices namely; emergency, dentistry, radiology and gastrointestinal endoscopy are discussed in this review article. Some procedures are painful, others painless. Therefore, goals of PSA vary widely. Sedation management can range from minimal sedation, to the extent of minimal anesthesia. Procedural sedation in emergency department (ED usually requires combinations of multiple agents to reach desired effects of analgesia plus anxiolysis. However, in dental practice, moderate sedation analgesia (known to the dentists as conscious sedation is usually what is required. It is usually most effective with the combined use of local anesthesia. The mainstay of success for painless imaging is absolute immobility. Immobility can be achieved by deep sedation or minimal anesthesia. On the other hand, moderate sedation, deep sedation, minimal anesthesia and conventional general anesthesia can be all utilized for management of gastrointestinal endoscopy.

  20. Comparing the operators' behavior in conducting emergency operating procedures with the complexity of procedural steps

    International Nuclear Information System (INIS)

    Park, Jin Kyun; Jung, Won Dea

    2003-01-01

    Many kinds of procedures have been used to reduce the operators' workload throughout various industries. However, significant portion of accidents or incidents was caused by procedure related human errors that are originated from non-compliance of procedures. According to related studies, several important factors for non-compliance behavior have been identified, and one if them is the complexity of procedures. This means that comparing the change of the operators' behavior with the complexity of procedures may be meaningful for investigating plausible reasons for the operators' non-compliance behavior. In this study, emergency training records were collected using a full scope simulator in order to obtain data related to the operators' non-compliance behavior. And then, collected data are compared with the complexity of procedural steps. As the result, two remarkable relationships are found, which indicate that the operators' behavior could be reasonably characterized by the complexity of procedural steps. Thus, these relationships can be used as meaningful clues not only to scrutinize the reason of non-compliance behavior but also to suggest appropriate remedies for the reduction of non-compliance behavior that can result in procedure related human errors

  1. Potential for waste reduction

    International Nuclear Information System (INIS)

    Warren, J.L.

    1990-01-01

    The author focuses on wastes considered hazardous under the Resource Conservation and Recovery Act. This chapter discusses wastes that are of interest as well as the factors affecting the quantity of waste considered available for waste reduction. Estimates are provided of the quantities of wastes generated. Estimates of the potential for waste reduction are meaningful only to the extent that one can understand the amount of waste actually being generated. Estimates of waste reduction potential are summarized from a variety of government and nongovernment sources

  2. Anesthesia for radiologic procedures

    International Nuclear Information System (INIS)

    Forestner, J.E.

    1987-01-01

    Anesthetic techniques for neurodiagnostic studies and radiation therapy have been recently reviewed, but anesthetic involvement in thoracic and abdominal radiology has received little attention. Patient reactions to radiologic contrast media may be of concern to the anesthesiologist, who is often responsible for injecting these agents during diagnostic procedures, and thus is included in this discussion. Finally, the difficulties of administering anesthesia for magnetic resonance imaging (MRI) scans are outlined, in an effort to help anesthesiologist to anticipate problems with this new technologic development. Although there are very few indications for the use of general anesthesia for diagnostic radiologic studies in adults, most procedures performed with children, the mentally retarded, or the combative adult require either heavy sedation or general anesthesia. In selecting an anesthetic technique for a specific procedure, both the patient's disease process and the requirements of the radiologist must be carefully balanced

  3. [Conversional and endoscopic procedures following bariatric surgery].

    Science.gov (United States)

    Zorron, R; Bothe, C; Junghans, T; Pratschke, J; Benzing, C; Krenzien, F

    2016-10-01

    The Roux-en-Y gastric bypass (RYGB) is the therapy of choice in bariatric surgery. Sleeve gastrectomy and gastric banding are showing higher rates of treatment failure, reducing obesity-associated morbidity and body weight insufficiently. Moreover, gastroesophageal reflux disease (GERD) can occur refractory to medication. Therefore, a laparoscopic conversion to RYGB can be reasonable as long as specific conditions are fulfilled.Endoscopic procedures are currently being applied to revise bariatric procedures. Therapy failure following RYGB occurs in up to 20 % of cases. Transoral outlet reduction is the minimally invasive method of choice to reduce gastrojejunal anastomosis of the alimentary limb. The diameter of a gastric sleeve can be unwantedly enlarged as well; that can be reduced by placement of a longitudinal full-thickness suture.Severe hypoglycemic episodes can be present in patients following RYGB. Hypoglycemic episodes have to be diagnosed first and can be treated conventionally. Alternatively, a laparoscopic approach according to Branco-Zorron can be used for non-responders. Hypoglycemic episodes can thus be prevented and body weight reduction can be assured.Conversional and endoscopic procedures can be used in patients with treatment failure following bariatric surgery. Note that non-invasive approaches should have been applied intensively before a revisional procedure is performed.

  4. Alternative Antimicrobial Commercial Egg Washing Procedures.

    Science.gov (United States)

    Hudson, Lauren K; Harrison, Mark A; Berrang, Mark E; Jones, Deana R

    2016-07-01

    Commercial table eggs are washed prior to packaging. Standard wash procedures use an alkaline pH and warm water. If a cool water method could be developed that would still provide a microbiologically safe egg, the industry may save energy costs associated with water heating. Four wash procedures were evaluated for Salmonella reduction: pH 11 at 48.9°C (industry standard), pH 11 at ambient temperature (∼20°C), pH 6 at 48.9°C, and pH 6 at ambient temperature. Alkaline washes contained potassium hydroxide-based detergent, while pH 6 washes contained approximately 200 ppm of chlorine and a proprietary chlorine stabilizer (T-128). When eggs were inoculated by immersion in a cell suspension of Salmonella Enteritidis and Salmonella Typhimurium, all treatments resulted in a slight and similar reduction of Salmonella numbers (approximately 0.77 log CFU/ml of shell emulsion reduction). When eggs were inoculated by droplet on the shell surface, Salmonella counts were reduced by approximately 5 log CFU when washed with chlorine plus the chlorine stabilizer at both temperatures and with the alkaline wash at the high temperature. The reductions in Salmonella by these treatments were not significantly (P > 0.05) different from each other but were significantly (P pH 11 warm water wash and may be a viable option to reduce cost, increase shelf life, and slow pathogen growth in and on shell eggs.

  5. Motive Criminal Procedure Evidence

    Directory of Open Access Journals (Sweden)

    В. В. Вапнярчук

    2015-03-01

    Full Text Available In the article the need for such a level of mental regulation of behavior of proving motivation. The latter refers to internal motivation conscious entity Criminal Procedure proof, due to specific needs, interests and goals that cause a person to act rishymist. Detailed attention is given to the first two determinants, namely the nature of needs and interests. In particular, analyzes highlighted in the literature variety of needs (physiological, ekzistentsionalni, social, prestige, cognitive, aesthetic and spiritual and the manifestation of some of them in the criminal procedural proof.

  6. Intussusception in children: Hydrostatic reduction under US guidance - own experience

    International Nuclear Information System (INIS)

    Roik, D.; Brzewski, M.; Biejat, A.; Marcinski, M.

    2008-01-01

    Intussusception in children is a common abdominal emergency. Recent years have brought a New promising method of nonsurgical invagination treatment, hydrostatic reduction under sonographic (US) guidance. The major advantage of this method is lack of the ionized radiation. The aim of our study is to asses the safety and effectiveness of hydrostatic reduction under US guidance used as a first choice method of invagination treatment in our department. >From July 2006 to December 2007, 33 procedures of hydrostatic reduction under US guidance were performed in 27 children, aged from 7 months to 6 years and 10 months. The procedure was performed in US room by radiologist and surgeon with the use of self-constructed set for saline enema. The sedation of patient was routinely performed. The initial procedure was effective in 23 patients (pts) (85%). In 5 pts the recurrence of intussusception occurred and in 3 of them next attempt of the reduction was successful. In 4 cases the initial procedures failed, and those children were operated. Total amount of 6 pts underwent an operation. We do not observe any complications connected with the procedure. Hydrostatic reduction of children intusussception under US-guidance is safe and effective method. Our initial results meet the recommended limits of successful reduction rates. It encouraged us to evaluation and further implementation of this method. Water enema is a first choice method of invagination treatment in our hospital. (authors)

  7. Clinical Efficacy and Safety of First-Line Dasatinib Therapy and the Relevance of Velocity of BCR-ABL1 Transcript Decline for Achievement of Molecular Responses in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Report from the Juntendo Yamanashi Cooperative Study Group.

    Science.gov (United States)

    Takaku, Tomoiku; Iriyama, Noriyoshi; Mitsumori, Toru; Sato, Eriko; Gotoh, Akihiko; Kirito, Keita; Noguchi, Masaaki; Koike, Michiaki; Sakamoto, Junichi; Oba, Koji; Komatsu, Norio

    2018-01-01

    The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses. The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels. Thirty-two patients with chronic-phase CML (CML-CP) were enrolled and 30 received 100 mg dasatinib once daily. At 24 months of follow-up, 21 (72%) and 24 (83%) patients achieved an MMR by 12 and 24 months, respectively; the rates of a deep molecular response (DMR) by 12 and 24 months were 48 and 59%, respectively. A shorter halving time of BCR-ABL1 transcripts (≤10.6 days) accurately predicted both an MMR and a DMR. The incidence of pleural effusion was 50%. Our study reconfirmed the efficacy and safety of dasatinib treatment in Japanese patients with newly diagnosed CML-CP. In addition, the usefulness of the halving time of BCR-ABL1 transcripts was validated. These data emphasize the significance of an early treatment response in achieving a DMR during dasatinib therapy. © 2017 S. Karger AG, Basel.

  8. Breast reduction (mammoplasty) - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100189.htm Breast reduction (mammoplasty) - series—Indications To use the sharing features ... Lickstein, MD, FACS, specializing in cosmetic and reconstructive plastic surgery, Palm Beach Gardens, FL. Review provided by ...

  9. Medical Errors Reduction Initiative

    National Research Council Canada - National Science Library

    Mutter, Michael L

    2005-01-01

    The Valley Hospital of Ridgewood, New Jersey, is proposing to extend a limited but highly successful specimen management and medication administration medical errors reduction initiative on a hospital-wide basis...

  10. Microbial reductive dehalogenation.

    OpenAIRE

    Mohn, W W; Tiedje, J M

    1992-01-01

    A wide variety of compounds can be biodegraded via reductive removal of halogen substituents. This process can degrade toxic pollutants, some of which are not known to be biodegraded by any other means. Reductive dehalogenation of aromatic compounds has been found primarily in undefined, syntrophic anaerobic communities. We discuss ecological and physiological principles which appear to be important in these communities and evaluate how widely applicable these principles are. Anaerobic commun...

  11. Air Layer Drag Reduction

    Science.gov (United States)

    Ceccio, Steven; Elbing, Brian; Winkel, Eric; Dowling, David; Perlin, Marc

    2008-11-01

    A set of experiments have been conducted at the US Navy's Large Cavitation Channel to investigate skin-friction drag reduction with the injection of air into a high Reynolds number turbulent boundary layer. Testing was performed on a 12.9 m long flat-plate test model with the surface hydraulically smooth and fully rough at downstream-distance-based Reynolds numbers to 220 million and at speeds to 20 m/s. Local skin-friction, near-wall bulk void fraction, and near-wall bubble imaging were monitored along the length of the model. The instrument suite was used to access the requirements necessary to achieve air layer drag reduction (ALDR). Injection of air over a wide range of air fluxes showed that three drag reduction regimes exist when injecting air; (1) bubble drag reduction that has poor downstream persistence, (2) a transitional regime with a steep rise in drag reduction, and (3) ALDR regime where the drag reduction plateaus at 90% ± 10% over the entire model length with large void fractions in the near-wall region. These investigations revealed several requirements for ALDR including; sufficient volumetric air fluxes that increase approximately with the square of the free-stream speed, slightly higher air fluxes are needed when the surface tension is reduced, higher air fluxes are required for rough surfaces, and the formation of ALDR is sensitive to the inlet condition.

  12. 76 FR 62092 - Filing Procedures

    Science.gov (United States)

    2011-10-06

    ... INTERNATIONAL TRADE COMMISSION Filing Procedures AGENCY: International Trade Commission. ACTION: Notice of issuance of Handbook on Filing Procedures. SUMMARY: The United States International Trade Commission (``Commission'') is issuing a Handbook on Filing Procedures to replace its Handbook on Electronic...

  13. A novel dic (17;18 (p13.1;q11.2 with loss of TP53 and BCR/ABL rearrangement in an Imatinib resistant chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Al-achkar Walid

    2012-08-01

    Full Text Available Abstract Background The so-called Philadelphia (Ph chromosome is present in more than 90% of chronic myeloid leukemia (CML cases. It results in juxtaposition of the 5′ part of the BCR gene on chromosome 22 to the 3′ part of the ABL gene on chromosome 9. Since the majority of CML cases are currently treated with Imatinib, variant rearrangements in general have no specific prognostic significance, although the mechanisms involved in resistance to therapy have yet to be investigated. The T315I mutation within the abl-gene is the most frequent one associated with resistance to tyrosine kinase inhibitors. Results This study evaluated a Ph chromosome positive CML case resistant to imatinib mesylate. A dic(17;18, loss of TP53 gene, co-expression of b2a2 and b3a2 fusions transcript and a T315I mutation were found. Conclusions We reported here a novel case of a Ph chromosome positive CML with a secondary abnormality [dic(17;18], resulting to Glivec resistance but good response to nilotinib. The dic(17;18 might be a marker for poor prognosis in CML. Our finding indicated for an aggressive progression of the disease. The patient died under the treatment due to unknown reasons.

  14. Electronic procedure distribution

    International Nuclear Information System (INIS)

    Slone, B.J. III; Richardson, C.E.

    1993-01-01

    Printed procedures can offer a mix of text and graphic information that improves readability and increases understanding. A typical procedure uses illustrations and graphics to clarify concepts, a variety of type styles and weights to make it easier to find different topics and sections, white space to improve readability, and familiar navigational clues such as page numbers and topic headers. Initially, electronic procedure systems had limited typeface options, often only a single typeface, with no capability for enhancing readability by varying type size bolding, italicizing, or underlining, and no ability to include graphics. Even recently, many text-only electronic procedures were originally created in a modern What-You-See-Is-What-You-Get (WYSI-WYG) document authoring system, only to be converted to pages and pages of plain type for electronic distribution. Given the choice of paper or on-line producers, most users have chosen paper for its readability. But current-generation electronic document systems that use formatted text and embedded graphics offer users vastly improved readability. Further, they are offering ever-better search tools to enable rapid location of material of interest

  15. The nuclear licensing procedure

    International Nuclear Information System (INIS)

    Wagner, H.

    1976-01-01

    To begin with, the present nuclear licensing procedure is illustrated by a diagram. The relationship between the state and the Laender, the various experts (GRS - IRS + LRA -, TUEV, DWD, university institutes, firms of consulting engineers, etc), participation of the public, e.g. publication of the relevant documents, questions, objections (made by individuals or by groups such as citizens' initiatives), public discussion, official notice, appeals against the decision, the right of immediate execution of the decision are shortly dealt with. Finally, ways to improve the licensing procedure are discussed, from the evaluation of the documents to be submitted, published, and examined by the authorities (and their experts) up to an improvement of the administrative procedure. An improved licensing procedure should satisfy the well-founded claims of the public for more transparency as well as the equally justifiable claims of industry and utilities in order to ensure that the citizens' legal right to have safe and adequate electric power is guaranteed. The updated energy programme established by the Federal Government is mentioned along with the effectiveness of dealing with nuclear problems on the various levels of a Land government. (orig.) [de

  16. OCRWM international procedures

    International Nuclear Information System (INIS)

    1986-03-01

    These international procedures provide guidance and assistance for the Office of Civilian Radioactive Waste Management (OCRWM) and for OCRWM Project Offices, contractors and subcontractors in conducting international activities. They supplement the relevant Department of Energy (DOE) orders (which are referenced), not supplant them

  17. Pneumomediastinum after odontologic procedure

    International Nuclear Information System (INIS)

    Olivella C, Fabio Alejandro; Bermudez G, Mary; Hidalgo M, Patricia; Sanchez M, Jully Mariana; Solarte R, Ivan; Uriza C, Felipe

    2005-01-01

    The sudden increase in alveolar pressure is a frequent cause of pneumomediastinum, but there are other reasons that could lead to it such as airway or esophagus trauma. The pneumomediastinum, which has been produced after dental procedures, is very rare and product deserves special attention by dentists and medical personnel in order to get its soon recognition and handling

  18. Educational Accounting Procedures.

    Science.gov (United States)

    Tidwell, Sam B.

    This chapter of "Principles of School Business Management" reviews the functions, procedures, and reports with which school business officials must be familiar in order to interpret and make decisions regarding the school district's financial position. Among the accounting functions discussed are financial management, internal auditing,…

  19. Robust procedures in chemometrics

    DEFF Research Database (Denmark)

    Kotwa, Ewelina

    properties of the analysed data. The broad theoretical background of robust procedures was given as a very useful supplement to the classical methods, and a new tool, based on robust PCA, aiming at identifying Rayleigh and Raman scatters in excitation-mission (EEM) data was developed. The results show...

  20. IXM gas sampling procedure

    International Nuclear Information System (INIS)

    Pingel, L.A.

    1995-01-01

    Ion Exchange Modules (IXMs) are used at the 105-KE and -KW Fuel Storage Basins to control radionuclide concentrations in the water. A potential safety concern relates to production of hydrogen gas by radiolysis of the water trapped in the ion exchange media of spent IXMs. This document provides a procedure for sampling the gases in the head space of the IXM

  1. 3. Procedures and Recursion

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 6. Algorithms Procedures and Recursion. R K Shyamasundar. Series Article Volume 1 ... Author Affiliations. R K Shyamasundar1. Computer Science Group, Tata Institute of Fundamental Research, Homi Bhabha Road Mumbai 400 005, India.

  2. The TOMAX-procedure

    NARCIS (Netherlands)

    Overgoor, M.L.E.

    2015-01-01

    Most patients with a low spinal lesion (LSL) have intact erectile function but no penile sensation, which can lead to frustration. To tackle this problem, we designed TOMAX, TOMAXimize sensation, sexuality and quality of life, a surgical procedure in which a functional "groin” nerve is connected to

  3. Experiments with Cloze Procedure

    Science.gov (United States)

    Evans, Gordon; Haastrup, Kirsten

    1976-01-01

    The Nordic Test Development Group prepared proficiency tests of English designed to provide reliable information on which to base decisions as to whether a candidate would be able to function in a job as described or whether he could be trained to do so. Two subtests used a modified cloze procedure. (Author/CFM)

  4. Formalizing physical security procedures

    NARCIS (Netherlands)

    Meadows, C.; Pavlovic, Dusko

    Although the problems of physical security emerged more than 10,000 years before the problems of computer security, no formal methods have been developed for them, and the solutions have been evolving slowly, mostly through social procedures. But as the traffic on physical and social networks is now

  5. Pediatric radiology fellows' experience with intussusception reduction

    International Nuclear Information System (INIS)

    Stein-Wexler, Rebecca; Bateni, Cyrus; Wootton-Gorges, Sandra L.; Li, Chin-Shang

    2011-01-01

    Intussusception reduction allows young children to avoid surgery. However, graduating residents have had relatively little training in intussusception reduction and, for the most part, consider themselves ill-prepared to perform this procedure. The goal of this study was to assess the extent of training in intussusception reduction during one year of a pediatric radiology fellowship and to determine whether graduating fellows consider themselves adequately trained in this technique. Pediatric radiology fellows were surveyed during June 2010 and asked to characterize their fellowship, to indicate the number of intussusception reductions performed (both the total number and those performed with faculty oversight but without active faculty involvement), and to assess the adequacy of their training. There were 31 responses, representing almost 1/3 of current fellows. Pediatric radiology fellows perform on average 6.9 reductions, 3.8 of which are with faculty oversight but without active faculty involvement. Ninety percent consider themselves well-trained in the technique, whereas 10% are uncertain (none consider their training inadequate). Almost all pediatric radiology fellows consider their training in intussusception reduction to be adequate. (orig.)

  6. Use of oxidative and reducing vapor generation for reducing the detection limits of iodine in biological samples by inductively coupled plasma atomic emission spectrometry

    International Nuclear Information System (INIS)

    Vtorushina, Eh.A.; Saprykin, A.I.; Knapp, G.

    2009-01-01

    Procedures of microwave combustion in an oxygen flow and microwave acid decomposition of biological samples were optimized for the subsequent determination of iodine. A new method was proposed for the generation of molecular iodine from periodate iona using hydrogen peroxide as a reductant. Procedures were developed for determining iodine in biological samples by inductively coupled plasma atomic emission spectrometry (ICP-AES) using oxidative and reducing vapor generation; these allowed the detection limit for iodine to be lowered by 3-4 orders of magnitude. The developed procedures were used to analyze certified reference materials of milk (Skim Milk Powder BCR 150) and seaweed (Sea Lettuce BCR 279) and a Supradyn vitamin complex

  7. Catalyzed reduction of nitrate in aqueous solutions

    International Nuclear Information System (INIS)

    Haas, P.A.

    1994-08-01

    Sodium nitrate and other nitrate salts in wastes is a major source of difficulty for permanent disposal. Reduction of nitrate using aluminum metal has been demonstrated, but NH 3 , hydrazine, or organic compounds containing oxygen would be advantageous for reduction of nitrate in sodium nitrate solutions. Objective of this seed money study was to determine minimum conditions for reduction. Proposed procedure was batchwise heating of aqueous solutions in closed vessels with monitoring of temperatures and pressures. A simple, convenient apparatus and procedure were demonstrated for observing formation of gaseous products and collecting samples for analyses. The test conditions were 250 degree C and 1000 psi max. Any useful reduction of sodium nitrate to sodium hydroxide as the primary product was not found. The nitrate present at pHs 3 or NH 4 NO 3 is easily decomposed, and the effect of nitromethane at these low pHs was confirmed. When acetic acid or formic acid was added, 21 to 56% of the nitrate in sodium nitrate solutions was reduced by methanol or formaldehyde. With hydrazine and acetic acid, 73 % of the nitrate was decomposed to convert NaNO 3 to sodium acetate. With hydrazine and formic acid, 36% of the nitrate was decomposed. If these products are more acceptable for final disposal than sodium nitrate, the reagents are cheap and the conversion conditions would be practical for easy use. Ammonium acetate or formate salts did not significantly reduce nitrate in sodium nitrate solutions

  8. Dose reduction at nuclear power plants

    International Nuclear Information System (INIS)

    Baum, J.W.; Dionne, B.J.

    1983-01-01

    The collective dose equivalent at nuclear power plants increased from 1250 rem in 1969 to nearly 54,000 rem in 1980. This rise is attributable primarily to an increase in nuclear generated power from 1289 MW-y to 29,155 MW-y; and secondly, to increased average plant age. However, considerable variation in exposure occurs from plant to plant depending on plant type, refueling, maintenance, etc. In order to understand the factors influencing these differences, an investigation was initiated to study dose-reduction techniques and effectiveness of as low as reasonably achievable (ALARA) planning at light water plants. Objectives are to: identify high-dose maintenance tasks and related dose-reduction techniques; investigate utilization of high-reliability, low-maintenance equipment; recommend improved radioactive waste handling equipment and procedures; examine incentives for dose reduction; and compile an ALARA handbook

  9. Cancer pancreatis, diagnostic procedures

    International Nuclear Information System (INIS)

    Graadal, Oe.; Schlichting, E.; Aasen, A.O.; Stadaas, J.O.

    1990-01-01

    151 patients treated for carcinoma of the pancreas at Ullevaal Hospital (Oslo University) during the period 1980-89 were studied. The most common initial symptom was abdominal pain. Other frequent debut symptoms were loss of weight and jaundice. ERCP and PTC were found to be the best diagnostic procedures. CT or ultrasonography were normal in 10-20% of the patients. Nearly all tumors of the pancreas were found by the ERCP procedure. Also angiography was used to evaluate operability of the pancreas tumor, but was found to be a very uncertain diagnostic method. This method will not be used in the future evaluation of patients with cancer of the pancreas. 13 refs., 1 fig., 2 tabs

  10. Subsea HIPPS design procedure

    International Nuclear Information System (INIS)

    Aaroe, R.; Lund, B.F.; Onshus, T.

    1995-01-01

    The paper is based on a feasibility study investigating the possibilities of using a HIPPS (High Integrity Pressure Protection System) to protect a subsea pipeline that is not rated for full wellhead shut-in pressure. The study was called the Subsea OPPS Feasibility Study, and was performed by SINTEF, Norway. Here, OPPS is an acronym for Overpressure Pipeline Protection System. A design procedure for a subsea HIPPS is described, based on the experience and knowledge gained through the ''Subsea OPPS Feasibility Study''. Before a subsea HIPPS can be applied, its technical feasibility, reliability and profitability must be demonstrated. The subsea HIPPS design procedure will help to organize and plan the design activities both with respect to development and verification of a subsea HIPPS. The paper also gives examples of how some of the discussed design steps were performed in the Subsea OPPS Feasibility Study. Finally, further work required to apply a subsea HIPPS is discussed

  11. Quantum theory without reduction

    International Nuclear Information System (INIS)

    Cini, Marcello; Levy-Leblond, J.-M.

    1990-01-01

    Quantum theory offers a strange, and perhaps unique, case in the history of science. Although research into its roots has provided important results in recent years, the debate goes on. Some theorists argue that quantum theory is weakened by the inclusion of the so called 'reduction of the state vector' in its foundations. Quantum Theory without Reduction presents arguments in favour of quantum theory as a consistent and complete theory without this reduction, and which is capable of explaining all known features of the measurement problem. This collection of invited contributions defines and explores different aspects of this issue, bringing an old debate into a new perspective, and leading to a more satisfying consensus about quantum theory. (author)

  12. Measuring mandibular ridge reduction

    International Nuclear Information System (INIS)

    Steen, W.H.A.

    1984-01-01

    This thesis investigates the mandibular reduction in height of complete denture wearers and overdenture wearers. To follow this reduction in the anterior region as well as in the lateral sections of the mandible, an accurate and reproducible measuring method is a prerequisite. A radiologic technique offers the best chance. A survey is given of the literature concerning the resorption process after the extraction of teeth. An oblique cephalometric radiographic technique is introduced as a promising method to measure mandibular ridge reduction. The reproducibility and the accuracy of the technique are determined. The reproducibility in the positioning of the mandible is improved by the introduction of a mandibular support which permits a precise repositioning of the edentulous jaw, even after long periods of investigation. (Auth.)

  13. Headache and endovascular procedures.

    Science.gov (United States)

    de Biase, Stefano; Longoni, Marco; Gigli, Gian Luigi; Agostoni, Elio

    2017-05-01

    The International Classification of Headache Disorders (ICHD-3 beta) includes headache attributed to intracranial endovascular procedures (EVPs). The aim of this review is to describe the clinical and pathophysiological aspects of headache related to vascular lesions and EVPs. Current studies regarding this issue are contradictory, although generally favouring headache improvement after EVPs. Further large studies are needed to adequately assess the effect of EVPs on headache.

  14. Internal Control Organization Procedure

    OpenAIRE

    Radu Dorin Lenghel

    2013-01-01

    Internal control represents the totality of policies and procedures adopted by management, which contribute: to the fulfilment of managerial objectives, to the prevention and detection of frauds or errors, to the accuracy and exhaustiveness of accounting entries, as well as to the preparation in due course of financial accounting information. Internal control represents a managerial instrument which assures the fulfilment of objectives of the entity, being an ongoing process in which administ...

  15. Analytical Procedures for Testability.

    Science.gov (United States)

    1983-01-01

    Beat Internal Classifications", AD: A018516. "A System of Computer Aided Diagnosis with Blood Serum Chemistry Tests and Bayesian Statistics", AD: 786284...6 LIST OF TALS .. 1. Truth Table ......................................... 49 2. Covering Problem .............................. 93 3. Primary and...quential classification procedure in a coronary care ward is evaluated. In the toxicology field "A System of Computer Aided Diagnosis with Blood Serum

  16. The TOMAX-procedure

    OpenAIRE

    Overgoor, M.L.E.

    2015-01-01

    Most patients with a low spinal lesion (LSL) have intact erectile function but no penile sensation, which can lead to frustration. To tackle this problem, we designed TOMAX, TOMAXimize sensation, sexuality and quality of life, a surgical procedure in which a functional "groin” nerve is connected to the non-functional “penile” nerve on one side to bypass the LSL. Our goal was to increase LSL patients’ sexual health by restoring penile sensation: we show that TOMAX can achieve dramatic improvem...

  17. Start-up procedure

    International Nuclear Information System (INIS)

    Marchl, A.; Krebs, W.D.; Aleite, W.

    1975-01-01

    The start-up procedure will be shown on a pressurized water reactor, although most of the activities will occur similarly in other reactor types. The commissioning time can be divided into 5 sections, the phases A to E together lasting 26 months. Subsequently there are a test run of one month and the handling-over of the plant to the operator. A survey of the commissioning sections with several important main events is shown. (orig./TK) [de

  18. SHERPA: A systematic human error reduction and prediction approach

    International Nuclear Information System (INIS)

    Embrey, D.E.

    1986-01-01

    This paper describes a Systematic Human Error Reduction and Prediction Approach (SHERPA) which is intended to provide guidelines for human error reduction and quantification in a wide range of human-machine systems. The approach utilizes as its basic current cognitive models of human performance. The first module in SHERPA performs task and human error analyses, which identify likely error modes, together with guidelines for the reduction of these errors by training, procedures and equipment redesign. The second module uses a SARAH approach to quantify the probability of occurrence of the errors identified earlier, and provides cost benefit analyses to assist in choosing the appropriate error reduction approaches in the third module

  19. Antibiotic prophylaxis in obstetric procedures.

    Science.gov (United States)

    van Schalkwyk, Julie; Van Eyk, Nancy

    2010-09-01

    prophylactic antibiotics at the time of postpartum dilatation and curettage for retained products of conception. (III) 4. Available evidence does not support the use of prophylactic antibiotics to reduce infectious morbidity following elective or emergency cerclage. (II-3) RECOMMENDATIONS: 1. All women undergoing elective or emergency Caesarean section should receive antibiotic prophylaxis. (I-A) 2. The choice of antibiotic for Caesarean section should be a single dose of a first-generation cephalosporin. If the patient has a penicillin allergy, clindamycin or erythromycin can be used. (I-A) 3. The timing of prophylactic antibiotics for Caesarean section should be 15 to 60 minutes prior to skin incision. No additional doses are recommended. (I-A) 4. If an open abdominal procedure is lengthy (>3 hours) or estimated blood loss is greater than 1500 mL, an additional dose of the prophylactic antibiotic may be given 3 to 4 hours after the initial dose. (III-L) 5. Prophylactic antibiotics may be considered for the reduction of infectious morbidity associated with repair of third and fourth degree perineal injury. (I-B) 6. In patients with morbid obesity (BMI>35), doubling the antibiotic dose may be considered. (III-B) 7. Antibiotics should not be administered solely to prevent endocarditis for patients who undergo an obstetrical procedure of any kind. (III-E).

  20. REDUCTIONS WITHOUT REGRET: SUMMARY

    Energy Technology Data Exchange (ETDEWEB)

    Swegle, J.; Tincher, D.

    2013-09-16

    This paper briefly summarizes the series in which we consider the possibilities for losing, or compromising, key capabilities of the U.S. nuclear force in the face of modernization and reductions. The first of the three papers takes an historical perspective, considering capabilities that were eliminated in past force reductions. The second paper is our attempt to define the needed capabilities looking forward in the context of the current framework for force modernization and the current picture of the evolving challenges of deterrence and assurance. The third paper then provides an example for each of our undesirable outcomes: the creation of roach motels, box canyons, and wrong turns.

  1. Vibration for Pain Reduction in a Plastic Surgery Clinic.

    Science.gov (United States)

    Eichhorn, Mitchell George; Karadsheh, Murad Jehad; Krebiehl, Johanna Ruth; Ford, Dawn Marie; Ford, Ronald D

    2016-01-01

    Patients can experience significant pain during routine procedures in the plastic surgery clinic. Methods for clinical pain reduction are often impractical, time-consuming, or ineffective. Vibration is a safe, inexpensive, and highly applicable modality for pain reduction that can be readily utilized for a wide variety of procedures. This study evaluated the use of vibration as a viable pain-reduction strategy in the clinical plastic surgery setting. Patients requiring at least 2 consecutive procedures that are considered painful were enrolled in the study. These included injections, staple removal, and suture removal. In the same patient, one half of the procedures were performed without vibration and the other half with vibration. After completing the procedures, the patients rated their pain with vibration and without vibration. The patient and the researcher also described the experience with a short questionnaire. Twenty-eight patients were enrolled in the study. Patients reported significantly less pain on the Numeric Rating Scale pain scale when vibration was used compared with the control group (p reduction. It significantly reduces the pain experienced by patients during minor office procedures. Given its practicality and ease of use, it is a welcome tool in the plastic surgery clinic.

  2. Reduction of dinitrogen ligands

    International Nuclear Information System (INIS)

    Richards, R.L.

    1983-01-01

    Processes of dinitrogen ligand reduction in complexes of transition metals are considered. The basic character of the dinitrogen ligand is underlined. Data on X-ray photoelectronic spectroscopy and intensities of bands ν (N 2 ) in IR-spectra of nitrogen complexes are given. The mechanism of protonation of an edge dinitrogen ligand is discussed. Model systems and mechanism of nitrogenogenase are compared

  3. Infinitary Combinatory Reduction Systems

    DEFF Research Database (Denmark)

    Ketema, Jeroen; Simonsen, Jakob Grue

    2011-01-01

    We define infinitary Combinatory Reduction Systems (iCRSs), thus providing the first notion of infinitary higher-order rewriting. The systems defined are sufficiently general that ordinary infinitary term rewriting and infinitary ¿-calculus are special cases. Furthermore,we generalise a number...

  4. Galactorrhea after reduction mammaplasty

    NARCIS (Netherlands)

    Schuurman, A. H.; Assies, J.; van der Horst, C. M.; Bos, K. E.

    1993-01-01

    A case of extremely painful swelling of the breasts following a reduction mammaplasty is presented. There were no signs of an abscess or hematoma. A milky white fluid due to galactorrhea was evacuated at operation, and further galactorrhea was inhibited by medication. The pathogenesis of

  5. (MTT) dye reduction assay.

    African Journals Online (AJOL)

    to inhibit proliferation of HeLa cells was determined using the 3443- dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) dye reduction assay. Extracts from roots of Agathisanthemum bojeri, Synaptolepis kirkii and Zanha africana and the leaf extract of Physalis peruviana at a concentration of 10 pg/ml inhibited cell ...

  6. Streaming Reduction Circuit

    NARCIS (Netherlands)

    Gerards, Marco Egbertus Theodorus; Kuper, Jan; Kokkeler, Andre B.J.; Molenkamp, Egbert

    2009-01-01

    Reduction circuits are used to reduce rows of floating point values to single values. Binary floating point operators often have deep pipelines, which may cause hazards when many consecutive rows have to be reduced. We present an algorithm by which any number of consecutive rows of arbitrary lengths

  7. Lake Nasser evaporation reduction study

    Directory of Open Access Journals (Sweden)

    Hala M.I. Ebaid

    2010-10-01

    Full Text Available This study aims to evaluate the reduction of evaporation of Lake Nasser’s water caused by disconnecting (fully or partially some of its secondary channels (khors. This evaluation integrates remote sensing, Geographic Information System (GIS techniques, aerodynamic principles, and Landsat7 ETM+ images. Three main procedures were carried out in this study; the first derived the surface temperature from Landsat thermal band; the second derived evaporation depth and approximate evaporation volume for the entire lake, and quantified evaporation loss to the secondary channels’ level over one month (March by applied aerodynamic principles on surface temperature of the raster data; the third procedure applied GIS suitability analysis to determine which of these secondary channels (khors should be disconnected. The results showed evaporation depth ranging from 2.73 mm/day at the middle of the lake to 9.58 mm/day at the edge. The evaporated water-loss value throughout the entire lake was about 0.86 billion m3/month (March. The analysis suggests that it is possible to save an approximate total evaporation volume loss of 19.7 million m3/month (March, and thus 2.4 billion m3/year, by disconnecting two khors with approximate construction heights of 8 m and 15 m. In conclusion, remote sensing and GIS are useful for applications in remote locations where field-based information is not readily available and thus recommended for decision makers remotely planning in water conservation and management.

  8. Coal pillar design procedures

    CSIR Research Space (South Africa)

    York, G

    2000-03-01

    Full Text Available Final Project Report Coal pillar design procedures G. York, I. Canbulat, B.W. Jack Research agency: CSIR Mining Technology Project number: COL 337 Date: March 2000 2 Executive Summary Examination of collapsed pillar cases outside of the empirical... in strength occurs with increasing specimen size. 45 40 35 30 25 20 15 10 5 0 20 40 60 80 100 120 140 160 UNIAX IA L COMPR EHEN SIV E S TR ENG TH (M Pa ) CUBE SIZE (cm) Figure 1...

  9. Emergency procedures in London

    International Nuclear Information System (INIS)

    Cree, D.

    1984-01-01

    This chapter discusses the following: emergency services (fire brigade, ambulance and police) that would be involved in dealing with an accident to a nuclear fuel flask in transport through London, with special reference to procedures used by the Metropolitan Police; geographical area covered by Metropolitan Police; initiation of action; decision whether to evacuate the area of the accident; examples of action taken to deal with non-radiation accidents (in absence of any example of relevant radiation accident); specific instructions, or advice, to police relating to the movement of irradiated fuel; training exercises. (U.K.)

  10. Expression of p89c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells

    International Nuclear Information System (INIS)

    Manzotti, G; Mariani, S A; Corradini, F; Bussolari, R; Cesi, V; Vergalli, J; Ferrari-Amorotti, G; Fragliasso, V; Soliera, A R; Cattelani, S; Raschellà, G; Holyoake, T L; Calabretta, B

    2012-01-01

    The c-Myb gene encodes the p75 c-Myb isoform and less-abundant proteins generated by alternatively spliced transcripts. Among these, the best known is p c-Mybex9b , which contains 121 additional amino acids between exon 9 and 10, in a domain involved in protein–protein interactions and negative regulation. In hematopoietic cells, expression of p c-Mybex9b accounts for 10–15% of total c-Myb; these levels may be biologically relevant because modest changes in c-Myb expression affects proliferation and survival of leukemic cells and lineage choice and frequency of normal hematopoietic progenitors. In this study, we assessed biochemical activities of p c-Mybex9b and the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75 c-Myb , p c-Mybex9b is more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of p c-Mybex9b enhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of p c-Mybex9b reduced proliferation and colony formation, enhanced IM sensitivity of K562 cells and markedly suppressed colony formation of CML CD34 + cells, without affecting the levels of p75 c-Myb . Together, these studies indicate that expression of the low-abundance p c-Mybex9b isoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells

  11. Regulations and Procedures Manual

    Energy Technology Data Exchange (ETDEWEB)

    Young, Lydia J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2011-07-25

    The purpose of the Regulations and Procedures Manual (RPM) is to provide LBNL personnel with a reference to University and Lawrence Berkeley National Laboratory (LBNL or Laboratory) policies and regulations by outlining normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory organizations. Much of the information in this manual has been condensed from detail provided in LBNL procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. RPM sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the LBNL organization responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which organization is responsible for a policy, please contact Requirements Manager Lydia Young or the RPM Editor.

  12. Regulations and Procedures Manual

    Energy Technology Data Exchange (ETDEWEB)

    Young, Lydia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2010-09-30

    The purpose of the Regulations and Procedures Manual (RPM) is to provide Laboratory personnel with a reference to University and Lawrence Berkeley National Laboratory policies and regulations by outlining the normal practices and answering most policy questions that arise in the day-to-day operations of Laboratory departments. Much of the information in this manual has been condensed from detail provided in Laboratory procedure manuals, Department of Energy (DOE) directives, and Contract DE-AC02-05CH11231. This manual is not intended, however, to replace any of those documents. The sections on personnel apply only to employees who are not represented by unions. Personnel policies pertaining to employees represented by unions may be found in their labor agreements. Questions concerning policy interpretation should be directed to the department responsible for the particular policy. A link to the Managers Responsible for RPM Sections is available on the RPM home page. If it is not clear which department should be called, please contact the Associate Laboratory Director of Operations.

  13. Spontaneous wave packet reduction

    International Nuclear Information System (INIS)

    Ghirardi, G.C.

    1994-06-01

    There are taken into account the main conceptual difficulties met by standard quantum mechanics in dealing with physical processes involving macroscopic system. It is stressed how J.A.Wheeler's remarks and lucid analysis have been relevant to pinpoint and to bring to its extreme consequences the puzzling aspects of quantum phenomena. It is shown how the recently proposed models of spontaneous dynamical reduction represent a consistent way to overcome the conceptual difficulties of the standard theory. Obviously, many nontrivial problems remain open, the first and more relevant one being that of generalizing the model theories considered to the relativistic case. This is the challenge of the dynamical reduction program. 43 refs, 2 figs

  14. Simplified Transit Procedure in Railway Transport

    Directory of Open Access Journals (Sweden)

    Željko Kokorović

    2008-11-01

    Full Text Available The current transit procedure in railway transport that iscarried out on the basis of the Customs Act [ 11 of the Republicof Croatia is applied only up to the border, i. e. the issued documentsand guarantees are valid only up to the border, and byjoining the Convention on Common transit procedure, i. e. integrationof the Republic of Croatia in the European Union, theRepublic of Croatia will also have to implement the regulationsand rules of Simplified transit procedure valid in each of thethirty member states. In international railway traffic, the transportof goods is regulated by the Convention concerning InternationalCarriage by Rail- COT IF [2 1 and usage of the CIMwaybill (Contract for International Carriage of Goods by Rail.If the goods are transported in Simplified transit procedure, theformalities regarding the transport of goods performed by railcarriers using the international waybill CIM will be significantlysimplified and accelerated. In principle there are no delays dueto customs on the borders when crossing the EU borders andborders of the Convention member states, contributing greatlyto the acceleration of the transport of goods, reduction of waitingcosts and paperwork, as well as influence on the schedulereliability.

  15. Postoperative infections in craniofacial reconstructive procedures.

    Science.gov (United States)

    Fialkov, J A; Holy, C; Forrest, C R; Phillips, J H; Antonyshyn, O M

    2001-07-01

    The rate of, and possible risk factors for, postoperative craniofacial infection is unclear. To investigate this problem, we reviewed 349 cases of craniofacial skeletal procedures performed from 1996 to 1999 at our institution. Infection rate was determined and correlated with the use of implants, operative site, and cause of deformity. The inclusion criteria consisted of all procedures requiring autologous or prosthetic implantation in craniofacial skeletal sites, as well as all procedures involving bone or cartilage resection, osteotomies, debridement, reduction and/or fixation. Procedures that did not involve bone or cartilage surgery were excluded. The criteria for diagnosis of infection included clinical confirmation and one or more of 1) intravenous or oral antibiotic treatment outside of the prophylactic surgical regimen; 2) surgical intervention for drainage, irrigation, and or debridement; and 3) microbiological confirmation. Among the 280 surgical cases that fit the inclusion criteria and had complete records, there were 23 cases of postoperative infection (8.2%). The most common site for postoperative infection was the mandible (infection rate = 16.7%). Multiple logistic regression analysis revealed gunshot wound to be the most significant predictor of postoperative infection. Additionally, porous polyethylene implantation through a transoral route was correlated with a significant risk of postoperative infection.

  16. COGNITIVE FATIGUE FACILITATES PROCEDURAL SEQUENCE LEARNING

    Directory of Open Access Journals (Sweden)

    Guillermo eBorragán

    2016-03-01

    Full Text Available Enhanced procedural learning has been evidenced in conditions where cognitive control is diminished, including hypnosis, disruption of prefrontal activity and non-optimal time of the day. Another condition depleting the availability of controlled resources is cognitive fatigue. We tested the hypothesis that cognitive fatigue, eventually leading to diminished cognitive control, facilitates procedural sequence learning. In a two-day experiment, twenty-three young healthy adults were administered a serial reaction time task (SRTT following the induction of high or low levels of cognitive fatigue, in a counterbalanced order. Cognitive fatigue was induced using the Time load Dual-back (TloadDback paradigm, a dual working memory task that allows tailoring cognitive load levels to the individual's optimal performance capacity. In line with our hypothesis, reaction times in the SRTT were faster in the high- than in the low-level fatigue condition, and performance improvement showed more of a benefit from the sequential components than from motor. Altogether, our results suggest a paradoxical, facilitating impact of cognitive fatigue on procedural motor sequence learning. We propose that facilitated learning in the high-level fatigue condition stems from a reduction in the cognitive resources devoted to cognitive control processes that normally oppose automatic procedural acquisition mechanisms.

  17. BP volume reduction equipment

    International Nuclear Information System (INIS)

    Kitamura, Yoshinori; Muroo, Yoji; Hamanaka, Isao

    2003-01-01

    A new type of burnable poison (BP) volume reduction system is currently being developed. Many BP rods, a subcomponent of spent fuel assemblies are discharged from nuclear power reactors. This new system reduces the overall volume of BP rods. The main system consists of BP rod cutting equipment, equipment for the recovery of BP cut pieces, and special transport equipment for the cut rods. The equipment is all operated by hydraulic press cylinders in water to reduce operator exposure to radioactivity. (author)

  18. Anaerobic azo dye reduction

    OpenAIRE

    Zee, van der, F.P.

    2002-01-01

    Azo dyes, aromatic moieties linked together by azo (-N=N-) chromophores, represent the largest class of dyes used in textile-processing and other industries. The release of these compounds into the environment is undesirable, not only because of their colour, but also because many azo dyes and their breakdown products are toxic and/or mutagenic to life. To remove azo dyes from wastewater, a biological treatment strategy based on anaerobic reduction of the azo dye...

  19. Fluidized bed volume reduction of diverse radwastes

    International Nuclear Information System (INIS)

    McFee, J.N.; McConnell, J.W.; Waddoups, D.A.; Gray, M.F.; Harwood, L.E.; Clayton, N.J.; Drown, D.C.

    1981-01-01

    Method and apparatus for a fluidized bed radwaste volume reduction system are claimed. Low level radioactive wastes, combustible solids, ion exchange resins and filter sludges, and liquids, emanating from a reactor facility are introduced separately through an integrated waste influent system into a common fluidized bed vessel where volume reduction either through incineration or calcination occurs. Addition of a substance to the ion exchange resin before incineration inhibits the formation of low-melting point materials which tend to form clinkers in the bed. Solid particles are scrubbed or otherwise removed from the gaseous effluent of the vessel in an off-gas system, before the cooled and cleaned off-gas is released to the atmosphere. Iodine is chemically or physically removed from the off-gas. Otherwise, the only egress materials from the volume reduction system are containerized dry solids and tramp material. The bed material used during each mode may be circulated, cleaned, stored and exchanged from within the bed vessel by use of a bed material handling system. An instrumentation and control system provides operator information, monitors performance characteristics, implements start up and shut down procedures, and initiates alarms and emergency procedures during abnormal conditions

  20. Thermochemical nitrate reduction

    International Nuclear Information System (INIS)

    Cox, J.L.; Lilga, M.A.; Hallen, R.T.

    1992-09-01

    A series of preliminary experiments was conducted directed at thermochemically converting nitrate to nitrogen and water. Nitrates are a major constituent of the waste stored in the underground tanks on the Hanford Site, and the characteristics and effects of nitrate compounds on stabilization techniques must be considered before permanent disposal operations begin. For the thermochemical reduction experiments, six reducing agents (ammonia, formate, urea, glucose, methane, and hydrogen) were mixed separately with ∼3 wt% NO 3 - solutions in a buffered aqueous solution at high pH (13); ammonia and formate were also mixed at low pH (4). Reactions were conducted in an aqueous solution in a batch reactor at temperatures of 200 degrees C to 350 degrees C and pressures of 600 to 2800 psig. Both gas and liquid samples were analyzed. The specific components analyzed were nitrate, nitrite, nitrous oxide, nitrogen, and ammonia. Results of experimental runs showed the following order of nitrate reduction of the six reducing agents in basic solution: formate > glucose > urea > hydrogen > ammonia ∼ methane. Airnmonia was more effective under acidic conditions than basic conditions. Formate was also effective under acidic conditions. A more thorough, fundamental study appears warranted to provide additional data on the mechanism of nitrate reduction. Furthermore, an expanded data base and engineering feasibility study could be used to evaluate conversion conditions for promising reducing agents in more detail and identify new reducing agents with improved performance characteristics

  1. How does the workload and work activities of procedural GPs compare to non-procedural GPs?

    Science.gov (United States)

    Russell, Deborah J; McGrail, Matthew R

    2017-08-01

    To investigate patterns of Australian GP procedural activity and associations with: geographical remoteness and population size hours worked in hospitals and in total; and availability for on-call DESIGN AND PARTICIPANTS: National annual panel survey (Medicine in Australia: Balancing Employment and Life) of Australian GPs, 2011-2013. Self-reported geographical work location, hours worked in different settings, and on-call availability per usual week, were analysed against GP procedural activity in anaesthetics, obstetrics, surgery or emergency medicine. Analysis of 9301 survey responses from 4638 individual GPs revealed significantly increased odds of GP procedural activity in anaesthetics, obstetrics or emergency medicine as geographical remoteness increased and community population size decreased, albeit with plateauing of the effect-size from medium-sized (population 5000-15 000) rural communities. After adjusting for confounders, procedural GPs work more hospital and more total hours each week than non-procedural GPs. In 2011 this equated to GPs practising anaesthetics, obstetrics, surgery, and emergency medicine providing 8% (95%CI 0, 16), 13% (95%CI 8, 19), 8% (95%CI 2, 15) and 18% (95%CI 13, 23) more total hours each week, respectively. The extra hours are attributable to longer hours worked in hospital settings, with no reduction in private consultation hours. Procedural GPs also carry a significantly higher burden of on-call. The longer working hours and higher on-call demands experienced by rural and remote procedural GPs demand improved solutions, such as changes to service delivery models, so that long-term procedural GP careers are increasingly attractive to current and aspiring rural GPs. © 2016 National Rural Health Alliance Inc.

  2. Radiation dose electrophysiology procedures

    International Nuclear Information System (INIS)

    Hernandez-Armas, J.; Rodriguez, A.; Catalan, A.; Hernandez Armas, O.; Luque Japon, L.; Moral, S.; Barroso, L.; Rfuez-Hdez, R.

    2006-01-01

    The aim of this paper has been to measure and analyse some of the parameters which are directly related with the doses given to patients in two electrophysiology procedures: diagnosis and ablation with radiofrequency. 16 patients were considered in this study. 13 them had an ablation with radiofrequency at the Unit of Electrophysiology at the University Hospital of the Canaries, La Laguna., Tenerife. The results of skin doses, in the ablation cases, were higher than 2 Gy (threshold of some deterministic effects). The average value was 1.1 Gy. The personal doses, measured under the lead apron, for physician and nurses were 4 and 3 micro Sievert. These results emphasised the necessity of radiation protection measures in order to reduce, ad much as possible, the doses to patients. (Author)

  3. Decommissioning licensing procedure

    International Nuclear Information System (INIS)

    Perello, M.

    1979-01-01

    Decommissioning or closure of a nuclear power plant, defined as the fact that takes place from the moment that the plant stops producing for the purpose it was built, is causing preocupation. So this specialist meeting on Regulatory Review seems to be the right place for presenting and discusing the need of considering the decommissioning in the safety analysis report. The main goal of this paper related to the licensing procedure is to suggest the need of a new chapter in the Preliminary Safety Analysis Report (P.S.A.R.) dealing with the decommissioning of the nuclear power plant. Therefore, after a brief introduction the problem is exposed from the point of view of nuclear safety and finally a format of the new chapter is proposed. (author)

  4. Toddler test or procedure preparation

    Science.gov (United States)

    ... a test or procedure: Explain the procedure in language your child understands, using plain words. Avoid abstract terms. Make sure your child understands the exact body part involved in the test, and that the ...

  5. Preschooler test or procedure preparation

    Science.gov (United States)

    ... your child during and after the procedure with books, songs, counting, deep breathing, or blowing bubbles. PLAY ... can be present during the procedure. Ask if anesthesia can be used to reduce your child's discomfort. ...

  6. Automation of the testing procedure

    International Nuclear Information System (INIS)

    Haas, H.; Fleischer, M.; Bachner, E.

    1979-01-01

    For the judgement of technologies applied and the testing of specific components of the HTR primary circuit, complex test procedures and data evaluations are required. Extensive automation of these test procedures is indispensable. (orig.) [de

  7. Vietnam; Poverty Reduction Strategy Paper

    OpenAIRE

    International Monetary Fund

    2004-01-01

    This paper assesses the Poverty Reduction Strategy Paper of Vietnam, known as the Comprehensive Poverty Reduction and Growth Strategy (CPRGS). It is an action program to achieve economic growth and poverty reduction objectives. This paper reviews the objectives and tasks of socio-economic development and poverty reduction. The government of Vietnam takes poverty reduction as a cutting-through objective in the process of country socio-economic development and declares its commitment to impleme...

  8. Quantization Procedures; Sistemas de cuantificacion

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera, J. A.; Martin, R.

    1976-07-01

    We present in this work a review of the conventional quantization procedure, the proposed by I.E. Segal and a new quantization procedure similar to this one for use in non linear problems. We apply this quantization procedures to different potentials and we obtain the appropriate equations of motion. It is shown that for the linear case the three procedures exposed are equivalent but for the non linear cases we obtain different equations of motion and different energy spectra. (Author) 16 refs.

  9. Cortical Blindness In Fat Embolism Syndrome Following Fracture Manipulative Procedure

    Directory of Open Access Journals (Sweden)

    A Shahrulazua

    2010-03-01

    Full Text Available Fat embolism syndrome is a well-recognised sequela of long bone trauma as well as intramedullary orthopaedic procedures. However, it has rarely been described following manipulation, reduction of fracture, and application of external fixator. Furthermore, bilateral ocular blindness is seldom the first manifestation; instead respiratory and other cerebral symptoms being most common. We describe a case with this rare presentation in a patient who underwent a trial of closed reduction, then open reduction of a femur fracture, followed by external fixation performed at day 47 post-initial trauma.

  10. Discrete Routh reduction

    International Nuclear Information System (INIS)

    Jalnapurkar, Sameer M; Leok, Melvin; Marsden, Jerrold E; West, Matthew

    2006-01-01

    This paper develops the theory of Abelian Routh reduction for discrete mechanical systems and applies it to the variational integration of mechanical systems with Abelian symmetry. The reduction of variational Runge-Kutta discretizations is considered, as well as the extent to which symmetry reduction and discretization commute. These reduced methods allow the direct simulation of dynamical features such as relative equilibria and relative periodic orbits that can be obscured or difficult to identify in the unreduced dynamics. The methods are demonstrated for the dynamics of an Earth orbiting satellite with a non-spherical J 2 correction, as well as the double spherical pendulum. The J 2 problem is interesting because in the unreduced picture, geometric phases inherent in the model and those due to numerical discretization can be hard to distinguish, but this issue does not appear in the reduced algorithm, where one can directly observe interesting dynamical structures in the reduced phase space (the cotangent bundle of shape space), in which the geometric phases have been removed. The main feature of the double spherical pendulum example is that it has a non-trivial magnetic term in its reduced symplectic form. Our method is still efficient as it can directly handle the essential non-canonical nature of the symplectic structure. In contrast, a traditional symplectic method for canonical systems could require repeated coordinate changes if one is evoking Darboux' theorem to transform the symplectic structure into canonical form, thereby incurring additional computational cost. Our method allows one to design reduced symplectic integrators in a natural way, despite the non-canonical nature of the symplectic structure

  11. Radioiodination of proteins by reductive alkylation

    International Nuclear Information System (INIS)

    Panuska, J.R.; Parker, C.W.

    1987-01-01

    The use of the aliphatic aldehyde, para-hydroxyphenylacetaldehyde as the reactive moiety in the radioiodination of proteins by reductive alkylation is described. The para-hydroxyphenyl group is radiolabeled with 125 I, reacted through its aliphatic aldehyde group with primary amino groups on proteins to form a reversible Schiff base linkage which can then be stabilized with the mild reducing agent NaCNBH 3 . The introduction of the methylene group between the benzene ring and the aldehyde group increases its reactivity with protein amino groups permitting efficient labeling at low aldehyde concentrations. Using this method, radioiodinated proteins with high specific activity can be produced. The reductive alkylation procedure is advantageous in that the labeling conditions are mild, the reaction is specific for lysyl residues, and the modification of the epsilon-ammonium group of lysine results in ionizable secondary amino groups avoiding major changes in protein charge

  12. Poisson-Jacobi reduction of homogeneous tensors

    International Nuclear Information System (INIS)

    Grabowski, J; Iglesias, D; Marrero, J C; Padron, E; Urbanski, P

    2004-01-01

    The notion of homogeneous tensors is discussed. We show that there is a one-to-one correspondence between multivector fields on a manifold M, homogeneous with respect to a vector field Δ on M, and first-order polydifferential operators on a closed submanifold N of codimension 1 such that Δ is transversal to N. This correspondence relates the Schouten-Nijenhuis bracket of multivector fields on M to the Schouten-Jacobi bracket of first-order polydifferential operators on N and generalizes the Poissonization of Jacobi manifolds. Actually, it can be viewed as a super-Poissonization. This procedure of passing from a homogeneous multivector field to a first-order polydifferential operator can also be understood as a sort of reduction; in the standard case-a half of a Poisson reduction. A dual version of the above correspondence yields in particular the correspondence between Δ-homogeneous symplectic structures on M and contact structures on N

  13. Outage risk reduction at Diablo Canyon

    International Nuclear Information System (INIS)

    Burnett, Tobias W.T.; Eugene Newman, C.

    2004-01-01

    A formal risk reduction program was conducted at the Diablo Canyon Nuclear Generating plant as part of EPRI's Outage Risk Assessment and Management Program. The program began with a probabilistic and deterministic assessment of the frequency of core coolant boiling and core uncovery during shutdown operations. This step identified important contributors to risk, periods of high vulnerability, and potential mechanisms for reducing risk. Next, recovery strategies were evaluated and procedures, training, and outage schedules modified. Twelve risk reduction enhancements were developed and implemented. These enhancements and their impact are described in this paper. These enhancements reduced the calculated risk of core uncovery by about a factor of four for a refueling outage without lengthening the outage schedule; increased the outage efficiency, contributing to completing 11 days ahead of schedule; and helped to earn the highest achievable SALP rating from the NRC. (author)

  14. A recursive reduction of tensor Feynman integrals

    International Nuclear Information System (INIS)

    Diakonidis, T.; Riemann, T.; Tausk, J.B.; Fleischer, J.

    2009-07-01

    We perform a recursive reduction of one-loop n-point rank R tensor Feynman integrals [in short: (n,R)-integrals] for n≤6 with R≤n by representing (n,R)-integrals in terms of (n,R-1)- and (n-1,R-1)-integrals. We use the known representation of tensor integrals in terms of scalar integrals in higher dimension, which are then reduced by recurrence relations to integrals in generic dimension. With a systematic application of metric tensor representations in terms of chords, and by decomposing and recombining these representations, we find the recursive reduction for the tensors. The procedure represents a compact, sequential algorithm for numerical evaluations of tensor Feynman integrals appearing in next-to-leading order contributions to massless and massive three- and four-particle production at LHC and ILC, as well as at meson factories. (orig.)

  15. Application of safeguards procedures

    International Nuclear Information System (INIS)

    1977-01-01

    The earliest applications of safeguards procedures took place in a political and technical climate far different from that of today. In the early 1960's there was a fear of the proliferation possibilities which could arise as more and more countries acquired nuclear power plants. Today nuclear power is being produced in some 20 countries without resulting in nuclear weapons proliferation. The export of equipment and technology for the nuclear fuel cycle, however, has become the subject of current concern. In view of these developments, it is not surprising that techniques in the application of safeguards have also changed. In order to appreciate the nature of these changes, it is important to be aware of the original general attitude towards the technical problems of safeguards applications. Originally, the common attitude was that the objectives of safeguards were self-evident and the methods, while in need of development, were known at least in outline. Today, it has become evident that before a safeguards procedure can be applied, the objectives must first be carefully defined, and the criteria against which success in meeting those objectives can be measured must also be developed. In line with this change, a significant part of the effort of the safeguards inspectorate is concerned with work preliminary and subsequent to the actual inspection work in the field. Over the last two years, for example, a considerable part of the work of experienced safeguards staff has been spent in analysing the possibilities of diverting material at each facility to be safeguarded. These analyses are carried out in depth by a 'facility officer' and are subjected to constructive criticism by teams composed of staff responsible for similar types of facilities as well as other technical experts. The analyses consider the measures currently considered practicable, to meet the diversion possibilities and where necessary list the development work needed to overcome any present

  16. Procedural-support music therapy in the healthcare setting: a cost-effectiveness analysis.

    Science.gov (United States)

    DeLoach Walworth, Darcy

    2005-08-01

    This comparative analysis examined the cost-effectiveness of music therapy as a procedural support in the pediatric healthcare setting. Many healthcare organizations are actively attempting to reduce the amount of sedation for pediatric patients undergoing various procedures. Patients receiving music therapy-assisted computerized tomography scans ( n = 57), echocardiograms ( n = 92), and other procedures ( n = 17) were included in the analysis. Results of music therapy-assisted procedures indicate successful elimination of patient sedation, reduction in procedural times, and decrease in the number of staff members present for procedures. Implications for nurses and music therapists in the healthcare setting are discussed.

  17. Predictive value of minimal residual disease in Philadelphia-chromosome-positive acute lymphoblastic leukemia treated with imatinib in the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia, based on immunoglobulin/T-cell receptor and BCR/ABL1 methodologies

    Science.gov (United States)

    Cazzaniga, Giovanni; De Lorenzo, Paola; Alten, Julia; Röttgers, Silja; Hancock, Jeremy; Saha, Vaskar; Castor, Anders; Madsen, Hans O.; Gandemer, Virginie; Cavé, Hélène; Leoni, Veronica; Köhler, Rolf; Ferrari, Giulia M.; Bleckmann, Kirsten; Pieters, Rob; van der Velden, Vincent; Stary, Jan; Zuna, Jan; Escherich, Gabriele; zur Stadt, Udo; Aricò, Maurizio; Conter, Valentino; Schrappe, Martin; Valsecchi, Maria Grazia; Biondi, Andrea

    2018-01-01

    The prognostic value of minimal residual disease (MRD) in Philadelphia-chromosome-positive (Ph+) childhood acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors is not fully established. We detected MRD by real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes (IG/TR) and/or BCR/ABL1 fusion transcript to investigate its predictive value in patients receiving Berlin-Frankfurt-Münster (BFM) high-risk (HR) therapy and post-induction intermittent imatinib (the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia (EsPhALL) study). MRD was monitored after induction (time point (TP)1), consolidation Phase IB (TP2), HR Blocks, reinductions, and at the end of therapy. MRD negativity progressively increased over time, both by IG/TR and BCR/ABL1. Of 90 patients with IG/TR MRD at TP1, nine were negative and none relapsed, while 11 with MRD<5×10−4 and 70 with MRD≥5×10−4 had a comparable 5-year cumulative incidence of relapse of 36.4 (15.4) and 35.2 (5.9), respectively. Patients who achieved MRD negativity at TP2 had a low relapse risk (5-yr cumulative incidence of relapse (CIR)=14.3[9.8]), whereas those who attained MRD negativity at a later date showed higher CIR, comparable to patients with positive MRD at any level. BCR/ABL1 MRD negative patients at TP1 had a relapse risk similar to those who were IG/TR MRD negative (1/8 relapses). The overall concordance between the two methods is 69%, with significantly higher positivity by BCR/ABL1. In conclusion, MRD monitoring by both methods may be functional not only for measuring response but also for guiding biological studies aimed at investigating causes for discrepancies, although from our data IG/TR MRD monitoring appears to be more reliable. Early MRD negativity is highly predictive of favorable outcome. The earlier MRD negativity is achieved, the better the prognosis. PMID

  18. Automated analysis for nitrate by hydrazine reduction

    Energy Technology Data Exchange (ETDEWEB)

    Kamphake, L J; Hannah, S A; Cohen, J M

    1967-01-01

    An automated procedure for the simultaneous determinations of nitrate and nitrite in water is presented. Nitrite initially present in the sample is determined by a conventional diazotization-coupling reaction. Nitrate in another portion of sample is quantitatively reduced with hydrazine sulfate to nitrite which is then determined by the same diazotization-coupling reaction. Subtracting the nitrite initially present in the sample from that after reduction yields nitrite equivalent to nitrate initially in the sample. The rate of analysis is 20 samples/hr. Applicable range of the described method is 0.05-10 mg/l nitrite or nitrate nitrogen; however, increased sensitivity can be obtained by suitable modifications.

  19. Incomplete Dirac reduction of constrained Hamiltonian systems

    Energy Technology Data Exchange (ETDEWEB)

    Chandre, C., E-mail: chandre@cpt.univ-mrs.fr

    2015-10-15

    First-class constraints constitute a potential obstacle to the computation of a Poisson bracket in Dirac’s theory of constrained Hamiltonian systems. Using the pseudoinverse instead of the inverse of the matrix defined by the Poisson brackets between the constraints, we show that a Dirac–Poisson bracket can be constructed, even if it corresponds to an incomplete reduction of the original Hamiltonian system. The uniqueness of Dirac brackets is discussed. The relevance of this procedure for infinite dimensional Hamiltonian systems is exemplified.

  20. Economical benzene emission reduction

    International Nuclear Information System (INIS)

    Schuetz, R.

    1999-01-01

    Benzene has been classified as a toxic compound under the Canadian Environmental Protection Act. This has prompted the Alberta Energy and Utilities Board (AEUB) to introduce specific reporting and monitoring guidelines for the oil and gas industry regarding excessive benzene emissions. Glycol dehydration units have been determined to be the major single source of benzene emissions causing air and soil pollution. DualTank Corp. has designed a condensation and storage tank unit to enhance emission reduction, odour elimination and liquid recovery from dehydration units. Their newly designed combined tank unit consists of a large, uninsulated surface area for cooling, and an excessive internal volume for increased retention time. The first prototype was installed in December 1998 at an Enerplus Resources Site. The system provides excellent benzene emission reduction and the elimination of odours and visual plumes. Effective January 1, 1999, the petroleum and natural gas industry must either clean up excessive emissions voluntarily or face government imposed regulations, facility shutdowns and/or fines. 1 fig

  1. LOFT data reduction

    International Nuclear Information System (INIS)

    Norman, N.L.

    1975-08-01

    The Loss-of-Fluid Test (LOFT) Facility is an experimental facility built around a ''scaled'' version of a large pressurized water reactor (LPWR). LOFT will be used to run loss-of-coolant experiments (LOCEs) and to acquire the necessary data required ''to evaluate the adequacy and improve the analytical methods currently used to predict the loss-of-coolant accident (LOCA) response of LPWRs'' and ''to identify and investigate any unexpected event(s) or threshold(s) in the response of either the plant or the engineered safety features and develop analytical techniques that adequately describe and account for the unexpected behavior(s)''. During the LOCE this required data will be acquired and recorded in both analog and digital modes. Subsequent to the test the analog data will also be converted to the raw digital mode. This raw digital data will be converted to the desired engineering units using the LOFT Data Reduction System. This system is implemented on the IBM 360/75 and is a part of a commercially available data processing program called MAC/RAN III. The theory of reducing LOFT data to engineering units and the application of the MAC/ RAN III system to accomplish this reduction is given. (auth)

  2. Islam and harm reduction.

    Science.gov (United States)

    Kamarulzaman, A; Saifuddeen, S M

    2010-03-01

    Although drugs are haram and therefore prohibited in Islam, illicit drug use is widespread in many Islamic countries throughout the world. In the last several years increased prevalence of this problem has been observed in many of these countries which has in turn led to increasing injecting drug use driven HIV/AIDS epidemic across the Islamic world. Whilst some countries have recently responded to the threat through the implementation of harm reduction programmes, many others have been slow to respond. In Islam, The Quran and the Prophetic traditions or the Sunnah are the central sources of references for the laws and principles that guide the Muslims' way of life and by which policies and guidelines for responses including that of contemporary social and health problems can be derived. The preservation and protection of the dignity of man, and steering mankind away from harm and destruction are central to the teachings of Islam. When viewed through the Islamic principles of the preservation and protection of the faith, life, intellect, progeny and wealth, harm reduction programmes are permissible and in fact provide a practical solution to a problem that could result in far greater damage to the society at large if left unaddressed. Copyright (c) 2009. Published by Elsevier B.V.

  3. Emergency planning zone reduction

    International Nuclear Information System (INIS)

    Edwards, C.

    2002-01-01

    This paper describes the process used by a large industrial Department of Energy (DOE) site to communicate changing hazards to its stakeholders and install the confidence necessary to implement the resulting emergency planning changes. Over the last decade as the sites missions have shifted from full-scale production to a greater emphasis on environmental restoration and waste management, the off-site threat from its operations has substantially decreased. The challenge was to clearly communicate the reduced hazards, install confidence in the technical analysis that documented the hazard reduction, and obtain stakeholder buy-in on the path forward to change the emergency management program. The most significant change to the emergency management program was the proposed reduction of the sites Emergency Planning Zone (EPZ). As the EPZ is defined as an area for which planning is needed to protect the public in the event of an accident, the process became politically challenging. An overview of how the site initially approached this problem and then learned to more substantially involve the state and local emergency preparedness agencies and the local Citizens Advisory Board will be presented. (author)

  4. BWR emergency procedure guidelines

    International Nuclear Information System (INIS)

    Post, J.S.; Karner, E.F.; Stratman, R.A.

    1984-01-01

    This chapter describes plans for dealing with reactor accidents developed by the Boiling Water Reactor (BWR) Owners' Group in response to post-Three Mile Island US NRC requirements. The devised Emergency Procedure Guidelines (EPGs), applicable to all BWRs, are symptom-based rather than event-based. According to the EPGs, the operator does not need to identify what event is occurring in the plant in order to decide what action to take, but need only observe the symptoms (values and trends of key control parameters) which exist and take appropriate action to control these symptoms. The original objective was to provide reactor operator guidance in responding to a small break loss-of-coolant accident (LOCA), but subsequent revisions have included other types of reactor accidents. Topics considered include the reactor pressure vessel (RPV) control guideline, the primary containment control guideline, the secondary containment control guideline, the radioactivity release control guideline, multiple failures vs. the design basis, safe limits vs. technical specifications, the technical status, licensing, and implementation. The EPGs are based upon maintaining both adequate core cooling and primary containment integrity

  5. Automated emergency operating procedures

    International Nuclear Information System (INIS)

    Perez-Ramirez, G.; Nelson, P.F.

    1990-01-01

    This paper describes the development of a training tool for the symptom oriented emergency operating procedures used at the Laguna Verde Nuclear Power Plant. EOPs and operator training are intended to assist the operator for managing accident situations. A prototype expert system based on the EOPs has been developed for operator training. The demonstration expert system was developed using a commercial shell. The knowledge base consists of two parts. The specific operator actions to be executed for 5 selected accident sequences and the EOPs steps for the reactor pressure vessel control of the water level, pressure, and power. The knowledge is expressed in the form of IF-THEN production rules. A typical training session will display a set of conditions and will prompt the trainee to indicate the appropriate step to perform. This mode will guide the trainee through selected accident sequences. A second mode of the expert system will prompt the trainee for the current plant conditions and the expert system will respond with the EOPs which are required to be performed under these conditions. This allows the trainee to study What if situations

  6. Computer software review procedures

    International Nuclear Information System (INIS)

    Mauck, J.L.

    1993-01-01

    This article reviews the procedures which are used to review software written for computer based instrumentation and control functions in nuclear facilities. The utilization of computer based control systems is becoming much more prevalent in such installations, in addition to being retrofit into existing systems. Currently, the Nuclear Regulatory System uses Regulatory Guide 1.152, open-quotes Criteria for Programmable Digital Computer System Software in Safety-Related Systems of Nuclear Power Plantsclose quotes and ANSI/IEEE-ANS-7-4.3.2-1982, open-quotes Application Criteria for Programmable Digital Computer Systems in Safety Systems of Nuclear Power Generating Stationsclose quotes for guidance when performing reviews of digital systems. There is great concern about the process of verification and validation of these codes, so when inspections are done of such systems, inspectors examine very closely the processes which were followed in developing the codes, the errors which were detected, how they were found, and the analysis which went into tracing down the causes behind the errors to insure such errors were not propagated again in the future

  7. [Costing nuclear medicine diagnostic procedures].

    Science.gov (United States)

    Markou, Pavlos

    2005-01-01

    To the Editor: Referring to a recent special report about the cost analysis of twenty-nine nuclear medicine procedures, I would like to clarify some basic aspects for determining costs of nuclear medicine procedure with various costing methodologies. Activity Based Costing (ABC) method, is a new approach in imaging services costing that can provide the most accurate cost data, but is difficult to perform in nuclear medicine diagnostic procedures. That is because ABC requires determining and analyzing all direct and indirect costs of each procedure, according all its activities. Traditional costing methods, like those for estimating incomes and expenses per procedure or fixed and variable costs per procedure, which are widely used in break-even point analysis and the method of ratio-of-costs-to-charges per procedure may be easily performed in nuclear medicine departments, to evaluate the variability and differences between costs and reimbursement - charges.

  8. Radiation dose during angiographic procedures

    International Nuclear Information System (INIS)

    Lavoie, Ch.; Rasuli, P.

    2001-01-01

    The use of angiographic procedures is becoming more prevalent as new techniques and equipment are developed. There have been concerns in the scientific community about the level of radiation doses received by patients, and indirectly by staff, during some of these radiological procedures. The purpose of this study was to assess the level of radiation dose from angiographic procedures to patient at the Ottawa Hospital, General Campus. Radiation dose measurements, using Thermo-Luminescent Dosimeters (TLDs), were performed on more than 100 patients on various procedures. The results show that while the patient dose from the great majority of angiographic procedures is less than 2 Gy, a significant number of procedures, especially interventional procedures may have doses greater than 2 Gy and may lead to deterministic effects. (author)

  9. Waste minimization assessment procedure

    International Nuclear Information System (INIS)

    Kellythorne, L.L.

    1993-01-01

    Perry Nuclear Power Plant began developing a waste minimization plan early in 1991. In March of 1991 the plan was documented following a similar format to that described in the EPA Waste Minimization Opportunity Assessment Manual. Initial implementation involved obtaining management's commitment to support a waste minimization effort. The primary assessment goal was to identify all hazardous waste streams and to evaluate those streams for minimization opportunities. As implementation of the plan proceeded, non-hazardous waste streams routinely generated in large volumes were also evaluated for minimization opportunities. The next step included collection of process and facility data which would be useful in helping the facility accomplish its assessment goals. This paper describes the resources that were used and which were most valuable in identifying both the hazardous and non-hazardous waste streams that existed on site. For each material identified as a waste stream, additional information regarding the materials use, manufacturer, EPA hazardous waste number and DOT hazard class was also gathered. Once waste streams were evaluated for potential source reduction, recycling, re-use, re-sale, or burning for heat recovery, with disposal as the last viable alternative

  10. Administrative Procedure Act and mass procedures (illustrated by the nuclear licensing procedure)

    International Nuclear Information System (INIS)

    Naumann, R.

    1977-01-01

    The report deals with the administrative procedure law of 25.5.76 of the Fed. Government, esp. with its meaning for the administrative procedures for the permission for nuclear power plants, as fas ar so-called mass procedures are concerned. (UN) [de

  11. Reduction operators of Burgers equation.

    Science.gov (United States)

    Pocheketa, Oleksandr A; Popovych, Roman O

    2013-02-01

    The solution of the problem on reduction operators and nonclassical reductions of the Burgers equation is systematically treated and completed. A new proof of the theorem on the special "no-go" case of regular reduction operators is presented, and the representation of the coefficients of operators in terms of solutions of the initial equation is constructed for this case. All possible nonclassical reductions of the Burgers equation to single ordinary differential equations are exhaustively described. Any Lie reduction of the Burgers equation proves to be equivalent via the Hopf-Cole transformation to a parameterized family of Lie reductions of the linear heat equation.

  12. Safeguards management inspection procedures

    International Nuclear Information System (INIS)

    Barth, M.J.; Dunn, D.R.

    1984-08-01

    The objective of this inspection module is to independently assess the contributions of licensee management to overall safeguards systems performance. The inspector accomplishes this objective by comparing the licensee's safeguards management to both the 10 CFR, parts 70 and 73, requirements and to generally accepted management practices. The vehicle by which this comparison is to be made consists of assessment questions and key issues which point the inspector to areas of primary concern to the NRC and which raise additional issues for the purpose of exposing management ineffectiveness. Further insight into management effectiveness is obtained through those assessment questions specifically directed toward the licensee's safeguards system performance. If the quality of the safeguards is poor, then the inspector should strongly suspect that management's role is ineffective and should attempt to determine management's influence (or lack thereof) on the underlying safeguards deficiencies. (The converse is not necessarily true, however.) The assessment questions in essence provide an opportunity for the inspector to identify, to single out, and to probe further, questionable management practices. Specific issues, circumstances, and concerns which point to questionable or inappropriate practices should be explicitly identified and referenced against the CFR and the assessment questions. The inspection report should also explain why the inspector feels certain management practices are poor, counter to the CFR, and/or point to ineffecive management. Concurrent with documenting the inspection results, the inspector should provide recommendations for alleviating observed management practices that are detrimental to effective safeguards. The recommendations could include: specific changes in the practices of the licensee, followup procedures on the part of NRC, and proposed license changes

  13. AGREED-UPON PROCEDURES, PROCEDURES FOR AUDITING EUROPEAN GRANTS

    Directory of Open Access Journals (Sweden)

    Daniel Petru VARTEIU

    2016-12-01

    The audit of EU-funded projects is an audit based on agreed-upon procedures, which are established by the Managing Authority or the Intermediate Body. Agreed-upon procedures can be defined as engagements made in accordance with ISRS 4400, applicable to agreed-upon procedures, where the auditor undertakes to carry out the agreed-upon procedures and issue a report on factual findings. The report provided by the auditor does not express any assurance. It allows users to form their own opinions about the conformity of the expenses with the project budget as well as the eligibility of the expenses.

  14. Oxygen Reduction on Platinum

    DEFF Research Database (Denmark)

    Nesselberger, Markus

    . The influence of the ion adsorption strength, which is observed in the “particle size studies” on the oxygen reduction rate on Pt/C catalysts, is further investigated under similar reaction conditions by infrared spectroscopy. The designed in situ electrochemical ATR-FTIR setup features a high level...... of instrument automation and online data treatment, and provides welldefined mass transport conditions enabling kinetic measurements. A modified electrochemical / spectroscopic interface is presented allowing the exclusive investigation of the Pt/C catalyst layer. Three types of potential dependent adsorption...... adsorption on Pt does not block the ORR directly. Instead, the onset of oxide formation with the concomitant conversion of the anion adsorbate layer is the decisive blocking mechanism....

  15. Multiple gas reduction strategy

    Energy Technology Data Exchange (ETDEWEB)

    A. Kurosawa [Institute of Applied Energy, Tokyo (Japan)

    2003-07-01

    Future global warming has a close relationship with the abatement potential of six greenhouse gases (GHGs), including carbon dioxide (CO{sub 2}), methane (CH{sub 4}), nitrous oxide (N{sub 2}O), hydrofluorocarbons (HFCs), perfluorocarbons (PFCs), and sulfur hexafluoride (SF6). Therefore, multiple gas reduction flexibility should be assessed. The emission of each non-CO{sub 2} GHG is calculated endogenously by the sum of the product of the emission factor and the endogenous activity index using an integrated assessment model, GRAPE (Global Relationship Assessment to Protect the Environment). The model consists of five modules dealing with issues on energy, climate, land use, macroeconomics and environmental impacts. The uncertainty in the non-CO{sub 2} GHG emission inventory and emission factors is discussed. 5 refs., 3 figs., 1 tab.

  16. Aircraft engine pollution reduction.

    Science.gov (United States)

    Rudey, R. A.

    1972-01-01

    The effect of engine operation on the types and levels of the major aircraft engine pollutants is described and the major factors governing the formation of these pollutants during the burning of hydrocarbon fuel are discussed. Methods which are being explored to reduce these pollutants are discussed and their application to several experimental research programs are pointed out. Results showing significant reductions in the levels of carbon monoxide, unburned hydrocarbons, and oxides of nitrogen obtained from experimental combustion research programs are presented and discussed to point out potential application to aircraft engines. An experimental program designed to develop and demonstrate these and other advanced, low pollution combustor design methods is described. Results that have been obtained to date indicate considerable promise for reducing advanced engine exhaust pollutants to levels significantly below current engines.

  17. Mindfulness-Based Stress Reduction

    Science.gov (United States)

    ... R S T U V W X Y Z Mindfulness-Based Stress Reduction (MBSR) Information 6 Things You ... Disease and Dementia (12/20/13) Research Spotlights Mindfulness-Based Stress Reduction, Cognitive-Behavioral Therapy Shown To ...

  18. Consumer's Guide to Radon Reduction

    Science.gov (United States)

    ... Labs and Research Centers Radon Contact Us Share Consumer's Guide to Radon Reduction: How to Fix Your ... See EPA’s About PDF page to learn more. Consumer's Guide to Radon Reduction: How to Fix Your ...

  19. Confluence reduction for Markov automata

    NARCIS (Netherlands)

    Timmer, Mark; Katoen, Joost P.; van de Pol, Jaco; Stoelinga, Mariëlle Ida Antoinette

    2016-01-01

    Markov automata are a novel formalism for specifying systems exhibiting nondeterminism, probabilistic choices and Markovian rates. As expected, the state space explosion threatens the analysability of these models. We therefore introduce confluence reduction for Markov automata, a powerful reduction

  20. Hazardous material reduction initiative

    International Nuclear Information System (INIS)

    Nichols, D.H.

    1995-02-01

    The Hazardous Material Reduction Initiative (HMRI) explores using the review of purchase requisitions to reduce both the use of hazardous materials and the generation of regulated and nonregulated wastes. Based on an 11-month program implemented at the Hanford Site, hazardous material use and waste generation was effectively reduced by using a centralized procurement control program known as HMRI. As expected, several changes to the original proposal were needed during the development/testing phase of the program to accommodate changing and actual conditions found at the Hanford Site. The current method requires a central receiving point within the Procurement Organization to review all purchase requisitions for potentially Occupational Safety and Health Administration (OSHA) hazardous products. Those requisitions (approximately 4% to 6% of the total) are then forwarded to Pollution Prevention personnel for evaluation under HMRI. The first step is to determine if the requested item can be filled by existing or surplus material. The requisitions that cannot filled by existing or surplus material are then sorted into two groups based on applicability to the HMRI project. For example, laboratory requests for analytical reagents or standards are excluded and the purchase requisitions are returned to Procurement for normal processing because, although regulated, there is little opportunity for source reduction due to the strict protocols followed. Each item is then checked to determine if it is regulated or not. Regulated items are prioritized based on hazardous contents, quantity requested, and end use. Copies of these requisitions are made and the originals are returned to Procurement within 1-hr. Since changes to the requisition can be made at later stages during procurement, the HMRI fulfills one of its original premises in that it does not slow the procurement process

  1. Dose Reduction Techniques

    International Nuclear Information System (INIS)

    WAGGONER, L.O.

    2000-01-01

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program

  2. Dose Reduction Techniques

    Energy Technology Data Exchange (ETDEWEB)

    WAGGONER, L.O.

    2000-05-16

    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program.

  3. October 2015 Phoenix pulmonary journal club: lung volume reduction

    Directory of Open Access Journals (Sweden)

    Mathew M

    2015-11-01

    Full Text Available No abstract available. Article truncated at 150 words. The October 2015 pulmonary journal club focused on the review of older studies evaluating lung volume reduction surgery and how this has transitioned toward the development of non-surgical modes of lung volume reduction. The physiology behind dyspnea in chronic obstructive pulmonary disease (COPD is a complex process. One of the proposed mechanisms has been hyperinflation associated with air trapping. In the mid 1990s studies by Cooper and Peterson (1 offered a promising approach in which lung volume reduction (LVR could improve ventilatory mechanics and improve dyspnea. As the procedure gained more popularity, additional larger scale trials were performed to support its validity. We reviewed 2 studies looking at lung volume reduction. The first was "The Effect of Lung Volume Reduction Surgery In Patients With Severe Emphysema” (2 . This was a smaller, randomized controlled trial (RCT that looked at 2 groups of 24 patients. Once group received LVR while the ...

  4. Uranium hexafluoride: Handling procedures and container descriptions

    International Nuclear Information System (INIS)

    1987-09-01

    The US Department of Energy (DOE) guidelines for packaging, measuring, and transferring uranium hexafluoride (UF 6 ) have been undergoing continual review and revision for several years to keep them in phase with developing agreements for the supply of enriched uranium. Initially, K-1323 ''A Brief Guide to UF 6 Handling,'' was issued in 1957. This was superceded by ORO-651, first issued in 1966, and reissued in 1967 to make editorial changes and to provide minor revisions in procedural information. In 1968 and 1972, Revisions 2 and 3, respectively, were issued as part of the continuing effort to present updated information. Revision 4 issued in 1977 included revisions to UF 6 cylinders, valves, and methods to use. Revision 5 adds information dealing with pigtails, overfilled cylinders, definitions and handling precautions, and cylinder heel reduction procedures. Weighing standards previously presented in ORO-671, Vol. 1 (Procedures for Handling and Analysis of UF 6 ) have also been included. This revision, therefore, supercedes ORO-671-1 as well as all prior issues of this report. These guidelines will normally apply in all transactions involving receipt or shipment of UF 6 by DOE, unless stipulated otherwise by contracts or agreements with DOE or by notices published in the Federal Register. Any questions or requests for additional information on the subject matter covered herein should be directed to the United States Department of Energy, P.O. Box E, Oak Ridge, Tennessee 37831, Attention: Director, Uranium Enrichment Operations Division. 33 figs., 12 tabs

  5. Alcohol harm reduction in Europe

    DEFF Research Database (Denmark)

    Herring, Rachel; Betsy, Thom; Beccaria, Franca

    2010-01-01

    The EMCDDA’s 10th scientific monograph, entitled Harm reduction: evidence, impacts and challenges provides a comprehensive overview of the harm reduction field. Part I of the monograph looks back at the emergence of harm reduction approaches and their diffusion, and explores the concept from diff...

  6. Rubin's CMS reduction method for general state-space models

    NARCIS (Netherlands)

    Kraker, de A.; Campen, van D.H.

    1996-01-01

    In this paper the Rubin CMS procedure for the reduction and successive coupling of undamped structural subsystems with symmetric system matrices will be modified for the case of general damping. The final coordinate transformation is based on the use of complex (residual) flexibility modes,

  7. Reactive power compensation and loss reduction in large industrial enterprises

    Energy Technology Data Exchange (ETDEWEB)

    Jovanovic, S; Gajic, B; Mijailovic, S [Institute Nikola Tesla, Beograd (Yugoslavia)

    1991-12-01

    This paper considers the reactive power compensation and the active power and energy loss reduction of large radial power networks in the Serbian mine and smelting industry. It gives an efficient optimization procedure for positioning and sizing capacitors in large industrial systems integrated with a simple network analysis method. (Author).

  8. Trochanteric reduction osteotomy as a treatment for refractory trochanteric bursitis

    NARCIS (Netherlands)

    Govaert, L. H. M.; van der Vis, H. M.; Marti, R. K.; Albers, G. H. R.

    2003-01-01

    We describe a new operative procedure for patients with chronic trochanteric bursitis. Between March 1994 and May 2000, a trochanteric reduction osteotomy was performed on ten patients (12 hips). All had received conservative treatment for at least one year. Previous surgical treatment with a

  9. A Reduction in Radiographic Exposure and Image Quality in Film ...

    African Journals Online (AJOL)

    Purpose: To develop a protocol for the optimization of diagnostic chest radiography examination, the effect of radiographic exposure reduction on image quality is investigated. Procedure: Fourty-eight adult patients presenting for posterior-anterior (PA) chest radiography in a tertiary health care centre were categorized into 3 ...

  10. A Behavioral Weight Reduction Model for Moderately Mentally Retarded Adolescents.

    Science.gov (United States)

    Rotatori, Anthony F.; And Others

    1980-01-01

    A behavioral weight reduction treatment and maintenance program for moderately mentally retarded adolescents which involves six phases from background information collection to followup relies on stimulus control procedures to modify eating behaviors. Data from pilot studies show an average weekly weight loss of .5 to 1 pound per S. (CL)

  11. Liposuction breast reduction: a prospective trial in African American women.

    Science.gov (United States)

    Moskovitz, Martin J; Baxt, Sherwood A; Jain, Aridaman K; Hausman, Robert E

    2007-02-01

    Recently published case reports and outcome studies support the use of liposuction alone as an effective technique for ameliorating symptoms of breast hypertrophy. This study is the first prospective trial to examine the effectiveness of liposuction breast reduction as a primary modality of breast reduction. In addition, this study examines the role that liposuction breast reduction can play in the treatment of African American women, given the known scarring difficulties that darker skinned patients can encounter with traditional breast reduction surgery. Twenty African American women were recruited through newspaper and Internet advertisements. Patients aged 20 to 60 years were serially accepted to the study. Patients with a chief complaint of breast ptosis were excluded. No other exclusion criteria were used. Previously validated questionnaire instruments were used preoperatively and postoperatively to measure breast-related symptoms, general patient health perception, bodily pain, and self-esteem. Comorbid conditions, demographics, financial status, prior treatments, and smoking history were also documented. Seventeen patients completed the preoperative and postoperative questionnaires. An average of 1075 cc of tissue was removed per breast during liposuction breast reduction surgery. Postoperative assessment showed a significant decrease in breast-related symptoms, a significant decrease in patient pain, and a significant improvement in overall patient health perception. Liposuction breast reduction is a useful breast reduction modality in the properly selected patient. African American women, who may traditionally forego breast reduction surgery because of scarring, are excellent candidates for this type of reduction procedure.

  12. Batch Covariance Relaxation (BCR) Adaptive Processing.

    Science.gov (United States)

    1981-08-01

    leads to the equivalent bandpass transfer function K Pk-8) Bpp (s) =17 - 22 where C2I is the radian IF frequency normalized by wc. Assuming, tacitly...transfer function in (2-3) is given by H +(f + fE) = H+ Bpp (I + 6 ) (2-13) provided that f and f, are understood to be normalized by fc = wc/2r. In...4..J - tj, 45I2 a I a N 1A CZ~ IJ~oa 1,1 2.0 X : Z 1-3 1 a * N -- e - -o 0 (A -1- 1U z 0 8 Or I W *IA O! IU fau a :at oc- -MZ a Iaaa a a m :wU I..- 1

  13. Characteristics of Mobile Payment Procedures

    OpenAIRE

    Kreyer, Nina; Pousttchi, Key; Turowski, Klaus

    2002-01-01

    Companies are not going to invest into the development of innovative applications or services unless these can be charged for appropriately. Thus, the existence of standardized and widely accepted mobile payment procedures is crucial for successful business-to-customer mobile commerce. The acceptance of mobile payment procedures depends on costs, security and convenience issues. For the latter, it is important that a procedure can be used over the different payment scenarios mobile commerce, ...

  14. Coding for urologic office procedures.

    Science.gov (United States)

    Dowling, Robert A; Painter, Mark

    2013-11-01

    This article summarizes current best practices for documenting, coding, and billing common office-based urologic procedures. Topics covered include general principles, basic and advanced urologic coding, creation of medical records that support compliant coding practices, bundled codes and unbundling, global periods, modifiers for procedure codes, when to bill for evaluation and management services during the same visit, coding for supplies, and laboratory and radiology procedures pertinent to urology practice. Detailed information is included for the most common urology office procedures, and suggested resources and references are provided. This information is of value to physicians, office managers, and their coding staff. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Acquisition Policy and Procedures Program

    National Research Council Canada - National Science Library

    2001-01-01

    This Instruction establishes policies, responsibilities, and procedures for the procurement of goods and services to include supplies, equipment, publications, furniture, and information technology...

  16. Electronic Procedures for Medical Operations

    Science.gov (United States)

    2015-01-01

    Electronic procedures are replacing text-based documents for recording the steps in performing medical operations aboard the International Space Station. S&K Aerospace, LLC, has developed a content-based electronic system-based on the Extensible Markup Language (XML) standard-that separates text from formatting standards and tags items contained in procedures so they can be recognized by other electronic systems. For example, to change a standard format, electronic procedures are changed in a single batch process, and the entire body of procedures will have the new format. Procedures can be quickly searched to determine which are affected by software and hardware changes. Similarly, procedures are easily shared with other electronic systems. The system also enables real-time data capture and automatic bookmarking of current procedure steps. In Phase II of the project, S&K Aerospace developed a Procedure Representation Language (PRL) and tools to support the creation and maintenance of electronic procedures for medical operations. The goal is to develop these tools in such a way that new advances can be inserted easily, leading to an eventual medical decision support system.

  17. Model Reduction in Biomechanics

    Science.gov (United States)

    Feng, Yan

    mechanical parameters from experimental results. However, in real biological world, these homogeneous and isotropic assumptions are usually invalidate. Thus, instead of using hypothesized model, a specific continuum model at mesoscopic scale can be introduced based upon data reduction of the results from molecular simulations at atomistic level. Once a continuum model is established, it can provide details on the distribution of stresses and strains induced within the biomolecular system which is useful in determining the distribution and transmission of these forces to the cytoskeletal and sub-cellular components, and help us gain a better understanding in cell mechanics. A data-driven model reduction approach to the problem of microtubule mechanics as an application is present, a beam element is constructed for microtubules based upon data reduction of the results from molecular simulation of the carbon backbone chain of alphabeta-tubulin dimers. The data base of mechanical responses to various types of loads from molecular simulation is reduced to dominant modes. The dominant modes are subsequently used to construct the stiffness matrix of a beam element that captures the anisotropic behavior and deformation mode coupling that arises from a microtubule's spiral structure. In contrast to standard Euler-Bernoulli or Timoshenko beam elements, the link between forces and node displacements results not from hypothesized deformation behavior, but directly from the data obtained by molecular scale simulation. Differences between the resulting microtubule data-driven beam model (MTDDBM) and standard beam elements are presented, with a focus on coupling of bending, stretch, shear deformations. The MTDDBM is just as economical to use as a standard beam element, and allows accurate reconstruction of the mechanical behavior of structures within a cell as exemplified in a simple model of a component element of the mitotic spindle.

  18. Pollutant Assessments Group procedures manual: Volume 2, Technical procedures

    Energy Technology Data Exchange (ETDEWEB)

    1992-03-01

    This is volume 2 of the manuals that describes the technical procedures currently in use by the Pollution Assessments Group. This manual incorporates new developments in hazardous waste assessment technology and administrative policy. Descriptions of the equipment, procedures and operations of such things as radiation detection, soil sampling, radionuclide monitoring, and equipment decontamination are included in this manual. (MB)

  19. Reduction of blue tungsten oxide

    International Nuclear Information System (INIS)

    Wilken, T.; Wert, C.; Woodhouse, J.; Morcom, W.

    1975-01-01

    A significant portion of commercial tungsten is produced by hydrogen reduction of oxides. Although several modes of reduction are possible, hydrogen reduction is used where high purity tungsten is required and where the addition of other elements or compounds is desired for modification of the metal, as is done for filaments in the lamp industry. Although several investigations of the reduction of oxides have been reported (1 to 5), few principles have been developed which can aid in assessment of current commercial practice. The reduction process was examined under conditions approximating commercial practice. The specific objectives were to determine the effects of dopants, of water vapor in the reducing atmosphere, and of reduction temperature upon: (1) the rate of the reaction by which blue tungsten oxide is reduced to tungsten metal, (2) the intermediate oxides associated with reduction, and (3) the morphology of the resulting tungsten powder

  20. Size reduction machine

    International Nuclear Information System (INIS)

    Fricke, V.

    1999-01-01

    The Size Reduction Machine (SRM) is a mobile platform capable of shearing various shapes and types of metal components at a variety of elevations. This shearing activity can be performed without direct physical movement and placement of the shear head by the operator. The base unit is manually moved and roughly aligned to each cut location. The base contains the electronics: hydraulic pumps, servos, and actuators needed to move the shear-positioning arm. The movable arm allows the shear head to have six axes of movement and to cut to within 4 inches of a wall surface. The unit has a slick electrostatic capture coating to assist in external decontamination. Internal contamination of the unit is controlled by a high-efficiency particulate air (HEPA) filter on the cooling inlet fan. The unit is compact enough to access areas through a 36-inch standard door opening. This paper is an Innovative Technology Summary Report designed to provide potential users with the information they need to quickly determine if a technology would apply to a particular environmental management problem. They also are designed for readers who may recommend that a technology be considered by prospective users

  1. Electrochemical reduction of NOx

    DEFF Research Database (Denmark)

    Traulsen, Marie Lund

    NO and NO2 (collectively referred to as NOx) are air pollutants, and the largest single contributor to NOx pollution is automotive exhaust. This study investigates electrochemical deNOx, a technology which aims to remove NOx from automotive diesel exhaust by electrochemical reduction of NOx to N2...... and O2. The focus in this study is on improving the activity and selectivity of solid oxide electrodes for electrochemical deNOx by addition of NOx storage compounds to the electrodes. Two different composite electrodes, La0.85Sr0.15MnO3-δ-Ce0.9Gd0.1O1.95 (LSM15-CGO10) and La0.85Sr0.15FeO3-δ-Ce0.9Gd0.1O......1.95 (LSF15-CGO10), have been investigated in combination with three different NOx storage compounds: BaO, K2O and MnOx. The main focus in the investigation has been on conversion measurements and electrochemical characterization, the latter by means of electrochemical impedance spectroscopy...

  2. Syncrude emissions reduction project

    Energy Technology Data Exchange (ETDEWEB)

    Fiedler, M.A. [Alstom Power Inc., Knoxville, TN (United States); Ibbotson, P. [Syncrude Canada Ltd., Calgary, AB (Canada)

    2008-07-01

    This paper described an emissions reduction project conducted by Syncrude Canada and various other companies currently developing and processing oil sands in Alberta. Syncrude's upgrader expansion program included the installation of an ammonia-based wet flue gas desulfurizer (FGD) designed to remove sulphur dioxide (SO{sub 2}) from a coker train. Syncrude is also installing the FGD technology at its existing plants. It is expected that installation of the FGDs will reduced total site emissions of SO{sub 2} by 60 per cent. The fluid cokers are used to crack the long hydrocarbon chain bitumen molecules into shorter molecules. It is expected that the FGD system will also reduce particulate and SO{sub 3} levels. The FGD system was selected after an evaluation of technologies used by the coal-fired power industry. A dry FGD system was selected to operate above the water saturation temperature of the flue gas. Calcium oxide was used as a reagent. Hot gas was quenched in a spray dryer absorber with a slurry of calcium hydroxide. Rotary atomizers were used to developer uniform droplets of slurry. The system's fabric filter was a low ratio reverse gas-cleaned unit. Particulate matter from the gases was deposited on the interior of the filter bags. Clean hot gas was drawn through reverse gas fans into a reverse gas manifold. A timeline of the FGD technology installation process was included. 3 tabs., 28 figs.

  3. 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

  4. Proof Rules for Recursive Procedures

    NARCIS (Netherlands)

    Hesselink, Wim H.

    1993-01-01

    Four proof rules for recursive procedures in a Pascal-like language are presented. The main rule deals with total correctness and is based on results of Gries and Martin. The rule is easier to apply than Martin's. It is introduced as an extension of a specification format for Pascal-procedures, with

  5. Laparoscopic reversal of Hartmann's procedure

    DEFF Research Database (Denmark)

    Svenningsen, Peter Olsen; Bulut, Orhan; Jess, Per

    2010-01-01

    of Hartmann's procedure as safely as in open surgery and with a faster recovery, shorter hospital stay and less blood loss despite a longer knife time. It therefore seems reasonable to offer patients a laparoscopic procedure at departments which are skilled in laparoscopic surgery and use it for standard...

  6. Developing Competency in Payroll Procedures

    Science.gov (United States)

    Jackson, Allen L.

    1975-01-01

    The author describes a sequence of units that provides for competency in payroll procedures. The units could be the basis for a four to six week minicourse and are adaptable, so that the student, upon completion, will be able to apply his learning to any payroll procedures system. (Author/AJ)

  7. Failure to Follow Written Procedures

    Science.gov (United States)

    2017-12-01

    Most tasks in aviation have a mandated written procedure to be followed specifically under the Code of Federal Regulations (CFR) Part 14, Section 43.13(a). However, the incidence of Failure to Follow Procedure (FFP) events continues to be a major iss...

  8. Procedure for taking physical inventories

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    This session is intended to apprise one of the various aspects of procedures and routines that Exxon Nuclear uses with respect to its nuclear materials physical inventory program. The presentation describes how plant physical inventories are planned and taken. The description includes the planning and preparation for taking the inventory, the clean-out procedures for converting in-process material to measurable items, the administrative procedures for establishing independent inventory teams and for inventorying each inventory area, the verification procedures used to include previously measured tamper-safed items in the inventory, and lastly, procedures used to reconcile the inventory and calculate MUF (materials unaccounted for). The purpose of the session is to enable participants to: (1) understand the planning and pre-inventorty procedures and their importance; (2) understand the need for and the required intensity of clean-out procedures; (3) understand how inventory teams are formed, and how the inventory is conducted; (4) understand the distinction between inventory previously measured tamper-safed items and other materials not so characterized; (5) understand the reconciliation procedures; and (6) calculate a MUF given the book and inventory results

  9. Deliberating emission reduction options

    Energy Technology Data Exchange (ETDEWEB)

    Dowd, A. M.; Rodriguez, M.; Jeanneret, T. [Commonwealth Scientific and Industrial Research Organisation CSIRO, 37 Graham Rd, Highett VIC 3190 (Australia); De Best-Waldhober, M.; Straver, K.; Mastop, J.; Paukovic, M. [Energy research Centre of the Netherlands ECN, Policy Studies, Amsterdam (Netherlands)

    2012-06-15

    For more than 20 years there has been a concerted international effort toward addressing climate change. International conventions, such as the United Nations Foreign Convention on Climate Change (UNFCCC; ratified in 1994), have been established by committed nations seeking to address global climate change through the reduction of greenhouse gases emitted into the Earth's atmosphere (Global CCS Institute, 2011). Long recognised as the most crucial of the greenhouse gases to impact global warming, the majority of carbon dioxide's anthropogenic global emissions are directly related to fuel combustion of which both Australia and the Netherlands' energy production is significantly reliant. Both these nations will need to consider many opinions and make hard decisions if alternative energy options are to be implemented at the scale that is required to meet international emission targets. The decisions that are required not only need to consider the many options available but also their consequences. Along with politicians, policy developers and industry, the general public also need to be active participants in deciding which energy options, and their subsequent consequences, are acceptable for implementation at the national level. Access to balanced and factual information is essential in establishing informed opinions on the many policy options available. Past research has used several methods to measure public perceptions and opinions yet for complex issues, such as emission reduction, some of these methods have shown to be problematic. For example, semi structured interviews can provide data that is flexible and context rich yet is does also come with the limitations such as it seldom provides a practical assessment that can be utilised from researcher to researcher, across disciplines and public participation techniques. Surveys on the other hand usually address these limitations but surveys that do not encourage comparison of information or ask participants to

  10. Deliberating emission reduction options

    Energy Technology Data Exchange (ETDEWEB)

    Dowd, A.M.; Rodriguez, M.; Jeanneret, T. [Commonwealth Scientific and Industrial Research Organisation CSIRO, 37 Graham Rd, Highett VIC 3190 (Australia); De Best-Waldhober, M.; Straver, K.; Mastop, J.; Paukovic, M. [Energy research Centre of the Netherlands ECN, Policy Studies, Amsterdam (Netherlands)

    2012-06-15

    For more than 20 years there has been a concerted international effort toward addressing climate change. International conventions, such as the United Nations Foreign Convention on Climate Change (UNFCCC; ratified in 1994), have been established by committed nations seeking to address global climate change through the reduction of greenhouse gases emitted into the Earth's atmosphere (Global CCS Institute, 2011). Long recognised as the most crucial of the greenhouse gases to impact global warming, the majority of carbon dioxide's anthropogenic global emissions are directly related to fuel combustion of which both Australia and the Netherlands' energy production is significantly reliant. Both these nations will need to consider many opinions and make hard decisions if alternative energy options are to be implemented at the scale that is required to meet international emission targets. The decisions that are required not only need to consider the many options available but also their consequences. Along with politicians, policy developers and industry, the general public also need to be active participants in deciding which energy options, and their subsequent consequences, are acceptable for implementation at the national level. Access to balanced and factual information is essential in establishing informed opinions on the many policy options available. Past research has used several methods to measure public perceptions and opinions yet for complex issues, such as emission reduction, some of these methods have shown to be problematic. For example, semi structured interviews can provide data that is flexible and context rich yet is does also come with the limitations such as it seldom provides a practical assessment that can be utilised from researcher to researcher, across disciplines and public participation techniques. Surveys on the other hand usually address these limitations but surveys that do not encourage comparison of information or ask

  11. Principal Components as a Data Reduction and Noise Reduction Technique

    Science.gov (United States)

    Imhoff, M. L.; Campbell, W. J.

    1982-01-01

    The potential of principal components as a pipeline data reduction technique for thematic mapper data was assessed and principal components analysis and its transformation as a noise reduction technique was examined. Two primary factors were considered: (1) how might data reduction and noise reduction using the principal components transformation affect the extraction of accurate spectral classifications; and (2) what are the real savings in terms of computer processing and storage costs of using reduced data over the full 7-band TM complement. An area in central Pennsylvania was chosen for a study area. The image data for the project were collected using the Earth Resources Laboratory's thematic mapper simulator (TMS) instrument.

  12. Optimization of wet digestion procedure of blood and tissue for selenium determination by means of 75Se tracer

    International Nuclear Information System (INIS)

    Holynska, B.; Lipinska, K.

    1977-01-01

    Selenium-75 tracer has been used for optimization of analytical procedure of selenium determination in blood and tissue. Wet digestion procedure and reduction of selenium to its elemental form with tellurium as coprecipitant have been tested. Recovery of selenium obtained with the use of optimized analytical procedure amounts up 95% and precision is equal to 4.2%. (author)

  13. An analysis of contingency statements in a DRO procedure: A case report.

    Science.gov (United States)

    Gerow, Stephanie; Rispoli, Mandy; Boles, Margot B; Neely, Leslie C

    2015-06-01

    To examine latency to criterion for reduction of challenging behaviour with and without stating a contingency statement immediately prior to a DRO procedure. An ABAC design in which A was baseline, B was used to evaluate the efficacy of a DRO procedure, and C was used to evaluate the efficacy of a DRO procedure with a contingency statement. The DRO with the contingency statement intervention was associated with a shorter latency to behaviour change than the DRO procedure without the contingency statement. These preliminary findings from this case study highlight the importance of examining the efficiency of behaviour change procedures. Directions for future research are provided.

  14. Biomass Compositional Analysis Laboratory Procedures | Bioenergy | NREL

    Science.gov (United States)

    Biomass Compositional Analysis Laboratory Procedures Biomass Compositional Analysis Laboratory Procedures NREL develops laboratory analytical procedures (LAPs) for standard biomass analysis. These procedures help scientists and analysts understand more about the chemical composition of raw biomass

  15. Simplified Laboratory Runoff Procedure (SLRP): Procedure and Application

    National Research Council Canada - National Science Library

    Price, Richard

    2000-01-01

    The Simplified Laboratory Runoff Procedure (SLRP) was developed to provide a faster, less expensive approach to evaluate surface runoff water quality from dredged material placed in an upland environment...

  16. Robust methods for data reduction

    CERN Document Server

    Farcomeni, Alessio

    2015-01-01

    Robust Methods for Data Reduction gives a non-technical overview of robust data reduction techniques, encouraging the use of these important and useful methods in practical applications. The main areas covered include principal components analysis, sparse principal component analysis, canonical correlation analysis, factor analysis, clustering, double clustering, and discriminant analysis.The first part of the book illustrates how dimension reduction techniques synthesize available information by reducing the dimensionality of the data. The second part focuses on cluster and discriminant analy

  17. Lithium aluminate spheroids prepared by emulsion procedure

    International Nuclear Information System (INIS)

    Mateos, A.G.; DiBello, P.M.; Zaleski, A.B.

    1991-01-01

    Lithium aluminate powders were prepared by emulsion evaporation method. The procedure involved preparation of water-in-oil emulsion, with the aqueous phase being a solution of Li and Al nitrates. The mixed salts precursor crystallized to gamma-LiAlO 2 at 700C. Single phase LiAlO 2 occurred as μm spherical particles with average crystallite size of 81 angstrom and surface area of 14 M 2 /g. After prolonged heating at 900C, the aluminate powder crystallite size grew by 5 times with a reduction in particle porosity. The emulsion technique promotes close control of particle size and shape of product and the technique facilitates chemical reaction of constituents and sinterability of resulting product

  18. Pelvic denervation procedures for dysmenorrhea.

    Science.gov (United States)

    Ramirez, Christina; Donnellan, Nicole

    2017-08-01

    Chronic pelvic pain and dysmenorrhea are common conditions affecting reproductive-age women. Surgical pelvic denervation procedures may be a treatment option for women with midline dysmenorrhea, in which medical management is declined by the patient, ineffective at managing symptoms, or medically contraindicated. This review describes the surgical techniques and complications associated with pelvic denervation procedures as well as the current evidence for these procedures in women with primary dysmenorrhea and dysmenorrhea secondary to endometriosis. Presacral neurectomy is the preferred pelvic denervation procedure in patients with primary dysmenorrhea and midline chronic pelvic pain associated with endometriosis. In patients with endometriosis presacral neurectomy is a useful adjunct to excision or ablation of all endometrial lesions to improve postoperative pain relief. There is no additional patient benefit of performing combined presacral neurectomy and uterine nerve ablation procedures. Pelvic denervation procedures can be performed safely and quickly with a low risk of complication if the surgeon is knowledgeable and skilled in operating in the presacral space. Patients should be adequately counseled on expected success rates and potential complications associated with pelvic denervation procedures.

  19. Fraction Reduction in Membrane Systems

    Directory of Open Access Journals (Sweden)

    Ping Guo

    2014-01-01

    Full Text Available Fraction reduction is a basic computation for rational numbers. P system is a new computing model, while the current methods for fraction reductions are not available in these systems. In this paper, we propose a method of fraction reduction and discuss how to carry it out in cell-like P systems with the membrane structure and the rules with priority designed. During the application of fraction reduction rules, synchronization is guaranteed by arranging some special objects in these rules. Our work contributes to performing the rational computation in P systems since the rational operands can be given in the form of fraction.

  20. Logistics Reduction: Heat Melt Compactor

    Data.gov (United States)

    National Aeronautics and Space Administration — The Advanced Exploration Systems (AES) Logistics Reduction (LR) project Heat Melt Compactor (HMC) technology is a waste management technology. Currently, there are...

  1. Nonlinear Model Reduction for RTCVD

    National Research Council Canada - National Science Library

    Newman, Andrew J; Krishnaprasad, P. S

    1998-01-01

    ...) for semiconductor manufacturing. They focus on model reduction for the ordinary differential equation model describing heat transfer to, from, and within a semiconductor wafer in the RTCVD chamber...

  2. Does fluoroscopy improve outcomes in paediatric forearm fracture reduction?

    International Nuclear Information System (INIS)

    Menachem, S.; Sharfman, Z.T.; Perets, I.; Arami, A.; Eyal, G.; Drexler, M.; Chechik, O.

    2016-01-01

    Aim: To compare the radiographic results of paediatric forearm fracture reduced with and without fluoroscopic enhancement to investigate whether fractures reduced under fluoroscopic guidance would have smaller residual deformities and lower rates of re-reduction and surgery. Materials and methods: A retrospective cohort analysis was conducted comparing paediatric patients with acute forearm fracture in two trauma centres. Demographics and radiographic data from paediatric forearm fractures treated in Trauma Centre A with the aid of a C-arm fluoroscopy were compared to those treated without fluoroscopy in Trauma Centre B. Re-reduction, late displacement, post-reduction deformity, and need for surgical intervention were compared between the two groups. Results: The cohort included 229 children (175 boys and 54 girls, mean age 9.41±3.2 years, range 1–16 years) with unilateral forearm fractures (83 manipulated with fluoroscopy and 146 without). Thirty-four (15%) children underwent re-reduction procedures in the emergency department. Fifty-three (23%) children had secondary displacement in the cast, of which 18 were operated on, 20 were re-manipulated, and the remaining 15 were kept in the cast with an acceptable deformity. Twenty-nine additional children underwent operation for reasons other than secondary displacement. There were no significant differences in re-reduction and surgery rates or in post-reduction deformities between the two groups. Conclusion: The use of fluoroscopy during reduction of forearm fractures in the paediatric population apparently does not have a significant effect on patient outcomes. Reductions performed without fluoroscopy were comparably accurate in correcting deformities in both coronal and sagittal planes. - Highlights: • Compared outcomes of pediatric forearm fracture reduction with and without fluoroscopy. • The use of fluoroscopy during reduction of forearm fractures in the pediatric population apparently does not have a

  3. Specified assurance level sampling procedure

    International Nuclear Information System (INIS)

    Willner, O.

    1980-11-01

    In the nuclear industry design specifications for certain quality characteristics require that the final product be inspected by a sampling plan which can demonstrate product conformance to stated assurance levels. The Specified Assurance Level (SAL) Sampling Procedure has been developed to permit the direct selection of attribute sampling plans which can meet commonly used assurance levels. The SAL procedure contains sampling plans which yield the minimum sample size at stated assurance levels. The SAL procedure also provides sampling plans with acceptance numbers ranging from 0 to 10, thus, making available to the user a wide choice of plans all designed to comply with a stated assurance level

  4. Environmental control procedures at the Savannah River Plant

    International Nuclear Information System (INIS)

    Sheldon, E.B.

    1975-01-01

    New environmental control activities in the past year at SRP have included improved control and reporting procedures for chemical spills, reclamation of high-value scrap from wastes, new disposal methods for solid wastes not suitable for the sanitary landfill, improved oil containment, and reduction of sediment discharges to on-plant streams. Interdepartmental committees provide the primary routes for planning and coordinating environmental protection throughout SRP. An improved site-use coordination procedure, developed and implemented by ERDA-SR, has provided more effective control and communication pertaining to activities of the several organizations actively using the 300-square-mile SRP site. (auth)

  5. Developing procedures for the handling of highly radioactive materials

    International Nuclear Information System (INIS)

    Wagner, M.L.

    1994-01-01

    Handling procedures for highly radioactive materials must be analyzed for the reduction of radiation dose. In keeping with ALARA principles, time, distance, and shielding must be used to maximum benefit during the job. After an initial risk assessment is accomplished, job pre-planning meetings and cold open-quotes walk-throughsclose quotes are held in order to engineer the best workable procedure given allocated resources, and to reduce personnel exposure. This paper shows the relationship between each step in the job development, over a number of actual jobs, drawing out how subtle changes in practice can affect the individual and team radiation dose

  6. Impact of Reduction Parameters on the Initial Performance and Stability of Ni/(Sc)YSZ Cermet Anodes for SOFCs

    DEFF Research Database (Denmark)

    Ebbehøj, Søren Lyng; Ramos, Tania; Mogensen, Mogens Bjerg

    2012-01-01

    In-situ reduction of Ni cermet anodes produces the porosity and influences the microstructure, performance and stability of the anodes. The impact on initial performance, stability and microstructure of two different reduction procedures currently in use at DTU Energy Conversion with reduction...

  7. ANAESTHESIA FOR OPHTHALMIC SURGICAL PROCEDURES

    African Journals Online (AJOL)

    Objective: To review factors influencing the choice of anaesthesia for ophthalmic surgical procedures. ... as risk associated with general anaesthesia (8) they are more .... Wilson ME, Pandey SK, Thakur J. Paediatric cataract blindness in the ...

  8. Adequate procedures for specific exams

    International Nuclear Information System (INIS)

    Staevie, G.L.G.; Gattringer, D.K.; Dal Mas, C.R.; Tessman, M.

    1996-01-01

    Some ideal procedures for specific radiographic exams are briefly presented. The aim is to improve the quality standard, establishing a specific method for each exam in order to decrease films waste and reduce the patient dose exposure

  9. An Analytical Cost Estimation Procedure

    National Research Council Canada - National Science Library

    Jayachandran, Toke

    1999-01-01

    Analytical procedures that can be used to do a sensitivity analysis of a cost estimate, and to perform tradeoffs to identify input values that can reduce the total cost of a project, are described in the report...

  10. Soil Gas Sampling Operating Procedure

    Science.gov (United States)

    EPA Region 4 Science and Ecosystem Support Division (SESD) document that describes general and specific procedures, methods, and considerations when collecting soil gas samples for field screening or laboratory analysis.

  11. Construction inspection manual of procedures

    Science.gov (United States)

    2009-01-01

    This manual provides highway construction personnel with relevant, practical information in order to perform accurate inspections and provide relevant construction procedural information for the various roadway and structures items of work. It is the...

  12. Fusion Imaging for Procedural Guidance.

    Science.gov (United States)

    Wiley, Brandon M; Eleid, Mackram F; Thaden, Jeremy J

    2018-05-01

    The field of percutaneous structural heart interventions has grown tremendously in recent years. This growth has fueled the development of new imaging protocols and technologies in parallel to help facilitate these minimally-invasive procedures. Fusion imaging is an exciting new technology that combines the strength of 2 imaging modalities and has the potential to improve procedural planning and the safety of many commonly performed transcatheter procedures. In this review we discuss the basic concepts of fusion imaging along with the relative strengths and weaknesses of static vs dynamic fusion imaging modalities. This review will focus primarily on echocardiographic-fluoroscopic fusion imaging and its application in commonly performed transcatheter structural heart procedures. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  13. Surface Environmental Surveillance Procedures Manual

    Energy Technology Data Exchange (ETDEWEB)

    Hanf, RW; Dirkes, RL

    1990-02-01

    This manual establishes the procedures for the collection of environmental samples and the performance of radiation surveys and other field measurements. Responsibilities are defined for those personnel directly involved in the collection of samples and the performance of field measurements.

  14. FFTF reactor plant procedures plan

    International Nuclear Information System (INIS)

    1972-01-01

    The document presented defines the plan to be used to coordinate the preparation, review, approval, and issuance of the operating procedure documents required to ensure safe and efficient operation of FFTF

  15. Adolescent test or procedure preparation

    Science.gov (United States)

    ... someone else) during the procedure Playing hand-held video games Using guided imagery Trying other distractions, such as ... effects the test may cause. Older teens may benefit from videos that show adolescents of the same age explaining ...

  16. Environmental protection and procedural law

    International Nuclear Information System (INIS)

    Mutschler, U.

    1978-01-01

    For the power industry which is 'independent of licensing', the Ule/Laubinger statement as well as its discussion on the 52th German legal experts' day are of considerable importance. It is therefore absolutely necessary to critically investigate the statements of this expert's opinion and the considerations on which they are based. This investigation is limited to those licensing procedures which in the terminology of experts, are 'similar to the plan approval procedure'. This applies mainly to the procedures according to paragraph 4 ff of the Federal Act on the Protection Against Nuisances and paragraph 7 of the Atomic Energy Law: Preliminaries publication of documents, inspection of files, public hearing, taking of evidence, persons with special responsibilities, administrative proceedings, actions by associations. The deficiencies in the execution of environmental procedural law is briefly mentioned. The notes in the article refer only to air pollution. (orig./HP) [de

  17. Urinary incontinence - vaginal sling procedures

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007376.htm Urinary incontinence - vaginal sling procedures To use the sharing features ... are types of surgeries that help control stress urinary incontinence . This is urine leakage that happens when you ...

  18. Loop Electrosurgical Excision Procedure (LEEP)

    Science.gov (United States)

    ... applied to your cervix to stop any bleeding. Electrocautery also may be used to control bleeding. The ... the uterus at the top of the vagina. Electrocautery: A procedure in which an instrument works with ...

  19. Spillover effects of Medicare fee reductions: evidence from ophthalmology.

    Science.gov (United States)

    Mitchell, Jean M; Hadley, Jack; Gaskin, Darrell J

    2002-09-01

    Relatively little research has examined physicians' supply responses to Medicare fee cuts especially whether fee reductions for specific procedures have "spillover" effects that cause physicians to increase the supply of other services they provide. In this study we investigate whether ophthalmologist changed their provision of non-cataract services to Medicare patients over the time period 1992-1994, when the Medicare Fee Schedule (MFS) resulted in a 17.4% reduction in the average fee paid for a cataract extraction. Following the McGuire-Pauly model of physician behavior (McGuire and Pauly, 1991), we estimated a supply function for non-cataract procedures that included three price variables (own-price, a Medicare cross-price and a private cross-price) and an income effect. The Medicare cross-price and income variables capture spillover effects. Consistent with the model's predictions, we found that the Medicare cross-price is significant and negative, implying that a 10% reduction in the fee for a cataract extraction will cause ophthalmologists to supply about 5% more non-cataract services. Second, the income variable is highly significant, but its impact on the supply of non-cataract services is trivial. The suggests that physicians behave more like profit maximizing firms than target income seekers. We also found that the own-price and the private cross-price variables are highly significant and have the expected positive and negative effects on the volume of non-cataract services respectively. Our results demonstrate the importance of evaluating volume responses to fee changes for the array of services the physician performs, not just the procedure whose fee has been reduced. Focusing only on the procedure whose fee has been cut will yield an incomplete picture of how fee reductions for specific procedures affect physician supply decisions.

  20. Parameter setting and input reduction

    NARCIS (Netherlands)

    Evers, A.; van Kampen, N.J.|info:eu-repo/dai/nl/126439737

    2008-01-01

    The language acquisition procedure identifies certain properties of the target grammar before others. The evidence from the input is processed in a stepwise order. Section 1 equates that order and its typical effects with an order of parameter setting. The question is how the acquisition procedure