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

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Álvaro Cuesta-Domínguez

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

Assessment of chromium biostabilization in contaminated soils using standard leaching and sequential extraction techniques

International Nuclear Information System (INIS)

Papassiopi, Nymphodora; Kontoyianni, Athina; Vaxevanidou, Katerina; Xenidis, Anthimos

2009-01-01

The iron reducing microorganism Desulfuromonas palmitatis was evaluated as potential biostabilization agent for the remediation of chromate contaminated soils. D. palmitatis were used for the treatment of soil samples artificially contaminated with Cr(VI) at two levels, i.e. 200 and 500 mg kg -1 . The efficiency of the treatment was evaluated by applying several standard extraction techniques on the soil samples before and after treatment, such as the EN12457 standard leaching test, the US EPA 3060A alkaline digestion method and the BCR sequential extraction procedure. The water soluble chromium as evaluated with the EN leaching test, was found to decrease after the biostabilization treatment from 13 to less than 0.5 mg kg -1 and from 120 to 5.6 mg kg -1 for the soil samples contaminated with 200 and 500 mg Cr(VI) per kg soil respectively. The BCR sequential extraction scheme, although not providing accurate estimates about the initial chromium speciation in contaminated soils, proved to be a useful tool for monitoring the relative changes in element partitioning, as a consequence of the stabilization treatment. After bioreduction, the percentage of chromium retained in the two least soluble BCR fractions, i.e. the 'oxidizable' and 'residual' fractions, increased from 54 and 73% to more than 96% in both soils

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

International Nuclear Information System (INIS)

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

1992-01-01

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

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

DEFF Research Database (Denmark)

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

2015-01-01

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

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

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Tasić Aleksandra M.

2016-01-01

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

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

DEFF Research Database (Denmark)

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

2010-01-01

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

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

Science.gov (United States)

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

2008-11-01

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

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

Science.gov (United States)

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

2017-01-31

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2005-01-01

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

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

OpenAIRE

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

1994-01-01

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

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

Science.gov (United States)

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

2017-03-02

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

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

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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.

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

Science.gov (United States)

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

2017-01-01

Approximately 15% of pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by gene expression similar to that of BCR-ABL1-positive disease and unfavorable prognosis. This BCR-ABL1-like subtype shows a high frequency of B-cell development gene aberrations and tyrosine kinase-activating lesions. To evaluate the clinical significance of tyrosine kinase gene fusions in children with BCP-ALL, we studied the frequency of recently identified tyrosine kinase fusions, associated genetic features, and prognosis in a representative Dutch/German cohort. We identified 14 tyrosine kinase fusions among 77 BCR-ABL1-like cases (18%) and none among 76 non-BCR-ABL1-like B-other cases. Novel exon fusions were identified for RCSD1-ABL2 and TERF2-JAK2. JAK2 mutation was mutually exclusive with tyrosine kinase fusions and only occurred in cases with high CRLF2 expression. The non/late response rate and levels of minimal residual disease in the fusion-positive BCR-ABL1-like group were higher than in the non-BCR-ABL1-like B-others (p<0.01), and also higher, albeit not statistically significant, compared with the fusion-negative BCR-ABL1-like group. The 8-year cumulative incidence of relapse in the fusion-positive BCR-ABL1-like group (35%) was comparable with that in the fusion-negative BCR-ABL1-like group (35%), and worse than in the non-BCR-ABL1-like B-other group (17%, p=0.07). IKZF1 deletions, predominantly other than the dominant-negative isoform and full deletion, co-occurred with tyrosine kinase fusions. This study shows that tyrosine kinase fusion-positive cases are a high-risk subtype of BCP-ALL, which warrants further studies with specific kinase inhibitors to improve outcome. PMID:27894077

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

Energy Technology Data Exchange (ETDEWEB)

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

2005-04-01

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

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

NARCIS (Netherlands)

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

1993-01-01

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

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

Science.gov (United States)

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

2014-07-01

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

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

Science.gov (United States)

Grebien, Florian; Hantschel, Oliver; Wojcik, John; Kaupe, Ines; Kovacic, Boris; Wyrzucki, Arkadiusz M; Gish, Gerald D; Cerny-Reiterer, Sabine; Koide, Akiko; Beug, Hartmut; Pawson, Tony; Valent, Peter; Koide, Shohei; Superti-Furga, Giulio

2011-10-14

Chronic myelogenous leukemia (CML) is caused by the constitutively active tyrosine kinase Bcr-Abl and treated with the tyrosine kinase inhibitor (TKI) imatinib. However, emerging TKI resistance prevents complete cure. Therefore, alternative strategies targeting regulatory modules of Bcr-Abl in addition to the kinase active site are strongly desirable. Here, we show that an intramolecular interaction between the SH2 and kinase domains in Bcr-Abl is both necessary and sufficient for high catalytic activity of the enzyme. Disruption of this interface led to inhibition of downstream events critical for CML signaling and, importantly, completely abolished leukemia formation in mice. Furthermore, disruption of the SH2-kinase interface increased sensitivity of imatinib-resistant Bcr-Abl mutants to TKI inhibition. An engineered Abl SH2-binding fibronectin type III monobody inhibited Bcr-Abl kinase activity both in vitro and in primary CML cells, where it induced apoptosis. This work validates the SH2-kinase interface as an allosteric target for therapeutic intervention. Copyright © 2011 Elsevier Inc. All rights reserved.

Associations of cadmium, zinc, and lead in soils from a lead and zinc mining area as studied by single and sequential extractions.

Science.gov (United States)

Anju, M; Banerjee, D K

2011-05-01

An exploratory study of the area surrounding a historical Pb-Zn mining and smelting area in Zawar, India, detected significant contamination of the terrestrial environment by heavy metals. Soils (n=87) were analyzed for pH, EC, total organic matter (TOM), Pb, Zn, Mn, and Cd levels. The statistical analysis indicated that the frequency distribution of the analyzed parameters for these soils was not normal. The median concentrations of metals in surface soils were: Pb 420.21 μ g/g, Zn 870.25 μ g/g, Mn 696.70 μ g/g, and Cd 2.09 μ g/g. Zn concentrations were significantly correlated with Cd (r=0.867), indicating that levels of Cd are dependent on Zn. However, pH, electrical conductivity and total organic matter were not correlated significantly with Cd, Pb, Zn, and Mn. To assess the potential mobility of Cd, Pb, and Zn in soils, single (EDTA) as well as sequential extraction scheme (modified BCR) were applied to representative (n=23) soil samples. The amount of Cd, Pb, and Zn extracted by EDTA and their total concentrations showed linear positive correlation, which are statistically significant (r values for Cd, Pb, and Zn being 0.901, 0.971, and 0.795, respectively, and P values being soils from all the locations. As indicated by single extraction, the apparent mobility and potential bioavailability of metals in soils followed the order: Cd ≥ Pb > > Zn. Soil samples were sequentially extracted (modified BCR) so that solid pools of Cd, Zn, and Pb could be partitioned into four operationally defined fractions viz. acid-soluble, reducible, oxidizable, and residual. Cadmium was present appreciably (39.41%) in the acid-soluble fraction and zinc was predominantly associated (32.42%) with residual fraction. Pb (66.86%) and Zn (30.44%) were present mainly in the reducible fraction. Assuming that the mobility and bioavailability are related to solubility of geochemical forms of metals and decrease in the order of extraction, the apparent mobility and potential metal

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Directory of Open Access Journals (Sweden)

Min Yu

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

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

Science.gov (United States)

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

1996-02-15

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

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

Czech Academy of Sciences Publication Activity Database

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

2010-01-01

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

Frequency of BCR-ABL Transcript Types in Syrian CML Patients

Directory of Open Access Journals (Sweden)

Sulaf Farhat-Maghribi

2016-01-01

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

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

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Miao GAO

2012-10-01

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

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

NARCIS (Netherlands)

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

2014-01-01

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

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

Science.gov (United States)

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

2018-02-01

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

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Science.gov (United States)

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

2009-01-01

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

Sequential extraction combined with isotope analysis as a tool for the investigation of lead mobilisation in soils: Application to organic-rich soils in an upland catchment in Scotland

International Nuclear Information System (INIS)

Bacon, Jeffrey R.; Farmer, John G.; Dunn, Sarah M.; Graham, Margaret C.; Vinogradoff, Susan I.

2006-01-01

Sequential extraction (modified BCR procedure) combined with isotope analysis has been investigated as a tool for assessing mobilisation of lead into streams at an upland catchment in NE Scotland. The maximum lead concentrations (up to 110 mg kg -1 in air-dried soil) occurred not at the surface but at about 10 cm depth. The lowest 206 Pb/ 207 Pb ratios in any profile occurred, with one exception, at 2.5-5 cm depth. In the one exception, closest to the only road in the area, significantly lower 206 Pb/ 207 Pb ratios in the surface soil together with much increased chloride concentrations (in comparison to other surface waters) indicated the possible mobilisation of roadside lead and transfer to the stream. The 206 Pb/ 207 Pb ratios in extractable fractions tended at depth towards the ratio measured in the residual phase but the ratios in the oxidizable fraction increased to a value higher than that of the residual phase. - Sequential extraction combined with isotope analysis was used as a tool to assess mobilisation of lead into streams

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

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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

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

Science.gov (United States)

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

2017-07-01

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

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

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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.

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

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

1991-09-25

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

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

Science.gov (United States)

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

2007-04-01

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

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

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Eduardo Vinícius Vieira Varejão

2009-08-01

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

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

Science.gov (United States)

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

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

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Mark L. Westbroek

2017-12-01

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

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.

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

International Nuclear Information System (INIS)

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

1998-01-01

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

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

Science.gov (United States)

Giere, I A; Larripa, I B

1996-08-01

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

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

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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.

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

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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.

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

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Pallavi Sontakke

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

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.

Exploring the sequential lineup advantage using WITNESS.

Science.gov (United States)

Goodsell, Charles A; Gronlund, Scott D; Carlson, Curt A

2010-12-01

Advocates claim that the sequential lineup is an improvement over simultaneous lineup procedures, but no formal (quantitatively specified) explanation exists for why it is better. The computational model WITNESS (Clark, Appl Cogn Psychol 17:629-654, 2003) was used to develop theoretical explanations for the sequential lineup advantage. In its current form, WITNESS produced a sequential advantage only by pairing conservative sequential choosing with liberal simultaneous choosing. However, this combination failed to approximate four extant experiments that exhibited large sequential advantages. Two of these experiments became the focus of our efforts because the data were uncontaminated by likely suspect position effects. Decision-based and memory-based modifications to WITNESS approximated the data and produced a sequential advantage. The next step is to evaluate the proposed explanations and modify public policy recommendations accordingly.

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

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Irene Larripa

2017-02-01

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

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

Science.gov (United States)

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

2017-01-01

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

The effect of zero-ischaemia laparoscopic minimally invasive partial nephrectomy using the modified sequential preplaced suture renorrhaphy technique on long-term renal functions.

Science.gov (United States)

Sönmez, Mehmet Giray; Kara, Cengiz

2017-09-01

Laparoscopic minimally invasive partial nephrectomy (MIPN) is the preferred technique in renal surgery, especially T1 phase kidney tumours, and it is recommended for the protection of renal functions in methods that do not involve ischaemia. To evaluate long-term renal functions of zero-ischaemia laparoscopic MIPN patients who underwent a modified sequential preplaced suture renorrhaphy technique. In a total of 17 renal units in 16 patients with kidney tumours that were determined incidentally and did not cause any complaints, the masses were extracted via laparoscopic partial nephrectomy (LPN) using the modified sequential preplaced suture renorrhaphy technique. Creatinine and estimated glomerular filtration rate (eGFR) values of the patients were measured preoperatively and on the first day and after 12 months postoperatively, and the results were compared. The differences between the pre- and postoperative values were statistically significant (p = 0.033, p = 0.045), but the changes in postoperative creatinine and eGFR values were clinically insignificant. While the differences between preoperative and first-day postoperative creatinine and eGFR values were found to be statistically significant (p = 0.039, p = 0.042, respectively), a statistically significant difference was not detected between preoperative and 12-month postoperative creatinine and eGFR values (p = 0.09, p = 0.065, respectively). The global percentage of functional recovery was measured as 92.5% on the first day and 95.9% at the 12 th month. The modified sequential preplaced suture renorrhaphy technique is an effective, reliable method for avoiding complications and preserving renal functions and nephrons in appropriate patients.

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

NARCIS (Netherlands)

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

1990-01-01

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

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

Science.gov (United States)

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

2012-04-01

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

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

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

2013-10-15

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

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

Science.gov (United States)

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

2018-01-01

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

Science.gov (United States)

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

2011-05-01

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

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

Directory of Open Access Journals (Sweden)

Eliza Vakana

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-05-24

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

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

DEFF Research Database (Denmark)

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

2011-01-01

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

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

International Nuclear Information System (INIS)

Vidal, M.; Rauret, G.

1993-01-01

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

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2016-04-15

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

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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.

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

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Soumya Panigrahi

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

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

OpenAIRE

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

2003-01-01

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

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

African Journals Online (AJOL)

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

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

Science.gov (United States)

Poplawski, Tomasz; Blasiak, Janusz

2010-06-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

Science.gov (United States)

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

2017-12-08

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

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

Science.gov (United States)

Woessner, David W; Lim, Carol S

2013-01-07

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

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

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

2017-06-01

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

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

Science.gov (United States)

2010-01-01

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

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

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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.

Sequential extraction applied to Peruibe black mud, SP, Brazil

International Nuclear Information System (INIS)

Torrecilha, Jefferson Koyaishi

2014-01-01

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

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

Science.gov (United States)

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

2018-03-01

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

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.

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

Science.gov (United States)

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

2012-03-01

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

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

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Janusz Blasiak

2013-08-01

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

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

Science.gov (United States)

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

2014-02-15

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

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

International Nuclear Information System (INIS)

Mundhada, Shailendra; Luthra, Rajyalakshmi; Cano, Pedro

2004-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

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

Directory of Open Access Journals (Sweden)

Anna Grazia Recchia

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

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

Science.gov (United States)

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

2018-04-01

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

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.

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.

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.

Dihydroazulene photoswitch operating in sequential tunneling regime

DEFF Research Database (Denmark)

Broman, Søren Lindbæk; Lara-Avila, Samuel; Thisted, Christine Lindbjerg

2012-01-01

to electrodes so that the electron transport goes by sequential tunneling. To assure weak coupling, the DHA switching kernel is modified by incorporating p-MeSC6H4 end-groups. Molecules are prepared by Suzuki cross-couplings on suitable halogenated derivatives of DHA. The synthesis presents an expansion of our......, incorporating a p-MeSC6H4 anchoring group in one end, has been placed in a silver nanogap. Conductance measurements justify that transport through both DHA (high resistivity) and VHF (low resistivity) forms goes by sequential tunneling. The switching is fairly reversible and reenterable; after more than 20 ON...

Truly costly sequential search and oligopolistic pricing

NARCIS (Netherlands)

Janssen, Maarten C W; Moraga-González, José Luis; Wildenbeest, Matthijs R.

We modify the paper of Stahl (1989) [Stahl, D.O., 1989. Oligopolistic pricing with sequential consumer search. American Economic Review 79, 700-12] by relaxing the assumption that consumers obtain the first price quotation for free. When all price quotations are costly to obtain, the unique

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

NARCIS (Netherlands)

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

1988-01-01

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

Sequential infiltration synthesis for advanced lithography

Energy Technology Data Exchange (ETDEWEB)

Darling, Seth B.; Elam, Jeffrey W.; Tseng, Yu-Chih; Peng, Qing

2017-10-10

A plasma etch resist material modified by an inorganic protective component via sequential infiltration synthesis (SIS) and methods of preparing the modified resist material. The modified resist material is characterized by an improved resistance to a plasma etching or related process relative to the unmodified resist material, thereby allowing formation of patterned features into a substrate material, which may be high-aspect ratio features. The SIS process forms the protective component within the bulk resist material through a plurality of alternating exposures to gas phase precursors which infiltrate the resist material. The plasma etch resist material may be initially patterned using photolithography, electron-beam lithography or a block copolymer self-assembly process.

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

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

1994-01-01

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

Computing sequential equilibria for two-player games

DEFF Research Database (Denmark)

Miltersen, Peter Bro

2006-01-01

Koller, Megiddo and von Stengel showed how to efficiently compute minimax strategies for two-player extensive-form zero-sum games with imperfect information but perfect recall using linear programming and avoiding conversion to normal form. Their algorithm has been used by AI researchers...... for constructing prescriptive strategies for concrete, often fairly large games. Koller and Pfeffer pointed out that the strategies obtained by the algorithm are not necessarily sequentially rational and that this deficiency is often problematic for the practical applications. We show how to remove this deficiency...... by modifying the linear programs constructed by Koller, Megiddo and von Stengel so that pairs of strategies forming a sequential equilibrium are computed. In particular, we show that a sequential equilibrium for a two-player zero-sum game with imperfect information but perfect recall can be found in polynomial...

Computing Sequential Equilibria for Two-Player Games

DEFF Research Database (Denmark)

Miltersen, Peter Bro; Sørensen, Troels Bjerre

2006-01-01

Koller, Megiddo and von Stengel showed how to efficiently compute minimax strategies for two-player extensive-form zero-sum games with imperfect information but perfect recall using linear programming and avoiding conversion to normal form. Koller and Pfeffer pointed out that the strategies...... obtained by the algorithm are not necessarily sequentially rational and that this deficiency is often problematic for the practical applications. We show how to remove this deficiency by modifying the linear programs constructed by Koller, Megiddo and von Stengel so that pairs of strategies forming...... a sequential equilibrium are computed. In particular, we show that a sequential equilibrium for a two-player zero-sum game with imperfect information but perfect recall can be found in polynomial time. In addition, the equilibrium we find is normal-form perfect. Our technique generalizes to general-sum games...

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

Science.gov (United States)

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

2003-06-01

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

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

Science.gov (United States)

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

2017-03-02

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

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

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Qianyin Li

2017-03-01

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

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

International Nuclear Information System (INIS)

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

1988-01-01

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

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

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Mohamed El Missiry

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Science.gov (United States)

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

2016-06-22

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

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

OpenAIRE

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

1988-01-01

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

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

Lifescience Database Archive (English)

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

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

DEFF Research Database (Denmark)

Järås, Marcus; Johnels, Petra; Agerstam, Helena

2009-01-01

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

Expression of p210 BCR/ABl increases hematopoietic progenitor cell radiosensitivity

International Nuclear Information System (INIS)

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

1993-01-01

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

Top-down attention affects sequential regularity representation in the human visual system.

Science.gov (United States)

Kimura, Motohiro; Widmann, Andreas; Schröger, Erich

2010-08-01

Recent neuroscience studies using visual mismatch negativity (visual MMN), an event-related brain potential (ERP) index of memory-mismatch processes in the visual sensory system, have shown that although sequential regularities embedded in successive visual stimuli can be automatically represented in the visual sensory system, an existence of sequential regularity itself does not guarantee that the sequential regularity will be automatically represented. In the present study, we investigated the effects of top-down attention on sequential regularity representation in the visual sensory system. Our results showed that a sequential regularity (SSSSD) embedded in a modified oddball sequence where infrequent deviant (D) and frequent standard stimuli (S) differing in luminance were regularly presented (SSSSDSSSSDSSSSD...) was represented in the visual sensory system only when participants attended the sequential regularity in luminance, but not when participants ignored the stimuli or simply attended the dimension of luminance per se. This suggests that top-down attention affects sequential regularity representation in the visual sensory system and that top-down attention is a prerequisite for particular sequential regularities to be represented. Copyright 2010 Elsevier B.V. All rights reserved.

Modified Sequential Therapy Regimen versus Conventional Triple Therapy for Helicobacter pylori Eradication in Duodenal Ulcer Patients in China: A Multicenter Clinical Comparative Study

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Ying-Qun Zhou

2012-01-01

Full Text Available Objective. Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. To observe the effect of eradicating Helicobacter pylori (H. pylori and the treatment of duodenal ulcer by 2 kinds of modified sequential therapy through comparing with that of 10-day standard triple therapy. Methods. A total of 210 patients who were confirmed in duodenal ulcer active or heal period by gastroscopy and H. pylori positive confirmed by rapid urease test, serum anti-H. pylori antibody (ELASE, or histological examination enrolled in the study. All the patients were randomly divided into three groups: group A (70 cases and group B (70 cases were provided 10-day modified sequential therapy; group C (70 cases was provided 10-day standard triple therapy. Patients of group A received 20 mg of Esomeprazole, 500 mg of Clarithromycin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group B received 20 mg of Esomeprazole, 1000 mg of Amoxicillin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group C received 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for standard 10-day therapy. All drugs were given twice daily. H. pylori eradication rate was checked four to eight weeks after taking the medicine by using a 13C urea breath test. In the first, second, third, seventh, twenty-first, thirty-fifth days respectively, the symptoms of patients such as epigastric gnawing, burning pain, and acidity were evaluated simultaneously. Results. Overall, 210 patients accomplished all therapy schemes, 9 case patients were excluded. The examination result indicated that the H. pylori eradication rate of each group was as follows: group A 92.5% (62/67, group B 86.8% (59/68, and group C 78.8% (52/66. The H. pylori

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

Science.gov (United States)

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

2016-01-01

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

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

OpenAIRE

Woessner, David W.; Lim, Carol S.

2012-01-01

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

Improved L-cysteine electrocatalysis through a sequential drop dry technique using multi-walled carbon nanotubes and cobalt tetraaminophthalocyanine conjugates

International Nuclear Information System (INIS)

Nyoni, Stephen; Mugadza, Tawanda; Nyokong, Tebello

2014-01-01

Graphical abstract: A sequential drop dry modification of a glassy carbon electrode where by multiwalled carbon nanotubes are first placed on to the electrode followed by cobalt tetraaminophthalocyanine gave a better catalytic response towards the oxidation of L-cysteine than when the two components were mixed, due to the higher catalytic activity of the former as judged by scanning electrochemical microscopy. - Highlights: • A glassy carbon electrode modified with multi-walled carbon nanotubes and cobalt tetraaminophthalocyanine by a sequential drop dry method. • The modified surface gave a better catalytic response towards the oxidation of L-cysteine than when the individual components were mixed. • Scanning electrochemical microscopy was employed for surface characterization. - Abstract: Voltammetry, chronoamperometry, scanning electrochemical microscopy and electrochemical impedance spectroscopy methods are used for characterization of a glassy carbon electrode modified with multi-walled carbon nanotubes (MWCNTs)–cobalt tetraaminophthalocyanine (CoTAPc) mixture or sequential drop dry modification technique whereby the MWCNTs are first placed on to the electrode followed by CoTAPc. The sequential drop dry CoTAPc–MWCNTs modified surface gave better catalytic responses with a catalytic rate constant of 2.2 × 10 5 M −1 s −1 , apparent electron transfer rate constant of 0.073 cm s −1 , and a limit of detection of 2.8 × 10 −7 M. Scanning electrochemical microscopy (SECM) surface characterization (topography and reactivity) further gave proof the better catalytic perfomance of the sequential drop dry CoTAPc–MWCNTs modified surface

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

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

Science.gov (United States)

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

2014-01-01

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

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.

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

Sequential infiltration synthesis for enhancing multiple-patterning lithography

Science.gov (United States)

Darling, Seth B.; Elam, Jeffrey W.; Tseng, Yu-Chih

2017-06-20

Simplified methods of multiple-patterning photolithography using sequential infiltration synthesis to modify the photoresist such that it withstands plasma etching better than unmodified resist and replaces one or more hard masks and/or a freezing step in MPL processes including litho-etch-litho-etch photolithography or litho-freeze-litho-etch photolithography.

Metal contamination of home garden soils and cultivated vegetables in the province of Brescia, Italy: Implications for human exposure

Energy Technology Data Exchange (ETDEWEB)

Ferri, Roberta [Occupational Health, University of Brescia (Italy); Hashim, Dana [Occupational and Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York (United States); Smith, Donald R. [Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA (United States); Guazzetti, Stefano [Public Health Service, Reggio Emilia (Italy); Donna, Filippo [Occupational Health, University of Brescia (Italy); Ferretti, Enrica; Curatolo, Michele; Moneta, Caterina [Department of Food Chemistry, Metal Laboratory, IZSLER, Brescia (Italy); Beone, Gian Maria [Institute of Agricultural and Environmental Chemistry, Università Cattolica, Piacenza (Italy); Lucchini, Roberto G. [Occupational Health, University of Brescia (Italy); Occupational and Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York (United States); Microbiology and Environmental Toxicology, University of California, Santa Cruz, CA (United States)

2015-06-15

Background: For the past century, ferroalloy industries in Brescia province, Italy produced particulate emissions enriched in manganese (Mn), lead (Pb), zinc (Zn), copper (Cu), cadmium (Cd), chromium (Cr), iron (Fe), and aluminum (Al). This study assessed metal concentrations in soil and vegetables of regions with varying ferroalloy industrial activity levels. Methods: Home gardens (n = 63) were selected in three regions of varying ferroalloy plant activity durations in Brescia province. Total soil metal concentration and extractability were measured by X-Ray Fluorescence (XRF), aqua regia extraction, and modified Community Bureau of Reference (BCR) sequential extraction. Unwashed and washed spinach and turnips cultivated in the same gardens were analyzed for metal concentrations by flame atomic absorption spectrometry. Results: Median soil Al, Cd, Fe, Mn, Pb, and Zn concentrations were significantly higher in home gardens near ferroalloy plants compared to reference home gardens. The BCR method yielded the most mobile soil fraction (the sum of extractable metals in Fractions 1 and 2) and all metal concentrations were higher in ferroalloy plant areas. Unwashed spinach showed higher metal concentrations compared to washed spinach. However, some metals in washed spinach were higher in the reference area likely due to history of agricultural product use. Over 60% of spinach samples exceeded the 2- to 4-fold Commission of European Communities and Codex Alimentarius Commission maximum Pb concentrations, and 10% of the same spinach samples exceeded 2- to 3-fold maximum Cd concentrations set by both organizations. Turnip metal concentrations were below maximum standard reference values. Conclusions: Prolonged industrial emissions increase median metal concentrations and most soluble fractions (BCR F1 + F2) in home garden soils near ferroalloy plants. Areas near ferroalloy plant sites had spinach Cd and Pb metal concentrations several-fold above maximum standard references

Metal contamination of home garden soils and cultivated vegetables in the province of Brescia, Italy: Implications for human exposure

International Nuclear Information System (INIS)

Ferri, Roberta; Hashim, Dana; Smith, Donald R.; Guazzetti, Stefano; Donna, Filippo; Ferretti, Enrica; Curatolo, Michele; Moneta, Caterina; Beone, Gian Maria; Lucchini, Roberto G.

2015-01-01

Background: For the past century, ferroalloy industries in Brescia province, Italy produced particulate emissions enriched in manganese (Mn), lead (Pb), zinc (Zn), copper (Cu), cadmium (Cd), chromium (Cr), iron (Fe), and aluminum (Al). This study assessed metal concentrations in soil and vegetables of regions with varying ferroalloy industrial activity levels. Methods: Home gardens (n = 63) were selected in three regions of varying ferroalloy plant activity durations in Brescia province. Total soil metal concentration and extractability were measured by X-Ray Fluorescence (XRF), aqua regia extraction, and modified Community Bureau of Reference (BCR) sequential extraction. Unwashed and washed spinach and turnips cultivated in the same gardens were analyzed for metal concentrations by flame atomic absorption spectrometry. Results: Median soil Al, Cd, Fe, Mn, Pb, and Zn concentrations were significantly higher in home gardens near ferroalloy plants compared to reference home gardens. The BCR method yielded the most mobile soil fraction (the sum of extractable metals in Fractions 1 and 2) and all metal concentrations were higher in ferroalloy plant areas. Unwashed spinach showed higher metal concentrations compared to washed spinach. However, some metals in washed spinach were higher in the reference area likely due to history of agricultural product use. Over 60% of spinach samples exceeded the 2- to 4-fold Commission of European Communities and Codex Alimentarius Commission maximum Pb concentrations, and 10% of the same spinach samples exceeded 2- to 3-fold maximum Cd concentrations set by both organizations. Turnip metal concentrations were below maximum standard reference values. Conclusions: Prolonged industrial emissions increase median metal concentrations and most soluble fractions (BCR F1 + F2) in home garden soils near ferroalloy plants. Areas near ferroalloy plant sites had spinach Cd and Pb metal concentrations several-fold above maximum standard references

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

Science.gov (United States)

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

2017-05-08

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

Fault detection in multiply-redundant measurement systems via sequential testing

International Nuclear Information System (INIS)

Ray, A.

1988-01-01

The theory and application of a sequential test procedure for fault detection and isolation. The test procedure is suited for development of intelligent instrumentation in strategic processes like aircraft and nuclear plants where redundant measurements are usually available for individual critical variables. The test procedure consists of: (1) a generic redundancy management procedure which is essentially independent of the fault detection strategy and measurement noise statistics, and (2) a modified version of sequential probability ratio test algorithm for fault detection and isolation, which functions within the framework of this redundancy management procedure. The sequential test procedure is suitable for real-time applications using commercially available microcomputers and its efficacy has been verified by online fault detection in an operating nuclear reactor. 15 references

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

African Journals Online (AJOL)

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

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

Science.gov (United States)

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

2012-10-02

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

Heavy metal speciation in various grain sizes of industrially contaminated street dust using multivariate statistical analysis.

Science.gov (United States)

Yıldırım, Gülşen; Tokalıoğlu, Şerife

2016-02-01

A total of 36 street dust samples were collected from the streets of the Organised Industrial District in Kayseri, Turkey. This region includes a total of 818 work places in various industrial areas. The modified BCR (the European Community Bureau of Reference) sequential extraction procedure was applied to evaluate the mobility and bioavailability of trace elements (Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn) in street dusts of the study area. The BCR was classified into three steps: water/acid soluble fraction, reducible and oxidisable fraction. The remaining residue was dissolved by using aqua regia. The concentrations of the metals in street dust samples were determined by flame atomic absorption spectrometry. Also the effect of the different grain sizes (dust samples on the mobility of the metals was investigated using the modified BCR procedure. The mobility sequence based on the sum of the first three phases (for grain size) was: Cd (71.3)>Cu (48.9)>Pb (42.8)=Cr (42.1)>Ni (41.4)>Zn (40.9)>Co (36.6)=Mn (36.3)>Fe (3.1). No significant difference was observed among metal partitioning for the three particle sizes. Correlation, principal component and cluster analysis were applied to identify probable natural and anthropogenic sources in the region. The principal component analysis results showed that this industrial district was influenced by traffic, industrial activities, air-borne emissions and natural sources. The accuracy of the results was checked by analysis of both the BCR-701 certified reference material and by recovery studies in street dust samples. Copyright © 2015 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Directory of Open Access Journals (Sweden)

Gardolinski Paulo C. F. C.

2002-01-01

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

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

NARCIS (Netherlands)

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

1984-01-01

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

Quantum chromodynamics as the sequential fragmenting with inactivation

International Nuclear Information System (INIS)

Botet, R.

1996-01-01

We investigate the relation between the modified leading log approximation of the perturbative QCD and the sequential binary fragmentation process. We will show that in the absence of inactivation, this process is equivalent to the QCD gluodynamics. The inactivation term yields a precise prescription of how to include the hadronization in the QCD equations. (authors)

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

Directory of Open Access Journals (Sweden)

Tadej Pajič

2012-12-01

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

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

Science.gov (United States)

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

2010-12-01

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

Quantum chromodynamics as the sequential fragmenting with inactivation

Energy Technology Data Exchange (ETDEWEB)

Botet, R. [Paris-11 Univ., 91 - Orsay (France). Lab. de Physique des Solides; Ploszajczak, M. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France)

1996-12-31

We investigate the relation between the modified leading log approximation of the perturbative QCD and the sequential binary fragmentation process. We will show that in the absence of inactivation, this process is equivalent to the QCD gluodynamics. The inactivation term yields a precise prescription of how to include the hadronization in the QCD equations. (authors). 15 refs.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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.

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

National Research Council Canada - National Science Library

Reddy, E. P

2007-01-01

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

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

Science.gov (United States)

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

2018-05-01

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

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

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

Science.gov (United States)

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

2017-01-01

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

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

Directory of Open Access Journals (Sweden)

Shantashri Vaidya

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

Fast regularizing sequential subspace optimization in Banach spaces

International Nuclear Information System (INIS)

Schöpfer, F; Schuster, T

2009-01-01

We are concerned with fast computations of regularized solutions of linear operator equations in Banach spaces in case only noisy data are available. To this end we modify recently developed sequential subspace optimization methods in such a way that the therein employed Bregman projections onto hyperplanes are replaced by Bregman projections onto stripes whose width is in the order of the noise level

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

International Nuclear Information System (INIS)

Pena, Francisco; Lavilla, Isela; Bendicho, Carlos

2008-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Pena, Francisco; Lavilla, Isela [Departamento de Quimica Analitica y Alimentaria, Area de Quimica Analitica, Facultad de Quimica, Universidad de Vigo, Campus As Lagoas-Marcosende, s/n, 36310 Vigo (Spain); Bendicho, Carlos [Departamento de Quimica Analitica y Alimentaria, Area de Quimica Analitica, Facultad de Quimica, Universidad de Vigo, Campus As Lagoas-Marcosende, s/n, 36310 Vigo (Spain)], E-mail: bendicho@uvigo.es

2008-04-15

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

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.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

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

2008-08-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Torrecilha, Jefferson Koyaishi

2014-07-01

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

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

African Journals Online (AJOL)

2015-05-12

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

Safeguarding a Lunar Rover with Wald's Sequential Probability Ratio Test

Science.gov (United States)

Furlong, Michael; Dille, Michael; Wong, Uland; Nefian, Ara

2016-01-01

The virtual bumper is a safeguarding mechanism for autonomous and remotely operated robots. In this paper we take a new approach to the virtual bumper system by using an old statistical test. By using a modified version of Wald's sequential probability ratio test we demonstrate that we can reduce the number of false positive reported by the virtual bumper, thereby saving valuable mission time. We use the concept of sequential probability ratio to control vehicle speed in the presence of possible obstacles in order to increase certainty about whether or not obstacles are present. Our new algorithm reduces the chances of collision by approximately 98 relative to traditional virtual bumper safeguarding without speed control.

Sequential fermentation using non-Saccharomyces yeasts for the reduction of alcohol content in wine

Directory of Open Access Journals (Sweden)

Ciani Maurizio

2014-01-01

Full Text Available Over the last few decades there has been a progressive increase in wine ethanol content due to global climate change and modified wine styles that involved viticulture and oenology practices. Among the different approaches and strategies to reduce alcohol content in wine we propose a sequential fermentation using immobilized non-Saccharomyces wine yeasts. Preliminary results showed that sequential fermentations with Hanseniaspora osmophila, Hanseniaspora uvarum, Metschnikowia pulcherrima, Starmerella bombicola and Saccharomyces cerevisiae strains showed an ethanol reduction when compared with pure S. cerevisiae fermentation trials.

Combined inhibition of β-catenin and Bcr-Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo.

Science.gov (United States)

Zhou, H; Mak, P Y; Mu, H; Mak, D H; Zeng, Z; Cortes, J; Liu, Q; Andreeff, M; Carter, B Z

2017-10-01

Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation, remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in granulocyte-macrophage progenitors, and highest among a novel CD34 + CD38 + CD123 hi Tim-3 hi subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells. A novel Wnt/β-catenin signaling modulator, C82, and nilotinib synergistically killed KBM5 T315I and TKI-resistant primary BC-CML cells with or without BCR-ABL kinase mutations even under leukemia/MSC co-culture conditions. Silencing of β-catenin by short interfering RNA restored sensitivity of primary BCR-ABL T315I/E255V BC-CML cells to nilotinib. Combining the C82 pro-drug, PRI-724, with nilotinib significantly prolonged the survival of NOD/SCID/IL2Rγ null mice injected with primary BCR-ABL T315I/E255V BC-CML cells. The combined treatment selectively targeted CML progenitors and inhibited CD44, c-Myc, survivin, p-CRKL and p-STAT5 expression. In addition, pretreating primary BC-CML cells with C82, or the combination, but not with nilotinib alone, significantly impaired their engraftment potential in NOD/SCID/IL2Rγ-null-3/GM/SF mice and significantly prolonged survival. Our data suggest potential benefit of concomitant β-catenin and Bcr-Abl inhibition to prevent or overcome Bcr-Abl kinase-dependent or -independent TKI resistance in BC-CML.

Kinetics of hydroxyapatite deposition on solid substrates modified by sequential implantation of Ca and P ions - Part I. FTIR and Raman spectroscopy study

Science.gov (United States)

Pecheva, Emilia V.; Pramatarova, Liliana D.; Maitz, Manfred F.; Pham, Mihn T.; Kondyuirin, Alexey V.

2004-07-01

In this work, the kinetics of hydroxyapatite (HA) deposition on solid substrates from liquid precursor (simulated body fluid, SBF) is investigated. The surfaces of stainless steel, silicon and silica glass substrates are modified by sequential implantation of Ca and P ions. Three groups of samples of each material: (i) ion-implanted; (ii) ion-implanted and thermally treated at 873 K in air for 60 min; and (iii) untreated are prepared. To investigate the kinetics of the HA deposition, all three groups of samples are introduced at equal conditions into SBF whose supersaturation is maintained during the whole 6-day period of immersion. The layers are analyzed by FTIR and Raman spectroscopy. Both techniques complement each other and show the formation of HA with incorporated CO 32- and HPO 42- groups. Following the kinetics of the deposition process, it is concluded that the speed of deposition is different on the three materials modified by Ca and P implantation and by oxidation, compared to untreated samples but in order to distinguish clearly the effect of the ion implantation and oxidation the very initial moment of nucleation and layer growth should be more carefully investigated.

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

Science.gov (United States)

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

2015-07-01

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

Chemical speciation and human health risk of trace metals in urban street dusts from a metropolitan city, Nanjing, SE China

Energy Technology Data Exchange (ETDEWEB)

Li, Huiming; Qian, Xin, E-mail: xqian@nju.edu.cn; Hu, Wei; Wang, Yulei; Gao, Hailong

2013-07-01

The modified BCR (the European Community Bureau of Reference) sequential extraction procedure was applied for partitioning and evaluating the mobility, availability and persistence of trace metals (Al, Cd, Co, Cr, Cu, Ni, Pb, Sr, V and Zn) in urban street dusts collected from different areas of Nanjing, China. The mobility sequence based on the sum of the BCR sequential extraction stages was: Sr (91.65%) > Pb (79.16%) > Zn (74.26%) > Cu (68.53%) > Co (45.98%) > Al (40.01%) ≈ V (38.45%) ≈ Ni (37.88%) > Cr (29.35%) > Cd (22.68%). Almost every trace metal had its highest total concentrations in the industrial area, except for Sr which had its highest concentration in the commercial area. Contamination factors (Cf), risk assessment code (RAC) and enrichment factor (Ef) were then calculated to further assess the environmental risk and provide a preliminary estimate of the main sources of trace metals in street dusts. Non-carcinogenic effects and carcinogenic effects due to exposure to urban street dusts were assessed for both children and adults. For non-carcinogenic effects, ingestion was the main route of exposure to street dusts for these metals, followed by dermal contact and inhalation. Hazard index values for all studied metals were lower than the safe level of 1, and Pb exhibited the highest risk value (0.125) in the case of children. The carcinogenic risk for Cd, Co, Cr and Ni were all below the acceptable level (< 10{sup −6}). - Highlights: • This study assesses a comprehensive environmental risk of urban trace metal pollution. • This study evaluates human health risk combined with the speciation of trace metals. • This study points the critical contaminated metals that need to be paid special attention. • This study supplies useful information and reference on the application of BCR SPE method.

Sequential and parallel image restoration: neural network implementations.

Science.gov (United States)

Figueiredo, M T; Leitao, J N

1994-01-01

Sequential and parallel image restoration algorithms and their implementations on neural networks are proposed. For images degraded by linear blur and contaminated by additive white Gaussian noise, maximum a posteriori (MAP) estimation and regularization theory lead to the same high dimension convex optimization problem. The commonly adopted strategy (in using neural networks for image restoration) is to map the objective function of the optimization problem into the energy of a predefined network, taking advantage of its energy minimization properties. Departing from this approach, we propose neural implementations of iterative minimization algorithms which are first proved to converge. The developed schemes are based on modified Hopfield (1985) networks of graded elements, with both sequential and parallel updating schedules. An algorithm supported on a fully standard Hopfield network (binary elements and zero autoconnections) is also considered. Robustness with respect to finite numerical precision is studied, and examples with real images are presented.

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

Energy Technology Data Exchange (ETDEWEB)

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

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

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

Science.gov (United States)

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

2014-01-01

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

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

Directory of Open Access Journals (Sweden)

P. Balsas

2017-03-01

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

Standardized method for reproducing the sequential X-rays flap

International Nuclear Information System (INIS)

Brenes, Alejandra; Molina, Katherine; Gudino, Sylvia

2009-01-01

A method is validated to estandardize in the taking, developing and analysis of bite-wing radiographs taken in sequential way, in order to compare and evaluate detectable changes in the evolution of the interproximal lesions through time. A radiographic positioner called XCP® is modified by means of a rigid acrylic guide, to achieve proper of the X ray equipment core positioning relative to the XCP® ring and the reorientation during the sequential x-rays process. 16 subjects of 4 to 40 years old are studied for a total number of 32 registries. Two x-rays of the same block of teeth of each subject have been taken in sequential way, with a minimal difference of 30 minutes between each one, before the placement of radiographic attachment. The images have been digitized with a Super Cam® scanner and imported to a software. The measurements in X and Y-axis for both x-rays were performed to proceed to compare. The intraclass correlation index (ICI) has shown that the proposed method is statistically related to measurement (mm) obtained in the X and Y-axis for both sequential series of x-rays (p=0.01). The measures of central tendency and dispersion have shown that the usual occurrence is indifferent between the two measurements (Mode 0.000 and S = 0083 and 0.109) and that the probability of occurrence of different values is lower than expected. (author) [es

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.

Sequential Power-Dependence Theory

NARCIS (Netherlands)

Buskens, Vincent; Rijt, Arnout van de

2008-01-01

Existing methods for predicting resource divisions in laboratory exchange networks do not take into account the sequential nature of the experimental setting. We extend network exchange theory by considering sequential exchange. We prove that Sequential Power-Dependence Theory—unlike

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Science.gov (United States)

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

2013-10-01

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

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.

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

OpenAIRE

Bäumler, Jörg

2006-01-01

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

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

OpenAIRE

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

2001-01-01

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

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

Treatment Variation of Sequential versus Concurrent Chemoradiotherapy in Stage III Non-Small Cell Lung Cancer Patients in the Netherlands and Belgium.

Science.gov (United States)

Walraven, I; Damhuis, R A; Ten Berge, M G; Rosskamp, M; van Eycken, L; de Ruysscher, D; Belderbos, J S A

2017-11-01

Concurrent chemoradiotherapy (CCRT) is considered the standard treatment regimen in non-surgical locally advanced non-small cell lung cancer (NSCLC) patients and sequential chemoradiotherapy (SCRT) is recommended in patients who are unfit to receive CCRT or when the treatment volume is considered too large. In this study, we investigated the proportion of CCRT/SCRT in the Netherlands and Belgium. Furthermore, patient and disease characteristics associated with SCRT were assessed. An observational study was carried out with data from three independent national registries: the Belgian Cancer Registry (BCR), the Netherlands Cancer Registry (NCR) and the Dutch Lung Cancer Audit-Radiotherapy (DLCA-R). Differences in patient and disease characteristics between CCRT and SCRT were tested with unpaired t-tests (for continuous variables) and with chi-square tests (for categorical variables). A prognostic model was constructed to determine patient and disease parameters predictive for the choice of SCRT. This study included 350 patients from the BCR, 780 patients from the NCR and 428 patients from the DLCA-R. More than half of the stage III NSCLC patients in the Netherlands (55%) and in Belgium more than a third (35%) were treated with CCRT. In both the Dutch and Belgian population, higher age and more advanced N-stage were significantly associated with SCRT. Performance score, pulmonary function, comorbidities and tumour volume were not associated with SCRT. In this observational population-based study, a large treatment variation in non-surgical stage III NSCLC patients was observed between and within the Netherlands and Belgium. Higher age and N-stage were significantly associated with the choice for SCRT. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Sequential phosphorylation of GRASP65 during mitotic Golgi disassembly

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Danming Tang

2012-09-01

GRASP65 phosphorylation during mitosis and dephosphorylation after mitosis are required for Golgi disassembly and reassembly during the cell cycle. At least eight phosphorylation sites on GRASP65 have been identified, but whether they are modified in a coordinated fashion during mitosis is so far unknown. In this study, we raised phospho-specific antibodies that recognize phosphorylated T220/T224, S277 and S376 residues of GRASP65, respectively. Biochemical analysis showed that cdc2 phosphorylates all three sites, while plk1 enhances the phosphorylation. Microscopic studies using these antibodies for double and triple labeling demonstrate sequential phosphorylation and dephosphorylation during the cell cycle. S277 and S376 are phosphorylated from late G2 phase through metaphase until telophase when the new Golgi is reassembled. T220/224 is not modified until prophase, but is highly modified from prometaphase to anaphase. In metaphase, phospho-T220/224 signal localizes on both Golgi haze and mitotic Golgi clusters that represent dispersed Golgi vesicles and Golgi remnants, respectively, while phospho-S277 and S376 labeling is more concentrated on mitotic Golgi clusters. Expression of a phosphorylation-resistant GRASP65 mutant T220A/T224A inhibited mitotic Golgi fragmentation to a much larger extent than the expression of the S277A and S376A mutants. In cytokinesis, T220/224 dephosphorylation occurs prior to that of S277, but after S376. This study provides evidence that GRASP65 is sequentially phosphorylated and dephosphorylated during mitosis at different sites to orchestrate Golgi disassembly and reassembly during cell division, with phosphorylation of the T220/224 site being most critical in the process.

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.

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

Directory of Open Access Journals (Sweden)

Juan C. Gomez-Gelvez, MD

2016-03-01

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

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

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

Directory of Open Access Journals (Sweden)

Thiago Cezar Fujita

2010-09-01

Full Text Available Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2 transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1. Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease.Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed

Comparison of three sequential extraction procedures to describe metal fractionation in anaerobic granular sludges

NARCIS (Netherlands)

Hullebusch, van E.D.; Sudarno, S.; Zandvoort, M.H.; Lens, P.N.L.

2005-01-01

In the last few decades. several sequential extraction procedures have been developed to quantify the chemical status of metals in the solid phase. In this study. three extraction techniques (modified [A. Tessier, P.G.C. Campbell, M. Bisson, Anal. Chem. 51 (1979) 844]: [R.C. Stover. L.E. Sommers,

Speciation of heavy metals in garden soils. Evidences from selective and sequential chemical leaching

Energy Technology Data Exchange (ETDEWEB)

Cheng, Zhongqi; Lee, Leda; Dayan, Sara; Grinshtein, Michael [Brooklyn College of The City Univ. of New York, Brooklyn, NY (United States). Environmental Sciences Analytical Cnter; Shaw, Richard [USDA-NRCS NYC Soil Survey, Staten Island, NY (United States)

2011-06-15

Purpose: Gardening (especially food growing) in urban areas is becoming popular, but urban soils are often very contaminated for historical reasons. There is lack of sufficient information as to the bioavailability of soil heavy metals to plants and human in urban environments. This study examines the relative leachability of Cr, Ni, As, Cd, Zn, and Pb for soils with varying characteristics. The speciation and mobility of these metals can be qualitatively inferred from the leaching experiments. The goal is to use the data to shed some light on their bioavailability to plant and human, as well as the basis for soil remediation. Materials and methods: Selective and sequential chemical leaching methods were both used to evaluate the speciation of Cr, Ni, As, Cd, Zn, and Pb in soil samples collected from New York City residential and community gardens. The sequential leaching experiment followed a standard BCR four-step procedure, while selective leaching involved seven different chemical extractants. Results and discussion: The results from selective and sequential leaching methods are consistent. In general, very little of the heavy metals were found in the easily soluble or exchangeable fractions. Larger fractions of Cd and Zn can be leached out than other metals. Lead appears predominantly in the organic or carbonate fractions, of which {proportional_to} 30-60% is in the easily soluble organic fraction. Most As cannot be leached out by any of the extractants used, but it could have been complicated by the ineffective dissolution of oxides by ammonium hydroxylamine. Ni and Cr were mostly in the residual fractions but some released in the oxidizable fractions. Therefore, the leachability of metals follow the order Cd/Zn > Pb > Ni/Cr. Conclusions: Despite of the controversy and inaccuracy surrounding chemical leaching methods for the speciation of metals, chemical leaching data provide important, general, and easy-to-access information on the mobility of heavy metals

Extractability and bioavailability of Pb and As in historically contaminated orchard soil: Effects of compost amendments

International Nuclear Information System (INIS)

Fleming, Margaret; Tai, Yiping; Zhuang, Ping; McBride, Murray B.

2013-01-01

The availability of Pb and As in an historically contaminated orchard soil, after amendment with compost and aging in the field, was determined by single-step chemical extraction with 1.0 M ammonium acetate at pH 4.8, sequential extraction using the modified BCR test, and a redworm bioassay in the laboratory. The efficiency of soil Pb extraction by ammonium acetate was greater at higher total soil Pb but was reduced by compost amendment. Conversely, the extraction efficiency of total soil As increased with compost amendment, but was not sensitive to total soil As. The redworm bioassay indicated Pb (but not As) bioavailability to be reduced by soil amendment with compost, a result consistent with the ammonium acetate extraction test but not reflected in modified BCR test. Electron microprobe studies of the orchard soil revealed Pb and As to be spatially associated in discrete particles along with phosphorus and iron. -- Highlights: ► Soil Pb and As in an old orchard were concentrated in discrete particles. ► Compost amendment of contaminated soil reduced Pb bioavailability. ► Compost amendment of contaminated soil did not reduce As bioavailability. ► Ammonium acetate extraction test reflected bioavailability of soil Pb and As. -- Remediating metal-contaminated orchard soils with compost reduced lead bioavailability but had little effect on arsenic

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

Science.gov (United States)

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

2006-01-01

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

Sequential voluntary cough and aspiration or aspiration risk in Parkinson's disease.

Science.gov (United States)

Hegland, Karen Wheeler; Okun, Michael S; Troche, Michelle S

2014-08-01

Disordered swallowing, or dysphagia, is almost always present to some degree in people with Parkinson's disease (PD), either causing aspiration or greatly increasing the risk for aspiration during swallowing. This likely contributes to aspiration pneumonia, a leading cause of death in this patient population. Effective airway protection is dependent upon multiple behaviors, including cough and swallowing. Single voluntary cough function is disordered in people with PD and dysphagia. However, the appropriate response to aspirate material is more than one cough, or sequential cough. The goal of this study was to examine voluntary sequential coughing in people with PD, with and without dysphagia. Forty adults diagnosed with idiopathic PD produced two trials of sequential voluntary cough. The cough airflows were obtained using pneumotachograph and facemask and subsequently digitized and recorded. All participants received a modified barium swallow study as part of their clinical care, and the worst penetration-aspiration score observed was used to determine whether the patient had dysphagia. There were significant differences in the compression phase duration, peak expiratory flow rates, and amount of air expired of the sequential cough produced by participants with and without dysphagia. The presence of dysphagia in people with PD is associated with disordered cough function. Sequential cough, which is important in removing aspirate material from large- and smaller-diameter airways, is also impaired in people with PD and dysphagia compared with those without dysphagia. There may be common neuroanatomical substrates for cough and swallowing impairment in PD leading to the co-occurrence of these dysfunctions.

A comprehensive target selectivity survey of the BCR-ABL kinase inhibitor INNO-406 by kinase profiling and chemical proteomics in chronic myeloid leukemia cells.

Science.gov (United States)

Rix, U; Remsing Rix, L L; Terker, A S; Fernbach, N V; Hantschel, O; Planyavsky, M; Breitwieser, F P; Herrmann, H; Colinge, J; Bennett, K L; Augustin, M; Till, J H; Heinrich, M C; Valent, P; Superti-Furga, G

2010-01-01

Resistance to the BCR-ABL tyrosine kinase inhibitor imatinib poses a pressing challenge in treating chronic myeloid leukemia (CML). This resistance is often caused by point mutations in the ABL kinase domain or by overexpression of LYN. The second-generation BCR-ABL inhibitor INNO-406 is known to inhibit most BCR-ABL mutants and LYN efficiently. Knowledge of its full target spectrum would provide the molecular basis for potential side effects or suggest novel therapeutic applications and possible combination therapies. We have performed an unbiased chemical proteomics native target profile of INNO-406 in CML cells combined with functional assays using 272 recombinant kinases thereby identifying several new INNO-406 targets. These include the kinases ZAK, DDR1/2 and various ephrin receptors. The oxidoreductase NQO2, inhibited by both imatinib and nilotinib, is not a relevant target of INNO-406. Overall, INNO-406 has an improved activity over imatinib but a slightly broader target profile than both imatinib and nilotinib. In contrast to dasatinib and bosutinib, INNO-406 does not inhibit all SRC kinases and most TEC family kinases and is therefore expected to elicit fewer side effects. Altogether, these properties may make INNO-406 a valuable component in the drug arsenal against CML.

Full coverage of perovskite layer onto ZnO nanorods via a modified sequential two-step deposition method for efficiency enhancement in perovskite solar cells

Science.gov (United States)

Ruankham, Pipat; Wongratanaphisan, Duangmanee; Gardchareon, Atcharawon; Phadungdhitidhada, Surachet; Choopun, Supab; Sagawa, Takashi

2017-07-01

Full coverage of perovskite layer onto ZnO nanorod substrates with less pinholes is crucial for achieving high-efficiency perovskite solar cells. In this work, a two-step sequential deposition method is modified to achieve an appropriate property of perovskite (MAPbI3) film. Surface treatment of perovskite layer and its precursor have been systematically performed and their morphologies have been investigated. By pre-wetting of lead iodide (PbI2) and letting it dry before reacting with methylammonium iodide (MAI) provide better coverage of perovskite film onto ZnO nanorod substrate than one without any treatment. An additional MAI deposition followed with toluene drop-casting technique on the perovskite film is also found to increase the coverage and enhance the transformation of PbI2 to MAPbI3. These lead to longer charge carrier lifetime, resulting in an enhanced power conversion efficiency (PCE) from 1.21% to 3.05%. The modified method could been applied to a complex ZnO nanorods/TiO2 nanoparticles substrate. The enhancement in PCE to 3.41% is observed. These imply that our introduced method provides a simple way to obtain the full coverage and better transformation to MAPbI3 phase for enhancement in performances of perovskite solar cells.

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

Science.gov (United States)

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

2015-12-01

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

CACTI: free, open-source software for the sequential coding of behavioral interactions.

Science.gov (United States)

Glynn, Lisa H; Hallgren, Kevin A; Houck, Jon M; Moyers, Theresa B

2012-01-01

The sequential analysis of client and clinician speech in psychotherapy sessions can help to identify and characterize potential mechanisms of treatment and behavior change. Previous studies required coding systems that were time-consuming, expensive, and error-prone. Existing software can be expensive and inflexible, and furthermore, no single package allows for pre-parsing, sequential coding, and assignment of global ratings. We developed a free, open-source, and adaptable program to meet these needs: The CASAA Application for Coding Treatment Interactions (CACTI). Without transcripts, CACTI facilitates the real-time sequential coding of behavioral interactions using WAV-format audio files. Most elements of the interface are user-modifiable through a simple XML file, and can be further adapted using Java through the terms of the GNU Public License. Coding with this software yields interrater reliabilities comparable to previous methods, but at greatly reduced time and expense. CACTI is a flexible research tool that can simplify psychotherapy process research, and has the potential to contribute to the improvement of treatment content and delivery.

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

Science.gov (United States)

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

2013-09-10

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

Element fractionation by sequential extraction in a soil with high carbonate content

International Nuclear Information System (INIS)

Sulkowski, Margareta; Hirner, Alfred V.

2006-01-01

The influence of carbonate and other buffering substances in soils on the results of a 3-step sequential extraction procedure (BCR) used for metal fractionation was investigated. Deviating from the original extraction scheme, where the extracts are analysed only for a limited number of metals, almost all elements in the soils were quantified by X-ray fluorescence spectroscopy, in the initial samples as well as in the residues of all extraction steps. Additionally, the mineral contents were determined by X-ray diffractometry. Using this methodology, it was possible to correlate changes in soil composition caused by the extraction procedure with the release of elements. Furthermore, the pH values of all extracts were monitored, and certain extraction steps were repeated until no significant pH-rise occurred. A soil with high dolomite content (27%) and a carbonate free soil were extracted. Applying the original BCR-sequence to the calcareous soil, carbonate was found in the residues of the first two steps and extract pH-values rose by around two units in the first and second step, caused mainly by carbonate dissolution. This led to wrong assignment of the carbonate elements Ca, Mg, Sr, Ba, and also to decreased desorption and increased re-adsorption of ions in those steps. After repetition of the acetic acid step until extract pH remained low, the carbonate was completely destroyed and the distributions of the elements Ca, Mg, Sr, Ba as well as those of Co, Ni, Cu, Zn and Pb were found to be quite different to those determined in the original extraction. Furthermore, it could be shown that the effectiveness of the reduction process in step two was reduced by increasing pH: Fe oxides were not significantly attacked by the repeated acetic acid treatments, but a 10-fold amount of Fe was mobilized by hydroxylamine hydrochloride after complete carbonate destruction. On the other hand, only small amounts of Fe were released anyway. Even repeated reduction steps did not

Modelling sequentially scored item responses

NARCIS (Netherlands)

Akkermans, W.

2000-01-01

The sequential model can be used to describe the variable resulting from a sequential scoring process. In this paper two more item response models are investigated with respect to their suitability for sequential scoring: the partial credit model and the graded response model. The investigation is

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

Czech Academy of Sciences Publication Activity Database

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

2006-01-01

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

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

Science.gov (United States)

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

2004-07-16

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

In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants.

Science.gov (United States)

Soverini, Simona; De Benedittis, Caterina; Castagnetti, Fausto; Gugliotta, Gabriele; Mancini, Manuela; Bavaro, Luana; Machova Polakova, Katerina; Linhartova, Jana; Iurlo, Alessandra; Russo, Domenico; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

2016-08-02

Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal

Fractionation and distribution of risk elements in soil profiles at a Czech shooting range

Czech Academy of Sciences Publication Activity Database

Ash, C.; Tejnecký, V.; Šebek, O.; Němeček, K.; Žahourová-Dubová, L.; Bakardjieva, Snejana; Drahota, P.; Drábek, O.

2013-01-01

Roč. 59, č. 3 (2013), s. 121-129 ISSN 1214-1178 Institutional support: RVO:61388980 Keywords : lead * inorganic contaminants * BCR sequential extraction * soil probe * alkaline soil Subject RIV: CA - Inorganic Chemistry Impact factor: 1.113, year: 2013

Multi-agent sequential hypothesis testing

KAUST Repository

Kim, Kwang-Ki K.

2014-12-15

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

Observation of non-classical correlations in sequential measurements of photon polarization

International Nuclear Information System (INIS)

Suzuki, Yutaro; Iinuma, Masataka; Hofmann, Holger F

2016-01-01

A sequential measurement of two non-commuting quantum observables results in a joint probability distribution for all output combinations that can be explained in terms of an initial joint quasi-probability of the non-commuting observables, modified by the resolution errors and back-action of the initial measurement. Here, we show that the error statistics of a sequential measurement of photon polarization performed at different measurement strengths can be described consistently by an imaginary correlation between the statistics of resolution and back-action. The experimental setup was designed to realize variable strength measurements with well-controlled imaginary correlation between the statistical errors caused by the initial measurement of diagonal polarizations, followed by a precise measurement of the horizontal/vertical polarization. We perform the experimental characterization of an elliptically polarized input state and show that the same complex joint probability distribution is obtained at any measurement strength. (paper)

Performance improvements of pouch-type flexible thin-film lithium-ion batteries by modifying sequential screen-printing process

International Nuclear Information System (INIS)

Kang, Kun-Young; Lee, Young-Gi; Shin, Dong Ok; Kim, Jin-Chul; Kim, Kwang Man

2014-01-01

A pouch-type flexible thin-film lithium-ion battery is fabricated by sequential screen-printing (wet) processes to produce consecutive layers of a current collector, positive and negative electrodes, and a gel polymer electrolyte. Optimum conditions of each process are determined by adjusting the paste or slurry compositions to achieve lower surface resistance of each layer (current collector and electrodes) and higher ionic conductivity of the gel polymer electrolyte. The fabricated flexible thin-film lithium-ion battery (5.5 × 5.5 cm 2 , 325 μm thick) shows superior electrochemical performance, including an energy density of 292.3 Wh L −1 based on electrode size (4.0 × 4.0 cm 2 ), an initial discharge capacity of 2.5 mAh cm −2 per electrode area, and capacity retention ratio of over 68% at the 50th cycle. To further improve the battery performance, the wet processes are modified by adopting hybrid (dry-wet) processes, which mainly consist of the formation of metallic current collector layers (Al and Cu) using a thermal evaporator and another optimized gel polymer electrolyte, to achieve an energy density of 332.8 Wh L −1 and capacity retention ratio of 84% at the 50th cycle. Cell flexibility is also confirmed by stable open circuit voltages after the system is subjected to several hundred iterations of bending, stretching, and even folding. There is the possibility that the suggested wet and dry-wet processes can be expanded to a high-speed mass-production roll-to-roll process

Enhancing anticoagulation and endothelial cell proliferation of titanium surface by sequential immobilization of poly(ethylene glycol) and collagen

International Nuclear Information System (INIS)

Pan, Chang-Jiang; Hou, Yan-Hua; Ding, Hong-Yan; Dong, Yun-Xiao

2013-01-01

In the present study, poly(ethylene glycol) (PEG) and collagen I were sequentially immobilized on the titanium surface to simultaneously improve the anticoagulation and endothelial cell proliferation. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy analysis confirmed that PEG and collagen I were successfully immobilized on the titanium surface. Water contact angle results suggested the excellent hydrophilic surface after the immobilization. The anticoagulation experiments demonstrated that the immobilized PEG and collagen I on the titanium surface could not only obviously prevent platelet adhesion and aggregation but also prolong activated partial thromboplastin time (APTT), leading to the improved blood compatibility. Furthermore, immobilization of collagen to the end of PEG chain did not abate the anticoagulation. As compared to those on the pristine and PEG-modified titanium surfaces, endothelial cells exhibited improved proliferative profiles on the surface modified by the sequential immobilization of PEG and collagen in terms of CCK-8 assay, implying that the modified titanium may promote endothelialization without abating the blood compatibility. Our method may be used to modify the surface of blood-contacting biomaterials such as titanium to promote endothelialization and improve the anticoagulation, it may be helpful for development of the biomedical devices such as coronary stents, where endothelializaton and excellent anticoagulation are required.

Sequential charged particle reaction

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Science.gov (United States)

2010-05-01

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

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

Science.gov (United States)

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

2011-10-01

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

Eyewitness confidence in simultaneous and sequential lineups: a criterion shift account for sequential mistaken identification overconfidence.

Science.gov (United States)

Dobolyi, David G; Dodson, Chad S

2013-12-01

Confidence judgments for eyewitness identifications play an integral role in determining guilt during legal proceedings. Past research has shown that confidence in positive identifications is strongly associated with accuracy. Using a standard lineup recognition paradigm, we investigated accuracy using signal detection and ROC analyses, along with the tendency to choose a face with both simultaneous and sequential lineups. We replicated past findings of reduced rates of choosing with sequential as compared to simultaneous lineups, but notably found an accuracy advantage in favor of simultaneous lineups. Moreover, our analysis of the confidence-accuracy relationship revealed two key findings. First, we observed a sequential mistaken identification overconfidence effect: despite an overall reduction in false alarms, confidence for false alarms that did occur was higher with sequential lineups than with simultaneous lineups, with no differences in confidence for correct identifications. This sequential mistaken identification overconfidence effect is an expected byproduct of the use of a more conservative identification criterion with sequential than with simultaneous lineups. Second, we found a steady drop in confidence for mistaken identifications (i.e., foil identifications and false alarms) from the first to the last face in sequential lineups, whereas confidence in and accuracy of correct identifications remained relatively stable. Overall, we observed that sequential lineups are both less accurate and produce higher confidence false identifications than do simultaneous lineups. Given the increasing prominence of sequential lineups in our legal system, our data argue for increased scrutiny and possibly a wholesale reevaluation of this lineup format. PsycINFO Database Record (c) 2013 APA, all rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-12-01

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

Characterization of the CDR3 structure of the Vβ21 T cell clone in patients with P210(BCR-ABL)-positive chronic myeloid leukemia and B-cell acute lymphoblastic leukemia.

Science.gov (United States)

Zha, Xianfeng; Chen, Shaohua; Yang, Lijian; Li, Bo; Chen, Yu; Yan, Xiaojuan; Li, Yangqiu

2011-10-01

The clonally expanded T cells identified in most cancer patients that respond to tumor-associated antigen such as P210(BCR-ABL) protein have definite, specific antitumor cytotoxicity. T cell receptor (TCR) Vβ CDR3 repertoire diversity was analyzed in patients with chronic myeloid leukemia (CML) and BCR-ABL(+) B-cell acute lymphoblastic leukemia (B-ALL) by GeneScan. A high frequency of oligoclonal expansion of the TCR Vβ21 subfamily was observed in the peripheral blood of CML and B-ALL patients. These clonally expanded Vβ21 T cells were correlated with the pathophysiologic process of CML. A conserved amino acid motif (SLxxV) was observed within the CDR3 region in only 3 patients with CML. Preferential usage of the Jβ segments was also observed in a minority of patients. The 3-dimensional structures of the CDR3 region containing the same motif or using the same Jβ segment displayed low similarity; on the contrary, the conformation of the CDR3 region containing no conserved motif in some T cell clones was highly similar. In conclusion, our findings indicate a high frequency of TCR Vβ21 subfamily expansion in p210(BCR-ABL)-positive CML and B-ALL patients. The characterization of the CDR3 structure was complex. Regrettably, at this time it was not possible to confirm that the Vβ21 T cell clones were derived from the stimulation of p210(BCR-ABL) protein. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Simultaneous versus Sequential Intratympanic Steroid Treatment for Severe-to-Profound Sudden Sensorineural Hearing Loss.

Science.gov (United States)

Yoo, Myung Hoon; Lim, Won Sub; Park, Joo Hyun; Kwon, Joong Keun; Lee, Tae-Hoon; An, Yong-Hwi; Kim, Young-Jin; Kim, Jong Yang; Lim, Hyun Woo; Park, Hong Ju

2016-01-01

Severe-to-profound sudden sensorineural hearing loss (SSNHL) has a poor prognosis. We aimed to compare the efficacy of simultaneous and sequential oral and intratympanic steroids for this condition. Fifty patients with severe-to-profound SSNHL (>70 dB HL) were included from 7 centers. The simultaneous group (27 patients) received oral and intratympanic steroid injections for 2 weeks. The sequential group (23 patients) was treated with oral steroids for 2 weeks and intratympanic steroids for the subsequent 2 weeks. Pure-tone averages (PTA) and word discrimination scores (WDS) were compared before treatment and 2 weeks and 1 and 2 months after treatment. Treatment outcomes according to the modified American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria were also analyzed. The improvement in PTA and WDS at the 2-week follow-up was 23 ± 21 dB HL and 20 ± 39% in the simultaneous group and 31 ± 29 dB HL and 37 ± 42% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-week follow-up was observed in 26% of the simultaneous group and 30% of the sequential group; this was also not significant. The improvement in PTA and WDS at the 2-month follow-up was 40 ± 20 dB HL and 37 ± 35% in the simultaneous group and 41 ± 25 dB HL and 48 ± 41% in the sequential group; this was not statistically significant. Complete or partial recovery at the 2-month follow-up was observed in 33% of the simultaneous group and 35% of the sequential group; this was also not significant. Seven patients in the sequential group did not need intratympanic steroid injections for sufficient improvement after oral steroids alone. Simultaneous oral/intratympanic steroid treatment yielded a recovery similar to that produced by sequential treatment. Because the addition of intratympanic steroids can be decided upon based on the improvement after an oral steroid, the sequential regimen can be recommended to avoid unnecessary

SÍNTESES E PROPRIEDADES DE FÁRMACOS INIBIDORES DA TIROSINA QUINASE BCR-ABL, UTILIZADOS NO TRATAMENTO DA LEUCEMIA MIELOIDE CRÔNICA

Directory of Open Access Journals (Sweden)

Liviane D. de Azevedo

Full Text Available The chronic myeloid leukemia (CML is characterized by presence of the Philadelphia chromosome (Ph, originated from the translocation between chromosomes 9 and 22. This chromosome generates an abnormal protein tyrosine kinase which is responsible for tumor cell proliferation. The emergence of tyrosine kinase inhibitors (TKIs has transformed the treatment of CML and imatinib being the first representative of this class. Although treatment with imatinib has reached surprising results, approximately 30% of patients exhibited resistance, especially in later stages of the disease. This fact stimulated the development of novel BCR-ABL enzyme inhibitors drugs classified as tyrosine kinase inhibitors (TKIs of second and third generations. The TKIs have different chemical functions in their structure, and the knowledge of synthetic methods for preparation of these compounds can be a powerful tool for the development of new derivatives. The five approved BCR-ABL Tyrosine Kinase inhibitors (TKI used in Chronic Myeloid Leukemia (CML are reviewed aiming the main synthetic routes, highlighting the advantages and disadvantages associated with them.

Overcoming imatinib resistance using Src inhibitor CGP76030, Abl inhibitor nilotinib and Abl/Lyn inhibitor INNO-406 in newly established K562 variants with BCR-ABL gene amplification.

Science.gov (United States)

Morinaga, Koji; Yamauchi, Takahiro; Kimura, Shinya; Maekawa, Taira; Ueda, Takanori

2008-06-01

Because imatinib (IM) resistance in chronic myeloid leukemia is primarily caused by the re-establishment of Abl kinase, new inhibitors may be efficacious. We evaluated 3 new agents against 2 new K562 variants, IM-R1 and IM-R2 cells, which were developed having 7- and 27-fold greater IM resistance, respectively, than the parental K562 cells. Both variants possessed BCR-ABL gene amplification along with elevated levels of its transcript and protein. Greater BCR-ABL gene amplification was observed in IM-R2 cells than in IM-R1 cells, which was consistent with the higher mRNA and protein levels of Bcr-Abl, and ultimately correlated with the greater IM resistance in IM-R2 cells. No mutation in the Abl kinase domain was detected in either variant. Despite the absence of Lyn overexpression, the Src kinase inhibitor CGP76030 showed positive cooperability with IM in inhibiting cell growth of not only K562 cells but also these 2 variants. This might be because of the augmented inhibition of Erk1/2 phosphorylation. The new Abl kinase inhibitor nilotinib was 10-fold more potent than IM in inhibiting the growth of K562 cells. Nilotinib inhibited the growth of IM-R1 and IM-R2 cells as potently as K562 cells. The combination of nilotinib with CGP76030 showed little additivity, because the potency of nilotinib masked the efficacy of CGP76030. The new dual Abl/Lyn inhibitor INNO-406 (formerly NS-187) was slightly more potent than nilotinib in inhibiting the growth of all 3 cell lines. Because BCR-ABL gene amplification occurs in blast crisis, these inhibitors might overcome IM resistance in such patients' leukemia. (c) 2008 Wiley-Liss, Inc.

Remarks on sequential designs in risk assessment

International Nuclear Information System (INIS)

Seidenfeld, T.

1982-01-01

The special merits of sequential designs are reviewed in light of particular challenges that attend risk assessment for human population. The kinds of ''statistical inference'' are distinguished and the problem of design which is pursued is the clash between Neyman-Pearson and Bayesian programs of sequential design. The value of sequential designs is discussed and the Neyman-Pearson vs. Bayesian sequential designs are probed in particular. Finally, warnings with sequential designs are considered, especially in relation to utilitarianism

Exploring Liquid Sequential Injection Chromatography to Teach Fundamentals of Separation Methods: A Very Fast Analytical Chemistry Experiment

Science.gov (United States)

Penteado, Jose C.; Masini, Jorge Cesar

2011-01-01

Influence of the solvent strength determined by the addition of a mobile-phase organic modifier and pH on chromatographic separation of sorbic acid and vanillin has been investigated by the relatively new technique, liquid sequential injection chromatography (SIC). This technique uses reversed-phase monolithic stationary phase to execute fast…

Contribution of nuclear analysis methods to the certification of BCR reference materials for non-metals in non-ferrous metals

International Nuclear Information System (INIS)

Pauwels, J.

1979-01-01

A number of reference materials for oxygen in different non-ferrous metals have been certified by BCR in the frame of a multidisciplinary Community project. The contribution of nuclear analysis methods is illustrated by several examples concerning the optimization of sample preparation techniques, the analysis of low and high oxygen non-ferrous metals and the extension of the program to other non-metals, especially nitrogen and carbon. (author)

Sequential lineup laps and eyewitness accuracy.

Science.gov (United States)

Steblay, Nancy K; Dietrich, Hannah L; Ryan, Shannon L; Raczynski, Jeanette L; James, Kali A

2011-08-01

Police practice of double-blind sequential lineups prompts a question about the efficacy of repeated viewings (laps) of the sequential lineup. Two laboratory experiments confirmed the presence of a sequential lap effect: an increase in witness lineup picks from first to second lap, when the culprit was a stranger. The second lap produced more errors than correct identifications. In Experiment 2, lineup diagnosticity was significantly higher for sequential lineup procedures that employed a single versus double laps. Witnesses who elected to view a second lap made significantly more errors than witnesses who chose to stop after one lap or those who were required to view two laps. Witnesses with prior exposure to the culprit did not exhibit a sequential lap effect.

Robustness of the Sequential Lineup Advantage

Science.gov (United States)

Gronlund, Scott D.; Carlson, Curt A.; Dailey, Sarah B.; Goodsell, Charles A.

2009-01-01

A growing movement in the United States and around the world involves promoting the advantages of conducting an eyewitness lineup in a sequential manner. We conducted a large study (N = 2,529) that included 24 comparisons of sequential versus simultaneous lineups. A liberal statistical criterion revealed only 2 significant sequential lineup…

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

Science.gov (United States)

Fujii, Soichiro; Miura, Ikuo; Tanaka, Hideo

2015-06-01

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

Multi-agent sequential hypothesis testing

KAUST Repository

Kim, Kwang-Ki K.; Shamma, Jeff S.

2014-01-01

incorporate costs of taking private/public measurements, costs of time-difference and disagreement in actions of agents, and costs of false declaration/choices in the sequential hypothesis testing. The corresponding sequential decision processes have well

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

Science.gov (United States)

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

2018-04-25

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

On the possibilities of high-resolution continuum source graphite furnace atomic absorption spectrometry for the simultaneous or sequential monitoring of multiple atomic lines

International Nuclear Information System (INIS)

Resano, M.; Rello, L.; Florez, M.; Belarra, M.A.

2011-01-01

This paper explores the potential of commercially available high-resolution continuum source graphite furnace atomic absorption spectrometry instrumentation for the simultaneous or sequential monitoring of various atomic lines, in an attempt to highlight the analytical advantages that can be derived from this strategy. In particular, it is demonstrated how i) the monitoring of multiplets may allow for the simple expansion of the linear range, as shown for the measurement of Ni using the triplet located in the vicinity of 234.6 nm; ii) the use of a suitable internal standard may permit improving the precision and help in correcting for matrix-effects, as proved for the monitoring of Ni in different biological samples; iii) direct and multi-element analysis of solid samples may be feasible on some occasions, either by monitoring various atomic lines that are sufficiently close (truly simultaneous monitoring, as demonstrated in the determination of Co, Fe and Ni in NIST 1566a Oyster tissue) or, alternatively, by opting for a selective and sequential atomization of the elements of interest during every single replicate. Determination of Cd and Ni in BCR 679 White cabbage is attempted using both approaches, which permits confirming that both methods can offer very similar and satisfactory results. However, it is important to stress that the second approach provides more flexibility, since analysis is no longer limited to those elements that show very close atomic lines (closer than 0.3 nm in the ultraviolet region) with a sensitivity ratio similar to the concentration ratio of the analytes in the samples investigated.

Sequential stochastic optimization

CERN Document Server

Cairoli, Renzo

1996-01-01

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

Sequential and simultaneous choices: testing the diet selection and sequential choice models.

Science.gov (United States)

Freidin, Esteban; Aw, Justine; Kacelnik, Alex

2009-03-01

We investigate simultaneous and sequential choices in starlings, using Charnov's Diet Choice Model (DCM) and Shapiro, Siller and Kacelnik's Sequential Choice Model (SCM) to integrate function and mechanism. During a training phase, starlings encountered one food-related option per trial (A, B or R) in random sequence and with equal probability. A and B delivered food rewards after programmed delays (shorter for A), while R ('rejection') moved directly to the next trial without reward. In this phase we measured latencies to respond. In a later, choice, phase, birds encountered the pairs A-B, A-R and B-R, the first implementing a simultaneous choice and the second and third sequential choices. The DCM predicts when R should be chosen to maximize intake rate, and SCM uses latencies of the training phase to predict choices between any pair of options in the choice phase. The predictions of both models coincided, and both successfully predicted the birds' preferences. The DCM does not deal with partial preferences, while the SCM does, and experimental results were strongly correlated to this model's predictions. We believe that the SCM may expose a very general mechanism of animal choice, and that its wider domain of success reflects the greater ecological significance of sequential over simultaneous choices.

Chemical and sequential analysis of some metals in sediments from the North Coast of the Gulf of Mexico

International Nuclear Information System (INIS)

Trinidad Martinez; Brenda Estanol; Miguel Angel Zuniga

2016-01-01

Sediments collected from the North Coast of the Gulf of Mexico got carefully mixed, dried, and finally subjected to physical and chemical analysis. Metal concentration was determined by energy dispersive X-ray fluorescence (EDXRF). Sequential chemical analysis was performed by modified TESSIER technique. Results and statistical analysis (α = 0.05) show concentrations of most elements (excepting Mn, Ca, Ga, As and Pb) in the range of those of the earth crust's values, which set a sampling zone base line. Sequential extraction shows the potential risk of mobilization of metals sequestered in particulate phases by oxidation of anoxic sediments or intense organic matter degradation. (author)

Sequential memory: Binding dynamics

Science.gov (United States)

Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

2015-10-01

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

Sequential Probability Ration Tests : Conservative and Robust

NARCIS (Netherlands)

Kleijnen, J.P.C.; Shi, Wen

2017-01-01

In practice, most computers generate simulation outputs sequentially, so it is attractive to analyze these outputs through sequential statistical methods such as sequential probability ratio tests (SPRTs). We investigate several SPRTs for choosing between two hypothesized values for the mean output

On Modeling Large-Scale Multi-Agent Systems with Parallel, Sequential and Genuinely Asynchronous Cellular Automata

International Nuclear Information System (INIS)

Tosic, P.T.

2011-01-01

We study certain types of Cellular Automata (CA) viewed as an abstraction of large-scale Multi-Agent Systems (MAS). We argue that the classical CA model needs to be modified in several important respects, in order to become a relevant and sufficiently general model for the large-scale MAS, and so that thus generalized model can capture many important MAS properties at the level of agent ensembles and their long-term collective behavior patterns. We specifically focus on the issue of inter-agent communication in CA, and propose sequential cellular automata (SCA) as the first step, and genuinely Asynchronous Cellular Automata (ACA) as the ultimate deterministic CA-based abstract models for large-scale MAS made of simple reactive agents. We first formulate deterministic and nondeterministic versions of sequential CA, and then summarize some interesting configuration space properties (i.e., possible behaviors) of a restricted class of sequential CA. In particular, we compare and contrast those properties of sequential CA with the corresponding properties of the classical (that is, parallel and perfectly synchronous) CA with the same restricted class of update rules. We analytically demonstrate failure of the studied sequential CA models to simulate all possible behaviors of perfectly synchronous parallel CA, even for a very restricted class of non-linear totalistic node update rules. The lesson learned is that the interleaving semantics of concurrency, when applied to sequential CA, is not refined enough to adequately capture the perfect synchrony of parallel CA updates. Last but not least, we outline what would be an appropriate CA-like abstraction for large-scale distributed computing insofar as the inter-agent communication model is concerned, and in that context we propose genuinely asynchronous CA. (author)

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

Science.gov (United States)

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

2015-09-01

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

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.

Sequential lineup presentation: Patterns and policy

OpenAIRE

Lindsay, R C L; Mansour, Jamal K; Beaudry, J L; Leach, A-M; Bertrand, M I

2009-01-01

Sequential lineups were offered as an alternative to the traditional simultaneous lineup. Sequential lineups reduce incorrect lineup selections; however, the accompanying loss of correct identifications has resulted in controversy regarding adoption of the technique. We discuss the procedure and research relevant to (1) the pattern of results found using sequential versus simultaneous lineups; (2) reasons (theory) for differences in witness responses; (3) two methodological issues; and (4) im...

Sequential Product of Quantum Effects: An Overview

Science.gov (United States)

Gudder, Stan

2010-12-01

This article presents an overview for the theory of sequential products of quantum effects. We first summarize some of the highlights of this relatively recent field of investigation and then provide some new results. We begin by discussing sequential effect algebras which are effect algebras endowed with a sequential product satisfying certain basic conditions. We then consider sequential products of (discrete) quantum measurements. We next treat transition effect matrices (TEMs) and their associated sequential product. A TEM is a matrix whose entries are effects and whose rows form quantum measurements. We show that TEMs can be employed for the study of quantum Markov chains. Finally, we prove some new results concerning TEMs and vector densities.

Optimal Sequential Rules for Computer-Based Instruction.

Science.gov (United States)

Vos, Hans J.

1998-01-01

Formulates sequential rules for adapting the appropriate amount of instruction to learning needs in the context of computer-based instruction. Topics include Bayesian decision theory, threshold and linear-utility structure, psychometric model, optimal sequential number of test questions, and an empirical example of sequential instructional…

Optical properties of multicomponent antimony-silver nanoclusters formed in silica by sequential ion implantation

International Nuclear Information System (INIS)

Zuhr, R.A.

1995-11-01

The linear and nonlinear optical properties of nanometer dimension metal colloids embedded in a dielectric depend explicitly on the electronic structure of the metal nanoclusters. The ability to control the electronic structure of the nanoclusters may make it possible to tailor the optical properties for enhanced performance. By sequential implantation of different metal ion species multi-component nanoclusters can be formed with significantly different optical properties than single element metal nanoclusters. The authors report the formation of multi-component Sb/Ag nanoclusters in silica by sequential implantation of Sb and Ag. Samples were implanted with relative ratios of Sb to Ag of 1:1 and 3:1. A second set of samples was made by single element implantations of Ag and Sb at the same energies and doses used to make the sequentially implanted samples. All samples were characterized using RBS and both linear and nonlinear optical measurements. The presence of both ions significantly modifies the optical properties of the composites compared to the single element nanocluster glass composites. In the sequentially implanted samples the optical density is lower, and the strong surface plasmon resonance absorption observed in the Ag implanted samples is not present. At the same time the nonlinear response of the these samples is larger than for the samples implanted with Sb alone, suggesting that the addition of Ag can increase the nonlinear response of the Sb particles formed. The results are consistent with the formation of multi-component Sb/Ag colloids

Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay.

Directory of Open Access Journals (Sweden)

J Matthew Mahoney

Full Text Available Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation.

Quantum Inequalities and Sequential Measurements

International Nuclear Information System (INIS)

Candelpergher, B.; Grandouz, T.; Rubinx, J.L.

2011-01-01

In this article, the peculiar context of sequential measurements is chosen in order to analyze the quantum specificity in the two most famous examples of Heisenberg and Bell inequalities: Results are found at some interesting variance with customary textbook materials, where the context of initial state re-initialization is described. A key-point of the analysis is the possibility of defining Joint Probability Distributions for sequential random variables associated to quantum operators. Within the sequential context, it is shown that Joint Probability Distributions can be defined in situations where not all of the quantum operators (corresponding to random variables) do commute two by two. (authors)

A comparison of a modified sequential oral sensory approach to an applied behavior-analytic approach in the treatment of food selectivity in children with autism spectrum disorder.

Science.gov (United States)

Peterson, Kathryn M; Piazza, Cathleen C; Volkert, Valerie M

2016-09-01

Treatments of pediatric feeding disorders based on applied behavior analysis (ABA) have the most empirical support in the research literature (Volkert & Piazza, 2012); however, professionals often recommend, and caregivers often use, treatments that have limited empirical support. In the current investigation, we compared a modified sequential oral sensory approach (M-SOS; Benson, Parke, Gannon, & Muñoz, 2013) to an ABA approach for the treatment of the food selectivity of 6 children with autism. We randomly assigned 3 children to ABA and 3 children to M-SOS and compared the effects of treatment in a multiple baseline design across novel, healthy target foods. We used a multielement design to assess treatment generalization. Consumption of target foods increased for children who received ABA, but not for children who received M-SOS. We subsequently implemented ABA with the children for whom M-SOS was not effective and observed a potential treatment generalization effect during ABA when M-SOS preceded ABA. © 2016 Society for the Experimental Analysis of Behavior.

Sequential Generalized Transforms on Function Space

Directory of Open Access Journals (Sweden)

Jae Gil Choi

2013-01-01

Full Text Available We define two sequential transforms on a function space Ca,b[0,T] induced by generalized Brownian motion process. We then establish the existence of the sequential transforms for functionals in a Banach algebra of functionals on Ca,b[0,T]. We also establish that any one of these transforms acts like an inverse transform of the other transform. Finally, we give some remarks about certain relations between our sequential transforms and other well-known transforms on Ca,b[0,T].

Forced Sequence Sequential Decoding

DEFF Research Database (Denmark)

Jensen, Ole Riis; Paaske, Erik

1998-01-01

We describe a new concatenated decoding scheme based on iterations between an inner sequentially decoded convolutional code of rate R=1/4 and memory M=23, and block interleaved outer Reed-Solomon (RS) codes with nonuniform profile. With this scheme decoding with good performance is possible as low...... as Eb/N0=0.6 dB, which is about 1.25 dB below the signal-to-noise ratio (SNR) that marks the cutoff rate for the full system. Accounting for about 0.45 dB due to the outer codes, sequential decoding takes place at about 1.7 dB below the SNR cutoff rate for the convolutional code. This is possible since...... the iteration process provides the sequential decoders with side information that allows a smaller average load and minimizes the probability of computational overflow. Analytical results for the probability that the first RS word is decoded after C computations are presented. These results are supported...

Nuclear topography and expression of the BCR/ABL fusion gene and its protein level influenced by cell differentiation and RNA interference

Czech Academy of Sciences Publication Activity Database

Bártová, Eva; Harničarová, Andrea; Pacherník, Jiří; Kozubek, Stanislav

2005-01-01

Roč. 29, č. 8 (2005), s. 901-913 ISSN 0145-2126 R&D Projects: GA AV ČR(CZ) 1QS500040508; GA ČR(CZ) GA202/04/0907; GA MZd NC6987; GA AV ČR(CZ) IAA5004306; GA MŠk(CZ) LC535 Institutional research plan: CEZ:AV0Z50040507 Keywords : BCR /ABL fusion gene * chromatin arrangement * gene expression Subject RIV: BO - Biophysics Impact factor: 2.372, year: 2005

Sequential probability ratio controllers for safeguards radiation monitors

International Nuclear Information System (INIS)

Fehlau, P.E.; Coop, K.L.; Nixon, K.V.

1984-01-01

Sequential hypothesis tests applied to nuclear safeguards accounting methods make the methods more sensitive to detecting diversion. The sequential tests also improve transient signal detection in safeguards radiation monitors. This paper describes three microprocessor control units with sequential probability-ratio tests for detecting transient increases in radiation intensity. The control units are designed for three specific applications: low-intensity monitoring with Poisson probability ratios, higher intensity gamma-ray monitoring where fixed counting intervals are shortened by sequential testing, and monitoring moving traffic where the sequential technique responds to variable-duration signals. The fixed-interval controller shortens a customary 50-s monitoring time to an average of 18 s, making the monitoring delay less bothersome. The controller for monitoring moving vehicles benefits from the sequential technique by maintaining more than half its sensitivity when the normal passage speed doubles

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

NARCIS (Netherlands)

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

2005-01-01

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

Application of EDTA decontamination on soils affected by mining activities and impact of treatment on the geochemical partition of metal contaminants.

Science.gov (United States)

Xia, Wenbin; Gao, Hui; Wang, Xianhai; Zhou, Chunhua; Liu, Yunguo; Fan, Ting; Wang, Xin

2009-05-30

Two soil samples were collected at mining areas located in southern Hunan Province, China. EDTA extraction of Pb, Zn, Cu and Cd from these two tailing soils was studied using column leaching experiments. The redistributions of heavy metals (HMs) were determined using the modified BCR (Community Bureau of Reference) sequential extraction procedure, before and after EDTA extraction. The results indicated that EDTA was an effective extractant because of its strong chelating ability for various HMs. The proportions of Pb, Zn, Cu and Cd in the four fractions varied largely after EDTA extraction. The extraction efficiency of EDTA of the acid-extractable fraction (AEX) was significant in shallow soil column, while in deeper soil column, decrease of the extraction efficiency of reduced (RED), oxidizable (OX) and residual fractions (RES) was obtained, which was mainly due to the decrease of EDTA concentration.

Biased lineups: sequential presentation reduces the problem.

Science.gov (United States)

Lindsay, R C; Lea, J A; Nosworthy, G J; Fulford, J A; Hector, J; LeVan, V; Seabrook, C

1991-12-01

Biased lineups have been shown to increase significantly false, but not correct, identification rates (Lindsay, Wallbridge, & Drennan, 1987; Lindsay & Wells, 1980; Malpass & Devine, 1981). Lindsay and Wells (1985) found that sequential lineup presentation reduced false identification rates, presumably by reducing reliance on relative judgment processes. Five staged-crime experiments were conducted to examine the effect of lineup biases and sequential presentation on eyewitness recognition accuracy. Sequential lineup presentation significantly reduced false identification rates from fair lineups as well as from lineups biased with regard to foil similarity, instructions, or witness attire, and from lineups biased in all of these ways. The results support recommendations that police present lineups sequentially.

Lineup composition, suspect position, and the sequential lineup advantage.

Science.gov (United States)

Carlson, Curt A; Gronlund, Scott D; Clark, Steven E

2008-06-01

N. M. Steblay, J. Dysart, S. Fulero, and R. C. L. Lindsay (2001) argued that sequential lineups reduce the likelihood of mistaken eyewitness identification. Experiment 1 replicated the design of R. C. L. Lindsay and G. L. Wells (1985), the first study to show the sequential lineup advantage. However, the innocent suspect was chosen at a lower rate in the simultaneous lineup, and no sequential lineup advantage was found. This led the authors to hypothesize that protection from a sequential lineup might emerge only when an innocent suspect stands out from the other lineup members. In Experiment 2, participants viewed a simultaneous or sequential lineup with either the guilty suspect or 1 of 3 innocent suspects. Lineup fairness was varied to influence the degree to which a suspect stood out. A sequential lineup advantage was found only for the unfair lineups. Additional analyses of suspect position in the sequential lineups showed an increase in the diagnosticity of suspect identifications as the suspect was placed later in the sequential lineup. These results suggest that the sequential lineup advantage is dependent on lineup composition and suspect position. (c) 2008 APA, all rights reserved

Author Details

African Journals Online (AJOL)

Ozcan, N., Ethiopia. Vol 27, No 2 (2013) - Articles Speciation of heavy metals in street dust samples from Sakarya I. Organized industrial district using the BCR sequential extraction procedure by ICP-OES Abstract PDF. ISSN: 1726-801X. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

Tradable permit allocations and sequential choice

Energy Technology Data Exchange (ETDEWEB)

MacKenzie, Ian A. [Centre for Economic Research, ETH Zuerich, Zurichbergstrasse 18, 8092 Zuerich (Switzerland)

2011-01-15

This paper investigates initial allocation choices in an international tradable pollution permit market. For two sovereign governments, we compare allocation choices that are either simultaneously or sequentially announced. We show sequential allocation announcements result in higher (lower) aggregate emissions when announcements are strategic substitutes (complements). Whether allocation announcements are strategic substitutes or complements depends on the relationship between the follower's damage function and governments' abatement costs. When the marginal damage function is relatively steep (flat), allocation announcements are strategic substitutes (complements). For quadratic abatement costs and damages, sequential announcements provide a higher level of aggregate emissions. (author)

Accurate determination of arsenic in arsenobetaine standard solutions of BCR-626 and NMIJ CRM 7901-a by neutron activation analysis coupled with internal standard method.

Science.gov (United States)

Miura, Tsutomu; Chiba, Koichi; Kuroiwa, Takayoshi; Narukawa, Tomohiro; Hioki, Akiharu; Matsue, Hideaki

2010-09-15

Neutron activation analysis (NAA) coupled with an internal standard method was applied for the determination of As in the certified reference material (CRM) of arsenobetaine (AB) standard solutions to verify their certified values. Gold was used as an internal standard to compensate for the difference of the neutron exposure in an irradiation capsule and to improve the sample-to-sample repeatability. Application of the internal standard method significantly improved linearity of the calibration curve up to 1 microg of As, too. The analytical reliability of the proposed method was evaluated by k(0)-standardization NAA. The analytical results of As in AB standard solutions of BCR-626 and NMIJ CRM 7901-a were (499+/-55)mgkg(-1) (k=2) and (10.16+/-0.15)mgkg(-1) (k=2), respectively. These values were found to be 15-20% higher than the certified values. The between-bottle variation of BCR-626 was much larger than the expanded uncertainty of the certified value, although that of NMIJ CRM 7901-a was almost negligible. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Applying the minimax principle to sequential mastery testing

NARCIS (Netherlands)

Vos, Hendrik J.

2002-01-01

The purpose of this paper is to derive optimal rules for sequential mastery tests. In a sequential mastery test, the decision is to classify a subject as a master, a nonmaster, or to continue sampling and administering another random item. The framework of minimax sequential decision theory (minimum

INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity.

Science.gov (United States)

Yokota, Asumi; Kimura, Shinya; Masuda, Satohiro; Ashihara, Eishi; Kuroda, Junya; Sato, Kiyoshi; Kamitsuji, Yuri; Kawata, Eri; Deguchi, Yasuyuki; Urasaki, Yoshimasa; Terui, Yasuhito; Ruthardt, Martin; Ueda, Takanori; Hatake, Kiyohiko; Inui, Ken-ichi; Maekawa, Taira

2007-01-01

Central nervous system (CNS) relapse accompanying the prolonged administration of imatinib mesylate has recently become apparent as an impediment to the therapy of Philadelphia chromosome-positive (Ph+) leukemia. CNS relapse may be explained by limited penetration of imatinib mesylate into the cerebrospinal fluid because of the presence of P-glycoprotein at the blood-brain barrier. To overcome imatinib mesylate-resistance mechanisms such as bcr-abl amplification, mutations within the ABL kinase domain, and activation of Lyn, we developed a dual BCR-ABL/Lyn inhibitor, INNO-406 (formerly NS-187), which is 25 to 55 times more potent than imatinib mesylate in vitro and at least 10 times more potent in vivo. The aim of this study was to investigate the efficacy of INNO-406 in treating CNS Ph+ leukemia. We found that INNO-406, like imatinib mesylate, is a substrate for P-glycoprotein. The concentrations of INNO-406 in the CNS were about 10% of those in the plasma. However, this residual concentration was enough to inhibit the growth of Ph+ leukemic cells which expressed not only wild-type but also mutated BCR-ABL in the murine CNS. Furthermore, cyclosporine A, a P-glycoprotein inhibitor, augmented the in vivo activity of INNO-406 against CNS Ph+ leukemia. These findings indicate that INNO-406 is a promising agent for the treatment of CNS Ph+ leukemia.

Classical and sequential limit analysis revisited

Science.gov (United States)

Leblond, Jean-Baptiste; Kondo, Djimédo; Morin, Léo; Remmal, Almahdi

2018-04-01

Classical limit analysis applies to ideal plastic materials, and within a linearized geometrical framework implying small displacements and strains. Sequential limit analysis was proposed as a heuristic extension to materials exhibiting strain hardening, and within a fully general geometrical framework involving large displacements and strains. The purpose of this paper is to study and clearly state the precise conditions permitting such an extension. This is done by comparing the evolution equations of the full elastic-plastic problem, the equations of classical limit analysis, and those of sequential limit analysis. The main conclusion is that, whereas classical limit analysis applies to materials exhibiting elasticity - in the absence of hardening and within a linearized geometrical framework -, sequential limit analysis, to be applicable, strictly prohibits the presence of elasticity - although it tolerates strain hardening and large displacements and strains. For a given mechanical situation, the relevance of sequential limit analysis therefore essentially depends upon the importance of the elastic-plastic coupling in the specific case considered.

Simultaneous versus sequential penetrating keratoplasty and cataract surgery.

Science.gov (United States)

Hayashi, Ken; Hayashi, Hideyuki

2006-10-01

To compare the surgical outcomes of simultaneous penetrating keratoplasty and cataract surgery with those of sequential surgery. Thirty-nine eyes of 39 patients scheduled for simultaneous keratoplasty and cataract surgery and 23 eyes of 23 patients scheduled for sequential keratoplasty and secondary phacoemulsification surgery were recruited. Refractive error, regular and irregular corneal astigmatism determined by Fourier analysis, and endothelial cell loss were studied at 1 week and 3, 6, and 12 months after combined surgery in the simultaneous surgery group or after subsequent phacoemulsification surgery in the sequential surgery group. At 3 and more months after surgery, mean refractive error was significantly greater in the simultaneous surgery group than in the sequential surgery group, although no difference was seen at 1 week. The refractive error at 12 months was within 2 D of that targeted in 15 eyes (39%) in the simultaneous surgery group and within 2 D in 16 eyes (70%) in the sequential surgery group; the incidence was significantly greater in the sequential group (P = 0.0344). The regular and irregular astigmatism was not significantly different between the groups at 3 and more months after surgery. No significant difference was also found in the percentage of endothelial cell loss between the groups. Although corneal astigmatism and endothelial cell loss were not different, refractive error from target refraction was greater after simultaneous keratoplasty and cataract surgery than after sequential surgery, indicating a better outcome after sequential surgery than after simultaneous surgery.

Adaptive sequential controller

Energy Technology Data Exchange (ETDEWEB)

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

1994-01-01

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

Adaptive sequential controller

Science.gov (United States)

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

1994-01-01

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

Trial Sequential Methods for Meta-Analysis

Science.gov (United States)

Kulinskaya, Elena; Wood, John

2014-01-01

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

Thermodynamic performance analysis of sequential Carnot cycles using heat sources with finite heat capacity

International Nuclear Information System (INIS)

Park, Hansaem; Kim, Min Soo

2014-01-01

The maximum efficiency of a heat engine is able to be estimated by using a Carnot cycle. Even though, in terms of efficiency, the Carnot cycle performs the role of reference very well, its application is limited to the case of infinite heat reservoirs, which is not that realistic. Moreover, considering that one of the recent key issues is to produce maximum work from low temperature and finite heat sources, which are called renewable energy sources, more advanced theoretical cycles, which can present a new standard, and the research about them are necessary. Therefore, in this paper, a sequential Carnot cycle, where multiple Carnot cycles are connected in parallel, is studied. The cycle adopts a finite heat source, which has a certain initial temperature and heat capacity, and an infinite heat sink, which is assumed to be ambient air. Heat transfer processes in the cycle occur with the temperature difference between a heat reservoir and a cycle. In order to resolve the heat transfer rate in those processes, the product of an overall heat transfer coefficient and a heat transfer area is introduced. Using these conditions, the performance of a sequential Carnot cycle is analytically calculated. Furthermore, as the efforts for enhancing the work of the cycle, the optimization research is also conducted with numerical calculation. - Highlights: • Modified sequential Carnot cycles are proposed for evaluating low grade heat sources. • Performance of sequential Carnot cycles is calculated analytically. • Optimization study for the cycle is conducted with numerical solver. • Maximum work from a heat source under a certain condition is obtained by equations

Sequentially pulsed traveling wave accelerator

Science.gov (United States)

Caporaso, George J [Livermore, CA; Nelson, Scott D [Patterson, CA; Poole, Brian R [Tracy, CA

2009-08-18

A sequentially pulsed traveling wave compact accelerator having two or more pulse forming lines each with a switch for producing a short acceleration pulse along a short length of a beam tube, and a trigger mechanism for sequentially triggering the switches so that a traveling axial electric field is produced along the beam tube in synchronism with an axially traversing pulsed beam of charged particles to serially impart energy to the particle beam.

Sequential growth factor application in bone marrow stromal cell ligament engineering.

Science.gov (United States)

Moreau, Jodie E; Chen, Jingsong; Horan, Rebecca L; Kaplan, David L; Altman, Gregory H

2005-01-01

In vitro bone marrow stromal cell (BMSC) growth may be enhanced through culture medium supplementation, mimicking the biochemical environment in which cells optimally proliferate and differentiate. We hypothesize that the sequential administration of growth factors to first proliferate and then differentiate BMSCs cultured on silk fiber matrices will support the enhanced development of ligament tissue in vitro. Confluent second passage (P2) BMSCs obtained from purified bone marrow aspirates were seeded on RGD-modified silk matrices. Seeded matrices were divided into three groups for 5 days of static culture, with medium supplement of basic fibroblast growth factor (B) (1 ng/mL), epidermal growth factor (E; 1 ng/mL), or growth factor-free control (C). After day 5, medium supplementation was changed to transforming growth factor-beta1 (T; 5 ng/mL) or C for an additional 9 days of culture. Real-time RT-PCR, SEM, MTT, histology, and ELISA for collagen type I of all sample groups were performed. Results indicated that BT supported the greatest cell ingrowth after 14 days of culture in addition to the greatest cumulative collagen type I expression measured by ELISA. Sequential growth factor application promoted significant increases in collagen type I transcript expression from day 5 of culture to day 14, for five of six groups tested. All T-supplemented samples surpassed their respective control samples in both cell ingrowth and collagen deposition. All samples supported spindle-shaped, fibroblast cell morphology, aligning with the direction of silk fibers. These findings indicate significant in vitro ligament development after only 14 days of culture when using a sequential growth factor approach.

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.

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

Science.gov (United States)

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

2017-01-01

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

An Efficient System Based On Closed Sequential Patterns for Web Recommendations

OpenAIRE

Utpala Niranjan; R.B.V. Subramanyam; V-Khana

2010-01-01

Sequential pattern mining, since its introduction has received considerable attention among the researchers with broad applications. The sequential pattern algorithms generally face problems when mining long sequential patterns or while using very low support threshold. One possible solution of such problems is by mining the closed sequential patterns, which is a condensed representation of sequential patterns. Recently, several researchers have utilized the sequential pattern discovery for d...

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

Science.gov (United States)

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

2017-10-01

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

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

Science.gov (United States)

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

2017-06-01

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

Dysphagia after sequential chemoradiation therapy for advanced head and neck cancer.

Science.gov (United States)

Goguen, Laura A; Posner, Marshall R; Norris, Charles M; Tishler, Roy B; Wirth, Lori J; Annino, Donald J; Gagne, Adele; Sullivan, Christopher A; Sammartino, Daniel E; Haddad, Robert I

2006-06-01

Assess impact of sequential chemoradiation therapy (SCRT) for advanced head and neck cancer (HNCA) on swallowing, nutrition, and quality of life. Prospective cohort study of 59 patients undergoing SCRT for advanced head and neck cancer. Follow-up median was 47.5 months. Regional Cancer Center. Median time to gastrostomy tube removal was 21 weeks. Eighteen of 23 patients who underwent modified barium swallow demonstrated aspiration; none developed pneumonia. Six of 7 with pharyngoesophageal stricture underwent successful dilatation. Functional Assessment of Cancer Therapy-Head and Neck Scale questionnaires at median 6 months after treatment revealed "somewhat" satisfaction with swallowing. At the time of analysis, 97% have the gastronomy tube removed and take soft/regular diet. Early after treatment dysphagia adversely affected weight, modified barium swallow results, and quality of life. Diligent swallow therapy, and dilation as needed, allowed nearly all patients to have their gastronomy tubes removed and return to a soft/regular diet. Dysphagia is significant after SCRT but generally slowly recovers 6 to 12 months after SCRT. C-4.

Metal contamination of home garden soils and cultivated vegetables in the province of Brescia, Italy: implications for human exposure.

Science.gov (United States)

Ferri, Roberta; Hashim, Dana; Smith, Donald R; Guazzetti, Stefano; Donna, Filippo; Ferretti, Enrica; Curatolo, Michele; Moneta, Caterina; Beone, Gian Maria; Lucchini, Roberto G

2015-06-15

For the past century, ferroalloy industries in Brescia province, Italy produced particulate emissions enriched in manganese (Mn), lead (Pb), zinc (Zn), copper (Cu), cadmium (Cd), chromium (Cr), iron (Fe), and aluminum (Al). This study assessed metal concentrations in soil and vegetables of regions with varying ferroalloy industrial activity levels. Home gardens (n=63) were selected in three regions of varying ferroalloy plant activity durations in Brescia province. Total soil metal concentration and extractability were measured by X-Ray Fluorescence (XRF), aqua regia extraction, and modified Community Bureau of Reference (BCR) sequential extraction. Unwashed and washed spinach and turnips cultivated in the same gardens were analyzed for metal concentrations by flame atomic absorption spectrometry. Median soil Al, Cd, Fe, Mn, Pb, and Zn concentrations were significantly higher in home gardens near ferroalloy plants compared to reference home gardens. The BCR method yielded the most mobile soil fraction (the sum of extractable metals in Fractions 1 and 2) and all metal concentrations were higher in ferroalloy plant areas. Unwashed spinach showed higher metal concentrations compared to washed spinach. However, some metals in washed spinach were higher in the reference area likely due to history of agricultural product use. Over 60% of spinach samples exceeded the 2- to 4-fold Commission of European Communities and Codex Alimentarius Commission maximum Pb concentrations, and 10% of the same spinach samples exceeded 2- to 3-fold maximum Cd concentrations set by both organizations. Turnip metal concentrations were below maximum standard reference values. Prolonged industrial emissions increase median metal concentrations and most soluble fractions (BCR F1+F2) in home garden soils near ferroalloy plants. Areas near ferroalloy plant sites had spinach Cd and Pb metal concentrations several-fold above maximum standard references. We recommend thorough washing of vegetables

Method development for the determination of arsenic by sequential injection/anodic stripping voltammetry using long-lasting gold-modified screen-printed carbon electrode.

Science.gov (United States)

Punrat, Eakkasit; Chuanuwatanakul, Suchada; Kaneta, Takashi; Motomizu, Shoji; Chailapakul, Orawon

2013-11-15

An automated method has been developed for determining the concentration of inorganic arsenic. The technique uses sequential injection/anodic stripping voltammetry with a long-lasting gold-modified screen-printed carbon electrode. The long-lasting gold electrode was electrochemically deposited onto a screen-printed carbon electrode at a potential of -0.5 V vs. Ag/AgCl in a supporting electrolyte solution of 1M hydrochloric acid. Under optimal conditions and the applied potentials, the electrode demonstrated that it can be used for a long time without a renewal process. The linear range for the determination of arsenic(III) was 1-100 μg L(-1), and the limit of detection (LOD) in standard solutions was as low as 0.03 μg L(-1) for a deposition time of 120 s and sample volume of 1 mL. This method was used to determine the concentration of arsenic(III) in water samples with satisfactory results. The LOD in real samples was found to be 0.5 μg L(-1). In addition, speciation between arsenic(III) and arsenic(V) has been achieved with the proposed method using deposition potentials of -0.5 V and -1.5 V for the determination of the arsenic(III) concentration and the total arsenic concentration, respectively; the results were acceptable. The proposed method is an automated system that offers a less expensive alternative for determining trace amounts of inorganic arsenic. © 2013 Elsevier B.V. All rights reserved.

Scarless and sequential gene modification in Pseudomonas using PCR product flanked by short homology regions

Directory of Open Access Journals (Sweden)

Liang Rubing

2010-08-01

Full Text Available Abstract Background The lambda Red recombination system has been used to inactivate chromosomal genes in various bacteria and fungi. The procedure consists of electroporating a polymerase chain reaction (PCR fragment containing antibiotic cassette flanked by homology regions to the target locus into a strain that can express the lambda Red proteins (Gam, Bet, Exo. Results Here a scarless gene modification strategy based on the Red recombination system has been developed to modify Pseudomonas genome DNA via sequential deletion of multiple targets. This process was mediated by plasmid pRKaraRed encoding the Red proteins regulated by PBAD promoter, which was functional in P. aeruginosa as well as in other bacteria. First the target gene was substituted for the sacB-bla cassette flanked by short homology regions (50 bp, and then this marker gene cassette could be replaced by the PCR fragment flanking itself, generating target-deleted genome without any remnants and no change happened to the surrounding region. Twenty genes involved in the synthesis and regulation pathways of the phenazine derivate, pyocyanin, were modified, including one single-point mutation and deletion of two large operons. The recombination efficiencies ranged from 88% to 98%. Multiple-gene modification was also achieved, generating a triple-gene deletion strain PCA (PAO1, ΔphzHΔphzMΔphzS, which could produce another phenazine derivate, phenazine-1-carboxylic acid (PCA, efficiently and exclusively. Conclusions This lambda Red-based technique can be used to generate scarless and sequential gene modification mutants of P. aeruginosa efficiently, using one-step PCR product flanked by short homology regions. Single-point mutation, scarless deletion of genes can be achieved easily in less than three days. This method may give a new way to construct genetically modified P. aeruginosa strains more efficiently and advance the regulatory network study of this organism.

An in vitro assay to study the recruitment and substrate specificity of chromatin modifying enzymes

Directory of Open Access Journals (Sweden)

Vermeulen Michiel

2004-01-01

Full Text Available Post-translational modifications of core histones play an important role in regulating fundamental biological processes such as DNA repair, transcription and replication. In this paper, we describe a novel assay that allows sequential targeting of distinct histone modifying enzymes to immobilized nucleosomal templates using recombinant chimeric targeting molecules. The assay can be used to study the histone substrate specificity of chromatin modifying enzymes as well as whether and how certain enzymes affect each other's histone modifying activities. As such the assay can help to understand how a certain histone code is established and interpreted.

Discrimination between sequential and simultaneous virtual channels with electrical hearing.

Science.gov (United States)

Landsberger, David; Galvin, John J

2011-09-01

In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation modes. For sequential VCs, the interpulse interval (IPI) varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud, loudness-balanced levels at a 250 pulse per second per electrode (ppse) stimulation rate. On average, CI subjects were able to reliably discriminate between sequential and simultaneous VCs. While there was no significant effect of IPI or stimulation mode on VC discrimination, some subjects exhibited better VC discrimination with BP + 1 stimulation. Subjects' discrimination between sequential and simultaneous VCs was correlated with electrode discrimination, suggesting that spatial selectivity may influence perception of sequential VCs. To maintain equal loudness, sequential VC amplitudes were nearly double those of simultaneous VCs, presumably resulting in a broader spread of excitation. These results suggest that perceptual differences between simultaneous and sequential VCs might be explained by differences in the spread of excitation. © 2011 Acoustical Society of America

Sequential versus simultaneous market delineation

DEFF Research Database (Denmark)

Haldrup, Niels; Møllgaard, Peter; Kastberg Nielsen, Claus

2005-01-01

and geographical markets. Using a unique data setfor prices of Norwegian and Scottish salmon, we propose a methodologyfor simultaneous market delineation and we demonstrate that comparedto a sequential approach conclusions will be reversed.JEL: C3, K21, L41, Q22Keywords: Relevant market, econometric delineation......Delineation of the relevant market forms a pivotal part of most antitrustcases. The standard approach is sequential. First the product marketis delineated, then the geographical market is defined. Demand andsupply substitution in both the product dimension and the geographicaldimension...

Effectiveness of the random sequential absorption algorithm in the analysis of volume elements with nanoplatelets

DEFF Research Database (Denmark)

Pontefisso, Alessandro; Zappalorto, Michele; Quaresimin, Marino

2016-01-01

In this work, a study of the Random Sequential Absorption (RSA) algorithm in the generation of nanoplatelet Volume Elements (VEs) is carried out. The effect of the algorithm input parameters on the reinforcement distribution is studied through the implementation of statistical tools, showing...... that the platelet distribution is systematically affected by these parameters. The consequence is that a parametric analysis of the VE input parameters may be biased by hidden differences in the filler distribution. The same statistical tools used in the analysis are implemented in a modified RSA algorithm...

Group-sequential analysis may allow for early trial termination

DEFF Research Database (Denmark)

Gerke, Oke; Vilstrup, Mie H; Halekoh, Ulrich

2017-01-01

BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT mea......BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG...

Sequential logic analysis and synthesis

CERN Document Server

Cavanagh, Joseph

2007-01-01

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

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

DEFF Research Database (Denmark)

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

2009-01-01

The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP......), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation...

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

International Nuclear Information System (INIS)

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

1990-01-01

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

Impact of controlling the sum of error probability in the sequential probability ratio test

Directory of Open Access Journals (Sweden)

Bijoy Kumarr Pradhan

2013-05-01

Full Text Available A generalized modified method is proposed to control the sum of error probabilities in sequential probability ratio test to minimize the weighted average of the two average sample numbers under a simple null hypothesis and a simple alternative hypothesis with the restriction that the sum of error probabilities is a pre-assigned constant to find the optimal sample size and finally a comparison is done with the optimal sample size found from fixed sample size procedure. The results are applied to the cases when the random variate follows a normal law as well as Bernoullian law.

Structural Consistency, Consistency, and Sequential Rationality.

OpenAIRE

Kreps, David M; Ramey, Garey

1987-01-01

Sequential equilibria comprise consistent beliefs and a sequentially ra tional strategy profile. Consistent beliefs are limits of Bayes ratio nal beliefs for sequences of strategies that approach the equilibrium strategy. Beliefs are structurally consistent if they are rationaliz ed by some single conjecture concerning opponents' strategies. Consis tent beliefs are not necessarily structurally consistent, notwithstan ding a claim by Kreps and Robert Wilson (1982). Moreover, the spirit of stru...

Constrained treatment planning using sequential beam selection

International Nuclear Information System (INIS)

Woudstra, E.; Storchi, P.R.M.

2000-01-01

In this paper an algorithm is described for automated treatment plan generation. The algorithm aims at delivery of the prescribed dose to the target volume without violation of constraints for target, organs at risk and the surrounding normal tissue. Pre-calculated dose distributions for all candidate orientations are used as input. Treatment beams are selected in a sequential way. A score function designed for beam selection is used for the simultaneous selection of beam orientations and weights. In order to determine the optimum choice for the orientation and the corresponding weight of each new beam, the score function is first redefined to account for the dose distribution of the previously selected beams. Addition of more beams to the plan is stopped when the target dose is reached or when no additional dose can be delivered without violating a constraint. In the latter case the score function is modified by importance factor changes to enforce better sparing of the organ with the limiting constraint and the algorithm is run again. (author)

Prognostic implications of 2005 Gleason grade modification

DEFF Research Database (Denmark)

Thomsen, Frederik Birkebæk; Folkvaljon, Yasin; Brasso, Klaus

2016-01-01

,890 men assessed with the modified Gleason classification, diagnosed between 2003 and 2007, underwent primary RP. Histopathology was reported according to the Gleason Grading Groups (GGG): GGG1 = Gleason score (GS) 6, GGG2 = GS 7(3 + 4), GGG3 = GS 7(4 + 3), GGG4 = GS 8 and GGG5 = GS 9-10. Cumulative...... incidence and multivariable Cox proportional hazards regression models were used to assess difference in BCR. RESULTS: The cumulative incidence of BCR was lower using the modified compared to the original classification: GGG2 (16% vs. 23%), GGG3 (21% vs. 35%) and GGG4 (18% vs. 34%), respectively. Risk......OBJECTIVE: To assess the impact of the 2005 modification of the Gleason classification on risk of biochemical recurrence (BCR) after radical prostatectomy (RP). PATIENTS AND METHODS: In the Prostate Cancer data Base Sweden (PCBaSe), 2,574 men assessed with the original Gleason classification and 1...

Precise Sequential DNA Ligation on A Solid Substrate: Solid-Based Rapid Sequential Ligation of Multiple DNA Molecules

Science.gov (United States)

Takita, Eiji; Kohda, Katsunori; Tomatsu, Hajime; Hanano, Shigeru; Moriya, Kanami; Hosouchi, Tsutomu; Sakurai, Nozomu; Suzuki, Hideyuki; Shinmyo, Atsuhiko; Shibata, Daisuke

2013-01-01

Ligation, the joining of DNA fragments, is a fundamental procedure in molecular cloning and is indispensable to the production of genetically modified organisms that can be used for basic research, the applied biosciences, or both. Given that many genes cooperate in various pathways, incorporating multiple gene cassettes in tandem in a transgenic DNA construct for the purpose of genetic modification is often necessary when generating organisms that produce multiple foreign gene products. Here, we describe a novel method, designated PRESSO (precise sequential DNA ligation on a solid substrate), for the tandem ligation of multiple DNA fragments. We amplified donor DNA fragments with non-palindromic ends, and ligated the fragment to acceptor DNA fragments on solid beads. After the final donor DNA fragments, which included vector sequences, were joined to the construct that contained the array of fragments, the ligation product (the construct) was thereby released from the beads via digestion with a rare-cut meganuclease; the freed linear construct was circularized via an intra-molecular ligation. PRESSO allowed us to rapidly and efficiently join multiple genes in an optimized order and orientation. This method can overcome many technical challenges in functional genomics during the post-sequencing generation. PMID:23897972

Generalized infimum and sequential product of quantum effects

International Nuclear Information System (INIS)

Li Yuan; Sun Xiuhong; Chen Zhengli

2007-01-01

The quantum effects for a physical system can be described by the set E(H) of positive operators on a complex Hilbert space H that are bounded above by the identity operator I. For A, B(set-membership sign)E(H), the operation of sequential product A(convolution sign)B=A 1/2 BA 1/2 was proposed as a model for sequential quantum measurements. A nice investigation of properties of the sequential product has been carried over [Gudder, S. and Nagy, G., 'Sequential quantum measurements', J. Math. Phys. 42, 5212 (2001)]. In this note, we extend some results of this reference. In particular, a gap in the proof of Theorem 3.2 in this reference is overcome. In addition, some properties of generalized infimum A sqcap B are studied

Efficiency enhancement of perovskite solar cells by fabricating as-prepared film before sequential spin-coating procedure

International Nuclear Information System (INIS)

Jiang, Jiajia; Tao, Hai jun; Chen, Shanlong; Tan, Bin; Zhou, Ning; Zhu, Lumin; Zhao, Yuan; Wang, Yuqiao; Tao, Jie

2016-01-01

Graphical abstract: Schematic illustration of modified two-step spin-coating procedure for MAPbI 3 perovskite thin films. - Highlights: • An as-prepared CH 3 NH 3 PbI 3 and PbI 2 film was introduced before the traditional two-step process. • Smooth morphology and trace amount of remaining PbI 2 benefit the performance of solar cell. • The optimal as-prepared film introduced improves the efficiency of CH 3 NH 3 PbI 3 solar cells from 9.11% to 11.16%. - Abstract: Sequential spin-coating procedure is a widely adopted strategy to prepare CH 3 NH 3 PbI 3 on mesostructured TiO 2 electrode for organolead halide perovskite-based solar cells. However, this method suffers from the rough surface and excessively residual PbI 2 in the resulting perovskite film, deteriorating the device performance seriously. Herein, a facial modified sequential solution deposition method, by introducing an as-prepared CH 3 NH 3 PbI 3 and PbI 2 film before the traditional two-step process, was proposed to fabricate the perovskite-based solar cell with smooth morphology and trace amount of remaining PbI 2 . The optimal as-prepared film introduced improves the efficiency of CH 3 NH 3 PbI 3 solar cells from 9.11% to 11.16%. The enhancement of device performance can be attributed to the increased light absorption ability and decreased recombination rate of carriers in CH 3 NH 3 PbI 3 absorber.

The use of bedside chest radiography at a university hospital. Data on a two-week period

International Nuclear Information System (INIS)

Delnevo, Alessandra; Tritella, Stefania; Carbonaro, Luca Alessandro; Bobrechova, Oxana; Di Leo, Giovanni; Sardanelli, Francesco

2012-01-01

Objective: To evaluate the requests for bedside chest radiography (BCR) by clinicians. Materials and methods: After IRB approval, we retrieved the patients’ clinical records for demographics, unit, and duration for recovery in a two weeks period. For each BCR, exposure data and the reason for BCR were registered. The BCR results were categorized as one or more of the followings: negative, regular/irregular device position, known finding(s) unmodified/modified in respect with the previous BCR, new expected finding(s) (pleural effusion, low ventilation), or new unexpected findings (pulmonary edema, pneumothorax). As a utility indicator of BCR, we considered the rate of chest CT performed in these patients during the study period and the following week. We have estimated the effective radiation dose. Results: A total of 337 BCRs (126 patients) entered the analysis, 74% of them being performed in post-surgery intensive care unit. Seventy-3 patients (58%) performed 1 or 2 BCRs, 53 (42%) 3 or more BCRs with a maximum of 13 BCRs performed on a newborn. The mean total effective dose was 0.2 mSv/patient (maximum 1 mSv). In post-surgery intensive care unit the mean daily BCR rate was 0.8/day (maximum 2/day). On 337 BCR requests, 49% showed no motivations at all, 42% reported the word “check” and in 9% a well-defined clinical query was specified. The rate of incorrect catheter position and new unexpected findings was 4%. One chest CT have been requested. Conclusion: BCR is often requested as a routine examination with a little rate of unexpected findings.

Sequential analysis in neonatal research-systematic review.

Science.gov (United States)

Lava, Sebastiano A G; Elie, Valéry; Ha, Phuong Thi Viet; Jacqz-Aigrain, Evelyne

2018-05-01

As more new drugs are discovered, traditional designs come at their limits. Ten years after the adoption of the European Paediatric Regulation, we performed a systematic review on the US National Library of Medicine and Excerpta Medica database of sequential trials involving newborns. Out of 326 identified scientific reports, 21 trials were included. They enrolled 2832 patients, of whom 2099 were analyzed: the median number of neonates included per trial was 48 (IQR 22-87), median gestational age was 28.7 (IQR 27.9-30.9) weeks. Eighteen trials used sequential techniques to determine sample size, while 3 used continual reassessment methods for dose-finding. In 16 studies reporting sufficient data, the sequential design allowed to non-significantly reduce the number of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674) with respect to a traditional trial. When the number of neonates finally included in the analysis was considered, the difference became significant: 35 (57%) patients (IQR 10 to 136.5, p = 0.0033). Sequential trial designs have not been frequently used in Neonatology. They might potentially be able to reduce the number of patients in drug trials, although this is not always the case. What is known: • In evaluating rare diseases in fragile populations, traditional designs come at their limits. About 20% of pediatric trials are discontinued, mainly because of recruitment problems. What is new: • Sequential trials involving newborns were infrequently used and only a few (n = 21) are available for analysis. • The sequential design allowed to non-significantly reduce the number of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674).

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

Directory of Open Access Journals (Sweden)

Dambrauskienė R

2017-06-01

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

Group-sequential analysis may allow for early trial termination

DEFF Research Database (Denmark)

Gerke, Oke; Vilstrup, Mie H; Halekoh, Ulrich

2017-01-01

BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT mea......BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG...... assumed to be normally distributed, and sequential one-sided hypothesis tests on the population standard deviation of the differences against a hypothesised value of 1.5 were performed, employing an alpha spending function. The fixed-sample analysis (N = 45) was compared with the group-sequential analysis...... strategies comprising one (at N = 23), two (at N = 15, 30), or three interim analyses (at N = 11, 23, 34), respectively, which were defined post hoc. RESULTS: When performing interim analyses with one third and two thirds of patients, sufficient agreement could be concluded after the first interim analysis...

Comparison of ablation centration after bilateral sequential versus simultaneous LASIK.

Science.gov (United States)

Lin, Jane-Ming; Tsai, Yi-Yu

2005-01-01

To compare ablation centration after bilateral sequential and simultaneous myopic LASIK. A retrospective randomized case series was performed of 670 eyes of 335 consecutive patients who had undergone either bilateral sequential (group 1) or simultaneous (group 2) myopic LASIK between July 2000 and July 2001 at the China Medical University Hospital, Taichung, Taiwan. The ablation centrations of the first and second eyes in the two groups were compared 3 months postoperatively. Of 670 eyes, 274 eyes (137 patients) comprised the sequential group and 396 eyes (198 patients) comprised the simultaneous group. Three months post-operatively, 220 eyes of 110 patients (80%) in the sequential group and 236 eyes of 118 patients (60%) in the simultaneous group provided topographic data for centration analysis. For the first eyes, mean decentration was 0.39 +/- 0.26 mm in the sequential group and 0.41 +/- 0.19 mm in the simultaneous group (P = .30). For the second eyes, mean decentration was 0.28 +/- 0.23 mm in the sequential group and 0.30 +/- 0.21 mm in the simultaneous group (P = .36). Decentration in the second eyes significantly improved in both groups (group 1, P = .02; group 2, P sequential group and 0.32 +/- 0.18 mm in the simultaneous group (P = .33). The difference of ablation center angles between the first and second eyes was 43.2 sequential group and 45.1 +/- 50.8 degrees in the simultaneous group (P = .42). Simultaneous bilateral LASIK is comparable to sequential surgery in ablation centration.

A Survey of Multi-Objective Sequential Decision-Making

NARCIS (Netherlands)

Roijers, D.M.; Vamplew, P.; Whiteson, S.; Dazeley, R.

2013-01-01

Sequential decision-making problems with multiple objectives arise naturally in practice and pose unique challenges for research in decision-theoretic planning and learning, which has largely focused on single-objective settings. This article surveys algorithms designed for sequential

Sequential lineups: shift in criterion or decision strategy?

Science.gov (United States)

Gronlund, Scott D

2004-04-01

R. C. L. Lindsay and G. L. Wells (1985) argued that a sequential lineup enhanced discriminability because it elicited use of an absolute decision strategy. E. B. Ebbesen and H. D. Flowe (2002) argued that a sequential lineup led witnesses to adopt a more conservative response criterion, thereby affecting bias, not discriminability. Height was encoded as absolute (e.g., 6 ft [1.83 m] tall) or relative (e.g., taller than). If a sequential lineup elicited an absolute decision strategy, the principle of transfer-appropriate processing predicted that performance should be best when height was encoded absolutely. Conversely, if a simultaneous lineup elicited a relative decision strategy, performance should be best when height was encoded relatively. The predicted interaction was observed, providing direct evidence for the decision strategies explanation of what happens when witnesses view a sequential lineup.

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

International Nuclear Information System (INIS)

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

2010-01-01

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

How to Read the Tractatus Sequentially

Directory of Open Access Journals (Sweden)

Tim Kraft

2016-11-01

Full Text Available One of the unconventional features of Wittgenstein’s Tractatus Logico-Philosophicus is its use of an elaborated and detailed numbering system. Recently, Bazzocchi, Hacker und Kuusela have argued that the numbering system means that the Tractatus must be read and interpreted not as a sequentially ordered book, but as a text with a two-dimensional, tree-like structure. Apart from being able to explain how the Tractatus was composed, the tree reading allegedly solves exegetical issues both on the local (e. g. how 4.02 fits into the series of remarks surrounding it and the global level (e. g. relation between ontology and picture theory, solipsism and the eye analogy, resolute and irresolute readings. This paper defends the sequential reading against the tree reading. After presenting the challenges generated by the numbering system and the two accounts as attempts to solve them, it is argued that Wittgenstein’s own explanation of the numbering system, anaphoric references within the Tractatus and the exegetical issues mentioned above do not favour the tree reading, but a version of the sequential reading. This reading maintains that the remarks of the Tractatus form a sequential chain: The role of the numbers is to indicate how remarks on different levels are interconnected to form a concise, surveyable and unified whole.

A minimax procedure in the context of sequential mastery testing

NARCIS (Netherlands)

Vos, Hendrik J.

1999-01-01

The purpose of this paper is to derive optimal rules for sequential mastery tests. In a sequential mastery test, the decision is to classify a subject as a master or a nonmaster, or to continue sampling and administering another random test item. The framework of minimax sequential decision theory

Multichannel, sequential or combined X-ray spectrometry

International Nuclear Information System (INIS)

Florestan, J.

1979-01-01

X-ray spectrometer qualities and defects are evaluated for sequential and multichannel categories. Multichannel X-ray spectrometer has time-coherency advantage and its results could be more reproducible; on the other hand some spatial incoherency limits low percentage and traces applications, specially when backgrounds are very variable. In this last case, sequential X-ray spectrometer would find again great usefulness [fr

Sequential chromatin immunoprecipitation to detect SUMOylated MeCP2 in neurons

Directory of Open Access Journals (Sweden)

Tao Wu

2016-03-01

Full Text Available The small ubiquitin-like modifier (SUMO is a short peptide that can be covalently linked to proteins altering their function. SUMOylation is an essential post-translational modification (PTM. Because of its dynamic nature, low abundance levels, and technical limitations, the occupation of endogenous SUMOylated transcription factors at genomic loci is challenging to detect. The chromatin regulator Methyl CpG binding protein 2 (MeCP2 is subjected to PTMs including SUMO. Mutations in MeCP2 lead to Rett syndrome, a severe neurodevelopmental disorder. Here, we present an efficient method to perform sequential chromatin immunoprecipitation (Seq-ChIP for detecting SUMOylated MeCP2 in neurons. This Seq-ChIP technique is a useful tool to determine the occupancy of SUMOylated transcription and chromatin factors at specific genomic regions.

Induction of simultaneous and sequential malolactic fermentation in durian wine.

Science.gov (United States)

Taniasuri, Fransisca; Lee, Pin-Rou; Liu, Shao-Quan

2016-08-02

This study represented for the first time the impact of malolactic fermentation (MLF) induced by Oenococcus oeni and its inoculation strategies (simultaneous vs. sequential) on the fermentation performance as well as aroma compound profile of durian wine. There was no negative impact of simultaneous inoculation of O. oeni and Saccharomyces cerevisiae on the growth and fermentation kinetics of S. cerevisiae as compared to sequential fermentation. Simultaneous MLF did not lead to an excessive increase in volatile acidity as compared to sequential MLF. The kinetic changes of organic acids (i.e. malic, lactic, succinic, acetic and α-ketoglutaric acids) varied with simultaneous and sequential MLF relative to yeast alone. MLF, regardless of inoculation mode, resulted in higher production of fermentation-derived volatiles as compared to control (alcoholic fermentation only), including esters, volatile fatty acids, and terpenes, except for higher alcohols. Most indigenous volatile sulphur compounds in durian were decreased to trace levels with little differences among the control, simultaneous and sequential MLF. Among the different wines, the wine with simultaneous MLF had higher concentrations of terpenes and acetate esters while sequential MLF had increased concentrations of medium- and long-chain ethyl esters. Relative to alcoholic fermentation only, both simultaneous and sequential MLF reduced acetaldehyde substantially with sequential MLF being more effective. These findings illustrate that MLF is an effective and novel way of modulating the volatile and aroma compound profile of durian wine. Copyright © 2016 Elsevier B.V. All rights reserved.

Spatial-sequential working memory in younger and older adults: age predicts backward recall performance within both age groups

OpenAIRE

Louise A. Brown

2016-01-01

Working memory is vulnerable to age-related decline, but there is debate regarding the age-sensitivity of different forms of spatial-sequential working memory task, depending on their passive or active nature. The functional architecture of spatial working memory was therefore explored in younger (18–40 years) and older (64–85 years) adults, using passive and active recall tasks. Spatial working memory was assessed using a modified version of the Spatial Span subtest of the Wechsler Memory Sc...

Investigating the role of the IGF axis as a predictor of biochemical recurrence in prostate cancer patients post-surgery.

Science.gov (United States)

Breen, Kieran J; O'Neill, Amanda; Murphy, Lisa; Fan, Yue; Boyce, Susie; Fitzgerald, Noel; Dorris, Emma; Brady, Lauren; Finn, Stephen P; Hayes, Brian D; Treacy, Ann; Barrett, Ciara; Aziz, Mardiana Abdul; Kay, Elaine W; Fitzpatrick, John M; Watson, R William G

2017-09-01

Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF-1 receptor (IGF-1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post-surgery. Tissue microarrays (TMA) of 130 patients post-radical prostatectomy (65 = BCR, 65 = non-BCR) were stained by immunohistochemistry for INSR, IGF-1R, PTEN, and AKT using optimized antibody protocols. INSR, IGF1-R, PTEN, and AKT expression between benign and cancerous tissue, and different Gleason grades was assessed. Kaplan-Meier survival curves were used to examine the relationship between proteins expression and BCR. INSR (P IGF-1R (P IGF-1R, or AKT expression in the cancerous tissue of non-BCR versus BCR patients (P = 0.149, P = 0.990, P = 0.399, respectively). There was a significant decrease in PTEN expression in the malignant tissue of BCR versus non-BCR patients (P = 0.011). Combinational analysis of the tissue proteins identified a combination of decreased PTEN and increased AKT or increased INSR was associated with worst outcome. We found that in each case, our hypothesized worst group was most likely to experience BCR and this was significant for combinations of PTEN+INSR and PTEN+AKT but not PTEN+IGF-1R (P = 0.023, P = 0.028, P = 0.078, respectively). Low PTEN is associated with BCR and this association is strongly modified by high INSR and high AKT expression. Measurement of these proteins could help inform appropriate patient selection for postoperative adjuvant therapy and prevent BCR. © 2017 Wiley Periodicals, Inc.

Sequential Banking.

OpenAIRE

Bizer, David S; DeMarzo, Peter M

1992-01-01

The authors study environments in which agents may borrow sequentially from more than one leader. Although debt is prioritized, additional lending imposes an externality on prior debt because, with moral hazard, the probability of repayment of prior loans decreases. Equilibrium interest rates are higher than they would be if borrowers could commit to borrow from at most one bank. Even though the loan terms are less favorable than they would be under commitment, the indebtedness of borrowers i...

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

Science.gov (United States)

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

2006-06-02

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

Multi-element analysis, bioavailability and fractionation of herbal tea products

Energy Technology Data Exchange (ETDEWEB)

Szymczycha-Madeja, Anna; Welna, Maja; Zyrnicki, Wieslaw, E-mail: anna.szymczycha@pwr.wroc.pl [Wroclaw University of Technology, Chemistry Department, Analytical Chemistry Division, Wroclaw (Poland)

2013-05-15

Herbal teas (Mentha piperitae foliumand mixture Marticaria chamomilla flos with Lavandula officinalis flos) were compared considering the total contents of micro (Al, Ba, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Sr, Ti, V) and macro (C, H, N, S, Ca, Mg, P) elements, bioavailability and fractionation. Different methods (inductively coupled plasma optical emission spectrometry (ICP OES), Fourier transform infrared spectroscopy (FTIR) and CHNS elemental analysis) were applied. The microwave-assisted digestion procedure was found to be more effective than the hot-plate heating for the wet acid digestion of tea. The application of the modified BCR (Community Bureau of Reference) sequential extraction procedure exhibited differences in the concentrations of metal bound to reducible and oxidizable fractions. The accuracy of method was verified by analysis of certified reference material INCT-TL{sup -1} Tea Leaves. The daily intake of all elements from the analyzed herbal tea infusion did not exceed the maximum permissible levels and does not constitute health risk. (author)

Multi-element analysis, bioavailability and fractionation of herbal tea products

International Nuclear Information System (INIS)

Szymczycha-Madeja, Anna; Welna, Maja; Zyrnicki, Wieslaw

2013-01-01

Herbal teas (Mentha piperitae foliumand mixture Marticaria chamomilla flos with Lavandula officinalis flos) were compared considering the total contents of micro (Al, Ba, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Sr, Ti, V) and macro (C, H, N, S, Ca, Mg, P) elements, bioavailability and fractionation. Different methods (inductively coupled plasma optical emission spectrometry (ICP OES), Fourier transform infrared spectroscopy (FTIR) and CHNS elemental analysis) were applied. The microwave-assisted digestion procedure was found to be more effective than the hot-plate heating for the wet acid digestion of tea. The application of the modified BCR (Community Bureau of Reference) sequential extraction procedure exhibited differences in the concentrations of metal bound to reducible and oxidizable fractions. The accuracy of method was verified by analysis of certified reference material INCT-TL -1 Tea Leaves. The daily intake of all elements from the analyzed herbal tea infusion did not exceed the maximum permissible levels and does not constitute health risk. (author)

Ecological Risk Assessment of Jarosite Waste Disposal

Directory of Open Access Journals (Sweden)

Mihone Kerolli-Mustafa

2015-07-01

Full Text Available Jarosite waste, originating from zinc extraction industry, is considered hazardous due to the presence and the mobility of toxic metals that it contains. Its worldwide disposal in many tailing damps has become a major ecological concern. Three different methods, namely modified Synthetic Precipitation Leaching Procedure (SPLP, three-stage BCR sequential extraction procedure and Potential Ecological Risk Index (PERI Method were used to access the ecological risk of jarosite waste disposal in Mitrovica Industrial Park, Kosovo. The combination of these methods can effectively identify the comprehensive and single pollution levels of heavy metals such as Zn, Pb, Cd, Cu, Ni and As present in jarosite waste. Moreover, the great positive relevance between leaching behavior of heavy metals and F1 fraction was supported by principal component analysis (PCA. PERI results indicate that Cd showed a very high risk class to the environment. The ecological risk of heavy metals declines in the following order: Cd>Zn>Cu>Pb>Ni>As.

Equivalence between quantum simultaneous games and quantum sequential games

OpenAIRE

Kobayashi, Naoki

2007-01-01

A framework for discussing relationships between different types of games is proposed. Within the framework, quantum simultaneous games, finite quantum simultaneous games, quantum sequential games, and finite quantum sequential games are defined. In addition, a notion of equivalence between two games is defined. Finally, the following three theorems are shown: (1) For any quantum simultaneous game G, there exists a quantum sequential game equivalent to G. (2) For any finite quantum simultaneo...

Accounting for Heterogeneous Returns in Sequential Schooling Decisions

NARCIS (Netherlands)

Zamarro, G.

2006-01-01

This paper presents a method for estimating returns to schooling that takes into account that returns may be heterogeneous among agents and that educational decisions are made sequentially.A sequential decision model is interesting because it explicitly considers that the level of education of each

Simultaneous Versus Sequential Ptosis and Strabismus Surgery in Children.

Science.gov (United States)

Revere, Karen E; Binenbaum, Gil; Li, Jonathan; Mills, Monte D; Katowitz, William R; Katowitz, James A

The authors sought to compare the clinical outcomes of simultaneous versus sequential ptosis and strabismus surgery in children. Retrospective, single-center cohort study of children requiring both ptosis and strabismus surgery on the same eye. Simultaneous surgeries were performed during a single anesthetic event; sequential surgeries were performed at least 7 weeks apart. Outcomes were ptosis surgery success (margin reflex distance 1 ≥ 2 mm, good eyelid contour, and good eyelid crease); strabismus surgery success (ocular alignment within 10 prism diopters of orthophoria and/or improved head position); surgical complications; and reoperations. Fifty-six children were studied, 38 had simultaneous surgery and 18 sequential. Strabismus surgery was performed first in 38/38 simultaneous and 6/18 sequential cases. Mean age at first surgery was 64 months, with mean follow up 27 months. A total of 75% of children had congenital ptosis; 64% had comitant strabismus. A majority of ptosis surgeries were frontalis sling (59%) or Fasanella-Servat (30%) procedures. There were no significant differences between simultaneous and sequential groups with regards to surgical success rates, complications, or reoperations (all p > 0.28). In the first comparative study of simultaneous versus sequential ptosis and strabismus surgery, no advantage for sequential surgery was seen. Despite a theoretical risk of postoperative eyelid malposition or complications when surgeries were performed in a combined manner, the rate of such outcomes was not increased with simultaneous surgeries. Performing ptosis and strabismus surgery together appears to be clinically effective and safe, and reduces anesthesia exposure during childhood.

Forced Sequence Sequential Decoding

DEFF Research Database (Denmark)

Jensen, Ole Riis

In this thesis we describe a new concatenated decoding scheme based on iterations between an inner sequentially decoded convolutional code of rate R=1/4 and memory M=23, and block interleaved outer Reed-Solomon codes with non-uniform profile. With this scheme decoding with good performance...... is possible as low as Eb/No=0.6 dB, which is about 1.7 dB below the signal-to-noise ratio that marks the cut-off rate for the convolutional code. This is possible since the iteration process provides the sequential decoders with side information that allows a smaller average load and minimizes the probability...... of computational overflow. Analytical results for the probability that the first Reed-Solomon word is decoded after C computations are presented. This is supported by simulation results that are also extended to other parameters....

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.

Sequential Service Restoration for Unbalanced Distribution Systems and Microgrids

International Nuclear Information System (INIS)

Chen, Bo; Chen, Chen; Wang, Jianhui; Butler-Purry, Karen L.

2017-01-01

The resilience and reliability of modern power systems are threatened by increasingly severe weather events and cyber-physical security events. An effective restoration methodology is desired to optimally integrate emerging smart grid technologies and pave the way for developing self-healing smart grids. In this paper, a sequential service restoration (SSR) framework is proposed to generate restoration solutions for distribution systems and microgrids in the event of large-scale power outages. The restoration solution contains a sequence of control actions that properly coordinate switches, distributed generators, and switchable loads to form multiple isolated microgrids. The SSR can be applied for three-phase unbalanced distribution systems and microgrids and can adapt to various operation conditions. Mathematical models are introduced for three-phase unbalanced power flow, voltage regulators, transformers, and loads. Furthermore, the SSR problem is formulated as a mixed-integer linear programming model, and its effectiveness is evaluated via the modified IEEE 123 node test feeder.

Reading Remediation Based on Sequential and Simultaneous Processing.

Science.gov (United States)

Gunnison, Judy; And Others

1982-01-01

The theory postulating a dichotomy between sequential and simultaneous processing is reviewed and its implications for remediating reading problems are reviewed. Research is cited on sequential-simultaneous processing for early and advanced reading. A list of remedial strategies based on the processing dichotomy addresses decoding and lexical…

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.

C-quence: a tool for analyzing qualitative sequential data.

Science.gov (United States)

Duncan, Starkey; Collier, Nicholson T

2002-02-01

C-quence is a software application that matches sequential patterns of qualitative data specified by the user and calculates the rate of occurrence of these patterns in a data set. Although it was designed to facilitate analyses of face-to-face interaction, it is applicable to any data set involving categorical data and sequential information. C-quence queries are constructed using a graphical user interface. The program does not limit the complexity of the sequential patterns specified by the user.

Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.

Directory of Open Access Journals (Sweden)

Gavin Churchyard

Full Text Available The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM, SAAVI MVA-C (2.9 x 109 pfu IM and Novartis V2-deleted subtype C gp140 (100 mcg with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa.Participants at three South African sites were randomized (1:1:1:1 to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P; concurrent MVA/gp140 (MP/MP; DNA prime, sequential MVA boost (D/D/M/M; DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP or placebo. Peak HIV specific humoral and cellular responses were measured.184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens.The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen.ClinicalTrials.gov NCT01418235.

Mining compressing sequential problems

NARCIS (Netherlands)

Hoang, T.L.; Mörchen, F.; Fradkin, D.; Calders, T.G.K.

2012-01-01

Compression based pattern mining has been successfully applied to many data mining tasks. We propose an approach based on the minimum description length principle to extract sequential patterns that compress a database of sequences well. We show that mining compressing patterns is NP-Hard and

Fast sequential Monte Carlo methods for counting and optimization

CERN Document Server

Rubinstein, Reuven Y; Vaisman, Radislav

2013-01-01

A comprehensive account of the theory and application of Monte Carlo methods Based on years of research in efficient Monte Carlo methods for estimation of rare-event probabilities, counting problems, and combinatorial optimization, Fast Sequential Monte Carlo Methods for Counting and Optimization is a complete illustration of fast sequential Monte Carlo techniques. The book provides an accessible overview of current work in the field of Monte Carlo methods, specifically sequential Monte Carlo techniques, for solving abstract counting and optimization problems. Written by authorities in the

Sensitivity Analysis in Sequential Decision Models.

Science.gov (United States)

Chen, Qiushi; Ayer, Turgay; Chhatwal, Jagpreet

2017-02-01

Sequential decision problems are frequently encountered in medical decision making, which are commonly solved using Markov decision processes (MDPs). Modeling guidelines recommend conducting sensitivity analyses in decision-analytic models to assess the robustness of the model results against the uncertainty in model parameters. However, standard methods of conducting sensitivity analyses cannot be directly applied to sequential decision problems because this would require evaluating all possible decision sequences, typically in the order of trillions, which is not practically feasible. As a result, most MDP-based modeling studies do not examine confidence in their recommended policies. In this study, we provide an approach to estimate uncertainty and confidence in the results of sequential decision models. First, we provide a probabilistic univariate method to identify the most sensitive parameters in MDPs. Second, we present a probabilistic multivariate approach to estimate the overall confidence in the recommended optimal policy considering joint uncertainty in the model parameters. We provide a graphical representation, which we call a policy acceptability curve, to summarize the confidence in the optimal policy by incorporating stakeholders' willingness to accept the base case policy. For a cost-effectiveness analysis, we provide an approach to construct a cost-effectiveness acceptability frontier, which shows the most cost-effective policy as well as the confidence in that for a given willingness to pay threshold. We demonstrate our approach using a simple MDP case study. We developed a method to conduct sensitivity analysis in sequential decision models, which could increase the credibility of these models among stakeholders.

The sequential structure of brain activation predicts skill.

Science.gov (United States)

Anderson, John R; Bothell, Daniel; Fincham, Jon M; Moon, Jungaa

2016-01-29

In an fMRI study, participants were trained to play a complex video game. They were scanned early and then again after substantial practice. While better players showed greater activation in one region (right dorsal striatum) their relative skill was better diagnosed by considering the sequential structure of whole brain activation. Using a cognitive model that played this game, we extracted a characterization of the mental states that are involved in playing a game and the statistical structure of the transitions among these states. There was a strong correspondence between this measure of sequential structure and the skill of different players. Using multi-voxel pattern analysis, it was possible to recognize, with relatively high accuracy, the cognitive states participants were in during particular scans. We used the sequential structure of these activation-recognized states to predict the skill of individual players. These findings indicate that important features about information-processing strategies can be identified from a model-based analysis of the sequential structure of brain activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

A one-sided sequential test

Energy Technology Data Exchange (ETDEWEB)

Racz, A.; Lux, I. [Hungarian Academy of Sciences, Budapest (Hungary). Atomic Energy Research Inst.

1996-04-16

The applicability of the classical sequential probability ratio testing (SPRT) for early failure detection problems is limited by the fact that there is an extra time delay between the occurrence of the failure and its first recognition. Chien and Adams developed a method to minimize this time for the case when the problem can be formulated as testing the mean value of a Gaussian signal. In our paper we propose a procedure that can be applied for both mean and variance testing and that minimizes the time delay. The method is based on a special parametrization of the classical SPRT. The one-sided sequential tests (OSST) can reproduce the results of the Chien-Adams test when applied for mean values. (author).

Mining Emerging Sequential Patterns for Activity Recognition in Body Sensor Networks

DEFF Research Database (Denmark)

Gu, Tao; Wang, Liang; Chen, Hanhua

2010-01-01

Body Sensor Networks oer many applications in healthcare, well-being and entertainment. One of the emerging applications is recognizing activities of daily living. In this paper, we introduce a novel knowledge pattern named Emerging Sequential Pattern (ESP)|a sequential pattern that discovers...... signicant class dierences|to recognize both simple (i.e., sequential) and complex (i.e., interleaved and concurrent) activities. Based on ESPs, we build our complex activity models directly upon the sequential model to recognize both activity types. We conduct comprehensive empirical studies to evaluate...

Efficacy and safety of sequential versus quadruple therapy as second-line treatment for helicobacter pylori infection-A randomized controlled trial.

Directory of Open Access Journals (Sweden)

Daniela Munteanu

Full Text Available Quadruple therapy is recommended as second-line treatment for Helicobacter pylori eradication failure. However, high cost, multiple side effects, and low adherence rates are major drawbacks to its routine use. Our aim was to compare the efficacy and safety of sequential versus quadruple regimens as second line treatment for persistent Helicobacter pylori infection.Prospective, randomized, open label trial was conducted at a large academic, tertiary care center in Israel. Patients who previously failed a standard triple treatment eradication course were randomly assigned (1:1 to receive a 10-day sequential therapy course, or a 14-day quadruple regimen. Compliance and adverse events were evaluated by telephone questionnaires. The primary endpoint for analysis was the rate of Helicobacter pylori eradication as defined by either a negative 13C-urea breath-test, or stool antigen test, 4-16 weeks after treatment assessed under the non-inferiority hypothesis. The trial was terminated prematurely due to low recruitment rates. See S1 Checklist for CONSORT checklist.One hundred and one patients were randomized. Per modified intention-to-treat analysis, eradication rate was 49% in the sequential versus 42.5% in the quadruple regimen group (p-value for non-inferiority 0.02. Forty-two (84.0% versus 33 (64.7% patients completed treatment in the sequential and quadruple groups respectively (p 0.027. Gastrointestinal side effects were more common in the quadruple regimen group.Sequential treatment when used as a second line regimen, was non-inferior to the standard of care quadruple regimen in achieving Helicobacter pylori eradication, and was associated with better compliance and fewer adverse effects. Both treatment protocols failed to show an adequate eradication rate in the population of Southern Israel.ClinicalTrials.gov NCT01481844.

Discrimination between sequential and simultaneous virtual channels with electrical hearing

OpenAIRE

Landsberger, David; Galvin, John J.

2011-01-01

In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation mode...

Hybrid Computerized Adaptive Testing: From Group Sequential Design to Fully Sequential Design

Science.gov (United States)

Wang, Shiyu; Lin, Haiyan; Chang, Hua-Hua; Douglas, Jeff

2016-01-01

Computerized adaptive testing (CAT) and multistage testing (MST) have become two of the most popular modes in large-scale computer-based sequential testing. Though most designs of CAT and MST exhibit strength and weakness in recent large-scale implementations, there is no simple answer to the question of which design is better because different…

Sequential dependencies in magnitude scaling of loudness

DEFF Research Database (Denmark)

Joshi, Suyash Narendra; Jesteadt, Walt

2013-01-01

Ten normally hearing listeners used a programmable sone-potentiometer knob to adjust the level of a 1000-Hz sinusoid to match the loudness of numbers presented to them in a magnitude production task. Three different power-law exponents (0.15, 0.30, and 0.60) and a log-law with equal steps in d......B were used to program the sone-potentiometer. The knob settings systematically influenced the form of the loudness function. Time series analysis was used to assess the sequential dependencies in the data, which increased with increasing exponent and were greatest for the log-law. It would be possible......, therefore, to choose knob properties that minimized these dependencies. When the sequential dependencies were removed from the data, the slope of the loudness functions did not change, but the variability decreased. Sequential dependencies were only present when the level of the tone on the previous trial...

Visual short-term memory for sequential arrays.

Science.gov (United States)

Kumar, Arjun; Jiang, Yuhong

2005-04-01

The capacity of visual short-term memory (VSTM) for a single visual display has been investigated in past research, but VSTM for multiple sequential arrays has been explored only recently. In this study, we investigate the capacity of VSTM across two sequential arrays separated by a variable stimulus onset asynchrony (SOA). VSTM for spatial locations (Experiment 1), colors (Experiments 2-4), orientations (Experiments 3 and 4), and conjunction of color and orientation (Experiment 4) were tested, with the SOA across the two sequential arrays varying from 100 to 1,500 msec. We find that VSTM for the trailing array is much better than VSTM for the leading array, but when averaged across the two arrays VSTM has a constant capacity independent of the SOA. We suggest that multiple displays compete for retention in VSTM and that separating information into two temporally discrete groups does not enhance the overall capacity of VSTM.

The target-to-foils shift in simultaneous and sequential lineups.

Science.gov (United States)

Clark, Steven E; Davey, Sherrie L

2005-04-01

A theoretical cornerstone in eyewitness identification research is the proposition that witnesses, in making decisions from standard simultaneous lineups, make relative judgments. The present research considers two sources of support for this proposal. An experiment by G. L. Wells (1993) showed that if the target is removed from a lineup, witnesses shift their responses to pick foils, rather than rejecting the lineups, a result we will term a target-to-foils shift. Additional empirical support is provided by results from sequential lineups which typically show higher accuracy than simultaneous lineups, presumably because of a decrease in the use of relative judgments in making identification decisions. The combination of these two lines of research suggests that the target-to-foils shift should be reduced in sequential lineups relative to simultaneous lineups. Results of two experiments showed an overall advantage for sequential lineups, but also showed a target-to-foils shift equal in size for simultaneous and sequential lineups. Additional analyses indicated that the target-to-foils shift in sequential lineups was moderated in part by an order effect and was produced with (Experiment 2) or without (Experiment 1) a shift in decision criterion. This complex pattern of results suggests that more work is needed to understand the processes which underlie decisions in simultaneous and sequential lineups.

Dynamics-based sequential memory: Winnerless competition of patterns

International Nuclear Information System (INIS)

Seliger, Philip; Tsimring, Lev S.; Rabinovich, Mikhail I.

2003-01-01

We introduce a biologically motivated dynamical principle of sequential memory which is based on winnerless competition (WLC) of event images. This mechanism is implemented in a two-layer neural model of sequential spatial memory. We present the learning dynamics which leads to the formation of a WLC network. After learning, the system is capable of associative retrieval of prerecorded sequences of patterns

Sequential, progressive, equal-power, reflective beam-splitter arrays

Science.gov (United States)

Manhart, Paul K.

2017-11-01

The equations to calculate equal-power reflectivity of a sequential series of beam splitters is presented. Non-sequential optical design examples are offered for uniform illumination using diode lasers. Objects created using Boolean operators and Swept Surfaces can create objects capable of reflecting light into predefined elevation and azimuth angles. Analysis of the illumination patterns for the array are also presented.

Basal ganglia and cortical networks for sequential ordering and rhythm of complex movements

Directory of Open Access Journals (Sweden)

Jeffery G. Bednark

2015-07-01

Full Text Available Voluntary actions require the concurrent engagement and coordinated control of complex temporal (e.g. rhythm and ordinal motor processes. Using high-resolution functional magnetic resonance imaging (fMRI and multi-voxel pattern analysis (MVPA, we sought to determine the degree to which these complex motor processes are dissociable in basal ganglia and cortical networks. We employed three different finger-tapping tasks that differed in the demand on the sequential temporal rhythm or sequential ordering of submovements. Our results demonstrate that sequential rhythm and sequential order tasks were partially dissociable based on activation differences. The sequential rhythm task activated a widespread network centered around the SMA and basal-ganglia regions including the dorsomedial putamen and caudate nucleus, while the sequential order task preferentially activated a fronto-parietal network. There was also extensive overlap between sequential rhythm and sequential order tasks, with both tasks commonly activating bilateral premotor, supplementary motor, and superior/inferior parietal cortical regions, as well as regions of the caudate/putamen of the basal ganglia and the ventro-lateral thalamus. Importantly, within the cortical regions that were active for both complex movements, MVPA could accurately classify different patterns of activation for the sequential rhythm and sequential order tasks. In the basal ganglia, however, overlapping activation for the sequential rhythm and sequential order tasks, which was found in classic motor circuits of the putamen and ventro-lateral thalamus, could not be accurately differentiated by MVPA. Overall, our results highlight the convergent architecture of the motor system, where complex motor information that is spatially distributed in the cortex converges into a more compact representation in the basal ganglia.

Effects of the buffering capacity of the soil on the mobilization of heavy metals. Equilibrium and kinetics.

Science.gov (United States)

Villen-Guzman, Maria; Paz-Garcia, Juan M; Amaya-Santos, Gema; Rodriguez-Maroto, Jose M; Vereda-Alonso, Carlos; Gomez-Lahoz, Cesar

2015-07-01

Understanding the possible pH-buffering processes is of maximum importance for risk assessment and remediation feasibility studies of heavy-metal contaminated soils. This paper presents the results about the effect of the buffering capacity of a polluted soil, rich in carbonates, on the pH and on the leaching evolution of its main contaminant (lead) when a weak acid (acetic acid) or a strong one (nitric acid) are slowly added. In both cases, the behavior of lead dissolution could be predicted using available (scientifically verified freeware) models assuming equilibrium between the solid and the aqueous phase. However, the experimental results indicate that the dissolution of calcium and magnesium carbonates is kinetically controlled. These kinetic limitations affect the overall behavior, and should be considered to understand also the response of the metals under local equilibrium. The well-known BCR sequential extraction procedure was used before- and after-treatment, to fractionate the lead concentration in the soil according to its mobility. The BCR results were also in agreement with the predictions of the equilibrium model. This agreement allows new insights about the information that could be derived from the BCR fractionation analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

The sequential price of anarchy for atomic congestion games

NARCIS (Netherlands)

de Jong, Jasper; Uetz, Marc Jochen; Liu, Tie-Yan; Qi, Qi; Ye, Yinyu

2014-01-01

In situations without central coordination, the price of anarchy relates the quality of any Nash equilibrium to the quality of a global optimum. Instead of assuming that all players choose their actions simultaneously, we consider games where players choose their actions sequentially. The sequential

Native Frames: Disentangling Sequential from Concerted Three-Body Fragmentation

Science.gov (United States)

Rajput, Jyoti; Severt, T.; Berry, Ben; Jochim, Bethany; Feizollah, Peyman; Kaderiya, Balram; Zohrabi, M.; Ablikim, U.; Ziaee, Farzaneh; Raju P., Kanaka; Rolles, D.; Rudenko, A.; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

2018-03-01

A key question concerning the three-body fragmentation of polyatomic molecules is the distinction of sequential and concerted mechanisms, i.e., the stepwise or simultaneous cleavage of bonds. Using laser-driven fragmentation of OCS into O++C++S+ and employing coincidence momentum imaging, we demonstrate a novel method that enables the clear separation of sequential and concerted breakup. The separation is accomplished by analyzing the three-body fragmentation in the native frame associated with each step and taking advantage of the rotation of the intermediate molecular fragment, CO2 + or CS2 + , before its unimolecular dissociation. This native-frame method works for any projectile (electrons, ions, or photons), provides details on each step of the sequential breakup, and enables the retrieval of the relevant spectra for sequential and concerted breakup separately. Specifically, this allows the determination of the branching ratio of all these processes in OCS3 + breakup. Moreover, we find that the first step of sequential breakup is tightly aligned along the laser polarization and identify the likely electronic states of the intermediate dication that undergo unimolecular dissociation in the second step. Finally, the separated concerted breakup spectra show clearly that the central carbon atom is preferentially ejected perpendicular to the laser field.

Gold electrode modified with a self-assembled glucose oxidase and 2,6-pyridinedicarboxylic acid as novel glucose bioanode for biofuel cells

NARCIS (Netherlands)

Ammam, Malika; Fransaer, Jan

2014-01-01

In this study, we have constructed a gold electrode modified with (3-aminopropyl)trimethoxysilane/2,6-pyridinedicarboxylic acid/glucose oxidase (abbreviated as, Au/ATS/PDA/GOx) by sequential chemical adsorption. Au/ATS/PDA/GOx electrode was characterized by Fourier Transform Infrared Spectroscopy

Implementing reduced-risk integrated pest management in fresh-market cabbage: influence of sampling parameters, and validation of binomial sequential sampling plans for the cabbage looper (Lepidoptera Noctuidae).

Science.gov (United States)

Burkness, Eric C; Hutchison, W D

2009-10-01

Populations of cabbage looper, Trichoplusiani (Lepidoptera: Noctuidae), were sampled in experimental plots and commercial fields of cabbage (Brasicca spp.) in Minnesota during 1998-1999 as part of a larger effort to implement an integrated pest management program. Using a resampling approach and the Wald's sequential probability ratio test, sampling plans with different sampling parameters were evaluated using independent presence/absence and enumerative data. Evaluations and comparisons of the different sampling plans were made based on the operating characteristic and average sample number functions generated for each plan and through the use of a decision probability matrix. Values for upper and lower decision boundaries, sequential error rates (alpha, beta), and tally threshold were modified to determine parameter influence on the operating characteristic and average sample number functions. The following parameters resulted in the most desirable operating characteristic and average sample number functions; action threshold of 0.1 proportion of plants infested, tally threshold of 1, alpha = beta = 0.1, upper boundary of 0.15, lower boundary of 0.05, and resampling with replacement. We found that sampling parameters can be modified and evaluated using resampling software to achieve desirable operating characteristic and average sample number functions. Moreover, management of T. ni by using binomial sequential sampling should provide a good balance between cost and reliability by minimizing sample size and maintaining a high level of correct decisions (>95%) to treat or not treat.

Campbell and moment measures for finite sequential spatial processes

NARCIS (Netherlands)

M.N.M. van Lieshout (Marie-Colette)

2006-01-01

textabstractWe define moment and Campbell measures for sequential spatial processes, prove a Campbell-Mecke theorem, and relate the results to their counterparts in the theory of point processes. In particular, we show that any finite sequential spatial process model can be derived as the vector

Efficiency enhancement of perovskite solar cells by fabricating as-prepared film before sequential spin-coating procedure

Energy Technology Data Exchange (ETDEWEB)

Jiang, Jiajia [Jiangsu Key Laboratory of Materials and Technology for Energy Conversion, College of material science and technology, Nanjing University of Aeronautics and Astronautics, Nanjing 211100 (China); Tao, Hai jun, E-mail: taohaijun@nuaa.edu.cn [Jiangsu Key Laboratory of Materials and Technology for Energy Conversion, College of material science and technology, Nanjing University of Aeronautics and Astronautics, Nanjing 211100 (China); Jiangsu Collaborative Innovation Center of Photovolatic Science and Engineering, Changzhou University, Changzhou 213164, Jiangsu (China); Chen, Shanlong; Tan, Bin [Jiangsu Key Laboratory of Materials and Technology for Energy Conversion, College of material science and technology, Nanjing University of Aeronautics and Astronautics, Nanjing 211100 (China); Zhou, Ning [Shanghai Electrochemical Energy Devices Research Center, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240 (China); Zhu, Lumin; Zhao, Yuan [Jiangsu Key Laboratory of Materials and Technology for Energy Conversion, College of material science and technology, Nanjing University of Aeronautics and Astronautics, Nanjing 211100 (China); Wang, Yuqiao [Jiangsu Optoelectronic Functional Materials and Engineering Laboratory, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189 (China); Tao, Jie [Jiangsu Key Laboratory of Materials and Technology for Energy Conversion, College of material science and technology, Nanjing University of Aeronautics and Astronautics, Nanjing 211100 (China)

2016-05-15

Graphical abstract: Schematic illustration of modified two-step spin-coating procedure for MAPbI{sub 3} perovskite thin films. - Highlights: • An as-prepared CH{sub 3}NH{sub 3}PbI{sub 3} and PbI{sub 2} film was introduced before the traditional two-step process. • Smooth morphology and trace amount of remaining PbI{sub 2} benefit the performance of solar cell. • The optimal as-prepared film introduced improves the efficiency of CH{sub 3}NH{sub 3}PbI{sub 3} solar cells from 9.11% to 11.16%. - Abstract: Sequential spin-coating procedure is a widely adopted strategy to prepare CH{sub 3}NH{sub 3}PbI{sub 3} on mesostructured TiO{sub 2} electrode for organolead halide perovskite-based solar cells. However, this method suffers from the rough surface and excessively residual PbI{sub 2} in the resulting perovskite film, deteriorating the device performance seriously. Herein, a facial modified sequential solution deposition method, by introducing an as-prepared CH{sub 3}NH{sub 3}PbI{sub 3} and PbI{sub 2} film before the traditional two-step process, was proposed to fabricate the perovskite-based solar cell with smooth morphology and trace amount of remaining PbI{sub 2}. The optimal as-prepared film introduced improves the efficiency of CH{sub 3}NH{sub 3}PbI{sub 3} solar cells from 9.11% to 11.16%. The enhancement of device performance can be attributed to the increased light absorption ability and decreased recombination rate of carriers in CH{sub 3}NH{sub 3}PbI{sub 3} absorber.

Sequential Dependencies in Driving

Science.gov (United States)

Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

2012-01-01

The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

Research on parallel algorithm for sequential pattern mining

Science.gov (United States)

Zhou, Lijuan; Qin, Bai; Wang, Yu; Hao, Zhongxiao

2008-03-01

Sequential pattern mining is the mining of frequent sequences related to time or other orders from the sequence database. Its initial motivation is to discover the laws of customer purchasing in a time section by finding the frequent sequences. In recent years, sequential pattern mining has become an important direction of data mining, and its application field has not been confined to the business database and has extended to new data sources such as Web and advanced science fields such as DNA analysis. The data of sequential pattern mining has characteristics as follows: mass data amount and distributed storage. Most existing sequential pattern mining algorithms haven't considered the above-mentioned characteristics synthetically. According to the traits mentioned above and combining the parallel theory, this paper puts forward a new distributed parallel algorithm SPP(Sequential Pattern Parallel). The algorithm abides by the principal of pattern reduction and utilizes the divide-and-conquer strategy for parallelization. The first parallel task is to construct frequent item sets applying frequent concept and search space partition theory and the second task is to structure frequent sequences using the depth-first search method at each processor. The algorithm only needs to access the database twice and doesn't generate the candidated sequences, which abates the access time and improves the mining efficiency. Based on the random data generation procedure and different information structure designed, this paper simulated the SPP algorithm in a concrete parallel environment and implemented the AprioriAll algorithm. The experiments demonstrate that compared with AprioriAll, the SPP algorithm had excellent speedup factor and efficiency.

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

Science.gov (United States)

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

2018-01-01

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

Framework for sequential approximate optimization

NARCIS (Netherlands)

Jacobs, J.H.; Etman, L.F.P.; Keulen, van F.; Rooda, J.E.

2004-01-01

An object-oriented framework for Sequential Approximate Optimization (SAO) isproposed. The framework aims to provide an open environment for thespecification and implementation of SAO strategies. The framework is based onthe Python programming language and contains a toolbox of Python

A Survey of Multi-Objective Sequential Decision-Making

OpenAIRE

Roijers, D.M.; Vamplew, P.; Whiteson, S.; Dazeley, R.

2013-01-01

Sequential decision-making problems with multiple objectives arise naturally in practice and pose unique challenges for research in decision-theoretic planning and learning, which has largely focused on single-objective settings. This article surveys algorithms designed for sequential decision-making problems with multiple objectives. Though there is a growing body of literature on this subject, little of it makes explicit under what circumstances special methods are needed to solve multi-obj...

A Sequential Multiplicative Extended Kalman Filter for Attitude Estimation Using Vector Observations

Science.gov (United States)

Qin, Fangjun; Jiang, Sai; Zha, Feng

2018-01-01

In this paper, a sequential multiplicative extended Kalman filter (SMEKF) is proposed for attitude estimation using vector observations. In the proposed SMEKF, each of the vector observations is processed sequentially to update the attitude, which can make the measurement model linearization more accurate for the next vector observation. This is the main difference to Murrell’s variation of the MEKF, which does not update the attitude estimate during the sequential procedure. Meanwhile, the covariance is updated after all the vector observations have been processed, which is used to account for the special characteristics of the reset operation necessary for the attitude update. This is the main difference to the traditional sequential EKF, which updates the state covariance at each step of the sequential procedure. The numerical simulation study demonstrates that the proposed SMEKF has more consistent and accurate performance in a wide range of initial estimate errors compared to the MEKF and its traditional sequential forms. PMID:29751538

A Sequential Multiplicative Extended Kalman Filter for Attitude Estimation Using Vector Observations

Directory of Open Access Journals (Sweden)

Fangjun Qin

2018-05-01

Full Text Available In this paper, a sequential multiplicative extended Kalman filter (SMEKF is proposed for attitude estimation using vector observations. In the proposed SMEKF, each of the vector observations is processed sequentially to update the attitude, which can make the measurement model linearization more accurate for the next vector observation. This is the main difference to Murrell’s variation of the MEKF, which does not update the attitude estimate during the sequential procedure. Meanwhile, the covariance is updated after all the vector observations have been processed, which is used to account for the special characteristics of the reset operation necessary for the attitude update. This is the main difference to the traditional sequential EKF, which updates the state covariance at each step of the sequential procedure. The numerical simulation study demonstrates that the proposed SMEKF has more consistent and accurate performance in a wide range of initial estimate errors compared to the MEKF and its traditional sequential forms.

Asynchronous Operators of Sequential Logic Venjunction & Sequention

CERN Document Server

Vasyukevich, Vadim

2011-01-01

This book is dedicated to new mathematical instruments assigned for logical modeling of the memory of digital devices. The case in point is logic-dynamical operation named venjunction and venjunctive function as well as sequention and sequentional function. Venjunction and sequention operate within the framework of sequential logic. In a form of the corresponding equations, they organically fit analytical expressions of Boolean algebra. Thus, a sort of symbiosis is formed using elements of asynchronous sequential logic on the one hand and combinational logic on the other hand. So, asynchronous

Particle connectedness and cluster formation in sequential depositions of particles: integral-equation theory.

Science.gov (United States)

Danwanichakul, Panu; Glandt, Eduardo D

2004-11-15

We applied the integral-equation theory to the connectedness problem. The method originally applied to the study of continuum percolation in various equilibrium systems was modified for our sequential quenching model, a particular limit of an irreversible adsorption. The development of the theory based on the (quenched-annealed) binary-mixture approximation includes the Ornstein-Zernike equation, the Percus-Yevick closure, and an additional term involving the three-body connectedness function. This function is simplified by introducing a Kirkwood-like superposition approximation. We studied the three-dimensional (3D) system of randomly placed spheres and 2D systems of square-well particles, both with a narrow and with a wide well. The results from our integral-equation theory are in good accordance with simulation results within a certain range of densities.

Human visual system automatically encodes sequential regularities of discrete events.

Science.gov (United States)

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

2010-06-01

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

A Bayesian Theory of Sequential Causal Learning and Abstract Transfer.

Science.gov (United States)

Lu, Hongjing; Rojas, Randall R; Beckers, Tom; Yuille, Alan L

2016-03-01

Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about abstract causal constraints? Recent empirical studies have revealed that experience with one set of causal cues can dramatically alter subsequent learning and performance with entirely different cues, suggesting that learning involves abstract transfer, and such transfer effects involve sequential presentation of distinct sets of causal cues. It has been demonstrated that pre-training (or even post-training) can modulate classic causal learning phenomena such as forward and backward blocking. To account for these effects, we propose a Bayesian theory of sequential causal learning. The theory assumes that humans are able to consider and use several alternative causal generative models, each instantiating a different causal integration rule. Model selection is used to decide which integration rule to use in a given learning environment in order to infer causal knowledge from sequential data. Detailed computer simulations demonstrate that humans rely on the abstract characteristics of outcome variables (e.g., binary vs. continuous) to select a causal integration rule, which in turn alters causal learning in a variety of blocking and overshadowing paradigms. When the nature of the outcome variable is ambiguous, humans select the model that yields the best fit with the recent environment, and then apply it to subsequent learning tasks. Based on sequential patterns of cue-outcome co-occurrence, the theory can account for a range of phenomena in sequential causal learning, including various blocking effects, primacy effects in some experimental conditions, and apparently abstract transfer of causal knowledge. Copyright © 2015

Impact of Diagrams on Recalling Sequential Elements in Expository Texts.

Science.gov (United States)

Guri-Rozenblit, Sarah

1988-01-01

Examines the instructional effectiveness of abstract diagrams on recall of sequential relations in social science textbooks. Concludes that diagrams assist significantly the recall of sequential relations in a text and decrease significantly the rate of order mistakes. (RS)

Quantum Probability Zero-One Law for Sequential Terminal Events

Science.gov (United States)

Rehder, Wulf

1980-07-01

On the basis of the Jauch-Piron quantum probability calculus a zero-one law for sequential terminal events is proven, and the significance of certain crucial axioms in the quantum probability calculus is discussed. The result shows that the Jauch-Piron set of axioms is appropriate for the non-Boolean algebra of sequential events.

A path-level exact parallelization strategy for sequential simulation

Science.gov (United States)

Peredo, Oscar F.; Baeza, Daniel; Ortiz, Julián M.; Herrero, José R.

2018-01-01

Sequential Simulation is a well known method in geostatistical modelling. Following the Bayesian approach for simulation of conditionally dependent random events, Sequential Indicator Simulation (SIS) method draws simulated values for K categories (categorical case) or classes defined by K different thresholds (continuous case). Similarly, Sequential Gaussian Simulation (SGS) method draws simulated values from a multivariate Gaussian field. In this work, a path-level approach to parallelize SIS and SGS methods is presented. A first stage of re-arrangement of the simulation path is performed, followed by a second stage of parallel simulation for non-conflicting nodes. A key advantage of the proposed parallelization method is to generate identical realizations as with the original non-parallelized methods. Case studies are presented using two sequential simulation codes from GSLIB: SISIM and SGSIM. Execution time and speedup results are shown for large-scale domains, with many categories and maximum kriging neighbours in each case, achieving high speedup results in the best scenarios using 16 threads of execution in a single machine.

Concatenated coding system with iterated sequential inner decoding

DEFF Research Database (Denmark)

Jensen, Ole Riis; Paaske, Erik

1995-01-01

We describe a concatenated coding system with iterated sequential inner decoding. The system uses convolutional codes of very long constraint length and operates on iterations between an inner Fano decoder and an outer Reed-Solomon decoder......We describe a concatenated coding system with iterated sequential inner decoding. The system uses convolutional codes of very long constraint length and operates on iterations between an inner Fano decoder and an outer Reed-Solomon decoder...

Lineup Composition, Suspect Position, and the Sequential Lineup Advantage

Science.gov (United States)

Carlson, Curt A.; Gronlund, Scott D.; Clark, Steven E.

2008-01-01

N. M. Steblay, J. Dysart, S. Fulero, and R. C. L. Lindsay (2001) argued that sequential lineups reduce the likelihood of mistaken eyewitness identification. Experiment 1 replicated the design of R. C. L. Lindsay and G. L. Wells (1985), the first study to show the sequential lineup advantage. However, the innocent suspect was chosen at a lower rate…

Trial Sequential Analysis in systematic reviews with meta-analysis

Directory of Open Access Journals (Sweden)

Jørn Wetterslev

2017-03-01

Full Text Available Abstract Background Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors and too many false negative conclusions (type II errors. Methods We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. Results The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D2 measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in

Heat accumulation during sequential cortical bone drilling.

Science.gov (United States)

Palmisano, Andrew C; Tai, Bruce L; Belmont, Barry; Irwin, Todd A; Shih, Albert; Holmes, James R

2016-03-01

Significant research exists regarding heat production during single-hole bone drilling. No published data exist regarding repetitive sequential drilling. This study elucidates the phenomenon of heat accumulation for sequential drilling with both Kirschner wires (K wires) and standard two-flute twist drills. It was hypothesized that cumulative heat would result in a higher temperature with each subsequent drill pass. Nine holes in a 3 × 3 array were drilled sequentially on moistened cadaveric tibia bone kept at body temperature (about 37 °C). Four thermocouples were placed at the center of four adjacent holes and 2 mm below the surface. A battery-driven hand drill guided by a servo-controlled motion system was used. Six samples were drilled with each tool (2.0 mm K wire and 2.0 and 2.5 mm standard drills). K wire drilling increased temperature from 5 °C at the first hole to 20 °C at holes 6 through 9. A similar trend was found in standard drills with less significant increments. The maximum temperatures of both tools increased from drill sizes was found to be insignificant (P > 0.05). In conclusion, heat accumulated during sequential drilling, with size difference being insignificant. K wire produced more heat than its twist-drill counterparts. This study has demonstrated the heat accumulation phenomenon and its significant effect on temperature. Maximizing the drilling field and reducing the number of drill passes may decrease bone injury. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Cost-effectiveness of simultaneous versus sequential surgery in head and neck reconstruction.

Science.gov (United States)

Wong, Kevin K; Enepekides, Danny J; Higgins, Kevin M

2011-02-01

To determine whether simultaneous (ablation and reconstruction overlaps by two teams) head and neck reconstruction is cost effective compared to sequentially (ablation followed by reconstruction) performed surgery. Case-controlled study. Tertiary care hospital. Oncology patients undergoing free flap reconstruction of the head and neck. A match paired comparison study was performed with a retrospective chart review examining the total time of surgery for sequential and simultaneous surgery. Nine patients were selected for both the sequential and simultaneous groups. Sequential head and neck reconstruction patients were pair matched with patients who had undergone similar oncologic ablative or reconstructive procedures performed in a simultaneous fashion. A detailed cost analysis using the microcosting method was then undertaken looking at the direct costs of the surgeons, anesthesiologist, operating room, and nursing. On average, simultaneous surgery required 3 hours 15 minutes less operating time, leading to a cost savings of approximately $1200/case when compared to sequential surgery. This represents approximately a 15% reduction in the cost of the entire operation. Simultaneous head and neck reconstruction is more cost effective when compared to sequential surgery.

High-precision ²⁷Al/²⁴Mg ratio determination using a modified isotope-dilution approach

DEFF Research Database (Denmark)

Paton, Chad; Schiller, Martin; Ulfbeck, David Garf

2012-01-01

saves time and minimises the risk of contamination of other samples with spike (which is added immediately prior to analysis). Repeat measurements of the BHVO-2, BCR-2, and BIR-1 international rock standards, as well as a gravimetrically prepared Al–Mg reference solution, indicate that our method......The precision of the 26Al–26Mg system—one of the most widely used chronometers for constraining the relative timing of events in the early solar system—is presently limited by methods for the determination of 27Al/24Mg ratios, which have seen little improvement in the last decade. We present...... a novel method for the measurement of 27Al/24Mg ratios in unpurified sample solutions by multiple-collector inductively coupled plasma mass spectrometry. Because Al is monoisotopic we use a modified isotope dilution approach that employs a mixed spike containing isotopically enriched 25Mg and natural 27Al...

Comparative kinetic studies of Mn2+-activated and fructose-1,6-P-modified Mg2+-activated pyruvate kinase from Concholepas concholepas.

Science.gov (United States)

Carvajal, N; González, R; Morán, A; Oyarce, A M

1985-01-01

Initial velocity and product inhibition studies of Mn2+-activated and FDP-modified Mg2+-activated pyruvate kinase from Concholepas concholepas, were performed. Evidence is presented to show that the Mn2+-enzyme catalyzes an ordered sequential mechanism, with ADP being the first substrate and pyruvate the last product. The results presented are consistent with a random combination of reactants with the FDP-modified Mg2+-activated enzyme and the formation of the dead-end complexes enzyme ADP-ATP and enzyme-PEP-ATP.

A Trust-region-based Sequential Quadratic Programming Algorithm

DEFF Research Database (Denmark)

Henriksen, Lars Christian; Poulsen, Niels Kjølstad

This technical note documents the trust-region-based sequential quadratic programming algorithm used in other works by the authors. The algorithm seeks to minimize a convex nonlinear cost function subject to linear inequalty constraints and nonlinear equality constraints.......This technical note documents the trust-region-based sequential quadratic programming algorithm used in other works by the authors. The algorithm seeks to minimize a convex nonlinear cost function subject to linear inequalty constraints and nonlinear equality constraints....

Sequential search leads to faster, more efficient fragment-based de novo protein structure prediction.

Science.gov (United States)

de Oliveira, Saulo H P; Law, Eleanor C; Shi, Jiye; Deane, Charlotte M

2018-04-01

Most current de novo structure prediction methods randomly sample protein conformations and thus require large amounts of computational resource. Here, we consider a sequential sampling strategy, building on ideas from recent experimental work which shows that many proteins fold cotranslationally. We have investigated whether a pseudo-greedy search approach, which begins sequentially from one of the termini, can improve the performance and accuracy of de novo protein structure prediction. We observed that our sequential approach converges when fewer than 20 000 decoys have been produced, fewer than commonly expected. Using our software, SAINT2, we also compared the run time and quality of models produced in a sequential fashion against a standard, non-sequential approach. Sequential prediction produces an individual decoy 1.5-2.5 times faster than non-sequential prediction. When considering the quality of the best model, sequential prediction led to a better model being produced for 31 out of 41 soluble protein validation cases and for 18 out of 24 transmembrane protein cases. Correct models (TM-Score > 0.5) were produced for 29 of these cases by the sequential mode and for only 22 by the non-sequential mode. Our comparison reveals that a sequential search strategy can be used to drastically reduce computational time of de novo protein structure prediction and improve accuracy. Data are available for download from: http://opig.stats.ox.ac.uk/resources. SAINT2 is available for download from: https://github.com/sauloho/SAINT2. saulo.deoliveira@dtc.ox.ac.uk. Supplementary data are available at Bioinformatics online.

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

Science.gov (United States)

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

2018-01-01

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

Determination of Thallium(I by Hybrid Mesoporous Silica (SBA-15 Modified Electrode

Directory of Open Access Journals (Sweden)

Geeta Rani

2016-01-01

Full Text Available Chemically modified mesoporous silica material (SBA-15 was used for the construction of Tl(I selective carbon paste electrode. The best response was found with the electrode containing 10% modifier as electrode material. The electrode has a lower detection limit of 6.0 × 10−9 M in a working concentration range of 1.0 × 10−8–1.0 × 10−1 M. The selectivity coefficient calculated by match potential method (MPM shows the high selectivity of electrode towards Tl(I over other tested ions. The electrode was successfully applied as an indicator electrode for the titration of 0.01 M TlNO3 solution with standards EDTA solution and for sequential titration of mixture of different anions.

Synthetic Aperture Sequential Beamforming

DEFF Research Database (Denmark)

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

2008-01-01

A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective is to im......A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective...... is to improve and obtain a more range independent lateral resolution compared to conventional dynamic receive focusing (DRF) without compromising frame rate. SASB is a two-stage procedure using two separate beamformers. First a set of Bmode image lines using a single focal point in both transmit and receive...... is stored. The second stage applies the focused image lines from the first stage as input data. The SASB method has been investigated using simulations in Field II and by off-line processing of data acquired with a commercial scanner. The performance of SASB with a static image object is compared with DRF...

Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

Science.gov (United States)

Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

2017-11-01

Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

Evaluation Using Sequential Trials Methods.

Science.gov (United States)

Cohen, Mark E.; Ralls, Stephen A.

1986-01-01

Although dental school faculty as well as practitioners are interested in evaluating products and procedures used in clinical practice, research design and statistical analysis can sometimes pose problems. Sequential trials methods provide an analytical structure that is both easy to use and statistically valid. (Author/MLW)

Attack Trees with Sequential Conjunction

NARCIS (Netherlands)

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

2015-01-01

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

The impact of eyewitness identifications from simultaneous and sequential lineups.

Science.gov (United States)

Wright, Daniel B

2007-10-01

Recent guidelines in the US allow either simultaneous or sequential lineups to be used for eyewitness identification. This paper investigates how potential jurors weight the probative value of the different outcomes from both of these types of lineups. Participants (n=340) were given a description of a case that included some exonerating and some incriminating evidence. There was either a simultaneous or a sequential lineup. Depending on the condition, an eyewitness chose the suspect, chose a filler, or made no identification. The participant had to judge the guilt of the suspect and decide whether to render a guilty verdict. For both simultaneous and sequential lineups an identification had a large effect,increasing the probability of a guilty verdict. There were no reliable effects detected between making no identification and identifying a filler. The effect sizes were similar for simultaneous and sequential lineups. These findings are important for judges and other legal professionals to know for trials involving lineup identifications.

Properties of simultaneous and sequential two-nucleon transfer

International Nuclear Information System (INIS)

Pinkston, W.T.; Satchler, G.R.

1982-01-01

Approximate forms of the first- and second-order distorted-wave Born amplitudes are used to study the overall structure, particularly the selection rules, of the amplitudes for simultaneous and sequential transfer of two nucleons. The role of the spin-state assumed for the intermediate deuterons in sequential (t, p) reactions is stressed. The similarity of one-step and two-step amplitudes for (α, d) reactions is exhibited, and the consequent absence of any obvious J-dependence in their interference is noted. (orig.)

Sequential contrast-enhanced MR imaging of the penis.

Science.gov (United States)

Kaneko, K; De Mouy, E H; Lee, B E

1994-04-01

To determine the enhancement patterns of the penis at magnetic resonance (MR) imaging. Sequential contrast material-enhanced MR images of the penis in a flaccid state were obtained in 16 volunteers (12 with normal penile function and four with erectile dysfunction). Subjects with normal erectile function showed gradual and centrifugal enhancement of the corpora cavernosa, while those with erectile dysfunction showed poor enhancement with abnormal progression. Sequential contrast-enhanced MR imaging provides additional morphologic information for the evaluation of erectile dysfunction.

Synthesizing genetic sequential logic circuit with clock pulse generator.

Science.gov (United States)

Chuang, Chia-Hua; Lin, Chun-Liang

2014-05-28

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

Sequential weak continuity of null Lagrangians at the boundary

Czech Academy of Sciences Publication Activity Database

Kalamajska, A.; Kraemer, S.; Kružík, Martin

2014-01-01

Roč. 49, 3/4 (2014), s. 1263-1278 ISSN 0944-2669 R&D Projects: GA ČR GAP201/10/0357 Institutional support: RVO:67985556 Keywords : null Lagrangians * nonhomogeneous nonlinear mappings * sequential weak/in measure continuity Subject RIV: BA - General Mathematics Impact factor: 1.518, year: 2014 http://library.utia.cas.cz/separaty/2013/MTR/kruzik-sequential weak continuity of null lagrangians at the boundary.pdf

[Variation in soil Mn fractions as affected by long-term manure amendment using atomic absorption spectrophotometer in a typical grassland of inner Mongolia].

Science.gov (United States)

Fu, Ming-ming; Jiang, Yong; Bai, Yong-fei; Zhang, Yu-ge; Xu, Zhu-wen; Li, Bo

2012-08-01

The effect of sheep manure amendment on soil manganese fractions was conducted in a 11 year experiment at inner Mongolia grassland, using sequential extraction procedure in modified Community Bureau of Reference, and determined by atomic absorption spectrophotometer. Five treatments with dry sheep manure addition rate 0, 50, 250, 750, and 1500 g x m(-2) x yr(-1), respectively, were carried out in this experiment. Results showed that the recovery rate for total Mn was 91.4%-105.9%, as the percentage recovered from the summation of the improved BCR results with aqua regia extractable contents, and it was 97.2%-102.9% from certified soil reference materials. Plant available exchangeable Mn could be enhanced by 47.89%, but reducible and total Mn contents decreased significantly under heavy application of manure at depth of 0-5 cm. The effect of manure amendment on Mn fractions was greater in 0-5 cm than in 5-10 cm soil layer. The results are benefit to micronutrient fractions determination and nutrient management in grassland soils.

Sequential and simultaneous SLAR block adjustment. [spline function analysis for mapping

Science.gov (United States)

Leberl, F.

1975-01-01

Two sequential methods of planimetric SLAR (Side Looking Airborne Radar) block adjustment, with and without splines, and three simultaneous methods based on the principles of least squares are evaluated. A limited experiment with simulated SLAR images indicates that sequential block formation with splines followed by external interpolative adjustment is superior to the simultaneous methods such as planimetric block adjustment with similarity transformations. The use of the sequential block formation is recommended, since it represents an inexpensive tool for satisfactory point determination from SLAR images.

Sequential Extraction Versus Comprehensive Characterization of Heavy Metal Species in Brownfield Soils

Energy Technology Data Exchange (ETDEWEB)

Dahlin, Cheryl L.; Williamson, Connie A.; Collins, W. Keith; Dahlin, David C.

2002-06-01

The applicability of sequential extraction as a means to determine species of heavy-metals was examined by a study on soil samples from two Superfund sites: the National Lead Company site in Pedricktown, NJ, and the Roebling Steel, Inc., site in Florence, NJ. Data from a standard sequential extraction procedure were compared to those from a comprehensive study that combined optical- and scanning-electron microscopy, X-ray diffraction, and chemical analyses. The study shows that larger particles of contaminants, encapsulated contaminants, and/or man-made materials such as slags, coke, metals, and plastics are subject to incasement, non-selectivity, and redistribution in the sequential extraction process. The results indicate that standard sequential extraction procedures that were developed for characterizing species of contaminants in river sediments may be unsuitable for stand-alone determinative evaluations of contaminant species in industrial-site materials. However, if employed as part of a comprehensive, site-specific characterization study, sequential extraction could be a very useful tool.

Imitation of the sequential structure of actions by chimpanzees (Pan troglodytes).

Science.gov (United States)

Whiten, A

1998-09-01

Imitation was studied experimentally by allowing chimpanzees (Pan troglodytes) to observe alternative patterns of actions for opening a specially designed "artificial fruit." Like problematic foods primates deal with naturally, with the test fruit several defenses had to be removed to gain access to an edible core, but the sequential order and method of defense removal could be systematically varied. Each subject repeatedly observed 1 of 2 alternative techniques for removing each defense and 1 of 2 alternative sequential patterns of defense removal. Imitation of sequential organization emerged after repeated cycles of demonstration and attempts at opening the fruit. Imitation in chimpanzees may thus have some power to produce cultural convergence, counter to the supposition that individual learning processes corrupt copied actions. Imitation of sequential organization was accompanied by imitation of some aspects of the techniques that made up the sequence.

Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup.

Science.gov (United States)

Hardarson, Thorir; Bungum, Mona; Conaghan, Joe; Meintjes, Marius; Chantilis, Samuel J; Molnar, Laszlo; Gunnarsson, Kristina; Wikland, Matts

2015-12-01

To study whether a culture medium that allows undisturbed culture supports human embryo development to the blastocyst stage equivalently to a well-established sequential media. Randomized, double-blinded sibling trial. Independent in vitro fertilization (IVF) clinics. One hundred twenty-eight patients, with 1,356 zygotes randomized into two study arms. Embryos randomly allocated into two study arms to compare embryo development on a time-lapse system using a single-step medium or sequential media. Percentage of good-quality blastocysts on day 5. Percentage of day 5 good-quality blastocysts was 21.1% (standard deviation [SD] ± 21.6%) and 22.2% (SD ± 22.1%) in the single-step time-lapse medium (G-TL) and the sequential media (G-1/G-2) groups, respectively. The mean difference (-1.2; 95% CI, -6.0; 3.6) between the two media systems for the primary end point was less than the noninferiority margin of -8%. There was a statistically significantly lower number of good-quality embryos on day 3 in the G-TL group [50.7% (SD ± 30.6%) vs. 60.8% (SD ± 30.7%)]. Four out of the 11 measured morphokinetic parameters were statistically significantly different for the two media used. The mean levels of ammonium concentration in the media at the end of the culture period was statistically significantly lower in the G-TL group as compared with the G-2 group. We have shown that a single-step culture medium supports blastocyst development equivalently to established sequential media. The ammonium concentrations were lower in the single-step media, and the measured morphokinetic parameters were modified somewhat. NCT01939626. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Sequential determination of important ecotoxic radionuclides in nuclear waste samples

International Nuclear Information System (INIS)

Bilohuscin, J.

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Marianna Greco

2013-01-01

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

A solution for automatic parallelization of sequential assembly code

Directory of Open Access Journals (Sweden)

Kovačević Đorđe

2013-01-01

Full Text Available Since modern multicore processors can execute existing sequential programs only on a single core, there is a strong need for automatic parallelization of program code. Relying on existing algorithms, this paper describes one new software solution tool for parallelization of sequential assembly code. The main goal of this paper is to develop the parallelizator which reads sequential assembler code and at the output provides parallelized code for MIPS processor with multiple cores. The idea is the following: the parser translates assembler input file to program objects suitable for further processing. After that the static single assignment is done. Based on the data flow graph, the parallelization algorithm separates instructions on different cores. Once sequential code is parallelized by the parallelization algorithm, registers are allocated with the algorithm for linear allocation, and the result at the end of the program is distributed assembler code on each of the cores. In the paper we evaluate the speedup of the matrix multiplication example, which was processed by the parallelizator of assembly code. The result is almost linear speedup of code execution, which increases with the number of cores. The speed up on the two cores is 1.99, while on 16 cores the speed up is 13.88.

Documentscape: Intertextuality, Sequentiality & Autonomy at Work

DEFF Research Database (Denmark)

Christensen, Lars Rune; Bjørn, Pernille

2014-01-01

On the basis of an ethnographic field study, this article introduces the concept of documentscape to the analysis of document-centric work practices. The concept of documentscape refers to the entire ensemble of documents in their mutual intertextual interlocking. Providing empirical data from...... a global software development case, we show how hierarchical structures and sequentiality across the interlocked documents are critical to how actors make sense of the work of others and what to do next in a geographically distributed setting. Furthermore, we found that while each document is created...... as part of a quasi-sequential order, this characteristic does not make the document, as a single entity, into a stable object. Instead, we found that the documents were malleable and dynamic while suspended in intertextual structures. Our concept of documentscape points to how the hierarchical structure...

Sequential series for nuclear reactions

International Nuclear Information System (INIS)

Izumo, Ko

1975-01-01

A new time-dependent treatment of nuclear reactions is given, in which the wave function of compound nucleus is expanded by a sequential series of the reaction processes. The wave functions of the sequential series form another complete set of compound nucleus at the limit Δt→0. It is pointed out that the wave function is characterized by the quantities: the number of degrees of freedom of motion n, the period of the motion (Poincare cycle) tsub(n), the delay time t sub(nμ) and the relaxation time tausub(n) to the equilibrium of compound nucleus, instead of the usual quantum number lambda, the energy eigenvalue Esub(lambda) and the total width GAMMAsub(lambda) of resonance levels, respectively. The transition matrix elements and the yields of nuclear reactions also become the functions of time given by the Fourier transform of the usual ones. The Poincare cycles of compound nuclei are compared with the observed correlations among resonance levels, which are about 10 -17 --10 -16 sec for medium and heavy nuclei and about 10 -20 sec for the intermediate resonances. (auth.)

A node linkage approach for sequential pattern mining.

Directory of Open Access Journals (Sweden)

Osvaldo Navarro

Full Text Available Sequential Pattern Mining is a widely addressed problem in data mining, with applications such as analyzing Web usage, examining purchase behavior, and text mining, among others. Nevertheless, with the dramatic increase in data volume, the current approaches prove inefficient when dealing with large input datasets, a large number of different symbols and low minimum supports. In this paper, we propose a new sequential pattern mining algorithm, which follows a pattern-growth scheme to discover sequential patterns. Unlike most pattern growth algorithms, our approach does not build a data structure to represent the input dataset, but instead accesses the required sequences through pseudo-projection databases, achieving better runtime and reducing memory requirements. Our algorithm traverses the search space in a depth-first fashion and only preserves in memory a pattern node linkage and the pseudo-projections required for the branch being explored at the time. Experimental results show that our new approach, the Node Linkage Depth-First Traversal algorithm (NLDFT, has better performance and scalability in comparison with state of the art algorithms.

Sequential Change-Point Detection via Online Convex Optimization

Directory of Open Access Journals (Sweden)

Yang Cao

2018-02-01

Full Text Available Sequential change-point detection when the distribution parameters are unknown is a fundamental problem in statistics and machine learning. When the post-change parameters are unknown, we consider a set of detection procedures based on sequential likelihood ratios with non-anticipating estimators constructed using online convex optimization algorithms such as online mirror descent, which provides a more versatile approach to tackling complex situations where recursive maximum likelihood estimators cannot be found. When the underlying distributions belong to a exponential family and the estimators satisfy the logarithm regret property, we show that this approach is nearly second-order asymptotically optimal. This means that the upper bound for the false alarm rate of the algorithm (measured by the average-run-length meets the lower bound asymptotically up to a log-log factor when the threshold tends to infinity. Our proof is achieved by making a connection between sequential change-point and online convex optimization and leveraging the logarithmic regret bound property of online mirror descent algorithm. Numerical and real data examples validate our theory.

Sequential decoders for large MIMO systems

KAUST Repository

Ali, Konpal S.; Abediseid, Walid; Alouini, Mohamed-Slim

2014-01-01

the Sequential Decoder using the Fano Algorithm for large MIMO systems. A parameter called the bias is varied to attain different performance-complexity trade-offs. Low values of the bias result in excellent performance but at the expense of high complexity

Development of modified flyash as a permeable reactive barrier medium for a former manufactured gas plant site, Northern Ireland

Science.gov (United States)

Doherty, R.; Phillips, D. H.; McGeough, K. L.; Walsh, K. P.; Kalin, R. M.

2006-05-01

A sequential biological permeable reactive barrier (PRB) was determined to be the best option for remediating groundwater that has become contaminated with a wide range of organic contaminants (i.e., benzene, toluene, ethylbenzene, xylene and polyaromatic hydrocarbons), heavy metals (i.e., lead and arsenic), and cyanide at a former manufactured gas plant after 150 years of operation in Portadown, Northern Ireland. The objective of this study was to develop a modified flyash that could be used in the initial cell within a sequential biological PRB to filter complex contaminated groundwater containing ammonium. Flyash modified with lime (CaOH) and alum was subjected to a series of batch tests which investigated the modified cation exchange capacity (CEC) and rate of removal of anions and cations from the solution. These tests showed that a high flyash composition medium (80%) could remove 8.65 mol of ammonium contaminant for every kilogram of medium. The modified CEC procedure ruled out the possibility of cation exchange as the major removal mechanism. The medium could also adsorb anions as well as cations (i.e., Pb and Cr), but not with the same capacity. The initial mechanism for Pb and Cr removal is probably precipitation. This is followed by sorption, which is possibly the only mechanism for the removal of dichromate anions. Scanning electron microscopic analysis revealed very small (productive zeolite formation. Surface area measurements showed that biofilm growth on the medium could be a major factor in the comparative reduction of surface area between real and synthetic contaminant groundwaters. The modified flyash was found to be a highly sorptive granular material that did not inhibit microbiological activity, however, leaching tests revealed that the medium would fail as a long-term barrier material.

Comment on: "Cell Therapy for Heart Disease: Trial Sequential Analyses of Two Cochrane Reviews"

DEFF Research Database (Denmark)

Castellini, Greta; Nielsen, Emil Eik; Gluud, Christian

2017-01-01

Trial Sequential Analysis is a frequentist method to help researchers control the risks of random errors in meta-analyses (1). Fisher and colleagues used Trial Sequential Analysis on cell therapy for heart diseases (2). The present article discusses the usefulness of Trial Sequential Analysis and...

Fabrication of anticoagulation layer on titanium surface by sequential immobilization of poly (ethylene glycol) and albumin.

Science.gov (United States)

Pan, Chang-Jiang; Hou, Yan-Hua; Zhang, Bin-Bin; Zhang, Lin-Cai

2014-01-01

This paper presents a simple method to sequentially immobilize poly (ethylene glycol) (PEG) and albumin on titanium surface to enhance the blood compatibility. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis indicated that PEG and albumin were successfully immobilized on the titanium surface. Water contact angle results showed a better hydrophilic surface after the immobilization. The immobilized PEG or albumin can not only obviously prevent platelet adhesion and activation but also prolong activated partial thromboplastin time (APTT), leading to the improved anticoagulation. Moreover, immobilization of albumin on PEG-modified surface can further improve the anticoagulation. The approach in the present study provides an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.

Efficient sequential and parallel algorithms for record linkage.

Science.gov (United States)

Mamun, Abdullah-Al; Mi, Tian; Aseltine, Robert; Rajasekaran, Sanguthevar

2014-01-01

Integrating data from multiple sources is a crucial and challenging problem. Even though there exist numerous algorithms for record linkage or deduplication, they suffer from either large time needs or restrictions on the number of datasets that they can integrate. In this paper we report efficient sequential and parallel algorithms for record linkage which handle any number of datasets and outperform previous algorithms. Our algorithms employ hierarchical clustering algorithms as the basis. A key idea that we use is radix sorting on certain attributes to eliminate identical records before any further processing. Another novel idea is to form a graph that links similar records and find the connected components. Our sequential and parallel algorithms have been tested on a real dataset of 1,083,878 records and synthetic datasets ranging in size from 50,000 to 9,000,000 records. Our sequential algorithm runs at least two times faster, for any dataset, than the previous best-known algorithm, the two-phase algorithm using faster computation of the edit distance (TPA (FCED)). The speedups obtained by our parallel algorithm are almost linear. For example, we get a speedup of 7.5 with 8 cores (residing in a single node), 14.1 with 16 cores (residing in two nodes), and 26.4 with 32 cores (residing in four nodes). We have compared the performance of our sequential algorithm with TPA (FCED) and found that our algorithm outperforms the previous one. The accuracy is the same as that of this previous best-known algorithm.

Automatic synthesis of sequential control schemes

International Nuclear Information System (INIS)

Klein, I.

1993-01-01

Of all hard- and software developed for industrial control purposes, the majority is devoted to sequential, or binary valued, control and only a minor part to classical linear control. Typically, the sequential parts of the controller are invoked during startup and shut-down to bring the system into its normal operating region and into some safe standby region, respectively. Despite its importance, fairly little theoretical research has been devoted to this area, and sequential control programs are therefore still created manually without much theoretical support to obtain a systematic approach. We propose a method to create sequential control programs automatically. The main ideas is to spend some effort off-line modelling the plant, and from this model generate the control strategy, that is the plan. The plant is modelled using action structures, thereby concentrating on the actions instead of the states of the plant. In general the planning problem shows exponential complexity in the number of state variables. However, by focusing on the actions, we can identify problem classes as well as algorithms such that the planning complexity is reduced to polynomial complexity. We prove that these algorithms are sound, i.e., the generated solution will solve the stated problem, and complete, i.e., if the algorithms fail, then no solution exists. The algorithms generate a plan as a set of actions and a partial order on this set specifying the execution order. The generated plant is proven to be minimal and maximally parallel. For a larger class of problems we propose a method to split the original problem into a number of simple problems that can each be solved using one of the presented algorithms. It is also shown how a plan can be translated into a GRAFCET chart, and to illustrate these ideas we have implemented a planing tool, i.e., a system that is able to automatically create control schemes. Such a tool can of course also be used on-line if it is fast enough. This

Sequential designs for sensitivity analysis of functional inputs in computer experiments

International Nuclear Information System (INIS)

Fruth, J.; Roustant, O.; Kuhnt, S.

2015-01-01

Computer experiments are nowadays commonly used to analyze industrial processes aiming at achieving a wanted outcome. Sensitivity analysis plays an important role in exploring the actual impact of adjustable parameters on the response variable. In this work we focus on sensitivity analysis of a scalar-valued output of a time-consuming computer code depending on scalar and functional input parameters. We investigate a sequential methodology, based on piecewise constant functions and sequential bifurcation, which is both economical and fully interpretable. The new approach is applied to a sheet metal forming problem in three sequential steps, resulting in new insights into the behavior of the forming process over time. - Highlights: • Sensitivity analysis method for functional and scalar inputs is presented. • We focus on the discovery of most influential parts of the functional domain. • We investigate economical sequential methodology based on piecewise constant functions. • Normalized sensitivity indices are introduced and investigated theoretically. • Successful application to sheet metal forming on two functional inputs

INAA and PIXE for the determination of the contents of extractable sediment

International Nuclear Information System (INIS)

Freitas, M.C.; Hipolito, C.S.

2007-01-01

The three-stage BCR sequential step reference extraction procedure was applied to the reference material BCR CRM 601, especially developed for fractionation studies. Extracted fractions were analyzed for Cr, Ni, Zn, Cd, and Pb, by k 0 -standardized instrumental neutron activation (k 0 INAA) and proton induced X-ray emission (PIXE), and flame atomic absorption spectrometry (FAAS). Sample preparation procedures were developed for both k 0 INAA and PIXE techniques, related to the evaporation of the solutions in order to get solid samples for neutron and proton irradiation. Quality control was assessed by intercomparison of the analytical results obtained by the applied techniques, which included results for a few certified reference materials. In the extracted fractions, chromium concentration was not determined accurately by both nuclear techniques. Concerning Cd, Ni, Pb, and Zn, the results were in general in good agreement with the certified values and FAAS. Some incomplete separation of the residue might have occurred. (author)

On the origin of reproducible sequential activity in neural circuits

Science.gov (United States)

Afraimovich, V. S.; Zhigulin, V. P.; Rabinovich, M. I.

2004-12-01

Robustness and reproducibility of sequential spatio-temporal responses is an essential feature of many neural circuits in sensory and motor systems of animals. The most common mathematical images of dynamical regimes in neural systems are fixed points, limit cycles, chaotic attractors, and continuous attractors (attractive manifolds of neutrally stable fixed points). These are not suitable for the description of reproducible transient sequential neural dynamics. In this paper we present the concept of a stable heteroclinic sequence (SHS), which is not an attractor. SHS opens the way for understanding and modeling of transient sequential activity in neural circuits. We show that this new mathematical object can be used to describe robust and reproducible sequential neural dynamics. Using the framework of a generalized high-dimensional Lotka-Volterra model, that describes the dynamics of firing rates in an inhibitory network, we present analytical results on the existence of the SHS in the phase space of the network. With the help of numerical simulations we confirm its robustness in presence of noise in spite of the transient nature of the corresponding trajectories. Finally, by referring to several recent neurobiological experiments, we discuss possible applications of this new concept to several problems in neuroscience.

Sequential spatial processes for image analysis

NARCIS (Netherlands)

M.N.M. van Lieshout (Marie-Colette); V. Capasso

2009-01-01

htmlabstractWe give a brief introduction to sequential spatial processes. We discuss their definition, formulate a Markov property, and indicate why such processes are natural tools in tackling high level vision problems. We focus on the problem of tracking a variable number of moving objects

Sequential models for coarsening and missingness

NARCIS (Netherlands)

Gill, R.D.; Robins, J.M.

1997-01-01

In a companion paper we described what intuitively would seem to be the most general possible way to generate Coarsening at Random mechanisms a sequential procedure called randomized monotone coarsening Counterexamples showed that CAR mechanisms exist which cannot be represented in this way Here we

Sequential bayes estimation algorithm with cubic splines on uniform meshes

International Nuclear Information System (INIS)

Hossfeld, F.; Mika, K.; Plesser-Walk, E.

1975-11-01

After outlining the principles of some recent developments in parameter estimation, a sequential numerical algorithm for generalized curve-fitting applications is presented combining results from statistical estimation concepts and spline analysis. Due to its recursive nature, the algorithm can be used most efficiently in online experimentation. Using computer-sumulated and experimental data, the efficiency and the flexibility of this sequential estimation procedure is extensively demonstrated. (orig.) [de

The sequential trauma score - a new instrument for the sequential mortality prediction in major trauma*

Directory of Open Access Journals (Sweden)

Huber-Wagner S

2010-05-01

Full Text Available Abstract Background There are several well established scores for the assessment of the prognosis of major trauma patients that all have in common that they can be calculated at the earliest during intensive care unit stay. We intended to develop a sequential trauma score (STS that allows prognosis at several early stages based on the information that is available at a particular time. Study design In a retrospective, multicenter study using data derived from the Trauma Registry of the German Trauma Society (2002-2006, we identified the most relevant prognostic factors from the patients basic data (P, prehospital phase (A, early (B1, and late (B2 trauma room phase. Univariate and logistic regression models as well as score quality criteria and the explanatory power have been calculated. Results A total of 2,354 patients with complete data were identified. From the patients basic data (P, logistic regression showed that age was a significant predictor of survival (AUCmodel p, area under the curve = 0.63. Logistic regression of the prehospital data (A showed that blood pressure, pulse rate, Glasgow coma scale (GCS, and anisocoria were significant predictors (AUCmodel A = 0.76; AUCmodel P + A = 0.82. Logistic regression of the early trauma room phase (B1 showed that peripheral oxygen saturation, GCS, anisocoria, base excess, and thromboplastin time to be significant predictors of survival (AUCmodel B1 = 0.78; AUCmodel P +A + B1 = 0.85. Multivariate analysis of the late trauma room phase (B2 detected cardiac massage, abbreviated injury score (AIS of the head ≥ 3, the maximum AIS, the need for transfusion or massive blood transfusion, to be the most important predictors (AUCmodel B2 = 0.84; AUCfinal model P + A + B1 + B2 = 0.90. The explanatory power - a tool for the assessment of the relative impact of each segment to mortality - is 25% for P, 7% for A, 17% for B1 and 51% for B2. A spreadsheet for the easy calculation of the sequential trauma

Sequential Foreign Investments, Regional Technology Platforms and the Evolution of Japanese Multinationals in East Asia

OpenAIRE

Song, Jaeyong

2001-01-01

IVABSTRACTIn this paper, we investigate the firm-level mechanisms that underlie the sequential foreign direct investment (FDI) decisions of multinational corporations (MNCs). To understand inter-firm heterogeneity in the sequential FDI behaviors of MNCs, we develop a firm capability-based model of sequential FDI decisions. In the setting of Japanese electronics MNCs in East Asia, we empirically examine how prior investments in firm capabilities affect sequential investments into existingprodu...

Retrieval of sea surface velocities using sequential ocean colour monitor (OCM) data

Digital Repository Service at National Institute of Oceanography (India)

Prasad, J.S.; Rajawat, A.S.; Pradhan, Y.; Chauhan, O.S.; Nayak, S.R.

velocities has been developed. The method is based on matching suspended sediment dispersion patterns, in sequential two time lapsed images. The pattern matching is performed on atmospherically corrected and geo-referenced sequential pair of images by Maximum...

A fast and accurate online sequential learning algorithm for feedforward networks.

Science.gov (United States)

Liang, Nan-Ying; Huang, Guang-Bin; Saratchandran, P; Sundararajan, N

2006-11-01

In this paper, we develop an online sequential learning algorithm for single hidden layer feedforward networks (SLFNs) with additive or radial basis function (RBF) hidden nodes in a unified framework. The algorithm is referred to as online sequential extreme learning machine (OS-ELM) and can learn data one-by-one or chunk-by-chunk (a block of data) with fixed or varying chunk size. The activation functions for additive nodes in OS-ELM can be any bounded nonconstant piecewise continuous functions and the activation functions for RBF nodes can be any integrable piecewise continuous functions. In OS-ELM, the parameters of hidden nodes (the input weights and biases of additive nodes or the centers and impact factors of RBF nodes) are randomly selected and the output weights are analytically determined based on the sequentially arriving data. The algorithm uses the ideas of ELM of Huang et al. developed for batch learning which has been shown to be extremely fast with generalization performance better than other batch training methods. Apart from selecting the number of hidden nodes, no other control parameters have to be manually chosen. Detailed performance comparison of OS-ELM is done with other popular sequential learning algorithms on benchmark problems drawn from the regression, classification and time series prediction areas. The results show that the OS-ELM is faster than the other sequential algorithms and produces better generalization performance.

Sequential spatial processes for image analysis

NARCIS (Netherlands)

Lieshout, van M.N.M.; Capasso, V.

2009-01-01

We give a brief introduction to sequential spatial processes. We discuss their definition, formulate a Markov property, and indicate why such processes are natural tools in tackling high level vision problems. We focus on the problem of tracking a variable number of moving objects through a video

Polarization control of direct (non-sequential) two-photon double ionization of He

International Nuclear Information System (INIS)

Pronin, E A; Manakov, N L; Marmo, S I; Starace, Anthony F

2007-01-01

An ab initio parametrization of the doubly-differential cross section (DDCS) for two-photon double ionization (TPDI) from an s 2 subshell of an atom in a 1 S 0 -state is presented. Analysis of the elliptic dichroism (ED) effect in the DDCS for TPDI of He and its comparison with the same effect in the concurrent process of sequential double ionization shows their qualitative and quantitative differences, thus providing a means to control and to distinguish sequential and non-sequential processes by measuring the relative ED parameter

A Bayesian sequential design using alpha spending function to control type I error.

Science.gov (United States)

Zhu, Han; Yu, Qingzhao

2017-10-01

We propose in this article a Bayesian sequential design using alpha spending functions to control the overall type I error in phase III clinical trials. We provide algorithms to calculate critical values, power, and sample sizes for the proposed design. Sensitivity analysis is implemented to check the effects from different prior distributions, and conservative priors are recommended. We compare the power and actual sample sizes of the proposed Bayesian sequential design with different alpha spending functions through simulations. We also compare the power of the proposed method with frequentist sequential design using the same alpha spending function. Simulations show that, at the same sample size, the proposed method provides larger power than the corresponding frequentist sequential design. It also has larger power than traditional Bayesian sequential design which sets equal critical values for all interim analyses. When compared with other alpha spending functions, O'Brien-Fleming alpha spending function has the largest power and is the most conservative in terms that at the same sample size, the null hypothesis is the least likely to be rejected at early stage of clinical trials. And finally, we show that adding a step of stop for futility in the Bayesian sequential design can reduce the overall type I error and reduce the actual sample sizes.

Sequential ensemble-based optimal design for parameter estimation: SEQUENTIAL ENSEMBLE-BASED OPTIMAL DESIGN

Energy Technology Data Exchange (ETDEWEB)

Man, Jun [Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou China; Zhang, Jiangjiang [Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou China; Li, Weixuan [Pacific Northwest National Laboratory, Richland Washington USA; Zeng, Lingzao [Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, Institute of Soil and Water Resources and Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou China; Wu, Laosheng [Department of Environmental Sciences, University of California, Riverside California USA

2016-10-01

The ensemble Kalman filter (EnKF) has been widely used in parameter estimation for hydrological models. The focus of most previous studies was to develop more efficient analysis (estimation) algorithms. On the other hand, it is intuitively understandable that a well-designed sampling (data-collection) strategy should provide more informative measurements and subsequently improve the parameter estimation. In this work, a Sequential Ensemble-based Optimal Design (SEOD) method, coupled with EnKF, information theory and sequential optimal design, is proposed to improve the performance of parameter estimation. Based on the first-order and second-order statistics, different information metrics including the Shannon entropy difference (SD), degrees of freedom for signal (DFS) and relative entropy (RE) are used to design the optimal sampling strategy, respectively. The effectiveness of the proposed method is illustrated by synthetic one-dimensional and two-dimensional unsaturated flow case studies. It is shown that the designed sampling strategies can provide more accurate parameter estimation and state prediction compared with conventional sampling strategies. Optimal sampling designs based on various information metrics perform similarly in our cases. The effect of ensemble size on the optimal design is also investigated. Overall, larger ensemble size improves the parameter estimation and convergence of optimal sampling strategy. Although the proposed method is applied to unsaturated flow problems in this study, it can be equally applied in any other hydrological problems.

The pursuit of balance in sequential randomized trials

Directory of Open Access Journals (Sweden)

Raymond P. Guiteras

2016-06-01

Full Text Available In many randomized trials, subjects enter the sample sequentially. Because the covariates for all units are not known in advance, standard methods of stratification do not apply. We describe and assess the method of DA-optimal sequential allocation (Atkinson, 1982 for balancing stratification covariates across treatment arms. We provide simulation evidence that the method can provide substantial improvements in precision over commonly employed alternatives. We also describe our experience implementing the method in a field trial of a clean water and handwashing intervention in Dhaka, Bangladesh, the first time the method has been used. We provide advice and software for future researchers.

Event-shape analysis: Sequential versus simultaneous multifragment emission

International Nuclear Information System (INIS)

Cebra, D.A.; Howden, S.; Karn, J.; Nadasen, A.; Ogilvie, C.A.; Vander Molen, A.; Westfall, G.D.; Wilson, W.K.; Winfield, J.S.; Norbeck, E.

1990-01-01

The Michigan State University 4π array has been used to select central-impact-parameter events from the reaction 40 Ar+ 51 V at incident energies from 35 to 85 MeV/nucleon. The event shape in momentum space is an observable which is shown to be sensitive to the dynamics of the fragmentation process. A comparison of the experimental event-shape distribution to sequential- and simultaneous-decay predictions suggests that a transition in the breakup process may have occurred. At 35 MeV/nucleon, a sequential-decay simulation reproduces the data. For the higher energies, the experimental distributions fall between the two contrasting predictions

Sequential approach to Colombeau's theory of generalized functions

International Nuclear Information System (INIS)

Todorov, T.D.

1987-07-01

J.F. Colombeau's generalized functions are constructed as equivalence classes of the elements of a specially chosen ultrapower of the class of the C ∞ -functions. The elements of this ultrapower are considered as sequences of C ∞ -functions, so in a sense, the sequential construction presented here refers to the original Colombeau theory just as, for example, the Mikusinski sequential approach to the distribution theory refers to the original Schwartz theory of distributions. The paper could be used as an elementary introduction to the Colombeau theory in which recently a solution was found to the problem of multiplication of Schwartz distributions. (author). Refs

Configural and component processing in simultaneous and sequential lineup procedures

OpenAIRE

Flowe, HD; Smith, HMJ; Karoğlu, N; Onwuegbusi, TO; Rai, L

2015-01-01

Configural processing supports accurate face recognition, yet it has never been examined within the context of criminal identification lineups. We tested, using the inversion paradigm, the role of configural processing in lineups. Recent research has found that face discrimination accuracy in lineups is better in a simultaneous compared to a sequential lineup procedure. Therefore, we compared configural processing in simultaneous and sequential lineups to examine whether there are differences...

The composite sequential clustering technique for analysis of multispectral scanner data

Science.gov (United States)

Su, M. Y.

1972-01-01

The clustering technique consists of two parts: (1) a sequential statistical clustering which is essentially a sequential variance analysis, and (2) a generalized K-means clustering. In this composite clustering technique, the output of (1) is a set of initial clusters which are input to (2) for further improvement by an iterative scheme. This unsupervised composite technique was employed for automatic classification of two sets of remote multispectral earth resource observations. The classification accuracy by the unsupervised technique is found to be comparable to that by traditional supervised maximum likelihood classification techniques. The mathematical algorithms for the composite sequential clustering program and a detailed computer program description with job setup are given.

Alternatives to the sequential lineup: the importance of controlling the pictures.

Science.gov (United States)

Lindsay, R C; Bellinger, K

1999-06-01

Because sequential lineups reduce false-positive choices, their use has been recommended (R. C. L. Lindsay, 1999; R. C. L. Lindsay & G. L. Wells, 1985). Blind testing is included in the recommended procedures. Police, concerned about blind testing, devised alternative procedures, including self-administered sequential lineups, to reduce use of relative judgments (G. L. Wells, 1984) while permitting the investigating officer to conduct the procedure. Identification data from undergraduates exposed to a staged crime (N = 165) demonstrated that 4 alternative identification procedures tested were less effective than the original sequential lineup. Allowing witnesses to control the photographs resulted in higher rates of false-positive identification. Self-reports of using relative judgments were shown to be postdictive of decision accuracy.

Managerial adjustment and its limits: sequential fault in comparative perspective

Directory of Open Access Journals (Sweden)

Flávio da Cunha Rezende

2008-01-01

Full Text Available This article focuses on explanations for sequential faults in administrative reform. It deals with the limits of managerial adjustment in an approach that attempts to connect theory and empirical data, articulating three levels of analysis. The first level presents comparative evidence of sequential fault within reforms in national governments through a set of indicators geared toward understanding changes in the role of the state. In light of analyses of a representative set of comparative studies on reform implementation, the second analytical level proceeds to identify four typical mechanisms that are present in explanations on managerial adjustment faults. In this way, we seek to configure an explanatory matrix for theories on sequential fault. Next we discuss the experience of management reform in the Brazilian context, conferring special attention on one of the mechanisms that creates fault: the control dilemma. The major hypotheses that guide our article are that reforms lead to sequential fault and that there are at least four causal mechanisms that produce reforms: a transactions costs involved in producing reforms; b performance legacy; c predominance of fiscal adjustment and d the control dilemma. These mechanisms act separately or in concert, and act to decrease chances for a transformation of State managerial patterns. Major evidence that is analyzed in these articles lend consistency to the general argument that reforms have failed in their attempts to reduce public expenses, alter patterns of resource allocation, reduce the labor force and change the role of the State. Our major conclusion is that reforms fail sequentially and managerial adjustment displays considerable limitations, particularly those of a political nature.

Mechanistic Understanding of Tungsten Oxide In-Plane Nanostructure Growth via Sequential Infiltration Synthesis

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Jin; Suh, Hyo Seon; Zhou, Chun; Mane, Anil U.; Lee, Byeongdu; Kim, Soojeong; Emery, Jonathan D.; Elam, Jeffrey W.; Nealey, Paul F.; Fenter, Paul; Fister, Timothy T.

2018-02-21

Tungsten oxide (WO3-x) nanostructures with hexagonal in-plane arrangements were fabricated by sequential infiltration synthesis (SIS), using the selective interaction of gas phase precursors with functional groups in one domain of a block copolymer (BCP) self-assembled template. Such structures are highly desirable for various practical applications and as model systems for fundamental studies. The nanostructures were characterized by cross-sectional scanning electron microscopy, grazing-incidence small/wide-angle X-ray scattering (GISAXS/GIWAXS), and X-ray absorption near edge structure (XANES) measurements at each stage during the SIS process and subsequent thermal treatments, to provide a comprehensive picture of their evolution in morphology, crystallography and electronic structure. In particular, we discuss the critical role of SIS Al2O3 seeds toward modifying the chemical affinity and free volume in a polymer for subsequent infiltration of gas phase precursors. The insights into SIS growth obtained from this study are valuable to the design and fabrication of a wide range of targeted nanostructures.

A Bayesian sequential processor approach to spectroscopic portal system decisions

Energy Technology Data Exchange (ETDEWEB)

Sale, K; Candy, J; Breitfeller, E; Guidry, B; Manatt, D; Gosnell, T; Chambers, D

2007-07-31

The development of faster more reliable techniques to detect radioactive contraband in a portal type scenario is an extremely important problem especially in this era of constant terrorist threats. Towards this goal the development of a model-based, Bayesian sequential data processor for the detection problem is discussed. In the sequential processor each datum (detector energy deposit and pulse arrival time) is used to update the posterior probability distribution over the space of model parameters. The nature of the sequential processor approach is that a detection is produced as soon as it is statistically justified by the data rather than waiting for a fixed counting interval before any analysis is performed. In this paper the Bayesian model-based approach, physics and signal processing models and decision functions are discussed along with the first results of our research.

Impact of Sequential Ammonia Fiber Expansion (AFEX) Pretreatment and Pelletization on the Moisture Sorption Properties of Corn Stover

Energy Technology Data Exchange (ETDEWEB)

Bonner, Ian J. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Thompson, David N. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Teymouri, Farzaneh [Michigan Biotechnology Inst., Lansing, MI (United States); Campbell, Timothy [Michigan Biotechnology Inst., Lansing, MI (United States); Bals, Bryan [Michigan Biotechnology Inst., Lansing, MI (United States); Tumuluru, Jaya Shankar [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-05-01

Combining ammonia fiber expansion (AFEX™) pretreatment with a depot processing facility is a promising option for delivering high-value densified biomass to the emerging bioenergy industry. However, because the pretreatment process results in a high moisture material unsuitable for pelleting or storage (40% wet basis), the biomass must be immediately dried. If AFEX pretreatment results in a material that is difficult to dry, the economics of this already costly operation would be at risk. This work tests the nature of moisture sorption isotherms and thin-layer drying behavior of corn (Zea mays L.) stover at 20°C to 60°C before and after sequential AFEX pretreatment and pelletization to determine whether any negative impacts to material drying or storage may result from the AFEX process. The equilibrium moisture content to equilibrium relative humidity relationship for each of the materials was determined using dynamic vapor sorption isotherms and modeled with modified Chung-Pfost, modified Halsey, and modified Henderson temperature-dependent models as well as the Double Log Polynomial (DLP), Peleg, and Guggenheim Anderson de Boer (GAB) temperature-independent models. Drying kinetics were quantified under thin-layer laboratory testing and modeled using the Modified Page's equation. Water activity isotherms for non-pelleted biomass were best modeled with the Peleg temperature-independent equation while isotherms for the pelleted biomass were best modeled with the Double Log Polynomial equation. Thin-layer drying results were accurately modeled with the Modified Page's equation. The results of this work indicate that AFEX pretreatment results in drying properties more favorable than or equal to that of raw corn stover, and pellets of superior physical stability in storage.

Sequential lineup presentation promotes less-biased criterion setting but does not improve discriminability.

Science.gov (United States)

Palmer, Matthew A; Brewer, Neil

2012-06-01

When compared with simultaneous lineup presentation, sequential presentation has been shown to reduce false identifications to a greater extent than it reduces correct identifications. However, there has been much debate about whether this difference in identification performance represents improved discriminability or more conservative responding. In this research, data from 22 experiments that compared sequential and simultaneous lineups were analyzed using a compound signal-detection model, which is specifically designed to describe decision-making performance on tasks such as eyewitness identification tests. Sequential (cf. simultaneous) presentation did not influence discriminability, but produced a conservative shift in response bias that resulted in less-biased choosing for sequential than simultaneous lineups. These results inform understanding of the effects of lineup presentation mode on eyewitness identification decisions.

Estimation After a Group Sequential Trial.

Science.gov (United States)

Milanzi, Elasma; Molenberghs, Geert; Alonso, Ariel; Kenward, Michael G; Tsiatis, Anastasios A; Davidian, Marie; Verbeke, Geert

2015-10-01

Group sequential trials are one important instance of studies for which the sample size is not fixed a priori but rather takes one of a finite set of pre-specified values, dependent on the observed data. Much work has been devoted to the inferential consequences of this design feature. Molenberghs et al (2012) and Milanzi et al (2012) reviewed and extended the existing literature, focusing on a collection of seemingly disparate, but related, settings, namely completely random sample sizes, group sequential studies with deterministic and random stopping rules, incomplete data, and random cluster sizes. They showed that the ordinary sample average is a viable option for estimation following a group sequential trial, for a wide class of stopping rules and for random outcomes with a distribution in the exponential family. Their results are somewhat surprising in the sense that the sample average is not optimal, and further, there does not exist an optimal, or even, unbiased linear estimator. However, the sample average is asymptotically unbiased, both conditionally upon the observed sample size as well as marginalized over it. By exploiting ignorability they showed that the sample average is the conventional maximum likelihood estimator. They also showed that a conditional maximum likelihood estimator is finite sample unbiased, but is less efficient than the sample average and has the larger mean squared error. Asymptotically, the sample average and the conditional maximum likelihood estimator are equivalent. This previous work is restricted, however, to the situation in which the the random sample size can take only two values, N = n or N = 2 n . In this paper, we consider the more practically useful setting of sample sizes in a the finite set { n 1 , n 2 , …, n L }. It is shown that the sample average is then a justifiable estimator , in the sense that it follows from joint likelihood estimation, and it is consistent and asymptotically unbiased. We also show why

Simultaneous optimization of sequential IMRT plans

International Nuclear Information System (INIS)

Popple, Richard A.; Prellop, Perri B.; Spencer, Sharon A.; Santos, Jennifer F. de los; Duan, Jun; Fiveash, John B.; Brezovich, Ivan A.

2005-01-01

Radiotherapy often comprises two phases, in which irradiation of a volume at risk for microscopic disease is followed by a sequential dose escalation to a smaller volume either at a higher risk for microscopic disease or containing only gross disease. This technique is difficult to implement with intensity modulated radiotherapy, as the tolerance doses of critical structures must be respected over the sum of the two plans. Techniques that include an integrated boost have been proposed to address this problem. However, clinical experience with such techniques is limited, and many clinicians are uncomfortable prescribing nonconventional fractionation schemes. To solve this problem, we developed an optimization technique that simultaneously generates sequential initial and boost IMRT plans. We have developed an optimization tool that uses a commercial treatment planning system (TPS) and a high level programming language for technical computing. The tool uses the TPS to calculate the dose deposition coefficients (DDCs) for optimization. The DDCs were imported into external software and the treatment ports duplicated to create the boost plan. The initial, boost, and tolerance doses were specified and used to construct cost functions. The initial and boost plans were optimized simultaneously using a gradient search technique. Following optimization, the fluence maps were exported to the TPS for dose calculation. Seven patients treated using sequential techniques were selected from our clinical database. The initial and boost plans used to treat these patients were developed independently of each other by dividing the tolerance doses proportionally between the initial and boost plans and then iteratively optimizing the plans until a summation that met the treatment goals was obtained. We used the simultaneous optimization technique to generate plans that met the original planning goals. The coverage of the initial and boost target volumes in the simultaneously optimized

Sequential assignment of proline-rich regions in proteins: Application to modular binding domain complexes

International Nuclear Information System (INIS)

Kanelis, Voula; Donaldson, Logan; Muhandiram, D.R.; Rotin, Daniela; Forman-Kay, Julie D.; Kay, Lewis E.

2000-01-01

Many protein-protein interactions involve amino acid sequences containing proline-rich motifs and even poly-proline stretches. The lack of amide protons in such regions complicates assignment, since 1 HN-based triple-resonance assignment strategies cannot be employed. Two such systems that we are currently studying include an SH2 domain from the protein Crk with a region containing 9 prolines in a 14 amino acid sequence, as well as a WW domain that interacts with a proline-rich target. A modified version of the HACAN pulse scheme, originally described by Bax and co-workers [Wang et al. (1995) J. Biomol. NMR, 5, 376-382], and an experiment which correlates the intra-residue 1 H α , 13 C α / 13 C β chemical shifts with the 15 N shift of the subsequent residue are presented and applied to the two systems listed above, allowing sequential assignment of the molecules

Optimal Sequential Resource Sharing and Exchange in Multi-Agent Systems

OpenAIRE

Xiao, Yuanzhang

2014-01-01

Central to the design of many engineering systems and social networks is to solve the underlying resource sharing and exchange problems, in which multiple decentralized agents make sequential decisions over time to optimize some long-term performance metrics. It is challenging for the decentralized agents to make optimal sequential decisions because of the complicated coupling among the agents and across time. In this dissertation, we mainly focus on three important classes of multi-agent seq...

S.M.P. SEQUENTIAL MATHEMATICS PROGRAM.

Science.gov (United States)

CICIARELLI, V; LEONARD, JOSEPH

A SEQUENTIAL MATHEMATICS PROGRAM BEGINNING WITH THE BASIC FUNDAMENTALS ON THE FOURTH GRADE LEVEL IS PRESENTED. INCLUDED ARE AN UNDERSTANDING OF OUR NUMBER SYSTEM, AND THE BASIC OPERATIONS OF WORKING WITH WHOLE NUMBERS--ADDITION, SUBTRACTION, MULTIPLICATION, AND DIVISION. COMMON FRACTIONS ARE TAUGHT IN THE FIFTH, SIXTH, AND SEVENTH GRADES. A…

Large-scale sequential quadratic programming algorithms

Energy Technology Data Exchange (ETDEWEB)

Eldersveld, S.K.

1992-09-01

The problem addressed is the general nonlinear programming problem: finding a local minimizer for a nonlinear function subject to a mixture of nonlinear equality and inequality constraints. The methods studied are in the class of sequential quadratic programming (SQP) algorithms, which have previously proved successful for problems of moderate size. Our goal is to devise an SQP algorithm that is applicable to large-scale optimization problems, using sparse data structures and storing less curvature information but maintaining the property of superlinear convergence. The main features are: 1. The use of a quasi-Newton approximation to the reduced Hessian of the Lagrangian function. Only an estimate of the reduced Hessian matrix is required by our algorithm. The impact of not having available the full Hessian approximation is studied and alternative estimates are constructed. 2. The use of a transformation matrix Q. This allows the QP gradient to be computed easily when only the reduced Hessian approximation is maintained. 3. The use of a reduced-gradient form of the basis for the null space of the working set. This choice of basis is more practical than an orthogonal null-space basis for large-scale problems. The continuity condition for this choice is proven. 4. The use of incomplete solutions of quadratic programming subproblems. Certain iterates generated by an active-set method for the QP subproblem are used in place of the QP minimizer to define the search direction for the nonlinear problem. An implementation of the new algorithm has been obtained by modifying the code MINOS. Results and comparisons with MINOS and NPSOL are given for the new algorithm on a set of 92 test problems.

Sequential sputtered Co-HfO{sub 2} granular films

Energy Technology Data Exchange (ETDEWEB)

Chadha, M.; Ng, V.

2017-03-15

A systematic study of magnetic, magneto-transport and micro-structural properties of Co-HfO{sub 2} granular films fabricated by sequential sputtering is presented. We demonstrate reduction in ferromagnetic-oxide formation by using HfO{sub 2} as the insulting matrix. Microstructure evaluation of the films showed that the film structure consisted of discrete hcp-Co grains embedded in HfO{sub 2} matrix. Films with varying compositions were prepared and their macroscopic properties were studied. We correlate the variation in these properties to the variation in film microstructure. Our study shows that Co-HfO{sub 2} films with reduced cobalt oxide and varying properties can be prepared using sequential sputtering technique. - Highlights: • Co-HfO{sub 2} granular films were prepared using sequential sputtering. • A reduction in ferromagnetic-oxide formation is observed. • Co-HfO{sub 2} films display superparamagnetism and tunnelling magneto-resistance. • Varying macroscopic properties were achieved by changing film composition. • Applications can be found in moderate MR sensors and high –frequency RF devices.

Involvement of Working Memory in College Students' Sequential Pattern Learning and Performance

Science.gov (United States)

Kundey, Shannon M. A.; De Los Reyes, Andres; Rowan, James D.; Lee, Bern; Delise, Justin; Molina, Sabrina; Cogdill, Lindsay

2013-01-01

When learning highly organized sequential patterns of information, humans and nonhuman animals learn rules regarding the hierarchical structures of these sequences. In three experiments, we explored the role of working memory in college students' sequential pattern learning and performance in a computerized task involving a sequential…

Double-blind photo lineups using actual eyewitnesses: an experimental test of a sequential versus simultaneous lineup procedure.

Science.gov (United States)

Wells, Gary L; Steblay, Nancy K; Dysart, Jennifer E

2015-02-01

Eyewitnesses (494) to actual crimes in 4 police jurisdictions were randomly assigned to view simultaneous or sequential photo lineups using laptop computers and double-blind administration. The sequential procedure used in the field experiment mimicked how it is conducted in actual practice (e.g., using a continuation rule, witness does not know how many photos are to be viewed, witnesses resolve any multiple identifications), which is not how most lab experiments have tested the sequential lineup. No significant differences emerged in rates of identifying lineup suspects (25% overall) but the sequential procedure produced a significantly lower rate (11%) of identifying known-innocent lineup fillers than did the simultaneous procedure (18%). The simultaneous/sequential pattern did not significantly interact with estimator variables and no lineup-position effects were observed for either the simultaneous or sequential procedures. Rates of nonidentification were not significantly different for simultaneous and sequential but nonidentifiers from the sequential procedure were more likely to use the "not sure" response option than were nonidentifiers from the simultaneous procedure. Among witnesses who made an identification, 36% (41% of simultaneous and 32% of sequential) identified a known-innocent filler rather than a suspect, indicating that eyewitness performance overall was very poor. The results suggest that the sequential procedure that is used in the field reduces the identification of known-innocent fillers, but the differences are relatively small.

Cortical responses following simultaneous and sequential retinal neurostimulation with different return configurations.

Science.gov (United States)

Barriga-Rivera, Alejandro; Morley, John W; Lovell, Nigel H; Suaning, Gregg J

2016-08-01

Researchers continue to develop visual prostheses towards safer and more efficacious systems. However limitations still exist in the number of stimulating channels that can be integrated. Therefore there is a need for spatial and time multiplexing techniques to provide improved performance of the current technology. In particular, bright and high-contrast visual scenes may require simultaneous activation of several electrodes. In this research, a 24-electrode array was suprachoroidally implanted in three normally-sighted cats. Multi-unit activity was recorded from the primary visual cortex. Four stimulation strategies were contrasted to provide activation of seven electrodes arranged hexagonally: simultaneous monopolar, sequential monopolar, sequential bipolar and hexapolar. Both monopolar configurations showed similar cortical activation maps. Hexapolar and sequential bipolar configurations activated a lower number of cortical channels. Overall, the return configuration played a more relevant role in cortical activation than time multiplexing and thus, rapid sequential stimulation may assist in reducing the number of channels required to activate large retinal areas.

Sequential Versus Simultaneous Market Delineation: The Relevant Antitrust Market for Salmon

DEFF Research Database (Denmark)

Haldrup, Niels; Peter, Møllgaard

Delineation of the relevant market forms a pivotal part of most antitrust cases. The standard approach is sequential. First the product market is delineated, then the geographical market is defined. Demand andsupply substitution in both the product dimension and the geographical dimension will no...... and geographical markets. Using a unique data set for prices of Norwegian and Scottish salmon, we propose a methodology for simultaneous market delineation and we demonstrate that compared to a sequential approach conclusions will be reversed.......Delineation of the relevant market forms a pivotal part of most antitrust cases. The standard approach is sequential. First the product market is delineated, then the geographical market is defined. Demand andsupply substitution in both the product dimension and the geographical dimension...

Endogenous sequential cortical activity evoked by visual stimuli.

Science.gov (United States)

Carrillo-Reid, Luis; Miller, Jae-Eun Kang; Hamm, Jordan P; Jackson, Jesse; Yuste, Rafael

2015-06-10

Although the functional properties of individual neurons in primary visual cortex have been studied intensely, little is known about how neuronal groups could encode changing visual stimuli using temporal activity patterns. To explore this, we used in vivo two-photon calcium imaging to record the activity of neuronal populations in primary visual cortex of awake mice in the presence and absence of visual stimulation. Multidimensional analysis of the network activity allowed us to identify neuronal ensembles defined as groups of cells firing in synchrony. These synchronous groups of neurons were themselves activated in sequential temporal patterns, which repeated at much higher proportions than chance and were triggered by specific visual stimuli such as natural visual scenes. Interestingly, sequential patterns were also present in recordings of spontaneous activity without any sensory stimulation and were accompanied by precise firing sequences at the single-cell level. Moreover, intrinsic dynamics could be used to predict the occurrence of future neuronal ensembles. Our data demonstrate that visual stimuli recruit similar sequential patterns to the ones observed spontaneously, consistent with the hypothesis that already existing Hebbian cell assemblies firing in predefined temporal sequences could be the microcircuit substrate that encodes visual percepts changing in time. Copyright © 2015 Carrillo-Reid et al.

Efficacy of premixed versus sequential administration of ...

African Journals Online (AJOL)

sequential administration in separate syringes on block characteristics, haemodynamic parameters, side effect profile and postoperative analgesic requirement. Trial design: This was a prospective, randomised clinical study. Method: Sixty orthopaedic patients scheduled for elective lower limb surgery under spinal ...

[Sequential degradation of p-cresol by photochemical and biological methods].

Science.gov (United States)

Karetnikova, E A; Chaĭkovskaia, O N; Sokolova, I V; Nikitina, L I

2008-01-01

Sequential photo- and biodegradation of p-cresol was studied using a mercury lamp, as well as KrCl and XeCl excilamps. Preirradiation of p-cresol at a concentration of 10(-4) M did not affect the rate of its subsequent biodegradation. An increase in the concentration of p-cresol to 10(-3) M and in the duration preliminary UV irradiation inhibited subsequent biodegradation. Biodegradation of p-cresol was accompanied by the formation of a product with a fluorescence maximum at 365 nm (lambdaex 280 nm), and photodegradation yielded a compound fluorescing at 400 nm (lambdaex 330 nm). Sequential UV and biodegradation led to the appearance of bands in the fluorescence spectra that were ascribed to p-cresol and its photolysis products. It was shown that sequential use of biological and photochemical degradation results in degradation of not only the initial toxicant but also the metabolites formed during its biodegradation.

Lexical decoder for continuous speech recognition: sequential neural network approach

International Nuclear Information System (INIS)

Iooss, Christine

1991-01-01

The work presented in this dissertation concerns the study of a connectionist architecture to treat sequential inputs. In this context, the model proposed by J.L. Elman, a recurrent multilayers network, is used. Its abilities and its limits are evaluated. Modifications are done in order to treat erroneous or noisy sequential inputs and to classify patterns. The application context of this study concerns the realisation of a lexical decoder for analytical multi-speakers continuous speech recognition. Lexical decoding is completed from lattices of phonemes which are obtained after an acoustic-phonetic decoding stage relying on a K Nearest Neighbors search technique. Test are done on sentences formed from a lexicon of 20 words. The results are obtained show the ability of the proposed connectionist model to take into account the sequentiality at the input level, to memorize the context and to treat noisy or erroneous inputs. (author) [fr

Optimal Energy Management of Multi-Microgrids with Sequentially Coordinated Operations

Directory of Open Access Journals (Sweden)

Nah-Oak Song

2015-08-01

Full Text Available We propose an optimal electric energy management of a cooperative multi-microgrid community with sequentially coordinated operations. The sequentially coordinated operations are suggested to distribute computational burden and yet to make the optimal 24 energy management of multi-microgrids possible. The sequential operations are mathematically modeled to find the optimal operation conditions and illustrated with physical interpretation of how to achieve optimal energy management in the cooperative multi-microgrid community. This global electric energy optimization of the cooperative community is realized by the ancillary internal trading between the microgrids in the cooperative community which reduces the extra cost from unnecessary external trading by adjusting the electric energy production amounts of combined heat and power (CHP generators and amounts of both internal and external electric energy trading of the cooperative community. A simulation study is also conducted to validate the proposed mathematical energy management models.

Effect of sequential isoproturon pulse exposure on Scenedesmus vacuolatus.

Science.gov (United States)

Vallotton, Nathalie; Eggen, Rik Ilda Lambertus; Chèvre, Nathalie

2009-04-01

Aquatic organisms are typically exposed to fluctuating concentrations of herbicides in streams. To assess the effects on algae of repeated peak exposure to the herbicide isoproturon, we subjected the alga Scenedesmus vacuolatus to two sequential pulse exposure scenarios. Effects on growth and on the inhibition of the effective quantum yield of photosystem II (PSII) were measured. In the first scenario, algae were exposed to short, 5-h pulses at high isoproturon concentrations (400 and 1000 microg/l), each followed by a recovery period of 18 h, while the second scenario consisted of 22.5-h pulses at lower concentrations (60 and 120 microg/l), alternating with short recovery periods (1.5 h). In addition, any changes in the sensitivity of the algae to isoproturon following sequential pulses were examined by determining the growth rate-EC(50) prior to and following exposure. In both exposure scenarios, we found that algal growth and its effective quantum yield were systematically inhibited during the exposures and that these effects were reversible. Sequential pulses to isoproturon could be considered a sequence of independent events. Nevertheless, a consequence of inhibited growth during the repeated exposures is the cumulative decrease in biomass production. Furthermore, in the second scenario, when the sequence of long pulses began to approach a scenario of continuous exposure, a slight increase in the tolerance of the algae to isoproturon was observed. These findings indicated that sequential pulses do affect algae during each pulse exposure, even if algae recover between the exposures. These observations could support an improved risk assessment of fluctuating exposures to reversibly acting herbicides.

Sequential-Simultaneous Analysis of Japanese Children's Performance on the Japanese McCarthy.

Science.gov (United States)

Ishikuma, Toshinori; And Others

This study explored the hypothesis that Japanese children perform significantly better on simultaneous processing than on sequential processing. The Kaufman Assessment Battery for Children (K-ABC) served as the criterion of the two types of mental processing. Regression equations to predict Sequential and Simultaneous processing from McCarthy…

Acquisition of Inductive Biconditional Reasoning Skills: Training of Simultaneous and Sequential Processing.

Science.gov (United States)

Lee, Seong-Soo

1982-01-01

Tenth-grade students (n=144) received training on one of three processing methods: coding-mapping (simultaneous), coding only, or decision tree (sequential). The induced simultaneous processing strategy worked optimally under rule learning, while the sequential strategy was difficult to induce and/or not optimal for rule-learning operations.…

Motor timing deficits in sequential movements in Parkinson disease are related to action planning: a motor imagery study.

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Laura Avanzino

Full Text Available Timing of sequential movements is altered in Parkinson disease (PD. Whether timing deficits in internally generated sequential movements in PD depends also on difficulties in motor planning, rather than merely on a defective ability to materially perform the planned movement is still undefined. To unveil this issue, we adopted a modified version of an established test for motor timing, i.e. the synchronization-continuation paradigm, by introducing a motor imagery task. Motor imagery is thought to involve mainly processes of movement preparation, with reduced involvement of end-stage movement execution-related processes. Fourteen patients with PD and twelve matched healthy volunteers were asked to tap in synchrony with a metronome cue (SYNC and then, when the tone stopped, to keep tapping, trying to maintain the same rhythm (CONT-EXE or to imagine tapping at the same rhythm, rather than actually performing it (CONT-MI. We tested both a sub-second and a supra-second inter-stimulus interval between the cues. Performance was recorded using a sensor-engineered glove and analyzed measuring the temporal error and the interval reproduction accuracy index. PD patients were less accurate than healthy subjects in the supra-second time reproduction task when performing both continuation tasks (CONT-MI and CONT-EXE, whereas no difference was detected in the synchronization task and on all tasks involving a sub-second interval. Our findings suggest that PD patients exhibit a selective deficit in motor timing for sequential movements that are separated by a supra-second interval and that this deficit may be explained by a defect of motor planning. Further, we propose that difficulties in motor planning are of a sufficient degree of severity in PD to affect also the motor performance in the supra-second time reproduction task.

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Mining of high utility-probability sequential patterns from uncertain databases.

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Binbin Zhang

Full Text Available High-utility sequential pattern mining (HUSPM has become an important issue in the field of data mining. Several HUSPM algorithms have been designed to mine high-utility sequential patterns (HUPSPs. They have been applied in several real-life situations such as for consumer behavior analysis and event detection in sensor networks. Nonetheless, most studies on HUSPM have focused on mining HUPSPs in precise data. But in real-life, uncertainty is an important factor as data is collected using various types of sensors that are more or less accurate. Hence, data collected in a real-life database can be annotated with existing probabilities. This paper presents a novel pattern mining framework called high utility-probability sequential pattern mining (HUPSPM for mining high utility-probability sequential patterns (HUPSPs in uncertain sequence databases. A baseline algorithm with three optional pruning strategies is presented to mine HUPSPs. Moroever, to speed up the mining process, a projection mechanism is designed to create a database projection for each processed sequence, which is smaller than the original database. Thus, the number of unpromising candidates can be greatly reduced, as well as the execution time for mining HUPSPs. Substantial experiments both on real-life and synthetic datasets show that the designed algorithm performs well in terms of runtime, number of candidates, memory usage, and scalability for different minimum utility and minimum probability thresholds.

Time scale of random sequential adsorption.

Science.gov (United States)

Erban, Radek; Chapman, S Jonathan

2007-04-01

A simple multiscale approach to the diffusion-driven adsorption from a solution to a solid surface is presented. The model combines two important features of the adsorption process: (i) The kinetics of the chemical reaction between adsorbing molecules and the surface and (ii) geometrical constraints on the surface made by molecules which are already adsorbed. The process (i) is modeled in a diffusion-driven context, i.e., the conditional probability of adsorbing a molecule provided that the molecule hits the surface is related to the macroscopic surface reaction rate. The geometrical constraint (ii) is modeled using random sequential adsorption (RSA), which is the sequential addition of molecules at random positions on a surface; one attempt to attach a molecule is made per one RSA simulation time step. By coupling RSA with the diffusion of molecules in the solution above the surface the RSA simulation time step is related to the real physical time. The method is illustrated on a model of chemisorption of reactive polymers to a virus surface.

Random sequential adsorption of cubes

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Cieśla, Michał; Kubala, Piotr

2018-01-01

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

Effects of sequential and discrete rapid naming on reading in Japanese children with reading difficulty.

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Wakamiya, Eiji; Okumura, Tomohito; Nakanishi, Makoto; Takeshita, Takashi; Mizuta, Mekumi; Kurimoto, Naoko; Tamai, Hiroshi

2011-06-01

To clarify whether rapid naming ability itself is a main underpinning factor of rapid automatized naming tests (RAN) and how deep an influence the discrete decoding process has on reading, we performed discrete naming tasks and discrete hiragana reading tasks as well as sequential naming tasks and sequential hiragana reading tasks with 38 Japanese schoolchildren with reading difficulty. There were high correlations between both discrete and sequential hiragana reading and sentence reading, suggesting that some mechanism which automatizes hiragana reading makes sentence reading fluent. In object and color tasks, there were moderate correlations between sentence reading and sequential naming, and between sequential naming and discrete naming. But no correlation was found between reading tasks and discrete naming tasks. The influence of rapid naming ability of objects and colors upon reading seemed relatively small, and multi-item processing may work in relation to these. In contrast, in the digit naming task there was moderate correlation between sentence reading and discrete naming, while no correlation was seen between sequential naming and discrete naming. There was moderate correlation between reading tasks and sequential digit naming tasks. Digit rapid naming ability has more direct effect on reading while its effect on RAN is relatively limited. The ratio of how rapid naming ability influences RAN and reading seems to vary according to kind of the stimuli used. An assumption about components in RAN which influence reading is discussed in the context of both sequential processing and discrete naming speed. Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

STABILIZED SEQUENTIAL QUADRATIC PROGRAMMING: A SURVEY

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Damián Fernández

2014-12-01

Full Text Available We review the motivation for, the current state-of-the-art in convergence results, and some open questions concerning the stabilized version of the sequential quadratic programming algorithm for constrained optimization. We also discuss the tools required for its local convergence analysis, globalization challenges, and extentions of the method to the more general variational problems.

Terminating Sequential Delphi Survey Data Collection

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Kalaian, Sema A.; Kasim, Rafa M.

2012-01-01

The Delphi survey technique is an iterative mail or electronic (e-mail or web-based) survey method used to obtain agreement or consensus among a group of experts in a specific field on a particular issue through a well-designed and systematic multiple sequential rounds of survey administrations. Each of the multiple rounds of the Delphi survey…

Sequential function approximation on arbitrarily distributed point sets

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Wu, Kailiang; Xiu, Dongbin

2018-02-01

We present a randomized iterative method for approximating unknown function sequentially on arbitrary point set. The method is based on a recently developed sequential approximation (SA) method, which approximates a target function using one data point at each step and avoids matrix operations. The focus of this paper is on data sets with highly irregular distribution of the points. We present a nearest neighbor replacement (NNR) algorithm, which allows one to sample the irregular data sets in a near optimal manner. We provide mathematical justification and error estimates for the NNR algorithm. Extensive numerical examples are also presented to demonstrate that the NNR algorithm can deliver satisfactory convergence for the SA method on data sets with high irregularity in their point distributions.

Configural and component processing in simultaneous and sequential lineup procedures.

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Flowe, Heather D; Smith, Harriet M J; Karoğlu, Nilda; Onwuegbusi, Tochukwu O; Rai, Lovedeep

2016-01-01

Configural processing supports accurate face recognition, yet it has never been examined within the context of criminal identification lineups. We tested, using the inversion paradigm, the role of configural processing in lineups. Recent research has found that face discrimination accuracy in lineups is better in a simultaneous compared to a sequential lineup procedure. Therefore, we compared configural processing in simultaneous and sequential lineups to examine whether there are differences. We had participants view a crime video, and then they attempted to identify the perpetrator from a simultaneous or sequential lineup. The test faces were presented either upright or inverted, as previous research has shown that inverting test faces disrupts configural processing. The size of the inversion effect for faces was the same across lineup procedures, indicating that configural processing underlies face recognition in both procedures. Discrimination accuracy was comparable across lineup procedures in both the upright and inversion condition. Theoretical implications of the results are discussed.

Cumulative pregnancy rates after sequential treatment with modified natural cycle IVF followed by IVF with controlled ovarian stimulation

NARCIS (Netherlands)

Pelinck, M. J.; Knol, H. M.; Vogel, N. E. A.; Arts, E. G. J. M.; Simons, A. H. M.; Heineman, M. J.; Hoek, A.

BACKGROUND: In modified natural cycle IVF (MNC-IVF), treatment is aimed at using the one follicle that spontaneously develops to dominance, using a GnRH-antagonist together with gonadotrophins in the late follicular phase only. The MNC-IVF is of interest because of its low-risk and patient-friendly

Cumulative pregnancy rates after sequential treatment with modified natural cycle IVF followed by IVF with controlled ovarian stimulation

NARCIS (Netherlands)

Pelinck, M. J.; Knol, H. M.; Vogel, N. E. A.; Arts, E. G. J. M.; Simons, A. H. M.; Heineman, M. J.; Hoek, A.

2008-01-01

BACKGROUND: In modified natural cycle IVF (MNC-IVF), treatment is aimed at using the one follicle that spontaneously develops to dominance, using a GnRH-antagonist together with gonadotrophins in the late follicular phase only. The MNC-IVF is of interest because of its low-risk and patient-friendly

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

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

2014-02-01

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

Adrenal vein sampling in primary aldosteronism: concordance of simultaneous vs sequential sampling.

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Almarzooqi, Mohamed-Karji; Chagnon, Miguel; Soulez, Gilles; Giroux, Marie-France; Gilbert, Patrick; Oliva, Vincent L; Perreault, Pierre; Bouchard, Louis; Bourdeau, Isabelle; Lacroix, André; Therasse, Eric

2017-02-01

Many investigators believe that basal adrenal venous sampling (AVS) should be done simultaneously, whereas others opt for sequential AVS for simplicity and reduced cost. This study aimed to evaluate the concordance of sequential and simultaneous AVS methods. Between 1989 and 2015, bilateral simultaneous sets of basal AVS were obtained twice within 5 min, in 188 consecutive patients (59 women and 129 men; mean age: 53.4 years). Selectivity was defined by adrenal-to-peripheral cortisol ratio ≥2, and lateralization was defined as an adrenal aldosterone-to-cortisol ratio ≥2, the contralateral side. Sequential AVS was simulated using right sampling at -5 min (t = -5) and left sampling at 0 min (t = 0). There was no significant difference in mean selectivity ratio (P = 0.12 and P = 0.42 for the right and left sides respectively) and in mean lateralization ratio (P = 0.93) between t = -5 and t = 0. Kappa for selectivity between 2 simultaneous AVS was 0.71 (95% CI: 0.60-0.82), whereas it was 0.84 (95% CI: 0.76-0.92) and 0.85 (95% CI: 0.77-0.93) between sequential and simultaneous AVS at respectively -5 min and at 0 min. Kappa for lateralization between 2 simultaneous AVS was 0.84 (95% CI: 0.75-0.93), whereas it was 0.86 (95% CI: 0.78-0.94) and 0.80 (95% CI: 0.71-0.90) between sequential AVS and simultaneous AVS at respectively -5 min at 0 min. Concordance between simultaneous and sequential AVS was not different than that between 2 repeated simultaneous AVS in the same patient. Therefore, a better diagnostic performance is not a good argument to select the AVS method. © 2017 European Society of Endocrinology.

Sequential motor skill: cognition, perception and action

NARCIS (Netherlands)

Ruitenberg, M.F.L.

2013-01-01

Discrete movement sequences are assumed to be the building blocks of more complex sequential actions that are present in our everyday behavior. The studies presented in this dissertation address the (neuro)cognitive underpinnings of such movement sequences, in particular in relationship to the role

Zips : mining compressing sequential patterns in streams

NARCIS (Netherlands)

Hoang, T.L.; Calders, T.G.K.; Yang, J.; Mörchen, F.; Fradkin, D.; Chau, D.H.; Vreeken, J.; Leeuwen, van M.; Faloutsos, C.

2013-01-01

We propose a streaming algorithm, based on the minimal description length (MDL) principle, for extracting non-redundant sequential patterns. For static databases, the MDL-based approach that selects patterns based on their capacity to compress data rather than their frequency, was shown to be

Improving the identification accuracy of senior witnesses: do prelineup questions and sequential testing help?

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Memon, Amina; Gabbert, Fiona

2003-04-01

Eyewitness research has identified sequential lineup testing as a way of reducing false lineup choices while maintaining accurate identifications. The authors examined the usefulness of this procedure for reducing false choices in older adults. Young and senior witnesses viewed a crime video and were later presented with target present orabsent lineups in a simultaneous or sequential format. In addition, some participants received prelineup questions about their memory for a perpetrator's face and about their confidence in their ability to identify the culprit or to correctly reject the lineup. The sequential lineup reduced false choosing rates among young and older adults in target-absent conditions. In target-present conditions, sequential testing significantly reduced the correct identification rate in both age groups.

Optimal Sequential Diagnostic Strategy Generation Considering Test Placement Cost for Multimode Systems

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Shigang Zhang

2015-10-01

Full Text Available Sequential fault diagnosis is an approach that realizes fault isolation by executing the optimal test step by step. The strategy used, i.e., the sequential diagnostic strategy, has great influence on diagnostic accuracy and cost. Optimal sequential diagnostic strategy generation is an important step in the process of diagnosis system construction, which has been studied extensively in the literature. However, previous algorithms either are designed for single mode systems or do not consider test placement cost. They are not suitable to solve the sequential diagnostic strategy generation problem considering test placement cost for multimode systems. Therefore, this problem is studied in this paper. A formulation is presented. Two algorithms are proposed, one of which is realized by system transformation and the other is newly designed. Extensive simulations are carried out to test the effectiveness of the algorithms. A real-world system is also presented. All the results show that both of them have the ability to solve the diagnostic strategy generation problem, and they have different characteristics.

Optimal Sequential Diagnostic Strategy Generation Considering Test Placement Cost for Multimode Systems

Science.gov (United States)

Zhang, Shigang; Song, Lijun; Zhang, Wei; Hu, Zheng; Yang, Yongmin

2015-01-01

Sequential fault diagnosis is an approach that realizes fault isolation by executing the optimal test step by step. The strategy used, i.e., the sequential diagnostic strategy, has great influence on diagnostic accuracy and cost. Optimal sequential diagnostic strategy generation is an important step in the process of diagnosis system construction, which has been studied extensively in the literature. However, previous algorithms either are designed for single mode systems or do not consider test placement cost. They are not suitable to solve the sequential diagnostic strategy generation problem considering test placement cost for multimode systems. Therefore, this problem is studied in this paper. A formulation is presented. Two algorithms are proposed, one of which is realized by system transformation and the other is newly designed. Extensive simulations are carried out to test the effectiveness of the algorithms. A real-world system is also presented. All the results show that both of them have the ability to solve the diagnostic strategy generation problem, and they have different characteristics. PMID:26457709

Inhibitory effect of sequential combined chemotherapy and radiotherapy on growth of implanted tumor in mice

International Nuclear Information System (INIS)

Okada, Kouji

1983-01-01

Sequential chemotherapy using FT-207, adriamycin and mitomycin C followed by radiotherapy was attempted to achieve effective inhibition against implanted tumor in C57BL/6 black mice bearing YM-12 tumors. Sequential combined chemotherapy was more effective than single drug chemotherapy or combined chemotherapy of other drugs. Addition of radiotherapy to the sequential combined chemotherapy was successful for enhancing therapeutic effect. (author)

The Bacterial Sequential Markov Coalescent.

Science.gov (United States)

De Maio, Nicola; Wilson, Daniel J

2017-05-01

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

Structural and Functional Impacts of ER Coactivator Sequential Recruitment.

Science.gov (United States)

Yi, Ping; Wang, Zhao; Feng, Qin; Chou, Chao-Kai; Pintilie, Grigore D; Shen, Hong; Foulds, Charles E; Fan, Guizhen; Serysheva, Irina; Ludtke, Steven J; Schmid, Michael F; Hung, Mien-Chie; Chiu, Wah; O'Malley, Bert W

2017-09-07

Nuclear receptors recruit multiple coactivators sequentially to activate transcription. This "ordered" recruitment allows different coactivator activities to engage the nuclear receptor complex at different steps of transcription. Estrogen receptor (ER) recruits steroid receptor coactivator-3 (SRC-3) primary coactivator and secondary coactivators, p300/CBP and CARM1. CARM1 recruitment lags behind the binding of SRC-3 and p300 to ER. Combining cryo-electron microscopy (cryo-EM) structure analysis and biochemical approaches, we demonstrate that there is a close crosstalk between early- and late-recruited coactivators. The sequential recruitment of CARM1 not only adds a protein arginine methyltransferase activity to the ER-coactivator complex, it also alters the structural organization of the pre-existing ERE/ERα/SRC-3/p300 complex. It induces a p300 conformational change and significantly increases p300 HAT activity on histone H3K18 residues, which, in turn, promotes CARM1 methylation activity on H3R17 residues to enhance transcriptional activity. This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. Copyright © 2017 Elsevier Inc. All rights reserved.

Sequential decay of Reggeons

International Nuclear Information System (INIS)

Yoshida, Toshihiro

1981-01-01

Probabilities of meson production in the sequential decay of Reggeons, which are formed from the projectile and the target in the hadron-hadron to Reggeon-Reggeon processes, are investigated. It is assumed that pair creation of heavy quarks and simultaneous creation of two antiquark-quark pairs are negligible. The leading-order terms with respect to ratio of creation probabilities of anti s s to anti u u (anti d d) are calculated. The production cross sections in the target fragmentation region are given in terms of probabilities in the initial decay of the Reggeons and an effect of manyparticle production. (author)

[Professor GAO Yuchun's experience on "sequential acupuncture leads to smooth movement of qi"].

Science.gov (United States)

Wang, Yanjun; Xing, Xiao; Cui, Linhua

2016-01-01

Professor GAO Yuchun is considered as the key successor of GAO's academic school of acupuncture and moxibustion in Yanzhao region. Professor GAO's clinical experience of, "sequential acupuncture" is introduced in details in this article. In Professor GAO's opinions, appropriate acupuncture sequence is the key to satisfactory clinical effects during treatment. Based on different acupoints, sequential acupuncture can achieve the aim of qi following needles and needles leading qi; based on different symptoms, sequential acupuncture can regulate qi movement; based on different body positions, sequential acupuncture can harmonize qi-blood and reinforcing deficiency and reducing excess. In all, according to the differences of disease condition and constitution, based on the accurate acupoint selection and appropriate manipulation, it is essential to capture the nature of diseases and make the order of acupuncture, which can achieve the aim of regulating qi movement and reinforcing deficiency and reducing excess.

TELEGRAPHS TO INCANDESCENT LAMPS: A SEQUENTIAL PROCESS OF INNOVATION

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Laurence J. Malone

2000-01-01

Full Text Available This paper outlines a sequential process of technological innovation in the emergence of the electrical industry in the United States from 1830 to 1880. Successive inventions that realize the commercial possibilities of electricity provided the foundation for an industry where technical knowledge, invention and diffusion were ultimately consolidated within the managerial structure of new firms. The genesis of the industry is traced, sequentially, through the development of the telegraph, arc light and incandescent lamp. Exploring the origins of the telegraph and incandescent lamp reveals a process where a series of inventions and firms result from successful efforts touse scientific principles to create new commodities and markets.

Results of simultaneous and sequential pediatric liver and kidney transplantation.

Science.gov (United States)

Rogers, J; Bueno, J; Shapiro, R; Scantlebury, V; Mazariegos, G; Fung, J; Reyes, J

2001-11-27

The indications for simultaneous and sequential pediatric liver (LTx) and kidney (KTx) transplantation have not been well defined. We herein report the results of our experience with these procedures in children with end-stage liver disease and/or subsequent end-stage renal disease. Between 1984 and 1995, 12 LTx recipients received 15 kidney allografts. Eight simultaneous and seven sequential LTx/KTx were performed. There were six males and six females, with a mean age of 10.9 years (1.5-23.7). One of the eight simultaneous LTx/KTx was part of a multivisceral allograft. Five KTx were performed at varied intervals after successful LTx, one KTx was performed after a previous simultaneous LTx/KTx, and one KTx was performed after previous sequential LTx/KTx. Immunosuppression was with tacrolimus or cyclosporine and steroids. Indications for LTx were oxalosis (four), congenital hepatic fibrosis (two), cystinosis (one), polycystic liver disease (one), A-1-A deficiency (one), Total Parenteral Nutrition (TPN)-related (one), cryptogenic cirrhosis (one), and hepatoblastoma (one). Indications for KTx were oxalosis (four), drug-induced (four), polycystic kidney disease (three), cystinosis (one), and glomerulonephritis (1). With a mean follow-up of 58 months (0.9-130), the overall patient survival rate was 58% (7/12). One-year and 5-year actuarial patient survival rates were 66% and 58%, respectively. Patient survival rates at 1 year after KTx according to United Network of Organ Sharing (liver) status were 100% for status 3, 50% for status 2, and 0% for status 1. The overall renal allograft survival rate was 47%. Actuarial renal allograft survival rates were 53% at 1 and 5 years. The overall hepatic allograft survival rate was equivalent to the overall patient survival rate (58%). Six of seven surviving patients have normal renal allograft function, and one patient has moderate chronic allograft nephropathy. All surviving patients have normal hepatic allograft function. Six

Redox-controlled release dynamics of thallium in periodically flooded arable soil.

Science.gov (United States)

Antić-Mladenović, Svetlana; Frohne, Tina; Kresović, Mirjana; Stärk, Hans-Joachim; Savić, Dubravka; Ličina, Vlado; Rinklebe, Jörg

2017-07-01

To our knowledge, this is the first work to mechanistically study the impact of the redox potential (E H ) and principal factors, such as pH, iron (Fe), manganese (Mn), dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), chlorides (Cl - ) and sulfates (SO 4 2- ), on the release dynamics of thallium (Tl) in periodically flooded soil. We simulated flooding using an automated biogeochemical microcosm system that allows for systematical control of pre-defined redox windows. The E H value was increased mechanistically at intervals of approximately 100 mV from reducing (-211 mV) to oxidizing (475 mV) conditions. Soluble Tl levels (0.02-0.28 μg L -1 ) increased significantly with increases in E H (r = 0.80, p Thallium mobilization was found to be related to several simultaneous processes involving the gradual oxidation of Tl-bearing sulfides, reductive dissolution of Fe-Mn oxides and desorption from mineral sorbents. Manganese oxides did not appear to have a considerable effect on Tl retention under oxidizing conditions. Before conducting the microcosm experiment, Tl geochemical fractionation was assessed using the modified BCR sequential extraction procedure. The BCR revealed a majority of Tl in the residual fraction (77.7%), followed by reducible (13.3%) and oxidizable fractions (5.9%). By generating high levels of Tl toxicity at low doses, Tl released under oxidizing conditions may pose an environmental threat. In the future, similar studies should be conducted on various soils along with a determination of the Tl species and monitoring of the Tl content in plants to achieve more detailed insight into soluble Tl behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multi-Stage Recognition of Speech Emotion Using Sequential Forward Feature Selection

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Liogienė Tatjana

2016-07-01

Full Text Available The intensive research of speech emotion recognition introduced a huge collection of speech emotion features. Large feature sets complicate the speech emotion recognition task. Among various feature selection and transformation techniques for one-stage classification, multiple classifier systems were proposed. The main idea of multiple classifiers is to arrange the emotion classification process in stages. Besides parallel and serial cases, the hierarchical arrangement of multi-stage classification is most widely used for speech emotion recognition. In this paper, we present a sequential-forward-feature-selection-based multi-stage classification scheme. The Sequential Forward Selection (SFS and Sequential Floating Forward Selection (SFFS techniques were employed for every stage of the multi-stage classification scheme. Experimental testing of the proposed scheme was performed using the German and Lithuanian emotional speech datasets. Sequential-feature-selection-based multi-stage classification outperformed the single-stage scheme by 12–42 % for different emotion sets. The multi-stage scheme has shown higher robustness to the growth of emotion set. The decrease in recognition rate with the increase in emotion set for multi-stage scheme was lower by 10–20 % in comparison with the single-stage case. Differences in SFS and SFFS employment for feature selection were negligible.

Thallium in fractions of sediments formed during the 2004 tsunami in Thailand.

Science.gov (United States)

Lukaszewski, Zenon; Karbowska, Bozena; Zembrzuski, Wlodzimierz; Siepak, Marcin

2012-06-01

Thallium is a highly toxic element. Its concentration in sediment fractions from the 2004 tsunami in Thailand was investigated. A modified BCR procedure was used for sequential extraction. Tl was determined by flow injection differential pulse anodic stripping voltammetry. It was found that the majority of thallium in the investigated tsunami sediments (86-97 percent) is entrapped in the alumosilicate parent matter i.e. it is entirely immovable. Only the total destruction of this residual fraction with hydrofluoric acid made this thallium available. The conclusion strongly supports the hypothesis that thallium is mainly entrapped in alumosilicate parent matter. Total thallium concentration in the investigated tsunami sediments was divergent in various samples from 0.37 to 1.13 μg g(-1) and significantly different from the reference area (0.05 μg g(-1)). Tsunami sediment fractions from different sampling points are divergent in terms of total thallium concentration and concentration of mobile thallium. Generally, mobile thallium concentration was growing in sequence: water soluble fractionthallium concentration in the reducible fraction was higher than in the oxidizable fraction. Copyright © 2012 Elsevier Inc. All rights reserved.

Tinnitus after Simultaneous and Sequential Bilateral Cochlear Implantation.

Science.gov (United States)

Ramakers, Geerte G J; Kraaijenga, Véronique J C; Smulders, Yvette E; van Zon, Alice; Stegeman, Inge; Stokroos, Robert J; Free, Rolien H; Frijns, Johan H M; Huinck, Wendy J; Van Zanten, Gijsbert A; Grolman, Wilko

2017-01-01

There is an ongoing global discussion on whether or not bilateral cochlear implantation should be standard care for bilateral deafness. Contrary to unilateral cochlear implantation, however, little is known about the effect of bilateral cochlear implantation on tinnitus. To investigate tinnitus outcomes 1 year after bilateral cochlear implantation. Secondarily, to compare tinnitus outcomes between simultaneous and sequential bilateral cochlear implantation and to investigate long-term follow-up (3 years). This study is a secondary analysis as part of a multicenter randomized controlled trial. Thirty-eight postlingually deafened adults were included in the original trial, in which the presence of tinnitus was not an inclusion criterion. All participants received cochlear implants (CIs) because of profound hearing loss. Nineteen participants received bilateral CIs simultaneously and 19 participants received bilateral CIs sequentially with an inter-implant interval of 2 years. The prevalence and severity of tinnitus before and after simultaneous and sequential bilateral cochlear implantation were measured preoperatively and each year after implantation with the Tinnitus Handicap Inventory (THI) and Tinnitus Questionnaire (TQ). The prevalence of preoperative tinnitus was 42% (16/38). One year after bilateral implantation, there was a median difference of -8 (inter-quartile range (IQR): -28 to 4) in THI score and -9 (IQR: -17 to -9) in TQ score in the participants with preoperative tinnitus. Induction of tinnitus occurred in five participants, all in the simultaneous group, in the year after bilateral implantation. Although the preoperative and also the postoperative median THI and TQ scores were higher in the simultaneous group, the median difference scores were equal in both groups. In the simultaneous group, tinnitus scores fluctuated in the 3 years after implantation. In the sequential group, four patients had an additional benefit of the second CI: a total

Learning sequential control in a Neural Blackboard Architecture for in situ concept reasoning

NARCIS (Netherlands)

van der Velde, Frank; van der Velde, Frank; Besold, Tarek R.; Lamb, Luis; Serafini, Luciano; Tabor, Whitney

2016-01-01

Simulations are presented and discussed of learning sequential control in a Neural Blackboard Architecture (NBA) for in situ concept-based reasoning. Sequential control is learned in a reservoir network, consisting of columns with neural circuits. This allows the reservoir to control the dynamics of

Microstructural evolution of reduced-activation martensitic steel under single and sequential ion irradiations

Energy Technology Data Exchange (ETDEWEB)

Luo, Fengfeng [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Guo, Liping, E-mail: guolp@whu.edu.cn [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Jin, Shuoxue; Li, Tiecheng; Zheng, Zhongcheng [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Yang, Feng; Xiong, Xuesong; Suo, Jinping [State Key Laboratory of Mould Technology, Institute of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

2013-07-15

Microstructural evolution of super-clean reduced-activation martensitic steels irradiated with single-beam (Fe{sup +}) and sequential-beam (Fe{sup +} plus He{sup +}) at 350 °C and 550 °C was studied. Sequential-beam irradiation induced smaller size and larger number density of precipitates compared to single-beam irradiation at 350 °C. The largest size of cavities was observed after sequential-beam irradiation at 550 °C. The segregation of Cr and W and depletion of Fe in carbides were observed, and the maximum depletion of Fe and enrichment of Cr occurred under irradiation at 350 °C.

Sequential and Simultaneous Logit: A Nested Model.

NARCIS (Netherlands)

van Ophem, J.C.M.; Schram, A.J.H.C.

1997-01-01

A nested model is presented which has both the sequential and the multinomial logit model as special cases. This model provides a simple test to investigate the validity of these specifications. Some theoretical properties of the model are discussed. In the analysis a distribution function is

Making Career Decisions--A Sequential Elimination Approach.

Science.gov (United States)

Gati, Itamar

1986-01-01

Presents a model for career decision making based on the sequential elimination of occupational alternatives, an adaptation for career decisions of Tversky's (1972) elimination-by-aspects theory of choice. The expected utility approach is reviewed as a representative compensatory model for career decisions. Advantages, disadvantages, and…

Sequential Computerized Mastery Tests--Three Simulation Studies

Science.gov (United States)

Wiberg, Marie

2006-01-01

A simulation study of a sequential computerized mastery test is carried out with items modeled with the 3 parameter logistic item response theory model. The examinees' responses are either identically distributed, not identically distributed, or not identically distributed together with estimation errors in the item characteristics. The…

Sequential Low Cost Interventions Double Hand Hygiene Rates ...

African Journals Online (AJOL)

Sequential Low Cost Interventions Double Hand Hygiene Rates Among Medical Teams in a Resource Limited Setting. Results of a Hand Hygiene Quality Improvement Project Conducted At University Teaching Hospital of Kigali (Chuk), Kigali, Rwanda.

Sequential optimization of matrix chain multiplication relative to different cost functions

KAUST Repository

Chikalov, Igor; Hussain, Shahid; Moshkov, Mikhail

2011-01-01

In this paper, we present a methodology to optimize matrix chain multiplication sequentially relative to different cost functions such as total number of scalar multiplications, communication overhead in a multiprocessor environment, etc. For n matrices our optimization procedure requires O(n 3) arithmetic operations per one cost function. This work is done in the framework of a dynamic programming extension that allows sequential optimization relative to different criteria. © 2011 Springer-Verlag Berlin Heidelberg.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Variation among heritage speakers: Sequential vs. simultaneous bilinguals

Directory of Open Access Journals (Sweden)

Teresa Lee

2013-08-01

Full Text Available This study examines the differences in the grammatical knowledge of two types of heritage speakers of Korean. Early simultaneous bilinguals are exposed to both English and the heritage language from birth, whereas early sequential bilinguals are exposed to the heritage language first and then to English upon schooling. A listening comprehension task involving relative clauses was conducted with 51 beginning-level Korean heritage speakers. The results showed that the early sequential bilinguals exhibited much more accurate knowledge than the early simultaneous bilinguals, who lacked rudimentary knowledge of Korean relative clauses. Drawing on the findings of adult and child Korean L1 data on the acquisition of relative clauses, the performance of each group is discussed with respect to attrition and incomplete acquisition of the heritage language.

Two-step sequential pretreatment for the enhanced enzymatic hydrolysis of coffee spent waste.

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Ravindran, Rajeev; Jaiswal, Swarna; Abu-Ghannam, Nissreen; Jaiswal, Amit K

2017-09-01

In the present study, eight different pretreatments of varying nature (physical, chemical and physico-chemical) followed by a sequential, combinatorial pretreatment strategy was applied to spent coffee waste to attain maximum sugar yield. Pretreated samples were analysed for total reducing sugar, individual sugars and generation of inhibitory compounds such as furfural and hydroxymethyl furfural (HMF) which can hinder microbial growth and enzyme activity. Native spent coffee waste was high in hemicellulose content. Galactose was found to be the predominant sugar in spent coffee waste. Results showed that sequential pretreatment yielded 350.12mg of reducing sugar/g of substrate, which was 1.7-fold higher than in native spent coffee waste (203.4mg/g of substrate). Furthermore, extensive delignification was achieved using sequential pretreatment strategy. XRD, FTIR, and DSC profiles of the pretreated substrates were studied to analyse the various changes incurred in sequentially pretreated spent coffee waste as opposed to native spent coffee waste. Copyright © 2017 Elsevier Ltd. All rights reserved.

Competitive interactions affect working memory performance for both simultaneous and sequential stimulus presentation.

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Ahmad, Jumana; Swan, Garrett; Bowman, Howard; Wyble, Brad; Nobre, Anna C; Shapiro, Kimron L; McNab, Fiona

2017-07-06

Competition between simultaneously presented visual stimuli lengthens reaction time and reduces both the BOLD response and neural firing. In contrast, conditions of sequential presentation have been assumed to be free from competition. Here we manipulated the spatial proximity of stimuli (Near versus Far conditions) to examine the effects of simultaneous and sequential competition on different measures of working memory (WM) for colour. With simultaneous presentation, the measure of WM precision was significantly lower for Near items, and participants reported the colour of the wrong item more often. These effects were preserved when the second stimulus immediately followed the first, disappeared when they were separated by 500 ms, and were partly recovered (evident for our measure of mis-binding but not WM precision) when the task was altered to encourage participants to maintain the sequentially presented items together in WM. Our results show, for the first time, that competition affects the measure of WM precision, and challenge the assumption that sequential presentation removes competition.

A framework for sequential multiblock component methods

NARCIS (Netherlands)

Smilde, A.K.; Westerhuis, J.A.; Jong, S.de

2003-01-01

Multiblock or multiset methods are starting to be used in chemistry and biology to study complex data sets. In chemometrics, sequential multiblock methods are popular; that is, methods that calculate one component at a time and use deflation for finding the next component. In this paper a framework

Interpretability degrees of finitely axiomatized sequential theories

NARCIS (Netherlands)

Visser, Albert

In this paper we show that the degrees of interpretability of finitely axiomatized extensions-in-the-same-language of a finitely axiomatized sequential theory-like Elementary Arithmetic EA, IΣ1, or the Gödel-Bernays theory of sets and classes GB-have suprema. This partially answers a question posed

Interpretability Degrees of Finitely Axiomatized Sequential Theories

NARCIS (Netherlands)

Visser, Albert

2012-01-01

In this paper we show that the degrees of interpretability of finitely axiomatized extensions-in-the-same-language of a finitely axiomatized sequential theory —like Elementary Arithmetic EA, IΣ1, or the Gödel-Bernays theory of sets and classes GB— have suprema. This partially answers a question

Adult Word Recognition and Visual Sequential Memory

Science.gov (United States)

Holmes, V. M.

2012-01-01

Two experiments were conducted investigating the role of visual sequential memory skill in the word recognition efficiency of undergraduate university students. Word recognition was assessed in a lexical decision task using regularly and strangely spelt words, and nonwords that were either standard orthographically legal strings or items made from…

The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization.

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Rossitto, Giacomo; Battistel, Michele; Barbiero, Giulio; Bisogni, Valeria; Maiolino, Giuseppe; Diego, Miotto; Seccia, Teresa M; Rossi, Gian Paolo

2018-02-01

The pulsatile secretion of adrenocortical hormones and a stress reaction occurring when starting adrenal vein sampling (AVS) can affect the selectivity and also the assessment of lateralization when sequential blood sampling is used. We therefore tested the hypothesis that a simulated sequential blood sampling could decrease the diagnostic accuracy of lateralization index for identification of aldosterone-producing adenoma (APA), as compared with bilaterally simultaneous AVS. In 138 consecutive patients who underwent subtyping of primary aldosteronism, we compared the results obtained simultaneously bilaterally when starting AVS (t-15) and 15 min after (t0), with those gained with a simulated sequential right-to-left AVS technique (R ⇒ L) created by combining hormonal values obtained at t-15 and at t0. The concordance between simultaneously obtained values at t-15 and t0, and between simultaneously obtained values and values gained with a sequential R ⇒ L technique, was also assessed. We found a marked interindividual variability of lateralization index values in the patients with bilaterally selective AVS at both time point. However, overall the lateralization index simultaneously determined at t0 provided a more accurate identification of APA than the simulated sequential lateralization indexR ⇒ L (P = 0.001). Moreover, regardless of which side was sampled first, the sequential AVS technique induced a sequence-dependent overestimation of lateralization index. While in APA patients the concordance between simultaneous AVS at t0 and t-15 and between simultaneous t0 and sequential technique was moderate-to-good (K = 0.55 and 0.66, respectively), in non-APA patients, it was poor (K = 0.12 and 0.13, respectively). Sequential AVS generates factitious between-sides gradients, which lower its diagnostic accuracy, likely because of the stress reaction arising upon starting AVS.

Effects of neostriatal 6-OHDA lesion on performance in a rat sequential reaction time task.

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Domenger, D; Schwarting, R K W

2008-10-31

Work in humans and monkeys has provided evidence that the basal ganglia, and the neurotransmitter dopamine therein, play an important role for sequential learning and performance. Compared to primates, experimental work in rodents is rather sparse, largely due to the fact that tasks comparable to the human ones, especially serial reaction time tasks (SRTT), had been lacking until recently. We have developed a rat model of the SRTT, which allows to study neural correlates of sequential performance and motor sequence execution. Here, we report the effects of dopaminergic neostriatal lesions, performed using bilateral 6-hydroxydopamine injections, on performance of well-trained rats tested in our SRTT. Sequential behavior was measured in two ways: for one, the effects of small violations of otherwise well trained sequences were examined as a measure of attention and automation. Secondly, sequential versus random performance was compared as a measure of sequential learning. Neurochemically, the lesions led to sub-total dopamine depletions in the neostriatum, which ranged around 60% in the lateral, and around 40% in the medial neostriatum. These lesions led to a general instrumental impairment in terms of reduced speed (response latencies) and response rate, and these deficits were correlated with the degree of striatal dopamine loss. Furthermore, the violation test indicated that the lesion group conducted less automated responses. The comparison of random versus sequential responding showed that the lesion group did not retain its superior sequential performance in terms of speed, whereas they did in terms of accuracy. Also, rats with lesions did not improve further in overall performance as compared to pre-lesion values, whereas controls did. These results support previous results that neostriatal dopamine is involved in instrumental behaviour in general. Also, these lesions are not sufficient to completely abolish sequential performance, at least when acquired

Eyewitness identification in simultaneous and sequential lineups: an investigation of position effects using receiver operating characteristics.

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Meisters, Julia; Diedenhofen, Birk; Musch, Jochen

2018-04-20

For decades, sequential lineups have been considered superior to simultaneous lineups in the context of eyewitness identification. However, most of the research leading to this conclusion was based on the analysis of diagnosticity ratios that do not control for the respondent's response criterion. Recent research based on the analysis of ROC curves has found either equal discriminability for sequential and simultaneous lineups, or higher discriminability for simultaneous lineups. Some evidence for potential position effects and for criterion shifts in sequential lineups has also been reported. Using ROC curve analysis, we investigated the effects of the suspect's position on discriminability and response criteria in both simultaneous and sequential lineups. We found that sequential lineups suffered from an unwanted position effect. Respondents employed a strict criterion for the earliest lineup positions, and shifted to a more liberal criterion for later positions. No position effects and no criterion shifts were observed in simultaneous lineups. This result suggests that sequential lineups are not superior to simultaneous lineups, and may give rise to unwanted position effects that have to be considered when conducting police lineups.

Hemodynamic analysis of sequential graft from right coronary system to left coronary system.

Science.gov (United States)

Wang, Wenxin; Mao, Boyan; Wang, Haoran; Geng, Xueying; Zhao, Xi; Zhang, Huixia; Xie, Jinsheng; Zhao, Zhou; Lian, Bo; Liu, Youjun

2016-12-28

Sequential and single grafting are two surgical procedures of coronary artery bypass grafting. However, it remains unclear if the sequential graft can be used between the right and left coronary artery system. The purpose of this paper is to clarify the possibility of right coronary artery system anastomosis to left coronary system. A patient-specific 3D model was first reconstructed based on coronary computed tomography angiography (CCTA) images. Two different grafts, the normal multi-graft (Model 1) and the novel multi-graft (Model 2), were then implemented on this patient-specific model using virtual surgery techniques. In Model 1, the single graft was anastomosed to right coronary artery (RCA) and the sequential graft was adopted to anastomose left anterior descending (LAD) and left circumflex artery (LCX). While in Model 2, the single graft was anastomosed to LAD and the sequential graft was adopted to anastomose RCA and LCX. A zero-dimensional/three-dimensional (0D/3D) coupling method was used to realize the multi-scale simulation of both the pre-operative and two post-operative models. Flow rates in the coronary artery and grafts were obtained. The hemodynamic parameters were also showed, including wall shear stress (WSS) and oscillatory shear index (OSI). The area of low WSS and OSI in Model 1 was much less than that in Model 2. Model 1 shows optimistic hemodynamic modifications which may enhance the long-term patency of grafts. The anterior segments of sequential graft have better long-term patency than the posterior segments. With rational spatial position of the heart vessels, the last anastomosis of sequential graft should be connected to the main branch.

Sequential test procedures for inventory differences

International Nuclear Information System (INIS)

Goldman, A.S.; Kern, E.A.; Emeigh, C.W.

1985-01-01

By means of a simulation study, we investigated the appropriateness of Page's and power-one sequential tests on sequences of inventory differences obtained from an example materials control unit, a sub-area of a hypothetical UF 6 -to-U 3 O 8 conversion process. The study examined detection probability and run length curves obtained from different loss scenarios. 12 refs., 10 figs., 2 tabs

Plasmon-driven sequential chemical reactions in an aqueous environment.

Science.gov (United States)

Zhang, Xin; Wang, Peijie; Zhang, Zhenglong; Fang, Yurui; Sun, Mengtao

2014-06-24

Plasmon-driven sequential chemical reactions were successfully realized in an aqueous environment. In an electrochemical environment, sequential chemical reactions were driven by an applied potential and laser irradiation. Furthermore, the rate of the chemical reaction was controlled via pH, which provides indirect evidence that the hot electrons generated from plasmon decay play an important role in plasmon-driven chemical reactions. In acidic conditions, the hot electrons were captured by the abundant H(+) in the aqueous environment, which prevented the chemical reaction. The developed plasmon-driven chemical reactions in an aqueous environment will significantly expand the applications of plasmon chemistry and may provide a promising avenue for green chemistry using plasmon catalysis in aqueous environments under irradiation by sunlight.

Comparative Effects of Biochar, Slag and Ferrous-Mn Ore on Lead and Cadmium Immobilization in Soil.

Science.gov (United States)

Mehmood, Sajid; Rizwan, Muhammad; Bashir, Saqib; Ditta, Allah; Aziz, Omar; Yong, Li Zhe; Dai, Zhihua; Akmal, Muhammad; Ahmed, Waqas; Adeel, Muhammad; Imtiaz, Muhammad; Tu, Shuxin

2018-02-01

A variety of remediation approaches have been applied to the heavy metals-contaminated soils, however, the immobilization of metals in co-contaminated soils still not cleared. Therefore, an incubation study was conducted to evaluate the instantaneous effects of different concentrations of biochar (BC), slag (SL) and Fe-Mn ore (FMO) on immobilization of Pb and Cd through the Toxicity Characteristic Leaching Procedure (TCLP) by following the the European Community Bureau of Reference (BCR), CaCl 2 and NH 4 NO 3 . The sequential extraction of BCR showed decrease in acid soluble fractions, while the residual proportions of Pb and Cd were enhanced with increasing concentrations of SL and BC. Addition of BC significantly lowered the extractable fractions of both metals by TCLP, NH 4 NO 3 and CaCl 2 as compared to SL and FMO. Among all amendments, BC incorporation into co-contaminated soil offered promising results for Pb and Cd immobilization. Overall, all amendments showed positive and long-term impact on the reclamation of co-contaminated soil with heavy metals and could deserve advance monitoring studies on a field scale.

Better together: reduced compliance after sequential versus simultaneous bilateral hearing aids fitting.

Science.gov (United States)

Lavie, Limor; Banai, Karen; Attias, Joseph; Karni, Avi

2014-03-01

The purpose of this study was to determine the effects of sequential versus simultaneous bilateral hearing aids fitting on patient compliance. Thirty-six older adults with hearing impairment participated in this study. Twelve were fitted with bilateral hearing aids simultaneously. The remaining participants were fitted sequentially: One hearing aid (to the left or to the right ear) was used initially; 1 month later, the other ear was also fitted with a hearing aid for bilateral use. Self-reports on usefulness and compliance were elicited after the first and second months of hearing aid use. In addition, the number of hours the hearing aids were used was extracted from the data loggings of each device. Simultaneous fitting resulted in high levels of compliance and consistent usage throughout the study period. Sequential fitting resulted in abrupt reduction in compliance and hours of use once the second hearing aid was added, both in the clinical scoring and in the data loggings. Simultaneous fitting of bilateral hearing aids results in better compliance compared with sequential fitting. The addition of a second hearing aid after a relatively short period of monaural use may lead to inconsistent use of both hearing aids.

Adjuvant sequential chemo and radiotherapy improves the oncological outcome in high risk endometrial cancer

Science.gov (United States)

Signorelli, Mauro; Lissoni, Andrea Alberto; De Ponti, Elena; Grassi, Tommaso; Ponti, Serena

2015-01-01

Objective Evaluation of the impact of sequential chemoradiotherapy in high risk endometrial cancer (EC). Methods Two hundred fifty-four women with stage IB grade 3, II and III EC (2009 FIGO staging), were included in this retrospective study. Results Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively. Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty-five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%) chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and 91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040; overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS, p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015) and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (≤65 years) and sequential chemoradiotherapy were statistically related to the prognosis. Conclusion Sequential chemoradiotherapy improves survival rates in high risk EC compared with chemotherapy or radiotherapy alone, in particular in stage III. PMID:26197768

Eyewitness decisions in simultaneous and sequential lineups: a dual-process signal detection theory analysis.

Science.gov (United States)

Meissner, Christian A; Tredoux, Colin G; Parker, Janat F; MacLin, Otto H

2005-07-01

Many eyewitness researchers have argued for the application of a sequential alternative to the traditional simultaneous lineup, given its role in decreasing false identifications of innocent suspects (sequential superiority effect). However, Ebbesen and Flowe (2002) have recently noted that sequential lineups may merely bring about a shift in response criterion, having no effect on discrimination accuracy. We explored this claim, using a method that allows signal detection theory measures to be collected from eyewitnesses. In three experiments, lineup type was factorially combined with conditions expected to influence response criterion and/or discrimination accuracy. Results were consistent with signal detection theory predictions, including that of a conservative criterion shift with the sequential presentation of lineups. In a fourth experiment, we explored the phenomenological basis for the criterion shift, using the remember-know-guess procedure. In accord with previous research, the criterion shift in sequential lineups was associated with a reduction in familiarity-based responding. It is proposed that the relative similarity between lineup members may create a context in which fluency-based processing is facilitated to a greater extent when lineup members are presented simultaneously.

Sequential and Simultaneous Processing Abilities of High-Functioning Autistic and Language-Impaired Children.

Science.gov (United States)

Allen, Mark H.; And Others

1991-01-01

This study found that a group of 20 children (ages 6-12) with autism and a group of 20 children with developmental receptive language disorder both manifested a relative sequential processing deficit. The groups did not differ significantly on overall sequential and simultaneous processing capabilities relative to their degree of language…

Sequential boundaries approach in clinical trials with unequal allocation ratios

Directory of Open Access Journals (Sweden)

Ayatollahi Seyyed

2006-01-01

Full Text Available Abstract Background In clinical trials, both unequal randomization design and sequential analyses have ethical and economic advantages. In the single-stage-design (SSD, however, if the sample size is not adjusted based on unequal randomization, the power of the trial will decrease, whereas with sequential analysis the power will always remain constant. Our aim was to compare sequential boundaries approach with the SSD when the allocation ratio (R was not equal. Methods We evaluated the influence of R, the ratio of the patients in experimental group to the standard group, on the statistical properties of two-sided tests, including the two-sided single triangular test (TT, double triangular test (DTT and SSD by multiple simulations. The average sample size numbers (ASNs and power (1-β were evaluated for all tests. Results Our simulation study showed that choosing R = 2 instead of R = 1 increases the sample size of SSD by 12% and the ASN of the TT and DTT by the same proportion. Moreover, when R = 2, compared to the adjusted SSD, using the TT or DTT allows to retrieve the well known reductions of ASN observed when R = 1, compared to SSD. In addition, when R = 2, compared to SSD, using the TT and DTT allows to obtain smaller reductions of ASN than when R = 1, but maintains the power of the test to its planned value. Conclusion This study indicates that when the allocation ratio is not equal among the treatment groups, sequential analysis could indeed serve as a compromise between ethicists, economists and statisticians.

Immediately sequential bilateral cataract surgery: advantages and disadvantages.

Science.gov (United States)

Singh, Ranjodh; Dohlman, Thomas H; Sun, Grace

2017-01-01

The number of cataract surgeries performed globally will continue to rise to meet the needs of an aging population. This increased demand will require healthcare systems and providers to find new surgical efficiencies while maintaining excellent surgical outcomes. Immediately sequential bilateral cataract surgery (ISBCS) has been proposed as a solution and is increasingly being performed worldwide. The purpose of this review is to discuss the advantages and disadvantages of ISBCS. When appropriate patient selection occurs and guidelines are followed, ISBCS is comparable with delayed sequential bilateral cataract surgery in long-term patient satisfaction, visual acuity and complication rates. In addition, the risk of bilateral postoperative endophthalmitis and concerns of poorer refractive outcomes have not been supported by the literature. ISBCS is cost-effective for the patient, healthcare payors and society, but current reimbursement models in many countries create significant financial barriers for facilities and surgeons. As demand for cataract surgery rises worldwide, ISBCS will become increasingly important as an alternative to delayed sequential bilateral cataract surgery. Advantages include potentially decreased wait times for surgery, patient convenience and cost savings for healthcare payors. Although they are comparable in visual acuity and complication rates, hurdles that prevent wide adoption include liability concerns as ISBCS is not an established standard of care, economic constraints for facilities and surgeons and inability to fine-tune intraocular lens selection in the second eye. Given these considerations, an open discussion regarding the advantages and disadvantages of ISBCS is important for appropriate patient selection.

Accurately controlled sequential self-folding structures by polystyrene film

Science.gov (United States)

Deng, Dongping; Yang, Yang; Chen, Yong; Lan, Xing; Tice, Jesse

2017-08-01

Four-dimensional (4D) printing overcomes the traditional fabrication limitations by designing heterogeneous materials to enable the printed structures evolve over time (the fourth dimension) under external stimuli. Here, we present a simple 4D printing of self-folding structures that can be sequentially and accurately folded. When heated above their glass transition temperature pre-strained polystyrene films shrink along the XY plane. In our process silver ink traces printed on the film are used to provide heat stimuli by conducting current to trigger the self-folding behavior. The parameters affecting the folding process are studied and discussed. Sequential folding and accurately controlled folding angles are achieved by using printed ink traces and angle lock design. Theoretical analyses are done to guide the design of the folding processes. Programmable structures such as a lock and a three-dimensional antenna are achieved to test the feasibility and potential applications of this method. These self-folding structures change their shapes after fabrication under controlled stimuli (electric current) and have potential applications in the fields of electronics, consumer devices, and robotics. Our design and fabrication method provides an easy way by using silver ink printed on polystyrene films to 4D print self-folding structures for electrically induced sequential folding with angular control.