WorldWideScience

Sample records for bcr process

  1. Main: 1BCR [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1BCR 小麦 Bread Wheat ... Triticum aestivum Serine Carboxypeptidase Ii Chains A And B Name=Cbp2; Tri ... .Remington 1bcr 25 Peptide Aldehyde Complexes With Wheat ... Serine 1bcr 26 Carboxypeptidase Ii 1bcr 27to Be Pu ... Microbial Peptide Aldehyde Inhibitor 1bcr 21 CBP2_WHEAT :259,6|CBP2_WHEAT :417,266|PIR; A29639; A29639.|PDB; ...

  2. Evaluation of Morpholino Antisense Oligos’ Role on BCR-ABL Gene Silencing in the K562 Cell Line

    Directory of Open Access Journals (Sweden)

    Bahman Delalat

    2010-01-01

    Full Text Available Objective: Chronic myeloid leukemia (CML develops when a hematopoietic stem cellacquires the BCR/ABL fusion gene. This causes these transformed hematopoietic cellsto have a greater than normal proliferation rate. Scientists attempt to improve the CMLtreatment process by silencing the BCR/ABL oncogene. In this work, we used morpholinoantisense oligos to silence the BCR/ABL oncogene.Materials and Methods: In this study, the K562 was used as a BCR/ABL fusion-genepositive cell line and the Jurkat cell line as a control. We explored the inhibiting capacityof morpholino antisense oligos in the the expression of the BCR/ABL oncogene andstudied their p210 BCR/ABL suppression, inhibition of cell proliferation and stimulation ofapoptosis in the K562 cells after 24 and 48 hours. Endo-Porter was used for delivery ofmorpholino antisense oligos into cell cytosols. Meanwhile, flow cytometric analysis wasperformed in order to determine the appropriate concentration of morpholino antisenseoligos.Results: Prolonged exposure of the K562 cell line to the morpholino antisense oligostargeted against the BCR-ABL gene showed proliferation inhibition as its main feature.After western blotting, we found that complete silencing of BCR/ABL was achieved, butflow cytometric analysis showed no broad apoptosis.Conclusion: The results indicate that the Morpholino antisense oligo is able to inhibitp210 BCR/ABL; however, it cannot induce broad apoptosis due to co-silencing of BCR.

  3. Instrumented testing of BCR Specimens

    International Nuclear Information System (INIS)

    Two times two reference batches of BCR material with nominal energies of 80J and 160J were impact tested on an instrumented machine. A good agreement was found between the friction-corrected dial energy and the integrated energy. Systematic differences have been detected between the two 80J batches: these differences do not occur in the typical force values and are a consequence of a post-maximum event. A small calibration difference exists for the 80J batches: this seems a consequence of the higher impact forces involved and suggests the influence of dynamic effects on the calibration (static, in-situ). The next step is to test similar batches on a non-instrumented impact tester to detect an eventual influence of the physical presence of instrumentation on the impact pot. It is expected that this effect will be minor

  4. Molecular Detection of BCR/ ABL Fusion Gene in Saudi Acute Lymphoblastic Leukemia Patients

    International Nuclear Information System (INIS)

    Background: Molecular cytogenetics is becoming one of the most useful tools targeting some genes which are generally considered to lead to leukemic transformation (as well as for numerical abnormalities). A fraction of acute lymphoblastic leukemia (ALL) cases carry the translocation t(9;22) (q34;ql1.2) which juxtaposes the ABL proto-oncogene to the BCR gene generating a chimeric gene, BCR/ABL. This aberration is more frequent in adult ALL (20%-40%) than in pediatric ALL >)5%), and predicts poor clinical outcome. Aim of our Work: Is to study BCR/ A BL fusion gene in ALL cases using fluorescent in situ hybridization. Patients and Methods: Twenty newly diagnosed ALL patients, 16 adult and 4 paediatric cases, were included in the study, 11 cases (55%) were of precursor B phenotype, S cases (40%) belonged to T lineage, while one case was bi phenotypic expressing mainly precursor B cell markers tether with CD13, CD33, CD117, Detection of BCR/ABL fusion gene was done using interphase FISH technique and was confirmed molecularly using the RT-PCR technique. Results: BCR/ ABL fusion gene was negative in all the examined cases, yet abnormality involving 9q34, ABL gene, either by addition or deletion was detected in three cases (15%). Two of these cases were associated with BCR gene extra copies (three and four copies, respectively). Conclusion: This may reflect the frequency of association of ABL gene and BCR gene abnormality in our cases, and that absence of fusion gene BCR/ABL does not exclude their role in the leukomogenic process, yet a larger study is required to confirm and detect the prevalence of these gene disturbances in ALL and their association

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

    OpenAIRE

    Roper, Nitin; DeAngelo, Daniel; Kuo, Frank; Cin, Paola Dal; Ghobrial, Irene; Aster, Jon C.

    2010-01-01

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

  6. Molecular Detection of BCR-ABL in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Qin, Ya-Zhen; Huang, Xiao-Jun

    2016-01-01

    All chronic myeloid leukemia (CML) patients have the BCR-ABL fusion gene. The constitutively activated BCR-ABL tyrosine kinase is a critical pathogenetic event in CML. Tyrosine kinase inhibitors (TKIs), such as imatinib, are synthesized small molecules that primarily target BCR-ABL tyrosine kinases and have become a first-line treatment for CML. Detection of BCR-ABL transcript level by real-time quantitative polymerase chain reaction (RQ-PCR) is a clinical routine for evaluating TKI treatment efficacy and predicting long-term response. Furthermore, because they are a main TKI resistance mechanism, the BCR-ABL tyrosine kinase domain (TKD) point mutations that are detected by Sanger sequencing can help clinicians make decisions on subsequent treatment selections. Here, we present protocols for the two abovementioned molecular methods for CML analysis. PMID:27581134

  7. 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.

  8. BCR-ABL Promotes PTEN Downregulation in Chronic Myeloid Leukemia

    OpenAIRE

    Cristina Panuzzo; Sabrina Crivellaro; Giovanna Carrà; Angelo Guerrasio; Giuseppe Saglio; Alessandro Morotti

    2014-01-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor suppressor PTEN plays a critical role in the pathogenesis of CML chronic phase, through non genomic loss of function mechanisms, such as protein down-regulation and impaired nuclear/cytoplasmic shuttling. Here we demonstrate that BCR-ABL promotes PTEN downregulation through a MEK dependent pathway. Furthermore, we describe a novel n...

  9. Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia

    OpenAIRE

    Feldhahn, Niklas; Arutyunyan, Anna; Stoddart, Sonia; ZHANG Bin; Schmidhuber, Sabine; Yi, Sun-ju; Kim, Yong-Mi; Groffen, John; Heisterkamp, Nora

    2012-01-01

    Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase i...

  10. BCR-ABL DERIVED PEPTIDE VACCINES FOR CHRONIC MYELOID LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    M. Bocchia

    2012-01-01

    Full Text Available Chronic Myeloid Leukemia (CML is a myeloproliferative pluripotent stem cell disorder characterized by the presence of a cytogenetic hallmark, the Philadelphia (Ph chromosome, and accounts for 15% of adult leukemias. The disease progresses from a chronic phase through an accelerated phase to a blast phase and its natural course accounts for a median 4 years survival1. The Ph chromosome is derived by a reciprocal translocation termed t(9;22 in which the c-abl oncogene has moved from chromosome 9 into the breakpoint cluster region (bcr, within the bcr gene on chromosome 22, resulting in a chimeric bcr-abl fusion gene that encodes a 210 KD protein (p210 with constitutive tyrosine kinase activity. Two major alternative chimeric p210 can result from this fusion gene: p210-b2a2 where the junction occurs between bcr exon 2 (b2 and abl exon 2 (a2 and p210-b3a2 where the the junction occurs between bcr exon 3 (b3 and abl exon 2 (a2. About 40% of CML patients harbor the p210-b2a2 and about 60% of them show the p210-b3a2.

  11. BCR certified reference materials for reactor neutron dosimetry

    International Nuclear Information System (INIS)

    A series of reference materials intended for use as activation or fission monitors for neutron fluence rate measurements has been prepared by the Joint Research Centre of the European Commission. Certification has been carried out by expert European laboratories and distribution of the certified reference materials (CRMs) is through the BCR programme of the Commission. The list (18 CRMs) includes materials to cover the complete energy spectrum, and suitable for different irradiation times. Fission monitors are 238UO2 or 237NpO2 in the form of microspheres. Activation monitors are high purity metals (Ni, Cu, Al, Fe, Nb, Rh, or Ti), certified for interfering trace impurities, or dilute aluminium-based alloys, where aluminium is chosen as a suitable matrix for reducing the neutron self-shielding effect. Newly certified materials are IRMM-530R Al-0.1%Au, replacing the exhausted IRMM-530 material, used as comparator for k0-standardization, and three new Al-Co alloys (0.01-1%Co). Two others, in the process of certification are Al-0.1%Ag and Al-2%Sc for thermal and epithermal fluence rate measurements. Other candidate reference materials currently being certified are two uranium-doped glass intended for dosimetry by the fission-track technique. (author)

  12. INHIBITION OF APOPTOSIS BY bcr-abl FUSION GENE IN K562 CELLS

    Institute of Scientific and Technical Information of China (English)

    WANG Chun-hong; SUN Bing-zhong; YUAN Yue-chuan

    1999-01-01

    Objective: To investigate the effect of bcr-abl fusion gene on CML cell apoptosis. Methods: Apoptosis of exvivo cultured K562 cells were observed after exposure to synthetic 18 mer antisense oligodeoxynucleotide complementary to the bcr-abl junction (b3a2). Results: Apoptosis of K562 cells was significantly increased associated with inhibition of bcr-abl expression. Conclusion: bcr-abl fusion gene formation due to chromosome translocation may be the major mechanism of CML via inhibition of apoptosis.

  13. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias

    OpenAIRE

    Weisberg, Ellen; Catley, Laurie; Wright, Renee D.; Moreno, Daisy; Banerji, Lolita; Ray, Arghya; Manley, Paul W; Mestan, Juergen; Fabbro, Doriano; Jiang, Jingrui; Hall-Meyers, Elizabeth; Callahan, Linda; DellaGatta, Jamie L.; Kung, Andrew L.; Griffin, James D.

    2007-01-01

    Drug resistance resulting from emergence of imatinib-resistant BCR-ABL point mutations is a significant problem in advanced-stage chronic myelogenous leukemia (CML). The BCR-ABL inhibitor, nilotinib (AMN107), is significantly more potent against BCR-ABL than imatinib, and is active against many imatinib-resistant BCR-ABL mutants. Phase 1/2 clinical trials show that nilotinib can induce remissions in patients who have previously failed imatinib, indicating that sequential therapy with these 2 ...

  14. Imatinib-dependent tyrosine phosphorylation profiling of Bcr-Abl-positive chronic myeloid leukemia cells

    OpenAIRE

    Preisinger, C.; Schwarz, J. P.; Bleijerveld, O.B.; et al

    2012-01-01

    Bcr-Abl is the major cause and pathogenetic principle of chronic myeloid leukemia (CML). Bcr-Abl results from a chromosomal translocation that fuses the bcr and abl genes, thereby generating a constitutively active tyrosine kinase, which stimulates several signaling networks required for proliferation and survival. peer-reviewed

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

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Wagner, Sebastian A; Beli, Petra; Gupta, Rajat; Kristiansen, Trine A; Malinova, Dessislava; Francavilla, Chiara; Tolar, Pavel; Bishop, Gail A; Hostager, Bruce S; Choudhary, Chuna Ram

    2015-01-01

    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...... provided datasets can serve as a valuable resource for further understanding BCR signaling networks....

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Puccetti Elena

    2006-11-01

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

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

    International Nuclear Information System (INIS)

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

  19. 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.

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

    International Nuclear Information System (INIS)

    Graphical abstract: Showing decrease in analytical uncertainty using the optimal (combined preconcentrated sample extract) method. nv (no value) where extract activities were 7Be geochemical behaviour is required to support tracer studies. ► Sequential extraction with natural 7Be 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 7Be 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 7Be with operationally defined soil phases. However, the subdivision of the low activity concentrations of fallout 7Be 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 7Be (t1/2 = 53.3 days). Here, three different methods of preparing and quantifying 7Be 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 7Be with metal oxyhydroxides to produce a thin source for gamma analysis. This method was applied to BCR extractions of natural 7Be 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 7Be fell between 84 and 112%. The stable Be data demonstrated that the extraction

  1. Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma

    Science.gov (United States)

    Amato, Teresa; Abate, Francesco; Piccaluga, Pierpaolo; Iacono, Michele; Fallerini, Chiara; Renieri, Alessandra; De Falco, Giulia; Ambrosio, Maria Raffaella; Mourmouras, Vaselious; Ogwang, Martin; Calbi, Valeria; Rabadan, Roul; Hummel, Michael; Pileri, Stefano; Bellan, Cristiana

    2016-01-01

    Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development. PMID:26712879

  2. Evaluation of the BCR sequential extraction procedure applied for two unpolluted Spanish soils

    International Nuclear Information System (INIS)

    The procedure of BCR sequential extraction has been applied to five samples from two unpolluted soils in southern Spain. Total concentrations of different elements have been calculated as the sum of the three fractions of BCR and the residue has been measured for each. Also, a total analysis based on INAA or total-digestion techniques has been performed for the same samples. BCR and total analysis closely agreed for As, Pb and Cd. For Cu, Co, Cr and Zn the comparison of the results did not provide definitive conclusions concerning the capability of BCR in measuring total concentrations. On the other hand, in these cases, a certain correlation was found between the concentrations measured and some soil characteristics, especially the clay, organic-matter and CaCO3 contents. BCR proved incapable of providing accurate measurements for Ni

  3. Gads (Grb2-related adaptor downstream of Shc) is required for BCR-ABL-mediated lymphoid leukemia

    Science.gov (United States)

    Gillis, LC; Berry, DM; Minden, MD; McGlade, CJ; Barber, DL

    2016-01-01

    Philadelphia chromosome-positive leukemias, including chronic myeloid leukemia and B-cell acute lymphoblastic leukemia (B-ALL), are driven by the oncogenic BCR-ABL fusion protein. Animal modeling experiments utilizing retroviral transduction and subsequent bone marrow transplantation have demonstrated that BCR-ABL generates both myeloid and lymphoid disease in mice receiving whole bone marrow transduced with BCR-ABL. Y177 of BCR-ABL is critical to the development of myeloid disease, and phosphorylation of Y177 has been shown to induce GRB2 binding to BCR-ABL, followed by activation of the Ras and phosphoinositide 3 kinase signaling pathways. We show that the GRB2-related adapter protein, GADS, also associates with BCR-ABL, specifically through Y177 and demonstrate that BCR-ABL-driven lymphoid disease requires Gads. BCR-ABL transduction of Gads(−/−) bone marrow results in short latency myeloid disease within 3–4 weeks of transplant, while wild-type mice succumb to both a longer latency lymphoid and myeloid diseases. We report that GADS mediates a unique BCR-ABL complex with SLP-76 in BCR-ABL-positive cell lines and B-ALL patient samples. These data suggest that GADS mediates lymphoid disease downstream of BCR-ABL through the recruitment of specific signaling intermediates. PMID:23399893

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

    Directory of Open Access Journals (Sweden)

    Chai Juin Hsien

    2011-12-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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

  5. Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells.

    Science.gov (United States)

    Mandanas, R A; Leibowitz, D S; Gharehbaghi, K; Tauchi, T; Burgess, G S; Miyazawa, K; Jayaram, H N; Boswell, H S

    1993-09-15

    The p21 RAS product has been implicated as part of the downstream signaling of certain nonreceptor tyrosine kinase oncogenes and several growth factor receptor-ligand interactions. We have reported that the chronic myelogenous leukemia oncogene p210 bcr-abl transforms a growth-factor-dependent myeloid cell line NFS/N1.H7 to interleukin-3 (IL-3) independence. In these p210 bcr-abl-transformed cells (H7 bcr-abl.A54) and in two other murine myeloid cell lines transformed to IL-3 independence by p210 bcr-abl, endogenous p21 RAS is activated as determined by an elevated ratio of associated guanosine triphosphate (GTP)/guanosine diphosphate (GDP), assayed by thin-layer chromatography of the nucleotides eluted from p21 RAS after immunoprecipitation with the Y13-259 antibody. Treatment of p210 bcr-abl-transformed cells with a specific tyrosine kinase inhibitor herbimycin A resulted in diminished tyrosine phosphorylation of p210 bcr-abl and associated proteins, without major reduction in expression of the p210 bcr-abl protein itself. Inhibition of p210 bcr-abl-dependent tyrosine phosphorylation resulted in a reduction of active p21RAS-GTP complexes in the transformed cells, in diminished expression of the nuclear early response genes c-jun and c-fos, and in lower cellular proliferation rate. To further implicate p21 RAS in these functional events downstream of p210 bcr-abl tyrosine phosphorylation, we targeted G-protein function directly by limiting the availability of GTP with the inosine monophosphate dehydrogenase inhibitor, tiazofurin (TR). In p210 bcr-abl-transformed cells treated for 4 hours with TR, in which the levels of GTP were reduced by 50%, but GDP, guanosine monophosphate, and adenosine triphosphate (ATP) were unaffected, p210 bcr-abl tyrosine phosphorylation was at control levels. However, expression of c-fos and c-jun nuclear proto-oncogenes were strongly inhibited and p21 RAS activity was downregulated. These findings show that p210 bcr-abl transduces

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

    International Nuclear Information System (INIS)

    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

  7. A Requirement for SOCS-1 and SOCS-3 Phosphorylation in Bcr-Abl-Induced Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Xiaoxue Qiu

    2012-06-01

    Full Text Available Suppressors of cytokine signaling 1 and 3 (SOCS-1 and SOCS-3 are inhibitors of the Janus tyrosine kinase (JAK/signal transducers and activators of transcription (STAT pathway and function in a negative feedback loop during cytokine signaling. Abl transformation is associated with constitutive activation of JAK/STAT-dependent signaling. However, the mechanism by which Abl oncoproteins bypass SOCS inhibitory regulation remains poorly defined. Here, we demonstrate that coexpression of Bcr-Abl with SOCS-1 or SOCS-3 results in tyrosine phosphorylation of these SOCS proteins. Interestingly, SOCS-1 is highly tyrosine phosphorylated in one of five primary chronic myelogenous leukemia samples. Bcr-Abl-dependent tyrosine phosphorylation of SOCS-1 and SOCS-3 occurs mainly on Tyr 155 and Tyr 204 residues of SOCS-1 and on Tyr 221 residue of SOCS-3. We observed that phosphorylation of these SOCS proteins was associated with their binding to Bcr-Abl. Bcr-Abl-dependent phosphorylation of SOCS-1 and SOCS-3 diminished their inhibitory effects on the activation of JAK and STAT5 and thereby enhanced JAK/STAT5 signaling. Strikingly, disrupting the tyrosine phosphorylation of SOCS-1 or SOCS-3 impaired the expression of Bcl-XL protein and sensitized K562 leukemic cells to undergo apoptosis. Moreover, selective mutation of tyrosine phosphorylation sites of SOCS-1 or SOCS-3 significantly blocked Bcr-Abl-mediated tumorigenesis in nude mice and inhibited Bcr-Abl-mediated murine bone marrow transformation. Together, these results reveal a mechanism of how Bcr-Abl may overcome SOCS-1 and SOCS-3 inhibition to constitutively activate the JAK/STAT-dependent signaling, and suggest that Bcr-Abl may critically requires tyrosine phosphorylation of SOCS-1 and SOCS-3 to mediate tumorigenesis when these SOCS proteins are present in cells.

  8. Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice

    OpenAIRE

    Vicente-Dueñas, Carolina; Barajas-Diego, Marcos; Romero-Camarero, Isabel; González-Herrero, Inés; Flores, Teresa; Sánchez García, Isidro

    2012-01-01

    The telomerase protein is constitutively activated in malignant cells from many patients with cancer, including the chronic myeloid leukemia (CML), but whether telomerase is essential for the pathogenesis of this disease is not known. Here, we used telomerase deficient mice to determine the requirement for telomerase in CML induced by BCR-ABL in mouse models of CML. Loss of one telomerase allele or complete deletion of telomerase prevented the development of leukemia induced by BCR-ABL. Howev...

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

    Directory of Open Access Journals (Sweden)

    Min Yu

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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.

  10. Reciprocal t(9;22 ABL/BCR fusion proteins: leukemogenic potential and effects on B cell commitment.

    Directory of Open Access Journals (Sweden)

    Xiaomin Zheng

    Full Text Available BACKGROUND: t(9;22 is a balanced translocation, and the chromosome 22 breakpoints (Philadelphia chromosome--Ph+ determine formation of different fusion genes that are associated with either Ph+ acute lymphatic leukemia (Ph+ ALL or chronic myeloid leukemia (CML. The "minor" breakpoint in Ph+ ALL encodes p185(BCR/ABL from der22 and p96(ABL/BCR from der9. The "major" breakpoint in CML encodes p210(BCR/ABL and p40(ABL/BCR. Herein, we investigated the leukemogenic potential of the der9-associated p96(ABL/BCR and p40(ABL/BCR fusion proteins and their roles in the lineage commitment of hematopoietic stem cells in comparison to BCR/ABL. METHODOLOGY: All t(9;22 derived proteins were retrovirally expressed in murine hematopoietic stem cells (SL cells and human umbilical cord blood cells (UCBC. Stem cell potential was determined by replating efficiency, colony forming--spleen and competitive repopulating assays. The leukemic potential of the ABL/BCR fusion proteins was assessed by in a transduction/transplantation model. Effects on the lineage commitment and differentiation were investigated by culturing the cells under conditions driving either myeloid or lymphoid commitment. Expression of key factors of the B-cell differentiation and components of the preB-cell receptor were determined by qRT-PCR. PRINCIPAL FINDINGS: Both p96(ABL/BCR and p40(ABL/BCR increased proliferation of early progenitors and the short term stem cell capacity of SL-cells and exhibited own leukemogenic potential. Interestingly, BCR/ABL gave origin exclusively to a myeloid phenotype independently from the culture conditions whereas p96(ABL/BCR and to a minor extent p40(ABL/BCR forced the B-cell commitment of SL-cells and UCBC. CONCLUSIONS/SIGNIFICANCE: Our here presented data establish the reciprocal ABL/BCR fusion proteins as second oncogenes encoded by the t(9;22 in addition to BCR/ABL and suggest that ABL/BCR contribute to the determination of the leukemic phenotype through their

  11. Kriging analysis of geochemical data obtained by sequential extraction procedure (BCR)

    Science.gov (United States)

    Fajkovic, Hana; Pitarević Svedružić, Lovorka; Prohić, Esad; Rončević, Sanda; Nemet, Ivan

    2015-04-01

    Field examination and laboratory analysis were performed to establish whether nonsanitary landfill Bastijunski brig has a negative influence on Vransko Lake, situated only 1500 m away. Vransko Lake is Croatia's largest natural lake, and it is a part of the Nature Park and ornithological reserve, which indicates its high biodiversity. Therefore it is necessary to understand the environmental processes and complex sediment/water interface. Lake sediments are considered to be a good "sinkhole'and are often the final recipients of anthropogenic and natural pollutants through adsorption onto the organic or clay fraction in sediments. Geochemical investigation were obtained throughout more than 50 lake sediments cores situated in different parts of the lake Speciation of heavy metals by modified BCR sequential extraction procedure with the addition of a first step of sequential extraction procedure by Tessier and analysis of residual by aqua regia were used to determine the amounts of selected elements (Al, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb, Zn) in different fractions. With such approach it is possible to determine which element will be extracted from sediment/soil in a different environmental conditions and can be valuable tool for interpretation of the mobile fraction of the elements, considered bioavailability, that present threat to biota in a case of a contaminant concentration magnification. All sediment and soil samples were analyzed by inductively coupled plasma atomic emission spectrometry. More accurate interpretation of data is an advantage of BCR sequential extraction procedure while high number of the data together with point data type could be considered as a drawback. Due to high amount of data, graphical presentation is advisable while interpolation tool is a first choice for point type of data, as it makes predictions for defined area based on the measurements. Distribution maps of analysed elements were obtained by kriging as a geostatistical method and

  12. Arsenic fractionation in sediments of different origins using BCR sequential and single extraction methods

    International Nuclear Information System (INIS)

    The arsenic (As) contaminated sediment serves as a long-term source of arsenic because its mobility and transport in the environment are strongly influenced to associated solid phase. A single extraction method based on the reagents employed in the BCR three steps sequential extraction scheme (BCR-SES) for partitioning of arsenic (As) in sediment samples has been developed. The single-step extraction enabled a reduction of extraction times, yielding extractable contents in accordance with those obtained by application of the BCR-SES, which can be regarded as a standard method and validated by using certified reference material BCR 701. The extractable As content associated with different phases in sediment samples were analysed by electrothermal atomic absorption spectrophotometer. The extraction efficiency of As by single-step extraction was slightly higher than BCR-SES, ranged (100-104%), while difference was not significant at 95% confidence limit with <10% precision. The sediment samples from different origins varied in their physico-chemical properties and total As content. The relative mobility of As obtained from different origins was found in increasing order as: acid soluble fraction < oxidizable fraction < reducible fraction. The acid soluble fraction of As was higher in lake sediment samples as compared to those of canal and river sediments, indicating the contamination of lake ecosystem.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-25

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

  14. Deletion of ABL/BCR on der(9 associated with severe basophilia

    Directory of Open Access Journals (Sweden)

    Shantashri Vaidya

    2011-01-01

    Full Text Available Chronic basophilic leukemia is a rare form in chronic myeloid leukemia patients. Only limited number of reports are available. Herein, we describe a patient who presented with fatigue, weight loss, leucocytosis, prominent basophilia, and mild eosinophilia. On biopsy, bone marrow was hypercellular with marked basophils. The immunophenotype showed abnormal expression of CD7, which is suggestive of basophilic maturation. Chromosomal analysis from GTG-banded metaphases revealed Ph positivity, and fluorescence in situ hybridization (FISH with BCR/ABL dual color, dual fusion probe showed single fusion on the der(22 chromosome and ABL/BCR fusion was deleted on the der(9 chromosome. The deletion (ABL/BCR on der(9 may be associated with basophilia which may be also indicative of the transformation of CML to acute myeloid leukemia.

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

    Directory of Open Access Journals (Sweden)

    Groffen John

    2007-10-01

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

  16. Comparative study of optimised BCR sequential extraction scheme and acid leaching of elements in the certified reference material NIST 2711

    International Nuclear Information System (INIS)

    The optimised BCR sequential extraction procedure and a 4 h 1 mol L-1 HCl partial extraction have been performed on the NIST 2711 reference material for a suite of 12 elements (Cd, Sb, Pb, Al, Cr, Mn, Fe, Co, Ni, Cu, Zn, As) using magnetic sector ICP-MS. A pseudo-total aqua regia digest of NIST 2711 has also been undertaken for quality assurance purposes, and comparison of the sum of the four BCR fractions, which included an aqua regia digest on the residue, with the pseudo-total aqua regia digest has been used to assess the accuracy of the BCR partitioning approach. As a result of this work, discrepancies between previous studies about BCR partitioning of elements in NIST 2711 have been discussed and an increase in confidence about the use of BCR partitioning scheme on seven elements (Cd, Pb, Al, Mn, Fe, Cu, Zn) in this standard material has been obtained. On the other hand, BCR partitioning for Sb, Cr, Co, Ni and As has been provided for the first time. Partial extraction results are also reported for the same 12 elements analysed by the optimised BCR procedure, with the partial extraction results exhibiting a strong correlation with the sum of the three labile steps of the BCR procedure

  17. Altered BCR signalling quality predisposes to autoimmune disease and a pre-diabetic state

    OpenAIRE

    Königsberger, Sebastian; Prodöhl, Jan; Stegner, David; Weis, Vanessa; Andreas, Martin; Stehling, Martin; Schumacher, Theresa; Böhmer, Ruben; Thielmann, Ina; van Eeuwijk, Judith M M; Nieswandt, Bernhard; Kiefer, Friedemann

    2012-01-01

    The related tyrosine kinases Syk and Zap-70 are key signalling proteins downstream of antigen receptors. A knock-in strategy reveals that the two kinases differentially affect BCR signalling, leading to aberrant B cell section and increased risk of autoimmune disease.

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

    Science.gov (United States)

    Farhat-Maghribi, Sulaf; Habbal, Wafa; Monem, Fawza

    2016-01-01

    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. PMID:27313614

  19. Harmonization of BCR-ABL mRNA quantification using a uniform multifunctional control plasmid in 37 international laboratories

    DEFF Research Database (Denmark)

    Müller, M C; Erben, P; Saglio, G; Gottardi, E; Nyvold, Charlotte Guldborg; Schenk, T; Ernst, T; Lauber, S; Kruth, J; Hehlmann, R; Hochhaus, A

    2008-01-01

    Individualized PCR strategies hamper comparability of molecular results between different laboratories in several fields of medicine. To harmonize BCR-ABL mRNA quantification an international multicenter trial involving 37 laboratories in 14 countries was initiated using 10 samples, each containing...... various dilutions (10, 2, 1 and 0.1%) of b3a2 or b2a2 BCR-ABL positive in normal leukocytes and negative controls. A novel control plasmid (pME-2) was designed for external calibration containing BCR-ABL and glucuronidase-beta (GUS) sequences. Median BCR-ABL/ABL ratios were 9.1, 1.8, 0.85 and 0.11% in b3a...... participating laboratories (13%) detected low BCR-ABL copy numbers in negative control samples; one laboratory failed to detect BCR-ABL in a low-level sample. We conclude that the use of a common control plasmid does indeed improve comparability of BCR-ABL mRNA quantification results. However, further...

  20. 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.

  1. p210 Bcr-Abl confers overexpression of inosine monophosphate dehydrogenase : an intrinsic pathway to drug resistance mediated by oncogene.

    Energy Technology Data Exchange (ETDEWEB)

    Gharehbaghi, K.; Burgess, G. S.; Collart, F. R.; Litz-Jackson, S.; Huberman, E.; Jayaram, H. N.; Boswell, H. S.; Center for Mechanistic Biology and Biotechnology; Lab. for Experimental Oncology; Indiana Univ. School of Medicine

    1994-01-01

    The p210 bcr-abl fusion protein tyrosine kinase oncogene has been implicated in the pathogenesis of chronic granulocytic leukemia (CGL). Specific intracellular functions performed by p210 bcr-abl have recently been delineated. We considered the possibility that p210 bcr-abl may also regulate the abundance of inosine 5'-monophosphate dehydrogenase (IMPDH) which is a rate-limiting enzyme for de novo guanylate synthesis. We performed studies of the inhibition of IMPDH by tiazofurin, which acts as a competitive inhibitor through its active species that mimics nicotinamide adenine dinucleotide (NAD), i.e. thiazole-4-carboxamide adenine dinucleotide (TAD). The mean inhibitory concentration (IC50) of tiazofurin for cellular proliferation inhibition was 2.3-2.8-fold greater in cells expressing p210 bcr-abl than in their corresponding parent cells proliferating under the influence of growth factors or in growth factor-independent derivative cells not expressing detectable p210 bcr-abl. IMPDH activity was 1.5-2.3-fold greater within cells expressing p210 bcr-abl than in their parent cells. This increase in enzyme activity was a result of 2-fold increased IMPDH protein as determined by immunoblotting. In addition, an increase in the Km value for NAD utilization by IMPDH was observed in p210 bcr-abl transformed cells, but this increase was within the range of resident NAD concentrations observed in the cells. Increased IMPDH protein in p210 bcr-abl transformed cells was traced to an increased level of IMP dehydrogenase II messenger RNA. Thus, regulation of IMPDH gene expression is mediated at least in part by the bcr-abl gene product and may therefore be indicative of a specific mechanism of intrinsic resistance to tiazofurin.

  2. p210 bcr-abl confers overexpression of inosine monophosphate dehydrogenase: an intrinsic pathway to drug resistance mediated by oncogene.

    Science.gov (United States)

    Gharehbaghi, K; Burgess, G S; Collart, F R; Litz-Jackson, S; Huberman, E; Jayaram, H N; Boswell, H S

    1994-08-01

    The p210 bcr-abl fusion protein tyrosine kinase oncogene has been implicated in the pathogenesis of chronic granulocytic leukemia (CGL). Specific intracellular functions performed by p210 bcr-abl have recently been delineated. We considered the possibility that p210 bcr-abl may also regulate the abundance of inosine 5'-monophosphate dehydrogenase (IMPDH) which is a rate-limiting enzyme for de novo guanylate synthesis. We performed studies of the inhibition of IMPDH by tiazofurin, which acts as a competitive inhibitor through its active species that mimics nicotinamide adenine dinucleotide (NAD), i.e. thiazole-4-carboxamide adenine dinucleotide (TAD). The mean inhibitory concentration (IC50) of tiazofurin for cellular proliferation inhibition was 2.3-2.8-fold greater in cells expressing p210 bcr-abl than in their corresponding parent cells proliferating under the influence of growth factors or in growth factor-independent derivative cells not expressing detectable p210 bcr-abl. IMPDH activity was 1.5-2.3-fold greater within cells expressing p210 bcr-abl than in their parent cells. This increase in enzyme activity was a result of 2-fold increased IMPDH protein as determined by immunoblotting. In addition, an increase in the Km value for NAD utilization by IMPDH was observed in p210 bcr-abl transformed cells, but this increase was within the range of resident NAD concentrations observed in the cells. Increased IMPDH protein in p210 bcr-abl transformed cells was traced to an increased level of IMP dehydrogenase II messenger RNA. Thus, regulation of IMPDH gene expression is mediated at least in part by the bcr-abl gene product and may therefore be indicative of a specific mechanism of intrinsic resistance to tiazofurin. PMID:7520100

  3. 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.

  4. 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.

  5. The human leukemia oncogene bcr-abl abrogates the anchorage requirement but not the growth factor requirement for proliferation.

    OpenAIRE

    Renshaw, M W; McWhirter, J R; Wang, J Y

    1995-01-01

    Proliferation of normal cells in a multicellular organism requires not only growth factors but also the proper attachment to the extracellular matrix. A hallmark of neoplastic transformation is the loss of anchorage dependence which usually accompanies the loss of growth factor requirement. The Bcr-Abl tyrosine kinase of human leukemias is shown here to abrogate only the anchorage, not the growth factor, requirement. Bcr-Abl-transformed cells grow in soft agar but do not proliferate in serum-...

  6. 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.

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

    OpenAIRE

    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 signi...

  8. B Cells Regulate CD4+ T cell Responses to Papain Following BCR-Independent Papain Uptake

    OpenAIRE

    Dwyer, Daniel F.; Woodruff, Matthew C.; Carroll, Michael C.; Austen, K. Frank; Gurish, Michael F.

    2014-01-01

    Papain, a cysteine protease allergen with inherent adjuvant activity, induces potent IL4 expression by T cells in the popliteal lymph nodes (PLN) of mice following footpad immunization. Here we identify a novel, non-BCR mediated capacity for B cells to rapidly bind and internalize papain. B cells subsequently regulate the adaptive immune response by enhancing Inducible T cell Costimulator (ICOS) expression on CD4+ T cells and amplifying Th2 and T follicular helper induction. Antibody blockade...

  9. Mutations in the BCR-ABL1 Kinase Domain and Elsewhere in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Soverini, Simona; de Benedittis, Caterina; Mancini, Manuela; Martinelli, Giovanni

    2015-06-01

    Chronic myeloid leukemia (CML) has been the first human malignancy to be associated, more than 50 years ago, with a consistent chromosomal abnormality--the t(9;22)(q34;q11) chromosomal translocation. The resulting BCR-ABL1 fusion gene, encoding a tyrosine kinase with deregulated activity, has a central role in the pathogenesis of CML. Ancestral or additional genetic events necessary for CML to develop have long been hypothesized but never really demonstrated. CML can successfully be treated with tyrosine kinase inhibitors (TKIs). Mutations in the BCR-ABL1 kinase domain might arise, however, that confer resistance to 1 or more of the currently available TKIs. Hence, the critical role of BCR-ABL1 mutation screening for optimal therapeutic management, with the current gold standard technique, conventional sequencing, likely to be replaced soon by ultra-deep sequencing. Mutations in genes other than BCR-ABL1 include ASXL1, TET2, RUNX1, DNMT3A, EZH2, and TP53 in chronic phase patients and RUNX1, ASXL1, IKZF1, WT1, TET2, NPM1, IDH1, IDH2, NRAS, KRAS, CBL, TP53, CDKN2A, RB1, and GATA-2 mutations in advanced phase patients. The latter also display additional cytogenetic abnormalities, including submicroscopic regions of gain or loss that only single nucleotide polymorphism arrays or array comparative genomic hybridization can detect. Whether whole genome/exome sequencing studies will uncover novel mutations relevant for pathogenesis, progression, and risk-adapted therapy is still unclear. PMID:26297264

  10. 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.

  11. 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.

  12. 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. PMID:21674065

  13. Identification of drug combinations containing imatinib for treatment of BCR-ABL+ leukemias.

    Directory of Open Access Journals (Sweden)

    Yunyi Kang

    Full Text Available The BCR-ABL translocation is found in chronic myeloid leukemia (CML and in Ph+ acute lymphoblastic leukemia (ALL patients. Although imatinib and its analogues have been used as front-line therapy to target this mutation and control the disease for over a decade, resistance to the therapy is still observed and most patients are not cured but need to continue the therapy indefinitely. It is therefore of great importance to find new therapies, possibly as drug combinations, which can overcome drug resistance. In this study, we identified eleven candidate anti-leukemic drugs that might be combined with imatinib, using three approaches: a kinase inhibitor library screen, a gene expression correlation analysis, and literature analysis. We then used an experimental search algorithm to efficiently explore the large space of possible drug and dose combinations and identified drug combinations that selectively kill a BCR-ABL+ leukemic cell line (K562 over a normal fibroblast cell line (IMR-90. Only six iterations of the algorithm were needed to identify very selective drug combinations. The efficacy of the top forty-nine combinations was further confirmed using Ph+ and Ph- ALL patient cells, including imatinib-resistant cells. Collectively, the drug combinations and methods we describe might be a first step towards more effective interventions for leukemia patients, especially those with the BCR-ABL translocation.

  14. 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.

  15. Association of HLA antigens and BCR-ABL transcripts in leukemia patients with the Philadelphia chromosome

    Directory of Open Access Journals (Sweden)

    Daiana Landenberger de Carvalho

    2012-01-01

    Full Text Available OBJECTIVE: This study aimed to verify the association between human leukocyte antigens and the bcr-abl fusion protein resulting from t(9;22(q34;q11 in chronic leukemia myeloid and acute lymphoblastic leukemia patients. METHODS: Forty-seven bcr-abl positive individuals were evaluated. Typing was performed bymicrolymphocytotoxicity and molecular biological methods (human leukocyte antigens Class I and Class II. A control group was obtained from the data of potential bone marrow donors registered in the Brazilian Bone Marrow Donor Registry (REDOME. RESULTS: Positive associations with HLA-A25 and HLA-B18 were found for the b2a2 transcript, as well as a tendency towards a positive association with HLA-B40 and a negative association with HLA-A68. The b3a2 transcript showed positive associations with HLA-B40 and HLA-DRB1*3. CONCLUSION: The negative association between human leukocyte antigens and the BCR-ABL transcript suggests that binding and presentation of peptides derived from the chimeric protein are effective to increase a cytotoxic T lymphocyte response appropriate for the destruction of leukemic cells.

  16. B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses.

    Science.gov (United States)

    Pone, Egest J; Lou, Zheng; Lam, Tonika; Greenberg, Milton L; Wang, Rui; Xu, Zhenming; Casali, Paolo

    2015-02-01

    Ig class switch DNA recombination (CSR) in B cells is crucial to the maturation of antibody responses. It requires IgH germline IH-CH transcription and expression of AID, both of which are induced by engagement of CD40 or dual engagement of a Toll-like receptor (TLR) and B cell receptor (BCR). Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS). LPS-mediated long-term primary class-switched antibody responses and memory-like antibody responses in vivo and induced generation of class-switched B cells and plasma cells in vitro. Consistent with the requirement for dual TLR and BCR engagement in CSR induction, LPS, which engages TLR4 through its lipid A moiety, triggered cytosolic Ca2+ flux in B cells through its BCR-engaging polysaccharidic moiety. In the presence of BCR crosslinking, LPS synergized with a TLR1/2 ligand (Pam3CSK4) in CSR induction, but much less efficiently with a TLR7 (R-848) or TLR9 (CpG) ligand. In the absence of BCR crosslinking, R-848 and CpG, which per se induced marginal CSR, virtually abrogated CSR to IgG1, IgG2a, IgG2b, IgG3 and/or IgA, as induced by LPS or CD154 (CD40 ligand) plus IL-4, IFN-γ or TGF-β, and reduced secretion of class-switched Igs, without affecting B cell proliferation or IgM expression. The CSR inhibition by TLR9 was associated with the reduction in AID expression and/or IgH germline IH-S-CH transcription, and required co-stimulation of B cells by CpG with LPS or CD154. Unexpectedly, B cells also failed to undergo CSR or plasma cell differentiation when co-stimulated by LPS and CD154. Overall, by addressing the interaction of TLR1/2, TLR4, TLR7 and TLR9 in the induction of CSR and modulation of TLR-dependent CSR by BCR and CD40, our study suggests the complexity of how different stimuli cross-regulate an important B cell differentiation process and an important role of TLRs in inducing

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

    International Nuclear Information System (INIS)

    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

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-12

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

  20. Inhibitory Effects of Omacetaxine on Leukemic Stem Cells and BCR-ABL-Induced Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia in Mice

    OpenAIRE

    Chen, Yaoyu; Hu, Yiguo; Michaels, Shawnya; Segal, David; Brown, Dennis; Li, Shaoguang

    2009-01-01

    Omacetaxine mepesuccinate (formerly homoharringtonine) is a molecule with a mechanism of action that is different from tyrosine kinase inhibitors and its activity in chronic myeloid leukemia (CML) seems to be independent of BCR-ABL mutation status. Using BCR-ABL-expressing myelogenous and lymphoid cell lines and mouse models of CML and B cell acute lymphoblastic leukemia (B-ALL) induced by wild type BCR-ABL or T315I mutant-BCR-ABL, we evaluated the inhibitory effects of omacetaxine on CML and...

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

    International Nuclear Information System (INIS)

    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

  2. Molecular Imaging of Bcr-Abl Phosphokinase in a Xenograft Model*

    OpenAIRE

    Wu, Ji Yuan; Yang, David J.; Angelo, Laura S.; Kohanim, Saady; Kurzrock, Razelle

    2009-01-01

    The purpose of this study was to determine whether the Bcr-Abl tyrosine kinase can be assessed by gamma imaging using an 111Indium-labeled anti-phosphotyrosine antibody, and if the response to treatment with imatinib could be detected using this imaging technique. Anti-phosphotyrosine antibody (APT) was labeled with indium (111In) using ethylenedicysteine (EC) as a chelator. To determine if 111In-EC-APT could assess a non-receptor tyrosine kinase, xenografts of the human chronic myelogenous l...

  3. Strong amorphization of high-entropy AlBCrSiTi nitride film

    International Nuclear Information System (INIS)

    Amorphous coatings, particular nitride systems, are of interest for numerous practical applications. Nevertheless, at present only a few amorphous nitride coating systems have been considered, the most notably being the (TM, Si)N system (transition metal (TM) = Ti, Zr, W, Mo). The present study provides an alternative approach for producing amorphous nitride films with high thermal stability up to 700 °C for 2 h. Films are deposited from an equimolar AlBCrSiTi target in various argon/nitrogen atmospheres at different substrate temperatures. It is found that above the nitrogen flow ratio (i.e. RN = N2/N2 + Ar) of 28.6% a near equal ratio between target elements and nitrogen is approached, thus indicating the coatings have the chemical formula of (AlBCrSiTi)N. The glancing-angle X-ray diffractometer and transmission electron microscope investigations indicate that the coatings, regardless of nitrogen concentration or deposition temperature (up to 500 °C), are amorphous. Thermal treatment shows that the amorphous structure of this (AlBCrSiTi)N coating is maintained up to 700 °C when annealing for 2 h in vacuum. At annealing temperatures of 800 °C and above, the amorphous films transform into a simple NaCl-type face-centered cubic solid solution. Even after annealing at 1000 °C for 2 h, the grain size is only 2 nm. High entropy effect, large lattice distortion effect, and sluggish diffusion effect are proposed to account for the formation of amorphous nitrides. - Highlights: ► Films are deposited from an equimolar AlBCrSiTi target in various argon/nitrogen atmospheres at different substrate temperatures. ► We provide an alternative approach for producing amorphous nitride films with high thermal stability up to 700 oC for 2 h. ► At annealing temperatures of 800 oC and above, the amorphous films transform into a simple NaCl-type face-centered cubic solid solution. ► Even after annealing at 1000 °C for 2 h, the grain size is only 2 nm.

  4. Evaluating CO2 mineralization capacity of sedimentary rock Using BCR sequential extraction procedures

    Science.gov (United States)

    Yang, Gang-Ting; Yu, Chi-Wen; Yang, Hsiao-Ming; Chiao, Chung-Hui; Yang, Ming-Wei

    2015-04-01

    To relief the high concentration of carbon dioxide in the atmosphere, carbon capture and storage (CCS) is gradually becoming an important concept to reduce greenhouse gas emissions. In IPCC Special Report on CCS, the storage mechanisms for geological formations are categorized into structural/stratigraphic, hydrodynamic and geochemical trappings. Geochemical trapping is considered as a storage mechanism, which can further increase storage capacity, effectiveness and security in terms of permanent CO2 sequestration. The injected CO2 can have geochemical interactions with pore fluid and reservoir rocks and transform into minerals. It is important to evaluate the capacity of reservoir rock for sequestrating CO2. In this study, sedimentary rock samples were collected from a 2-km-deep well in Midwestern Taiwan; and, the BCR sequential extraction experiments developed by European Union Measurement and Testing Programme were conducted. BCR was designed for extracting three major phases from soil, including exchangeable phase and carbonates (the first stage), reducible phase (the second stage) and oxidizable phase (the third stage). The chemistry of extracted solutions and rock residues were measured with ICP-MS and XRF, respectively. According to the results of XRF, considerable amounts of calcium and iron can be extracted by BCR procedures but other cations are negligible. In general, shale has a higher capacity of CO2 sequestration than sandstone. The first stage of extraction can release about 6 (sandstone) to 18.5 (shale) g of calcium from 1 kg rock, which are equivalent to 6.6 and 20.4 g CO2/kg rock, respectively. In the second stage extraction, 0.71 (sandstone) to 1.38 (shale) g/kg rock of iron can be released and can mineralized 0.56 to 1.08 g CO2/kg rock. However, there are no considerable cations extracted in the third stage of BCR as shown by the XRF analysis. In addition, the results of ICP-MS show that Mg can be released in the order of 10-3 g from 1 kg rock

  5. Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1.

    Science.gov (United States)

    Gu, Shengqing; Chan, Wayne W; Mohi, Golam; Rosenbaum, Joel; Sayad, Azin; Lu, Zhibin; Virtanen, Carl; Li, Shaoguang; Neel, Benjamin G; Van Etten, Richard A

    2016-04-01

    Tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1, the product of the Philadelphia (Ph) chromosome, have revolutionized treatment of patients with chronic myeloid leukemia (CML). However, acquired resistance to TKIs is a significant clinical problem in CML, and TKI therapy is much less effective against Ph(+)B-cell acute lymphoblastic leukemia (B-ALL). BCR-ABL1, via phosphorylated Tyr177, recruits the adapter GRB2-associated binding protein 2 (GAB2) as part of a GRB2/GAB2 complex. We showed previously that GAB2 is essential for BCR-ABL1-evoked myeloid transformation in vitro. Using a genetic strategy and mouse models of CML and B-ALL, we show here that GAB2 is essential for myeloid and lymphoid leukemogenesis by BCR-ABL1. In the mouse model, recipients of BCR-ABL1-transducedGab2(-/-)bone marrow failed to develop CML-like myeloproliferative neoplasia. Leukemogenesis was restored by expression of GAB2 but not by GAB2 mutants lacking binding sites for its effectors phosphatidylinositol 3-kinase (PI3K) or SRC homology 2-containing phosphotyrosine phosphatase 2 (SHP2). GAB2 deficiency also attenuated BCR-ABL1-induced B-ALL, but only the SHP2 binding site was required. The SHP2 and PI3K binding sites were differentially required for signaling downstream of GAB2. Hence, GAB2 transmits critical transforming signals from Tyr177 to PI3K and SHP2 for CML pathogenesis, whereas only the GAB2-SHP2 pathway is essential for lymphoid leukemogenesis. Given that GAB2 is dispensable for normal hematopoiesis, GAB2 and its effectors PI3K and SHP2 represent promising targets for therapy in Ph(+)hematologic neoplasms. PMID:26773044

  6. The Role of MEK Kinase 1 in Bcr-Abl-Induced Self-Renewal Activity of Embryonic Stem Cells

    OpenAIRE

    NAKAMURA, Yukinori; Yujiri, Toshiaki; Tanizawa, Yukio

    2006-01-01

    BCR-ABL oncogene, the moecular hallmark of chronic mylogenous leukemia, arises in a promitive hematopoietic stem cell that has the capacity for both differentiation and self-renewal. Its product, Bcr-Abl protein, has been shown to sctivate signal transducers and activators of transcription 3 (STAT3) and to promote self-renewal in embryonic stem (ES)cells, even in the absencs of leukemia in hibitory factor (LIF). MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase ...

  7. 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.

  8. WT1-mediated repression of the proapoptotic transcription factor ZNF224 is triggered by the BCR-ABL oncogene

    Science.gov (United States)

    Montano, Giorgia; Vidovic, Karina; Palladino, Chiara; Cesaro, Elena; Sodaro, Gaetano; Quintarelli, Concetta; De Angelis, Biagio; Errichiello, Santa; Pane, Fabrizio; Izzo, Paola; Grosso, Michela; Gullberg, Urban; Costanzo, Paola

    2015-01-01

    The Kruppel-like protein ZNF224 is a co-factor of the Wilms’ tumor 1 protein, WT1. We have previously shown that ZNF224 exerts a specific proapoptotic role in chronic myelogenous leukemia (CML) K562 cells and contributes to cytosine arabinoside-induced apoptosis, by modulating WT1-dependent transcription of apoptotic genes. Here we demonstrate that ZNF224 gene expression is down-regulated both in BCR-ABL positive cell lines and in primary CML samples and is restored after imatinib and second generation tyrosine kinase inhibitors treatment. We also show that WT1, whose expression is positively regulated by BCR-ABL, represses transcription of the ZNF224 gene. Finally, we report that ZNF224 is significantly down-regulated in patients with BCR-ABL positive chronic phase-CML showing poor response or resistance to imatinib treatment as compared to high-responder patients. Taken as a whole, our data disclose a novel pathway activated by BCR-ABL that leads to inhibition of apoptosis through the ZNF224 repression. ZNF224 could thus represent a novel promising therapeutic target in CML. PMID:26320177

  9. A multiple reaction monitoring (MRM method to detect Bcr-Abl kinase activity in CML using a peptide biosensor.

    Directory of Open Access Journals (Sweden)

    Tzu-Yi Yang

    Full Text Available The protein kinase Bcr-Abl plays a major role in the pathogenesis of chronic myelogenous leukemia (CML, and is the target of the breakthrough drug imatinib (Gleevec™. While most patients respond well to imatinib, approximately 30% never achieve remission or develop resistance within 1-5 years of starting imatinib treatment. Evidence from clinical studies suggests that achieving at least 50% inhibition of a patient's Bcr-Abl kinase activity (relative to their level at diagnosis is associated with improved patient outcomes, including reduced occurrence of resistance and longer maintenance of remission. Accordingly, sensitive assays for detecting Bcr-Abl kinase activity compatible with small amounts of patient material are desirable as potential companion diagnostics for imatinib. Here we report the detection of Bcr-Abl activity and inhibition by imatinib in the human CML cell line K562 using a cell-penetrating peptide biosensor and multiple reaction monitoring (MRM on a triple quadrupole mass spectrometer. MRM enabled reproducible, selective detection of the peptide biosensor at fmol levels from aliquots of cell lysate equivalent to ~15,000 cells. This degree of sensitivity will facilitate the miniaturization of the entire assay procedure down to cell numbers approaching 15,000, making it practical for translational applications in patient cells in which the limited amount of available patient material often presents a major challenge.

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-01-01

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

  12. Chibby drives β catenin cytoplasmic accumulation leading to activation of the unfolded protein response in BCR-ABL1+ cells.

    Science.gov (United States)

    Mancini, Manuela; Leo, Elisa; Takemaru, Ken-Ichi; Campi, Virginia; Borsi, Enrica; Castagnetti, Fausto; Gugliotta, Gabriele; Santucci, Maria Alessandra; Martinelli, Giovanni

    2013-09-01

    Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the constitutive tyrosine kinase (TK) activity of the BCR-ABL fusion protein. However, the phenotype of leukemic stem cells (LSC) is sustained by β catenin rather than by the BCR-ABL TK. β catenin activity in CML is contingent upon its stabilization proceeding from the BCR-ABL-induced phosphorylation at critical residues for interaction with the Adenomatous polyposis coli (APC)/Axin/glycogen synthase kinase 3 (GSK3) destruction complex or GSK3 inactivating mutations. Here we studied the impact of β catenin antagonist Chibby (CBY) on β catenin signaling in BCR-ABL1+ cells. CBY is a small conserved protein which interacts with β catenin and impairs β catenin-mediated transcriptional activation through two distinct molecular mechanisms: 1) competition with T cell factor (TCF) or lymphoid enhancer factor (LEF) for β catenin binding; and 2) nuclear export of β catenin via interaction with 14-3-3. We found that its enforced expression in K562 cell line promoted β catenin cytoplasmic translocation resulting in inhibition of target gene transcription. Moreover, cytoplasmic accumulation of β catenin activated the endoplasmic reticulum (ER) stress-associated pathway known as unfolded protein response (UPR). CBY-driven cytoplasmic accumulation of β catenin is also a component of BCR-ABL1+ cell response to the TK inhibitor Imatinib (IM). It evoked the UPR activation leading to the induction of BCL2-interacting mediator of cell death (BIM) by UPR sensors. BIM, in turn, contributed to the execution phase of apoptosis in the activation of ER resident caspase 12 and mobilization of Ca(2+) stores. PMID:23707389

  13. MEK kinase 1 is essential for Bcr-Abl-induced STAT3 and self-renewal activity in embryonic stem cells.

    Science.gov (United States)

    Nakamura, Yukinori; Yujiri, Toshiaki; Nawata, Ryouhei; Tagami, Kozo; Tanizawa, Yukio

    2005-11-17

    BCR-ABL oncogene, the molecular hallmark of chronic myelogenous leukemia, arises in a primitive hematopoietic stem cell that has the capacity for both differentiation and self-renewal. Its product, Bcr-Abl protein, has been shown to activate signal transducers and activators of transcription 3 (STAT3) and to promote self-renewal in embryonic stem (ES) cells, even in the absence of leukemia inhibitory factor (LIF). MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase involved in Bcr-Abl signal transduction. To investigate the role of MEKK1 in Bcr-Abl-induced transformation of stem cells, p210 Bcr-Abl was stably transfected into wild-type (WT(p210)) and MEKK1-/- (MEKK1-/-(p210)) ES cells. Bcr-Abl enhanced MEKK1 expression in ES transfectants, as it does in other Bcr-Abl-transformed cells. In the absence of LIF, WT(p210) cells showed constitutive STAT3 activation and formed rounded, compact colonies having strong alkaline phosphatase activity, a characteristic phenotype of undifferentiated ES cells. MEKK1-/-(p210) cells, by contrast, showed less STAT3 activity than WT(p210) cells and formed large, flattened colonies having weak alkaline phosphatase activity, a phenotype of differentiated ES cells. These results indicate that MEKK1 plays a key role in Bcr-Abl-induced STAT3 activation and in ES cells' capacity for LIF-independent self-renewal, and may thus be involved in Bcr-Abl-mediated leukemogenesis in stem cells. PMID:16044153

  14. A certified plasmid reference material for the standardisation of BCR-ABL1 mRNA quantification by real-time quantitative PCR

    OpenAIRE

    White, Helen; DEPREZ LIESBET; Corbisier, Philippe; HALL Victoria; Lin, Feng; Mazoua, Stephane; TRAPMANN Stefanie; AGGERHOLM Annie; Andrikovics, Hajnalka; AKIKI Susanna; Barbany, Gisela; Boeckx, Nancy; Bench, Anthony; CATHERWOOD Mark; Cayuela, Jean-Michel

    2014-01-01

    Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasm...

  15. 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 ated by interleukin-7, the preBCR, and hemokinin-1during B-cell development. Authors Milne CD, Fleming HE, Z...ng) (.svg) (.html) (.csml) Show Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1during B-cell developme...14962188 Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1during B-cell develop...ment. Milne CD, Fleming HE, Zhang Y, Paige CJ. Immunol Rev. 2004 Feb;197:75-88. (.p...nt. PubmedID 14962188 Title Mechanisms of selection medi

  16. High risk acute lymphoblastic leukemia cells with bcr-abl and INK4A/ARF mutations retain susceptibility to alloreactive T cells

    OpenAIRE

    Young, Faith M.; Campbell, Andrew; Emo, Kris Lambert; Jansson, Johan; Wang, Pin-Yi; Jordan, Craig T.; Mullen, Craig A.

    2008-01-01

    INK4A/ARF mutations are acquired in bcr/abl+ lymphoid blast phase chronic myelogenous leukemia (CML) and bcr/abl+ acute lymphoblastic leukemia (ALL). Donor lymphocyte infusion and graft versus leukemia are generally ineffective in such ALL’s, while GVL is highly active against bcr/abl+ CML that does not have a lesion in the INK4A/ARF locus. The mechanisms for the ineffectiveness of GVL are not fully known and it is possible that intrinsic resistance of acute lymphoid leukemias to immune effec...

  17. Time saving modified BCR sequential extraction procedure for the fraction of Cd, Cr, Cu, Ni, Pb and Zn in sediment samples of polluted lake

    International Nuclear Information System (INIS)

    The mobility, availability and persistence of heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) in contaminated lake sediment samples were evaluated by means of sequential extraction scheme, proposed by the Community Bureau of Reference protocol (BCR). The metal content in the extracts was measured by atomic absorption spectrometry. The precision and accuracy of the proposed procedure were evaluated by using a certified reference material BCR 701. The maximum recoveries for heavy metals (HMs) were observed for all three steps of BCR protocol at 32 h total shaking period instead of previously reported 51 h, with p > 0.05. The lixiviation tests (DIN 38414-S4) were used to evaluate the leaching of HMs from sediment samples and it was observed that levels of water extractable HMs were low as compared to those values obtained by acid-soluble fraction of the BCR protocol

  18. Ibrutinib inhibits BCR and NF-κB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL

    OpenAIRE

    Herman, Sarah E. M.; Mustafa, Rashida Z.; Gyamfi, Jennifer A.; Pittaluga, Stefania; Chang, Stella; Chang, Betty; Farooqui, Mohammed; Wiestner, Adrian

    2014-01-01

    Ibrutinib inhibits both BCR and NF-κB signaling in lymph node and bone marrow resident CLL cells.Rapid and sustained reduction of cellular activation and tumor proliferation was achieved in all anatomic compartments.

  19. 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)

    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

  20. Curcumin synergistically augments bcr/abl phosphorethieate antisense oligonucleotides to inhibit growth of chronic myelogenous leukemia cells

    Institute of Scientific and Technical Information of China (English)

    Kun-zhong ZHANG; Jian-hua XU; Xiu-wang HUANG; Li-xian WU; Yu SU; Yuan-zhong CHEN

    2007-01-01

    Aim: To investigate the growth inhibition effect of the combination of bcr/abl phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and the possible mechanisms of cur on the chronic myelogenous leukemia cell line K562. Methods: The K562 cell line was used as a P210bcr/abl-positive cell model in vitro and was exposed to different concentrations of PS-ASODN (0-20 μmol/L), cur (0-20 μmol/L), or a combination of both. Growth inhibition and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent staining, respec-tively. The expression levels of P210bct/abl, NF-κB and heat shock protein 90 (Hsp90) were assessed by Western blot. Results: Exposure to cur (5-20 μmol/L) and PS-ASODN (5-20 μmol/L) resulted in a synergistic inhibitory effect on cell growth.Growth inhibition was associated with the inhibition of the proliferation and in-duction of apoptosis. Western blot analysis showed that the drugs synergisti-cally downregulated the level of P210bcr/abl and NF-κB. Cur downregulated Hsp90,whereas no synergism was observed when cur was combined with PS-ASODN.Conclusion: PS-ASODN and cur exhibited a synergistic inhibitory effect on the cell growth of K562. The synergistic growth inhibition was mediated through different mechanisms that involved the inhibition of P210bcr/abl.

  1. A clinical and laboratory study of chronic myeloid leukemia with atypical BCR-ABL fusion gene subtypes

    Institute of Scientific and Technical Information of China (English)

    桂晓敏

    2014-01-01

    Objective To explore the clinical and laboratory features of chronic myeloid leukemia(CML)with atypical e14a3 and e19a2 BCR-ABL fusion gene subtypes.Methods We retrospectively analyzed a cohort of CML patients with Ph chromosome positive confirmed by cytogenetic and FISH but classical e13a3(b2a2),e14a2(b3a2)and e1a2 fusion transcripts negative identified by

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

    OpenAIRE

    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 treatmen...

  3. NK cells are dysfunctional in human chronic myelogenous leukemia before and on imatinib treatment and in BCR-ABL-positive mice.

    Science.gov (United States)

    Chen, C I-U; Koschmieder, S; Kerstiens, L; Schemionek, M; Altvater, B; Pscherer, S; Gerss, J; Maecker, H T; Berdel, W E; Juergens, H; Lee, P P; Rossig, C

    2012-03-01

    Although BCR-ABL+ stem cells in chronic myeloid leukemia (CML) resist elimination by targeted pharmacotherapy in most patients, immunological graft-versus-leukemia effects can cure the disease. Besides cytotoxic T cells, natural killer (NK) cells may have a role in immune control of CML. Here, we explored the functionality of NK cells in CML patients and in a transgenic inducible BCR-ABL mouse model. Compared with controls, NK-cell proportions among lymphocytes were decreased at diagnosis of CML and did not recover during imatinib-induced remission for 10-34 months. Functional experiments revealed limited in vitro expansion of NK cells from CML patients and a reduced degranulation response to K562 target cells both at diagnosis and during imatinib therapy. Consistent with the results in human CML, relative numbers of NK1.1+ NK cells were reduced following induction of BCR-ABL expression in mice, and the defects persisted after BCR-ABL reversion. Moreover, target-induced degranulation by expanded BCR-ABL+ NK cells was compromised. We conclude that CML is associated with quantitative and functional defects within the NK-cell compartment, which is reproduced by induced BCR-ABL expression in mice. Further work will aim at identifying the mechanisms of NK-cell deficiency in CML and at developing strategies to exploit NK cells for immunotherapy. PMID:21904381

  4. Additive antileukemia effects by GFI1B- and BCR-ABL-specific siRNA in advanced phase chronic myeloid leukemic cells.

    Science.gov (United States)

    Koldehoff, M; Zakrzewski, J L; Beelen, D W; Elmaagacli, A H

    2013-07-01

    Previous studies demonstrated selective inhibition of the BCR-ABL (breakpoint cluster region-Abelson murine leukemia oncogene) tyrosine kinase by RNA interference in leukemic cells. In this study, we evaluated the effect of BCR-ABL small interfering RNA (siRNA) and GFI1B siRNA silencing on chronic myeloid leukemia (CML) cells in myeloid blast crises. The GFI1B gene was mapped to chromosome 9 and is, therefore, located downstream of the BCR-ABL translocation in CML cells. Co-transfection of BCR-ABL siRNA and GFI1B siRNA dramatically decreased cell viability and significantly induced apoptosis and inhibited proliferation in K562 cells (P<0.0001) and primary advanced phase CML cells (P<0.0001) versus controls. Furthermore, combining of BCR-ABL siRNA and GFI1B siRNA significantly modified the expression of several relevant genes including Myc, MDR1, MRP1 and tyrosyl-phosphoproteins in primary CML cells. Our data suggest that silencing of both BCR-ABL siRNA and GFI1B siRNA is associated with an additive antileukemic effect against K562 cells and primary advanced CML cells, further validating these genes as attractive therapeutic targets. PMID:23788109

  5. 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.

  6. Investigation of trace elements in agricultural Edirne soils by BCR sequential extraction method and its transfer to wheat plants

    International Nuclear Information System (INIS)

    Complete text of publication follows. In this study, soil samples were collected from Edirne-Turkey and subjected to a sequential procedure in order to evaluate the precision of the procedure and determine metal partitioning and concentrations of elements and to investigate the predictability of trace element on plant uptake. The samples were subjected to a three stage extraction procedure proposed by the Community Bureau of Reference (BCR) (G. Rauret et al., J. Environ. Monit., 1 (1999) 57-61.) .The three phases that were separated out were (1) carbonate, exchangeable, (2) Fe-Mn oxides and (3) organic matter. Metal concentrations were determined by ICP-OES. The wheat samples were prepared to analysis using microwave acid digestion procedure (E.P. Nardi et al., food Chem., 112 (2009) 727-732.). The pseudo-total concentrations of metals were determinated after aqua regia digestion (S. Melaku et al., Anal. Chim. Acta, 543 (2005) 117-123.). The analytical accuracy of the method was determinated by using the Standard Reference Materials ( BCR 142R Light Sandy Soil, NIST 2711 Montana Soil, NIST 2704 Buffalo River Sediment) The sum of the metal contents obtained from the modified BCR sequential extraction procedure and pseudo-total metal contents for soil samples were used to calculate recovery values (a. Tokalioglu et al., Intern. J. Environ. Anal. Chem., 86 (2006) 417-430.). In order to evaluate the bioavailability of metals, the relationships between the wheat-metal and soil-extractable metal concentrations were examined.

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

    International Nuclear Information System (INIS)

    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.

  8. INTERNAL RATING – AN ACTIVE INSTRUMENT IN THE MANAGEMENT OF BANKING RISKS. CASE STUDY BCR

    Directory of Open Access Journals (Sweden)

    PhD Gabriela Cornelia Piciu

    2013-06-01

    Full Text Available This paper aims to clarify some aspects regarding the banking activity in general, of crediting, in particular, because it involves a risk by the very elements of anticipation underlying the decision of the banking specialists. For the bank it is very important to know this risk, to make an evaluation as close as possible to reality, and to reject or accept it in full awareness. The contribution of the internal rating in terms of efficiency and stability of a bank is shown via a case study – the Romanian Commercial Bank. The internal rating used by BCR is an active instrument for making credit decisions it provides valuable indicators to the banking analysts that can be used to develop de risk management policies and the prudential measures for the balanced risk dispersion. Given the fact that the credit rating contributes to the objective, professional analysis, the system must be continuously improved and developed by categories of clients and types of risk, so that the included criteria and the resulting conclusions are relevant.

  9. Application of methods (sequential extraction procedures and high-pressure digestion method) to fly ash particles to determine the element constituents: A case study for BCR 176

    International Nuclear Information System (INIS)

    Sequential extraction procedures and the high-pressure digestion method were selected to determine the element constituents of fly ash samples. Sequential extraction is one of the most useful methods used to measure the various elements from municipal solid waste incineration ash and contaminated soils. The extract from each step is analyzed using various techniques and equipments, and the results are then evaluated. In this work, a six-step extraction procedure modified from that of Tessier et al. and Wang et al. was performed and applied to the certified reference material BCR 176 (city waste incineration ash). Analyses were carried out by various techniques such as inductively coupled plasma atomic emission spectrometry (ICP-AES), inductively coupled plasma-mass spectrometry (ICP-MS), scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX), and X-ray powder diffraction (XRPD) to evaluate the characteristics of fly ash. The extraction efficiency of many elements was higher than 80%, and the relative standard deviations (RSD) for recovery of most elements were within 10%. In addition, an H2O2 + HNO3 + HF mixed acid digestion solution processed using a low-temperature evaporation procedure was selected as the optimal process for fly ash digestion. The results of this work provide information on the chemical composition, distribution, and potential mobility of the investigated elements

  10. 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.

  11. Speciation of heavy metals by modified BCR sequential extraction procedure in different depths of sediments from Sungai Buloh, Selangor, Malaysia

    International Nuclear Information System (INIS)

    Highlights: → A BCR sequential extraction procedure was applied for measurement of heavy metals in Sungai Buloh sediments in different depths. → The amounts of CF and percentage of RAC was measured in this study too. → Highest CF was obtained for Cd, Co, Pb and Zn in these samples. → Zn at S3 and Cd at S3-S7 showed a high risk for the sediment samples. There were no elements of very high risk conditions in the selected samples. - Abstract: The sequential extraction procedure proposed by the European Standard, Measurements and Testing (SM and T) program, formerly the Community Bureau of Reference (BCR), was applied for partitioning of heavy metals (HMs) in river sediments collected along the course of Sungai Buloh and the Straits of Malacca in Selangor, Malaysia. Eight elements (V, Pb, Cd, Cr, Co, Ni, Cu and Zn) from seven stations (S1-S7) and at different depths were analyzed using the modified BCR Sequential Extraction Procedure (SEP) in combination with ICP-MS to obtain the metal distribution patterns in this region. The results showed that heavy metal contaminations at S2 and S3 was more severe than at other sampling sites, especially for Zn, Cu, Ni and Pb. Nevertheless, the element concentrations from top to bottom layers decreased predominantly. The samples from the Straits of Malacca (S4-S7) the highest contamination factors obtained were for Co, Zn and Pb while the lowest were found for V and Cr, similar to Sungai Buloh sediments. The sediments showed a low risk for V, Cr, Cu and Pb with RAC values of less than 10%, but medium risk for Co, Zn (except S3), Cd at S1 and S2 and Ni at S1, S3 and S5. Zn at S3 and Cd at S3-S7 showed high risk to our sediment samples. There is not any element of very high risk conditions in the selected samples.

  12. Differential expression of Toll-like receptor (TLR) and B cell receptor (BCR) signaling molecules in primary diffuse large B-cell lymphoma of the central nervous system.

    Science.gov (United States)

    Akhter, Ariz; Masir, Noraidah; Elyamany, Ghaleb; Phang, Kean-Chang; Mahe, Etienne; Al-Zahrani, Ali Matar; Shabani-Rad, Meer-Taher; Stewart, Douglas Allan; Mansoor, Adnan

    2015-01-01

    Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a distinct and aggressive lymphoma that is confined to CNS. Since, central nervous system is barrier-protected and immunologically silent; role of TLR/BCR signaling in pathogenesis and biology of CNS DLBCL is intriguing. Genomic mutations in key regulators of TLR/BCR signaling pathway (MYD88/CD79B/CARD11) have recently been reported in this disease. These observations raised possible implications in novel targeted therapies; however, expression pattern of molecules related to TLR/BCR pathways in this lymphoma remains unknown. We have analyzed the expression of 19 genes encoding TLR/BCR pathways and targets in CNS DLBCLs (n = 20) by Nanostring nCounter™ analysis and compared it with expression patterns in purified reactive B-lymphocytes and systemic diffuse large B cell lymphoma (DLBCL) (n = 20). Relative expression of TLR4, TLR5, TLR9, CD79B and BLNK was higher in CNS DLBCLs than in control B-lymphocytes; where as TLR7, MALT1, BCL10, CD79A and LYN was lower in CNS DLBCLs (P 1.5 fold change; P < 0.01). The B cell receptor molecules like BLNK and CD79B were also associated with higher expression of MYD88 dependent TLRs (TLR4/5/9). In conclusion, we have shown over expression of TLR/BCR related genes or their targets, where genomic mutations have commonly been identified in CNS DLBCL. We have also demonstrated that TLR over expression closely relate with up regulation of genes associated with BCR pathway like CD79B/BLNK and CARD11, which play an important role in NF-kB pathway activation. Our results provide an important insight into the possibility of TLR and/or B-cell receptor signaling molecules as possible therapeutic targets in CNS DLBCL. PMID:25391967

  13. Involvement of primary mesenchymal precursors and hematopoietic bone marrow cells from chronic myeloid leukemia patients by BCR-ABL1 fusion gene.

    Science.gov (United States)

    Chandia, Mauricio; Sayagués, José-María; Gutiérrez, María-Laura; Chillón, María-Laura; Aristizábal, José-Alejandro; Corrales, Alejandro; Castellanos, Marta; Melón, Alberto; Sánchez, María-Luz; Bárcena, Paloma; Matarraz, Sergio; González-González, María; Barrena, Susana; López, Antonio; Cañizo, María-Consuelo; Sánchez-Guijo, Fermín; Orfao, Alberto

    2014-03-01

    For decades now, it is well established that chronic myeloid leukemia (CML) is a hematopoietic stem cell(HPC) disorder. However, it remains to be determined whether BCR-ABL1 gene rearrangement occurs in a HPC or at an earlier stem cell and whether the degree of involvement of hematopoiesis by the BCR-ABL1 fusion gene relates to the response to therapy. Here, we have investigated by interphase fluorescence in situ hybridization (iFISH) the distribution of BCR-ABL1 fusion gene in FACS-sorted bone marrow (BM) populations of mesenchymal precursor cells (MPC) and other hematopoietic cell populations from 18 newly diagnosed CML patients. Overall, our results showed systematic involvement at relatively high percentages of BM maturing neutrophils (97%615%), basophils (95%612%), eosinophils (90%68%), CD341 precursors cells (90%67%),monocytes (84%630%), nucleated red blood cells (87%624%), and mast cells (77%633%). By contrast, MPC(30%634%), B-cells (15%627%), T-lymphocytes (50%626%), and NK-cells (35%634%) were involved at lower percentages. In 8/18 CML patients, 2 tumor BCR-ABL11 subclones were detected by iFISH. Of note, all tumor cell subclones were systematically detected in CD341 cells, whereas MPC were only involved by the ancestral tumor cell subclone. In summary, here we confirm the presence at diagnosis of the BCR-ABL1 fusion gene inMPC, CD341 precursors, and other different BM hematopoietic myeloid cell lineages from CML patients,including also in a significant fraction of cases, a smaller percentage of T, B, and NK lymphocytes.Interestingly, involvement of MPC was restricted to the ancestral BCR-ABL11 subclone. PMID:24779036

  14. Allelic expression imbalance of JAK2 V617F mutation in BCR-ABL negative myeloproliferative neoplasms.

    Directory of Open Access Journals (Sweden)

    Hye-Ran Kim

    Full Text Available The discovery of a single point mutation in the JAK2 gene in patients with BCR/ABL-negative myeloproliferative neoplasms (MPNs has not only brought new insights and pathogenesis, but also has made the diagnosis of MPNs much easier. Although, to date, several mechanisms for the contribution of single JAK2V617F point mutation to phenotypic diversity of MPNs have been suggested in multiple studies, but it is not clear how a unique mutation can cause the phenotypic diversity of MPNs. In this study, our results show that allelic expression imbalance of JAK2 V617F mutant frequently occurs and contributes to phenotypic diversity of BCR-ABL-negative MPNs. The proportion of JAK2 V617F mutant allele was significantly augmented in RNA levels as compared with genomic DNA differently by distinct MPNs subtypes. In detail, preferential expression of JAK2 mutant allele showed threefold increase from the cDNA compared with the genomic DNA from patients with essential thrombocythemia and twofold increase in polycythemia vera. In conclusion, allelic expression imbalance of JAK2 V617F mutant proposes another plausible mechanism for the contribution of single JAK2 point mutation to phenotypic diversity of MPNs.

  15. Conditional knockdown of BCL2A1 reveals rate-limiting roles in BCR-dependent B-cell survival.

    Science.gov (United States)

    Sochalska, M; Ottina, E; Tuzlak, S; Herzog, S; Herold, M; Villunger, A

    2016-04-01

    Bcl2 family proteins control mitochondrial apoptosis and its members exert critical cell type and differentiation stage-specific functions, acting as barriers against autoimmunity or transformation. Anti-apoptotic Bcl2a1/Bfl1/A1 is frequently deregulated in different types of blood cancers in humans but its physiological role is poorly understood as quadruplication of the Bcl2a1 gene locus in mice hampers conventional gene targeting strategies. Transgenic overexpression of A1, deletion of the A1-a paralogue or constitutive knockdown in the hematopoietic compartment of mice by RNAi suggested rate-limiting roles in lymphocyte development, granulopoiesis and mast cell activation. Here we report on the consequences of conditional knockdown of A1 protein expression using a reverse transactivator (rtTA)-driven approach that highlights a critical role for this Bcl2 family member in the maintenance of mature B-cell homeostasis. Furthermore, we define the A1/Bim (Bcl-2 interacting mediator of cell death) axis as a target of key kinases mediating B-cell receptor (BCR)-dependent survival signals, such as, spleen tyrosine kinase (Syk) and Brutons tyrosine kinase (Btk). As such, A1 represents a putative target for the treatment of B-cell-related pathologies depending on hyperactivation of BCR-emanating survival signals and loss of A1 expression accounts, in part, for the pro-apoptotic effects of Syk- or Btk inhibitors that rely on the 'BH3-only' protein Bim for cell killing. PMID:26450454

  16. 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

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

    OpenAIRE

    Al-Achkar, Walid; Wafa, Abdulsamad; ALMEDANI, SUHER

    2010-01-01

    The well-known typical fusion gene BCR/ABL is observed in connection with a complex translocation event in 5–8% of cases of chronic myeloid leukemia (CML). The present study described an exceptional CML case with complex chromosomal aberrations not previously observed. Aberrations included a translocated BCR to the derivative chromosome 2 [der(2)] that also involved a four-chromosome translocation, implying chromosomal regions 1p32 and 2q21, besides 9q34 and 22q11.2, which were characterized ...

  18. 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)

    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)

  19. 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), o...

  20. 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.

  1. 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

  2. An evaluation of the accuracy and precision of X-ray microanalysis techniques using BCR-126A glass reference material

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Morilla, Inmaculada [Ion Beam Centre, Advanced Technology Institute, University of Surrey, Guildford GU2 7XH (United Kingdom)]. E-mail: i.gomez-morilla@surrey.ac.uk; Simon, Aliz [Institute of Nuclear research of the Hungarian Academy of Sciences (ATOMKI), P.O. Box 51, H-4001 Debrecen (Hungary); Simon, Rolf [Institute for Synchrotron Radiation, Forschungszentrum Karlsruhe GmbH, Hermann von Helmholtz Platz 1, Eggenstein-Leopoldshafen D-76344 (Germany); Williams, C. Terry [Department of Mineralogy, The Natural History Museum, London SW7 5BD (United Kingdom); Kiss, Arpad Z. [Institute of Nuclear research of the Hungarian Academy of Sciences (ATOMKI), P.O. Box 51, H-4001 Debrecen (Hungary); Grime, Geoffrey W. [Department of Physics, University of Surrey, Guildford GU2 7XH (United Kingdom)

    2006-08-15

    The precision and accuracy of four different X-ray analytical techniques at the micrometre level, PIXE-RBS, PIXE-PIXE, {mu}-SRXRF and WDS, have been investigated and compared. A range of different reference materials was considered for this purpose, and the glass BCR 126A was selected for the inter-comparison study, due to its homogeneity, chemical stability and elemental composition. The experimental protocols were tailored to employ the standard, optimal measurement conditions for each technique and material, but still retaining comparable measurement parameters between the different methods. The results show that the different techniques can complement each other without compromising in accuracy, and that they agree with each other to better than 5%.

  3. An evaluation of the accuracy and precision of X-ray microanalysis techniques using BCR-126A glass reference material

    International Nuclear Information System (INIS)

    The precision and accuracy of four different X-ray analytical techniques at the micrometre level, PIXE-RBS, PIXE-PIXE, μ-SRXRF and WDS, have been investigated and compared. A range of different reference materials was considered for this purpose, and the glass BCR 126A was selected for the inter-comparison study, due to its homogeneity, chemical stability and elemental composition. The experimental protocols were tailored to employ the standard, optimal measurement conditions for each technique and material, but still retaining comparable measurement parameters between the different methods. The results show that the different techniques can complement each other without compromising in accuracy, and that they agree with each other to better than 5%

  4. Modeling the presentation of C3d-coated antigen by B lymphocytes: enhancement by CR1/2-BCR co-ligation is selective for the co-ligating antigen.

    Science.gov (United States)

    Prechl, József; Baiu, Dana C; Horváth, Attila; Erdei, Anna

    2002-03-01

    We have used a set of single-chain variable fragment antibodies (sc) genetically fused with an influenza hemagglutinin-derived peptide as a means to investigate the role of CR1 and CR2 in antigen presentation by B cells. When incubated with the B cell lymphoma 2PK3, peptide-containing sc specific for either CR1 or CR1/2 mediated activation of the hemagglutinin peptide-specific T cell line IP-12-7, as assessed by IL-2 production. Efficient presentation was dependent on the binding of the constructs to CR1/2, implying that receptor-mediated endocytosis is responsible for the effect. Cross-linkage of CR1/2 or CD19 by mAb did not increase the extent of T cell activation. However, when CR1/2 was co-ligated with the BCR--using either polyclonal goat anti-mouse IgG or recombinant protein LA--the antigen concentration required to activate T cells decreased by two orders of magnitude. Moreover, this enhancement was selective for the antigen included in these complexes and did not affect the presentation of a free peptide or of antigen bound to CR1/2 excluded from the complexes. These results suggest that B cells may bind various C3d-coated antigens at a time, but only the one which reacts with the BCR will be processed with high efficiency. This mechanism may ensure the specificity of cognate T cell help. PMID:11867560

  5. Perturbation of energy metabolism by fatty-acid derivative AIC-47 and imatinib in BCR-ABL-harboring leukemic cells.

    Science.gov (United States)

    Shinohara, Haruka; Kumazaki, Minami; Minami, Yosuke; Ito, Yuko; Sugito, Nobuhiko; Kuranaga, Yuki; Taniguchi, Kohei; Yamada, Nami; Otsuki, Yoshinori; Naoe, Tomoki; Akao, Yukihiro

    2016-02-01

    In Ph-positive leukemia, imatinib brought marked clinical improvement; however, further improvement is needed to prevent relapse. Cancer cells efficiently use limited energy sources, and drugs targeting cellular metabolism improve the efficacy of therapy. In this study, we characterized the effects of novel anti-cancer fatty-acid derivative AIC-47 and imatinib, focusing on cancer-specific energy metabolism in chronic myeloid leukemia cells. AIC-47 and imatinib in combination exhibited a significant synergic cytotoxicity. Imatinib inhibited only the phosphorylation of BCR-ABL; whereas AIC-47 suppressed the expression of the protein itself. Both AIC-47 and imatinib modulated the expression of pyruvate kinase M (PKM) isoforms from PKM2 to PKM1 through the down-regulation of polypyrimidine tract-binding protein 1 (PTBP1). PTBP1 functions as alternative splicing repressor of PKM1, resulting in expression of PKM2, which is an inactive form of pyruvate kinase for the last step of glycolysis. Although inactivation of BCR-ABL by imatinib strongly suppressed glycolysis, compensatory fatty-acid oxidation (FAO) activation supported glucose-independent cell survival by up-regulating CPT1C, the rate-limiting FAO enzyme. In contrast, AIC-47 inhibited the expression of CPT1C and directly fatty-acid metabolism. These findings were also observed in the CD34(+) fraction of Ph-positive acute lymphoblastic leukemia cells. These results suggest that AIC-47 in combination with imatinib strengthened the attack on cancer energy metabolism, in terms of both glycolysis and compensatory activation of FAO. PMID:26607903

  6. MicroRNA-1301-Mediated RanGAP1 Downregulation Induces BCR-ABL Nuclear Entrapment to Enhance Imatinib Efficacy in Chronic Myeloid Leukemia Cells.

    Directory of Open Access Journals (Sweden)

    Tsung-Yao Lin

    Full Text Available Chronic myeloid leukemia (CML is a myeloproliferative disease. Imatinib (IM, the first line treatment for CML, is excessively expensive and induces various side effects in CML patients. Therefore, it is essential to investigate a new strategy for improving CML therapy. Our immunoblot data revealed that RanGTPase activating protein 1 (RanGAP1 protein levels increased by approximately 30-fold in K562 cells compared with those in normal cells. RanGAP1 is one of the important components of RanGTPase system, which regulates the export of nuclear protein. However, whether RanGAP1 level variation influences BCR-ABL nuclear export is still unknown. In this report, using shRNA to downregulate RanGAP1 expression level augmented K562 cell apoptosis by approximately 40% after treatment with 250 nM IM. Immunofluorescence assay also indicated that three-fold of nuclear BCR-ABL was detected. These data suggest that BCR-ABL nuclear entrapment induced by RanGAP1 downregulation can be used to improve IM efficacy. Moreover, our qRT-PCR data indicated a trend of inverse correlation between the RanGAP1 and microRNA (miR-1301 levels in CML patients. MiR-1301, targeting the RanGAP1 3' untranslated region, decreased by approximately 100-fold in K562 cells compared with that in normal cells. RanGAP1 downregulation by miR-1301 transfection impairs BCR-ABL nuclear export to increase approximately 60% of cell death after treatment of 250 nM IM. This result was almost the same as treatment with 1000 nM IM alone. Furthermore, immunofluorescence assay demonstrated that Tyr-99 of nuclear P73 was phosphorylated accompanied with nuclear entrapment of BCR-ABL after transfection with RanGAP1 shRNA or miR-1301 in IM-treated K562 cells. Altogether, we demonstrated that RanGAP1 downregulation can mediate BCR-ABL nuclear entrapment to activate P73-dependent apoptosis pathway which is a novel strategy for improving current IM treatment for CML.

  7. Extramedullary blast crisis as initial presentation in chronic myeloid leukemia with the e1a2 BCR-ABL1 transcript: A case report

    Science.gov (United States)

    AI, DI; LIU, WEI; LU, GARY; PATEL, KEYUR PRAVINCHANDRA; CHEN, ZI

    2015-01-01

    A 23-year-old woman presented with enlarged right inguinal lymph nodes. The pathological examination of the nodes revealed infiltration by myeloid sarcoma. A bone marrow smear and biopsy revealed cytogenetic abnormalities, with 46,XX,t(9;22) and chronic myeloid leukemia (CML) was diagnosed. The e1a2 BCR-ABL1 fusion transcript was detected. The patient received imatinib-based combined chemotherapy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusions and dasatinib treatment. The patient achieved complete response and has remained leukemia-free for >48 months. To the best of our knowledge, this is the first case report of CML with the e1a2 BCR-ABL1 transcript, with extramedullary blast crisis as the initial presentation. The aim of the present study was to discuss this special case with reference to the literature. PMID:26807241

  8. 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.

  9. 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

    2016-01-01

    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. PMID:27329306

  10. 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.

  11. BCR-ABL transcript variations in chronic phase chronic myelogenous leukemia patients on imatinib first-line: Possible role of the autologous immune system.

    Science.gov (United States)

    Clapp, Geoffrey D; Lepoutre, Thomas; Nicolini, Franck E; Levy, Doron

    2016-05-01

    Many chronic myelogenous leukemia (CML) patients in chronic phase who respond well to imatinib therapy show fluctuations in their leukemic loads in the long-term. We developed a mathematical model of CML that incorporates the intervention of an autologous immune response. Our results suggest that the patient's immune system plays a crucial role in imatinib therapy in maintaining disease control over time. The observed BCR-ABL/ABL oscillations in such patients provide a signature of the autologous immune response. PMID:27467931

  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

    International Nuclear Information System (INIS)

    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. 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)

    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)

  14. Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of chronic lymphocytic leukemia B cells.

    Directory of Open Access Journals (Sweden)

    M Lia Palomba

    Full Text Available PURPOSE: Chronic Lymphocytic Leukemia (CLL is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. EXPERIMENTAL DESIGN: We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR. Results from multidimensional modeling were validated using an independent test cohort of 38 patients. RESULTS: We identified a dynamic and variable imbalance between proximal (pSYK, pBTK and distal (pPLCγ2, pBLNK, ppERK phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness. CONCLUSION: Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets.

  15. Location of CTP-OD1-HA and CTP-OD2-HA fusion peptide in K562 cells and its interaction with BCR-ABL protein

    Directory of Open Access Journals (Sweden)

    Heng XIAO

    2013-11-01

    Full Text Available Objective To investigate the intracellular location of cytoplasmic transduction peptide-oligomerization domain 1-hemagglutinin (CTP-OD1-HA and cytoplasmic transduction peptide-oligomerization domain 2-hemagglutinin (CTP-OD2-HA fusion peptide and interaction with BCR-ABL protein in chronic myelocytic leukemia (CML K562 cells. Methods The prepared CTP-OD1-HA and CTP-OD2-HA fusion peptide were transduced into K562 cells, and the cytoplasmic transduction peptideoligomerization domain-hemagglutinin (CTP-OD-HA peptide was used as positive control, and cytoplasmic transduction peptidehemagglutinin (CTP-HA and PBS were used as negative control. The intracellular location of the fusion peptide was demonstrated by immunofluorescence and Western blotting. The interactions between the fusion peptides and BCR-ABL protein were detected by His-pull down and CoIP test. Results Immunofluorescence assay showed that both fusion peptides CTP-OD1-HA and CTP-OD2-HA could penetrate the cell membrane, and they were mainly localized in cytoplasm. Western blotting also confirmed the existence of the two fusion peptides in the cytoplasm. His-pull down showed that CTP-OD1-HA and CTP-OD2-HA could directly bind BCRABL protein outside the cells, and CoIP experiment showed that both fusion peptides could interact with BCR-ABL protein and form complex in the K562 cells. The negative control CTP-HA fusion peptide and PBS showed no such effects. Conclusion CTPOD1-HA and CTP-OD2-HA fusion peptides can successfully target into CML K562 cells and locate in cytoplasm, and it interacts with BCR-ABL protein. DOI: 10.11855/j.issn.0577-7402.2013.11.006

  16. 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)

    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

  17. 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.

  18. Coupling a universal DNA circuit with graphene sheets/polyaniline/AuNPs nanocomposites for the detection of BCR/ABL fusion gene

    International Nuclear Information System (INIS)

    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

  19. 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.

  20. Speciation of Heavy Metals by Modified BCR Sequential Extraction in Soils Contaminated by Phosphogypsum in Sfax, Tunisia

    Directory of Open Access Journals (Sweden)

    Ahmed Wali

    2015-01-01

    Full Text Available The accumulation of trace metals in soil is a serious environmental problem that creates a hazard when metals are transferred to water or plants. To understand the mobility and bioavailability of trace metals, the concentrations and distributions of trace metals must be established for different physical and chemical phases of the soil. We determined the concentrations of trace metals (Zn, Pb, Cu, Cr, Co, Ni, Mn, and Fe in soil using the sequential extraction method recommended by Community Bureau of Reference (BCR and analysed chemical properties, such as the pH, cation exchange capacity, total organic carbon, electrical conductivity, and calcium carbonate. Our results revealed higher concentrations of trace metals in topsoil samples (0–20 cm than in subsoil samples (20–40 cm and 40–60 cm for most metals at four sites. Zn in the topsoil was mostly associated with the non-resistant fraction at all sites. Approximately 60% more Pb was bound to the non-residual, exchangeable and reducible fractions at all sites, and soil depths. Cr, Cu, Ni and Fe were mainly in the residual fraction, whereas Mn was largely present in the non-resistant fraction. The global contamination factor of trace metals decreased with soil depth. The mobility and bioavailability were greatest for Zn, followed by Cu and Pb. DOI: http://dx.doi.org/10.5755/j01.erem.70.4.7807

  1. Myeloproliferative neoplasms (BCR-ABL1 negative) and myelodysplastic/myeloproliferative neoplasms: current diagnostic principles and upcoming updates.

    Science.gov (United States)

    Geyer, J T; Orazi, A

    2016-05-01

    Since the publication of the latest World Health Organization (WHO) classification in 2008, there has been a significant effort for clarification of unresolved questions, especially with the help of the rapidly developing field of molecular genetic studies, next-generation sequencing in particular. Numerous entities within the WHO categories of myeloproliferative neoplasms (MPNs) and myelodysplastic (MDS)/MPNs have been extensively studied, with large published series attempting to characterize and better define their morphologic and molecular genetic features. This emerging genetic landscape maintains a robust correlation with the various disease entities recognized by the WHO classification scheme based on a careful integration of detailed clinical information, bone marrow and peripheral blood morphology, immunohistology, and genomics. This brief review summarizes the current guidelines as they apply to diagnosing both the classical BCR-ABL1 negative MPN (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) and the more common subtypes of MDS/MPN overlap syndromes. The more important recent molecular updates as well as the upcoming changes to the current WHO classification, expected to be published in late 2016, will also be briefly reviewed. PMID:27161873

  2. Effects of modified zeolite on the removal and stabilization of heavy metals in contaminated lake sediment using BCR sequential extraction.

    Science.gov (United States)

    Wen, Jia; Yi, Yuanjie; Zeng, Guangming

    2016-08-01

    Sediment can be applied on land as a soil conditioner. However, toxic substances such as heavy metals within the sediment often lead to soil contamination if no proper management is conducted prior to land application. In order to reduce the bioavailable portion of heavy metals such as Pb, Cu, Zn and Cd, zeolite as a kind of stabilizer was investigated on the effect of metal stabilization in sediment. Zeolite was firstly modified and screened to get the best condition for removal of heavy metals. Results showed that the granulated zeolite with NaCl conditioning had the highest CEC and metal sorption. Using BCR sequential extraction, the selected modified zeolite effectively stabilized Pb, Cu, Zn and Cd in sediment to different extents. It was most suitable for Cd stabilization by reducing its acid exchangeable fraction while increasing the contents of the reducible and residual fractions. Modified zeolite also immobilized Cu, Zn and Pb in sediment by enhancing one stable fraction while decreasing the acid exchangeable fraction. PMID:27136618

  3. 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; Junior, Sidney F Salles; Marques, Marcia; Moreira, Josino C; Pérez, Daniel V

    2014-11-01

    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

  4. 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.

  5. A report case of mixed phenotype acute leukemia with BCR - ABL positive and literature review%BCR - ABL 融合基因阳性的急性混合细胞白血病1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    符爽; 张男; 陈芳; 刘璇; 胡延平; 张旻昱; 张继红

    2014-01-01

    Objective:To investigate the clinical characteristics,biological features,clinical curative effect and out-come of mixed PhenotyPe acute leukemia(MPAL). Methods:Results of clinical data,cell morPhology,immunoPheno-tyPe,cytogenetics and molecular genetics of the MPAL Patient with BCR - ABL Positive were analyzed with literature reviews. Results:The clinical and hematological findings were comPatible with the diagnosis of MPAL. LymPhoid and myeloid markers were Positive on the leukemia cells. KaryotyPe analysis showed that the Patient had t(9;22)(q34;q11)translocation. Quantitative reverse transcriPtion PCR results showed that BCR - ABL(P210)exPressed 100% . And no deletion,Point or insert mutation was found among C - Kit(8,17 exon),FLT3 - ITD/ TKD,NPM1 and CEBPα. Conclusion:Primary MPAL with BCR - ABL Positive is rarely rePorted which have a Poor Prognosis. Some of them are cases of chronic myeloid leukemia blast crisis. BCR - ABL gene exPression is closely related to Patients' Prognosis.%目的:探讨 BCR - ABL 融合基因阳性表达的急性混合细胞白血病(MPAL)的临床特点、生物学特性、临床疗效及预后。方法:对1例 BCR - ABL 融合基因阳性的急性混合细胞白血病患者的临床资料、细胞形态学、免疫分型、细胞遗传学及分子生物学的检测结果进行综合分析。结果:患者的临床表现和实验室检测结果均符合急性混合细胞白血病诊断标准,免疫表型分析白血病细胞同时表达髓系和淋系抗原,染色体核型为46,XX,t(9;22)(q34;q11),荧光定量 PCR 检测结果示 BCR - ABL(P210)融合基因表达100%,白血病预后基因检测结果示患者 C - Kit(8、17 exon)、FLT3- ITD/ TKD、NPM1和 CEBPα基因均为野生型。结论:初发的 BCR - ABL 融合基因阳性的急性混合细胞白血病病例罕见,部分病例由慢性粒细胞白血病急变而来,预后差。BCR - ABL 基因阳性与患者预后密切相关。

  6. Fifth symposium on surface mining and reclamation. NCA/BCR coal conference and Expo IV

    Energy Technology Data Exchange (ETDEWEB)

    None

    1977-01-01

    The Fifth Symposium on Surface Mining and Reclamation, sponsored by the National Coal Association and Bituminous Coal Research, Inc., was held at the Kentucky Fair and Exposition Center, Louisville, Kentucky, October 18-20, 1977. Twenty-six papers from the proceedings have been entered individually into EDB and ERA. Topics covered include spoil bank revegetation, use of aerial photography, reclamation for row crop production, hydrology, computer programs related to this work, subirrigated alluvial valley floors, reclamation on steep slopes, mountain top removal, surface mine road design, successional processes involved in reclamation, land use planning, etc. (LTN)

  7. 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)

    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 206Pb, the contamination of exogenous Pb2+ 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

  8. 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.

  9. Allogeneic Stem Cell Transplantation for Patients with T315I BCR-ABL Mutated Chronic Myeloid Leukemia.

    Science.gov (United States)

    Xu, Lan-Ping; Xu, Zheng-Li; Zhang, Xiao-Hui; Chen, Huan; Chen, Yu-Hong; Han, Wei; Chen, Yao; Wang, Feng-Rong; Wang, Jing-Zhi; Wang, Yu; Yan, Chen-Hua; Mo, Xiao-Dong; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-06-01

    Allogeneic stem cell transplantation (SCT) is currently the only curative treatment option for chronic myeloid leukemia (CML) patients with BCR-ABL T315I mutations. We report the outcome of SCT in 22 patients with T315I(+) CML, most (n = 16) from haploidentical family donors (HID-SCT). At the time the mutation was detected, 8 patients were in the chronic phase (CP), 7 in the accelerated phase (AP), and 7 in the blast phase (BP). At the time of SCT 7 were in the CP, 8 in the AP or returning to the CP post-AP (AP/AP-CPn), and 7 in the BP or returning to CP post-BP (BP/BP-CPn). The cumulative incidence of grades III to IV acute graft-versus-host disease was 9.1%. Chronic graft-versus-host disease was observed in 60.0% of patients, including 25.0% who suffered from severe disease. Four patients died of transplant-related complications at a median interval from SCT of 16.3 months. The estimated 2-year leukemia-free survival rate was 80.0%, 72.9%, and 0% in CP, AP/AP-CPn and BP/BP-CPn groups at the time of SCT, respectively. After a median follow-up of 17.3 months from SCT, 14 patients are alive, including 13 in complete molecular response and 1 with an extramedullary relapse. In conclusion, HID-SCT is a potentially curative treatment for T315I + CML patients. For patients in CP/AP, immediate SCT might result in promising survival. The outcome of patients in BP with T315I(+) mutation remains very poor. PMID:26995693

  10. miR-29b suppresses CML cell proliferation and induces apoptosis via regulation of BCR/ABL1 protein

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally and are critical for many cellular pathways. Recent evidence has shown that aberrant miRNA expression profiles and unique miRNA signaling pathways are present in many cancers. Here, we demonstrate that miR-29b is markedly lower expressed in CML patient samples. Bioinformatics analysis reveals a conserved target site for miR-29b in the 3′-untranslated region (UTR) of ABL1. miR-29b significantly suppresses the activity of a luciferase reporter containing ABL1-3′UTR and this activity is not observed in cells transfected with mutated ABL1-3′UTR. Enforced expression of miR-29b in K562 cells inhibits cell growth and colony formation ability thereby inducing apoptosis through cleavage of procaspase 3 and PARP. Furthermore, K562 cells transfected with a siRNA targeting ABL1 show similar growth and apoptosis phenotypes as cells overexpression of miR-29b. Collectively, our results suggest that miR-29b may function as a tumor suppressor by targeting ABL1 and BCR/ABL1. - Highlights: ► miR-29b expression was downregulated in CML patients. ► ABL1 was identified as a direct target gene of miR-29b. ► Enforced expression of miR-29b inhibits cell proliferation and induces apoptosis. ► miR-29b might be a therapeutic target to CML

  11. In-silico identification of inhibitors against mutated BCR-ABL protein of chronic myeloid leukemia: a virtual screening and molecular dynamics simulation study.

    Science.gov (United States)

    Kumar, Himansu; Raj, Utkarsh; Gupta, Saurabh; Varadwaj, Pritish Kumar

    2016-10-01

    Aberrant and proliferative expression of the oncogene BCR-ABL in the bone marrow cells had been proven as the prime cause of chronic myeloid leukemia (CML). It has been established that tyrosine kinase domain of BCR-ABL protein is a potential therapeutic target for the treatment of CML. Imatinib is considered as a first-generation drug that can inhibit the enzymatic action by inhibiting the ATP binding with BCR-ABL protein. Later on, insensitivity of CML cells towards Imatinib has been observed may be due to mutation in tyrosine kinase domain of the ABL receptor. Subsequently, some other second-generation drugs have also been reported viz. Baustinib, Nilotinib, Dasatinib, Ponatinib, Bafetinib, etc., which can able to combat against mutated domain of ABL tyrosine kinase protein. By taking into account of bioavailability and resistance developed, there is an utmost need to find some more inhibitors for the mutated ABL tyrosine kinase protein. For virtual screening, a data-set has been generated by collecting the all available drug like natural compounds from ZINC and Drug Bank databases. Comparative docking analysis was also carried out on the active site of ABL tyrosine kinase receptor with reported reference inhibitors. Molecular dynamics simulation of the best screened interacting complex was done for 50 ns to validate the stability of the system. These selected inhibitors were further validated and analyzed through pharmacokinetics properties and series of ADMET parameters by in silico methods. Considering the above said parameters proposed molecules are concluded as potential leads for drug designing pipeline against CML. PMID:26479578

  12. Down-regulation of Thanatos-associated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression.

    Science.gov (United States)

    Nakamura, Satoki; Yokota, Daisuke; Tan, Lin; Nagata, Yasuyuki; Takemura, Tomonari; Hirano, Isao; Shigeno, Kazuyuki; Shibata, Kiyoshi; Fujisawa, Shinya; Ohnishi, Kazunori

    2012-03-01

    Bcr-Abl activates various signaling pathways in chronic myelogenous leukemia (CML) cells. The proliferation of Bcr-Abl transformed cells is promoted by c-Myc through the activation of Akt, JAK2 and NF-κB. However, the mechanism by which c-Myc regulates CML cell proliferation is unclear. In our study, we investigated the role of Thanatos-associated protein 11 (THAP11), which inhibits c-Myc transcription, in CML cell lines and in hematopoietic progenitor cells derived from CML patients. The induction of THAP11 expression by Abl kinase inhibitors in CML cell lines and in CML-derived hematopoietic progenitor cells resulted in the suppression of c-Myc. In addition, over-expression of THAP11 inhibited CML cell proliferation. In colony forming cells derived from CML-aldehyde dehydrogenase (ALDH)(hi) /CD34(+) cells, treatment with Abl kinase inhibitors and siRNA depletion of Bcr-Abl induced THAP11 expression and reduced c-Myc expression, resulting in inhibited colony formation. Moreover, overexpression of THAP11 significantly decreased the colony numbers, and also inhibited the expression of c-myc target genes such as Cyclin D1, ODC and induced the expression of p21(Cip1) . The depletion of THAP11 inhibited JAK2 or STAT5 inactivation-mediated c-Myc reduction in ALDH(hi) /CD34(+) CML cells. Thus, the induced THAP11 might be one of transcriptional regulators of c-Myc expression in CML cell. Therefore, the induction of THAP11 has a potential possibility as a target for the inhibition of CML cell proliferation. PMID:21400515

  13. 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)

    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 is

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

    Science.gov (United States)

    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 is

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

    Directory of Open Access Journals (Sweden)

    Axel Weber

    2015-03-01

    Full Text Available Signal transducers and activators of transcription (Stats play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML and Jak2(V617F in other myeloproliferative diseases (MPD. We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL

  16. The validation of Kayzero-assisted NAA in Budapest, Rez, and Ljubljana via the analysis of three BCR certified reference materials.

    Science.gov (United States)

    De Corte, F; van Sluijs, R; Simonits, A; Kucera, J; Smodis, B; Byrne, A R; De Wispelaere, A; Bossus, D; Frána, J; Horák, Z; Jaćimović, R

    2001-05-01

    After installation and calibration of k0-assisted NAA in three Central European research institutes (AEKI-Budapest, NPI-Rez, and IJS, Ljubljana), its validation was established via the analysis of three BCR certified reference materials. The matrices of choice were: CRM 277 estuarine sediment, CRM 038 coal fly ash from pulverized coal, and CRM 101 spruce needles. For some elements, e.g. Zn, Cd, and Hg, the analyses were not only performed instrumentally (INAA), but also in the radiochemical mode (RNAA). The work was performed in the framework of a European Copernicus Project. PMID:11393234

  17. Standardization of real-time quantitative polymerase chain reaction for detection of the JAK2V617F mutation in BCR-ABL1 negative myeloproliferative neoplasms: A tertiary care centre experience

    Directory of Open Access Journals (Sweden)

    Tathagat Chatterjee

    2015-01-01

    Full Text Available Background: Identification of JAK2V617F mutations has led to a significant development in our understanding of the pathogenesis and therapy of BCR-ABL1 negative myeloproliferative neoplasms (MPNs. However, not all cases of BCR-ABL1 negative MPNs carry JAK2V617F mutations. The present study was undertaken with an aim to standardize the real-time quantitative polymerase chain reaction (PCR for the detection of JAK2V617F mutations and to find the prevalence of Janus kinase 2 (JAK2 mutations in MPNs in the Indian scenario. Materials and Methods: Real-time quantitative PCR was used to detect the JAK2V617F mutation. Standardization of the detection procedure was carried out using recommended guidelines to ensure the accuracy and reproducibility of results. Forty-nine patients of BCR-ABL1 negative MPNs were included in the study. Results: The JAK2V617F mutation was detected in 63.3% patients of BCR-ABL1 negative MPNs. On classification of these BCR-ABL1 negative MPNs, JAK2V617F mutation was detected in 78.3% patients with polycythemia vera (PV, 62.5% patients with essential thrombocythemia (ET, and 44.4% patients with Primary myelofibrosis (PMF. Conclusion: Role of detection of JAK2 mutations in BCR-ABL1 negative MPN has begun to be described and can be used in the diagnosis of PV, ET, and PMF along with other criterias. In future, it may be suitable for treatment monitoring and prognostication.

  18. Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage.

    Directory of Open Access Journals (Sweden)

    Mingqiang Ren

    Full Text Available Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19(+ IgM(- CD43(+ immunophenotype was seen both in primary tumors and two cell lines derived from these tumors. In all primary tumors, subpopulations of these CD19(+ IgM(- CD43(+ were also either B220(+ or B220(-, suggesting a block in differentiation at the pro-B cell stage. The B220(- phenotype was retained in one of the cell lines while the other was B220(+. When the two cell lines were transplanted into syngeneic mice, all animals developed the same B-lymphoblastic leukemia within 2-weeks. Thus, the murine model described here closely mimics the human disease with bilineage myeloid and B-cell leukemia/lymphoma which provides a representative model to investigate therapeutic intervention and a better understanding of the etiology of the disease.

  19. The diagnosis of BCR/ABL-negative chronic myeloproliferative diseases (CMPD): a comprehensive approach based on morphology, cytogenetics, and molecular markers.

    Science.gov (United States)

    Haferlach, Torsten; Bacher, Ulrike; Kern, Wolfgang; Schnittger, Susanne; Haferlach, Claudia

    2008-01-01

    Recent years showed significant progress in the molecular characterization of the chronic myeloproliferative disorders (CMPD) which are classified according to the WHO classification of 2001 as polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET), CMPD/unclassifiable (CMPD-U), chronic neutrophilic leukemia, and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome, all to be delineated from BCR/ABL-positive chronic myeloid leukemia (CML). After 2001, the detection of the high frequency of the JAK2V617F mutation in PV, CIMF, and ET, and of the FIP1L1-PDGFRA fusion gene in CEL further added important information in the diagnosis of CMPD. These findings also enhanced the importance of tyrosine kinase mutations in CMPD and paved the way to a more detailed classification and to an improved definition of prognosis using also novel minimal residual disease (MRD) markers. Simultaneously, the broadening of therapeutic strategies in the CMPD, e.g., due to reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation and the introduction of tyrosine kinase inhibitors in CML, in CEL, and in other ABL and PDGRFB rearrangements, increased the demands to diagnostics. Therefore, today, a multimodal diagnostic approach combining cytomorphology, cytogenetics, and individual molecular methods is needed in BCR/ABL-negative CMPD. A stringent diagnostic algorithm for characterization, choice of treatment, and monitoring of MRD will be proposed in this review. PMID:17938925

  20. 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.

  1. GENE THERAPY USING RETROVIRAL VECTOR OF bcr-abl SPECIFIC MULTI-UNIT RIBOZYMES COULD INHIBIT CML CELL GROWTH AND INDUCE APOPTOSIS

    Institute of Scientific and Technical Information of China (English)

    冯琦; 孙凯; 赵永同; 张涛; 尚振川; 王莎; 王玮; 赵宁; 颜真; 韩苇; 张英起; 孙秉中

    2003-01-01

    Objective: To investigate the in vitro cleavage ability and effects on apoptosis and cell growth of the bcr-abl fusion gene specific multi-unit ribozymes. Methods: Three fusion point specific ribozymes were designed and the multi-unit ribozymes' in vitro transcription vector and retroviral vector were constructed. The in vitro cleavage ability was tested. The retroviral vector was transfected into K562 cell and the effects on proliferation, apoptosis, cell cycle and cell structure were observed. Results: Multi-unit ribozymes had in vitro cleavage efficiency of 70.8%, which was more efficient than single-unit and double-unit ribozymes. Transfection of the retroviral vector of the ribozyme into K562 cells, induced inhibition of cell growth and apoptosis. The incorporation rate of DNA in ribozymes transfected K562 cells was greatly decreased along with time passed, with an inhibition rate of more than 50% after 96 h of transfection. Under FCM, 18.4% of the cells underwent apoptosis 72 h after transfection and more cells were blocked in G phase, with the ratio in S phase greatly decreased (41.9%). Under electron microscope, compaction of nuclear chromatin and apoptosis bodies were observed.Conclusion: Multi-unit ribozymes specific to bcr-abl fusion gene can be used to treat CML and to purge bone marrow for self-grafting.

  2. 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.

  3. 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

    OpenAIRE

    Gonzálo Vásquez Palacio; José Domingo Torres Hernández; Francisco Cuéllar Ambrossi; Carlos Enrique Muskus; Carlos Alberto Paya

    2006-01-01

    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.

  4. Increased acetylation of lysine 317/320 of p53 caused by BCR-ABL protects from cytoplasmic translocation of p53 and mitochondria-dependent apoptosis in response to DNA damage

    NARCIS (Netherlands)

    Kusio-Kobialka, Monika; Wolanin, Kamila; Podszywalow-Bartnicka, Paulina; Sikora, Ewa; Skowronek, Krzysztof; McKenna, Sharon L.; Ghizzoni, Massimo; Dekker, Frank J.; Piwocka, Katarzyna

    2012-01-01

    Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cells caused by the expression of BCR-ABL. Loss of p53 has not been implicated as important for the development of CML. Mutations in p53 protein are infrequent, however they correlate with the disease progression. The absence of p53

  5. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance.

    Science.gov (United States)

    Kantarjian, Hagop M; Giles, Francis; Gattermann, Norbert; Bhalla, Kapil; Alimena, Giuliana; Palandri, Francesca; Ossenkoppele, Gert J; Nicolini, Franck-Emmanuel; O'Brien, Stephen G; Litzow, Mark; Bhatia, Ravi; Cervantes, Francisco; Haque, Ariful; Shou, Yaping; Resta, Debra J; Weitzman, Aaron; Hochhaus, Andreas; le Coutre, Philipp

    2007-11-15

    Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in pre-clinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase 2 open-label study, 400 mg nilotinib was administered orally twice daily to 280 patients with Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia in chronic phase (CML-CP) after imatinib failure or intolerance. Patients had at least 6 months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At 6 months, the rate of major cytogenetic response (Ph < or = 35%) was 48%: complete (Ph = 0%) in 31%, and partial (Ph = 1%-35%) in 16%. The estimated survival at 12 months was 95%. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 29% of patients; pleural or pericardial effusions were observed in 1% (none were severe). In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707. PMID:17715389

  6. 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

  7. CHEMICALLY ACTIVE FLUID-BED PROCESS FOR SULPHUR REMOVAL DURING GASIFICATION OF HEAVY FUEL OIL - SECOND PHASE

    Science.gov (United States)

    The report describes the second phase of studies on the CAFB process for desulfurizing gasification of heavy fuel oil in a bed of hot lime. The first continuous pilot plant test with U.S. limestone BCR 1691 experienced local stone sintering and severe production of sticky dust du...

  8. SPR Detection and Discrimination of the Oligonucleotides Related to the Normal and the Hybrid bcr-abl Genes by Two Stringency Control Strategies.

    Science.gov (United States)

    Matsishin, M J; Ushenin, Iu V; Rachkov, A E; Solatkin, A P

    2016-12-01

    In this study, we applied two stringency control strategies for surface plasmon resonance (SPR) detection of DNA hybridization and discrimination of completely and partially complementary 24-mer sequences. These sequences are specific to the human normal bcr and the hybrid bcr-abl genes, protein products of which are responsible for some leukemia. SPR sensors based on resonance phenomena in nanoscale gold films are well suited for label-free, real-time investigations of the macromolecule interactions. Thermodynamic parameters obtained using the web server DINAMelt allowed supposing the possibility for realization (a) stringency control based on the ionic strength of the hybridization buffer and (b) stringency control based on the temperature elevation. The first one resulted in that the discrimination index of completely complementary and partially complementary oligonucleotides depending on the target concentration varied from 1.3 to 1.8 in 2 × SSC and from 2.0 to 2.9 in 0.5 × SSC. For implementation of the second stringency control strategy, SPR spectrometer measuring flow cell with built-in high-precision temperature control and regulation as well as corresponding software was created. It is shown that the duplexes formed by the immobilized probes mod-Ph and completely complementary oligonucleotides P1 remained without significant changes until ~50 °C, while the duplexes formed with partially complementary oligonucleotide Bcrex14 almost entirely disrupted at 40 °C. Thus, the absolutely effective thermodiscrimination of this pair of oligonucleotides was achieved in this temperature range (40-50 °C). PMID:26759355

  9. SPR Detection and Discrimination of the Oligonucleotides Related to the Normal and the Hybrid bcr-abl Genes by Two Stringency Control Strategies

    Science.gov (United States)

    Matsishin, M. J.; Ushenin, Iu. V.; Rachkov, A. E.; Solatkin, A. P.

    2016-01-01

    In this study, we applied two stringency control strategies for surface plasmon resonance (SPR) detection of DNA hybridization and discrimination of completely and partially complementary 24-mer sequences. These sequences are specific to the human normal bcr and the hybrid bcr-abl genes, protein products of which are responsible for some leukemia. SPR sensors based on resonance phenomena in nanoscale gold films are well suited for label-free, real-time investigations of the macromolecule interactions. Thermodynamic parameters obtained using the web server DINAMelt allowed supposing the possibility for realization (a) stringency control based on the ionic strength of the hybridization buffer and (b) stringency control based on the temperature elevation. The first one resulted in that the discrimination index of completely complementary and partially complementary oligonucleotides depending on the target concentration varied from 1.3 to 1.8 in 2 × SSC and from 2.0 to 2.9 in 0.5 × SSC. For implementation of the second stringency control strategy, SPR spectrometer measuring flow cell with built-in high-precision temperature control and regulation as well as corresponding software was created. It is shown that the duplexes formed by the immobilized probes mod-Ph and completely complementary oligonucleotides P1 remained without significant changes until ~50 °C, while the duplexes formed with partially complementary oligonucleotide Bcrex14 almost entirely disrupted at 40 °C. Thus, the absolutely effective thermodiscrimination of this pair of oligonucleotides was achieved in this temperature range (40-50 °C).

  10. Next-generation sequencing for sensitive detection of BCR-ABL1 mutations relevant to tyrosine kinase inhibitor choice in imatinib-resistant patients

    Science.gov (United States)

    Soverini, Simona; De Benedittis, Caterina; Polakova, Katerina Machova; Linhartova, Jana; Castagnetti, Fausto; Gugliotta, Gabriele; Papayannidis, Cristina; Mancini, Manuela; Klamova, Hana; Salvucci, Marzia; Crugnola, Monica; Iurlo, Alessandra; Albano, Francesco; Russo, Domenico; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

    2016-01-01

    In chronic myeloid leukemia (CML) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) patients who fail imatinib treatment, BCR-ABL1 mutation profiling by Sanger sequencing (SS) is recommended before changing therapy since detection of specific mutations influences second-generation tyrosine kinase inhibitor (2GTKI) choice. We aimed to assess i) in how many patients who relapse on second-line 2GTKI therapy next generation sequencing (NGS) may track resistant mutations back to the sample collected at the time of imatinib resistance, before 2GTKI start (switchover sample) and ii) whether low level mutations identified by NGS always undergo clonal expansion. To this purpose, we used NGS to retrospectively analyze 60 imatinib-resistant patients (CML, n = 45; Ph+ ALL, n = 15) who had failed second-line 2GTKI therapy and had acquired BCR-ABL1 mutations (Group 1) and 25 imatinib-resistant patients (CML, n = 21; Ph+ ALL, n = 4) who had responded to second-line 2GTKI therapy, for comparison (Group 2). NGS uncovered that in 26 (43%) patients in Group 1, the 2GTKI-resistant mutations that triggered relapse were already detectable at low levels in the switchover sample (median mutation burden, 5%; range 1.1%–18.4%). Importantly, none of the low level mutations detected by NGS in switchover samples failed to expand whenever the patient received the 2GTKI to whom they were insensitive. In contrast, no low level mutation that was resistant to the 2GTKI the patients subsequently received was detected in the switchover samples from Group 2. NGS at the time of imatinib failure reliably identifies clinically relevant mutations, thus enabling a more effective therapeutic tailoring. PMID:26980736

  11. 用COLD-PCR方法提高BCR-ABL1激酶区耐药突变检测灵敏度%Application of COLD-PCR for improved detection of BCR-ABL1 kinase domain drug-resistant mutation

    Institute of Scientific and Technical Information of China (English)

    李庆; 刘红星; 孙慧; 王倩; 张之芬; 武焕玲; 李元堂; 陈永金; 田文君

    2013-01-01

    Objective To evaluate the feasibility of the co-amplification using a low denaturation temperature PCR (COLD-PCR) method in improving the detection of BCR-ABL1 fusion gene kinase domain drug-resistant mutation.Methods Conventional nested PCR (CN-PCR) and COLD-PCR protocol were designed to amplify full-length of BCR-ABL1 kinase domain.PCR products were purified and then Sanger sequenced to detect BCR-ABL1 kinase domain mutation (KDM).20 newly diagnosed CML patients and 32 Imatinib (IM) resistant patients were chosen and peripheral blood or bone marrow samples were collected.PCR products of the clinical specimens were purified and then cloned to evaluate the proportion of the KDM allele.Standard samples with different proportion of KDMs were prepared using T-A vectors with KDM and wild type BCR-ABL1 kinase domain sequence,and then CN-PCR,COLD-PCR and Sanger sequencing were performed to compare the detection sensitivity.Results In the 32 IM-resistant patients,23 were identified KDM-positive using CN-PCR and 28 KDM-positive using COLD-PCR.In the 20 newly diagnosed CML patients,none was identified KDM-positive using CN-PCR and 1 was identified carrying a lower proportion of KDM using COLD-PCR.For 16 different types of KDMs,COLD-PCR method could improve the detection sensitivity 4-12 times.Conclusion Detection sensitivity of BCR-ABL1 drug-resistant kinase domain mutation can be effectively improved by using COLD-PCR method and may contribute to early detection of resistance KDMs.%目的 探讨用低变性温度共扩增PCR(COLD-PCR)方法提高BCR-ABL1融合基因激酶区耐药突变检测灵敏度的可行性.方法 本研究为实验诊断研究.设计常规巢式PCR(CN-PCR)和COLD-PCR方案扩增BCR-ABL1激酶区全长,扩增产物纯化后用Sanger测序法检测激酶区突变(KDM).采集32例经伊马替尼(IM)治疗并出现耐药的慢性粒细胞性白血病(CML)患者和20例初诊CML患者外周血或骨髓标本,用上述2种方案检测标本中的KDM.

  12. 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

    2016-04-28

    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

  13. 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

  14. Synthesis and characterization of a BODIPY conjugate of the BCR-ABL kinase inhibitor Tasigna® (Nilotinib): Evidence for transport of Tasigna® and its fluorescent derivative by ABC drug transporters

    OpenAIRE

    Shukla, Suneet; Skoumbourdis, Amanda P.; Walsh, Martin J.; Hartz, Anika M. S.; Fung, King Leung; Wu, Chung-pu; Gottesman, Michael M.; Bauer, Björn; Thomas, Craig J.; Suresh V Ambudkar

    2011-01-01

    Tasigna® (Nilotinib) is a recently approved BCR-ABL kinase inhibitor by the Food and Drug Administration, which is indicated for the treatment of drug-resistant chronic myelogenous leukemia (CML). The efflux of tyrosine kinase inhibitors by ATP-binding cassette (ABC) drug transporters, which actively pump these drugs out of cells utilizing ATP as an energy source, has been linked to the development of drug resistance in CML patients. We report here synthesis and characterization of a fluoresc...

  15. Failure of CDKN2A/B (INK4A/B–ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL

    OpenAIRE

    Mullighan, Charles G.; Williams, Richard T.; Downing, James R.; Sherr, Charles J.

    2008-01-01

    Deletions of the CDKN2A/B tumor suppressor locus and of the IKAROS and PAX5 genes that promote B-lineage development occur frequently in lymphoid, but not myeloid leukemias initiated by the BCR-ABL tyrosine kinase. Why is this the case, and how do these genetic lesions contribute to an aggressive disease that fails to durably respond to targeted kinase inhibitors?

  16. Cell sorting enables interphase fluorescence in situ hybridization detection of low BCR-ABL1 producing stem cells in chronic myeloid leukaemia patients beyond deep molecular remission

    DEFF Research Database (Denmark)

    van Kooten Niekerk, Peter Buur; Petersen, Charlotte Christie; Nyvold, Charlotte Guldborg;

    2014-01-01

    The exact disease state of chronic myeloid leukaemia (CML) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (qPCR) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate......) ), n = 11) using both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH). Despite evaluating fewer cells, iFISH proved superior to mRNA-based qPCR in detecting residual Ph(+) stem cells (P = 0·005), and detected Ph(+) stem- and progenitor cells in 9/10 patients at frequencies of 2......-14%. Moreover, while all qPCR(+) samples also were iFISH(+) , 9/33 samples were qPCR-/iFISH(+) , including all positive samples from MR(4) patients. Our findings show that residual Ph(+) cells are low BCR-ABL1 producers, and that DNA-based methods are required to assess the content of persisting Ph(+) stem...

  17. miR-146b-5p within BCR-ABL1-Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells.

    Science.gov (United States)

    Zhang, Hong-Mei; Li, Qing; Zhu, Xiaojian; Liu, Wei; Hu, Hui; Liu, Teng; Cheng, Fanjun; You, Yong; Zhong, Zhaodong; Zou, Ping; Li, Qiubai; Chen, Zhichao; Guo, An-Yuan

    2016-05-15

    Evidence is accumulating that extracellular microvesicles (MV) facilitate progression and relapse in cancer. Using a model in which MVs derived from K562 chronic myelogenous leukemia (CML) cells transform normal hematopoietic transplants into leukemia-like cells, we defined the underlying mechanisms of this process through gene-expression studies and network analyses of transcription factors (TF) and miRNAs. We found that antitumor miRNAs were increased and several defense pathways were initiated during the early phases of oncogenic transformation. Later, oncomiRs and genes involved in cell cycle, DNA repair, and energy metabolism pathways were upregulated. Regulatory network analyses revealed that a number of TFs and miRNAs were responsible for the pathway dysregulation and the oncogenic transformation. In particular, we found that miR-146b-5p, which was highly expressed in MVs, coordinated the regulation of cancer-related genes to promote cell-transforming processes. Notably, treatment of recipient cells with MV derived from K562 cells expressing mimics of miR-146b-5p revealed that it accelerated the transformation process in large part by silencing the tumor-suppressor NUMB High levels of miR-146b-5p also enhanced reactive oxygen species levels and genome instability of recipient cells. Taken together, our finding showed how upregulation of oncogenic miRNAs in MVs promote hematopoetic cells to a leukemic state, as well as a demonstration for TF and miRNA coregulatory analysis in exploring the dysregulation of cancers and discovering key factors. Cancer Res; 76(10); 2901-11. ©2016 AACR. PMID:27013199

  18. 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

  19. Relationship between JAK2 gene V617F mutation and clinical characteristics in patients with BCR-ABL-negative myeloproliferative neoplasms%BCR-ABL阴性的骨髓增殖性肿瘤JAK2基因V617F突变分析

    Institute of Scientific and Technical Information of China (English)

    张燕香; 魏蓉

    2013-01-01

    目的:探讨BCR-ABL阴性的骨髓增殖性肿瘤(myeloproliferative neoplasms,MPN)患者蛋白质酪氨酸激酶基因(JAK2)V617F突变的发生率及其与患者临床特征的关系.方法:抽提65例MPN患者骨髓细胞DNA(其中真性红细胞增多症28例,特发性血小板增多症30例,特发性骨髓纤维化7例),应用等位基因特异性PCR技术(allele specific PCR,AS-PCR)分析JAK2基因V617F突变的发生率,并分析此突变与外周血细胞计数及血栓发生率等临床特征的关系.结果:65例MPN患者的V617F突变阳性率为64.62% (42/65).其中真性红细胞增多症患者的阳性率为75.00% (21/28),其白细胞及血小板计数较非突变者均显著增高(P<0.001);特发性血小板增多症患者该突变的阳性率为56.67% (17/30),其白细胞计数和血红蛋白水平均较非突变者显著增高(P<0.05);而7例特发性骨髓纤维化患者中4例被检出此突变阳性,其白细胞、血小板计数及血红蛋白水平与非突变者比较,差异则无统计学意义.同时,携带V617F突变的MPN患者血栓发生率明显高于非突变者(P<0.05).结论:JAK2基因V617F突变是我国BCR-ABL阴性MPN患者主要的分子遗传标志,可作为临床诊断的指标之一,而此突变对临床特征有一定影响.%Objective:To investigate the relationship between V617F mutation in JAK2 gene and clinical characteristics in patients with BCR-ABL-negative myeloproliferative neoplasms (MPN).Methods:Sixty-five patients with MPN,including 28 subjects with polycythemia vera (PV),30 subjects with essential thrombocythemia (ET) and 7 subjects with idiopathic myelofibrosis (IMF) were enrolled in this study.Bone marrow cell DNA was extracted from MPN patients,and V617F mutation in JAK2 gene was identified by allele specific PCR (AS-PCR).The correlation between V617F mutation and clinical characteristics such as peripheral blood cell count and incidence of thrombosis were analyzed.Results:Of the 65 patients

  20. Outcome of treatment in adults with Philadelphia chromosome-positive and/or BCR-ABL--positive acute lymphoblastic leukemia-retrospective analysis of Polish Adult Leukemia Group (PALG).

    Science.gov (United States)

    Wrzesień-Kuś, A; Robak, T; Pluta, A; Zwolińska, M; Wawrzyniak, E; Wierzbowska, A; Skotnicki, A; Jakubas, B; Hołowiecki, J; Nowak, K; Kuliczkowski, K; Mazur, G; Haus, O; Dmoszyńska, A; Adamczyk-Cioch, M; Jedrzejczak, W W; Paluszewska, M; Konopka, L; Pałynyczko, G

    2006-06-01

    Patients with Philadelphia chromosome-positive (Ph+) and/or BCR-ABL+ acute lymphoblastic leukemia (ALL) have extremely poor prognoses. Most of these patients have additional, heterogenous karyotype abnormalities, the majority of which have uncertain clinical significance. In this study we analyzed the clinical characteristics, karyotype abnormalities, and outcome of 77 patients with Ph+ and/or BCR-ABL+ ALL registered in Poland in 1997-2004. In 31/55 patients with known karyotype, the sole t(9;22)(q34;q11) abnormality had been diagnosed; in one patient, variant translocation t(4;9;22)(q21q31.1;q34;q11), and additional abnormalities in 23 (42%) patients, had been diagnosed. The characteristics of the patients with Ph chromosome and additional abnormalities were not significantly different when compared with the entire analyzed group. Out of 77 patients, 54 (70%) achieved first complete remission (CR1) after one or more induction cycles. The overall survival (OS) probability of 2 years was 63, 43, and 17% for patients treated with allogeneic stem cell transplantation (alloSCT), autologous SCT, and chemotherapy, respectively (log rank p=0.002). Median OS from the time of alloSCT was significantly longer for patients transplanted in CR1 compared with alloSCT in CR >1 (p=0.032). There were no significant differences in CR rate, disease-free survival (DFS), and OS for patients with t(9;22) and additional abnormalities compared with the whole group. Only WBC >20 G/l at diagnosis adversely influenced OS probability (log rank p=0.0017). In conclusion, our data confirm poor outcome of Ph+ and/or BCR-ABL+ ALL. Only patients who received alloSCT in CR1 had longer DFS and OS. We have shown that additional karyotype abnormalities did not influence the clinical characteristics of the patients; however, their influence on treatment results needs to be further assessed. PMID:16523310

  1. 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.

  2. 利用 BCR法和 Maiz法提取蔗田土壤中重金属的研究%Study on Extraction of Heavy Metals from Soil of Sugarcane Field by BCR Method and Maiz Method

    Institute of Scientific and Technical Information of China (English)

    王晓飞; 许桂苹; 洪欣; 陈丽君; 梁晓曦

    2015-01-01

    分别采用BCR法和Maiz法两种连续提取法,对蔗田土壤样品中重金属元素Cu、Zn、Pb、Cd和Ni进行了形态分析。结果表明:Cu、Zn、Pb、Cd和Ni均主要以残渣态的形式赋存,具有较低的潜在生物有效性;Pb主要以可还原态或螯合态的形式存在,具有一定的潜在生物有效性;BCR法得到的重金属回收率高于Maiz法的,但是Maiz法测得的有效态Cu、Zn、Pb、Cd和Ni的量均高于BCR法测得的弱酸提取态的量。%The occurrence characteristics of heavy metals Cu, Zn, Pb, Cd and Ni in the soil samples of sugarcane fields in Guangxi were analyzed by using BCR and Maiz sequential extraction procedures respectively.The results showed that Cu, Zn, Pb, Cd and Ni existed mainly in residual fraction, and they had a lower potential bioavailability.Pb existed mainly in reducible fraction or chelated fraction, and it possessed a certain potential bioavailability.In addition, BCR method acquired higher recovery rate of heavy metal than Maiz method, but the quantity of effective-state Cu, Zn, Pb, Cd and Ni measured by Maiz method was all higher than that of weak-acid-extractable-state Cu, Zn, Pb, Cd and Ni measured by BCR method.

  3. Pharmacophore Modeling of Nilotinib as an Inhibitor of ATP-Binding Cassette Drug Transporters and BCR-ABL Kinase Using a Three-Dimensional Quantitative Structure–Activity Relationship Approach

    OpenAIRE

    Shukla, Suneet; Kouanda, Abdul; Silverton, Latoya; Talele, Tanaji T.; Suresh V Ambudkar

    2014-01-01

    Nilotinib (Tasigna) is a tyrosine kinase inhibitor approved by the FDA to treat chronic phase chronic myeloid leukemia patients. It is also a transport substrate of the ATP-binding cassette (ABC) drug efflux transporters ABCB1 (P-glycoprotein, P-gp) and ABCG2 (BCRP), which may have an effect on the pharmacokinetics and toxicity of this drug. The goal of this study was to identify pharmacophoric features of nilotinib in order to potentially develop specific inhibitors of BCR-ABL kinase with mi...

  4. 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

  5. BCR/ABL-negative primitive progenitors suitable for transplantation can be selected from the marrow of most early-chronic phase but not accelerated-phase chronic myelogenous leukemia patients

    OpenAIRE

    Verfaillie, Catherine; R Bhatia; Miller, W.; F. Mortari; Van Roy, V.; Burger, S.; Mccullough, J; Stieglbauer, K; Dewald, G; Heimfeld, S; Miller, J. S.; McGlave, P B

    1996-01-01

    We have previously reported that selection of marrow cells on the basis of the CD34+HLA-DR- phenotype (34+DR-) may result in the recovery of Philadelphia chromosome (Ph)- and BCR/ABL-negative long-term culture-initiating cells (LTC-IC) in selected patients with chronic myelogenous leukemia (CML). We now present data on 27 early chronic-phase ([ECP] studied within 1 year after diagnosis) and 23 advanced-phase ([AP] late chronic phase, ie, studied >1 year from diagnosis, or accelerated phase) C...

  6. B cell TLR1/2, TLR4, TLR7 and TLR9 interact in induction of class switch DNA recombination: modulation by BCR and CD40, and relevance to T-independent antibody responses

    OpenAIRE

    Pone, Egest J; Lou, Zheng; Lam, Tonika; Greenberg, Milton L.; Wang, Rui; Xu, Zhenming; Casali, Paolo

    2015-01-01

    Ig class switch DNA recombination (CSR) in B cells is crucial to the maturation of antibody responses. It requires IgH germline IH-CH transcription and expression of AID, both of which are induced by engagement of CD40 or dual engagement of a Toll-like receptor (TLR) and B cell receptor (BCR). Here, we have addressed cross-regulation between two different TLRs or between a TLR and CD40 in CSR induction by using a B cell stimulation system involving lipopolysaccharides (LPS). LPS mediated long...

  7. Simultaneous N, C, S isotopic analyses using purge and trap EA technology. Application to δ34S analyses of natural phosphate material NBS120c and BCR32

    Science.gov (United States)

    Fourel, F. P.; Lecuyer, C.; Martineau, F.

    2013-12-01

    The first example of stable isotope analyses in continuous flow mode by Preston et al in 19861 involved Elemental Analyser Isotopic Ratio Mass Spectrometry (EA-IRMS) dedicated to carbon isotopes in combustion mode. EA-IRMS has since then evolved to allow 34S/32S determinations still in combustion mode and mainly to access pyrolysis reaction for O and H isotopes. As far as combustion EA-IRMS is concerned the technique itself has remained unchanged since the development of 'purge and trap' separation techniques online with IRMS instruments. Here we have used a high-precision, easy, low-cost and rapid method of simultaneous carbon, nitrogen and sulphur isotope analysis using this new type of elemental analyser based on 'purge and trap' technology 2,3. Simultaneous determinations, performed on the same aliquot of 13C, 15N and 34S are demonstrated. Emphasis is put on the high quality of 34S/32S determinations. First concentrating on peak shapes, yields of conversion and preliminary results. Then the reliability and accuracy of such a technique is illustrated using analyses from various international reference materials. Alongside international reference material working NCS calibrated material has been selected and characterized prior to apply this technology to calibrate natural phosphate material used as compositional reference material BCR32 and NBS120c. δ34S values of respectively 15.62×0.32‰ and 16.5×0.17‰ are proposed for those samples with sulphur concentrations below the 1% level. The possibility to reliably measure S isotopes on that kind of samples opens up new fields of investigation especially for paleoenvironmental reconstructions. Keywords: carbon, nitrogen, sulfur, isotope, combustion, phosphate, elemental-analyser 1. T. Preston, N.J.P. Owens: Preliminary 13C Measurements using a Gas Chromatograph Interfaced to an Isotope Ratio Mass Spectrometer. Biomedical. Mass Spectrom. 1985, 12-9, 510. 2. H.P. Sieper, H.J. Kupka, L. Lange, A. Rossmann, N. Tanz

  8. BCR-ABL1: Test

    Science.gov (United States)

    ... Complete Blood Count ; Bone Marrow Aspiration and Biopsy ; Blood Smear ; WBC Differential At a Glance Test Sample The ... are often evaluated as part of the initial diagnosis, but the majority of follow-up monitoring is performed on blood samples. There is significant test variability among laboratories ...

  9. 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.

  10. 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

    International Nuclear Information System (INIS)

    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

  11. 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.

  12. RT-PCR ANALYSIS OF E2A-PBX1, TEL-AML1, BCR-ABL AND MLL-AF4 FUSION GENE TRANSCRIPTS IN B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Iuliu-Cristian Ivanov

    2013-11-01

    Full Text Available Acute lymphoblastic leukemia represents a heterogeneous group of hematological malignancies, defined by clonal proliferation of lymphoid cells. Immunophenotyping by flow cytometry and molecular analysis for the detection of genetic anomalies are clinical standard procedures for diagnosis, sub-classification and post-therapeutic evaluation. Samples from 105 patients diagnosed with acute lymphoblastic leukemia were immunophenotyped at diagnosis and were investigated by molecular analysis in order to identify the occurrence of four fusion genes: MLL-AF4, TEL-AML-1, BCR-ABL-p190, E2A-PBX-1. There were no associations found between the immunophenotype and the presence of any fusion genes evaluated. Both methods in combination remain a prerequisite for an improved subclassification of hematological malignancies, therapeutic decision, and evaluation of treatment response.

  13. Three-way principal component analysis as a tool to evaluate the chemical stability of metal bearing residues from wastewater treatment by the ferrite process

    Energy Technology Data Exchange (ETDEWEB)

    Pardo, Rafael, E-mail: rpardo@qa.uva.es; Vega, Marisol; Barrado, Enrique; Castrillejo, Yolanda; Sánchez, Isabel

    2013-11-15

    Highlights: • Metal fractionation of residues from the ferrite process was investigated by n-way PCA. • BCR sequential extraction procedure used for metal fractionation. • Tucker3 algorithm originated a coherent two-term trilinear model. • Metal fractionation patterns correlate with magnetic character of solids. -- Abstract: The chemical fractionation patterns of eight metals (Cd, Co, Cu, Cr, Mn, Ni, Pb and Zn) have been determined in 27 metal-bearing residues by using the BCR sequential extraction procedure. The residues were generated as by-products during the optimization of a semi-continuous reactor for metal removal from wastewater based on ferrite synthesis by co-precipitation. The three-dimensional X dataset (samples × metals × fractions) obtained by applying the BCR procedure has been analyzed by multivariate methods: matrix augmentation (MA-PCA) and three-way principal component analysis, 3-PCA (PARAFAC and Tucker3 models). MA-PCA and PARAFAC methods led to two-factor models giving a satisfactory but incomplete picture of the metal fractionation patterns, but the Tucker3 [2,1,2] model allowed to simultaneously describe both the ‘pseudo-total’ (acid-soluble) contents and the chemical fractionation by means of two non-null interactions g{sub 111} and g{sub 212} which explain 53.5% and 18.0% of the total variance, respectively. The A-mode loadings of the g{sub 212} interaction showed the close relationship between the magnetic character of the solid residues, i.e. the crystalline structure, and the chemical fractionation patterns of the metals resulting from the application of the BCR sequential extraction procedure.

  14. Three-way principal component analysis as a tool to evaluate the chemical stability of metal bearing residues from wastewater treatment by the ferrite process

    International Nuclear Information System (INIS)

    Highlights: • Metal fractionation of residues from the ferrite process was investigated by n-way PCA. • BCR sequential extraction procedure used for metal fractionation. • Tucker3 algorithm originated a coherent two-term trilinear model. • Metal fractionation patterns correlate with magnetic character of solids. -- Abstract: The chemical fractionation patterns of eight metals (Cd, Co, Cu, Cr, Mn, Ni, Pb and Zn) have been determined in 27 metal-bearing residues by using the BCR sequential extraction procedure. The residues were generated as by-products during the optimization of a semi-continuous reactor for metal removal from wastewater based on ferrite synthesis by co-precipitation. The three-dimensional X dataset (samples × metals × fractions) obtained by applying the BCR procedure has been analyzed by multivariate methods: matrix augmentation (MA-PCA) and three-way principal component analysis, 3-PCA (PARAFAC and Tucker3 models). MA-PCA and PARAFAC methods led to two-factor models giving a satisfactory but incomplete picture of the metal fractionation patterns, but the Tucker3 [2,1,2] model allowed to simultaneously describe both the ‘pseudo-total’ (acid-soluble) contents and the chemical fractionation by means of two non-null interactions g111 and g212 which explain 53.5% and 18.0% of the total variance, respectively. The A-mode loadings of the g212 interaction showed the close relationship between the magnetic character of the solid residues, i.e. the crystalline structure, and the chemical fractionation patterns of the metals resulting from the application of the BCR sequential extraction procedure

  15. Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.

    Science.gov (United States)

    Polivkova, Vaclava; Rohon, Peter; Klamova, Hana; Cerna, Olga; Divoka, Martina; Curik, Nikola; Zach, Jan; Novak, Martin; Marinov, Iuri; Soverini, Simona; Faber, Edgar; Machova Polakova, Katerina

    2016-01-01

    Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy. PMID:27214026

  16. Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients.

    Directory of Open Access Journals (Sweden)

    Vaclava Polivkova

    Full Text Available Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy.

  17. Interferon-α Revisited: Individualized Treatment Management Eased the Selective Pressure of Tyrosine Kinase Inhibitors on BCR-ABL1 Mutations Resulting in a Molecular Response in High-Risk CML Patients

    Science.gov (United States)

    Polivkova, Vaclava; Rohon, Peter; Klamova, Hana; Cerna, Olga; Divoka, Martina; Curik, Nikola; Zach, Jan; Novak, Martin; Marinov, Iuri; Soverini, Simona; Faber, Edgar; Machova Polakova, Katerina

    2016-01-01

    Bone marrow transplantation or ponatinib treatment are currently recommended strategies for management of patients with chronic myeloid leukemia (CML) harboring the T315I mutation and compound or polyclonal mutations. However, in some individual cases, these treatment scenarios cannot be applied. We used an alternative treatment strategy with interferon-α (IFN-α) given solo, sequentially or together with TKI in a group of 6 cases of high risk CML patients, assuming that the TKI-independent mechanism of action may lead to mutant clone repression. IFN-α based individualized therapy decreases of T315I or compound mutations to undetectable levels as assessed by next-generation deep sequencing, which was associated with a molecular response in 4/6 patients. Based on the observed results from immune profiling, we assumed that the principal mechanism leading to the success of the treatment was the immune activation induced with dasatinib pre-treatment followed by restoration of immunological surveillance after application of IFN-α therapy. Moreover, we showed that sensitive measurement of mutated BCR-ABL1 transcript levels augments the safety of this individualized treatment strategy. PMID:27214026

  18. A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Xia, D.Y.; Liu, L.; Hao, M.W.; Liu, Q.; Chen, R.A.; Liang, Y.M. [Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi' an (China)

    2014-10-14

    p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA) also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor resistance in CML.

  19. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia.

    Science.gov (United States)

    le Coutre, Philipp; Ottmann, Oliver G; Giles, Francis; Kim, Dong-Wook; Cortes, Jorge; Gattermann, Norbert; Apperley, Jane F; Larson, Richard A; Abruzzese, Elisabetta; O'Brien, Stephen G; Kuliczkowski, Kazimierz; Hochhaus, Andreas; Mahon, Francois-Xavier; Saglio, Giuseppe; Gobbi, Marco; Kwong, Yok-Lam; Baccarani, Michele; Hughes, Timothy; Martinelli, Giovanni; Radich, Jerald P; Zheng, Ming; Shou, Yaping; Kantarjian, Hagop

    2008-02-15

    Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2-611 days). An HR was observed in 56 patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and lipase elevations occurred in 9% and 18% of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228. PMID:18048643

  20. 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)

    The c-Myb gene encodes the p75c-Myb isoform and less-abundant proteins generated by alternatively spliced transcripts. Among these, the best known is pc-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 pc-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 pc-Mybex9b and the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75c-Myb, pc-Mybex9b is more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of pc-Mybex9b enhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of pc-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 p75c-Myb. Together, these studies indicate that expression of the low-abundance pc-Mybex9b isoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells

  1. Mechanical characterization of Cu-Zn wire electrode base used in EDM and study of influence of the process of machining on its properties

    Energy Technology Data Exchange (ETDEWEB)

    Sedjal, H., E-mail: hasedjal@yahoo.fr; Amirat, B. [Département of Mechanical engineering, University of M.MAMMERI, Tizi Ouzou (Algeria); Aichour, M.; Marouf, T.; Chitroub, M. [Engineering and Material Sciences Laboratory, Department of Metallurgy, Polytechnic national school, Algiers (Algeria)

    2015-03-30

    This work is part of a Research National project (PNR) carried out by the group of research of the engineering and material sciences laboratory of the polytechnic national school at Algiers in collaboration with company BCR, which relates to “the characterization of the wire intended for the EDM of matrices metal. The goal of this work is to bring metallographic explanations on the wire electrode used by the machine ROBOFIL 290P, mechanically characterized this wire as of knowing of advantage about the process of its manufacturing (wiredrawing, .) The methods of studies used are it micro Vickers pyramid hardness, the tensile test, optical microscopy and scan electronic microscopy SEM.

  2. Process Accounting

    OpenAIRE

    Gilbertson, Keith

    2002-01-01

    Standard utilities can help you collect and interpret your Linux system's process accounting data. Describes the uses of process accounting, standard process accounting commands, and example code that makes use of process accounting utilities.

  3. Primary Processing

    NARCIS (Netherlands)

    Mulder, W.J.; Harmsen, P.F.H.; Sanders, J.P.M.; Carre, P.; Kamm, B.; Schoenicke, P.

    2012-01-01

    Primary processing of oil-containing material involves pre-treatment processes, oil recovery processes and the extraction and valorisation of valuable compounds from waste streams. Pre-treatment processes, e.g. thermal, enzymatic, electrical and radio frequency, have an important effect on the oil r

  4. Budgeting Process

    Science.gov (United States)

    Hentschke, Guilbert C.; Shaughnessy, John

    1973-01-01

    Attempts to describe the budgeting process in school districts. Discusses general budget calendars and explains the process of constructing a Program Evaluation and Review Technique (PERT) chart of the budgeting process. Presents a detailed list of activities to be included in the budgeting process and a PERT chart indicating how these activities…

  5. Elektrokemiske Processer

    DEFF Research Database (Denmark)

    Bech-Nielsen, Gregers

    1997-01-01

    Electrochemical processes in: Power sources, Electrosynthesis, Corrosion.Pourbaix-diagrams.Decontamination of industrial waste water for heavy metals.......Electrochemical processes in: Power sources, Electrosynthesis, Corrosion.Pourbaix-diagrams.Decontamination of industrial waste water for heavy metals....

  6. Process mining

    DEFF Research Database (Denmark)

    van der Aalst, W.M.P.; Rubin, V.; Verbeek, H.M.W.;

    2010-01-01

    Process mining includes the automated discovery of processes from event logs. Based on observed events (e.g., activities being executed or messages being exchanged) a process model is constructed. One of the essential problems in process mining is that one cannot assume to have seen all possible...... behavior. At best, one has seen a representative subset. Therefore, classical synthesis techniques are not suitable as they aim at finding a model that is able to exactly reproduce the log. Existing process mining techniques try to avoid such “overfitting” by generalizing the model to allow for more...

  7. Data processing

    CERN Document Server

    Fry, T F

    2013-01-01

    Data Processing discusses the principles, practices, and associated tools in data processing. The book is comprised of 17 chapters that are organized into three parts. The first part covers the characteristics, systems, and methods of data processing. Part 2 deals with the data processing practice; this part discusses the data input, output, and storage. The last part discusses topics related to systems and software in data processing, which include checks and controls, computer language and programs, and program elements and structures. The text will be useful to practitioners of computer-rel

  8. Food processing

    International Nuclear Information System (INIS)

    The paper discusses the processes involved in food preparation for consumption and technological processing that could be used to reduce contamination of foodstuffs. The food processing transfer parameters - food processing retention factor, processing efficiency and the food processing factor - are defined and their relationships discussed. Data are presented for vegetables, fruit, cereals, dairy products, meat (mammals, birds and fish-edible fraction), fungi, seafoods and drinks. Processing procedures considered includes: simple washing and boiling for fruit, vegetables and mushrooms, boiling and milling for cereals, cooking and curing for meats, butter and cheese productions for dairy products and washing and cooking for seafoods. Storage times for foodstuffs have also been considered. A wide range of chemical elements are considered, with the majority of data presented caesium, strontium and iodine, stable element databases have been reviewed and relevant data used to extend the data set. A discussion of application of the data is presented with consideration of areas where cautions is needed. (author)

  9. Synthesis and Characterization of Five New F-bearing Basalt Reference Materials (Fba Glasses): Quantifying the Fluorine Content of the Basaltic Glass Standards BCR-2G, BHVO-2G. GSA-1G, GSC-1G, GSD-1G, GSE-1G, ML3B-G, KL2-G, and ALV-519-4

    Science.gov (United States)

    Guggino, S. N.; Hervig, R. L.

    2011-12-01

    -, detection of low-energy negative secondary ions (-5 kV), and a mass resolution that resolved 18OH. Homogeneity of the Fba glasses was established by both SIMS and EPMA. Glasses labeled Fba-2, -3. -4, and -5 pass statistical tests for homogeneity and may be used as EPMA or SIMS standards. SIMS calibration curves were constructed using the Fba glasses and other F standards of varying silica, iron, and sodium content, including Bt-3, F-phlog, NIST 610, KE-12, and UTR-2. The calibration curves revealed large matrix effects for the analysis of F by SIMS (~ 50%) between an Fba:Bt-3 curve and a high-silica glass:F-phlog curve. The Fba:Bt-3 calibration curve was used to determine the F contents (ppm ± 1 σ) of the following nine commonly used basaltic glass standards: BCR-2G (321 ± 15), BHVO-2G (297 ± 14), GSA-1G (7 ± 0.1), GSC-1G (9 ± 0.5), GSD-1G (18 ± 1), GSE-1G (154 ± 7), ML3B-G (47 ± 2), KL2-G (82 ± 4), ALV-519-4 (76 ± 4).

  10. Processing trends

    International Nuclear Information System (INIS)

    This paper identifies trends associated with the performance of automatic film processors in hospitals and nonhospital facilities, including chiropractic facilities. Automatic film processors were evaluated in more than 1,700 facilities as a part of the Nationwide Evaluation of x-ray Trends (NEXT) program. Processing was evaluated with use of the Sensitometric Technique for Evaluation of Processing (STEP) procedure, which involves the exposure of control film to a calibrated light sensitometer and evaluation of the resultant film density. A processing speed index of 100 means that the processor is processing films according to the film manufacturers' normal recommended specifications; deviation from this value suggest underprocessing or overprocessing conditions

  11. Design Processes

    DEFF Research Database (Denmark)

    Ovesen, Nis

    2009-01-01

    Inspiration for most research and optimisations on design processes still seem to focus within the narrow field of the traditional design practise. The focus in this study turns to associated businesses of the design professions in order to learn from their development processes. Through interviews...... advantages and challenges of agile processes in mobile software and web businesses are identified. The applicability of these agile processes is discussed in re- gards to design educations and product development in the domain of Industrial Design and is briefly seen in relation to the concept of dromology...

  12. Data processing

    International Nuclear Information System (INIS)

    The 1988 progress report of the Data Processing laboratory (Polytechnic School, France), is presented. The laboratory research fields are: the semantics, the tests and the semantic analysis of the codes, the formal calculus, the software applications, the algorithms, the neuron networks and VLSI (Very Large Scale Integration). The investigations concerning the polynomial rings are performed by means of the standard basis approach. Among the research topics, the Pascal codes, the parallel processing, the combinatorial, statistical and asymptotic properties of the fundamental data processing tools, the signal processing and the pattern recognition. The published papers, the congress communications and the thesis are also included

  13. Stochastic processes

    CERN Document Server

    Parzen, Emanuel

    2015-01-01

    Well-written and accessible, this classic introduction to stochastic processes and related mathematics is appropriate for advanced undergraduate students of mathematics with a knowledge of calculus and continuous probability theory. The treatment offers examples of the wide variety of empirical phenomena for which stochastic processes provide mathematical models, and it develops the methods of probability model-building.Chapter 1 presents precise definitions of the notions of a random variable and a stochastic process and introduces the Wiener and Poisson processes. Subsequent chapters examine

  14. Kreative processer

    DEFF Research Database (Denmark)

    Schoch, Odilo

    2010-01-01

    Explaining the way of understanding processes and the development of visionary goals - linked to the daily business in archtiectural practise.......Explaining the way of understanding processes and the development of visionary goals - linked to the daily business in archtiectural practise....

  15. Sustainable processing

    DEFF Research Database (Denmark)

    Kristensen, Niels Heine

    2004-01-01

    Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3...

  16. Organizing Process

    DEFF Research Database (Denmark)

    Hull Kristensen, Peer; Bojesen, Anders

    This paper invites to discuss the processes of individualization and organizing being carried out under what we might see as an emerging regime of change. The underlying argumentation is that in certain processes of change, competence becomes questionable at all times. The hazy characteristics of...

  17. Peat Processing

    Science.gov (United States)

    1986-01-01

    Humics, Inc. already had patented their process for separating wet peat into components and processing it when they consulted NERAC regarding possible applications. The NERAC search revealed numerous uses for humic acid extracted from peat. The product improves seed germination, stimulates root development, and improves crop yields. There are also potential applications in sewage disposal and horticultural peat, etc.

  18. Process automation

    International Nuclear Information System (INIS)

    Process automation technology has been pursued in the chemical processing industries and to a very limited extent in nuclear fuel reprocessing. Its effective use has been restricted in the past by the lack of diverse and reliable process instrumentation and the unavailability of sophisticated software designed for process control. The Integrated Equipment Test (IET) facility was developed by the Consolidated Fuel Reprocessing Program (CFRP) in part to demonstrate new concepts for control of advanced nuclear fuel reprocessing plants. A demonstration of fuel reprocessing equipment automation using advanced instrumentation and a modern, microprocessor-based control system is nearing completion in the facility. This facility provides for the synergistic testing of all chemical process features of a prototypical fuel reprocessing plant that can be attained with unirradiated uranium-bearing feed materials. The unique equipment and mission of the IET facility make it an ideal test bed for automation studies. This effort will provide for the demonstration of the plant automation concept and for the development of techniques for similar applications in a full-scale plant. A set of preliminary recommendations for implementing process automation has been compiled. Some of these concepts are not generally recognized or accepted. The automation work now under way in the IET facility should be useful to others in helping avoid costly mistakes because of the underutilization or misapplication of process automation. 6 figs

  19. Grants Process

    Science.gov (United States)

    The NCI Grants Process provides an overview of the end-to-end lifecycle of grant funding. Learn about the types of funding available and the basics for application, review, award, and on-going administration within the NCI.

  20. Membrane Processes.

    Science.gov (United States)

    Pellegrin, Marie-Laure; Burbano, Marie S; Sadler, Mary E; Diamond, Jason; Baker, Simon; Greiner, Anthony D; Arabi, Sara; Wong, Joseph; Doody, Alexandra; Padhye, Lokesh P; Sears, Keith; Kistenmacher, Peter; Kent, Fraser; Tootchi, Leila; Aguinaldo, Jorge; Saddredini, Sara; Schilling, Bill; Min, Kyungnan; McCandless, Robert; Danker, Bryce; Gamage, Neranga P; Wang, Sunny; Aerts, Peter

    2016-10-01

    This review, for literature published in 2015, contains information related to membrane processes for municipal and industrial applications. This review is a subsection of the Treatment Systems section of the annual Water Environment Federation literature review and covers the following topics: pretreatment, membrane bioreactor (MBR) configuration, design, nutrient removal, operation, industrial treatment, anaerobic membrane systems, reuse, microconstituents removal, membrane technology advances, membrane fouling, and modeling. Other sub-sections of the Treatment Systems section that might relate to this literature review include: Biological Fixed-Film Systems, Activated Sludge and Other Aerobic Suspended Culture Processes, Anaerobic Processes, Water Reclamation and Reuse. The following sections might also have related information on membrane processes: Industrial Wastes, Hazardous Wastes, and Fate and Effects of Pollutants. PMID:27620084

  1. Electrochemical Processes

    DEFF Research Database (Denmark)

    Bech-Nielsen, Gregers

    1997-01-01

    The notes describe in detail primary and secondary galvanic cells, fuel cells, electrochemical synthesis and electroplating processes, corrosion: measurments, inhibitors, cathodic and anodic protection, details of metal dissolution reactions, Pourbaix diagrams and purification of waste water from...

  2. Processing Proteases

    DEFF Research Database (Denmark)

    Ødum, Anders Sebastian Rosenkrans

    Processing proteases are proteases which proteolytically activate proteins and peptides into their biologically active form. Processing proteases play an important role in biotechnology as tools in protein fusion technology. Fusion strategies where helper proteins or peptide tags are fused to the...... protein of interest are an elaborate method to optimize expression or purification systems. It is however critical that fusion proteins can be removed and processing proteases can facilitate this in a highly specific manner. The commonly used proteases all have substrate specificities to the N-terminal of...... the scissile bond, leaving C-terminal fusions to have non-native C-termini after processing. A solution yielding native C-termini would allow novel expression and purification systems for therapeutic proteins and peptides.The peptidyl-Lys metallopeptidase (LysN) of the fungus Armillaria mellea (Am) is...

  3. Membrane Processes.

    Science.gov (United States)

    Pellegrin, Marie-Laure; Sadler, Mary E; Greiner, Anthony D; Aguinaldo, Jorge; Min, Kyungnan; Zhang, Kai; Arabi, Sara; Burbano, Marie S; Kent, Fraser; Shoaf, Robert

    2015-10-01

    This review, for literature published in 2014, contains information related to membrane processes for municipal and industrial applications. This review is a subsection of the Treatment Systems section of the annual Water Environment Federation literature review and covers the following topics: pretreatment, membrane bioreactor (MBR) configuration, design, nutrient removal, operation, industrial treatment, fixed film and anaerobic membrane systems, reuse, microconstituents removal, membrane technology advances, membrane fouling, and modeling. Other sub-sections of the Treatment Systems section that might relate to this literature review include: Biological Fixed-Film Systems, Activated Sludge and Other Aerobic Suspended Culture Processes, Anaerobic Processes, Water Reclamation and Reuse. The following sections might also have related information on membrane processes: Industrial Wastes, Hazardous Wastes, and Fate and Effects of Pollutants. PMID:26420079

  4. Renewal processes

    CERN Document Server

    Mitov, Kosto V

    2014-01-01

    This monograph serves as an introductory text to classical renewal theory and some of its applications for graduate students and researchers in mathematics and probability theory. Renewal processes play an important part in modeling many phenomena in insurance, finance, queuing systems, inventory control and other areas. In this book, an overview of univariate renewal theory is given and renewal processes in the non-lattice and lattice case are discussed. A pre-requisite is a basic knowledge of probability theory.

  5. Wastes processing

    Energy Technology Data Exchange (ETDEWEB)

    Farinet, J.L. (CIRAD-CA, 34 - Montpellier (France)); Copin, Y. (CEREMHER, 34 - Meze (France))

    1994-01-01

    The Transpaille procedure is used for the recovery and processing of organic wastes using methane fermentation; gas and compost are produced. The system was installed at the slaughterhouse in Thies, Senegal, in 1988-89. It consists of a 40 cubic metres horizontal cylinder. The slaughterhouse produces 480 metric tonnes of wastes per year and 35.5 cubic metres of biogas per day at a process temperature of 31 deg C. Lagooning is used for the first time as a water purification technique at a slaughterhouse in West Africa. This technique reproduces the process by which water purifies itself biologically, by accelerating and controlling the phenomenon. The procedure includes pre-processing, a decanter/digester and three lagoons. The organic matter is degraded by bacteria, producing water, carbon dioxide and mineral elements, which are then assimilated by micro-algae and macrophytes (Pistia stratiotes). The tropical climate is convenient for this processing method, which is optimum of temperatures of between 25 deg C and 35 deg C. (authors).

  6. Sewer Processes

    DEFF Research Database (Denmark)

    Hvitved-Jacobsen, Thorkild; Vollertsen, Jes; Nielsen, Asbjørn Haaning

    Since the first edition was published over a decade ago, advancements have been made in the design, operation, and maintenance of sewer systems, and new problems have emerged. For example, sewer processes are now integrated in computer models, and simultaneously, odor and corrosion problems caused...... and valuable information on the sewer as a chemical and biological reactor. It focuses on how to predict critical impacts and control adverse effects. It also provides an integrated description of sewer processes in modeling terms. This second edition is full of illustrative examples and figures, includes...... revisions of chapters from the previous edition, adds three new chapters, and presents extensive study questions. • Presents new modeling tools for the design and operation of sewer networks • Establishes sewer processes as a key element in preserving water quality • Includes greatly expanded coverage...

  7. Clustering processes

    CERN Document Server

    Ryabko, Daniil

    2010-01-01

    The problem of clustering is considered, for the case when each data point is a sample generated by a stationary ergodic process. We propose a very natural asymptotic notion of consistency, and show that simple consistent algorithms exist, under most general non-parametric assumptions. The notion of consistency is as follows: two samples should be put into the same cluster if and only if they were generated by the same distribution. With this notion of consistency, clustering generalizes such classical statistical problems as homogeneity testing and process classification. We show that, for the case of a known number of clusters, consistency can be achieved under the only assumption that the joint distribution of the data is stationary ergodic (no parametric or Markovian assumptions, no assumptions of independence, neither between nor within the samples). If the number of clusters is unknown, consistency can be achieved under appropriate assumptions on the mixing rates of the processes. (again, no parametric ...

  8. Copula Processes

    CERN Document Server

    Wilson, Andrew Gordon

    2010-01-01

    We define a copula process which describes the dependencies between arbitrarily many random variables independently of their marginal distributions. As an example, we develop a stochastic volatility model, Gaussian Copula Process Volatility (GCPV), to predict the latent standard deviations of a sequence of random variables. To learn the parameters of GCPV we use Bayesian inference, with the Laplace approximation, and with Markov chain Monte Carlo as an alternative. We find both methods comparable. We also find our model can outperform GARCH, on simulated and financial data. And unlike GARCH, GCPV can easily handle missing data, incorporate covariates other than time, and model a rich class of covariance structures.

  9. Extraction process

    International Nuclear Information System (INIS)

    A process is described for extracting at least two desired constituents from a mineral, using a liquid reagent which produces the constituents, or compounds thereof, in separable form and independently extracting those constituents, or compounds. The process is especially valuable for the extraction of phosphoric acid and metal values from acidulated phosphate rock, the slurry being contacted with selective extractants for phosphoric acid and metal (e.g. uranium) values. In an example, uranium values are oxidized to uranyl form and extracted using an ion exchange resin. (U.K.)

  10. Process simulation

    International Nuclear Information System (INIS)

    The search for an optimal design of a heavy water plant is done by means of a simulation model for the mass and enthalpy balances of the SH2-H2O exchange process. A symplified model for the simulation diagram where the entire plant is represented by a sole tray tower with recicles, and heat and mass feeds/extractions was used. The tower is simulated by the method developed by Tomich with the convergence part given by the algorithm of Broyden. The concluding part of the work is centered in setting the design parameters (flowrates, heat exchange rates, number of plates) wich give the desired process operating conditions. (author)

  11. Film processing

    International Nuclear Information System (INIS)

    The processing was made not only to show what are in the film but also to produce radiograph with high quality where the information gathered really presented level of the quality of the object inspected. Besides that, good procedure will make the film with good quality can keep the film in long time for reference. Here, more detailed on how the dark room functioned and its design. So, the good procedure while processed the film will be discussed detailed in this chapter from entering the dark room to exit from there.

  12. Offshoring Process

    DEFF Research Database (Denmark)

    Slepniov, Dmitrij; Sørensen, Brian Vejrum; Katayama, Hiroshi

    2011-01-01

    The purpose of this chapter is to contribute to the knowledge on how production offshoring and international operations management vary across cultural contexts. The chapter attempts to shed light on how companies approach the process of offshoring in different cultural contexts. In order...... of globalisation. Yet there are clear differences in how offshoring is conducted in Denmark and Japan. The main differences are outlined in a framework and explained employing cultural variables. The findings lead to a number of propositions suggesting that the process of offshoring is not simply a uniform...

  13. Causticizing process

    Energy Technology Data Exchange (ETDEWEB)

    Engdal, H.

    1987-03-10

    This invention seeks to provide a method in which the soda lye obtained as a result of cellulose cooking process and unslaked lime are used for producing white liquor which can be re-used in the cooking process. In this method, the heat released by the slaking of lime with soda lye is recovered by a high pressure slaking process wherein the heat is transferred, either to the steam separating from the lye, which steam is then led to the desired application, or to some other medium to be heated. The invention is characterized in that the soda lye to be causticized is divided into two parts, one of which is used for the slaking of lime by adding to it all the unslaked lime needed for the causticizing process, and that, following slaking, the two volumes are brought together for the actual causticizing reaction involving the total amount of lye needed. This invention provides the advantage that the amount of lye needed is smaller, and so the temperature can be increased.

  14. BENTONITE PROCESSING

    Directory of Open Access Journals (Sweden)

    Anamarija Kutlić

    2012-07-01

    Full Text Available Bentonite has vide variety of uses. Special use of bentonite, where its absorbing properties are employed to provide water-tight sealing is for an underground repository in granites In this paper, bentonite processing and beneficiation are described.

  15. Signal Processing

    International Nuclear Information System (INIS)

    Signal processing techniques, extensively used nowadays to maximize the performance of audio and video equipment, have been a key part in the design of hardware and software for high energy physics detectors since pioneering applications in the UA1 experiment at CERN in 1979

  16. Transplant Process

    Science.gov (United States)

    ... typing, including high-resolution typing A complete health history and physical exam Evaluation of your psychological and emotional strengths Identifying who will be your primary caregiver throughout the transplant process Bone marrow biopsy CT (computed tomography) scan or MRI (magnetic ...

  17. Processing Needs

    International Nuclear Information System (INIS)

    Concerning processing needs the following recommendations can be made: Encourage and support spectrum-averaged cross section measurements for data validation. For example, measurements of constants for neutron activation analysis (thermal capture and resonance integrals), astrophysics cross sections (MACS, e.g. corresponding to a 30 keV Maxwellian spectrum), 252Cf spontaneous fission spectrum averaged cross sections, etc. The latter could help to resolve many issues related to uncertainties in the capture cross section in the energy region between 100 keV and a few MeV; Continue to develop and improve web based and off-line data visualisation tools, striving for generality as well as user-friendliness; Continue to support developments for the generation of covariance data of experimental measurements as well as evaluated nuclear data; Regarding the issue of independent processing codes, the generally available PREPRO series is highly esteemed and truly valuable, but it lacks, by design the following: a module to generate scattering matrices; a module to generate temperature dependent self-shielded cross sections in the unresolved resonance region; processing of fission neutron multiplicity; treatment of covariances; Perhaps Red Cullen might be willing to undertake this work. The details of additional modules to be developed include also treatment of covariances. All these modules should be clearly identified. Enhancement of the processing of covariance matrices could be sought by acquiring and making generally available a code that is already developed (e.g. drawing from the experience in Japan)

  18. Innovation process

    DEFF Research Database (Denmark)

    Kolodovski, A.

    2006-01-01

    Purpose of this report: This report was prepared for RISO team involved in design of the innovation system Report provides innovation methodology to establish common understanding of the process concepts and related terminology The report does not includeRISO- or Denmark-specific cultural, economic...

  19. Process validation for radiation processing

    International Nuclear Information System (INIS)

    Process validation concerns the establishment of the irradiation conditions that will lead to the desired changes of the irradiated product. Process validation therefore establishes the link between absorbed dose and the characteristics of the product, such as degree of crosslinking in a polyethylene tube, prolongation of shelf life of a food product, or degree of sterility of the medical device. Detailed international standards are written for the documentation of radiation sterilization, such as EN 552 and ISO 11137, and the steps of process validation that are described in these standards are discussed in this paper. They include material testing for the documentation of the correct functioning of the product, microbiological testing for selection of the minimum required dose and dose mapping for documentation of attainment of the required dose in all parts of the product. The process validation must be maintained by reviews and repeated measurements as necessary. This paper presents recommendations and guidance for the execution of these components of process validation. (author)

  20. Restoration Process

    Science.gov (United States)

    1979-01-01

    In the accompanying photos, a laboratory technician is restoring the once-obliterated serial number of a revolver. The four-photo sequence shows the gradual progression from total invisibility to clear readability. The technician is using a new process developed in an applications engineering project conducted by NASA's Lewis Research Center in conjunction with Chicago State University. Serial numbers and other markings are frequently eliminated from metal objects to prevent tracing ownership of guns, motor vehicles, bicycles, cameras, appliances and jewelry. To restore obliterated numbers, crime laboratory investigators most often employ a chemical etching technique. It is effective, but it may cause metal corrosion and it requires extensive preparatory grinding and polishing. The NASA-Chicago State process is advantageous because it can be applied without variation to any kind of metal, it needs no preparatory work and number recovery can be accomplished without corrosive chemicals; the liquid used is water.

  1. Innovation process

    OpenAIRE

    Kolodovski, A.

    2006-01-01

    Purpose of this report: This report was prepared for RISO team involved in design of the innovation system Report provides innovation methodology to establish common understanding of the process concepts and related terminology The report does not includeRISO- or Denmark-specific cultural, economic, and political challenges, which will be considered in a separate report on implementation The report was written in February 2005.

  2. Biogas processing

    OpenAIRE

    Kudláč, Adam

    2010-01-01

    The diploma thesis includes proposals suitable for usage of the technologies for clearing the biogas into a quality of substitute natural gas (SNG). The most suitable technology is chosen for the clearing the biogas out of the septic tanks of the laboratory for biologically decomposable waste treatment at Institute of process and environmental engineering. There is a calculation , a proposal and a realisation of the experimental unit for clearing the biogas performed.

  3. Radiopharmaceutical process

    International Nuclear Information System (INIS)

    A process is described in which a dispersion of denatured aggregates of serum albumin to which tin is attached, suitable for radioactive labelling and use as a diagnostic agent is prepared and lyophilized. Where the physical and chemical properties degrade during lyophilization or aging an improvement is described comprising additionally including in as a protective agent, a mixture of a polycarboxylic acid and a disaccharide or monosaccharide in a sufficient amount to reduce degradation of the physical and chemical properties of the dispersion during lyophilization and aging

  4. Image processing

    International Nuclear Information System (INIS)

    The nuclear medical methods developed over the last ten years for cardiological diagnosis are especially suited to evaluating the functional performance of the left ventricle, and myocardial perfusion. Computed tomography and subtraction angiography are two other, non-invasive radiological methods for examining the size and topography of the cavities of the heart, and echocardiography has meanwhile taken the first position in the diagnosis of morphological heart disease. Fourier analysis and the Fourier tansformation technique allow acquisition, recording and evaluation of quantitative data of the radionuclide ventriculography. Due to the weak spatial resolution of the scintigraphic phase analysis, the next logical development was to apply Fourier analysis to the cine-ventriculography, which unfortunately requires considerable computing efforts and time. A solution has now been found that combines the two image processing systems and thus creates the basis for applying the Fourier analysis to all the diagnostic imaging methods, such as echocardiography, radiography, and nuclear medical methods. (orig.)

  5. Image Processing

    Science.gov (United States)

    1993-01-01

    Electronic Imagery, Inc.'s ImageScale Plus software, developed through a Small Business Innovation Research (SBIR) contract with Kennedy Space Flight Center for use on space shuttle Orbiter in 1991, enables astronauts to conduct image processing, prepare electronic still camera images in orbit, display them and downlink images to ground based scientists for evaluation. Electronic Imagery, Inc.'s ImageCount, a spin-off product of ImageScale Plus, is used to count trees in Florida orange groves. Other applications include x-ray and MRI imagery, textile designs and special effects for movies. As of 1/28/98, company could not be located, therefore contact/product information is no longer valid.

  6. Lithospheric processes

    Energy Technology Data Exchange (ETDEWEB)

    Baldridge, W. [and others

    2000-12-01

    The authors used geophysical, geochemical, and numerical modeling to study selected problems related to Earth's lithosphere. We interpreted seismic waves to better characterize the thickness and properties of the crust and lithosphere. In the southwestern US and Tien Shari, crust of high elevation is dynamically supported above buoyant mantle. In California, mineral fabric in the mantle correlate with regional strain history. Although plumes of buoyant mantle may explain surface deformation and magmatism, our geochemical work does not support this mechanism for Iberia. Generation and ascent of magmas remains puzzling. Our work in Hawaii constrains the residence of magma beneath Hualalai to be a few hundred to about 1000 years. In the crust, heat drives fluid and mass transport. Numerical modeling yielded robust and accurate predictions of these processes. This work is important fundamental science, and applies to mitigation of volcanic and earthquake hazards, Test Ban Treaties, nuclear waste storage, environmental remediation, and hydrothermal energy.

  7. Welding process

    International Nuclear Information System (INIS)

    This invention relates to a process for making a large number of weld beads as separate contours, spaced out from each other, by means of an automatic welding head. Under this invention, after striking the arc in the prescribed manner and positioning the torch on the first contour to be welded and having made the first weld bead, the torch current is reduced to bring about a part fade out of the arc. The torch is then moved to the starting position on a second contour to be welded where a static timed pre-fusion is effected by resumption of the welding current to carry out the second weld bead by following the second welding contour in the same manner and so forth. The invention particularly applies to the welding of tube ends to a tube plate

  8. Lithospheric processes

    International Nuclear Information System (INIS)

    The authors used geophysical, geochemical, and numerical modeling to study selected problems related to Earth's lithosphere. We interpreted seismic waves to better characterize the thickness and properties of the crust and lithosphere. In the southwestern US and Tien Shari, crust of high elevation is dynamically supported above buoyant mantle. In California, mineral fabric in the mantle correlate with regional strain history. Although plumes of buoyant mantle may explain surface deformation and magmatism, our geochemical work does not support this mechanism for Iberia. Generation and ascent of magmas remains puzzling. Our work in Hawaii constrains the residence of magma beneath Hualalai to be a few hundred to about 1000 years. In the crust, heat drives fluid and mass transport. Numerical modeling yielded robust and accurate predictions of these processes. This work is important fundamental science, and applies to mitigation of volcanic and earthquake hazards, Test Ban Treaties, nuclear waste storage, environmental remediation, and hydrothermal energy

  9. Detailed conformation dynamics and activation process of wild type c-Abl and T315I mutant

    Science.gov (United States)

    Yang, Li-Jun; Zhao, Wen-Hua; Liu, Qian

    2014-10-01

    Bcr-Abl is an important target for therapy against chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). The synergistic effect between myristyl pocket and the ATP pocket has been found. But its detailed information based on molecular level still has not been achieved. In this study, conventional molecular dynamics (CMD) and target molecular dynamics (TMD) simulations were performed to explore the effect of T315I mutation on dynamics and activation process of Abl containing the N-terminal cap (Ncap). The CMD simulation results reveal the increasing flexibility of ATP pocket in kinase domain (KD) after T315I mutation which confirms the disability of ATP-pocket inhibitors to the Abl-T315I mutant. On the contrary, the T315I mutation decreased the flexibility of remote helix αI which suggests the synergistic effect between them. The mobility of farther regions containing Ncap, SH3, SH2 and SH2-KD linker were not affected by T315I mutation. The TMD simulation results show that the activation process of wild type Abl and Abl-T315I mutant experienced global conformation change. Their differences were elucidated by the activation motion of subsegments including A-loop, P-loop and Ncap. Besides, the T315I mutation caused decreasing energy barrier and increasing intermediate number in activation process, which results easier activation process. The TMD and CMD results indicate that a drug targeting only the ATP pocket is not enough to inhibit the Abl-T315I mutant. An effective way to inhibit the abnormal activity of Abl-T315I mutant is to combine the ATP-pocket inhibitors with inhibitors binding at non-ATP pockets mainly related to Ncap, SH2-KD linker and myristyl pocket.

  10. Information Processing - Administrative Data Processing

    Science.gov (United States)

    Bubenko, Janis

    A three semester, 60-credit course package in the topic of Administrative Data Processing (ADP), offered in 1966 at Stockholm University (SU) and the Royal Institute of Technology (KTH) is described. The package had an information systems engineering orientation. The first semester focused on datalogical topics, while the second semester focused on the infological topics. The third semester aimed to deepen the students’ knowledge in different parts of ADP and at writing a bachelor thesis. The concluding section of this paper discusses various aspects of the department’s first course effort. The course package led to a concretisation of our discipline and gave our discipline an identity. Our education seemed modern, “just in time”, and well adapted to practical needs. The course package formed the first concrete activity of a group of young teachers and researchers. In a forty-year perspective, these people have further developed the department and the topic to an internationally well-reputed body of knowledge and research. The department has produced more than thirty professors and more than one hundred doctoral degrees.

  11. Lumping Processes of Periodic ARMA Processes

    OpenAIRE

    Smadi, Abdullah A. [عبد الله الصمادي

    2004-01-01

    In this article various lumping processes are defined for periodic ARMA (PARMA) processes, namely, the forward, the backward and the cyclic lumping processes. The inter-relations between the parameters of these lumping processes are obtained. It is then proved that stationarity of any lumped process implies sta¬tionarity of all other lumped processes.

  12. AN ADVANCED OXIDATION PROCESS : FENTON PROCESS

    Directory of Open Access Journals (Sweden)

    Engin GÜRTEKİN

    2008-03-01

    Full Text Available Biological wastewater treatment is not effective treatment method if raw wastewater contains toxic and refractory organics. Advanced oxidation processes are applied before or after biological treatment for the detoxification and reclamation of this kind of wastewaters. The advanced oxidation processes are based on the formation of powerful hydroxyl radicals. Among advanced oxidation processes Fenton process is one of the most promising methods. Because application of Fenton process is simple and cost effective and also reaction occurs in a short time period. Fenton process is applied for many different proposes. In this study, Fenton process was evaluated as an advanced oxidation process in wastewater treatment.

  13. AN ADVANCED OXIDATION PROCESS : FENTON PROCESS

    OpenAIRE

    Engin GÜRTEKİN; Nusret ŞEKERDAĞ

    2008-01-01

    Biological wastewater treatment is not effective treatment method if raw wastewater contains toxic and refractory organics. Advanced oxidation processes are applied before or after biological treatment for the detoxification and reclamation of this kind of wastewaters. The advanced oxidation processes are based on the formation of powerful hydroxyl radicals. Among advanced oxidation processes Fenton process is one of the most promising methods. Because application of Fenton process is simple ...

  14. Auditory Processing Disorders

    Science.gov (United States)

    Auditory Processing Disorders Auditory processing disorders (APDs) are referred to by many names: central auditory processing disorders , auditory perceptual disorders , and central auditory disorders . APDs ...

  15. Extensible packet processing architecture

    Science.gov (United States)

    Robertson, Perry J.; Hamlet, Jason R.; Pierson, Lyndon G.; Olsberg, Ronald R.; Chun, Guy D.

    2013-08-20

    A technique for distributed packet processing includes sequentially passing packets associated with packet flows between a plurality of processing engines along a flow through data bus linking the plurality of processing engines in series. At least one packet within a given packet flow is marked by a given processing engine to signify by the given processing engine to the other processing engines that the given processing engine has claimed the given packet flow for processing. A processing function is applied to each of the packet flows within the processing engines and the processed packets are output on a time-shared, arbitered data bus coupled to the plurality of processing engines.

  16. 豆渣馒头加工工艺研究%Processing Technology of Steamed Bread Made with Bean Curd Residue

    Institute of Scientific and Technical Information of China (English)

    李波; 芦菲; 王东玲; 孙俊良

    2011-01-01

    研究了豆腐渣粉、谷朊粉、酵母添加量对馒头感官品质和质构特性(TPA)的影响,通过单因素和正交试验确定豆渣馒头的最佳工艺条件,并采用环境扫描电镜研究豆渣馒头的微观结构.结果表明:小麦面粉85 g、豆腐渣粉15 g、谷朊粉1g、活性干酵母0.6g、发酵时间120 min时制作的豆渣馒头具有良好的品质和口感.电镜分析显示,豆渣粉的加入影响了面筋网络结构的形成,添加谷朊粉能够改善面筋网络结构,优化产品品质.%Bean curd residue(BCR)is the by-product of tofu and soybean milk manufactures. It contains 36.2% dietary fiber and 17.8% protein,and can improve the nutritional value when adding it into steamed bread. The objective of this paper was to assess the sensory qualities and textural properties of steamed breads made with BCR addition at different levels. The effects of the addition amounts of BCR powder, gluten and yeast on the sensory qualities, specific volume and texture profile analysis (TPA) properties of steamed breads prepared with traditional method were investigated. Based on single factor and orthogonal experiment,the optimal technical parameters for steamed bread were wheat flour 85 g,BCR powder 15 g, gluten 1 g, yeast 0.6 g,and fermentation time 120 min. The steamed bread made with these conditions had good sensory and textural qualities. The observation of environmental scanning electron microscope (ESEM) of steamed breads showed that the addition of BCR had negative effect on gluten network and influenced the water absorption and gelatinization of starch for the stronger hydroscopicity of BCR. Adding gluten powder could improve gluten network and increase the gas retention ability,as a result many bigger gas pores were kept in steamed bread. The results of this study demonstrate that replacing part of wheat flour with BCR to make steamed bread was a potential effective way for utilizing BCR.

  17. Process mineralogy IX

    Energy Technology Data Exchange (ETDEWEB)

    Petruk, W.; Hagni, R.D.; Pignolet-Brandom, S.; Hausen, D.M. (eds.) (Canada Centre for Mineral and Energy Technology, Ottawa, ON (Canada))

    1990-01-01

    54 papers are presented under the headings: keynote address; process mineralogy applications to mineral processing; process mineralogy applications to gold; process mineralogy applications to pyrometallurgy and hydrometallurgy; process mineralogy applications to environment and health; and process mineralogy applications to synthetic materials. Subject and author indexes are provided. Three papers have been abstracted separately.

  18. Thinning spatial point processes into Poisson processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Schoenberg, Frederic Paik

    2010-01-01

    In this paper we describe methods for randomly thinning certain classes of spatial point processes. In the case of a Markov point process, the proposed method involves a dependent thinning of a spatial birth-and-death process, where clans of ancestors associated with the original points are ident......, thus, can be used as a graphical exploratory tool for inspecting the goodness-of-fit of a spatial point process model. Several examples, including clustered and inhibitive point processes, are considered.......In this paper we describe methods for randomly thinning certain classes of spatial point processes. In the case of a Markov point process, the proposed method involves a dependent thinning of a spatial birth-and-death process, where clans of ancestors associated with the original points...... are identified, and where we simulate backwards and forwards in order to obtain the thinned process. In the case of a Cox process, a simple independent thinning technique is proposed. In both cases, the thinning results in a Poisson process if and only if the true Papangelou conditional intensity is used, and...

  19. Thinning spatial point processes into Poisson processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Schoenberg, Frederic Paik

    This paper describes methods for randomly thinning certain classes of spatial point processes. In the case of a Markov point process, the proposed method involves a dependent thinning of a spatial birth-and-death process, where clans of ancestors associated with the original points are identified...... be used as a diagnostic for assessing the goodness-of-fit of a spatial point process model. Several examples, including clustered and inhibitive point processes, are considered.......This paper describes methods for randomly thinning certain classes of spatial point processes. In the case of a Markov point process, the proposed method involves a dependent thinning of a spatial birth-and-death process, where clans of ancestors associated with the original points are identified......, and where one simulates backwards and forwards in order to obtain the thinned process. In the case of a Cox process, a simple independent thinning technique is proposed. In both cases, the thinning results in a Poisson process if and only if the true Papangelou conditional intensity is used, and thus can...

  20. Modelingof the Biotransformation Processes

    OpenAIRE

    Vrsalovic Presecki, A.; Findrik, Z.; Zelic, B.

    2006-01-01

    Modeling and simulation of biotransformation processes have a large potential in searching for optimal process conditions, development and process design, control, scale-up, identifying of the process cost structure, and comparing process alternatives. Modeling and simulation leads to better understanding and quantification of the investigated process and could lead to significant material and costs savings especially in the early phases of the process development. In this review modeling and...

  1. Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

    Science.gov (United States)

    Corso, Jasmin; Pan, Kuan-Ting; Walter, Roland; Doebele, Carmen; Mohr, Sebastian; Bohnenberger, Hanibal; Ströbel, Philipp; Lenz, Christof; Slabicki, Mikolaj; Hüllein, Jennifer; Comoglio, Federico; Rieger, Michael A; Zenz, Thorsten; Wienands, Jürgen; Engelke, Michael; Serve, Hubert; Urlaub, Henning; Oellerich, Thomas

    2016-05-17

    Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∼16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments. PMID:27155012

  2. Food Processing and Allergenicity

    NARCIS (Netherlands)

    Verhoeckx, K.; Vissers, Y.; Baumert, J.L.; Faludi, R.; Fleys, M.; Flanagan, S.; Herouet-Guicheney, C.; Holzhauser, T.; Shimojo, R.; Bolt, van der Nieke; Wichers, H.J.; Kimber, I.

    2015-01-01

    Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed.

    In this review the impact of processing (heat and non

  3. Refactoring Process Models in Large Process Repositories.

    OpenAIRE

    Weber, B.; Reichert, M.U.

    2008-01-01

    With the increasing adoption of process-aware information systems (PAIS), large process model repositories have emerged. Over time respective models have to be re-aligned to the real-world business processes through customization or adaptation. This bears the risk that model redundancies are introduced and complexity is increased. If no continuous investment is made in keeping models simple, changes are becoming increasingly costly and error-prone. Though refactoring techniques are widely use...

  4. Process Intensification: A Perspective on Process Synthesis

    DEFF Research Database (Denmark)

    Lutze, Philip; Gani, Rafiqul; Woodley, John

    2010-01-01

    design tools with a clear focus on specific PI tasks exist. Therefore, in this paper, the concept of a general systematic framework for synthesis and design of PI options in hierarchical steps through analyzing an existing process, generating PI options in a superstructure and evaluating intensified...... of options to potentially improve the process but to identify the set of feasible solutions for PI in which the optimal can be found takes considerable resources. Hence, a process synthesis tool to achieve PI would potentially assist in the generation and evaluation of PI options. Currently, several process...... of the main concepts is illustrated through an example involving the operation of a membrane reactor....

  5. Natural Process Processing: Discovering Process Models from Plain Text

    OpenAIRE

    Martinez Puerto, Didac-Joan

    2016-01-01

    Aquest projecte consisteix en la implementació i estudi d'un mètode de generació automàtica de models Business Process Model and Notation(BPMN) mitjançant l'aplicació de tècniques de Natural Language Processing (NLP) i regles sintàctiques sobre textos que descriuen processos de negoci.

  6. Blood Donation Process

    Science.gov (United States)

    ... Home > Donating Blood > Donation Process Printable Version Donation Process View Video Getting Ready for Your Donation The ... worry about. Make a Donation Appointment The Donation Process Step by Step Donating blood is a simple ...

  7. Special parallel processing workshop

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-01

    This report contains viewgraphs from the Special Parallel Processing Workshop. These viewgraphs deal with topics such as parallel processing performance, message passing, queue structure, and other basic concept detailing with parallel processing.

  8. A dynamic contagion process

    OpenAIRE

    Dassios, Angelos; Zhao, Hongbiao

    2011-01-01

    We introduce a new point process, the dynamic contagion process, by generalising the Hawkes process and the Cox process with shot noise intensity. Our process includes both self-excited and externally excited jumps, which could be used to model the dynamic contagion impact from endogenous and exogenous factors of the underlying system. We have systematically analysed the theoretical distributional properties of this new process, based on the piecewise-deterministic Markov pr...

  9. Contracting process innovation

    OpenAIRE

    Nissen, Mark E.

    2001-01-01

    Process innovation pertains to making dramatic improvements in performance of enterprise processes. Stemming from total quality management, business process reengineering and other widely-accepted approaches to performance improvement in the business enterprise, process innovation has largely been practiced without a systematic method and required expertise only possessed by a few, highly-talented people. Now, as the result of research in this area, the process of process innovation now has a...

  10. Exclusive Processes at Colliders

    OpenAIRE

    Szczurek, Antoni

    2009-01-01

    A few examples of exclusive processes at high energy are discussed. Several mechanisms are presented. The differential distributions are shown. The possibilities to measure the processes are discussed.

  11. Product Development Process Modeling

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The use of Concurrent Engineering and other modern methods of product development and maintenance require that a large number of time-overlapped "processes" be performed by many people. However, successfully describing and optimizing these processes are becoming even more difficult to achieve. The perspective of industrial process theory (the definition of process) and the perspective of process implementation (process transition, accumulation, and inter-operations between processes) are used to survey the method used to build one base model (multi-view) process model.

  12. Integrated Process Capability Analysis

    Institute of Scientific and Technical Information of China (English)

    Chen; H; T; Huang; M; L; Hung; Y; H; Chen; K; S

    2002-01-01

    Process Capability Analysis (PCA) is a powerful too l to assess the ability of a process for manufacturing product that meets specific ations. The larger process capability index implies the higher process yield, a nd the larger process capability index also indicates the lower process expected loss. Chen et al. (2001) has applied indices C pu, C pl, and C pk for evaluating the process capability for a multi-process product wi th smaller-the-better, larger-the-better, and nominal-the-best spec...

  13. Conscious processing and the process goal paradox.

    Science.gov (United States)

    Mullen, Richard; Hardy, Lew

    2010-06-01

    The three experiments reported here examined the process goal paradox, which has emerged from the literature on goal setting and conscious processing. We predicted that skilled but anxious performers who adopted a global movement focus using holistic process goals would outperform those who used part-oriented process goals. In line with the conscious processing hypothesis, we also predicted that performers using part process goals would experience performance impairment in test compared with baseline conditions. In all three experiments, participants performed motor tasks in baseline and test conditions. Cognitive state anxiety increased in all of the test conditions. The results confirmed our first prediction; however, we failed to find unequivocal evidence to support our second prediction. The consistent pattern of the results lends support to the suggestion that, for skilled athletes who perform under competitive pressure, using a holistic process goal that focuses attention on global aspects of a motor skill is a more effective attentional focus strategy than using a part process goal. PMID:20587818

  14. Idaho Chemical Processing Plant Process Efficiency improvements

    Energy Technology Data Exchange (ETDEWEB)

    Griebenow, B.

    1996-03-01

    In response to decreasing funding levels available to support activities at the Idaho Chemical Processing Plant (ICPP) and a desire to be cost competitive, the Department of Energy Idaho Operations Office (DOE-ID) and Lockheed Idaho Technologies Company have increased their emphasis on cost-saving measures. The ICPP Effectiveness Improvement Initiative involves many activities to improve cost effectiveness and competitiveness. This report documents the methodology and results of one of those cost cutting measures, the Process Efficiency Improvement Activity. The Process Efficiency Improvement Activity performed a systematic review of major work processes at the ICPP to increase productivity and to identify nonvalue-added requirements. A two-phase approach was selected for the activity to allow for near-term implementation of relatively easy process modifications in the first phase while obtaining long-term continuous improvement in the second phase and beyond. Phase I of the initiative included a concentrated review of processes that had a high potential for cost savings with the intent of realizing savings in Fiscal Year 1996 (FY-96.) Phase II consists of implementing long-term strategies too complex for Phase I implementation and evaluation of processes not targeted for Phase I review. The Phase II effort is targeted for realizing cost savings in FY-97 and beyond.

  15. Idaho Chemical Processing Plant Process Efficiency improvements

    International Nuclear Information System (INIS)

    In response to decreasing funding levels available to support activities at the Idaho Chemical Processing Plant (ICPP) and a desire to be cost competitive, the Department of Energy Idaho Operations Office (DOE-ID) and Lockheed Idaho Technologies Company have increased their emphasis on cost-saving measures. The ICPP Effectiveness Improvement Initiative involves many activities to improve cost effectiveness and competitiveness. This report documents the methodology and results of one of those cost cutting measures, the Process Efficiency Improvement Activity. The Process Efficiency Improvement Activity performed a systematic review of major work processes at the ICPP to increase productivity and to identify nonvalue-added requirements. A two-phase approach was selected for the activity to allow for near-term implementation of relatively easy process modifications in the first phase while obtaining long-term continuous improvement in the second phase and beyond. Phase I of the initiative included a concentrated review of processes that had a high potential for cost savings with the intent of realizing savings in Fiscal Year 1996 (FY-96.) Phase II consists of implementing long-term strategies too complex for Phase I implementation and evaluation of processes not targeted for Phase I review. The Phase II effort is targeted for realizing cost savings in FY-97 and beyond

  16. Competencies of process managers

    OpenAIRE

    Matej Jevšček

    2016-01-01

    Abstract: Research Question (RQ): Effectiveness of managers differs in implementation of the process approach. Which competencies affect performance effectiveness of managers in the process approach? Purpose:The aim of the research is to specify a set of competencies which affect performance effectiveness of managers in the process approach. Method: The theoretical part examines the current state and terminology from the field of processes ...

  17. Spatial Process Generation

    OpenAIRE

    Kroese, Dirk P.; Botev, Zdravko I.

    2013-01-01

    The generation of random spatial data on a computer is an important tool for understanding the behavior of spatial processes. In this paper we describe how to generate realizations from the main types of spatial processes, including Gaussian and Markov random fields, point processes, spatial Wiener processes, and Levy fields. Concrete MATLAB code is provided.

  18. Recursive Markov Process

    OpenAIRE

    Hidaka, Shohei

    2015-01-01

    A Markov process, which is constructed recursively, arises in stochastic games with Markov strategies. In this study, we defined a special class of random processes called the recursive Markov process, which has infinitely many states but can be expressed in a closed form. We derive the characteristic equation which the marginal stationary distribution of an arbitrary recursive Markov process needs to satisfy.

  19. On Permanental Processes

    OpenAIRE

    Eisenbaum, Nathalie; Kaspi, Haya

    2006-01-01

    Permanental processes can be viewed as a generalisation of squared centered Gaussian processes. We develop in this paper two main subjects. The first one analyses the connections of these processes with the local times of general Markov processes. The second deals with Bosonian point processes and the Bose-Einstein condensation. The obtained results in both directions are related and based on the notion of infinite divisibility.

  20. IMPLEMENTING BUSINESS PROCESS MANAGEMENT

    OpenAIRE

    Vlad BALANESCU; Mihaela MASCU

    2014-01-01

    Business Process Management (BPM) is considered to be the third wave in business process theory. Appearing as a response to the critique formulated regarding Business Process Reengineering, BPM tries to be a more holistic and integrated approach to management and processes. In a time where complex solutions are needed solution that incorporates elements from various concepts, Business Process Management can be, in my opinion, a link between these ideas. After a short introduction presenting g...

  1. Thin film processes

    CERN Document Server

    Vossen, John L

    1978-01-01

    Remarkable advances have been made in recent years in the science and technology of thin film processes for deposition and etching. It is the purpose of this book to bring together tutorial reviews of selected filmdeposition and etching processes from a process viewpoint. Emphasis is placed on the practical use of the processes to provide working guidelines for their implementation, a guide to the literature, and an overview of each process.

  2. Software Process Improvement Framework

    OpenAIRE

    Nikitina, Natalja

    2014-01-01

    Many software development organizations today are keen on improving their software development processes in order to develop software products faster, cheaper or better. For that reason, Software Process Improvement (SPI) has received significant attention from the research community over the last few decades. Process maturity models have become widely known for benchmarking software processes against predefined practices and for identifying processes to be improved or implemented, whereas pr...

  3. Hyperspectral processing in graphical processing units

    Science.gov (United States)

    Winter, Michael E.; Winter, Edwin M.

    2011-06-01

    With the advent of the commercial 3D video card in the mid 1990s, we have seen an order of magnitude performance increase with each generation of new video cards. While these cards were designed primarily for visualization and video games, it became apparent after a short while that they could be used for scientific purposes. These Graphical Processing Units (GPUs) are rapidly being incorporated into data processing tasks usually reserved for general purpose computers. It has been found that many image processing problems scale well to modern GPU systems. We have implemented four popular hyperspectral processing algorithms (N-FINDR, linear unmixing, Principal Components, and the RX anomaly detection algorithm). These algorithms show an across the board speedup of at least a factor of 10, with some special cases showing extreme speedups of a hundred times or more.

  4. Gaussian Processes for Nonlinear Signal Processing

    OpenAIRE

    Pérez-Cruz, Fernando; Van Vaerenbergh, Steven; Murillo-Fuentes, Juan José; Lázaro-Gredilla, Miguel; Santamaria, Ignacio

    2013-01-01

    Gaussian processes (GPs) are versatile tools that have been successfully employed to solve nonlinear estimation problems in machine learning, but that are rarely used in signal processing. In this tutorial, we present GPs for regression as a natural nonlinear extension to optimal Wiener filtering. After establishing their basic formulation, we discuss several important aspects and extensions, including recursive and adaptive algorithms for dealing with non-stationarity, low-complexity solutio...

  5. Digital image processing.

    Science.gov (United States)

    Seeram, Euclid

    2004-01-01

    Digital image processing is now commonplace in radiology, nuclear medicine and sonography. This article outlines underlying principles and concepts of digital image processing. After completing this article, readers should be able to: List the limitations of film-based imaging. Identify major components of a digital imaging system. Describe the history and application areas of digital image processing. Discuss image representation and the fundamentals of digital image processing. Outline digital image processing techniques and processing operations used in selected imaging modalities. Explain the basic concepts and visualization tools used in 3-D and virtual reality imaging. Recognize medical imaging informatics as a new area of specialization for radiologic technologists. PMID:15352557

  6. Drug Development Process

    Science.gov (United States)

    ... Device Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing ... Pin it Email Print Step 1 Discovery and Development Discovery and Development Research for a new drug ...

  7. Nonlinear Markov processes

    Energy Technology Data Exchange (ETDEWEB)

    Frank, T.D. [Center for the Ecological Study of Perception and Action, Department of Psychology, University of Connecticut, 406 Babbidge Road, Storrs, CT 06269 (United States)], E-mail: till.frank@uconn.edu

    2008-06-16

    Some elementary properties and examples of Markov processes are reviewed. It is shown that the definition of the Markov property naturally leads to a classification of Markov processes into linear and nonlinear ones.

  8. The Integrated Renovation Process

    DEFF Research Database (Denmark)

    Galiotto, Nicolas; Heiselberg, Per; Knudstrup, Mary-Ann

    The Integrated Renovation Process (IRP) is a user customized methodology based on judiciously selected constructivist and interactive multi-criteria decision making methods (Galiotto, Heiselberg, & Knudstrup, 2014 (expected)). When applied for home renovation, the Integrated Renovation Process for...

  9. Natural Language Processing.

    Science.gov (United States)

    Chowdhury, Gobinda G.

    2003-01-01

    Discusses issues related to natural language processing, including theoretical developments; natural language understanding; tools and techniques; natural language text processing systems; abstracting; information extraction; information retrieval; interfaces; software; Internet, Web, and digital library applications; machine translation for…

  10. Process evaluation distributed system

    Science.gov (United States)

    Moffatt, Christopher L. (Inventor)

    2006-01-01

    The distributed system includes a database server, an administration module, a process evaluation module, and a data display module. The administration module is in communication with the database server for providing observation criteria information to the database server. The process evaluation module is in communication with the database server for obtaining the observation criteria information from the database server and collecting process data based on the observation criteria information. The process evaluation module utilizes a personal digital assistant (PDA). A data display module in communication with the database server, including a website for viewing collected process data in a desired metrics form, the data display module also for providing desired editing and modification of the collected process data. The connectivity established by the database server to the administration module, the process evaluation module, and the data display module, minimizes the requirement for manual input of the collected process data.

  11. Process innovation laboratory

    DEFF Research Database (Denmark)

    Møller, Charles

    2007-01-01

    models. The process innovation laboratory facilitates innovation by using an integrated action learning approach to process modelling in a controlled environment. The study is based on design science and the paper also discusses the implications to EIS research and practice...... thus to create a new methodology for developing and exploring process models and applications. The paper outlines the process innovation laboratory as a new approach to BPI. The process innovation laboratory is a comprehensive framework and a collaborative workspace for experimenting with process......Most organizations today are required not only to operate effective business processes but also to allow for changing business conditions at an increasing rate. Today nearly every business relies on their enterprise information systems (EIS) for process integration and future generations of EIS...

  12. Group Decision Process Support

    DEFF Research Database (Denmark)

    Gøtze, John; Hijikata, Masao

    1997-01-01

    Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists.......Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists....

  13. Nonlinear Markov processes

    International Nuclear Information System (INIS)

    Some elementary properties and examples of Markov processes are reviewed. It is shown that the definition of the Markov property naturally leads to a classification of Markov processes into linear and nonlinear ones

  14. Flavor changing lepton processes

    International Nuclear Information System (INIS)

    The flavor changing lepton processes, or in another words the lepton flavor changing processes, are described with emphasis on the updated theoretical motivations and the on-going experimental progress on a new high-intense muon source. (author)

  15. Dissection of Kinesin's Processivity

    OpenAIRE

    Adio, Sarah; Jaud, Johann; Ebbing, Bettina; Rief, Matthias; Woehlke, Günther

    2009-01-01

    The protein family of kinesins contains processive motor proteins that move stepwise along microtubules. This mechanism requires the precise coupling of the catalytic steps in the two heads, and their precise mechanical coordination. Here we show that these functionalities can be uncoupled in chimera of processive and non-processive kinesins. A chimera with the motor domain of Kinesin-1 and the dimerization domain of a non-processive Kinesin-3 motor behaves qualitatively as conventional kines...

  16. Grind hardening process

    CERN Document Server

    Salonitis, Konstantinos

    2015-01-01

    This book presents the grind-hardening process and the main studies published since it was introduced in 1990s.  The modelling of the various aspects of the process, such as the process forces, temperature profile developed, hardness profiles, residual stresses etc. are described in detail. The book is of interest to the research community working with mathematical modeling and optimization of manufacturing processes.

  17. Software Process Improvement Defined

    DEFF Research Database (Denmark)

    Aaen, Ivan

    2002-01-01

    This paper argues in favor of the development of explanatory theory on software process improvement. The last one or two decades commitment to prescriptive approaches in software process improvement theory may contribute to the emergence of a gulf dividing theorists and practitioners. It is...... proposed that this divide be met by the development of theory evaluating prescriptive approaches and informing practice with a focus on the software process policymaking and process control aspects of improvement efforts...

  18. Modeling multiphase materials processes

    CERN Document Server

    Iguchi, Manabu

    2010-01-01

    ""Modeling Multiphase Materials Processes: Gas-Liquid Systems"" describes the methodology and application of physical and mathematical modeling to multi-phase flow phenomena in materials processing. The book focuses on systems involving gas-liquid interaction, the most prevalent in current metallurgical processes. The performance characteristics of these processes are largely dependent on transport phenomena. This volume covers the inherent characteristics that complicate the modeling of transport phenomena in such systems, including complex multiphase structure, intense turbulence, opacity of

  19. Business Process Modeling Notation

    OpenAIRE

    Robert Flowers; Charles Edeki

    2013-01-01

    Models as representations of real world entities may appear to the novice to be an unnecessary abstraction. Indeed, in small organizations where there are relatively few processes, there is little need to abstract activities. When it comes to large organizations, with hundreds or thousands of processes, thecreation of models becomes an essential activity. Even if the process itself does not change in the form of new process re-engineering efforts or new applications, there are new employees a...

  20. Hawkes processes in finance

    OpenAIRE

    Emmanuel Bacry; Iacopo Mastromatteo; Jean-Fran\\c{c}ois Muzy

    2015-01-01

    In this paper we propose an overview of the recent academic literature devoted to the applications of Hawkes processes in finance. Hawkes processes constitute a particular class of multivariate point processes that has become very popular in empirical high frequency finance this last decade. After a reminder of the main definitions and properties that characterize Hawkes processes, we review their main empirical applications to address many different problems in high frequency finance. Becaus...

  1. Fuel gas conditioning process

    Science.gov (United States)

    Lokhandwala, Kaaeid A.

    2000-01-01

    A process for conditioning natural gas containing C.sub.3+ hydrocarbons and/or acid gas, so that it can be used as combustion fuel to run gas-powered equipment, including compressors, in the gas field or the gas processing plant. Compared with prior art processes, the invention creates lesser quantities of low-pressure gas per unit volume of fuel gas produced. Optionally, the process can also produce an NGL product.

  2. Mining processes in dentistry

    OpenAIRE

    R. S. Mans; Reijers, H.A.; Genuchten, van, MJIM Michiel; Wismeijer, D.

    2012-01-01

    Business processes in dentistry are quickly evolving towards "digital dentistry". This means that many steps in the dental process will increasingly deal with computerized information or computerized half products. A complicating factor in the improvement of process performance in dentistry, however, is the large number of independent dental professionals that are involved in the entire process. In order to reap the benefits of digital dentistry, it is essential to obtain an accurate view on ...

  3. Stochastic Processes in Finance

    OpenAIRE

    Madan, Dilip B.

    2010-01-01

    Stochastic processes arising in the description of the risk-neutral evolution of equity prices are reviewed. Starting with Brownian motion, I review extensions to Lévy and Sato processes. These processes have independent increments; the former are homogeneous in time, whereas the latter are inhomogeneous. One-dimensional Markov processes such as local volatility and local Lévy are discussed next. Finally, I take up two forms of stochastic volatility that are due to either space scaling or tim...

  4. Modeling Design Process

    OpenAIRE

    TAKEDA, Hideaki; Veerkamp, Paul; Yoshikawa, Hiroyuki

    1990-01-01

    This article discusses building a computable design process model, which is a prerequisite for realizing intelligent computer-aided design systems. First, we introduce general design theory, from which a descriptive model of design processes is derived. In this model, the concept of metamodels plays a crucial role in describing the evolutionary nature of design. Second, we show a cognitive design process model obtained by observing design processes using a protocol analysis method. We then di...

  5. Lithography process control

    CERN Document Server

    Levinson, Harry J

    1999-01-01

    This text covers lithography process control at several levels, from fundamental through advanced topics. The book is a self-contained tutorial that works both as an introduction to the technology and as a reference for the experienced lithographer. It reviews the foundations of statistical process control as background for advanced topics such as complex processes and feedback. In addition, it presents control methodologies that may be applied to process development pilot lines.

  6. Multiphoton processes: conference proceedings

    International Nuclear Information System (INIS)

    The chapters of this volume represent the invited papers delivered at the conference. They are arranged according to thermatic proximity beginning with atoms and continuing with molecules and surfaces. Section headings include multiphoton processes in atoms, field fluctuations and collisions in multiphoton process, and multiphoton processes in molecules and surfaces. Abstracts of individual items from the conference were prepared separately for the data base

  7. Business Process Management - Methodologies

    OpenAIRE

    PROKOP, Jan

    2008-01-01

    The main objective of this thesis is to map some of the business process management, business process reengineering methodologies and compare it according to several criteria. Part of this thesis is survey of the state of business process management in Czech Republic and Hungary.

  8. Semisolid Metal Processing Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Apelian,Diran

    2002-01-10

    Mathematical modeling and simulations of semisolid filling processes remains a critical issue in understanding and optimizing the process. Semisolid slurries are non-Newtonian materials that exhibit complex rheological behavior. There the way these slurries flow in cavities is very different from the way liquid in classical casting fills cavities. Actually filling in semisolid processing is often counter intuitive

  9. Statistical Process Control for KSC Processing

    Science.gov (United States)

    Ford, Roger G.; Delgado, Hector; Tilley, Randy

    1996-01-01

    The 1996 Summer Faculty Fellowship Program and Kennedy Space Center (KSC) served as the basis for a research effort into statistical process control for KSC processing. The effort entailed several tasks and goals. The first was to develop a customized statistical process control (SPC) course for the Safety and Mission Assurance Trends Analysis Group. The actual teaching of this course took place over several weeks. In addition, an Internet version of the same course complete with animation and video excerpts from the course when it was taught at KSC was developed. The application of SPC to shuttle processing took up the rest of the summer research project. This effort entailed the evaluation of SPC use at KSC, both present and potential, due to the change in roles for NASA and the Single Flight Operations Contractor (SFOC). Individual consulting on SPC use was accomplished as well as an evaluation of SPC software for KSC use in the future. A final accomplishment of the orientation of the author to NASA changes, terminology, data format, and new NASA task definitions will allow future consultation when the needs arise.

  10. Biomass process handbook

    Energy Technology Data Exchange (ETDEWEB)

    1983-01-01

    Descriptions are given of 42 processes which use biomass to produce chemical products. Marketing and economic background, process description, flow sheets, costs, major equipment, and availability of technology are given for each of the 42 processes. Some of the chemicals discussed are: ethanol, ethylene, acetaldehyde, butanol, butadiene, acetone, citric acid, gluconates, itaconic acid, lactic acid, xanthan gum, sorbitol, starch polymers, fatty acids, fatty alcohols, glycerol, soap, azelaic acid, perlargonic acid, nylon-11, jojoba oil, furfural, furfural alcohol, tetrahydrofuran, cellulose polymers, products from pulping wastes, and methane. Processes include acid hydrolysis, enzymatic hydrolysis, fermentation, distillation, Purox process, and anaerobic digestion.

  11. Theory of Markov processes

    CERN Document Server

    Dynkin, E B

    1960-01-01

    Theory of Markov Processes provides information pertinent to the logical foundations of the theory of Markov random processes. This book discusses the properties of the trajectories of Markov processes and their infinitesimal operators.Organized into six chapters, this book begins with an overview of the necessary concepts and theorems from measure theory. This text then provides a general definition of Markov process and investigates the operations that make possible an inspection of the class of Markov processes corresponding to a given transition function. Other chapters consider the more c

  12. Evaluation of steelmaking processes

    Energy Technology Data Exchange (ETDEWEB)

    Fruehan, R.J. [Carnegie-Mellon Univ., Pittsburgh, PA (United States)

    1994-01-01

    Objective of the AISI Direct Steelmaking Program is to develop a process for producing steel directly from ore and coal; the process should be less capital intensive, consume less energy, and have higher productivity. A task force was formed to examine available processes: trough, posthearth, IRSID, Electric Arc Furnace, energy optimizing furnace. It is concluded that there is insufficient incentive to replace a working BOF with any of these processes to refine hot metal; however, if new steelmaking capacity is required, IRSID and EOF should be considered. A fully continuous process should not be considered until direct ironmaking and continuous refining are perfected.

  13. Data processing made simple

    CERN Document Server

    Wooldridge, Susan

    2013-01-01

    Data Processing: Made Simple, Second Edition presents discussions of a number of trends and developments in the world of commercial data processing. The book covers the rapid growth of micro- and mini-computers for both home and office use; word processing and the 'automated office'; the advent of distributed data processing; and the continued growth of database-oriented systems. The text also discusses modern digital computers; fundamental computer concepts; information and data processing requirements of commercial organizations; and the historical perspective of the computer industry. The

  14. Colloid process engineering

    CERN Document Server

    Peukert, Wolfgang; Rehage, Heinz; Schuchmann, Heike

    2015-01-01

    This book deals with colloidal systems in technical processes and the influence of colloidal systems by technical processes. It explores how new measurement capabilities can offer the potential for a dynamic development of scientific and engineering, and examines the origin of colloidal systems and its use for new products. The future challenges to colloidal process engineering are the development of appropriate equipment and processes for the production and obtainment of multi-phase structures and energetic interactions in market-relevant quantities. The book explores the relevant processes and for controlled production and how they can be used across all scales.

  15. Thin film processes II

    CERN Document Server

    Kern, Werner

    1991-01-01

    This sequel to the 1978 classic, Thin Film Processes, gives a clear, practical exposition of important thin film deposition and etching processes that have not yet been adequately reviewed. It discusses selected processes in tutorial overviews with implementation guide lines and an introduction to the literature. Though edited to stand alone, when taken together, Thin Film Processes II and its predecessor present a thorough grounding in modern thin film techniques.Key Features* Provides an all-new sequel to the 1978 classic, Thin Film Processes* Introduces new topics, and sever

  16. Nonaqueous processing methods

    International Nuclear Information System (INIS)

    A high-temperature process utilizing molten salt extraction from molten metal alloys has been developed for purification of spent power reactor fuels. Experiments with laboratory-scale processing operations show that purification and throughput parameters comparable to the Barnwell Purex process can be achieved by pyrochemical processing in equipment one-tenth the size, with all wastes being discharged as stable metal alloys at greatly reduced volume and disposal cost. This basic technology can be developed for large-scale processing of spent reactor fuels. 13 references, 4 figures

  17. Dynamical laser spike processing

    CERN Document Server

    Shastri, Bhavin J; Tait, Alexander N; Rodriguez, Alejandro W; Wu, Ben; Prucnal, Paul R

    2015-01-01

    Novel materials and devices in photonics have the potential to revolutionize optical information processing, beyond conventional binary-logic approaches. Laser systems offer a rich repertoire of useful dynamical behaviors, including the excitable dynamics also found in the time-resolved "spiking" of neurons. Spiking reconciles the expressiveness and efficiency of analog processing with the robustness and scalability of digital processing. We demonstrate that graphene-coupled laser systems offer a unified low-level spike optical processing paradigm that goes well beyond previously studied laser dynamics. We show that this platform can simultaneously exhibit logic-level restoration, cascadability and input-output isolation---fundamental challenges in optical information processing. We also implement low-level spike-processing tasks that are critical for higher level processing: temporal pattern detection and stable recurrent memory. We study these properties in the context of a fiber laser system, but the addit...

  18. Future Steelmaking Processes

    Energy Technology Data Exchange (ETDEWEB)

    Prof. R. J. Fruehan

    2004-09-20

    There is an increasing demand for an ironmaking process with lower capital cost, energy consumption and emissions than a blast furnace. It is the hypothesis of the present work that an optimized combination of two reasonable proven technologies will greatly enhance the overall process. An example is a rotary hearth furnace (RHF) linked to a smelter (e.g., AISI, HIsmelt). The objective of this research is to select promising process combinations, develop energy, materials balance and productivity models for the individual processes, conduct a limited amount of basic research on the processes and evaluate the process combinations. Three process combinations were selected with input from the industrial partners. The energy-materials and productivity models for the RHF, smelter, submerged arc furnace and CIRCOFER were developed. Since utilization of volatiles in coal is critical for energy and CO{sub 2} emission reduction, basic research on this topic was also conducted. The process models developed are a major product developed in this research. These models can be used for process evaluation by the industry. The process combinations of an RHF-Smelter and a simplified CIRCOFER-Smelter appear to be promising. Energy consumption is reduced and productivity increased. Work on this project is continuing using funds from other sources.

  19. Candidate BCR reference materials for arsenic and selenium determinations in human serum and urine

    International Nuclear Information System (INIS)

    The pilot production of candidate reference materials for the quality assurance and statistical control of methods to determine toxic trace elements in biological samples is described. In the initial phase the project concerns a lyophilized human blood material containing Cd and Pb, a lyophilized human urine material containing As, Cd, Co and Cr, and a liquid human serum material with Al, Se and Zn at three different levels, representative of environmental and occupational exposure. The homogeneity and stability of the pilot batches were investigated by determining Al and Zn in serum, As in urine, Cd and Pb in blood at the medium level. The pilot batches produced were deemed to be homogeneous with respect to all the trace elements tested, and there was no indication of thermal instability except that the arsenic levels decreased significantly with time at 200 deg., 370 deg. and 450 deg. C. Thirty-two laboratories from 12 different countries participated in an intercomparison round organized to test the suitability of the reference material and validate the methodological approaches for certification purposes. Focusing on the neutron activation results, the outcome of this first intercomparison exercise demonstrates that the comparability of the calibration standards needs improvement. Therefore, for the certification round stronger efforts will be undertaken to document the spiked concentrations and to reduce their uncertainties, and the laboratories will be required to meet defined quality criteria for the checking and documentation of traceability. (author)

  20. Recent advances in the bcr-abl negative chronic myeloproliferative diseases

    Directory of Open Access Journals (Sweden)

    Stroncek David F

    2006-10-01

    Full Text Available Abstract The chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders of unknown etiology. In one of these (chronic myeloid leukemia, there is an associated pathognomonic chromosomal abnormality known as the Philadelphia chromosome. This leads to constitutive tyrosine kinase activity which is responsible for the disease and is used as a target for effective therapy. This review concentrates on the search in the other conditions (polycythemia vera, essential thrombocythemia and idiopathic mylofibrosis for a similar biological marker with therapeutic potential. There is no obvious chromosomal marker in these conditions and yet evidence of clonality can be obtained in females by the use of X-inactivation patterns. PRV-1mRNA over expression, raised vitamin B12 levels and raised neutrophil alkaline phosphatase scores are evidence that cells in these conditions have received excessive signals for proliferation, maturation and reduced apoptosis. The ability of erythroid colonies to grow spontaneously without added external erythropoietin in some cases, provided a useful marker and a clue to this abnormal signaling. In the past year several important discoveries have been made which go a long way in elucidating the involved pathways. The recently discovered JAK2 V617F mutation which occurs in the majority of cases of polycythemia vera and in about half of the cases with the two other conditions, enables constitutive tyrosine kinase activity without the need for ligand binding to hematopoietic receptors. This mutation has become the biological marker for these conditions and has spurred the development of a specific therapy to neutralize its effects. The realization that inherited mutations in the thrombopoietin receptor (c-Mpl can cause a phenotype of thrombocytosis such as in Mpl Baltimore (K39N and in a Japanese family with S505A, has prompted the search for acquired mutations in this receptor in chronic myeloproliferative disease. Recently, two mutations have been found; W515L and W515K. These mutations have been evident in patients with essential thrombocythemia and idiopathic myelofibrosis but not in polycythemia vera. They presumably act by causing constitutional, activating conformational changes in the receptor. The discovery of JAK2 and Mpl mutations is leading to rapid advancements in understanding the pathophysiology and in the treatment of these diseases.

  1. Coexistance of JAK2V617F mutation and BCR/ABL translocation in one patient

    Directory of Open Access Journals (Sweden)

    Murat Albayrak

    2010-09-01

    Full Text Available Dear Editor,The myeloproliferative disorders (MPDs constitute a subcategory of chronic myeloid disorders and include chronic myeloid leukemia (CML, essential thrombocytemia (ET, polycythemia vera (PV and myelofibrosis (MF. In 1960, the discovery of the Philadelphia chromosome (Ph became a cornerstone in CML treatment and led to the development of moleculary targeted therapy. Recently, an acquired mutation in the Janus kinase 2 (JAK2 gene has been discovered in nearly all patents with PV and approximately half of the patients with primary MF and ET. Subsequently, the mutation has been demonstrated in atypical MPDs (chronic neutrophilic leukemia, unclassified, de novo myelodysplastic syndrome or acute myeloid leukemia.1 It has been hoped that targeted inhibition of JAK2V617F should achieve similar disease control as thyrosine kinases has produced in CML.

  2. Molecular approach to diagnose BCR/ABL negative chronic myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Michelle Maccarini Barcelos

    2011-01-01

    Full Text Available Chronic myeloproliferative neoplasms arise from clonal proliferation of hematopoietic stem cells. According to the World Health Organization myeloproliferative neoplasms are classified as: chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia, hypereosinophilic syndrome, mast cell disease, and unclassifiable myeloproliferative neoplasms. In the revised 2008 WHO diagnostic criteria for myeloproliferative neoplasms, mutation screening for JAK2V617F is considered a major criterion for polycythemia vera diagnosis and also for essential thrombocythemia and primary myelofibrosis, the presence of this mutation represents a clonal marker. There are currently two hypotheses explaining the role of the JAK2V617F mutation in chronic myeloproliferative neoplasms. According to these theories, the mutation plays either a primary or secondary role in disease development. The discovery of the JAK2V617F mutation has been essential in understanding the genetic basis of chronic myeloproliferative neoplasms, providing some idea on how a single mutation can result in three different chronic myeloproliferative neoplasm phenotypes. But there are still some issues to be clarified. Thus, studies are still needed to determine specific molecular markers for each subtype of chronic myeloproliferative neoplasm.

  3. Third symposium on coal preparation. NCA/BCR coal conference and Expo IV

    Energy Technology Data Exchange (ETDEWEB)

    None

    1977-01-01

    The third Symposium on Coal preparation, sponsored by the National Coal Association and Bituminous Coal Research, Inc., was held at the Kentucky Fair and Exposition Center, Louisville, Kentucky, October 18-20, 1977. Fourteen papers from the proceedings have been entered individually into EDB and ERA; five additional papers had been entered previously from other sources. Topics covered involved chemical comminution and chemical desulfurization of coal (aimed at reducing sulfur sufficiently with some coals to meet air quality standards without flue gas desulfurization), coal cleaning concepts, removing coal fines and recycling wash water, comparative evaluation of coal preparation methods, coal refuse disposal without polluting the environment, spoil bank reprocessing, noise control in coal preparation plants, etc. (LTN)

  4. Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene[S

    OpenAIRE

    Burns, Tara Ann; Subathra, Marimuthu; signorelli, Paola; Choi, Young; Yang, Xiaofeng; Wang, Yong; Villani, Maristella; Bhalla, Kapil; Zhou, Daohong; Luberto, Chiara

    2013-01-01

    Sphingomyelin synthase (SMS) produces sphingomyelin while consuming ceramide (a negative regulator of cell proliferation) and forming diacylglycerol (DAG) (a mitogenic factor). Therefore, enhanced SMS activity could favor cell proliferation. To examine if dysregulated SMS contributes to leukemogenesis, we measured SMS activity in several leukemic cell lines and found that it is highly elevated in K562 chronic myelogenous leukemia (CML) cells. The increased SMS in K562 cells was caused by the ...

  5. BCR-ABL negative myeloproliferative neoplasia: a review of involved molecular mechanisms.

    Science.gov (United States)

    Koopmans, Suzanne M; Schouten, Harry C; van Marion, Ariënne M W

    2015-02-01

    The clonal bone marrow stem cell disorders essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) belong to the group of Philadelphia chromosome negative myeloproliferative neoplasia (Ph- MPN). In 2005 the JAK2(V617F) mutation was discovered which has generated more insight in the pathogenetic mechanism of the MPNs. More mutations have been detected in MPN patients since. However, the underlying cause of MPN has not been discovered so far. The mechanism of increased angiogenesis in MPNs and the development of fibrosis in the bone marrow in PMF patients and in some ET and PV patients is still not known. This review will focus on the most important molecular pathogenetic mechanisms in MPN patients. PMID:25196073

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

    International Nuclear Information System (INIS)

    The Group of High Frequency Specialists from Belgium, France, Germany, The Netherlands and the UK, was awarded contracts in 1975 to carry out a programme of measurements on the high frequency dielectric properties of materials. The object of this first phase of a projected three phase programme was to establish the reliability of existing methods of measurement and to examine the possibilities of specifying and producing some standard reference materials, both liquid and solid, which could be used for calibrating and checking the performance of industrial measurement equipment. The liquids chosen for the first phase were cyclohexane, cis and trans decalin, chlorobenzene and 0.1, 1, and 10% solutions of chlorobenzene in cyclohexane. Each group had a limited frequency range over which it could make meaningful measurements but there was sufficient overlap to ensure that all random and systematic errors could be quantitatively assayed. The real (epsilon') and imaginary (epsilon'') components of the complex permittivity for all the liquids were measured over the frequency range 10 - 3,000 GHz and for the two most lossy liquids (chlorobenzene and 10% chlorobenzene in cyclohexane) this range was extended downwards to one GHz. The programme established for the first time the possible experimental imprecisions to be expected in high frequency dielecric measurements and showed that the chosen liquids could be useful standard reference materials if sufficiently pure specimens could be obtained commercially at a reasonable price. The programme did however reveal an unexpected snag in that the liquids, especially cyclohexane, were found to be rather more liable to contamination than expected. Since cyclohexane is a very low-loss liquid, only a small amount of a lossy contaminant need be absorbed to make the observed loss increase dramatically. This report contains all the measured results in both tabular and graphical form and in addition full technical details are given of the measurement procedures

  7. Seventh symposium on coal mine drainage research. NCA/BCR coal conference and Expo IV

    Energy Technology Data Exchange (ETDEWEB)

    None

    1977-01-01

    The Seventh Symposium on Coal Mine Drainage Research, sponsored by the National Coal Association and Bituminous Coal Research, Inc., was held at the Kentucky Fair and Exposition Center, Louisville, Kentucky, October 18-20, 1977. Seventeen papers from the proceedings have been entered individually into EDB and ERA. Topics covered include chemical reactions of pyrite oxidation and acid formation in spoil banks, abandoned mines, etc., formation of small acid lakes from the drainage and their neutralization by natural and other neutralization measures, trace elements in acid mine drainage, ground water contamination, limnology, effects of surface mined ground reclamation and neutralization, water purification and treatment, mining and coal preparation plant waste disposal, ash and fly ash disposal (to minimize leaching from the wastes), runoff from large coal storage stockpiles during storms (prevention of environmental effects by collection and neutralization by passing through an ash pond). (LTN)

  8. 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

    , still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome-positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic...

  9. Determination of trace elements in BCR single cell protein via destructive neutron activation analyses

    International Nuclear Information System (INIS)

    The amount of some trace elements in single cell protein (SCP), a product of BP Research Centre at Sunbury-at-Thames, England, was determined by neutron activation analysis. The SCP-samples were irradiated in the reactor of the Interuniversity Reactor Institute at Delft in a neutron flux of 1.0x1013 n/cm2s for 12 hours. Samples of Bowen's Kale were used as reference material. After a decay of two or three days the samples were chemically destroyed, and the trace elements were separated. The quantity of the following elements was determined by measuring the γ-activity by means of a scintillation counter: antimony, cadmium, mercury, arsenic and selenium. The amounts of these elements in the SCP and in the reference material were tabled

  10. Determination of selenium in BCR single cell protein via destructive neutron activation analysis

    International Nuclear Information System (INIS)

    The amount of selenium in single cell protein (SCP), a product of BP Research Centre at Sunbury-at-Thames, England, was determined by neutron activation analysis. The SCP-samples were irradiated in the reactor of the Interuniversity Reactor Institute at Delft, in a neutron flux of 1.0 x 1013 n/cm2s for 24 hours. After chemical destruction of the samples the amount of selenium was determined by measuring the γ-peaks of selenium-75

  11. Comparative Study on the Banking Performances at BCR ERSTE BANK, BRD – GSG and Raiffeisen Bank

    Directory of Open Access Journals (Sweden)

    Claudia MITITELU

    2014-11-01

    Full Text Available This paper aims to make a comparison between the performances of three banks in the banking system in Romania, considered the most representative but also to achieve their classifications and identify correlations between a number of used indicators and indicators expressing banking performance.

  12. 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

    , still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome-positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic...... myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011...

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

    International Nuclear Information System (INIS)

    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

  14. STUDY ON QUANTITATIVE SPECIATION, BY BCR METHOD, OF ZINC CONTENT FROM RIVER SEDIMENTS

    Directory of Open Access Journals (Sweden)

    Georgiana Vasile

    2008-06-01

    Full Text Available The present work presents the results obtained during investigation of the zinc content of the water and river sediments in an area polluted by mining activities, to provide information on the mobility and availability of this element. Sediment and water samples have been collected from significant sites in a former mining area in which with some sterile pits, which represent a major environmental hazard.

  15. Mercury speciation in coastal sediments from the central east coast of India by modified BCR method.

    Digital Repository Service at National Institute of Oceanography (India)

    Chakraborty, P.; Babu, P.V.R.; Vudamala, K.; Ramteke, D.; Chennuri, K.

    of India as shown in Figure 1. The sites were (1) Bheemili (BHI), (2) Vishakhapatnam (VSKP), and (3) Gangavaram (GVM) (4) Goutami Godavari Estuary (GGE) (5) Kakinada (KKD). The Bheemili (BHI) site is located in the north of Andhra Pradesh. This city... is not industrially developed. The approximate population of this city is ~50,000. Vishakhapatnam (VSKP) is the second largest city in the state of Andhra Pradesh and the third largest city (after Kolkata and Chennai) in the east coast of India. VSKP has become a...

  16. Spitzer Telemetry Processing System

    Science.gov (United States)

    Stanboli, Alice; Martinez, Elmain M.; McAuley, James M.

    2013-01-01

    The Spitzer Telemetry Processing System (SirtfTlmProc) was designed to address objectives of JPL's Multi-mission Image Processing Lab (MIPL) in processing spacecraft telemetry and distributing the resulting data to the science community. To minimize costs and maximize operability, the software design focused on automated error recovery, performance, and information management. The system processes telemetry from the Spitzer spacecraft and delivers Level 0 products to the Spitzer Science Center. SirtfTlmProc is a unique system with automated error notification and recovery, with a real-time continuous service that can go quiescent after periods of inactivity. The software can process 2 GB of telemetry and deliver Level 0 science products to the end user in four hours. It provides analysis tools so the operator can manage the system and troubleshoot problems. It automates telemetry processing in order to reduce staffing costs.

  17. Radioactive sodium processing apparatus

    International Nuclear Information System (INIS)

    Purpose: To enable safety, continuous and economical disposal for radioactive sodium while preventing radioactive contaminations. Constitution: Reaction gas introduction pipe for introducing oxygen and carbon dioxygen, and steams for accelerating the processing speed, as well as a discharge pipe for sodium carbonate as reaction products are connected to the lower side wall of a radioactive sodium processing container. A screw conveyor is mounted within the radioactive sodium processing container and a torque meter is disposed in the central axis of the conveyor. Signals from the torque meter are sent to an oxygen introduction control device. V-shaped recesses are formed to the screw blades of the conveyor for improving the separating efficiency between sodium carbonate produced through the procession and not-processed radioactive sodium. Since sodium is converted after the process into sodium carbonate, it can be handled and stored within ease. (Yoshihara, H.)

  18. Computers for symbolic processing

    Science.gov (United States)

    Wah, Benjamin W.; Lowrie, Matthew B.; Li, Guo-Jie

    1989-01-01

    A detailed survey on the motivations, design, applications, current status, and limitations of computers designed for symbolic processing is provided. Symbolic processing computations are performed at the word, relation, or meaning levels, and the knowledge used in symbolic applications may be fuzzy, uncertain, indeterminate, and ill represented. Various techniques for knowledge representation and processing are discussed from both the designers' and users' points of view. The design and choice of a suitable language for symbolic processing and the mapping of applications into a software architecture are then considered. The process of refining the application requirements into hardware and software architectures is treated, and state-of-the-art sequential and parallel computers designed for symbolic processing are discussed.

  19. Badge Office Process Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Haurykiewicz, John Paul [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dinehart, Timothy Grant [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Parker, Robert Young [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-12

    The purpose of this process analysis was to analyze the Badge Offices’ current processes from a systems perspective and consider ways of pursuing objectives set forth by SEC-PS, namely increased customer flow (throughput) and reduced customer wait times. Information for the analysis was gathered for the project primarily through Badge Office Subject Matter Experts (SMEs), and in-person observation of prevailing processes. Using the information gathered, a process simulation model was constructed to represent current operations and allow assessment of potential process changes relative to factors mentioned previously. The overall purpose of the analysis was to provide SEC-PS management with information and recommendations to serve as a basis for additional focused study and areas for potential process improvements in the future.

  20. Linearity in Process Languages

    DEFF Research Database (Denmark)

    Nygaard, Mikkel; Winskel, Glynn

    2002-01-01

    The meaning and mathematical consequences of linearity (managing without a presumed ability to copy) are studied for a path-based model of processes which is also a model of affine-linear logic. This connection yields an affine-linear language for processes, automatically respecting open-map bisi......The meaning and mathematical consequences of linearity (managing without a presumed ability to copy) are studied for a path-based model of processes which is also a model of affine-linear logic. This connection yields an affine-linear language for processes, automatically respecting open......-map bisimulation, in which a range of process operations can be expressed. An operational semantics is provided for the tensor fragment of the language. Different ways to make assemblies of processes lead to different choices of exponential, some of which respect bisimulation....

  1. NASA Hazard Analysis Process

    Science.gov (United States)

    Deckert, George

    2010-01-01

    This viewgraph presentation reviews The NASA Hazard Analysis process. The contents include: 1) Significant Incidents and Close Calls in Human Spaceflight; 2) Subsystem Safety Engineering Through the Project Life Cycle; 3) The Risk Informed Design Process; 4) Types of NASA Hazard Analysis; 5) Preliminary Hazard Analysis (PHA); 6) Hazard Analysis Process; 7) Identify Hazardous Conditions; 8) Consider All Interfaces; 9) Work a Preliminary Hazard List; 10) NASA Generic Hazards List; and 11) Final Thoughts

  2. Operating System Process Schedulers

    OpenAIRE

    ŠEKORANJA, MATEJ

    2016-01-01

    Process scheduling is one of the key tasks of every operating system. Proper implementation of a scheduler reflects itself in a system responsiveness, especially when processes require execution in real-time. Multimedia playback is one of these processes, also being one of the most common operating system tasks nowadays. In the beginning of this thesis, I present theoretical basics of scheduling: its goals, different scheduling types and basics algorithms. I cover scheduling in single-proces...

  3. Basic digital signal processing

    CERN Document Server

    Lockhart, Gordon B

    1985-01-01

    Basic Digital Signal Processing describes the principles of digital signal processing and experiments with BASIC programs involving the fast Fourier theorem (FFT). The book reviews the fundamentals of the BASIC program, continuous and discrete time signals including analog signals, Fourier analysis, discrete Fourier transform, signal energy, power. The text also explains digital signal processing involving digital filters, linear time-variant systems, discrete time unit impulse, discrete-time convolution, and the alternative structure for second order infinite impulse response (IIR) sections.

  4. Transnational Learning Processes

    DEFF Research Database (Denmark)

    Nedergaard, Peter

    This paper analyses and compares the transnational learning processes in the employment field in the European Union and among the Nordic countries. Based theoretically on a social constructivist model of learning and methodologically on a questionnaire distributed to the relevant participants......, a number of hypotheses concerning transnational learning processes are tested. The paper closes with a number of suggestions regarding an optimal institutional setting for facilitating transnational learning processes.Key words: Transnational learning, Open Method of Coordination, Learning, Employment...

  5. Process Improvement Essentials

    CERN Document Server

    Persse, James R

    2006-01-01

    Process Improvement Essentials combines the foundation needed to understand process improvement theory with the best practices to help individuals implement process improvement initiatives in their organization. The three leading programs: ISO 9001:2000, CMMI, and Six Sigma--amidst the buzz and hype--tend to get lumped together under a common label. This book delivers a combined guide to all three programs, compares their applicability, and then sets the foundation for further exploration.

  6. Multiphoton processes: conference proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Lambropoulos, P.; Smith, S.J. (eds.)

    1984-01-01

    The chapters of this volume represent the invited papers delivered at the conference. They are arranged according to thermatic proximity beginning with atoms and continuing with molecules and surfaces. Section headings include multiphoton processes in atoms, field fluctuations and collisions in multiphoton process, and multiphoton processes in molecules and surfaces. Abstracts of individual items from the conference were prepared separately for the data base. (GHT)

  7. TEP process flow diagram

    Energy Technology Data Exchange (ETDEWEB)

    Wilms, R Scott [Los Alamos National Laboratory; Carlson, Bryan [Los Alamos National Laboratory; Coons, James [Los Alamos National Laboratory; Kubic, William [Los Alamos National Laboratory

    2008-01-01

    This presentation describes the development of the proposed Process Flow Diagram (PFD) for the Tokamak Exhaust Processing System (TEP) of ITER. A brief review of design efforts leading up to the PFD is followed by a description of the hydrogen-like, air-like, and waterlike processes. Two new design values are described; the mostcommon and most-demanding design values. The proposed PFD is shown to meet specifications under the most-common and mostdemanding design values.

  8. Olfactory Signal Processing

    OpenAIRE

    Varshney, Kush R.; Varshney, Lav R.

    2014-01-01

    Olfaction, the sense of smell, has received scant attention from a signal processing perspective in comparison to audition and vision. In this paper, we develop a signal processing paradigm for olfactory signals based on new scientific discoveries including the psychophysics concept of olfactory white. We describe a framework for predicting the perception of odorant compounds from their physicochemical features and use the prediction as a foundation for several downstream processing tasks. We...

  9. Software Radar signal processing

    OpenAIRE

    T. Grydeland; Lind, F. D.; Erickson, P J; J. M. Holt

    2005-01-01

    Software infrastructure is a growing part of modern radio science systems. As part of developing a generic infrastructure for implementing Software Radar systems, we have developed a set of reusable signal processing components. These components are generic software-based implementations for use on general purpose computing systems. The components allow for the implementation of signal processing chains for radio frequency signal reception, correlation-based data processing, and cross-correla...

  10. Business process transformation

    CERN Document Server

    Grover, Varun

    2015-01-01

    Featuring contributions from prominent thinkers and researchers, this volume in the ""Advances in Management Information Systems"" series provides a rich set of conceptual, empirical, and introspective studies that epitomize fundamental knowledge in the area of Business Process Transformation. Processes are interpreted broadly to include operational and managerial processes within and between organizations, as well as those involved in knowledge generation. Transformation includes radical and incremental change, its conduct, management, and outcome. The editors and contributing authors pay clo

  11. Free Jacobi Process

    OpenAIRE

    Demni, Nizar

    2006-01-01

    Using a matrix approach, we define the free Jacobi process as the limit of the complex Jacobi matrix process. The we derive a free SDE which is analogous to its classical counterpart. To proceed, we prove that fro suitable parameters the process remains injective if it is initially injective and then use the polar decomposition. In the stationnary case, this will be easily deduced from the explicit expression of the spectral measure. In the general setting we derive a recurrence formula for t...

  12. Software Engineering Process Metamodels

    OpenAIRE

    Ragna Steenweg; Marco Kuhrmann; Daniel Méndez Fernández

    2013-01-01

    Software processes help to structure and organize software projects. Since software projects are complex endeavors and continuously grow in terms of size, budget, and complexity, software processes are used to coordinate people and teams, to define inter- faces in a multi-site project setting in global distributed development, and to provide a shared terminology and knowledge base. Since much process knowledge is available, appropriate tools are required to structure knowledge and to make it ...

  13. Polygon mesh processing

    CERN Document Server

    Botsch, Mario; Pauly, Mark; Alliez, Pierre; Levy, Bruno

    2010-01-01

    Geometry processing, or mesh processing, is a fast-growing area of research that uses concepts from applied mathematics, computer science, and engineering to design efficient algorithms for the acquisition, reconstruction, analysis, manipulation, simulation, and transmission of complex 3D models. Applications of geometry processing algorithms already cover a wide range of areas from multimedia, entertainment, and classical computer-aided design, to biomedical computing, reverse engineering, and scientific computing. Over the last several years, triangle meshes have become increasingly popular,

  14. Hierarchical Dirichlet Scaling Process

    OpenAIRE

    Kim, Dongwoo; Oh, Alice

    2014-01-01

    We present the \\textit{hierarchical Dirichlet scaling process} (HDSP), a Bayesian nonparametric mixed membership model. The HDSP generalizes the hierarchical Dirichlet process (HDP) to model the correlation structure between metadata in the corpus and mixture components. We construct the HDSP based on the normalized gamma representation of the Dirichlet process, and this construction allows incorporating a scaling function that controls the membership probabilities of the mixture components. ...

  15. TEP process flow diagram

    International Nuclear Information System (INIS)

    This presentation describes the development of the proposed Process Flow Diagram (PFD) for the Tokamak Exhaust Processing System (TEP) of ITER. A brief review of design efforts leading up to the PFD is followed by a description of the hydrogen-like, air-like, and waterlike processes. Two new design values are described; the mostcommon and most-demanding design values. The proposed PFD is shown to meet specifications under the most-common and mostdemanding design values.

  16. Financial information processing

    Institute of Scientific and Technical Information of China (English)

    Shuo BAI; Shouyang WANG; Lean YU; Aoying ZHOU

    2009-01-01

    @@ The rapid growth in financial data volume has made financial information processing more and more difficult due to the increase in complexity, which has forced businesses and academics alike to turn to sophisticated information processing technologies for better solutions. A typical feature is that high-performance computers and advanced computational techniques play ever-increasingly important roles for business and industries to have competitive advantages. Accordingly, financial information processing has emerged as a new cross-disciplinary field integrating computer science, mathematics, financial economics, intelligent techniques, and computer simulations to make different decisions based on processed financial information.

  17. Multimodal Processes Rescheduling

    DEFF Research Database (Denmark)

    Bocewicz, Grzegorz; Banaszak, Zbigniew A.; Nielsen, Peter;

    2013-01-01

    -cuted in these kinds of systems can be considered using a declarative modeling framework. Proposed representation provides a unified way for performance evaluation of local cyclic as well as supported by them multimodal processes. The main question regards of reachability of a SCCP cyclic behavior. In this context......Cyclic scheduling problems concerning multimodal processes are usually observed in FMSs producing multi-type parts where the Automated Guided Vehicles System (AGVS) plays a role of a material handling system. Schedulability analysis of concurrently flowing cyclic processes (SCCP) exe......, the sufficient conditions guarantee the reachability of both local and multimodal processes cyclic steady state spaces are discussed....

  18. Processing and recycling

    International Nuclear Information System (INIS)

    Participants of the meeting reported on materials and methods of industrial waste recycling and waste processing: development of sampling techniques for bulk quantities, characterization of electronic scrap, mechanical-biological treatment of residual wastes, comminution, ultrasonic dispersion of solids, control of particle size, fractionation, mills, wet benefication of heavy minerals from sand dunes, processing of slags and ashes, processing of polypropylene, computerized simulation of processing machines, recycling of photovoltaic Cadmium Telluride thin layer modules, compacting of hard coal, production of AIM (Auto Ignition Materials) pellets for airbags, oxidic solder for conditioning of radioactive wasteshydrocyclons, gasification of biomass, recycling of non-ferrous metals, mechanochemical dechlorination of PCB, dioxins, pentachlorphenol and pesticides, ceramics. (uke)

  19. The Critical Design Process

    DEFF Research Database (Denmark)

    Brunsgaard, Camilla; Knudstrup, Mary-Ann; Heiselberg, Per

    2014-01-01

    . Data analysis showed that the majority of the consortiums worked in an integrated manner; though there was room for improvment. Additionally, the paper discusses the challanges of implementing the integrated design process in practice and suggests ways of overcomming some of the barriers . In doing so...... within Danish tradition of architecture and construction. The objective of the research presented in this paper, is to compare the different design processes behind the making of passive houses in a Danish context. We evaluated the process with regard to the integrated and traditional design process...

  20. Cooperative internal conversion process

    CERN Document Server

    Kálmán, Péter

    2015-01-01

    A new phenomenon, called cooperative internal conversion process, in which the coupling of bound-free electron and neutron transitions due to the dipole term of their Coulomb interaction permits cooperation of two nuclei leading to neutron exchange if it is allowed by energy conservation, is discussed theoretically. General expression of the cross section of the process is reported in one particle nuclear and spherical shell models as well in the case of free atoms (e.g. noble gases). A half-life characteristic of the process is also determined. The case of $Ne$ is investigated numerically. The process may have significance in fields of nuclear waste disposal and nuclear energy production.

  1. Living olefin polymerization processes

    Science.gov (United States)

    Schrock, Richard R.; Baumann, Robert

    1999-01-01

    Processes for the living polymerization of olefin monomers with terminal carbon-carbon double bonds are disclosed. The processes employ initiators that include a metal atom and a ligand having two group 15 atoms and a group 16 atom or three group 15 atoms. The ligand is bonded to the metal atom through two anionic or covalent bonds and a dative bond. The initiators are particularly stable under reaction conditions in the absence of olefin monomer. The processes provide polymers having low polydispersities, especially block copolymers having low polydispersities. It is an additional advantage of these processes that, during block copolymer synthesis, a relatively small amount of homopolymer is formed.

  2. Fuels Processing Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — NETL’s Fuels Processing Laboratory in Morgantown, WV, provides researchers with the equipment they need to thoroughly explore the catalytic issues associated with...

  3. Process modeling style

    CERN Document Server

    Long, John

    2014-01-01

    Process Modeling Style focuses on other aspects of process modeling beyond notation that are very important to practitioners. Many people who model processes focus on the specific notation used to create their drawings. While that is important, there are many other aspects to modeling, such as naming, creating identifiers, descriptions, interfaces, patterns, and creating useful process documentation. Experience author John Long focuses on those non-notational aspects of modeling, which practitioners will find invaluable. Gives solid advice for creating roles, work produ

  4. Chemical process hazards analysis

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-02-01

    The Office of Worker Health and Safety (EH-5) under the Assistant Secretary for the Environment, Safety and Health of the US Department (DOE) has published two handbooks for use by DOE contractors managing facilities and processes covered by the Occupational Safety and Health Administration (OSHA) Rule for Process Safety Management of Highly Hazardous Chemicals (29 CFR 1910.119), herein referred to as the PSM Rule. The PSM Rule contains an integrated set of chemical process safety management elements designed to prevent chemical releases that can lead to catastrophic fires, explosions, or toxic exposures. The purpose of the two handbooks, ``Process Safety Management for Highly Hazardous Chemicals`` and ``Chemical Process Hazards Analysis,`` is to facilitate implementation of the provisions of the PSM Rule within the DOE. The purpose of this handbook ``Chemical Process Hazards Analysis,`` is to facilitate, within the DOE, the performance of chemical process hazards analyses (PrHAs) as required under the PSM Rule. It provides basic information for the performance of PrHAs, and should not be considered a complete resource on PrHA methods. Likewise, to determine if a facility is covered by the PSM rule, the reader should refer to the handbook, ``Process Safety Management for Highly Hazardous Chemicals`` (DOE- HDBK-1101-96). Promulgation of the PSM Rule has heightened the awareness of chemical safety management issues within the DOE. This handbook is intended for use by DOE facilities and processes covered by the PSM rule to facilitate contractor implementation of the PrHA element of the PSM Rule. However, contractors whose facilities and processes not covered by the PSM Rule may also use this handbook as a basis for conducting process hazards analyses as part of their good management practices. This handbook explains the minimum requirements for PrHAs outlined in the PSM Rule. Nowhere have requirements been added beyond what is specifically required by the rule.

  5. EARSEC SAR processing system

    Science.gov (United States)

    Protheroe, Mark; Sloggett, David R.; Sieber, Alois J.

    1994-12-01

    Traditionally, the production of high quality Synthetic Aperture Radar imagery has been an area where a potential user would have to expend large amounts of money in either the bespoke development of a processing chain dedicated to his requirements or in the purchase of a dedicated hardware platform adapted using accelerator boards and enhanced memory management. Whichever option the user adopted there were limitations based on the desire for a realistic throughput in data load and time. The user had a choice, made early in the purchase, for either a system that adopted innovative algorithmic manipulation, to limit the processing time of the purchase of expensive hardware. The former limits the quality of the product, while the latter excludes the user from any visibility into the processing chain. Clearly there was a need for a SAR processing architecture that gave the user a choice into the methodology to be adopted for a particular processing sequence, allowing him to decide on either a quick (lower quality) product or a detailed slower (high quality) product, without having to change the algorithmic base of his processor or the hardware platform. The European Commission, through the Advanced Techniques unit of the Joint Research Centre (JRC) Institute for Remote Sensing at Ispra in Italy, realizing the limitations on current processing abilities, initiated its own program to build airborne SAR and Electro-Optical (EO) sensor systems. This program is called the European Airborne Remote Sensing Capabilities (EARSEC) program. This paper describes the processing system developed for the airborne SAR sensor system. The paper considers the requirements for the system and the design of the EARSEC Airborne SAR Processing System. It highlights the development of an open SAR processing architecture where users have full access to intermediate products that arise from each of the major processing stages. It also describes the main processing stages in the overall

  6. Facilitated exclusion process and Pfaffian Schur processes

    OpenAIRE

    Baik, Jinho; Barraquand, Guillaume; Corwin, Ivan; Suidan, Toufic

    2016-01-01

    We study the Facilitated TASEP, an interacting particle system on the one dimensional integer lattice. We prove that starting from step initial condition, the position of the rightmost particle has Tracy Widom GSE statistics on a cube root time scale, while the statistics in the bulk of the rarefaction fan are GUE. This uses a mapping with last-passage percolation in a half-quadrant, which we study using the formalism of Pfaffian Schur processes. For the model with exponential weights, we pro...

  7. Technologies for Optical Processing

    DEFF Research Database (Denmark)

    Stubkjær, Kristian

    2008-01-01

    The article consists of a Powerpoint presentation on technologies for optical processing. The paper concludes that the nonlinear elements based on SOA, fibers and waveguide structures have capabilities of simple processing at data rates of 100-600 Gb/s. Switching powers comparable to electronics...

  8. Competencies of process managers

    Directory of Open Access Journals (Sweden)

    Matej Jevšček

    2016-03-01

    Full Text Available Abstract: Research Question (RQ: Effectiveness of managers differs in implementation of the process approach. Which competencies affect performance effectiveness of managers in the process approach? Purpose:The aim of the research is to specify a set of competencies which affect performance effectiveness of managers in the process approach. Method: The theoretical part examines the current state and terminology from the field of processes and competencies. The empirical part is based on a quantitative research. An online survey questionnaire was used for data collection. The survey was conducted among auditors of management systems worldwide. Results: The research indicates that there are significant differences between influences of different competencies on performance effectiveness of managers in the process approach. The studied competencies are presented in an array from the most to the least influential. Organization: The research directly affects the development of the HR function in organizations in practice. It enables an easier and more oriented personnel selection process and development of managers in the field of process performance. Society: The research enables easier orientation in competencies development that can improve the social order as well as social responsibility and the environment indirectly. Originality: The research originally offers a set of competencies that are relevant to process management. Limitations/Future Research: The research is restricted to the population of auditors.Future studies could examine the research question from a point of view of other professional groups

  9. Hybrid quantum information processing

    Energy Technology Data Exchange (ETDEWEB)

    Furusawa, Akira [Department of Applied Physics, School of Engineering, The University of Tokyo (Japan)

    2014-12-04

    I will briefly explain the definition and advantage of hybrid quantum information processing, which is hybridization of qubit and continuous-variable technologies. The final goal would be realization of universal gate sets both for qubit and continuous-variable quantum information processing with the hybrid technologies. For that purpose, qubit teleportation with a continuousvariable teleporter is one of the most important ingredients.

  10. HYDROMODELLING OF CASTING PROCESSES

    Directory of Open Access Journals (Sweden)

    E. I. Marukovich

    2016-02-01

    Full Text Available The description of equipment for hydrodynamic experiments and methods of hydromodeling of foundry processes, allowing to carry out three-dimensional modeling of filling process, is given. This method can be used for identification of numerical models and development of casting technology of the new types of production.

  11. Applying Mathematical Processes (AMP)

    Science.gov (United States)

    Kathotia, Vinay

    2011-01-01

    This article provides insights into the "Applying Mathematical Processes" resources, developed by the Nuffield Foundation. It features Nuffield AMP activities--and related ones from Bowland Maths--that were designed to support the teaching and assessment of key processes in mathematics--representing a situation mathematically, analysing,…

  12. Fleksibilitet i strategiske processer

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther

    2012-01-01

    Hvad vil det sige at strategiske processer er fleksible? Kan man lede sådanne fleksible processer? Hvilke udfordringer, muligheder, dilemmaer, - og for den sags skyld - glæder og frustrationer er der knyttet til dette? Dette paper vil forsøge at behandle og diskutere disse spørgsmål....

  13. Image processing mini manual

    Science.gov (United States)

    Matthews, Christine G.; Posenau, Mary-Anne; Leonard, Desiree M.; Avis, Elizabeth L.; Debure, Kelly R.; Stacy, Kathryn; Vonofenheim, Bill

    1992-01-01

    The intent is to provide an introduction to the image processing capabilities available at the Langley Research Center (LaRC) Central Scientific Computing Complex (CSCC). Various image processing software components are described. Information is given concerning the use of these components in the Data Visualization and Animation Laboratory at LaRC.

  14. Hyperspectral image processing methods

    Science.gov (United States)

    Hyperspectral image processing refers to the use of computer algorithms to extract, store and manipulate both spatial and spectral information contained in hyperspectral images across the visible and near-infrared portion of the electromagnetic spectrum. A typical hyperspectral image processing work...

  15. Hyperspectral image processing

    Science.gov (United States)

    Hyperspectral image processing refers to the use of computer algorithms to extract, store and manipulate both spatial and spectral information contained in hyperspectral images across the visible and near-infrared portion of the electromagnetic spectrum. A typical hyperspectral image processing work...

  16. Relational Processing Following Stroke

    Science.gov (United States)

    Andrews, Glenda; Halford, Graeme S.; Shum, David; Maujean, Annick; Chappell, Mark; Birney, Damian

    2013-01-01

    The research examined relational processing following stroke. Stroke patients (14 with frontal, 30 with non-frontal lesions) and 41 matched controls completed four relational processing tasks: sentence comprehension, Latin square matrix completion, modified Dimensional Change Card Sorting, and n-back. Each task included items at two or three…

  17. Contaminated nickel scrap processing

    International Nuclear Information System (INIS)

    The DOE will soon choose between treating contaminated nickel scrap as a legacy waste and developing high-volume nickel decontamination processes. In addition to reducing the volume of legacy wastes, a decontamination process could make 200,000 tons of this strategic metal available for domestic use. Contaminants in DOE nickel scrap include 234Th, 234Pa, 137Cs, 239Pu (trace), 60Co, U, 99Tc, and 237Np (trace). This report reviews several industrial-scale processes -- electrorefining, electrowinning, vapormetallurgy, and leaching -- used for the purification of nickel. Conventional nickel electrolysis processes are particularly attractive because they use side-stream purification of process solutions to improve the purity of nickel metal. Additionally, nickel purification by electrolysis is effective in a variety of electrolyte systems, including sulfate, chloride, and nitrate. Conventional electrorefining processes typically use a mixed electrolyte which includes sulfate, chloride, and borate. The use of an electrorefining or electrowinning system for scrap nickel recovery could be combined effectively with a variety of processes, including cementation, solvent extraction, ion exchange, complex-formation, and surface sorption, developed for uranium and transuranic purification. Selected processes were reviewed and evaluated for use in nickel side-stream purification. 80 refs

  18. The Analytical Hierarchy Process

    DEFF Research Database (Denmark)

    Barfod, Michael Bruhn

    2007-01-01

    The technical note gathers the theory behind the Analytical Hierarchy Process (AHP) and present its advantages and disadvantages in practical use.......The technical note gathers the theory behind the Analytical Hierarchy Process (AHP) and present its advantages and disadvantages in practical use....

  19. The process of entrepreneurship:

    DEFF Research Database (Denmark)

    Neergaard, Helle

    2003-01-01

    Growing a technology-based new venture is a complex process because these ventures are embedded in turbulent environments that require fast organisational and managerial transformation. This chapter addresses the evolutionary process of such ventures. It seeks to provide insight into the link bet...

  20. The Integrated Renovation Process

    DEFF Research Database (Denmark)

    Galiotto, Nicolas; Heiselberg, Per; Knudstrup, Mary-Ann

    2015-01-01

    the purpose of overcoming such barriers, a new scheme was proposed: the Integrated Renovation Process. In this paper, the scheme is applied to two single-family homes and is called the Integrated Renovation Process for Homes (IRP4homes). In both case studies, the newly developed methodology...

  1. Uranium processing and properties

    CERN Document Server

    2013-01-01

    Covers a broad spectrum of topics and applications that deal with uranium processing and the properties of uranium Offers extensive coverage of both new and established practices for dealing with uranium supplies in nuclear engineering Promotes the documentation of the state-of-the-art processing techniques utilized for uranium and other specialty metals

  2. Auditory processing models

    DEFF Research Database (Denmark)

    Dau, Torsten

    2008-01-01

    present topics on signal processing which are important in a specific area of acoustics. These will be of interest to specialists in these areas because they will be presented from their technical perspective, rather than a generic engineering approach to signal processing. Non-specialists, or specialists...

  3. FOOD PROCESSING ASSETS

    OpenAIRE

    Gallo, Anthony E.

    1996-01-01

    U.S. food processing sector assets are valued at about $360 billion, or about 12 percent of all manufacturing assets. Profit and sales returns on assets in food processing are among the highest in the U.S. economy. Foreign holdings comprise a significant portion of food processors' assets.

  4. Laser processing of plastics

    Science.gov (United States)

    Atanasov, Peter A.

    1995-03-01

    CO2-laser processing of plastics has been studied experimentally and theoretically. Welding of cylindrical parts made from polycarbonate and polypropylene, cutting of polymethyl-methacrylate plates, and drilling holes in polypropylene are presented as examples. A good coincidence between theoretical and experimental results in case of laser welding has been found. Some practical aspects of laser processing of plastics has been given.

  5. Microsystem process networks

    Science.gov (United States)

    Wegeng, Robert S.; TeGrotenhuis, Ward E.; Whyatt, Greg A.

    2006-10-24

    Various aspects and applications of microsystem process networks are described. The design of many types of microsystems can be improved by ortho-cascading mass, heat, or other unit process operations. Microsystems having exergetically efficient microchannel heat exchangers are also described. Detailed descriptions of numerous design features in microcomponent systems are also provided.

  6. Dosimetry in process control

    International Nuclear Information System (INIS)

    Measurement of absorbed dose and dose distribution in irradiated medical products relies on the use of quality dosimetry systems, trained personnel and a thorough understanding of the energy deposition process. The interrelationship of these factors will be discussed with emphasis on the current and future practices of process control dosimetry. (author)

  7. Manufacturing processes 4 forming

    CERN Document Server

    Klocke, Fritz

    2013-01-01

    This book provides essential information on metal forming, utilizing a practical distinction between bulk and sheet metal forming. In the field of bulk forming, it examines processes of cold, warm and hot bulk forming, as well as rolling and a new addition, the process of thixoforming. As for the field of sheet metal working, on the one hand it deals with sheet metal forming processes (deep drawing, flange forming, stretch drawing, metal spinning and bending). In terms of special processes, the chapters on internal high-pressure forming and high rate forming have been revised and refined. On the other, the book elucidates and presents the state of the art in sheet metal separation processes (shearing and fineblanking). Furthermore, joining by forming has been added to the new edition as a new chapter describing mechanical methods for joining sheet metals. The new chapter “Basic Principles” addresses both sheet metal and bulk forming, in addition to metal physics, plastomechanics and computational basics; ...

  8. New Processes for Annulation

    Institute of Scientific and Technical Information of China (English)

    Liu Hsing-Jang

    2004-01-01

    Making use of the high propensity of 2-cyano-2-cycloalkenones to undergo conjugate addition with various carbanions and the high reactivity of the ensuing α -cyano ketone system, a number of new annulation processes have been developed recently in our laboratories. As shown in Eq. 1 (n=1) with a specific example, one such process involves the addition of 3-butenylmagnesium bromide, followed by a palladium (Ⅱ) acetate mediated oxidative cyclization, to facilitate methylenecyclopentane ring formation. This annulation process could be readily extended to effect methylenecyclohexane ring formation (Eq. 1, n=2), using 4-pentenylmagnesinm bromide as the initial reagent, and to install the carbomethoxy-substituted methylenecyclopentane and methylenecyclohexane rings, using the carbanions derived from methyl 4-pentenoate and methyl 5-hexenoate, respectively (Eq. 2). In another annulation process, the addition of the enolate of methyl 5-chloropentanoate is involved initially, and the ring formation is readily effected by an intramolecular alkylation process. A specific example is given in Eq. 3.

  9. Identification of wastewater processes

    DEFF Research Database (Denmark)

    Carstensen, Niels Jacob

    The introduction of on-line sensors for monitoring of nutrient salts concentrations on wastewater treatment plants with nutrient removal, opens a wide new area of modelling wastewater processes. The subject of this thesis is the formulation of operational dynamic models based on time series...... of ammonia, nitrate, and phosphate concentrations, which are measured in the aeration tanks of the biological nutrient removal system. The alternatign operation modes of the BIO-DENITRO and BIO-DENIPHO processes are of particular interest. Time series models of the hydraulic and biological processes are very......-known theory of the processes with the significant effects found in data. These models are called grey box models, and they contain rate expressions for the processes of influent load of nutrients, transport of nutrients between the aeration tanks, hydrolysis and growth of biomass, nitrification...

  10. Economics of polysilicon processes

    Science.gov (United States)

    Yaws, C. L.; Li, K. Y.; Chou, S. M.

    1986-02-01

    Techniques are being developed to provide lower cost polysilicon material for solar cells. Existing technology which normally provides semiconductor industry polysilicon material is undergoing changes and also being used to provide polysilicon material for solar cells. Economics of new and existing technologies are presented for producing polysilicon. The economics are primarily based on the preliminary process design of a plant producing 1,000 metric tons/year of silicon. The polysilicon processes include: Siemen's process (hydrogen reduction of trichlorosilane); Union Carbide process (silane decomposition); and Hemlock Semiconductor process (hydrogen reduction of dichlorosilane). The economics include cost estimates of capital investment and product cost to produce polysilicon via the technology. Sensitivity analysis results are also presented to disclose the effect of major paramentes such as utilities, labor, raw materials and capital investment.

  11. In Process Beam Monitoring

    Science.gov (United States)

    Steen, W. M.; Weerasinghe, V. M.

    1986-11-01

    The industrial future of lasers in material processing lies in the combination of the laser with automatic machinery. One possible form of such a combination is an intelligent workstation which monitors the process as it occurs and adjusts itself accordingly, either by self teaching or by comparison to a process data bank or algorithm. In order to achieve this attractive goal in-process signals are required. Two devices are described in this paper. One is the Laser Beam Analyser which is now maturing into a second generation with computerised output. The other is the Acoustic Mirror, a totally novel analytic technique, not yet fully understood, but which nevertheless can act as a very effective process monitor.

  12. Branching processes in biology

    CERN Document Server

    Kimmel, Marek

    2015-01-01

    This book provides a theoretical background of branching processes and discusses their biological applications. Branching processes are a well-developed and powerful set of tools in the field of applied probability. The range of applications considered includes molecular biology, cellular biology, human evolution and medicine. The branching processes discussed include Galton-Watson, Markov, Bellman-Harris, Multitype, and General Processes. As an aid to understanding specific examples, two introductory chapters, and two glossaries are included that provide background material in mathematics and in biology. The book will be of interest to scientists who work in quantitative modeling of biological systems, particularly probabilists, mathematical biologists, biostatisticians, cell biologists, molecular biologists, and bioinformaticians. The authors are a mathematician and cell biologist who have collaborated for more than a decade in the field of branching processes in biology for this new edition. This second ex...

  13. Formed HIP Can Processing

    Energy Technology Data Exchange (ETDEWEB)

    Clarke, Kester Diederik [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-27

    The intent of this report is to document a procedure used at LANL for HIP bonding aluminum cladding to U-10Mo fuel foils using a formed HIP can for the Domestic Reactor Conversion program in the NNSA Office of Material, Management and Minimization, and provide some details that may not have been published elsewhere. The HIP process is based on the procedures that have been used to develop the formed HIP can process, including the baseline process developed at Idaho National Laboratory (INL). The HIP bonding cladding process development is summarized in the listed references. Further iterations with Babcock & Wilcox (B&W) to refine the process to meet production and facility requirements is expected.

  14. Conceptualizing operations strategy processes

    DEFF Research Database (Denmark)

    Rytter, Niels Gorm; Boer, Harry; Koch, Christian

    2007-01-01

    Purpose - The purpose of this paper is to present insights into operations strategy (OS) in practice. It outlines a conceptualization and model of OS processes and, based on findings from an in-depth and longitudinal case study, contributes to further development of extant OS models and methods...... which presently mainly focus on OS content, as distinct from process issues. DesignImethodology/approach - The methodology combines action research and a longitudinal single site case study of OS processes in practice. Findings - The paper conceptualises an OS process as: events of dialogue and action...... provides a useful tool for describing and analyzing real-time OS processes unfolding in practice. Research limitations/implications - The research is based on a single case, which limits the generalizability of the findings. Practical implications - The findings suggest that, in order to obtain successful...

  15. Beryllium chemistry and processing

    CERN Document Server

    Walsh, Kenneth A

    2009-01-01

    This book introduces beryllium; its history, its chemical, mechanical, and physical properties including nuclear properties. The 29 chapters include the mineralogy of beryllium and the preferred global sources of ore bodies. The identification and specifics of the industrial metallurgical processes used to form oxide from the ore and then metal from the oxide are thoroughly described. The special features of beryllium chemistry are introduced, including analytical chemical practices. Beryllium compounds of industrial interest are identified and discussed. Alloying, casting, powder processing, forming, metal removal, joining and other manufacturing processes are covered. The effect of composition and process on the mechanical and physical properties of beryllium alloys assists the reader in material selection. The physical metallurgy chapter brings conformity between chemical and physical metallurgical processing of beryllium, metal, alloys, and compounds. The environmental degradation of beryllium and its all...

  16. Posttranslational processing of progastrin

    DEFF Research Database (Denmark)

    Bundgaard, Jens René; Rehfeld, Jens F.

    2010-01-01

    Gastrin and cholecystokinin (CCK) are homologous hormones with important functions in the brain and the gut. Gastrin is the main regulator of gastric acid secretion and gastric mucosal growth, whereas cholecystokinin regulates gall bladder emptying, pancreatic enzyme secretion and besides acts as a...... processing progastrin is often greatly disturbed in neoplastic cells.The posttranslational phase of the biogenesis of gastrin and the various progastrin products in gastrin gene-expressing tissues is now reviewed here. In addition, the individual contributions of the processing enzymes are discussed, as are...... structural features of progastrin that are involved in the precursor activation process. Thus, the review describes how the processing depends on the cell-specific expression of the processing enzymes and kinetics in the secretory pathway....

  17. Quantum independent increment processes

    CERN Document Server

    Franz, Uwe

    2006-01-01

    This is the second of two volumes containing the revised and completed notes of lectures given at the school "Quantum Independent Increment Processes: Structure and Applications to Physics". This school was held at the Alfried-Krupp-Wissenschaftskolleg in Greifswald in March, 2003, and supported by the Volkswagen Foundation. The school gave an introduction to current research on quantum independent increment processes aimed at graduate students and non-specialists working in classical and quantum probability, operator algebras, and mathematical physics. The present second volume contains the following lectures: "Random Walks on Finite Quantum Groups" by Uwe Franz and Rolf Gohm, "Quantum Markov Processes and Applications in Physics" by Burkhard Kümmerer, Classical and Free Infinite Divisibility and Lévy Processes" by Ole E. Barndorff-Nielsen, Steen Thorbjornsen, and "Lévy Processes on Quantum Groups and Dual Groups" by Uwe Franz.

  18. Business process support

    Energy Technology Data Exchange (ETDEWEB)

    Carle, Adriana; Fiducia, Daniel [Transportadora de Gas del Sur S.A. (TGS), Buenos Aires (Argentina)

    2005-07-01

    This paper is about the own development of business support software. The developed applications are used to support two business processes: one of them is the process of gas transportation and the other is the natural gas processing. This software has interphases with the ERP SAP, software SCADA and on line gas transportation simulation software. The main functionalities of the applications are: entrance on line real time of clients transport nominations, transport programming, allocation of the clients transport nominations, transport control, measurements, balanced pipeline, allocation of gas volume to the gas processing plants, calculate of product tons processed in each plant and tons of product distributed to clients. All the developed software generates information to the internal staff, regulatory authorities and clients. (author)

  19. Heavy oils processing materials requirements crude processing

    Energy Technology Data Exchange (ETDEWEB)

    Sloley, Andrew W. [CH2M Hill, Englewood, CO (United States)

    2012-07-01

    Over time, recommended best practices for crude unit materials selection have evolved to accommodate new operating requirements, feed qualities, and product qualities. The shift to heavier oil processing is one of the major changes in crude feed quality occurring over the last 20 years. The three major types of crude unit corrosion include sulfidation attack, naphthenic acid attack, and corrosion resulting from hydrolyzable chlorides. Heavy oils processing makes all three areas worse. Heavy oils have higher sulfur content; higher naphthenic acid content; and are more difficult to desalt, leading to higher chloride corrosion rates. Materials selection involves two major criteria, meeting required safety standards, and optimizing economics of the overall plant. Proper materials selection is only one component of a plant integrity approach. Materials selection cannot eliminate all corrosion. Proper materials selection requires appropriate support from other elements of an integrity protection program. The elements of integrity preservation include: materials selection (type and corrosion allowance); management limits on operating conditions allowed; feed quality control; chemical additives for corrosion reduction; and preventive maintenance and inspection (PMI). The following discussion must be taken in the context of the application of required supporting work in all the other areas. Within that context, specific materials recommendations are made to minimize corrosion due to the most common causes in the crude unit. (author)

  20. Welding processes handbook

    CERN Document Server

    Weman, Klas

    2003-01-01

    Deals with the main commercially significant and commonly used welding processes. This title takes the student or novice welder through the individual steps involved in each process in an easily understood way. It covers many of the requirements referred to in European Standards including EN719, EN 729, EN 729 and EN 287.$bWelding processes handbook is a concise, explanatory guide to the main commercially significant and commonly-used welding processes. It takes the novice welder or student through the individual steps involved in each process in a clear and easily understood way. It is intended to provide an up-to-date reference to the major applications of welding as they are used in industry. The contents have been arranged so that it can be used as a textbook for European welding courses in accordance with guidelines from the European Welding Federation. Welding processes and equipment necessary for each process are described so that they can be applied to all instruction levels required by the EWF and th...

  1. Plutonium monitor: data processing

    International Nuclear Information System (INIS)

    The principle of the real time determination of air voluminal activity from the measurement of the activity of the filter. The ''Pu'' measurement processing has to comple the Pu/natural radioactivity discrimination that the sampler cannot do alone. The basic process of the measurement processing is described. For the operation checkout and the examination of performance of the processing, and for the technical success of a measurement-processing system, it is possible to use a real-time simulation of the different sensors; in the case of ''Pu'' processing, a mockup of the sampler has been prefered; it gives the elementary countings due to the natural radioactivity for the two ''Pu'' and ''RaA'' windows; it has been associated to a simulator giving the pulses corresponding in the ''Pu'' window to only ''Pu'', according the chosen profile. The main results obtained after several hundreds simulations are given; eight diagrams, quite representative, are presented. To concludes the performence of the BFSA monitor, for plutonium aerosol monitoring, in which the TMAPU2 measurement processing system and a performant detection head are associated, are reviewed

  2. Monitoring of Microalgal Processes.

    Science.gov (United States)

    Havlik, Ivo; Scheper, Thomas; Reardon, Kenneth F

    2016-01-01

    Process monitoring, which can be defined as the measurement of process variables with the smallest possible delay, is combined with process models to form the basis for successful process control. Minimizing the measurement delay leads inevitably to employing online, in situ sensors where possible, preferably using noninvasive measurement methods with stable, low-cost sensors. Microalgal processes have similarities to traditional bioprocesses but also have unique monitoring requirements. In general, variables to be monitored in microalgal processes can be categorized as physical, chemical, and biological, and they are measured in gaseous, liquid, and solid (biological) phases. Physical and chemical process variables can be usually monitored online using standard industrial sensors. The monitoring of biological process variables, however, relies mostly on sensors developed and validated using laboratory-scale systems or uses offline methods because of difficulties in developing suitable online sensors. Here, we review current technologies for online, in situ monitoring of all types of process parameters of microalgal cultivations, with a focus on monitoring of biological parameters. We discuss newly introduced methods for measuring biological parameters that could be possibly adapted for routine online use, should be preferably noninvasive, and are based on approaches that have been proven in other bioprocesses. New sensor types for measuring physicochemical parameters using optical methods or ion-specific field effect transistor (ISFET) sensors are also discussed. Reviewed methods with online implementation or online potential include measurement of irradiance, biomass concentration by optical density and image analysis, cell count, chlorophyll fluorescence, growth rate, lipid concentration by infrared spectrophotometry, dielectric scattering, and nuclear magnetic resonance. Future perspectives are discussed, especially in the field of image analysis using in situ

  3. Lasers in chemical processing

    International Nuclear Information System (INIS)

    The high cost of laser energy is the crucial issue in any potential laser-processing application. It is expensive relative to other forms of energy and to most bulk chemicals. We show those factors that have previously frustrated attempts to find commercially viable laser-induced processes for the production of materials. Having identified the general criteria to be satisfied by an economically successful laser process and shown how these imply the laser-system requirements, we present a status report on the uranium laser isotope separation (LIS) program at the Lawrence Livermore National Laboratory

  4. Irreversible processes kinetic theory

    CERN Document Server

    Brush, Stephen G

    2013-01-01

    Kinetic Theory, Volume 2: Irreversible Processes deals with the kinetic theory of gases and the irreversible processes they undergo. It includes the two papers by James Clerk Maxwell and Ludwig Boltzmann in which the basic equations for transport processes in gases are formulated, together with the first derivation of Boltzmann's ""H-theorem"" and a discussion of this theorem, along with the problem of irreversibility.Comprised of 10 chapters, this volume begins with an introduction to the fundamental nature of heat and of gases, along with Boltzmann's work on the kinetic theory of gases and s

  5. Getting Started with Processing

    CERN Document Server

    Reas, Casey

    2010-01-01

    Learn computer programming the easy way with Processing, a simple language that lets you use code to create drawings, animation, and interactive graphics. Programming courses usually start with theory, but this book lets you jump right into creative and fun projects. It's ideal for anyone who wants to learn basic programming, and serves as a simple introduction to graphics for people with some programming skills. Written by the founders of Processing, this book takes you through the learning process one step at a time to help you grasp core programming concepts. You'll learn how to sketch wi

  6. IT Project Prioritization Process

    DEFF Research Database (Denmark)

    Shollo, Arisa; Constantiou, Ioanna

    2013-01-01

    In most of the large companies IT project prioritization process is designed based on principles of evidencebased management. We investigate a case of IT project prioritization in a financial institution, and in particular, how managers practice evidence-based management during this process. We use...... a rich dataset built from a longitudinal study of the prioritization process for the IT projects. Our findings indicate that managers reach a decision not only by using evidence but from the interplay between the evidence and the judgment devices that managers employ. The interplay between evidence...

  7. The image processing handbook

    CERN Document Server

    Russ, John C

    2006-01-01

    Now in its fifth edition, John C. Russ's monumental image processing reference is an even more complete, modern, and hands-on tool than ever before. The Image Processing Handbook, Fifth Edition is fully updated and expanded to reflect the latest developments in the field. Written by an expert with unequalled experience and authority, it offers clear guidance on how to create, select, and use the most appropriate algorithms for a specific application. What's new in the Fifth Edition? ·       A new chapter on the human visual process that explains which visual cues elicit a response from the vie

  8. Advanced uranium enrichment processes

    International Nuclear Information System (INIS)

    Three advanced Uranium enrichment processes are dealt with in the report: AVLIS (Atomic Vapour LASER Isotope Separation), MLIS (Molecular LASER Isotope Separation) and PSP (Plasma Separation Process). The description of the physical and technical features of the processes constitutes a major part of the report. If further presents comparisons with existing industrially used enrichment technologies, gives information on actual development programmes and budgets and ends with a chapter on perspectives and conclusions. An extensive bibliography of the relevant open literature is added to the different subjects discussed. The report was drawn up by the nuclear research Centre (CEA) Saclay on behalf of the Commission of the European Communities

  9. Study on Glulam Process

    Institute of Scientific and Technical Information of China (English)

    PENG Limin; WANG Haiqing; HE Weili

    2006-01-01

    This paper selected lumbers of Manchurian ash (Fraxinus rnandshurica), Manchurian walnut (Juglans mandshuricd) and Spruce (Picea jezoensis vai.kornamvii) for manufacturing glulam with water-borne polymeric-isocyanate adhesive to determine process variables. The process variables that include specific pressure, pressing time and adhesive application amount influencing the shear strength of the glulam, were investigated through the orthogonal test. The results indicated that optimum process variables for glulam manufacturing were as follows: Specific pressure of 1.5 MPa for Spruce and 2,0 MPa both for Manchurian ash and Manchurian walnut, pressing time of 60 min and adhesive application amount of 250 g/m2.

  10. Quantum Information Processing

    CERN Document Server

    Leuchs, Gerd

    2005-01-01

    Quantum processing and communication is emerging as a challenging technique at the beginning of the new millennium. This is an up-to-date insight into the current research of quantum superposition, entanglement, and the quantum measurement process - the key ingredients of quantum information processing. The authors further address quantum protocols and algorithms. Complementary to similar programmes in other countries and at the European level, the German Research Foundation (DFG) started a focused research program on quantum information in 1999. The contributions - written by leading experts - bring together the latest results in quantum information as well as addressing all the relevant questions

  11. Visual color image processing

    Science.gov (United States)

    Qiu, Guoping; Schaefer, Gerald

    1999-12-01

    In this paper, we propose a color image processing method by combining modern signal processing technique with knowledge about the properties of the human color vision system. Color signals are processed differently according to their visual importance. The emphasis of the technique is on the preservation of total visual quality of the image and simultaneously taking into account computational efficiency. A specific color image enhancement technique, termed Hybrid Vector Median Filtering is presented. Computer simulations have been performed to demonstrate that the new approach is technically sound and results are comparable to or better than traditional methods.

  12. Ultrasonic Processing of Materials

    Energy Technology Data Exchange (ETDEWEB)

    Meek, Thomas T.; Han, Qingyou; Jian, Xiaogang; Xu, Hanbing

    2005-06-30

    The purpose of this project was to determine the impact of a new breakthrough technology, ultrasonic processing, on various industries, including steel, aluminum, metal casting, and forging. The specific goals of the project were to evaluate core principles and establish quantitative bases for the ultrasonc processing of materials, and to demonstrate key applications in the areas of grain refinement of alloys during solidification and degassing of alloy melts. This study focussed on two classes of materials - aluminum alloys and steels - and demonstrated the application of ultrasonic processing during ingot casting.

  13. Process of performance assessment

    International Nuclear Information System (INIS)

    Performance assessment is the process used to evaluate the environmental consequences of disposal of radioactive waste in the biosphere. An introductory review of the subject is presented. Emphasis is placed on the process of performance assessment from the standpoint of defining the process. Performance assessment, from evolving experience at DOE sites, has short-term and long-term subprograms, the components of which are discussed. The role of mathematical modeling in performance assessment is addressed including the pros and cons of current approaches. Finally, the system/site/technology issues as the focal point of this symposium are reviewed

  14. Robot welding process control

    Science.gov (United States)

    Romine, Peter L.

    1991-01-01

    This final report documents the development and installation of software and hardware for Robotic Welding Process Control. Primary emphasis is on serial communications between the CYRO 750 robotic welder, Heurikon minicomputer running Hunter & Ready VRTX, and an IBM PC/AT, for offline programming and control and closed-loop welding control. The requirements for completion of the implementation of the Rocketdyne weld tracking control are discussed. The procedure for downloading programs from the Intergraph, over the network, is discussed. Conclusions are made on the results of this task, and recommendations are made for efficient implementation of communications, weld process control development, and advanced process control procedures using the Heurikon.

  15. Digital Differential Geometry Processing

    Institute of Scientific and Technical Information of China (English)

    Xin-Guo Liu; Hu-Jun Bao; Qun-Sheng Peng

    2006-01-01

    The theory and methods of digital geometry processing has been a hot research area in computer graphics, as geometric models serves as the core data for 3D graphics applications. The purpose of this paper is to introduce some recent advances in digital geometry processing, particularly mesh fairing, surface parameterization and mesh editing, that heavily use differential geometry quantities. Some related concepts from differential geometry, such as normal, curvature, gradient,Laplacian and their counterparts on digital geometry are also reviewed for understanding the strength and weakness of various digital geometry processing methods.

  16. Historical film processing

    Science.gov (United States)

    Wu, Yi; Suter, David

    1995-08-01

    This paper describes work using historical film material, including what is believed to be the world's first feature length film. The digital processing of historical film material permits many new facilities: digital restoration, electronic storage, automated indexing, and electronic delivery to name a few. Although the work aims ultimately to support all of the previously mentioned facilities, this paper concentrated upon automatic scene change detection, brightness correction, and frame registration. These processes are fundamental to a more complete and complex processing system, but, by themselves, could be immediately used in computer-assisted film cataloging.

  17. Lapis SOI Pixel Process

    OpenAIRE

    Okihara, Masao; Kasai, Hiroki; Miura, Noriyuki; Kuriyama, Naoya; Nagatomo, Yoshiki

    2015-01-01

    0.2 um fully-depleted SOI technology has been developed a for X-ray pixel detectors. To improve the detector performance, some advanced process technologies are developing continuously. To utilize the high resistivity FZ-SOI, slow ramp up and ramp down recipes are applied for the thermal processes in both of SOI wafer fabrication and pixel detector process. The suitable backside treatment is also applied to prevent increase of leakage current at backside damaged layer in the case of full depl...

  18. Radioactive waste processing method

    International Nuclear Information System (INIS)

    When granular materials comprising radioactive wastes containing phosphorus are processed at first in a fluidized bed type furnace, if the granular materials are phosphorus-containing activated carbon, granular materials comprising alkali compound such as calcium hydroxide and barium hydroxide are used as fluidizing media. Even granular materials of slow burning speed can be burnt stably in a fluidizing state by high temperature heat of the fluidizing media, thereby enabling to take a long burning processing time. Accordingly, radioactive activated carbon wastes can be processed by burning treatment. (T.M.)

  19. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...

  20. Scintigraphy in retrobulbar processes

    International Nuclear Information System (INIS)

    The results of scintigrphic investigation of 12 patients with retrobulbar processes are presented. Use was made of different radiopharmaceutical agents. In inflammatory diseases 99mTc04- and 99mTc DTPA give more reliable positive finding than 67-gallium citrate. The latter shows nonspecifity in retrobulbar processes and cannot distinguish inflammatory from neoplastic process. The negative scintigraphic finding in investigation with 99mTc compounds makes it necessary in case of clinical suspicion to utilize also tumourotropic, osteotropic and other radiopharmaceutical agents which increases the scope of positiveness of the data

  1. Plasma processing for VLSI

    CERN Document Server

    Einspruch, Norman G

    1984-01-01

    VLSI Electronics: Microstructure Science, Volume 8: Plasma Processing for VLSI (Very Large Scale Integration) discusses the utilization of plasmas for general semiconductor processing. It also includes expositions on advanced deposition of materials for metallization, lithographic methods that use plasmas as exposure sources and for multiple resist patterning, and device structures made possible by anisotropic etching.This volume is divided into four sections. It begins with the history of plasma processing, a discussion of some of the early developments and trends for VLSI. The second section

  2. Modeling robot contour processes

    Science.gov (United States)

    Whitney, D. E.; Edsall, A. C.

    Robot contour processes include those with contact force like car body grinding or deburring of complex castings, as well as those with little or no contact force like inspection. This paper describes ways of characterizing, identifying, and estimating contours and robot trajectories. Contour and robot are modeled as stochastic processes in order to emphasize that both successive robot cycles and successive industrial workpieces are similar but not exactly the same. The stochastic models can be used to identify the state of a workpiece or process, or to design a filter to estimate workpiece, shape and robot position from robot-based measurements.

  3. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    Science.gov (United States)

    2016-08-05

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

  4. Tree-Indexed Processes

    OpenAIRE

    Pemantle, Robin

    1995-01-01

    This article examines a recent body of work on stochastic processes indexed by a tree. Emphasis is on the application of this new framework to existing probability models. Proofs are largely omitted, with references provided.

  5. Processer i undervisningen

    DEFF Research Database (Denmark)

    Bundsgaard, Jeppe

    Undersøgelsen har fokus på processer i undervisningen – og derigennem på hvordan digitale læremidler kan understøtte eller integreres i typiske processer. Undersøgelsen hviler på deltagende observation på Abildgårdskolen i Odense. Gennem observationerne er der identificeret en række eksempler på...... udfordringer for at gennemføre de undervisningsmæssige processer og givet bud på digitale læremidler der forventes at kunne understøtte processerne. Undersøgelsen viser samtidig hvordan fokus på processer kan fungere som en metode til brugerdreven innovation....

  6. WWTP Process Tank Modelling

    DEFF Research Database (Denmark)

    Laursen, Jesper

    solution of the Navier-Stokes equations in a multiphase scheme. After a general introduction to the activated sludge tank as a system, the activated sludge tank model is gradually setup in separate stages. The individual sub-processes that are often occurring in activated sludge tanks are initially...... investigated individually, with the purpose of obtaining a better understanding before the final integrated model is setup. In the sub-process investigations focus is addressed especially at aeration by bottom mounted diffusers and mechanical mixing of the activated sludge suspension via slowly rotating...... hydrofoil shaped propellers. These two sub-processes deliver the main part of the supplied energy to the activated sludge tank, and for this reason they are important for the mixing conditions in the tank. For other important processes occurring in the activated sludge tank, existing models and measurements...

  7. Markovian risk process

    Institute of Scientific and Technical Information of China (English)

    WANG Han-xing; YAN Yun-zhi; ZHAO Fei; FANG Da-fan

    2007-01-01

    A Markovian risk process is considered in this paper, which is the generalization of the classical risk model. It is proper that a risk process with large claims is modelled as the Markovian risk model. In such a model, the occurrence of claims is described by a point process {N(t)}t≥o with N(t) being the number of jumps during the interval (0, t] for a Markov jump process. The ruin probability Ψ(u) of a company facing such a risk model is mainly studied. An integral equation satisfied by the ruin probability function Ψ(u) is obtained and the bounds for the convergence rate of the ruin probability Ψ(u) are given by using a generalized renewal technique developed in the paper.

  8. Business Model Process Configurations

    DEFF Research Database (Denmark)

    Taran, Yariv; Nielsen, Christian; Thomsen, Peter;

    2015-01-01

    Purpose – The paper aims: 1) To develop systematically a structural list of various business model process configuration and to group (deductively) these selected configurations in a structured typological categorization list. 2) To facilitate companies in the process of BM innovation......, by developing (inductively) an ontological classification framework, in view of the BM process configurations typology developed. Design/methodology/approach – Given the inconsistencies found in the business model studies (e.g. definitions, configurations, classifications) we adopted the analytical induction...... method of data analysis. Findings - A comprehensive literature review and analysis resulted in a list of business model process configurations systematically organized under five classification groups, namely, revenue model; value proposition; value configuration; target customers, and strategic...

  9. Analysing the process

    International Nuclear Information System (INIS)

    To achieve optimum process control of mineral extraction and production, efficient on-line or in-plant analysis is essential and nuclear techniques are making an increasingly important contribution in this area

  10. Logistics Innovation Process Revisited

    DEFF Research Database (Denmark)

    Gammelgaard, Britta; Su, Shong-Iee Ivan; Yang, Su-Lan

    2011-01-01

    Purpose – The purpose of this paper is to learn more about logistics innovation processes and their implications for the focal organization as well as the supply chain, especially suppliers. Design/methodology/approach – The empirical basis of the study is a longitudinal action research project...... that was triggered by the practical needs of new ways of handling material flows of a hospital. This approach made it possible to revisit theory on logistics innovation process. Findings – Apart from the tangible benefits reported to the case hospital, five findings can be extracted from this study: the logistics...... innovation process model may include not just customers but also suppliers; logistics innovation in buyer-supplier relations may serve as an alternative to outsourcing; logistics innovation processes are dynamic and may improve supplier partnerships; logistics innovations in the supply chain are as dependent...

  11. Radiation processing in Japan

    International Nuclear Information System (INIS)

    Economic scale of radiation application in the field of industry, agriculture and medicine in Japan in 1997 was investigated to compare its economic impacts with that of nuclear energy industry. Total production value of radiation application accounted for 54% of nuclear industry including nuclear energy industry and radiation applications in three fields above. Industrial radiation applications were further divided into five groups, namely nondestructive test, RI instruments, radiation facilities, radiation processing and ion beam processing. More than 70% of the total production value was brought about by ion beam processing for use with IC and semiconductors. Future economic prospect of radiation processing of polymers, for example cross-linking, EB curing, graft polymerization and degradation, is reviewed. Particular attention was paid to radiation vulcanization of natural rubber latex and also to degradation of natural polymers. (S. Ohno)

  12. Processing NOAA Spectroradiometric Data

    OpenAIRE

    Broenkow, William W.; Greene, Nancy, T.; Feinholz, Michael, E.

    1993-01-01

    This report outlines the NOAA spectroradiometer data processing system implemented by the MLML_DBASE programs. This is done by presenting the algorithms and graphs showing the effects of each step in the algorithms. [PDF contains 32 pages

  13. Desalination processes and technologies

    International Nuclear Information System (INIS)

    Reasons of the development of desalination processes, the modern desalination technologies, such as multi-stage flash evaporation, multi-effect distillation, reverse osmosis, and the prospects of using nuclear power for desalination purposes are discussed. 9 refs

  14. Processed Products Database System

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Collection of annual data on processed seafood products. The Division provides authoritative advice, coordination and guidance on matters related to the collection,...

  15. Radiation processing in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Makuuchi, Keizo [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

    2001-03-01

    Economic scale of radiation application in the field of industry, agriculture and medicine in Japan in 1997 was investigated to compare its economic impacts with that of nuclear energy industry. Total production value of radiation application accounted for 54% of nuclear industry including nuclear energy industry and radiation applications in three fields above. Industrial radiation applications were further divided into five groups, namely nondestructive test, RI instruments, radiation facilities, radiation processing and ion beam processing. More than 70% of the total production value was brought about by ion beam processing for use with IC and semiconductors. Future economic prospect of radiation processing of polymers, for example cross-linking, EB curing, graft polymerization and degradation, is reviewed. Particular attention was paid to radiation vulcanization of natural rubber latex and also to degradation of natural polymers. (S. Ohno)

  16. Cooperative processing data bases

    Science.gov (United States)

    Hasta, Juzar

    1991-01-01

    Cooperative processing for the 1990's using client-server technology is addressed. The main theme is concepts of downsizing from mainframes and minicomputers to workstations on a local area network (LAN). This document is presented in view graph form.

  17. Enrichment: centrifuge process

    International Nuclear Information System (INIS)

    This short course is divided into three sections devoted respectively to the physics of the process, some practical problems raised by the design of a centrifuge and the present situation of centrifugation in the World. 31 figs., 18 refs

  18. Technology or Process First?

    DEFF Research Database (Denmark)

    Siurdyban, Artur Henryk; Svejvig, Per; Møller, Charles

    Enterprise Systems Management (ESM) and Business Pro- cess Management (BPM), although highly correlated, have evolved as alternative and mutually exclusive approaches to corporate infrastruc- ture. As a result, companies struggle to nd the right balance between technology and process factors...

  19. Dissolution processes. [224 references

    Energy Technology Data Exchange (ETDEWEB)

    Silver, G.L.

    1976-10-22

    This review contains more than 100 observations and 224 references on the dissolution phenomenon. The dissolution processes are grouped into three categories: methods of aqueous attack, fusion methods, and miscellaneous observations on phenomena related to dissolution problems. (DLC)

  20. George: Gaussian Process regression

    Science.gov (United States)

    Foreman-Mackey, Daniel

    2015-11-01

    George is a fast and flexible library, implemented in C++ with Python bindings, for Gaussian Process regression useful for accounting for correlated noise in astronomical datasets, including those for transiting exoplanet discovery and characterization and stellar population modeling.

  1. Communicating Quantum Processes

    CERN Document Server

    Gay, S; Gay, Simon; Nagarajan, Rajagopal

    2004-01-01

    We define a language CQP (Communicating Quantum Processes) for modelling systems which combine quantum and classical communication and computation. CQP combines the communication primitives of the pi-calculus with primitives for measurement and transformation of quantum state; in particular, quantum bits (qubits) can be transmitted from process to process along communication channels. CQP has a static type system which classifies channels, distinguishes between quantum and classical data, and controls the use of quantum state. We formally define the syntax, operational semantics and type system of CQP, prove that the semantics preserves typing, and prove that typing guarantees that each qubit is owned by a unique process within a system. We illustrate CQP by defining models of several quantum communication systems, and outline our plans for using CQP as the foundation for formal analysis and verification of combined quantum and classical systems.

  2. Product and Process Modelling

    DEFF Research Database (Denmark)

    Cameron, Ian T.; Gani, Rafiqul

    This book covers the area of product and process modelling via a case study approach. It addresses a wide range of modelling applications with emphasis on modelling methodology and the subsequent in-depth analysis of mathematical models to gain insight via structural aspects of the models....... These approaches are put into the context of life cycle modelling, where multiscale and multiform modelling is increasingly prevalent in the 21st century. The book commences with a discussion of modern product and process modelling theory and practice followed by a series of case studies drawn from a variety...... to biotechnology applications, food, polymer and human health application areas. The book highlights to important nature of modern product and process modelling in the decision making processes across the life cycle. As such it provides an important resource for students, researchers and industrial practitioners....

  3. Assessing Process and Product

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael E.

    2006-01-01

    The final assessment of a course must reflect its goals, and contents. An important goal of our introductory programming course is that the students learn a systematic approach for the development of computer programs. Having the programming process as learning objective naturally raises the ques......The final assessment of a course must reflect its goals, and contents. An important goal of our introductory programming course is that the students learn a systematic approach for the development of computer programs. Having the programming process as learning objective naturally raises...... the question how to include this in assessments. Traditional assessments (e.g. oral, written, or multiple choice) are unsuitable to test the programming process. We describe and evaluate a practical lab examination that assesses the students' programming process as well as the developed programs...

  4. Dosimetry for radiation processing

    DEFF Research Database (Denmark)

    Miller, Arne

    1986-01-01

    During the past few years significant advances have taken place in the different areas of dosimetry for radiation processing, mainly stimulated by the increased interest in radiation for food preservation, plastic processing and sterilization of medical products. Reference services both by...... and sterilization dosimetry, optichromic dosimeters in the shape of small tubes for food processing, and ESR spectroscopy of alanine for reference dosimetry. In this paper the special features of radiation processing dosimetry are discussed, several commonly used dosimeters are reviewed, and factors...... international organizations (IAEA) and national laboratories have helped to improve the reliability of dose measurements. Several dosimeter systems like calorimetry, perspex, and radiochromic dye films are being improved and new systems have emerged, e.g. spectrophotometry of dichromate solution for reference...

  5. Customer Innovation Process Leadership

    DEFF Research Database (Denmark)

    Lindgren, Peter; Jørgensen, Jacob Høj; Goduscheit, René Chester

    2007-01-01

    Innovation leadership has traditionally been focused on leading the companies' product development fast, cost effectively and with an optimal performance driven by technological inventions or by customers´ needs. To improve the efficiency of the product development process focus has been on...... to handle shorter and faster product life cycles. Continuously changing customer needs are pushing companies' competence of continuous innovation to a maximum - but still this seems not to be enough to stay competitive on the global market and reach the goals of growth. This article therefore...... suggests another outlook to future innovation leadership - Customer Innovation Process Leadership - CIP-leadership. CIP-leadership moves the company's innovation process closer to the customer innovation process and discusses how companies can be involved and innovate in customers' future needs and lead...

  6. Organ Donation: The Process

    Science.gov (United States)

    ... Español Search Register with your state as an Organ Donor Home Why Donate Becoming a Donor About Donation & ... Plan Your Finances After Your Transplant Contact Your Donor Family Organ Donation: The Process Enrolling as a Donor : The ...

  7. Organic food processing

    DEFF Research Database (Denmark)

    Kahl, Johannes; Alborzi, Farnaz; Beck, Alexander;

    2014-01-01

    In 2007 EU Regulation (EC) 834/2007 introduced principles and criteria for organic food processing. These regulations have been analysed and discussed in several scientific publications and research project reports. Recently, organic food quality was described by principles, aspects and criteria...... product identity as the underlying paradigm and a holistic quality view connected to naturalness as consumers' perception of organic food quality. In a European study, the quality concept was applied to the organic food chain, resulting in a problem, namely that clear principles and related criteria were...... food as well as on organic processing. The proposed definition connects organic processing to related systems such as minimal, sustainable and careful, gentle processing, and describes clear principles and related criteria. Based on food examples, such as milk with different heat treatments, the...

  8. Cauchy cluster process

    DEFF Research Database (Denmark)

    Ghorbani, Mohammad

    2013-01-01

    In this paper we introduce an instance of the well-know Neyman–Scott cluster process model with clusters having a long tail behaviour. In our model the offspring points are distributed around the parent points according to a circular Cauchy distribution. Using a modified Cramér-von Misses test...... statistic and the simulated pointwise envelopes it is shown that this model fits better than the Thomas process to the frequently analyzed long-leaf pine data-set....

  9. GELATIN DRYING PROCESS

    OpenAIRE

    Silva, E A; I. Neitzel; L.H.M. Silva

    2001-01-01

    In one of the stages of the gelatin production process, a highly concentrated solution of gel is cooled and extruded to form gelatin noodles, which are then laid on a drying belt. Gelatin is a molecular colloid that is not porous under these drying conditions, and as a consequence, water migration occurs solely by diffusive processes. To achieve a commercial standard of dryness, the dependence of the diffusion coefficient as a function of temperature is used. This set of circumstances favors ...

  10. Hydrogen production processes

    International Nuclear Information System (INIS)

    The goals of this first Gedepeon workshop on hydrogen production processes are: to stimulate the information exchange about research programs and research advances in the domain of hydrogen production processes, to indicate the domains of interest of these processes and the potentialities linked with the coupling of a nuclear reactor, to establish the actions of common interest for the CEA, the CNRS, and eventually EDF, that can be funded in the framework of the Gedepeon research group. This document gathers the slides of the 17 presentations given at this workshop and dealing with: the H2 question and the international research programs (Lucchese P.); the CEA's research program (Lucchese P., Anzieu P.); processes based on the iodine/sulfur cycle: efficiency of a facility - flow-sheets, efficiencies, hard points (Borgard J.M.), R and D about the I/S cycle: Bunsen reaction (Colette S.), R and D about the I/S cycle: the HI/I2/H2O system (Doizi D.), demonstration loop/chemical engineering (Duhamet J.), materials and corrosion (Terlain A.); other processes under study: the Westinghouse cycle (Eysseric C.), other processes under study at the CEA (UT3, plasma,...) (Lemort F.), database about thermochemical cycles (Abanades S.), Zn/ZnO cycle (Broust F.), H2 production by cracking, high temperature reforming with carbon trapping (Flamant G.), membrane technology (De Lamare J.); high-temperature electrolysis: SOFC used as electrolyzers (Grastien R.); generic aspects linked with hydrogen production: technical-economical evaluation of processes (Werkoff F.), thermodynamic tools (Neveu P.), the reactor-process coupling (Aujollet P.). (J.S.)

  11. Analyzing business process management

    OpenAIRE

    Skjæveland, Børge

    2013-01-01

    Within the Oil & Gas Industry, the market is constantly growing more competitive, forcing companies to continually adapt to changes. Companies need to cut costs and improve the business efficiency. One way of successfully managing these challenges is to implement business process management in the organization. This thesis will analyze how Oceaneering Asset Integrity AS handled the implementation of a Business Process Management System and the effects it had on the employees. The main goal...

  12. Business process management

    OpenAIRE

    Hantry F.; Papazoglou M.; Van Den Heuvel W.-J.; Haque R.; Whelan E.; Carroll N.; Karastoyanova D.; Leymann F.; Nikolaou C.; Lammersdorf W.

    2009-01-01

    Background. A feature of teaching IT-cycle subjects at economic universities is that the technologies which are needed to teach students are constantly updated. This relates to the fact that the market of IT-products is rapidly changing. At the moment a new class of information systems Business Process Management Suite (BPMS) has appeared. It allows to manage business processes at a whole new level. Nowadays BPM is becoming more popular, and that is why students of economic universities shoul...

  13. Differentially Private Gaussian Processes

    OpenAIRE

    Smith, Michael Thomas; Zwiessele, Max; Lawrence, Neil D.

    2016-01-01

    A major challenge for machine learning is increasing the availability of data while respecting the privacy of individuals. Differential privacy is a framework which allows algorithms to have provable privacy guarantees. Gaussian processes are a widely used approach for dealing with uncertainty in functions. This paper explores differentially private mechanisms for Gaussian processes. We compare binning and adding noise before regression with adding noise post-regression. For the former we dev...

  14. Resolved Photon Processes

    OpenAIRE

    Godbole, RM

    1998-01-01

    After giving a very brief introduction to the resolved photon processes, I will summarise the latest experimental information from HERA, on resolved photon contribution to large pt jet production as well as to direct photon production. I will point out the interesting role that resolved photon processes can play in increasing our understanding of the dynamics of the Quarkonium production. I will then discuss the newer information on the parton content of virtual photons as well as the kt dist...

  15. The Aluminum Smelting Process

    OpenAIRE

    Kvande, Halvor

    2014-01-01

    This introduction to the industrial primary aluminum production process presents a short description of the electrolytic reduction technology, the history of aluminum, and the importance of this metal and its production process to modern society. Aluminum's special qualities have enabled advances in technologies coupled with energy and cost savings. Aircraft capabilities have been greatly enhanced, and increases in size and capacity are made possible by advances in aluminum technology. The me...

  16. Image Processing Software

    Science.gov (United States)

    1992-01-01

    To convert raw data into environmental products, the National Weather Service and other organizations use the Global 9000 image processing system marketed by Global Imaging, Inc. The company's GAE software package is an enhanced version of the TAE, developed by Goddard Space Flight Center to support remote sensing and image processing applications. The system can be operated in three modes and is combined with HP Apollo workstation hardware.

  17. Novel food processing techniques

    OpenAIRE

    Vesna Lelas

    2006-01-01

    Recently, a lot of investigations have been focused on development of the novel mild food processing techniques with the aim to obtain the high quality food products. It is presumed also that they could substitute some of the traditional processes in the food industry. The investigations are primarily directed to usage of high hydrostatic pressure, ultrasound, tribomechanical micronization, microwaves, pulsed electrical fields. The results of the scientific researches refer to the fact that a...

  18. Apple Image Processing Educator

    Science.gov (United States)

    Gunther, F. J.

    1981-01-01

    A software system design is proposed and demonstrated with pilot-project software. The system permits the Apple II microcomputer to be used for personalized computer-assisted instruction in the digital image processing of LANDSAT images. The programs provide data input, menu selection, graphic and hard-copy displays, and both general and detailed instructions. The pilot-project results are considered to be successful indicators of the capabilities and limits of microcomputers for digital image processing education.

  19. Compactifications for Dual Processes

    OpenAIRE

    Glover, Joseph

    1980-01-01

    We develop a general theory of duality for Markov processes satisfying Meyer's hypothesis (L) and possessing an excessive reference measure. We make use of a compactification introduced by Walsh which allows a right process and its moderate dual to have strong Markov versions on an enlarged state space. The representation theory for potentials of additive functionals due to Revuz and Sharpe can be extended to this setting. Using this theory, we show that the conatural additive functionals int...

  20. Electron-attachment processes

    International Nuclear Information System (INIS)

    Topics covered include: (1) modes of production of negative ions, (2) techniques for the study of electron attachment processes, (3) dissociative electron attachment to ground-state molecules, (4) dissociative electron attachment to hot molecules (effects of temperature on dissociative electron attachment), (5) molecular parent negative ions, and (6) negative ions formed by ion-pair processes and by collisions of molecules with ground state and Rydberg atoms

  1. Cognitive Processes in Writing

    Institute of Scientific and Technical Information of China (English)

    李莹

    2009-01-01

    Writing has become one of important topic to discuss in the new age.Its theories could be generally learnt,but its nature needs to handle in specific contents.In another words,every one who can write must generate his/her thinking or cognitive processes.Because writing thinking is to do meaningful activities,how to solove writing problems could be managed through cognitive process.

  2. Biomedical signal processing

    CERN Document Server

    Akay, Metin

    1994-01-01

    Sophisticated techniques for signal processing are now available to the biomedical specialist! Written in an easy-to-read, straightforward style, Biomedical Signal Processing presents techniques to eliminate background noise, enhance signal detection, and analyze computer data, making results easy to comprehend and apply. In addition to examining techniques for electrical signal analysis, filtering, and transforms, the author supplies an extensive appendix with several computer programs that demonstrate techniques presented in the text.

  3. Dynamic business process management

    OpenAIRE

    Soroush, Kahkesh

    2012-01-01

    Open e-PRIOR is an open source e-Procurement system developed by the European Commission. Currently Open e-PRIOR system is handling simple choreographies based on the exchange of a single main object. However, these different objects are related and part of larger business process and by handling the objects separately the full overview is lost. Business process management (BPM) helps organizations to understand and maintain complicated business workflow. This master thesis focuses on how ...

  4. Signal processing for hybridization

    OpenAIRE

    Caceres Duran, Mauricio A.; Closas Gómez, Pau; Falletti, Emanuela; Fernández Prades, Carlos; Nájar Martón, Montserrat; Sottile, Francesco

    2011-01-01

    This chapter presents several signal processing strategies to combine together, in a seamless estimation process, position-related measurements coming from different technologies and/or systems (e.g., TOA and TDOA measurements in terrestrial networks, TOA and RSS measurements, or even satellite and terrestrial systems, or satellite and inertial navigation systems). This approach, generally indicated as “hybridization”, promises to provide better accuracy with respect to its stand-alone counte...

  5. Language and Speech Processing

    CERN Document Server

    Mariani, Joseph

    2008-01-01

    Speech processing addresses various scientific and technological areas. It includes speech analysis and variable rate coding, in order to store or transmit speech. It also covers speech synthesis, especially from text, speech recognition, including speaker and language identification, and spoken language understanding. This book covers the following topics: how to realize speech production and perception systems, how to synthesize and understand speech using state-of-the-art methods in signal processing, pattern recognition, stochastic modelling computational linguistics and human factor studi

  6. Adaptive Mobile Work Processes

    OpenAIRE

    Hauso, Frode; Røed, Øivind

    2005-01-01

    Systems that efficiently provide support for adaptive work processes in a mobile environment do not exist according to our knowledge. Such systems would increase efficiency and safety in environments where work is inherently mobile, ad-hoc, and requires input from a set of heterogeneous sources. Traditional work support systems are normally not capable of dynamic change and plans must be made before work is started. This conflicts with most work processes, which are dynamic and where plans ca...

  7. Solar Flares: Magnetohydrodynamic Processes

    OpenAIRE

    Kazunari Shibata; Tetsuya Magara

    2011-01-01

    This paper outlines the current understanding of solar flares, mainly focused on magnetohydrodynamic (MHD) processes responsible for producing a flare. Observations show that flares are one of the most explosive phenomena in the atmosphere of the Sun, releasing a huge amount of energy up to about 10^32 erg on the timescale of hours. Flares involve the heating of plasma, mass ejection, and particle acceleration that generates high-energy particles. The key physical processes for producing a fl...

  8. Granger Independent Martingale Processes

    OpenAIRE

    Cherubini, Umberto; Gobbi, Fabio; Mulinacci, Sabrina; Romagnoli, Silvia

    2016-01-01

    We introduce a new class of processes for the evaluation of multivariate equity derivatives. The proposed setting is well suited for the application of the standard copula function theory to processes, rather than variables, and easily enables to enforce the martingale pricing requirement. The martingale condition is imposed in a general multidimensional Markov setting to which we only add the restriction of no-Granger-causality of the increments (Granger-independent increments). We call this...

  9. Radiopharmaceutical drug review process

    International Nuclear Information System (INIS)

    To ensure proper radioactive drug use (such as quality, diagnostic improvement, and minimal radioactive exposure), the Food and Drug Administration evaluates new drugs with respect to safety, effectiveness, and accuracy and adequacy of the labeling. The IND or NDA process is used for this purpose. A brief description of the process, including the Chemical Classification System and the therapeutic potential classification, is presented as it applies to radiopharmaceuticals. Also, the status of the IND or NDA review of radiopharmaceuticals is given

  10. Catalytic Processes in Biorefinery

    OpenAIRE

    Vitiello, Rosa

    2015-01-01

    The biorefinery is a system that uses as feedstocks biomasses and recover from these energy, fuel and chemicals. There are many processes considered in the biorefinery system, but in this thesis the biorefinery that uses as feedstock oil, in particular dedicated crops and waste vegetable oils were considered. In the first part of this thesis the biodiesel production process was studied. One possible route to produce biodiesel from waste oils (carachetrized by high concentrations of Fr...

  11. Reward Processing in Autism

    OpenAIRE

    Scott-Van Zeeland, Ashley A.; DAPRETTO, MIRELLA; Ghahremani, Dara G.; Poldrack, Russell A.; Bookheimer, Susan Y.

    2010-01-01

    The social motivation hypothesis of autism posits that infants with autism do not experience social stimuli as rewarding, thereby leading to a cascade of potentially negative consequences for later development. While possible downstream effects of this hypothesis such as altered face and voice processing have been examined, there has not been a direct investigation of social reward processing in autism. Here we use functional magnetic resonance imaging to examine social and monetary rewarded ...

  12. Integral Politics as Process

    OpenAIRE

    Tom Atlee

    2010-01-01

    Using the definition proposed here, integral politics can be a process of integrating diverse perspectives into wholesome guidance for a community or society. Characteristics that follow from this definition have ramifications for understanding what such political processes involve. Politics becomes integral as it transcends partisan battle and nurtures generative conversation toward the common good. Problems, conflicts and crises become opportunities for new (or renewed) social coherence. Co...

  13. Synroc processing options

    International Nuclear Information System (INIS)

    Synroc is a titanate-based ceramic material currently being developed for immobilizing high-level nuclear reactor wastes in solid form. Synroc D is a unique variation of Synroc. It can contain the high-level defense wastes, particularly those in storage at the Savannah River Plant. In this report, we review the early development of the initial Synroc process, discuss modification and other options that simplify it overall, and recommend the future direction of research and development in the processing area. A reference Synroc process is described briefly and contrasted with the Savannah River Laboratory glass-based reference case. Preliminary engineering layouts show Synroc to be a more complex processing operation and, thus, more expensive than the glass-based process. However, we believe that simplifications, which will significantly reduce the cost difference, are possible. Further research and development will continue in the areas of slurry processing, fluidized bed calcination, and mineralization. This last will use sintering, hot uniaxial pressing, or hot isostatic pressing

  14. Helium process cycle

    Science.gov (United States)

    Ganni, Venkatarao

    2007-10-09

    A unique process cycle and apparatus design separates the consumer (cryogenic) load return flow from most of the recycle return flow of a refrigerator and/or liquefier process cycle. The refrigerator and/or liquefier process recycle return flow is recompressed by a multi-stage compressor set and the consumer load return flow is recompressed by an independent consumer load compressor set that maintains a desirable constant suction pressure using a consumer load bypass control valve and the consumer load return pressure control valve that controls the consumer load compressor's suction pressure. The discharge pressure of this consumer load compressor is thereby allowed to float at the intermediate pressure in between the first and second stage recycle compressor sets. Utilizing the unique gas management valve regulation, the unique process cycle and apparatus design in which the consumer load return flow is separate from the recycle return flow, the pressure ratios of each recycle compressor stage and all main pressures associated with the recycle return flow are allowed to vary naturally, thus providing a naturally regulated and balanced floating pressure process cycle that maintains optimal efficiency at design and off-design process cycle capacity and conditions automatically.

  15. Helium process cycle

    Science.gov (United States)

    Ganni, Venkatarao

    2008-08-12

    A unique process cycle and apparatus design separates the consumer (cryogenic) load return flow from most of the recycle return flow of a refrigerator and/or liquefier process cycle. The refrigerator and/or liquefier process recycle return flow is recompressed by a multi-stage compressor set and the consumer load return flow is recompressed by an independent consumer load compressor set that maintains a desirable constant suction pressure using a consumer load bypass control valve and the consumer load return pressure control valve that controls the consumer load compressor's suction pressure. The discharge pressure of this consumer load compressor is thereby allowed to float at the intermediate pressure in between the first and second stage recycle compressor sets. Utilizing the unique gas management valve regulation, the unique process cycle and apparatus design in which the consumer load return flow is separate from the recycle return flow, the pressure ratios of each recycle compressor stage and all main pressures associated with the recycle return flow are allowed to vary naturally, thus providing a naturally regulated and balanced floating pressure process cycle that maintains optimal efficiency at design and off-design process cycle capacity and conditions automatically.

  16. Process Correlation Analysis Model for Process Improvement Identification

    OpenAIRE

    Su-jin Choi; Dae-Kyoo Kim; Sooyong Park

    2014-01-01

    Software process improvement aims at improving the development process of software systems. It is initiated by process assessment identifying strengths and weaknesses and based on the findings, improvement plans are developed. In general, a process reference model (e.g., CMMI) is used throughout the process of software process improvement as the base. CMMI defines a set of process areas involved in software development and what to be carried out in process areas in terms of goals and practice...

  17. Radiation processing of polysaccharides

    International Nuclear Information System (INIS)

    Radiation processing is a very convenient tool for imparting desirable effects in polymeric materials and it has been an area of enormous interest in the last few decades. The success of radiation technology for processing of synthetic polymers can be attributed to two reasons namely, their ease of processing in various shapes and sizes, and secondly, most of these polymers undergo crosslinking reaction upon exposure to radiation. In recent years, natural polymers are being looked at with renewed interest because of their unique characteristics, such as inherent biocompatibility, biodegradability and easy availability. Traditionally, the commercial exploitation of natural polymers like carrageenans, alginates or starch etc. has been based, to a large extent, on empirical knowledge. But now, the applications of natural polymers are being sought in knowledge - demanding areas such as pharmacy and biotechnology, which is acting as a locomotive for further scientific research in their structure-function relationship. Selected success stories concerning radiation processed natural polymers and application of their derivatives in the health care products industries and agriculture are reported. This publication will be of interest to individuals at nuclear institutions worldwide that have programmes of R and D and applications in radiation processing technologies. New developments in radiation processing of polymers and other natural raw materials give insight into converting them into useful products for every day life, human health and environmental remediation. The book will also be of interest to other field specialists, readers including managers and decision makers in industry (health care, food and agriculture) helping them to understand the important role of radiation processing technology in polysaccharides

  18. Advanced materials processing

    International Nuclear Information System (INIS)

    Advanced materials will require improved processing methods due to high melting points, low toughness or ductility values, high reactivity with air or ceramics and typically complex crystal structures with significant anisotropy in flow and/or fracture stress. Materials for structural applications at elevated temperature in critical systems will require processing with a high degree of control. This requires an improved understanding of the relationship between process variables and microstructure to enable control systems to achieve consistently high quality. One avenue to the required level of understanding is computer simulation. Past attempts to do process modeling have been hampered by incomplete data regarding thermophysical or mechanical material behavior. Some of the required data can be calculated. Due to the advances in software and hardware, accuracy and costs are in the realm of acquiring experimental data. Such calculations can, for example, be done at an atomic level to compute lattice energy, fault energies, density of states and charge densities. These can lead to fundamental information about the competition between slip and fracture, anisotropy of bond strength (and therefore cleavage strength), cohesive strength, adhesive strength, elastic modulus, thermal expansion and possibly other quantities which are difficult (and therefore expensive to measure). Some of these quantities can be fed into a process model. It is probable that temperature dependencies can be derived numerically as well. Examples are given of the beginnings of such an approach for Ni3Al and MoSi2. Solidification problems are examples of the state-of-the-art process modeling and adequately demonstrate the need for extensive input data. Such processes can be monitored in terms of interfacial position vs. time, cooling rate and thermal gradient

  19. Novel food processing techniques

    Directory of Open Access Journals (Sweden)

    Vesna Lelas

    2006-12-01

    Full Text Available Recently, a lot of investigations have been focused on development of the novel mild food processing techniques with the aim to obtain the high quality food products. It is presumed also that they could substitute some of the traditional processes in the food industry. The investigations are primarily directed to usage of high hydrostatic pressure, ultrasound, tribomechanical micronization, microwaves, pulsed electrical fields. The results of the scientific researches refer to the fact that application of some of these processes in particular food industry can result in lots of benefits. A significant energy savings, shortening of process duration, mild thermal conditions, food products with better sensory characteristics and with higher nutritional values can be achieved. As some of these techniques act also on the molecular level changing the conformation, structure and electrical potential of organic as well as inorganic materials, the improvement of some functional properties of these components may occur. Common characteristics of all of these techniques are treatment at ambient or insignificant higher temperatures and short time of processing (1 to 10 minutes. High hydrostatic pressure applied to various foodstuffs can destroy some microorganisms, successfully modify molecule conformation and consequently improve functional properties of foods. At the same time it acts positively on the food products intend for freezing. Tribomechanical treatment causes micronization of various solid materials that results in nanoparticles and changes in structure and electrical potential of molecules. Therefore, the significant improvement of some rheological and functional properties of materials occurred. Ultrasound treatment proved to be potentially very successful technique of food processing. It can be used as a pretreatment to drying (decreases drying time and improves functional properties of food, as extraction process of various components

  20. 21 CFR 1271.220 - Processing and process controls.

    Science.gov (United States)

    2010-04-01

    ... mixed in a single receptacle) during manufacturing. (c) In-process control and testing. You must ensure... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Processing and process controls. 1271.220 Section... process controls. (a) General. If you are an establishment that processes HCT/Ps, you must process...

  1. Carbon dioxide reducing processes; Koldioxidreducerande processer

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Fredrik

    1999-12-01

    This thesis discusses different technologies to reduce or eliminate the carbon dioxide emissions, when a fossil fuel is used for energy production. Emission reduction can be accomplished by separating the carbon dioxide for storage or reuse. There are three different ways of doing the separation. The carbon dioxide can be separated before the combustion, the process can be designed so that the carbon dioxide can be separated without any energy consumption and costly systems or the carbon dioxide can be separated from the flue gas stream. Two different concepts of separating the carbon dioxide from a combined cycle are compared, from the performance and the economical point of view, with a standard natural gas fired combined cycle where no attempts are made to reduce the carbon dioxide emissions. One concept is to use absorption technologies to separate the carbon dioxide from the flue gas stream. The other concept is based on a semi-closed gas turbine cycle using carbon dioxide as working fluid and combustion with pure oxygen, generated in an air-separating unit. The calculations show that the efficiency (power) drop is smaller for the first concept than for the second, 8.7 % points compared to 13.7 % points, when power is produced. When both heat and power are produced, the relation concerning the efficiency (power) remains. Regarding the overall efficiency (heat and power) the opposite relation is present. A possible carbon dioxide tax must exceed 0.21 SEK/kg CO{sub 2} for it to be profitable to separate carbon dioxide with any of these technologies.

  2. VLSI signal processing technology

    CERN Document Server

    Swartzlander, Earl

    1994-01-01

    This book is the first in a set of forthcoming books focussed on state-of-the-art development in the VLSI Signal Processing area. It is a response to the tremendous research activities taking place in that field. These activities have been driven by two factors: the dramatic increase in demand for high speed signal processing, especially in consumer elec­ tronics, and the evolving microelectronic technologies. The available technology has always been one of the main factors in determining al­ gorithms, architectures, and design strategies to be followed. With every new technology, signal processing systems go through many changes in concepts, design methods, and implementation. The goal of this book is to introduce the reader to the main features of VLSI Signal Processing and the ongoing developments in this area. The focus of this book is on: • Current developments in Digital Signal Processing (DSP) pro­ cessors and architectures - several examples and case studies of existing DSP chips are discussed in...

  3. GELATIN DRYING PROCESS

    Directory of Open Access Journals (Sweden)

    E.A. Silva

    2001-12-01

    Full Text Available In one of the stages of the gelatin production process, a highly concentrated solution of gel is cooled and extruded to form gelatin noodles, which are then laid on a drying belt. Gelatin is a molecular colloid that is not porous under these drying conditions, and as a consequence, water migration occurs solely by diffusive processes. To achieve a commercial standard of dryness, the dependence of the diffusion coefficient as a function of temperature is used. This set of circumstances favors the appearance of sharp concentration gradients inside the gel. In a numerical simulation of the drying process these characteristics create difficult conditions for use of the traditional methods for solution of time-dependent partial differential equation models. This paper evaluates an implementation of the boundary element method to determine surface conditions of the gelatin particle.

  4. Business Process Requirement Engineering

    Directory of Open Access Journals (Sweden)

    Atsa Etoundi Roger,

    2010-12-01

    Full Text Available Requirement engineering is as an increasingly important discipline for supporting business process and workflow modeling, as these are designed to satisfy diverse customer needs, and increase the productivity of enterprise. Moreover, most customers hesitate to adopt a given product or service if the added value is not conformed to their desires. Dealing with customers, with a wide range of perspective, within an enterprise, is very complex. These perspectives are grounded in differences in skills, responsibility, knowledge and expertise of stakeholders. This holds more in the domain of business processes and workflows where the satisfaction of the customers is the must if these enterprises wish to deal with the pressure of the network economy. Based on the requirement engineering, we present in this paper an integration of RE approach in the modeling of business process and workflows. (Abstract

  5. s-process chronometers

    International Nuclear Information System (INIS)

    The radionuclei 40K, 81Kr, 87Rb, 93Zr, 107Pd, 147Sm, 176Lu and 205Pb are built up totally or partially by the s-process. Due to their long half life they are potential chronometers for the age and the development of the s-process. The usefulness of the various nuclei is discussed. For the determination of the mean age of the s-process synthesis and with it the age of the galaxy, 176Lu is best suited. It is demonstrated that this age can be calculated solely from measured cross section and abundance ratios. Various effects which can limit the usefulness of 176Lu as a clock are discussed. (orig.)

  6. COTS software selection process.

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, William M. (Strike Wire Technologies, Louisville, CO); Lin, Han Wei; McClelland, Kelly (U.S. Security Associates, Livermore, CA); Ullrich, Rebecca Ann; Khanjenoori, Soheil; Dalton, Karen; Lai, Anh Tri; Kuca, Michal; Pacheco, Sandra; Shaffer-Gant, Jessica

    2006-05-01

    Today's need for rapid software development has generated a great interest in employing Commercial-Off-The-Shelf (COTS) software products as a way of managing cost, developing time, and effort. With an abundance of COTS software packages to choose from, the problem now is how to systematically evaluate, rank, and select a COTS product that best meets the software project requirements and at the same time can leverage off the current corporate information technology architectural environment. This paper describes a systematic process for decision support in evaluating and ranking COTS software. Performed right after the requirements analysis, this process provides the evaluators with more concise, structural, and step-by-step activities for determining the best COTS software product with manageable risk. In addition, the process is presented in phases that are flexible to allow for customization or tailoring to meet various projects' requirements.

  7. Generalised Wishart Processes

    CERN Document Server

    Wilson, Andrew Gordon

    2011-01-01

    We introduce a stochastic process with Wishart marginals: the generalised Wishart process (GWP). It is a collection of positive semi-definite random matrices indexed by any arbitrary dependent variable. We use it to model dynamic (e.g. time varying) covariance matrices. Unlike existing models, it can capture a diverse class of covariance structures, it can easily handle missing data, the dependent variable can readily include covariates other than time, and it scales well with dimension; there is no need for free parameters, and optional parameters are easy to interpret. We describe how to construct the GWP, introduce general procedures for inference and predictions, and show that it outperforms its main competitor, multivariate GARCH, even on financial data that especially suits GARCH. We also show how to predict the mean of a multivariate process while accounting for dynamic correlations.

  8. Foundations of signal processing

    CERN Document Server

    Vetterli, Martin; Goyal, Vivek K

    2014-01-01

    This comprehensive and engaging textbook introduces the basic principles and techniques of signal processing, from the fundamental ideas of signals and systems theory to real-world applications. Students are introduced to the powerful foundations of modern signal processing, including the basic geometry of Hilbert space, the mathematics of Fourier transforms, and essentials of sampling, interpolation, approximation and compression. The authors discuss real-world issues and hurdles to using these tools, and ways of adapting them to overcome problems of finiteness and localisation, the limitations of uncertainty and computational costs. Standard engineering notation is used throughout, making mathematical examples easy for students to follow, understand and apply. It includes over 150 homework problems and over 180 worked examples, specifically designed to test and expand students' understanding of the fundamentals of signal processing, and is accompanied by extensive online materials designed to aid learning, ...

  9. Modern coating processes

    International Nuclear Information System (INIS)

    Articles collected in this volume explain both the present state of technique and current developments and problems in the environment of the following coating processes: - Hardfacing welding and soldering; - Thermal spraying; - Thin film technique (CVD, PVD); - Galvanising. Apart from basic representation of the conventional use of the different processes, both the new technological and material developments are to the fore. In this context, the purposeful post-treatment of coatings and the combination of different processes to achieve special coating properties should be mentioned. Examples of this show the hot isostatic pressing or laser melting of sprayed coatings, the simultaneous spraying and shot-blasting and the combination of galvanic and thin film techniques for the manufacture of hybrid systems. A further important group of subjects concerns the testing of various coatings. (orig.)

  10. Laser Processing and Chemistry

    CERN Document Server

    Bäuerle, Dieter

    2011-01-01

    This book gives an overview of the fundamentals and applications of laser-matter interactions, in particular with regard to laser material processing. Special attention is given to laser-induced physical and chemical processes at gas-solid, liquid-solid, and solid-solid interfaces. Starting with the background physics, the book proceeds to examine applications of lasers in “standard” laser machining and laser chemical processing (LCP), including the patterning, coating, and modification of material surfaces. This fourth edition has been enlarged to cover the rapid advances in the understanding of the dynamics of materials under the action of ultrashort laser pulses, and to include a number of new topics, in particular the increasing importance of lasers in various different fields of surface functionalizations and nanotechnology. In two additional chapters, recent developments in biotechnology, medicine, art conservation and restoration are summarized. Graduate students, physicists, chemists, engineers, a...

  11. Stochastic processes inference theory

    CERN Document Server

    Rao, Malempati M

    2014-01-01

    This is the revised and enlarged 2nd edition of the authors’ original text, which was intended to be a modest complement to Grenander's fundamental memoir on stochastic processes and related inference theory. The present volume gives a substantial account of regression analysis, both for stochastic processes and measures, and includes recent material on Ridge regression with some unexpected applications, for example in econometrics. The first three chapters can be used for a quarter or semester graduate course on inference on stochastic processes. The remaining chapters provide more advanced material on stochastic analysis suitable for graduate seminars and discussions, leading to dissertation or research work. In general, the book will be of interest to researchers in probability theory, mathematical statistics and electrical and information theory.

  12. Topological signal processing

    CERN Document Server

    Robinson, Michael

    2014-01-01

    Signal processing is the discipline of extracting information from collections of measurements. To be effective, the measurements must be organized and then filtered, detected, or transformed to expose the desired information.  Distortions caused by uncertainty, noise, and clutter degrade the performance of practical signal processing systems. In aggressively uncertain situations, the full truth about an underlying signal cannot be known.  This book develops the theory and practice of signal processing systems for these situations that extract useful, qualitative information using the mathematics of topology -- the study of spaces under continuous transformations.  Since the collection of continuous transformations is large and varied, tools which are topologically-motivated are automatically insensitive to substantial distortion. The target audience comprises practitioners as well as researchers, but the book may also be beneficial for graduate students.

  13. Cryogenic process simulation

    International Nuclear Information System (INIS)

    Combining accurate fluid property databases with a commercial equation-solving software package running on a desktop computer allows simulation of cryogenic processes without extensive computer programming. Computer simulation can be a powerful tool for process development or optimization. Most engineering simulations to date have required extensive programming skills in languages such as Fortran, Pascal, etc. Authors of simulation code have also usually been responsible for choosing and writing the particular solution algorithm. This paper describes a method of simulating cryogenic processes with a commercial software package on a desktop personal computer that does not require these traditional programming tasks. Applications include modeling of cryogenic refrigerators, heat exchangers, vapor-cooled power leads, vapor pressure thermometers, and various other engineering problems

  14. Lapis SOI Pixel Process

    CERN Document Server

    Okihara, Masao; Miura, Noriyuki; Kuriyama, Naoya; Nagatomo, Yoshiki

    2015-01-01

    0.2 um fully-depleted SOI technology has been developed a for X-ray pixel detectors. To improve the detector performance, some advanced process technologies are developing continuously. To utilize the high resistivity FZ-SOI, slow ramp up and ramp down recipes are applied for the thermal processes in both of SOI wafer fabrication and pixel detector process. The suitable backside treatment is also applied to prevent increase of leakage current at backside damaged layer in the case of full depletion of substrate. Large detector chip about 66mm width and 30mm height can be obtained by stitching exposure technique for large detector chip. To improve cross-talk and radiation tolerance, the nested well structure and double- SOI wafer are now under investigation for advanced pixel structure.

  15. Quantum independent increment processes

    CERN Document Server

    Franz, Uwe

    2005-01-01

    This volume is the first of two volumes containing the revised and completed notes lectures given at the school "Quantum Independent Increment Processes: Structure and Applications to Physics". This school was held at the Alfried-Krupp-Wissenschaftskolleg in Greifswald during the period March 9 – 22, 2003, and supported by the Volkswagen Foundation. The school gave an introduction to current research on quantum independent increment processes aimed at graduate students and non-specialists working in classical and quantum probability, operator algebras, and mathematical physics. The present first volume contains the following lectures: "Lévy Processes in Euclidean Spaces and Groups" by David Applebaum, "Locally Compact Quantum Groups" by Johan Kustermans, "Quantum Stochastic Analysis" by J. Martin Lindsay, and "Dilations, Cocycles and Product Systems" by B.V. Rajarama Bhat.

  16. Beyond the search process

    DEFF Research Database (Denmark)

    Hyldegård, Jette

    2009-01-01

    concluded that the ISP-model does not fully comply with group members' problem solving process and the involved information seeking behavior. Further, complex academic problem solving seems to be even more complex when it is performed in a group based setting. The study contributes with a new conceptual......This paper reports on the findings from a longitudinal case study exploring Kuhlthau's information search process (ISP)-model in a group based academic setting. The research focus is on group members' activities and cognitive and emotional experiences during the task process of writing an...... assignment. It is investigated if group members' information behavior differ from the individual information seeker in the ISP-model and to what extent this behavior is influenced by contextual (work task) and social (group work) factors. Three groups of LIS students were followed during a 14 weeks period in...

  17. Orchestrator Telemetry Processing Pipeline

    Science.gov (United States)

    Powell, Mark; Mittman, David; Joswig, Joseph; Crockett, Thomas; Norris, Jeffrey

    2008-01-01

    Orchestrator is a software application infrastructure for telemetry monitoring, logging, processing, and distribution. The architecture has been applied to support operations of a variety of planetary rovers. Built in Java with the Eclipse Rich Client Platform, Orchestrator can run on most commonly used operating systems. The pipeline supports configurable parallel processing that can significantly reduce the time needed to process a large volume of data products. Processors in the pipeline implement a simple Java interface and declare their required input from upstream processors. Orchestrator is programmatically constructed by specifying a list of Java processor classes that are initiated at runtime to form the pipeline. Input dependencies are checked at runtime. Fault tolerance can be configured to attempt continuation of processing in the event of an error or failed input dependency if possible, or to abort further processing when an error is detected. This innovation also provides support for Java Message Service broadcasts of telemetry objects to clients and provides a file system and relational database logging of telemetry. Orchestrator supports remote monitoring and control of the pipeline using browser-based JMX controls and provides several integration paths for pre-compiled legacy data processors. At the time of this reporting, the Orchestrator architecture has been used by four NASA customers to build telemetry pipelines to support field operations. Example applications include high-volume stereo image capture and processing, simultaneous data monitoring and logging from multiple vehicles. Example telemetry processors used in field test operations support include vehicle position, attitude, articulation, GPS location, power, and stereo images.

  18. NTP comparison process

    Science.gov (United States)

    Corban, Robert

    The systems engineering process for the concept definition phase of the program involves requirements definition, system definition, and consistent concept definition. The requirements definition process involves obtaining a complete understanding of the system requirements based on customer needs, mission scenarios, and nuclear thermal propulsion (NTP) operating characteristics. A system functional analysis is performed to provide a comprehensive traceability and verification of top-level requirements down to detailed system specifications and provides significant insight into the measures of system effectiveness to be utilized in system evaluation. The second key element in the process is the definition of system concepts to meet the requirements. This part of the process involves engine system and reactor contractor teams to develop alternative NTP system concepts that can be evaluated against specific attributes, as well as a reference configuration against which to compare system benefits and merits. Quality function deployment (QFD), as an excellent tool within Total Quality Management (TQM) techniques, can provide the required structure and provide a link to the voice of the customer in establishing critical system qualities and their relationships. The third element of the process is the consistent performance comparison. The comparison process involves validating developed concept data and quantifying system merits through analysis, computer modeling, simulation, and rapid prototyping of the proposed high risk NTP subsystems. The maximum amount possible of quantitative data will be developed and/or validated to be utilized in the QFD evaluation matrix. If upon evaluation of a new concept or its associated subsystems determine to have substantial merit, those features will be incorporated into the reference configuration for subsequent system definition and comparison efforts.

  19. Process Damping Parameters

    International Nuclear Information System (INIS)

    The phenomenon of process damping as a stabilising effect in milling has been encountered by machinists since milling and turning began. It is of great importance when milling aerospace alloys where maximum surface speed is limited by excessive tool wear and high speed stability lobes cannot be attained. Much of the established research into regenerative chatter and chatter avoidance has focussed on stability lobe theory with different analytical and time domain models developed to expand on the theory first developed by Trusty and Tobias. Process damping is a stabilising effect that occurs when the surface speed is low relative to the dominant natural frequency of the system and has been less successfully modelled and understood. Process damping is believed to be influenced by the interference of the relief face of the cutting tool with the waveform traced on the cut surface, with material properties and the relief geometry of the tool believed to be key factors governing performance. This study combines experimental trials with Finite Element (FE) simulation in an attempt to identify and understand the key factors influencing process damping performance in titanium milling. Rake angle, relief angle and chip thickness are the variables considered experimentally with the FE study looking at average radial and tangential forces and surface compressive stress. For the experimental study a technique is developed to identify the critical process damping wavelength as a means of measuring process damping performance. For the range of parameters studied, chip thickness is found to be the dominant factor with maximum stable parameters increased by a factor of 17 in the best case. Within the range studied, relief angle was found to have a lesser effect than expected whilst rake angle had an influence.

  20. AERONET Version 3 processing

    Science.gov (United States)

    Holben, B. N.; Slutsker, I.; Giles, D. M.; Eck, T. F.; Smirnov, A.; Sinyuk, A.; Schafer, J.; Rodriguez, J.

    2014-12-01

    The Aerosol Robotic Network (AERONET) database has evolved in measurement accuracy, data quality products, availability to the scientific community over the course of 21 years with the support of NASA, PHOTONS and all federated partners. This evolution is periodically manifested as a new data version release by carefully reprocessing the entire database with the most current algorithms that fundamentally change the database and ultimately the data products used by the community. The newest processing, Version 3, will be released in 2015 after the entire database is reprocessed and real-time data processing becomes operational. All V 3 algorithms have been developed, individually vetted and represent four main categories: aerosol optical depth (AOD) processing, inversion processing, database management and new products. The primary trigger for release of V 3 lies with cloud screening of the direct sun observations and computation of AOD that will fundamentally change all data available for analysis and all subsequent retrieval products. This presentation will illustrate the innovative approach used for cloud screening and assesses the elements of V3 AOD relative to the current version. We will also present the advances in the inversion product processing with emphasis on the random and systematic uncertainty estimates. This processing will be applied to the new hybrid measurement scenario intended to provide inversion retrievals for all solar zenith angles. We will introduce automatic quality assurance criteria that will allow near real time quality assured aerosol products necessary for real time satellite and model validation and assimilation. Last we will introduce the new management structure that will improve access to the data database. The current version 2 will be supported for at least two years after the initial release of V3 to maintain continuity for on going investigations.

  1. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process......This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...

  2. Stochastic conditional intensity processes

    DEFF Research Database (Denmark)

    Bauwens, Luc; Hautsch, Nikolaus

    2006-01-01

    model allows for a wide range of (cross-)autocorrelation structures in multivariate point processes. The model is estimated by simulated maximum likelihood (SML) using the efficient importance sampling (EIS) technique. By modeling price intensities based on NYSE trading, we provide significant evidence......In this article, we introduce the so-called stochastic conditional intensity (SCI) model by extending Russell’s (1999) autoregressive conditional intensity (ACI) model by a latent common dynamic factor that jointly drives the individual intensity components. We show by simulations that the proposed...... for a joint latent factor and show that its inclusion allows for an improved and more parsimonious specification of the multivariate intensity process...

  3. Radiation processed polysaccharide products

    International Nuclear Information System (INIS)

    Radiation crosslinking, degradation and grafting techniques for modification of polymeric materials including natural polysaccharides have been providing many unique products. In this communication, typical products from radiation processed polysaccharides particularly plant growth promoter from alginate, plant protector and elicitor from chitosan, super water absorbent containing starch, hydrogel sheet containing carrageenan/CM-chitosan as burn wound dressing, metal ion adsorbent from partially deacetylated chitin were described. The procedures for producing those above products were also outlined. Future development works on radiation processing of polysaccharides were briefly presented. (author)

  4. Hard exclusive QCD processes

    Energy Technology Data Exchange (ETDEWEB)

    Kugler, W.

    2007-01-15

    Hard exclusive processes in high energy electron proton scattering offer the opportunity to get access to a new generation of parton distributions, the so-called generalized parton distributions (GPDs). This functions provide more detailed informations about the structure of the nucleon than the usual PDFs obtained from DIS. In this work we present a detailed analysis of exclusive processes, especially of hard exclusive meson production. We investigated the influence of exclusive produced mesons on the semi-inclusive production of mesons at fixed target experiments like HERMES. Further we give a detailed analysis of higher order corrections (NLO) for the exclusive production of mesons in a very broad range of kinematics. (orig.)

  5. The Recruitment Process:

    DEFF Research Database (Denmark)

    Holm, Anna

    The aim of this research was to determine whether the introduction of e-recruitment has an impact on the process and underlying tasks, subtasks and activities of recruitment. Three large organizations with well-established e-recruitment practices were included in the study. The three case studies......, which were carried out in Denmark in 2008-2009 using qualitative research methods, revealed changes in the sequence, divisibility and repetitiveness of a number of recruitment tasks and subtasks. The new recruitment process design was identified and presented in the paper. The study concluded that the...

  6. Image Processing System

    Science.gov (United States)

    1986-01-01

    Mallinckrodt Institute of Radiology (MIR) is using a digital image processing system which employs NASA-developed technology. MIR's computer system is the largest radiology system in the world. It is used in diagnostic imaging. Blood vessels are injected with x-ray dye, and the images which are produced indicate whether arteries are hardened or blocked. A computer program developed by Jet Propulsion Laboratory known as Mini-VICAR/IBIS was supplied to MIR by COSMIC. The program provides the basis for developing the computer imaging routines for data processing, contrast enhancement and picture display.

  7. Advanced Polymer Processing Facility

    Energy Technology Data Exchange (ETDEWEB)

    Muenchausen, Ross E. [Los Alamos National Laboratory

    2012-07-25

    Some conclusions of this presentation are: (1) Radiation-assisted nanotechnology applications will continue to grow; (2) The APPF will provide a unique focus for radiolytic processing of nanomaterials in support of DOE-DP, other DOE and advanced manufacturing initiatives; (3) {gamma}, X-ray, e-beam and ion beam processing will increasingly be applied for 'green' manufacturing of nanomaterials and nanocomposites; and (4) Biomedical science and engineering may ultimately be the biggest application area for radiation-assisted nanotechnology development.

  8. Semantic and Process Interoperability

    Directory of Open Access Journals (Sweden)

    Félix Oscar Fernández Peña

    2010-05-01

    Full Text Available Knowledge management systems support education at different levels of the education. This is very important for the process in which the higher education of Cuba is involved. Structural transformations of teaching are focused on supporting the foundation of the information society in the country. This paper describes technical aspects of the designing of a model for the integration of multiple knowledgemanagement tools supporting teaching. The proposal is based on the definition of an ontology for the explicit formal description of the semantic of motivations of students and teachers in the learning process. Its target is to facilitate knowledge spreading.

  9. Reversible brazing process

    Science.gov (United States)

    Pierce, Jim D.; Stephens, John J.; Walker, Charles A.

    1999-01-01

    A method of reversibly brazing surfaces together. An interface is affixed to each surface. The interfaces can be affixed by processes such as mechanical joining, welding, or brazing. The two interfaces are then brazed together using a brazing process that does not defeat the surface to interface joint. Interfaces of materials such as Ni-200 can be affixed to metallic surfaces by welding or by brazing with a first braze alloy. The Ni-200 interfaces can then be brazed together using a second braze alloy. The second braze alloy can be chosen so that it minimally alters the properties of the interfaces to allow multiple braze, heat and disassemble, rebraze cycles.

  10. Biomedical Image Processing

    CERN Document Server

    Deserno, Thomas Martin

    2011-01-01

    In modern medicine, imaging is the most effective tool for diagnostics, treatment planning and therapy. Almost all modalities have went to directly digital acquisition techniques and processing of this image data have become an important option for health care in future. This book is written by a team of internationally recognized experts from all over the world. It provides a brief but complete overview on medical image processing and analysis highlighting recent advances that have been made in academics. Color figures are used extensively to illustrate the methods and help the reader to understand the complex topics.

  11. Solar industrial process heat

    Energy Technology Data Exchange (ETDEWEB)

    Lumsdaine, E.

    1981-04-01

    The aim of the assessment reported is to candidly examine the contribution that solar industrial process heat (SIPH) is realistically able to make in the near and long-term energy futures of the United States. The performance history of government and privately funded SIPH demonstration programs, 15 of which are briefly summarized, and the present status of SIPH technology are discussed. The technical and performance characteristics of solar industrial process heat plants and equipment are reviewed, as well as evaluating how the operating experience of over a dozen SIPH demonstration projects is influencing institutional acceptance and economoc projections. Implications for domestic energy policy and international implications are briefly discussed. (LEW)

  12. Algebraic Signal Processing Theory

    OpenAIRE

    Pueschel, Markus; Moura, Jose M. F.

    2006-01-01

    This paper presents an algebraic theory of linear signal processing. At the core of algebraic signal processing is the concept of a linear signal model defined as a triple (A, M, phi), where familiar concepts like the filter space and the signal space are cast as an algebra A and a module M, respectively, and phi generalizes the concept of the z-transform to bijective linear mappings from a vector space of, e.g., signal samples, into the module M. A signal model provides the structure for a p...

  13. Mutually Testing Processes

    OpenAIRE

    Bernardi, Giovanni; Hennessy, Matthew

    2015-01-01

    In the standard testing theory of DeNicola-Hennessy one process is considered to be a refinement of another if every test guaranteed by the former is also guaranteed by the latter. In the domain of web services this has been recast, with processes viewed as servers and tests as clients. In this way the standard refinement preorder between servers is determined by their ability to satisfy clients. But in this setting there is also a natural refinement preorder between clients, determined by th...

  14. Power plant process computer

    International Nuclear Information System (INIS)

    The concept of instrumentation and control in nuclear power plants incorporates the use of process computers for tasks which are on-line in respect to real-time requirements but not closed-loop in respect to closed-loop control. The general scope of tasks is: - alarm annunciation on CRT's - data logging - data recording for post trip reviews and plant behaviour analysis - nuclear data computation - graphic displays. Process computers are used additionally for dedicated tasks such as the aeroball measuring system, the turbine stress evaluator. Further applications are personal dose supervision and access monitoring. (orig.)

  15. Signal processing for microcalorimeters

    Science.gov (United States)

    Szymkowiak, A. E.; Kelley, R. L.; Moseley, S. H.; Stahle, C. K.

    1993-11-01

    Most of the power in the signals from microcalorimeters occurs at relatively low frequencies. At these frequencies, typical amplifiers will have significant amounts of 1/f noise. Our laboratory systems can also suffer from pickup at several harmonics of the AC power line, and from microphonic pickup at frequencies that vary with the configuration of the apparatus. We have developed some optimal signal processing techniques in order to construct the best possible estimates of our pulse heights in the presence of these non-ideal effects. In addition to a discussion of our laboratory systems, we present our plans for providing this kind of signal processing in flight experiments.

  16. Food irradiation processing

    International Nuclear Information System (INIS)

    An international symposium on food irradiation processing dealing with issues which affect the commercial introduction of the food irradiation process was held in Vienna in 1985. The symposium, which attracted close to 300 participants, was planned to interest not only scientists and food technologists, but also representatives of government agencies, the food industry, trade associations and consumer organizations. The symposium included a discussion of the technological and economic feasibility of applying ionizing energy for the preservation of food, and focused on the specific needs of developing countries. Separate abstracts were prepared for the various presentations at this meeting

  17. Thermal stir welding process

    Science.gov (United States)

    Ding, R. Jeffrey (Inventor)

    2012-01-01

    A welding method is provided for forming a weld joint between first and second elements of a workpiece. The method includes heating the first and second elements to form an interface of material in a plasticized or melted state interface between the elements. The interface material is then allowed to cool to a plasticized state if previously in a melted state. The interface material, while in the plasticized state, is then mixed, for example, using a grinding/extruding process, to remove any dendritic-type weld microstructures introduced into the interface material during the heating process.

  18. Statecharts Via Process Algebra

    Science.gov (United States)

    Luttgen, Gerald; vonderBeeck, Michael; Cleaveland, Rance

    1999-01-01

    Statecharts is a visual language for specifying the behavior of reactive systems. The Language extends finite-state machines with concepts of hierarchy, concurrency, and priority. Despite its popularity as a design notation for embedded system, precisely defining its semantics has proved extremely challenging. In this paper, a simple process algebra, called Statecharts Process Language (SPL), is presented, which is expressive enough for encoding Statecharts in a structure-preserving and semantic preserving manner. It is establish that the behavioral relation bisimulation, when applied to SPL, preserves Statecharts semantics

  19. Genomic signal processing

    CERN Document Server

    Shmulevich, Ilya

    2014-01-01

    Genomic signal processing (GSP) can be defined as the analysis, processing, and use of genomic signals to gain biological knowledge, and the translation of that knowledge into systems-based applications that can be used to diagnose and treat genetic diseases. Situated at the crossroads of engineering, biology, mathematics, statistics, and computer science, GSP requires the development of both nonlinear dynamical models that adequately represent genomic regulation, and diagnostic and therapeutic tools based on these models. This book facilitates these developments by providing rigorous mathema

  20. Exoplanet atmospheres physical processes

    CERN Document Server

    Seager, Sara

    2010-01-01

    Over the past twenty years, astronomers have identified hundreds of extrasolar planets--planets orbiting stars other than the sun. Recent research in this burgeoning field has made it possible to observe and measure the atmospheres of these exoplanets. This is the first textbook to describe the basic physical processes--including radiative transfer, molecular absorption, and chemical processes--common to all planetary atmospheres, as well as the transit, eclipse, and thermal phase variation observations that are unique to exoplanets. In each chapter, Sara Seager offers a conceptual introdu