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

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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.

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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.

Disaster and Contingency Planning for Scientific Shared Resource Cores

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Wilkerson, Amy

2016-01-01

Progress in biomedical research is largely driven by improvements, innovations, and breakthroughs in technology, accelerating the research process, and an increasingly complex collaboration of both clinical and basic science. This increasing sophistication has driven the need for centralized shared resource cores (“cores”) to serve the scientific community. From a biomedical research enterprise perspective, centralized resource cores are essential to increased scientific, operational, and cost effectiveness; however, the concentration of instrumentation and resources in the cores may render them highly vulnerable to damage from severe weather and other disasters. As such, protection of these assets and the ability to recover from a disaster is increasingly critical to the mission and success of the institution. Therefore, cores should develop and implement both disaster and business continuity plans and be an integral part of the institution’s overall plans. Here we provide an overview of key elements required for core disaster and business continuity plans, guidance, and tools for developing these plans, and real-life lessons learned at a large research institution in the aftermath of Superstorm Sandy. PMID:26848285

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.

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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.

Frequency of BCR-ABL Transcript Types in Syrian CML Patients

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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.

Development and psychometric evaluation of the Core Nurse Resource Scale.

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Simpson, Michelle R

2010-11-01

To examine the factor structure, internal consistency reliability and concurrent-related validity of the Core Nurse Resource Scale. A cross-sectional survey study design was used to obtain a sample of 149 nurses and nursing staff [Registered Nurse (RNs), Licensed Practical Nurse (LPNs) and Certified Nursing Assistant (CNAs)] working in long-term care facilities. Exploratory factor analysis, Cronbach's alpha and bivariate correlations were used to evaluate validity and reliability. Exploratory factor analysis yielded a scale with 18 items on three factors, accounting for 52% of the variance in scores. Internal consistency reliability for the composite and Core Nurse Resource Scale factors ranged from 0.79 to 0.91. The Core Nurse Resource Scale composite scale and subscales correlated positively with a measure of work engagement (r=0.247-0.572). The initial psychometric evaluation of the Core Nurse Resource Scale demonstrates it is a sound measure. Further validity and reliability assessment will need to be explored and assessed among nurses and other nursing staff working in other practice settings. The intent of the Core Nurse Resource Scale is to evaluate the presence of physical, psychological and social resources of the nursing work environment, to identify workplaces at risk for disengaged (low work engagement) nursing staff and to provide useful diagnostic information to healthcare administrators interested in interventions to improve the nursing work environment. © 2010 The Author. Journal compilation © 2010 Blackwell Publishing Ltd.

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

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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.

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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.

Family Resources and Flourishing at Work: The Role of Core Self-Evaluations

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Larissa Maria David Gabardo-Martins

Full Text Available Abstract: According to the Work-Home Resources Model, contextual family resources increase personal resources, which, in turn, improve work outcomes. The present study investigated the direct effects of two contextual family resources (work- family enrichment and perceived social support from family and one personal resource (core self-evaluations on a work outcome (flourishing at work. The mediational role of core self-evaluations in these relationships was also investigated. The sample was composed of 519 Brazilian psychologists of both sexes. The Structural Equation Modeling showed that the contextual family resources and the personal resource predicted flourishing at work and that core self-evaluations mediated the relationships between contextual resources and flourishing at work. It was concluded that the acquisition of resources within the family and the positive evaluation of one’s own life can promote flourishing at work.

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

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Costa Juliana

2010-11-01

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

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.

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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.

Core competencies for natural resource negotiation

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Gillette, S.C.; Lamb, B.L.

2005-01-01

Natural resource negotiation often involves multiple parties with overlapping interests and issues that can provide opportunities for mutually beneficial solutions. These opportunities can be missed, however, if negotiators are unable to comprehend the facts of a negotiation, understand the interests of other parties, or accurately evaluate the options that increase the size of the negotiation pie. Through structured personal interviews with more than 60 representatives from seven different hydropower negotiations, respondents identified core competencies that help negotiators succeed at accurately comprehending the facts of a negotiation, comprehending the interests of other parties, and fully understanding the available options and alternatives. We categorized those core competencies into three dimensions of negotiation - interpersonal, organizational, and operational.

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

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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.

Resource-agnostic programming for many-core microgrids

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Bernard, T.A.M.; Grelck, C.; Hicks, M.A.; Jesshope, C.R.; Poss, R.; Forsell, M.; Träff, J.L.

2010-01-01

Many-core architectures are a commercial reality, but programming them efficiently is still a challenge, especially if the mix is heterogeneous. Here granularity must be addressed, i.e. when to make use of concurrency resources and when not to. We have designed a data-driven, fine-grained concurrent

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.

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

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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

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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

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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.

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

International Nuclear Information System (INIS)

Sutherland, Ross A.

2010-01-01

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

The core business web a guide to key information resources

CERN Document Server

White, Gary W

2013-01-01

The best Business Web sites at your fingertips—24/7! The Core Business Web: A Guide to Key Information Resources is an essential resource that saves you from spending hours searching through thousands of Web sites for the business information you need. A distinguished panel of authors, all active in business librarianship, explores Web sites in their subject areas, selecting the very best from 25 functional areas of business. Each site was chosen based on the timeliness, relevance and reliability of its content, the site's ease of navigation and use, and the authority of the site's author or publisher. The rapid growth of the Internet has resulted in an ever-increasing number of Web sites offering potentially useful business information. The Core Business Web identifies, evaluates, and summarizes the most significant sites, including gateways or portals, directories, and meta-sites, to organize online resources into easy-to-follow links that allow you to access information quickly. Sites are categorized and ...

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

Directory of Open Access Journals (Sweden)

Irene Larripa

2017-02-01

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

Multi-core job submission and grid resource scheduling for ATLAS AthenaMP

CERN Document Server

Crooks, D; The ATLAS collaboration; Harrington, R; Purdie, S; Severini, H; Skipsey, S; Tsulaia, V; Washbrook, A

2012-01-01

AthenaMP is the multi-core implementation of the ATLAS software framework and allows the efficient sharing of memory pages between multiple threads of execution. This has now been validated for production and delivers a significant reduction on overall memory footprint with negligible CPU overhead. Before AthenaMP can be routinely run on the LHC Computing Grid, it must be determined how the computing resources available to ATLAS can best exploit the notable improvements delivered by switching to this multi-process model. In particular, there is a need to identify and assess the potential impact of scheduling issues where single core and multi-core job queues have access to the same underlying resources. A study into the effectiveness and scalability of AthenaMP in a production environment will be presented. Submitting AthenaMP tasks to the Tier-0 and candidate Tier-2 sites will allow detailed measurement of worker node performance and also highlight the relative performance of local resource management system...

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.

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.

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....

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

Science.gov (United States)

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

2009-01-01

SUMMARY Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABLT315I mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and pre-clinical evaluation of AP24534, a potent, orally available multi-targeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABLT315I-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML. PMID:19878872

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-09-07

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

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

Directory of Open Access Journals (Sweden)

Cano Pedro

2004-06-01

Full Text Available Abstract Background Based on the site of breakpoint in t(9;22 (q34;q11, bcr-abl fusion in leukemia patients is associated with different types of transcript proteins. In this study we have seen the association of HLA genes with different types of bcr-abl transcripts. The association could predict the bcr-abl peptide presentation by particular HLA molecules. Methods The study included a total of 189 patients of mixed ethnicity with chronic myelogenous leukemia and acute lymphocytic leukemia who were being considered for bone marrow transplantation. Typing of bcr-abl transcripts was done by reverse transcriptase PCR method. HLA typing was performed by molecular methods. The bcr-abl and HLA association was studied by calculating the relative risks and chi-square test. Results Significant negative associations (p Conclusions The negative associations of a particular bcr-abl transcript with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and eliciting a successful T-cell cytotoxic response. Knowledge of differential associations between HLA phenotypes and bcr-abl fusion transcript types would help in developing better strategies for immunization with the bcr-abl peptides against t(9;22 (q34;q11-positive leukemia.

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

Directory of Open Access Journals (Sweden)

Soumya Panigrahi

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

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 ...

Structure analysis and core community detection of embodied resources networks among regional industries

Science.gov (United States)

He, Xijun; Dong, Yanbo; Wu, Yuying; Wei, Guodan; Xing, Lizhi; Yan, Jia

2017-08-01

To address the double pressure of scarce resources and regional industrial isomorphism, this paper applied the concepts of exergy and embodied resources based on economic input-output (I-O) data. We constructed the embodied resources networks among the regional industries of Beijing-Tianjin-Hebei (also known as Jing-Jin-Ji) in China. We analyzed the rules of embodied resources consumption in the area's industries, identified the core community structures, and studied the characteristics of industrial homogeneity through regional comparisons. The results showed that the dependence on scarce resources of industrial operations in Beijing was less than in Jin-Ji, while the dependence on finance, technology, information, and other service resources in Beijing was higher than in Jin-Ji. The I-O efficiency of embodied resources among industries and the agglomeration of correlation relationships in industries with large embodied resources were higher than in Jin-Ji. The industrial coincidence degree in the ;bridge; industries and in the core community in Jin-Ji was higher than in Jing-Jin and Jing-Ji, which means the industrial homogeneous competition of Jin-Ji was higher, too. This study makes a significant contribution toward promoting the dislocation development of regional industries, accelerating the coordination of resources, and reducing homogeneity competition.

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.

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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.

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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.

How Well Are American Students Learning? With Sections on Reading and Math in the Common Core Era, Tracking and Advanced Placement (AP), and Principals as Instructional Leaders. The 2016 Brown Center Report on American Education. Volume 3, Number 5

Science.gov (United States)

Loveless, Tom

2016-01-01

The 2016 edition of the Brown Center Report (BCR) is number five in the third volume and the 15th issue overall. As is customary, this year's BCR contains three studies. Part one is on the Common Core State Standards (CCSS) and instruction in math and reading. National Assessment of Educational Progress (NAEP) data indicate that nonfiction is…

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.

Nuclear Human Resources Development Program using Educational Core Simulator

International Nuclear Information System (INIS)

Choi, Yu Sun; Hong, Soon Kwan

2015-01-01

KHNP-CRI(Korea Hydro and Nuclear Power Co.-Central Research Institute) has redesigned the existing Core Simulator(CoSi) used as a sort of training tools for reactor engineers in operating nuclear power plant to support Nuclear Human Resources Development (NHRD) Program focusing on the nuclear department of Dalat university in Vietnam. This program has been supported by MOTIE in Korea and cooperated with KNA(Korea Nuclear Association for International Cooperation) and HYU(Hanyang University) for enhancing the nuclear human resources of potential country in consideration with Korean Nuclear Power Plant as a next candidate energy sources. KHNP-CRI has provided Edu-CoSi to Dalat University in Vietnam in order to support Nuclear Human Resources Development Program in Vietnam. Job Qualification Certificates Program in KHNP is utilized to design a training course for Vietnamese faculty and student of Dalat University. Successfully, knowhow on lecturing the ZPPT performance, training and maintaining Edu-CoSi hardware are transferred by several training courses which KHNP-CRI provides

Nuclear Human Resources Development Program using Educational Core Simulator

Energy Technology Data Exchange (ETDEWEB)

Choi, Yu Sun; Hong, Soon Kwan [KHNP-CRI, Daejeon (Korea, Republic of)

2015-10-15

KHNP-CRI(Korea Hydro and Nuclear Power Co.-Central Research Institute) has redesigned the existing Core Simulator(CoSi) used as a sort of training tools for reactor engineers in operating nuclear power plant to support Nuclear Human Resources Development (NHRD) Program focusing on the nuclear department of Dalat university in Vietnam. This program has been supported by MOTIE in Korea and cooperated with KNA(Korea Nuclear Association for International Cooperation) and HYU(Hanyang University) for enhancing the nuclear human resources of potential country in consideration with Korean Nuclear Power Plant as a next candidate energy sources. KHNP-CRI has provided Edu-CoSi to Dalat University in Vietnam in order to support Nuclear Human Resources Development Program in Vietnam. Job Qualification Certificates Program in KHNP is utilized to design a training course for Vietnamese faculty and student of Dalat University. Successfully, knowhow on lecturing the ZPPT performance, training and maintaining Edu-CoSi hardware are transferred by several training courses which KHNP-CRI provides.

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.

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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.

Dynamic optical resource allocation for mobile core networks with software defined elastic optical networking.

Science.gov (United States)

Zhao, Yongli; Chen, Zhendong; Zhang, Jie; Wang, Xinbo

2016-07-25

Driven by the forthcoming of 5G mobile communications, the all-IP architecture of mobile core networks, i.e. evolved packet core (EPC) proposed by 3GPP, has been greatly challenged by the users' demands for higher data rate and more reliable end-to-end connection, as well as operators' demands for low operational cost. These challenges can be potentially met by software defined optical networking (SDON), which enables dynamic resource allocation according to the users' requirement. In this article, a novel network architecture for mobile core network is proposed based on SDON. A software defined network (SDN) controller is designed to realize the coordinated control over different entities in EPC networks. We analyze the requirement of EPC-lightpath (EPCL) in data plane and propose an optical switch load balancing (OSLB) algorithm for resource allocation in optical layer. The procedure of establishment and adjustment of EPCLs is demonstrated on a SDON-based EPC testbed with extended OpenFlow protocol. We also evaluate the OSLB algorithm through simulation in terms of bandwidth blocking ratio, traffic load distribution, and resource utilization ratio compared with link-based load balancing (LLB) and MinHops algorithms.

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.

Optimisation of beryllium-7 gamma analysis following BCR sequential extraction

International Nuclear Information System (INIS)

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

2012-01-01

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

Core clerkship directors: their current resources and the rewards of the role.

Science.gov (United States)

Ephgrave, Kimberly; Margo, Katherine L; White, Christopher; Hammoud, Maya; Brodkey, Amy; Painter, Thomas; Juel, Vern C; Shaw, Darlene; Ferguson, Kristi

2010-04-01

To conduct a national multidisciplinary investigation assessing core clinical clerkships and their directors, variances in resources from national guidelines, and the impact of the clerkship director role on faculty members' academic productivity, advancement, and satisfaction. A multidisciplinary working group of the Alliance for Clinical Education (ACE), representing all seven core clinical disciplines, created and distributed a survey to clerkship directors at 125 U.S. MD-granting medical schools, in academic year 2006-2007. A total of 544 clerkship directors from Internal Medicine (96), Family Medicine (91), Psychiatry, (91), Pediatrics (79), Surgery (71), Neurology (60), and Obstetrics-Gynecology (56) responded, representing over 60% of U.S. core clinical clerkships. The clerkship directors were similar across disciplines in demographics and academic productivity, though clinical and clerkship activities varied. Departmental staff support for clerkships averaged 0.69 people, distinctly less than the ACE's 2003 guideline of a full-time coordinator in all disciplines' clerkships. Clerkship directors reported heavy clinical responsibilities, which, as in previous studies, were negatively related to academic productivity. However, many clerkship directors felt the role enhanced their academic advancement; a large majority felt it significantly enhanced their career satisfaction. The resources and rewards of the clerkship director role were similar across disciplines. Expectations of clerkship directors were considerable, including responsibility for clinical material and the learning environment. Resources for many fall short of those stated in the ACE guidelines, particularly regarding support staff. However, the findings indicate that the clerkship director role can have benefits for academic advancement and strongly enhances career satisfaction.

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

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.

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

Directory of Open Access Journals (Sweden)

Qianyin Li

2017-03-01

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

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.

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

The Value Creation Strategies and Core Resources of the Companies in the Digital Archives Industry

Directory of Open Access Journals (Sweden)

Mei-Ya Wang

2012-06-01

Full Text Available The digital archives industry that adds value to digitized cultural assets is of high interest today. The current study adopted a value creation perspective to examine and compare two case companies’ business strategies and core resources upon which value is created. Case A represented a value adding approach, in which the company’s business activities are concentrated on the upstream and downstream authorization of the digital objects. Case B represented a design and application approach, in which profits were generated from the creative use of cultural elements extracted from digital archives in original product design. The core resources of the two cases varied accordingly. Case A drew on its reputation, ownership of use rights, management capabilities, relation networks, and operational capabilities, while Case B drew on resources including reputation, management capabilities, and expertise in product design and commercialization. [Article content in Chinese

Partnership between CTSI and business schools can promote best practices for core facilities and resources.

Science.gov (United States)

Reeves, Lilith; Dunn-Jensen, Linda M; Baldwin, Timothy T; Tatikonda, Mohan V; Cornetta, Kenneth

2013-08-01

Biomedical research enterprises require a large number of core facilities and resources to supply the infrastructure necessary for translational research. Maintaining the financial viability and promoting efficiency in an academic environment can be particularly challenging for medical schools and universities. The Indiana Clinical and Translational Sciences Institute sought to improve core and service programs through a partnership with the Indiana University Kelley School of Business. The program paired teams of Masters of Business Administration students with cores and programs that self-identified the need for assistance in project management, financial management, marketing, or resource efficiency. The projects were developed by CTSI project managers and business school faculty using service-learning principles to ensure learning for students who also received course credit for their participation. With three years of experience, the program demonstrates a successful partnership that improves clinical research infrastructure by promoting business best practices and providing a valued learning experience for business students. © 2013 Wiley Periodicals, Inc.

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

Evaluation of Selected Resource Allocation and Scheduling Methods in Heterogeneous Many-Core Processors and Graphics Processing Units

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Ciznicki Milosz

2014-12-01

Full Text Available Heterogeneous many-core computing resources are increasingly popular among users due to their improved performance over homogeneous systems. Many developers have realized that heterogeneous systems, e.g. a combination of a shared memory multi-core CPU machine with massively parallel Graphics Processing Units (GPUs, can provide significant performance opportunities to a wide range of applications. However, the best overall performance can only be achieved if application tasks are efficiently assigned to different types of processor units in time taking into account their specific resource requirements. Additionally, one should note that available heterogeneous resources have been designed as general purpose units, however, with many built-in features accelerating specific application operations. In other words, the same algorithm or application functionality can be implemented as a different task for CPU or GPU. Nevertheless, from the perspective of various evaluation criteria, e.g. the total execution time or energy consumption, we may observe completely different results. Therefore, as tasks can be scheduled and managed in many alternative ways on both many-core CPUs or GPUs and consequently have a huge impact on the overall computing resources performance, there are needs for new and improved resource management techniques. In this paper we discuss results achieved during experimental performance studies of selected task scheduling methods in heterogeneous computing systems. Additionally, we present a new architecture for resource allocation and task scheduling library which provides a generic application programming interface at the operating system level for improving scheduling polices taking into account a diversity of tasks and heterogeneous computing resources characteristics.

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...

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.

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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

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.

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 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

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

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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.

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

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.

Optimisation of beryllium-7 gamma analysis following BCR sequential extraction

Energy Technology Data Exchange (ETDEWEB)

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

2012-03-30

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

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

Directory of Open Access Journals (Sweden)

Eduardo Vinícius Vieira Varejão

2009-08-01

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

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

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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.

Proteomics Core

Data.gov (United States)

Federal Laboratory Consortium — Proteomics Core is the central resource for mass spectrometry based proteomics within the NHLBI. The Core staff help collaborators design proteomics experiments in a...

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.

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 ...

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

International Nuclear Information System (INIS)

Kartal, Senol; Aydin, Zeki; Tokalioglu, Serife

2006-01-01

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

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.

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.

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.)

Prevention and control of rheumatic heart disease: Overcoming core challenges in resource-poor environments

Science.gov (United States)

Dougherty, Scott; Beaton, Andrea; Nascimento, Bruno R; Zühlke, Liesl J; Khorsandi, Maziar; Wilson, Nigel

2018-01-01

Rheumatic heart disease (RHD) has long receded as a significant threat to public health in high-income countries. In low-resource settings, however, the specter of RHD remains unabated, as exemplified by recent data from the Global Burden of Diseases Study. There are many complex reasons for this ongoing global disparity, including inadequate data on disease burden, challenges in effective advocacy, ongoing poverty and inequality, and weak health systems, most of which predominantly affect developing nations. In this review, we discuss how each of these acts as a core challenge in RHD prevention and control. We then examine key lessons learnt from successful control programs in the past and highlight resources that have been developed to help create strong national RHD control programs. PMID:29440834

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.

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.

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

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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

Reconfiguration of Computation and Communication Resources in Multi-Core Real-Time Embedded Systems

DEFF Research Database (Denmark)

Pezzarossa, Luca

-core platform. Our approach is to associate reconfiguration with operational mode changes where the system, during normal operation, changes a subset of the executing tasks to adapt its behaviour to new conditions. Reconfiguration is therefore used during a mode change to modify the real-time guaranteed services...... of the communication channels between the tasks that are affected by the reconfiguration. This thesis investigates the use of reconfiguration in the context of multicore realtime systems targeting embedded applications. We address the reconfiguration of both the computation and the communication resources of a multi...... by the communication fabric between the cores of the platform. To support this, we present a new network on chip architecture, named Argo 2, that allows instantaneous and time-predictable reconfiguration of the communication channels. Our reconfiguration-capable architecture is prototyped using the existing time...

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.

Low expression of miR-196b enhances the expression of BCR-ABL1 and HOXA9 oncogenes in chronic myeloid leukemogenesis.

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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

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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

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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

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

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.

Discovery and publishing of primary biodiversity data associated with multimedia resources: The Audubon Core strategies and approaches

Directory of Open Access Journals (Sweden)

Robert A Morris

2013-07-01

Full Text Available The Audubon Core Multimedia Resource Metadata Schema is a representation-free vocabulary for the description of biodiversity multimedia resources and collections, now in the final stages as a proposed Biodiversity Informatics Standards (TDWG standard. By defining only six terms as mandatory, it seeks to lighten the burden for providing or using multimedia useful for biodiversity science. At the same time it offers rich optional metadata terms that can help curators of multimedia collections provide authoritative media that document species occurrence, ecosystems, identification tools, ontologies, and many other kinds of biodiversity documents or data. About half of the vocabulary is re-used from other relevant controlled vocabularies that are often already in use for multimedia metadata, thereby reducing the mapping burden on existing repositories. A central design goal is to allow consuming applications to have a high likelihood of discovering suitable resources, reducing the human examination effort that might be required to decide if the resource is fit for the purpose of the application.

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.

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.

CMS readiness for multi-core workload scheduling

Science.gov (United States)

Perez-Calero Yzquierdo, A.; Balcas, J.; Hernandez, J.; Aftab Khan, F.; Letts, J.; Mason, D.; Verguilov, V.

2017-10-01

In the present run of the LHC, CMS data reconstruction and simulation algorithms benefit greatly from being executed as multiple threads running on several processor cores. The complexity of the Run 2 events requires parallelization of the code to reduce the memory-per- core footprint constraining serial execution programs, thus optimizing the exploitation of present multi-core processor architectures. The allocation of computing resources for multi-core tasks, however, becomes a complex problem in itself. The CMS workload submission infrastructure employs multi-slot partitionable pilots, built on HTCondor and GlideinWMS native features, to enable scheduling of single and multi-core jobs simultaneously. This provides a solution for the scheduling problem in a uniform way across grid sites running a diversity of gateways to compute resources and batch system technologies. This paper presents this strategy and the tools on which it has been implemented. The experience of managing multi-core resources at the Tier-0 and Tier-1 sites during 2015, along with the deployment phase to Tier-2 sites during early 2016 is reported. The process of performance monitoring and optimization to achieve efficient and flexible use of the resources is also described.

CMS Readiness for Multi-Core Workload Scheduling

Energy Technology Data Exchange (ETDEWEB)

Perez-Calero Yzquierdo, A. [Madrid, CIEMAT; Balcas, J. [Caltech; Hernandez, J. [Madrid, CIEMAT; Aftab Khan, F. [NCP, Islamabad; Letts, J. [UC, San Diego; Mason, D. [Fermilab; Verguilov, V. [CLMI, Sofia

2017-11-22

In the present run of the LHC, CMS data reconstruction and simulation algorithms benefit greatly from being executed as multiple threads running on several processor cores. The complexity of the Run 2 events requires parallelization of the code to reduce the memory-per- core footprint constraining serial execution programs, thus optimizing the exploitation of present multi-core processor architectures. The allocation of computing resources for multi-core tasks, however, becomes a complex problem in itself. The CMS workload submission infrastructure employs multi-slot partitionable pilots, built on HTCondor and GlideinWMS native features, to enable scheduling of single and multi-core jobs simultaneously. This provides a solution for the scheduling problem in a uniform way across grid sites running a diversity of gateways to compute resources and batch system technologies. This paper presents this strategy and the tools on which it has been implemented. The experience of managing multi-core resources at the Tier-0 and Tier-1 sites during 2015, along with the deployment phase to Tier-2 sites during early 2016 is reported. The process of performance monitoring and optimization to achieve efficient and flexible use of the resources is also described.

Multi-core processing and scheduling performance in CMS

CERN Multimedia

CERN. Geneva

2012-01-01

Commodity hardware is going many-core. We might soon not be able to satisfy the job memory needs per core in the current single-core processing model in High Energy Physics. In addition, an ever increasing number of independent and incoherent jobs running on the same physical hardware not sharing resources might significantly affect processing performance. It will be essential to effectively utilize the multi-core architecture. CMS has incorporated support for multi-core processing in the event processing framework and the workload management system. Multi-core processing jobs share common data in memory, such us the code libraries, detector geometry and conditions data, resulting in a much lower memory usage than standard single-core independent jobs. Exploiting this new processing model requires a new model in computing resource allocation, departing from the standard single-core allocation for a job. The experiment job management system needs to have control over a larger quantum of resource since multi-...

Effect of serum testosterone and percent tumor volume on extra-prostatic extension and biochemical recurrence after laparoscopic radical prostatectomy

Directory of Open Access Journals (Sweden)

Eu Chang Hwang

2016-01-01

Full Text Available Several studies have revealed that the preoperative serum testosterone and percent tumor volume (PTV predict extra-prostatic extension (EPE and biochemical recurrence (BCR after radical prostatectomy. This study investigated the prognostic significance of serum testosterone and PTV in relation to EPE and BCR after laparoscopic radical prostatectomy (LRP. We reviewed 520 patients who underwent LRP between 2004 and 2012. PTV was determined as the sum of all visually estimated tumor foci in every section. BCR was defined as two consecutive increases in the postoperative prostate-specific antigen (PSA >0.2 ng ml−1 . The threshold for serum total testosterone was 3.0 ng ml−1 . Multivariate logistic regression was used to define the effect of variables on the risk of EPE and BCR. A low serum testosterone (<3.0 ng ml−1 was associated with a high serum PSA, Gleason score, positive core percentage of the prostate biopsy, PTV, and all pathological variables. On multivariate analysis, similar to previous studies, the serum PSA, biopsy positive core percentage, Gleason score, and pathological variables predicted EPE and BCR. In addition, low serum testosterone (<3.0 ng ml−1 , adjusted OR, 8.52; 95% CI, 5.04-14.4, P= 0.001 predicted EPE and PTV (adjusted OR, 1.02; 95% CI, 1.01-1.05, P= 0.046 predicted BCR. In addition to previous predictors of EPE and BCR, low serum testosterone and PTV are valuable predictors of EPE and BCR after LRP.

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-01-30

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Hardware Implementation of LMS-Based Adaptive Noise Cancellation Core with Low Resource Utilization

Directory of Open Access Journals (Sweden)

Omid Sharifi Tehrani

2011-10-01

Full Text Available A hardware implementation of adaptive noise cancellation (ANC core is proposed. Adaptive filters are widely used in different applications such as adaptive noise cancellation, prediction, equalization, inverse modeling and system identification. FIR adaptive filters are mostly used because of their low computation costs and their linear phase. Least mean squared algorithm (LMS is used to train FIR adaptive filter weights. Advances in semiconductor technology especially in digital signal processors (DSP and field programmable gate arrays (FPGA with hundreds of mega hertz in speed, will allow digital designers to embed essential digital signal processing units in small chips. But designing a synthesizable core on an FPGA is not always as simple as DSP chips due to complexity and limitations of FPGAs. In this paper we design anLMS-based FIR adaptive filter for adaptive noise cancellation based on VHDL97 hardware description language (HDL and Xilinx SPARTAN3E (XC3S500E which utilizes low resources and is high performance and FPGA-brand independent so can be implemented on different FPGA brands (Xilinx, ALTERA, ACTEL. Simulations are done in MODELSIM and MATLAB and implementation is done with Xilinx ISE. Finally, result are compared with other papers for better judgment.

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.

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.

IGCSE core mathematics

CERN Document Server

Wall, Terry

2013-01-01

Give your core level students the support and framework they require to get their best grades with this book dedicated to the core level content of the revised syllabus and written specifically to ensure a more appropriate pace. This title has been written for Core content of the revised Cambridge IGCSE Mathematics (0580) syllabus for first teaching from 2013. ? Gives students the practice they require to deepen their understanding through plenty of practice questions. ? Consolidates learning with unique digital resources on the CD, included free with every book. We are working with Cambridge

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.

Multi-core processing and scheduling performance in CMS

International Nuclear Information System (INIS)

Hernández, J M; Evans, D; Foulkes, S

2012-01-01

Commodity hardware is going many-core. We might soon not be able to satisfy the job memory needs per core in the current single-core processing model in High Energy Physics. In addition, an ever increasing number of independent and incoherent jobs running on the same physical hardware not sharing resources might significantly affect processing performance. It will be essential to effectively utilize the multi-core architecture. CMS has incorporated support for multi-core processing in the event processing framework and the workload management system. Multi-core processing jobs share common data in memory, such us the code libraries, detector geometry and conditions data, resulting in a much lower memory usage than standard single-core independent jobs. Exploiting this new processing model requires a new model in computing resource allocation, departing from the standard single-core allocation for a job. The experiment job management system needs to have control over a larger quantum of resource since multi-core aware jobs require the scheduling of multiples cores simultaneously. CMS is exploring the approach of using whole nodes as unit in the workload management system where all cores of a node are allocated to a multi-core job. Whole-node scheduling allows for optimization of the data/workflow management (e.g. I/O caching, local merging) but efficient utilization of all scheduled cores is challenging. Dedicated whole-node queues have been setup at all Tier-1 centers for exploring multi-core processing workflows in CMS. We present the evaluation of the performance scheduling and executing multi-core workflows in whole-node queues compared to the standard single-core processing workflows.

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.

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)

[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.

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.

Towards Core Modelling Practices in Integrated Water Resource Management: An Interdisciplinary View of the Modelling Process

Science.gov (United States)

Jakeman, A. J.; Elsawah, S.; Pierce, S. A.; Ames, D. P.

2016-12-01

The National Socio-Environmental Synthesis Center (SESYNC) Core Modelling Practices Pursuit is developing resources to describe core practices for developing and using models to support integrated water resource management. These practices implement specific steps in the modelling process with an interdisciplinary perspective; however, the particular practice that is most appropriate depends on contextual aspects specific to the project. The first task of the pursuit is to identify the various steps for which implementation practices are to be described. This paper reports on those results. The paper draws on knowledge from the modelling process literature for environmental modelling (Jakeman et al., 2006), engaging stakeholders (Voinov and Bousquet, 2010) and general modelling (Banks, 1999), as well as the experience of the consortium members. We organise the steps around the four modelling phases. The planning phase identifies what is to be achieved, how and with what resources. The model is built and tested during the construction phase, and then used in the application phase. Finally, models that become part of the ongoing policy process require a maintenance phase. For each step, the paper focusses on what is to be considered or achieved, rather than how it is performed. This reflects the separation of the steps from the practices that implement them in different contexts. We support description of steps with a wide range of examples. Examples are designed to be generic and do not reflect any one project or context, but instead are drawn from common situations or from extremely different ones so as to highlight some of the issues that may arise at each step. References Banks, J. (1999). Introduction to simulation. In Proceedings of the 1999 Winter Simulation Conference. Jakeman, A. J., R. A. Letcher, and J. P. Norton (2006). Ten iterative steps in development and evaluation of environmental models. Environmental Modelling and Software 21, 602-614. Voinov, A

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

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.

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

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

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

Constructing Web subject gateways using Dublin Core, the Resource Description Framework and Topic Maps

Directory of Open Access Journals (Sweden)

Jesús Tramullas

2006-01-01

Full Text Available Introduction. Specialised subject gateways have become an essential tool for locating and accessing digital information resources, with the added value of organisation and previous evaluation catering for the needs of the varying communities using these. Within the framework of a research project on the subject, a software tool has been developed that enables subject gateways to be developed and managed. Method. General guidelines for the work were established which set out the main principles for the technical aspects of the application, on one hand, and on aspects of the treatment and management of information, on the other. All this has been integrated into a prototype model for developing software tools. Analysis. The needs analysis established the conditions to be fulfilled by the application. A detailed study of the available options for the treatment of information on metadata proved that the best option was to use the Dublin Core, and that the metadata set should be included, in turn, in RDF tags, or in tags based on XML. Results. The project has resulted in the development of two versions of an application called Potnia (versions 1 and 2, which fulfil the requirements set out in the main principles, and which have been tested by users in real application environments. Conclusion. The tagging layout found to be the best, and the one used by the writers, is based on integrating the Dublin Core metadata set within the Topic Maps paradigm, formatted in XTM.

Human Resources Operational Data Store Core Services

Data.gov (United States)

Social Security Administration — This database contains only a very small subset of the Human Resources Operational Data Store data. It supports the SSA Employee and Office Data Retrieval (SEODR)...

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.

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.

Quality of core collections for effective utilisation of genetic resources review, discussion and interpretation.

Science.gov (United States)

Odong, T L; Jansen, J; van Eeuwijk, F A; van Hintum, T J L

2013-02-01

Definition of clear criteria for evaluation of the quality of core collections is a prerequisite for selecting high-quality cores. However, a critical examination of the different methods used in literature, for evaluating the quality of core collections, shows that there are no clear guidelines on the choices of quality evaluation criteria and as a result, inappropriate analyses are sometimes made leading to false conclusions being drawn regarding the quality of core collections and the methods to select such core collections. The choice of criteria for evaluating core collections appears to be based mainly on the fact that those criteria have been used in earlier publications rather than on the actual objectives of the core collection. In this study, we provide insight into different criteria used for evaluating core collections. We also discussed different types of core collections and related each type of core collection to their respective evaluation criteria. Two new criteria based on genetic distance are introduced. The consequences of the different evaluation criteria are illustrated using simulated and experimental data. We strongly recommend the use of the distance-based criteria since they not only allow the simultaneous evaluation of all variables describing the accessions, but they also provide intuitive and interpretable criteria, as compared with the univariate criteria generally used for the evaluation of core collections. Our findings will provide genebank curators and researchers with possibilities to make informed choices when creating, comparing and using core collections.

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.

PERIPHERY/CORE RELATIONS IN THE INCA EMPIRE CARROTS AND STICKS IN AN ANDEAN WORLD SYSTEM

OpenAIRE

Lawrence A. Kuznar

2015-01-01

The Inca Empire exhibited labor exploitation and the rational extraction of resources from peripheral polities by a core polity. These characteristics fit the general definition of a world empire, although core/periphery relations were diverse. The nature of core/periphery relations depended on several attributes of the conquered polity including population size, political power, natural resources, and distance from the Inca core at Cuzco. A dynamic picture of core/periphery relations emerges...

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.

Statistics Online Computational Resource for Education

Science.gov (United States)

Dinov, Ivo D.; Christou, Nicolas

2009-01-01

The Statistics Online Computational Resource (http://www.SOCR.ucla.edu) provides one of the largest collections of free Internet-based resources for probability and statistics education. SOCR develops, validates and disseminates two core types of materials--instructional resources and computational libraries. (Contains 2 figures.)

FORMATION OF ENTERPRISE INTELLECTUAL CAPITAL IN CONTEXT OF RESOURCE THEORY

Directory of Open Access Journals (Sweden)

N. Revutska

2013-08-01

Full Text Available The main content of the resource theory and description of it evolution in three stages were considered in this article. The first stage was the formation of the classical concept of the resource, the second – the origin and development of the concept of core competencies and dynamic organizational capabilities, and the third is associated with the formation of the theory of resource advantages. The nature and the necessity to identify new resource elements (core competencies, dynamic capabilities and organizational routines were characterized in the context of the selected stages. The signs of sustainable competitive advantage and types of economic rents that arise on the resource base were generalized. There is a connection between resource theory and concept of knowledge management based on identification of intellectual component in the economic nature of the core competencies and organizational abilities. The basic approach to the classification of resources and their elements, which form the intellectual capital of the company was described. New elements of economic resources such as competencies, organizational abilities, rutin and elements of intellectual capital are in close connection. It is concluded that the core competencies are best developed in human client and networking elements of intellectual capital, dynamic organizational capability in innovative capital and routines in process capital of an enterprise.

Compact multipurpose sub-sampling and processing of in-situ cores with press (pressurized core sub-sampling and extrusion system)

Energy Technology Data Exchange (ETDEWEB)

Anders, E.; Muller, W.H. [Technical Univ. of Berlin, Berlin (Germany). Chair of Continuum Mechanics and Material Theory

2008-07-01

Climate change, declining resources and over-consumption result in a need for sustainable resource allocation, habitat conservation and claim for new technologies and prospects for damage-containment. In order to increase knowledge of the environment and to define potential hazards, it is necessary to get an understanding of the deep biosphere. In addition, the benthic conditions of sediment structure and gas hydrates, temperature, pressure and bio-geochemistry must be maintained during the sequences of sampling, retrieval, transfer, storage and downstream analysis. In order to investigate highly instable gas hydrates, which decomposes under pressure and temperature change, a suite of research technologies have been developed by the Technische Universitat Berlin (TUB), Germany. This includes the pressurized core sub-sampling and extrusion system (PRESS) that was developed in the European Union project called HYACE/HYACINTH. The project enabled well-defined sectioning and transfer of drilled pressure-cores obtained by a rotary corer and fugro pressure corer into transportation and investigation chambers. This paper described HYACINTH pressure coring and the HYACINTH core transfer. Autoclave coring tools and HYACINTH core logging, coring tools, and sub-sampling were also discussed. It was concluded that possible future applications include, but were not limited to, research in shales and other tight formations, carbon dioxide sequestration, oil and gas exploration, coalbed methane, and microbiology of the deep biosphere. To meet the corresponding requirements and to incorporate the experiences from previous expeditions, the pressure coring system would need to be redesigned to adapt it to the new applications. 3 refs., 5 figs.

Sharing network resources

CERN Document Server

Parekh, Abhay

2014-01-01

Resource Allocation lies at the heart of network control. In the early days of the Internet the scarcest resource was bandwidth, but as the network has evolved to become an essential utility in the lives of billions, the nature of the resource allocation problem has changed. This book attempts to describe the facets of resource allocation that are most relevant to modern networks. It is targeted at graduate students and researchers who have an introductory background in networking and who desire to internalize core concepts before designing new protocols and applications. We start from the fun

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.)

Digital Core Modelling for Clastic Oil and Gas Reservoir

Science.gov (United States)

Belozerov, I.; Berezovsky, V.; Gubaydullin, M.; Yur’ev, A.

2018-05-01

"Digital core" is a multi-purpose tool for solving a variety of tasks in the field of geological exploration and production of hydrocarbons at various stages, designed to improve the accuracy of geological study of subsurface resources, the efficiency of reproduction and use of mineral resources, as well as applying the results obtained in production practice. The actuality of the development of the "Digital core" software is that even a partial replacement of natural laboratory experiments with mathematical modelling can be used in the operative calculation of reserves in exploratory drilling, as well as in the absence of core material from wells. Or impossibility of its research by existing laboratory methods (weakly cemented, loose, etc. rocks). 3D-reconstruction of the core microstructure can be considered as a cheap and least time-consuming method for obtaining petrophysical information about the main filtration-capacitive properties and fluid motion in reservoir rocks.

[caCORE: core architecture of bioinformation on cancer research in America].

Science.gov (United States)

Gao, Qin; Zhang, Yan-lei; Xie, Zhi-yun; Zhang, Qi-peng; Hu, Zhang-zhi

2006-04-18

A critical factor in the advancement of biomedical research is the ease with which data can be integrated, redistributed and analyzed both within and across domains. This paper summarizes the Biomedical Information Core Infrastructure built by National Cancer Institute Center for Bioinformatics in America (NCICB). The main product from the Core Infrastructure is caCORE--cancer Common Ontologic Reference Environment, which is the infrastructure backbone supporting data management and application development at NCICB. The paper explains the structure and function of caCORE: (1) Enterprise Vocabulary Services (EVS). They provide controlled vocabulary, dictionary and thesaurus services, and EVS produces the NCI Thesaurus and the NCI Metathesaurus; (2) The Cancer Data Standards Repository (caDSR). It provides a metadata registry for common data elements. (3) Cancer Bioinformatics Infrastructure Objects (caBIO). They provide Java, Simple Object Access Protocol and HTTP-XML application programming interfaces. The vision for caCORE is to provide a common data management framework that will support the consistency, clarity, and comparability of biomedical research data and information. In addition to providing facilities for data management and redistribution, caCORE helps solve problems of data integration. All NCICB-developed caCORE components are distributed under open-source licenses that support unrestricted usage by both non-profit and commercial entities, and caCORE has laid the foundation for a number of scientific and clinical applications. Based on it, the paper expounds caCORE-base applications simply in several NCI projects, of which one is CMAP (Cancer Molecular Analysis Project), and the other is caBIG (Cancer Biomedical Informatics Grid). In the end, the paper also gives good prospects of caCORE, and while caCORE was born out of the needs of the cancer research community, it is intended to serve as a general resource. Cancer research has historically

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.

PERIPHERY/CORE RELATIONS IN THE INCA EMPIRE CARROTS AND STICKS IN AN ANDEAN WORLD SYSTEM

Directory of Open Access Journals (Sweden)

Lawrence A. Kuznar

2015-08-01

Full Text Available The Inca Empire exhibited labor exploitation and the rational extraction of resources from peripheral polities by a core polity. These characteristics fit the general definition of a world empire, although core/periphery relations were diverse. The nature of core/periphery relations depended on several attributes of the conquered polity including population size, political power, natural resources, and distance from the Inca core at Cuzco. A dynamic picture of core/periphery relations emerges as the outcome of Inca demands for labor and raw materials, and peripheral peoples' desire for control over their autonomy while seeking benefits from the Inca state.

New value added to network services through software-defined optical core networking

Science.gov (United States)

Yamada, Akiko; Nakatsugawa, Keiichi; Yamashita, Shinji; Soumiya, Toshio

2016-02-01

If an optical core network can be handled flexibly, it can be used not only as network infrastructure but also as a temporary broadband resource when customers have to transfer a large volume of data quickly, which will in turn lead to new WAN services. We propose "software-defined optical core networking", which achieves flexible optical network control, meaning it virtualizes optical transport network/wavelength-division multiplexing resources and controls them with resources from other layers, such as Ether/MPLS. We developed a testbed system and verified that users could request broadband resources easily, and our controller could quickly set up an optical channel data unit path for the request.

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.

Energy-aware Thread and Data Management in Heterogeneous Multi-core, Multi-memory Systems

Energy Technology Data Exchange (ETDEWEB)

Su, Chun-Yi [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States)

2014-12-16

By 2004, microprocessor design focused on multicore scaling—increasing the number of cores per die in each generation—as the primary strategy for improving performance. These multicore processors typically equip multiple memory subsystems to improve data throughput. In addition, these systems employ heterogeneous processors such as GPUs and heterogeneous memories like non-volatile memory to improve performance, capacity, and energy efficiency. With the increasing volume of hardware resources and system complexity caused by heterogeneity, future systems will require intelligent ways to manage hardware resources. Early research to improve performance and energy efficiency on heterogeneous, multi-core, multi-memory systems focused on tuning a single primitive or at best a few primitives in the systems. The key limitation of past efforts is their lack of a holistic approach to resource management that balances the tradeoff between performance and energy consumption. In addition, the shift from simple, homogeneous systems to these heterogeneous, multicore, multi-memory systems requires in-depth understanding of efficient resource management for scalable execution, including new models that capture the interchange between performance and energy, smarter resource management strategies, and novel low-level performance/energy tuning primitives and runtime systems. Tuning an application to control available resources efficiently has become a daunting challenge; managing resources in automation is still a dark art since the tradeoffs among programming, energy, and performance remain insufficiently understood. In this dissertation, I have developed theories, models, and resource management techniques to enable energy-efficient execution of parallel applications through thread and data management in these heterogeneous multi-core, multi-memory systems. I study the effect of dynamic concurrent throttling on the performance and energy of multi-core, non-uniform memory access

Advanced Marketing Core Curriculum. Test Items and Assessment Techniques.

Science.gov (United States)

Smith, Clifton L.; And Others

This document contains duties and tasks, multiple-choice test items, and other assessment techniques for Missouri's advanced marketing core curriculum. The core curriculum begins with a list of 13 suggested textbook resources. Next, nine duties with their associated tasks are given. Under each task appears one or more citations to appropriate…

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.

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.

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.

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.

CSIR eNews: Natural resources & the environment

CSIR Research Space (South Africa)

CSIR

2008-12-01

Full Text Available The CSIR conducts core research and develops competencies in various strategically critical areas of the natural resources and the environment (NRE) fields of study. Through relevant and focused research, CSIR Natural Resources and the Environment...

CSIR eNews: Natural resources and environment

CSIR Research Space (South Africa)

CSIR

2009-09-01

Full Text Available The CSIR conducts core research and develops competencies in various strategically critical areas of the natural resources and the environment (NRE) fields of study. Through relevant and focused research, CSIR Natural Resources and the Environment...

Core microbiomes for sustainable agroecosystems.

Science.gov (United States)

Toju, Hirokazu; Peay, Kabir G; Yamamichi, Masato; Narisawa, Kazuhiko; Hiruma, Kei; Naito, Ken; Fukuda, Shinji; Ushio, Masayuki; Nakaoka, Shinji; Onoda, Yusuke; Yoshida, Kentaro; Schlaeppi, Klaus; Bai, Yang; Sugiura, Ryo; Ichihashi, Yasunori; Minamisawa, Kiwamu; Kiers, E Toby

2018-05-01

In an era of ecosystem degradation and climate change, maximizing microbial functions in agroecosystems has become a prerequisite for the future of global agriculture. However, managing species-rich communities of plant-associated microbiomes remains a major challenge. Here, we propose interdisciplinary research strategies to optimize microbiome functions in agroecosystems. Informatics now allows us to identify members and characteristics of 'core microbiomes', which may be deployed to organize otherwise uncontrollable dynamics of resident microbiomes. Integration of microfluidics, robotics and machine learning provides novel ways to capitalize on core microbiomes for increasing resource-efficiency and stress-resistance of agroecosystems.

An FPGA computing demo core for space charge simulation

International Nuclear Information System (INIS)

Wu, Jinyuan; Huang, Yifei

2009-01-01

In accelerator physics, space charge simulation requires large amount of computing power. In a particle system, each calculation requires time/resource consuming operations such as multiplications, divisions, and square roots. Because of the flexibility of field programmable gate arrays (FPGAs), we implemented this task with efficient use of the available computing resources and completely eliminated non-calculating operations that are indispensable in regular micro-processors (e.g. instruction fetch, instruction decoding, etc.). We designed and tested a 16-bit demo core for computing Coulomb's force in an Altera Cyclone II FPGA device. To save resources, the inverse square-root cube operation in our design is computed using a memory look-up table addressed with nine to ten most significant non-zero bits. At 200 MHz internal clock, our demo core reaches a throughput of 200 M pairs/s/core, faster than a typical 2 GHz micro-processor by about a factor of 10. Temperature and power consumption of FPGAs were also lower than those of micro-processors. Fast and convenient, FPGAs can serve as alternatives to time-consuming micro-processors for space charge simulation.

An FPGA computing demo core for space charge simulation

Energy Technology Data Exchange (ETDEWEB)

Wu, Jinyuan; Huang, Yifei; /Fermilab

2009-01-01

In accelerator physics, space charge simulation requires large amount of computing power. In a particle system, each calculation requires time/resource consuming operations such as multiplications, divisions, and square roots. Because of the flexibility of field programmable gate arrays (FPGAs), we implemented this task with efficient use of the available computing resources and completely eliminated non-calculating operations that are indispensable in regular micro-processors (e.g. instruction fetch, instruction decoding, etc.). We designed and tested a 16-bit demo core for computing Coulomb's force in an Altera Cyclone II FPGA device. To save resources, the inverse square-root cube operation in our design is computed using a memory look-up table addressed with nine to ten most significant non-zero bits. At 200 MHz internal clock, our demo core reaches a throughput of 200 M pairs/s/core, faster than a typical 2 GHz micro-processor by about a factor of 10. Temperature and power consumption of FPGAs were also lower than those of micro-processors. Fast and convenient, FPGAs can serve as alternatives to time-consuming micro-processors for space charge simulation.

Collaborating with Undergraduates To Contribute to Biochemistry Community Resources.

Science.gov (United States)

Haas, Kathryn L; Heemstra, Jennifer M; Medema, Marnix H; Charkoudian, Louise K

2018-01-30

Course-based undergraduate research experiences (CUREs) have gained traction as effective ways to expand the impact of undergraduate research while fulfilling pedagogical goals. In this Perspective, we present innovative ways to incorporate fundamental benefits and principles of CUREs into a classroom environment through information/technology-based research projects that lead to student-generated contributions to digital community resources (CoRes). These projects represent an attractive class of CUREs because they are less resource-intensive than laboratory-based CUREs, and the projects align with the expectations of today's students to create rapid and publicly accessible contributions to society. We provide a detailed discussion of two example types of CoRe projects that can be implemented in courses to impact research and education at the chemistry-biology interface: bioinformatics annotations and development of educational tools. Finally, we present current resources available for faculty interested in incorporating CUREs or CoRe projects into their pedagogical practices. In sharing these stories and resources, we hope to lower the barrier for widespread adoption of CURE and CoRe approaches and generate discussions about how to utilize the classroom experience to make a positive impact on our students and the future of the field of biochemistry.

MIMI: multimodality, multiresource, information integration environment for biomedical core facilities.

Science.gov (United States)

Szymanski, Jacek; Wilson, David L; Zhang, Guo-Qiang

2009-10-01

The rapid expansion of biomedical research has brought substantial scientific and administrative data management challenges to modern core facilities. Scientifically, a core facility must be able to manage experimental workflow and the corresponding set of large and complex scientific data. It must also disseminate experimental data to relevant researchers in a secure and expedient manner that facilitates collaboration and provides support for data interpretation and analysis. Administratively, a core facility must be able to manage the scheduling of its equipment and to maintain a flexible and effective billing system to track material, resource, and personnel costs and charge for services to sustain its operation. It must also have the ability to regularly monitor the usage and performance of its equipment and to provide summary statistics on resources spent on different categories of research. To address these informatics challenges, we introduce a comprehensive system called MIMI (multimodality, multiresource, information integration environment) that integrates the administrative and scientific support of a core facility into a single web-based environment. We report the design, development, and deployment experience of a baseline MIMI system at an imaging core facility and discuss the general applicability of such a system in other types of core facilities. These initial results suggest that MIMI will be a unique, cost-effective approach to addressing the informatics infrastructure needs of core facilities and similar research laboratories.

Immobilization of Three-Mile Island core debris

International Nuclear Information System (INIS)

Welch, J.M.; Miller, R.L.; Flinn, J.E.

1983-01-01

The immobilization of Three-Mile Island core debris in iron-enriched basalt (IEB), a fused-cast nuclear waste form, was considered. The amount of zirconium clad UO 2 fuel assemblies that can be dissolved in IEB using the Zr to UO 2 ratio present in the core was bracketed between 25 and 30% at 1500 0 C. The factors controlling the rate of dissolution of fuel pellets and Inconel, a structural component of the core, were investigated. Since the UO 2 dissolved in IEB could be a valuable resource in the future, the recovery of uranium from IEB using conventional ore-dressing and leaching techniques was assessed

Modeling of Core Competencies in the Registrar's Office

Science.gov (United States)

Pikowsky, Reta

2009-01-01

The Office of the Registrar at the Georgia Institute of Technology, in cooperation with the Office of Human Resources, has been engaged since February 2008 in a pilot project to model core competencies for the leadership team and the staff. It is the hope of the office of Human resources that this pilot will result in a model that can be used…

Resource sharing under global scheduling with partial processor bandwidth

NARCIS (Netherlands)

Afshar, Sara; Behnam, Moris; Bril, Reinder J.; Nolte, Thomas

2015-01-01

Resource efficient approaches are of great importance for resource constrained embedded systems. In this paper, we present an approach targeting systems where tasks of a critical application are partitioned on a multi-core platform and by using resource reservation techniques, the remaining

Impact of Globalization on the Human Resource Management ...

African Journals Online (AJOL)

Impact of Globalization on the Human Resource Management Function in ... impact on the management of human resources in developing countries including Kenya. ... The non-core jobs have been outsourced which has led to an increase in ...

The core content of clinical ultrasonography fellowship training.

Science.gov (United States)

Lewiss, Resa E; Tayal, Vivek S; Hoffmann, Beatrice; Kendall, John; Liteplo, Andrew S; Moak, James H; Panebianco, Nova; Noble, Vicki E

2014-04-01

The purpose of developing a core content for subspecialty training in clinical ultrasonography (US) is to standardize the education and qualifications required to provide oversight of US training, clinical use, and administration to improve patient care. This core content would be mastered by a fellow as a separate and unique postgraduate training, beyond that obtained during an emergency medicine (EM) residency or during medical school. The core content defines the training parameters, resources, and knowledge of clinical US necessary to direct clinical US divisions within medical specialties. Additionally, it is intended to inform fellowship directors and candidates for certification of the full range of content that might appear in future examinations. This article describes the development of the core content and presents the core content in its entirety. © 2014 by the Society for Academic Emergency Medicine.

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.

T-CREST: Time-predictable multi-core architecture for embedded systems

DEFF Research Database (Denmark)

Schoeberl, Martin; Abbaspourseyedi, Sahar; Jordan, Alexander

2015-01-01

-core architectures that are optimized for the WCET instead of the average-case execution time. The resulting time-predictable resources (processors, interconnect, memory arbiter, and memory controller) and tools (compiler, WCET analysis) are designed to ease WCET analysis and to optimize WCET performance. Compared...... domain shows that the WCET can be reduced for computation-intensive tasks when distributing the tasks on several cores and using the network-on-chip for communication. With three cores the WCET is improved by a factor of 1.8 and with 15 cores by a factor of 5.7.The T-CREST project is the result...

Does Wyoming's Core Area Policy Protect Winter Habitats for Greater Sage-Grouse?

Science.gov (United States)

Smith, Kurt T.; Beck, Jeffrey L.; Pratt, Aaron C.

2016-10-01

Conservation reserves established to protect important habitat for wildlife species are used world-wide as a wildlife conservation measure. Effective reserves must adequately protect year-round habitats to maintain wildlife populations. Wyoming's Sage-Grouse Core Area policy was established to protect breeding habitats for greater sage-grouse ( Centrocercus urophasianus). Protecting only one important seasonal habitat could result in loss or degradation of other important habitats and potential declines in local populations. The purpose of our study was to identify the timing of winter habitat use, the extent which individuals breeding in Core Areas used winter habitats, and develop resource selection functions to assess effectiveness of Core Areas in conserving sage-grouse winter habitats in portions of 5 Core Areas in central and north-central Wyoming during winters 2011-2015. We found that use of winter habitats occured over a longer period than current Core Area winter timing stipulations and a substantial amount of winter habitat outside of Core Areas was used by individuals that bred in Core Areas, particularly in smaller Core Areas. Resource selection functions for each study area indicated that sage-grouse were selecting habitats in response to landscapes dominated by big sagebrush and flatter topography similar to other research on sage-grouse winter habitat selection. The substantial portion of sage-grouse locations and predicted probability of selection during winter outside small Core Areas illustrate that winter requirements for sage-grouse are not adequately met by existing Core Areas. Consequently, further considerations for identifying and managing important winter sage-grouse habitats under Wyoming's Core Area Policy are warranted.

Do AAO-HNSF CORE Grants Predict Future NIH Funding Success?

Science.gov (United States)

Eloy, Jean Anderson; Svider, Peter F; Kanumuri, Vivek V; Folbe, Adam J; Setzen, Michael; Baredes, Soly

2014-08-01

To determine (1) whether academic otolaryngologists who have received an American Academy of Otolaryngology- Head and Neck Surgery Foundation (AAO-HNSF) Centralized Otolaryngology Research Efforts (CORE) grant are more likely to procure future National Institutes of Health (NIH) funding; (2) whether CORE grants or NIH Career Development (K) awards have a stronger association with scholarly impact. Historical cohort. Scholarly impact, as measured by the h-index, publication experience, and prior grant history, were determined for CORE-funded and non-CORE-funded academic otolaryngologists. All individuals were assessed for NIH funding history. Of 192 academic otolaryngologists with a CORE funding history, 39.6% had active or prior NIH awards versus 15.1% of 1002 non-CORE-funded faculty (P productivity than those with CORE funding history. Both cohorts had higher scholarly impact values than previously published figures among academic otolaryngologists, highlighting that both CORE grants and NIH K-grants awards are effective career development resources. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Research on TQCS Strategy of Digital Manufacturing Resource Management

Institute of Scientific and Technical Information of China (English)

ZHOU Zude; ZHANG Huifu

2006-01-01

Heterogeneous in nature, digitized manufacturing resources are geographically distributed, and owned by different organizations each having their own resource management policies and different access-and-cost models. In this paper, by means of stateful serviceData, we make manufacturing resources as grid nodes. Considering TQCS requirements of resources in the manufacturing industry, we capture the essentials of grid resource management models and propose the TQCS market model to inquire, browse and use manufacturing resources. The manufacturing resource integration will integrate and organize the manufacture technology resource to form the core manufacture powers.

300 MWe Burner Core Design with two Enrichment Zoning

International Nuclear Information System (INIS)

Song, Hoon; Kim, Sang Ji; Kim, Yeong Il

2008-01-01

KAERI has been developing the KALIMER-600 core design with a breakeven fissile conversion ratio. The core is loaded with a ternary metallic fuel (TRU-U-10Zr), and the breakeven characteristics are achieved without any blanket assembly. As an alternative plan, a KALIMER-600 burner core design has been also performed. In the early stage of the development of a fast reactor, the main purpose is an economical use of a uranium resource but nowadays in addition to the maximum utilization of a uranium resource, the burning of a high level radioactive waste is taken as an additional interest for the harmony of the environment. In way of constructing the commercial size reactor which has the power level ranging from 800 MWe to 1600 MWe, the demonstration reactor which has the power level ranging from 200 MWe to 600 MWe was usually constructed for the midterm stage to commercial size reactor. In this paper, a 300 MWe burner core design was performed with purpose of demonstration reactor for KALIMER-600 burner of 600 MWe. As a means to flatten the power distribution, instead of a single fuel enrichment scheme adapted in design of KALIMER-600 burner, the 2 enrichment zoning approach was adapted

Making It Happen: Common Core Standards

Science.gov (United States)

National Council of Teachers of Mathematics, 2011

2011-01-01

This one-of-a-kind guide identifies and highlights the ways in which NCTM (National Council of Teachers of Mathematics) resources can support teachers as they implement and supplement the Common Core State Standards for Mathematics (CCSSM) in their states. The guide and accompanying charts are tools to help educators as they continue to make…

The Darwin Core extension for genebanks opens up new opportunities for sharing genebank datasets

Directory of Open Access Journals (Sweden)

Dag Terje Filip Endresen

2012-07-01

Full Text Available Darwin Core (DwC defines a standard set of terms to describe the primary biodiversity data. Primary biodiversity data are data records derived from direct observation of species occurrences in nature or describing specimens in biological collections. The Darwin Core terms can be seen as an extension to the standard Dublin Core metadata terms. The new Darwin Core extension for genebanks declares the additional terms required for describing genebank datasets, and is based on established standards from the plant genetic resources community. The Global Biodiversity Information Facility (GBIF provides an information infrastructure for biodiversity data including a suite of software tools for data publishing, distributed data access, and the capture of biodiversity data. The Darwin Core extension for genebanks is a key component that provides access for the genebanks and the plant genetic resources community to the GBIF informatics infrastructure including the new toolkits for data exchange. This paper provides one of the first examples and guidelines for how to create extensions to the Darwin Core standard.

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

Lesson Planning with the Common Core

Science.gov (United States)

Estes, Linda A.; McDuffie, Amy Roth; Tate, Cathie

2014-01-01

Planning a lesson can be similar to planning a road trip--a metaphor the authors use to describe how they applied research and theory to their lesson planning process. A map and mode of transportation, the Common Core State Standards for Mathematics (CCSSM) and textbooks as resources, can lead to desired destinations, such as students engaging in…

Measuring Performance of Soft Real-Time Tasks on Multi-core Systems

OpenAIRE

Rafiq, Salman

2011-01-01

Multi-core platforms are well established, and they are slowly moving into the area of embedded and real-time systems. Nowadays to take advantage of multi-core systems in terms of throughput, soft real-time applications are run together with general purpose applications under an operating system such as Linux. But due to shared hardware resources in multi-core architectures, it is likely that these applications will interfere and compete with each other. This can cause slower response times f...

Disallowing Same-program Co-schedules to Improve Efficiency in Quad-core Servers

OpenAIRE

de Blanche, Andreas; Lundqvist, Thomas

2017-01-01

Programs running on different cores in a multicore server are often forced to share resources like off-chip memory, caches, I/O devices, etc. This resource sharing often leads to degraded performance, a slowdown, for the programs that share the resources. A job scheduler can improve performance by co-scheduling programs that use different resources on the same server. The most common approach to solve this co-scheduling problem has been to make job-schedulers resource aware, finding ways to c...

Korrelasjon mellom core styrke, core stabilitet og utholdende styrke i core

OpenAIRE

Berg-Olsen, Andrea Marie; Fugelsøy, Eivor; Maurstad, Ann-Louise

2010-01-01

Formålet med studien var å se hvilke korrelasjon det er mellom core styrke, core stabilitet og utholdende styrke i core. Testingen bestod av tre hoveddeler hvor vi testet core styrke, core stabilitet og utholdende styrke i core. Innenfor core styrke og utholdende styrke i core ble tre ulike tester utført. Ved måling av core stabilitet ble det gjennomført kun en test. I core styrke ble isometrisk abdominal fleksjon, isometrisk rygg ekstensjon og isometrisk lateral fleksjon testet. Sit-ups p...

NMR-MPar: A Fault-Tolerance Approach for Multi-Core and Many-Core Processors

Directory of Open Access Journals (Sweden)

Vanessa Vargas

2018-03-01

Full Text Available Multi-core and many-core processors are a promising solution to achieve high performance by maintaining a lower power consumption. However, the degree of miniaturization makes them more sensitive to soft-errors. To improve the system reliability, this work proposes a fault-tolerance approach based on redundancy and partitioning principles called N-Modular Redundancy and M-Partitions (NMR-MPar. By combining both principles, this approach allows multi-/many-core processors to perform critical functions in mixed-criticality systems. Benefiting from the capabilities of these devices, NMR-MPar creates different partitions that perform independent functions. For critical functions, it is proposed that N partitions with the same configuration participate of an N-modular redundancy system. In order to validate the approach, a case study is implemented on the KALRAY Multi-Purpose Processing Array (MPPA-256 many-core processor running two parallel benchmark applications. The traveling salesman problem and matrix multiplication applications were selected to test different device’s resources. The effectiveness of NMR-MPar is assessed by software-implemented fault-injection. For evaluation purposes, it is considered that the system is intended to be used in avionics. Results show the improvement of the application reliability by two orders of magnitude when implementing NMR-MPar on the system. Finally, this work opens the possibility to use massive parallelism for dependable applications in embedded systems.

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.

Core story creation: analysing narratives to construct stories for learning.

Science.gov (United States)

Petty, Julia; Jarvis, Joy; Thomas, Rebecca

2018-03-16

Educational research uses narrative enquiry to gain and interpret people's experiences. Narrative analysis is used to organise and make sense of acquired narrative. 'Core story creation' is a way of managing raw data obtained from narrative interviews to construct stories for learning. To explain how core story creation can be used to construct stories from raw narratives obtained by interviewing parents about their neonatal experiences and then use these stories to educate learners. Core story creation involves reconfiguration of raw narratives. Reconfiguration includes listening to and rereading transcribed narratives, identifying elements of 'emplotment' and reordering these to form a constructed story. Thematic analysis is then performed on the story to draw out learning themes informed by the participants. Core story creation using emplotment is a strategy of narrative reconfiguration that produces stories which can be used to develop resources relating to person-centred education about the patient experience. Stories constructed from raw narratives in the context of constructivism can provide a medium or an 'end product' for use in learning resource development. This can then contribute to educating students or health professionals about patients' experiences. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

Cambridge IGCSE mathematics core and extended

CERN Document Server

Pimentel, Ric

2013-01-01

The most cost effective and straightforward way to teach the revised syllabus, with all the core and extended content covered by a single book and accompanying free digital resources.  . This title has been written for the revised Cambridge IGCSE Mathematics (0580) syllabus, for first teaching from 2013.  . ·         Gives students the practice they require to deepen their understanding through plenty of questions. ·         Consolidates learning with unique digital resources on the CD, included free with every Student's Book.  . We are working with Cambridge International Examinations to gain

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.

Methodological approach to assessment of organizational resources of the productive activity

Directory of Open Access Journals (Sweden)

Alexander Miller

2017-05-01

Full Text Available The purpose of this article is to solve the problem connected with development of theoretical and methodological provisions of formation of the assessment procedure of organizational resources of the productive activity. Theoretical results of our research are: improvement of the concept of development of organizational resources of the productive activity; identifying the impact of organizational resources on the productive activity; justification of the basic principles of formation of the assessment system of efficiency of the organizational resources' use. We proposed a unified methodological approach allowing to combine the complexity of assessment of both quantity of core resources of the productive activity and organizational resources, which significantly develops traditional systems of the productive activity management based on identifying quantitative parameters of the subsystems, their assessment, comparison and analysis. We also substantiated our opinion on assessment of organizational resources' values. It is focused on the development of the productive activity and allows to use the developed tools of the methodological approach for forecast assessment of the impact of the quantity of core resources, used in the productive activity, and organizational resources of the productive activity on the economic results of the enterprise.

Core curriculum illustration: rib fractures.

Science.gov (United States)

Dunham, Gregor M; Perez-Girbes, Alexandre; Linnau, Ken F

2017-06-01

This is the 24th installment of a series that will highlight one case per publication issue from the bank of cases available online as part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online, please visit the ASER Core Curriculum and Recommendations for Study online at http://www.aseronline.org/curriculum/toc.htm .

Study on core design for reduced-moderation water reactors

International Nuclear Information System (INIS)

Okubo, Tsutomu

2002-01-01

The Reduced-Moderation Water Reactor (RMWR) is a water-cooled reactor with the harder neutron spectrum comparing with the LWR, resulting from low neutron moderation due to reduced water volume fraction. Based on the difference from the spectrum from the LWR, the conversion from U-238 to Pu-239 is promoted and the new cores preferable to effective utilization of uranium resource can be possible Design study of the RMWR core started in 1997 and new four core concepts (three BWR cores and one PWR core) are recently evaluated in terms of control rod worths, plutonium multiple recycle, high burnup and void coefficient. Comparative evaluations show needed incorporation of control rod programming and simplified PUREX process as well as development of new fuel cans for high burnup of 100 GW-d/t. Final choice of design specifications will be made at the next step aiming at realization of the RMWR. (T. Tanaka)

Study on core design for reduced-moderation water reactors

Energy Technology Data Exchange (ETDEWEB)

Okubo, Tsutomu [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

2002-12-01

The Reduced-Moderation Water Reactor (RMWR) is a water-cooled reactor with the harder neutron spectrum comparing with the LWR, resulting from low neutron moderation due to reduced water volume fraction. Based on the difference from the spectrum from the LWR, the conversion from U-238 to Pu-239 is promoted and the new cores preferable to effective utilization of uranium resource can be possible Design study of the RMWR core started in 1997 and new four core concepts (three BWR cores and one PWR core) are recently evaluated in terms of control rod worths, plutonium multiple recycle, high burnup and void coefficient. Comparative evaluations show needed incorporation of control rod programming and simplified PUREX process as well as development of new fuel cans for high burnup of 100 GW-d/t. Final choice of design specifications will be made at the next step aiming at realization of the RMWR. (T. Tanaka)

Vermont's Forest Resources, 2006

Science.gov (United States)

R.S. Morin; R. De Geus

2008-01-01

This publication provides an overview of forest resource attributes for Vermont based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information regarding past inventory reports...

Connecticut's forest resources, 2010

Science.gov (United States)

Brett J. Butler; Cassandra Kurtz; Christopher Martin; W. Keith Moser

2011-01-01

This publication provides an overview of forest resource attributes for Connecticut based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of this report...

Connecticut's forest resources, 2009

Science.gov (United States)

Brett J. Butler; Christopher Martin

2011-01-01

This publication provides an overview of forest resource attributes for Connecticut based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of this report...

Pennsylvania's forest resources, 2012

Science.gov (United States)

G.L. McCaskill; W.H. McWilliams; C.J. Barnett

2013-01-01

This publication provides an overview of forest resource attributes for Pennsylvania based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of...

Pennsylvania's forest resources, 2009

Science.gov (United States)

G.L. McCaskill; W.H. McWilliams; B.J. Butler; D.M. Meneguzzo; C.J. Barnett; M.H. Hansen

2011-01-01

This publication provides an overview of forest resource attributes for Pennsylvania based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of...

Pennsylvania's forest resources, 2011

Science.gov (United States)

G.L. McCaskill; W.H. McWilliams; C.J. Barnett

2012-01-01

This publication provides an overview of forest resource attributes for Pennsylvania based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of...

Pennsylvania's forest resources, 2008

Science.gov (United States)

G.L. McCaskill; W.H. McWilliams; B.J. Butler; D.M. Meneguzzo; C.J. Barnett; M.H. Hansen

2011-01-01

This publication provides an overview of forest resource attributes for Pennsylvania based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of...

Pennsylvania's forest resources, 2010

Science.gov (United States)

G.L. McCaskill; W.H. McWilliams; C.J. Barnett

2011-01-01

This publication provides an overview of forest resource attributes for Pennsylvania based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of...

Pennsylvania's forest resources, 2007

Science.gov (United States)

G.L. McCaskill; W.H. McWilliams; B.J. Butler; D.M. Meneguzzo; C.J. Barnett; M.H. Hansen

2011-01-01

This publication provides an overview of forest resource attributes for Pennsylvania based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information, please refer to page 6 of...

Wisconsin's forest resources, 2010

Science.gov (United States)

C.H. Perry

2011-01-01

This publication provides an overview of forest resource attributes for Wisconsin based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of this report...

Wisconsin's forest resources, 2006

Science.gov (United States)

C.H. Perry; V.A. Everson

2007-01-01

Figure 2 was revised by the author in August 2008. This publication provides an overview of forest resource attributes for Wisconsin based on an annual inventory conducted by the Forest Inventory and Analysis program at the Northern Research Station of the U.S. Forest Service from 2002-2006. These estimates, along with associated core tables postedon the Internet, are...

Wisconsin's Forest Resources, 2007

Science.gov (United States)

C.H. Perry; V.A. Everson

2008-01-01

This publication provides an overview of forest resource attributes for Wisconsin based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program of the U.S. Forest Service, Northern Research Station. These estimates, along with web-posted core tables, are updated annually. For more information please refer to page 4 of this report.

Wisconsin's forest resources, 2009

Science.gov (United States)

C.H. Perry

2011-01-01

This publication provides an overview of forest resource attributes for Wisconsin based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information, please refer to page 4 of this report...

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

Science.gov (United States)

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

2000-06-01

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

Behavior-aware cache hierarchy optimization for low-power multi-core embedded systems

Science.gov (United States)

Zhao, Huatao; Luo, Xiao; Zhu, Chen; Watanabe, Takahiro; Zhu, Tianbo

2017-07-01

In modern embedded systems, the increasing number of cores requires efficient cache hierarchies to ensure data throughput, but such cache hierarchies are restricted by their tumid size and interference accesses which leads to both performance degradation and wasted energy. In this paper, we firstly propose a behavior-aware cache hierarchy (BACH) which can optimally allocate the multi-level cache resources to many cores and highly improved the efficiency of cache hierarchy, resulting in low energy consumption. The BACH takes full advantage of the explored application behaviors and runtime cache resource demands as the cache allocation bases, so that we can optimally configure the cache hierarchy to meet the runtime demand. The BACH was implemented on the GEM5 simulator. The experimental results show that energy consumption of a three-level cache hierarchy can be saved from 5.29% up to 27.94% compared with other key approaches while the performance of the multi-core system even has a slight improvement counting in hardware overhead.

Darwin Core: An Evolving Community-Developed Biodiversity Data Standard

Science.gov (United States)

Wieczorek, John; Bloom, David; Guralnick, Robert; Blum, Stan; Döring, Markus; Giovanni, Renato; Robertson, Tim; Vieglais, David

2012-01-01

Biodiversity data derive from myriad sources stored in various formats on many distinct hardware and software platforms. An essential step towards understanding global patterns of biodiversity is to provide a standardized view of these heterogeneous data sources to improve interoperability. Fundamental to this advance are definitions of common terms. This paper describes the evolution and development of Darwin Core, a data standard for publishing and integrating biodiversity information. We focus on the categories of terms that define the standard, differences between simple and relational Darwin Core, how the standard has been implemented, and the community processes that are essential for maintenance and growth of the standard. We present case-study extensions of the Darwin Core into new research communities, including metagenomics and genetic resources. We close by showing how Darwin Core records are integrated to create new knowledge products documenting species distributions and changes due to environmental perturbations. PMID:22238640

What does the Development of the European Core Curriculum for Cardiovascular Nurses Mean for Australia?

Science.gov (United States)

Neubeck, Lis; Lin, Stella Hsi-Man; Ferry, Cate; Gallagher, Robyn

2016-04-01

A core curriculum for the continuing professional development of nurses has recently been published by the Council on Cardiovascular Nursing and Allied Professions of the European Society of Cardiology. This core curriculum was envisaged to bridge the educational gap between qualification as a nurse and an advance practice role. In addition, the shared elements and international consensus on core themes creates a strong pathway for nursing career development that is directly relevant to Australia. Education programs for nurses in Australia must meet the mandatory standards of the Australian Nursing and Midwifery Accreditation Council (ANMAC), but without a national core curriculum, there can be considerable variation in the content of such courses. The core curriculum is developed to be adapted locally, allowing the addition of nationally relevant competencies, for example, culturally appropriate care of Aboriginal and Torres Strait Islander individuals. Two existing specialist resources could be utilised to deliver a tailored cardiovascular core curriculum; the Heart Education Assessment and Rehabilitation Toolkit (HEART) online (www.heartonline.org.au) and HeartOne (www.heartone.com.au). Both resources could be further enhanced by incorporating the core curriculum. The release of the European core curriculum should be viewed as a call to action for Australia to develop a core curriculum for cardiovascular nurses. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

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.

Leading Change: Transitioning to the Common Core

Science.gov (United States)

Brandt, Brian

2012-01-01

For many school districts in the United States, making the transition to the Common Core State Standards (CCSS) is proving to be a challenge at a time when they are already facing many obstacles, not the least of which is dwindling financial resources. A change of this magnitude cannot be made haphazardly; to be successful in its goal of helping…

Core@shell Nanoparticles: Greener Synthesis Using Natural Plant Products

Directory of Open Access Journals (Sweden)

Mehrdad Khatami

2018-03-01

Full Text Available Among an array of hybrid nanoparticles, core-shell nanoparticles comprise of two or more materials, such as metals and biomolecules, wherein one of them forms the core at the center, while the other material/materials that were located around the central core develops a shell. Core-shell nanostructures are useful entities with high thermal and chemical stability, lower toxicity, greater solubility, and higher permeability to specific target cells. Plant or natural products-mediated synthesis of nanostructures refers to the use of plants or its extracts for the synthesis of nanostructures, an emerging field of sustainable nanotechnology. Various physiochemical and greener methods have been advanced for the synthesis of nanostructures, in contrast to conventional approaches that require the use of synthetic compounds for the assembly of nanostructures. Although several biological resources have been exploited for the synthesis of core-shell nanoparticles, but plant-based materials appear to be the ideal candidates for large-scale green synthesis of core-shell nanoparticles. This review summarizes the known strategies for the greener production of core-shell nanoparticles using plants extract or their derivatives and highlights their salient attributes, such as low costs, the lack of dependence on the use of any toxic materials, and the environmental friendliness for the sustainable assembly of stabile nanostructures.

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

Energy Technology Data Exchange (ETDEWEB)

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

2008-12-15

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

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

Science.gov (United States)

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

2017-04-01

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

South Dakota's forest resources, 2011

Science.gov (United States)

Brian F. Walters

2012-01-01

This publication provides an overview of forest resource attributes for South Dakota based on an annual inventory conducted by the Forest Inventory and Analysis program of the U.S. Forest Service, Northern Research Station. These estimates, along with web-posted core tables, will be updated annually. For more information regarding past inventory reports for South...

South Dakota's forest resources, 2009

Science.gov (United States)

Ronald J. Piva

2010-01-01

This publication provides an overview of forest resource attributes for South Dakota based on an annual inventory conducted by the Forest Inventory and Analysis program of the U.S. Forest Service, Northern Research Station. These estimates, along with web-posted core tables, will be updated annually. For more information regarding past inventory reports for South...

South Dakota's forest resources, 2010

Science.gov (United States)

Brian F. Walters; Ronald J. Piva

2011-01-01

This publication provides an overview of forest resource attributes for South Dakota based on an annual inventory conducted by the Forest Inventory and Analysis program of the U.S. Forest Service, Northern Research Station. These estimates, along with web-posted core tables, will be updated annually. For more information regarding past inventory reports for South...

South Dakota's Forest Resources, 2007

Science.gov (United States)

Ronald J. Piva; Andrew J. Lister; Douglas Haugan

2009-01-01

This publication provides an overview of forest resource attributes for South Dakota based on an annual inventory conducted by the Forest Inventory and Analysis program of the U.S. Forest Service, Northern Research Station. These estimates, along with web-posted core tables, will be updated annually. For more information regarding past inventory reports for South...

South Dakota's forest resources, 2008

Science.gov (United States)

Ronald J. Piva

2010-01-01

This publication provides an overview of forest resource attributes for South Dakota based on an annual inventory conducted by the Forest Inventory and Analysis program of the U.S. Forest Service, Northern Research Station. These estimates, along with web-posted core tables, will be updated annually. For more information regarding past inventory reports for South...

Opportunities and Challenges of Linking Scientific Core Samples to the Geoscience Data Ecosystem

Science.gov (United States)

Noren, A. J.

2016-12-01

Core samples generated in scientific drilling and coring are critical for the advancement of the Earth Sciences. The scientific themes enabled by analysis of these samples are diverse, and include plate tectonics, ocean circulation, Earth-life system interactions (paleoclimate, paleobiology, paleoanthropology), Critical Zone processes, geothermal systems, deep biosphere, and many others, and substantial resources are invested in their collection and analysis. Linking core samples to researchers, datasets, publications, and funding agencies through registration of globally unique identifiers such as International Geo Sample Numbers (IGSNs) offers great potential for advancing several frontiers. These include maximizing sample discoverability, access, reuse, and return on investment; a means for credit to researchers; and documentation of project outputs to funding agencies. Thousands of kilometers of core samples and billions of derivative subsamples have been generated through thousands of investigators' projects, yet the vast majority of these samples are curated at only a small number of facilities. These numbers, combined with the substantial similarity in sample types, make core samples a compelling target for IGSN implementation. However, differences between core sample communities and other geoscience disciplines continue to create barriers to implementation. Core samples involve parent-child relationships spanning 8 or more generations, an exponential increase in sample numbers between levels in the hierarchy, concepts related to depth/position in the sample, requirements for associating data derived from core scanning and lithologic description with data derived from subsample analysis, and publications based on tens of thousands of co-registered scan data points and thousands of analyses of subsamples. These characteristics require specialized resources for accurate and consistent assignment of IGSNs, and a community of practice to establish norms

The core to regulatory reform

International Nuclear Information System (INIS)

Partridge, J.W. Jr.

1993-01-01

Federal Energy Regulatory Commission (FERC) Orders 436, 500, and 636, the Clean Air Act Amendments of 1990, Public Utility Holding Company Act reform, and the 1992 Energy Policy Act all can have significant effects on an LDC's operations. Such changes in an LDC's environments must be balanced by changes within the utility, its marketplace, and its state regulatory environment. The question is where to start. For Columbia Gas Distribution Cos., based in Columbus, OH, the new operating foundation begins with each employee. Internal strength is critical in designing initiatives that meet the needs of the marketplace and are well-received by regulators. Employees must understand not only the regulatory environment in which the LDC operates, but also how their work contributes to a positive regulatory relationship. To achieve this, Columbia initiated the COntinuing Regulatory Education program, or CORE, in 1991. CORE is a regulatory-focused, information-initiative program coordinated by Columbia's Regulatory Policy, Planning, and Government Affairs Department. The CORE programs can take many forms, such as emerging issue discussions, dialogues with regulators and key parties, updates on regulatory fillings, regulatory policy meetings, and formal training classes. The speakers and discussion facilitators can range from human resource department trainers to senior officers, from regulatory department staff members to external experts, or from state commissioners to executives from other LDCs. The goals of CORE initiatives are to: Support a professional level of regulatory expertise through employee participation in well-developed regulatory programs presented by credible experts. Encourage a constructive state regulatory environment founded on communication and cooperation. CORE achieves these goals via five program levels: introductory basics, advanced learning, professional expertise, crossfunctional dialogues, and external idea exchanges

Application of Core Theory to the Airline Industry

Science.gov (United States)

Raghavan, Sunder

2003-01-01

Competition in the airline industry has been fierce since the industry was deregulated in 1978. The proponents of deregulation believed that more competition would improve efficiency and reduce prices and bring overall benefits to the consumer. In this paper, a case is made based on core theory that under certain demand and cost conditions more competition can actually lead to harmful consequences for industries like the airline industry or cause an empty core problem. Practices like monopolies, cartels, price discrimination, which is considered inefficient allocation of resources in many other industries, can actually be beneficial in the case of the airline industry in bringing about an efficient equilibrium.

FRBRizing an E-Library : Migrating from Dublin Core to FRBR and MODS

Directory of Open Access Journals (Sweden)

Jeremy Nelson

2010-12-01

Full Text Available Western State College in Gunnison, Colorado developed an open-source eCataloger Framework, based on Dublin Core metadata, on Google's App Engine to manage and serve electronic resources to the library's patrons. Pressed to find new solutions for failing manual workflows for serials and government document resource management, the eCataloger Framework was extended to FRBR to automate and enhance serials management and government documents receiving. Based on successfully FRBRizing the eCataloger, Western State College converted their e-Library management from Dublin Core to FRBR and MODS. This paper examines the processes of each of these implementations using Python, AJAX, and jQuery, the details of the FRBR data model, including using FRBRoo, and the successful user interface supported by a FRBRized catalog.

South Dakota's forest resources, 2012

Science.gov (United States)

Brian F. Walters

2013-01-01

This publication provides an overview of forest resource attributes for South Dakota based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program of the U.S. Forest Service, Northern Research Station. These estimates, along with Web-posted core tables, will be updated annually. For more information regarding past inventory reports for South...

North Dakota's forest resources, 2010

Science.gov (United States)

D.E. Haugen; R.A. Harsel

2011-01-01

This publication provides an overview of forest resource attributes for North Dakota based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information, please refer to page 4 of this...

North Dakota's forest resources, 2011

Science.gov (United States)

D.E. Haugen; R.A. Harsel

2012-01-01

This publication provides an overview of forest resource attributes for North Dakota based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information, please refer to page 4 of this...

North Dakota's forest resources, 2012

Science.gov (United States)

D.E. Haugen

2013-01-01

This publication provides an overview of forest resource attributes for North Dakota based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with Web-posted core tables, will be updated annually. For more information, please refer to page 4 of this...

North Dakota's forest resources, 2008

Science.gov (United States)

D.E. Haugen; A.J. Lister

2010-01-01

This publication provides an overview of forest resource attributes for North Dakota based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information, please refer to page 4 of this...

North Dakota's forest resources, 2009

Science.gov (United States)

D.E. Haugen

2010-01-01

This publication provides an overview of forest resource attributes for North Dakota based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information, please refer to page 4 of this...

New Hampshire's Forest Resources, 2006

Science.gov (United States)

R.S. Morin; M. Tansey

2008-01-01

This publication provides an overview of forest resource attributes for New Hampshire based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information regarding past inventory...

West Virginia's forest resources, 2009

Science.gov (United States)

R.H. Widmann; G.W. Cook

2011-01-01

This publication provides an overview of forest resource attributes for West Virginia based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information, please refer to page 4 of this...

West Virginia's forest resources, 2010

Science.gov (United States)

R.H. Widmann; G.W. Cook

2011-01-01

This publication provides an overview of forest resource attributes for West Virginia based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of this...

West Virginia's Forest Resources, 2006

Science.gov (United States)

Richard H. Widmann; Gregory W. Cook

2008-01-01

This publication provides an overview of forest resource attributes for this state based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These annual estimates, along with web-posted core tables, will be updated annually. For more information regarding past inventory...

West Virginia's forest resources, 2008

Science.gov (United States)

R.H. Widmann; B.J. Butler; G.W. Cook

2010-01-01

This publication provides an overview of forest resource attributes for West Virginia based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 4 of this...

U.S. Geological Survey Energy and Minerals science strategy: a resource lifecycle approach

Science.gov (United States)

Ferrero, Richard C.; Kolak, Jonathan J.; Bills, Donald J.; Bowen, Zachary H.; Cordier, Daniel J.; Gallegos, Tanya J.; Hein, James R.; Kelley, Karen D.; Nelson, Philip H.; Nuccio, Vito F.; Schmidt, Jeanine M.; Seal, Robert R.

2013-01-01

The economy, national security, and standard of living of the United States depend heavily on adequate and reliable supplies of energy and mineral resources. Based on population and consumption trends, the Nation’s use of energy and minerals can be expected to grow, driving the demand for ever broader scientific understanding of resource formation, location, and availability. In addition, the increasing importance of environmental stewardship, human health, and sustainable growth places further emphasis on energy and mineral resources research and understanding. Collectively, these trends in resource demand and the interconnectedness among resources will lead to new challenges and, in turn, require cutting- edge science for the next generation of societal decisions. The long and continuing history of U.S. Geological Survey contributions to energy and mineral resources science provide a solid foundation of core capabilities upon which new research directions can grow. This science strategy provides a framework for the coming decade that capitalizes on the growth of core capabilities and leverages their application toward new or emerging challenges in energy and mineral resources research, as reflected in five interrelated goals.

Remarks of Honorable Eleanor Norrie, Minister of the Nova Scotia Department of Natural Resources at the 1996 CORE conference

Energy Technology Data Exchange (ETDEWEB)

Norrie, E.

1996-10-01

Speaking notes used by the Nova Scotia Minister of Natural Resources at the 1996 CORE Conference were provided. The presentation focused on the new Sable Offshore Energy Project, an important new offshore gas field being developed by Mobil Oil. The project represents a total investment of $3 billion, the biggest capital project ever undertaken in Nova Scotia, and is completely funded by the private sector. Nearly 4,000 jobs will be created during the offshore and onshore construction phase, as well as future tax revenues for the province, new business opportunities, infrastructure for future projects, and an estimated 11,000 `spin-off` jobs. To expedite the development process, the Government of Nova Scotia has recently established the Nova Scotia Offshore Energy Office to work exclusively on the Sable gas and pipeline project. Future plans include a gas processing plant for Guysborough County. The gas will be transported by pipeline across New Brunswick to the New England market. A proposal by Gaz Metropolitain is also expected which would have some of the gas transported to Quebec.

Remarks of Honorable Eleanor Norrie, Minister of the Nova Scotia Department of Natural Resources at the 1996 CORE conference

International Nuclear Information System (INIS)

Norrie, E.

1996-10-01

Speaking notes used by the Nova Scotia Minister of Natural Resources at the 1996 CORE Conference were provided. The presentation focused on the new Sable Offshore Energy Project, an important new offshore gas field being developed by Mobil Oil. The project represents a total investment of $3 billion, the biggest capital project ever undertaken in Nova Scotia, and is completely funded by the private sector. Nearly 4,000 jobs will be created during the offshore and onshore construction phase, as well as future tax revenues for the province, new business opportunities, infrastructure for future projects, and an estimated 11,000 'spin-off' jobs. To expedite the development process, the Government of Nova Scotia has recently established the Nova Scotia Offshore Energy Office to work exclusively on the Sable gas and pipeline project. Future plans include a gas processing plant for Guysborough County. The gas will be transported by pipeline across New Brunswick to the New England market. A proposal by Gaz Metropolitain is also expected which would have some of the gas transported to Quebec

战略性人力资源管理视角下国企核心员工流失风险管理研究%Research on the Risk Management of the Turnover of Core Staff in State-owned Enterprises from the Perspective of Strategic Human Resource Management

Institute of Scientific and Technical Information of China (English)

何叶; 冯倩瑜

2013-01-01

战略性人力资源管理理论认为，核心员工是企业的重要战略资源，吸引并保留核心员工是企业建立和保持竞争优势的基础。当前我国国有企业核心员工流失问题非常严重，构建战略性人力资源管理体系对解决我国国有企业核心员工流失问题有着非同寻常的作用与意义。%According to strategic human resource management theory, core staff is one of the most important strategic resources in a company. Attracting and retaining core staff is the foundation to establish and maintain a competitive advantage. Turnover of core staff is a severe problem in state-owned enterprises in China. It's of unique significance to build a strategic human resource management system to solve the problem.

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Freedland, Stephen J., E-mail: steve.freedland@duke.edu [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Gerber, Leah [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S. [Myriad Genetics, Inc, Salt Lake City, Utah (United States); Salama, Joseph K. [Department of Radiation Oncology, Durham VA Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Stone, Steven [Myriad Genetics, Inc, Salt Lake City, Utah (United States)

2013-08-01

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.

Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

International Nuclear Information System (INIS)

Freedland, Stephen J.; Gerber, Leah; Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S.; Salama, Joseph K.; Stone, Steven

2013-01-01

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy

West Virginia's forest resources, 2007

Science.gov (United States)

R.H. Widmann; G.M. McCaskill; W. McWilliams; G.W. Cook

2010-01-01

This publication provides an overview of forest resource attributes for this state based on an annual inventory conducted by the Forest Inventory and Analysis (FIA) program at the Northern Research Station of the U.S. Forest Service. These estimates, along with web-posted core tables, will be updated annually. For more information please refer to page 5 of this report...

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

Science.gov (United States)

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

2014-02-01

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

Experimental Investigation of Crack Extension Patterns in Hydraulic Fracturing with Shale, Sandstone and Granite Cores

Directory of Open Access Journals (Sweden)

Jianming He

2016-12-01

Full Text Available Hydraulic fracturing is an important method of reservoir stimulation in the exploitation of geothermal resources, and conventional and unconventional oil and gas resources. In this article, hydraulic fracturing experiments with shale, sandstone cores (from southern Sichuan Basin, and granite cores (from Inner Mongolia were conducted to investigate the different hydraulic fracture extension patterns in these three reservoir rocks. The different reactions between reservoir lithology and pump pressure can be reflected by the pump pressure monitoring curves of hydraulic fracture experiments. An X-ray computer tomography (CT scanner was employed to obtain the spatial distribution of hydraulic fractures in fractured shale, sandstone, and granite cores. From the microscopic and macroscopic observation of hydraulic fractures, different extension patterns of the hydraulic fracture can be analyzed. In fractured sandstone, symmetrical hydraulic fracture morphology could be formed, while some micro cracks were also induced near the injection hole. Although the macroscopic cracks in fractured granite cores are barely observed by naked eye, the results of X-ray CT scanning obviously show the morphology of hydraulic fractures. It is indicated that the typical bedding planes well developed in shale formation play an important role in the propagation of hydraulic fractures in shale cores. The results also demonstrated that heterogeneity influenced the pathway of the hydraulic fracture in granite cores.

Evaluation of Treatments to Reduce Hardness of Agave americana Core

Directory of Open Access Journals (Sweden)

José A. Ramírez

2006-01-01

Full Text Available Agave americana contains inulin as storage carbohydrate. Therefore, agave is interesting to be used for the extraction of inulin by pressing. The yield of the process is low due to the high hardness of the core. The objective of this work was to evaluate pretreatments to reduce the hardness in the process of obtaining inulin by pressing. Treatments with water, sulphuric acid 1 % (by mass or sodium hydroxide 1 % (by mass were tested and optimized. The pretreatment of the core of A. americana with sulphuric acid 1 % allowed the reduction of hardness from 30 000 g to 2000 g of breaking force. The mathematical model obtained predicts an optimum processing at 84 °C during 75 min. The treatment with sulphuric acid 1 % also allows white core of A. americana to be obtained, while the other treatments provide yellow core. These results open a good alternative to obtain value added products from this resource.

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.

Cloud resource orchestration programming : Overview, issues and directions

NARCIS (Netherlands)

Ranjan, Rajiv; Benatallah, Boualem; Dustdar, Schahram; Papazoglou, M.

Cloud computing provides on-demand access to affordable hardware (e.g., multi-core CPUs, GPUs, disks, and networking equipment) and software (e.g., databases, application servers, load-balancers, data processing frameworks, etc.) resources. The pervasiveness and power of cloud computing alleviates

On-chip COMA cache-coherence protocol for microgrids of microthreaded cores

NARCIS (Netherlands)

Zhang, L.; Jesshope, C.

2008-01-01

This paper describes an on-chip COMA cache coherency protocol to support the microthread model of concurrent program composition. The model gives a sound basis for building multi-core computers as it captures concurrency, abstracts communication and identifies resources, such as processor groups

Core Hunter 3: flexible core subset selection.

Science.gov (United States)

De Beukelaer, Herman; Davenport, Guy F; Fack, Veerle

2018-05-31

Core collections provide genebank curators and plant breeders a way to reduce size of their collections and populations, while minimizing impact on genetic diversity and allele frequency. Many methods have been proposed to generate core collections, often using distance metrics to quantify the similarity of two accessions, based on genetic marker data or phenotypic traits. Core Hunter is a multi-purpose core subset selection tool that uses local search algorithms to generate subsets relying on one or more metrics, including several distance metrics and allelic richness. In version 3 of Core Hunter (CH3) we have incorporated two new, improved methods for summarizing distances to quantify diversity or representativeness of the core collection. A comparison of CH3 and Core Hunter 2 (CH2) showed that these new metrics can be effectively optimized with less complex algorithms, as compared to those used in CH2. CH3 is more effective at maximizing the improved diversity metric than CH2, still ensures a high average and minimum distance, and is faster for large datasets. Using CH3, a simple stochastic hill-climber is able to find highly diverse core collections, and the more advanced parallel tempering algorithm further increases the quality of the core and further reduces variability across independent samples. We also evaluate the ability of CH3 to simultaneously maximize diversity, and either representativeness or allelic richness, and compare the results with those of the GDOpt and SimEli methods. CH3 can sample equally representative cores as GDOpt, which was specifically designed for this purpose, and is able to construct cores that are simultaneously more diverse, and either are more representative or have higher allelic richness, than those obtained by SimEli. In version 3, Core Hunter has been updated to include two new core subset selection metrics that construct cores for representativeness or diversity, with improved performance. It combines and outperforms the

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)

Pressure-Coring of the Gas-bearing Devonian Black Shales

Energy Technology Data Exchange (ETDEWEB)

Zielinski, R. E.; Dixon, J. A.; McIver, R. D.

1979-10-01

A Christensen model pressure-retaining core barrel is being used in the drilling of two EGSP research wells. This effort supported by two other techniques is designed to evaluate the most effective technique to provide meaningful resource assessments. One well has been successfully drilled and the accumulated samples are currently being evaluated. The second well is currently being drilled.

Settlements in an Arctic Resource Frontier Region

NARCIS (Netherlands)

Hacquebord, L.; Avango, D.

2009-01-01

In this article we use a core-periphery model in order to understand the general trends in the history of natural resource exploitation in the polar regions. The study focuses on whaling, hunting, and coal mining activities on the European High Arctic archipelago of Spitsbergen, from the seventeenth

U.S. Department of Energy Workshop Report: Solar Resources and Forecasting

Energy Technology Data Exchange (ETDEWEB)

Stoffel, T.

2012-06-01

This report summarizes the technical presentations, outlines the core research recommendations, and augments the information of the Solar Resources and Forecasting Workshop held June 20-22, 2011, in Golden, Colorado. The workshop brought together notable specialists in atmospheric science, solar resource assessment, solar energy conversion, and various stakeholders from industry and academia to review recent developments and provide input for planning future research in solar resource characterization, including measurement, modeling, and forecasting.

Hydrothermal Alteration of Open Fractures in Prospective Geothermal Drill Cores, Akutan Island, Alaska

Science.gov (United States)

Kent, T.

2011-12-01

The goal of this study is to constrain the most recent thermal alteration of two drill cores (HSB2/HSB4) from the Island of Akutan in the Aleutian Islands of Alaska. These cores are characterized by identifying mineralogy using x-ray diffraction spectra, energy dispersive spectroscopy with a scanning electron microscope and optical mineralogy. This is then compared with the coincident thermal data gathered on site in order to help constrain the most recent thermal activity of this dynamic resource. Using multiple temperature diagnostic minerals and their paragenesis, a relative thermal history is produced of expansive propylitic alteration. When combined with the wireline temperature gradients of the cores a model of downward migration emerges. Shallow occurrences of high temperature minerals that lie above the boiling point to depth curve indicate higher hydrostatic pressures in the past which can be attributed to a combination of glacial effects, including a significant amount of glacial erosion that is recognized due to a lack of significant clay cap to the geothermal resource.

Planetary Drilling and Resources at the Moon and Mars

Science.gov (United States)

George, Jeffrey A.

2012-01-01

Drilling on the Moon and Mars is an important capability for both scientific and resource exploration. The unique requirements of spaceflight and planetary environments drive drills to different design approaches than established terrestrial technologies. A partnership between NASA and Baker Hughes Inc. developed a novel approach for a dry rotary coring wireline drill capable of acquiring continuous core samples at multi-meter depths for low power and mass. The 8.5 kg Bottom Hole Assembly operated at 100 We and without need for traditional drilling mud or pipe. The technology was field tested in the Canadian Arctic in sandstone, ice and frozen gumbo. Planetary resources could play an important role in future space exploration. Lunar regolith contains oxygen and metals, and water ice has recently been confirmed in a shadowed crater at the Moon.s south pole. Mars possesses a CO2 atmosphere, frozen water ice at the poles, and indications of subsurface aquifers. Such resources could provide water, oxygen and propellants that could greatly simplify the cost and complexity of exploration and survival. NASA/JSC/EP/JAG

Smart Money? Philanthropic and Federal Funding for the Common Core

Science.gov (United States)

Kornhaber, Mindy L.; Barkauskas, Nikolaus J.; Griffith, Kelly M.

2016-01-01

The Common Core State Standards Initiative seeks to prepare all students to graduate high school without remedial needs, to improve transparency across states' accountability systems, and to foster efficiencies in the development and distribution of educational resources. The reform was adopted in more than 40 states and has been described as…

Diversity of macrofungal community in Bifeng Gorge: the core giant ...

African Journals Online (AJOL)

Macrofungi not only play an important role in pollution control and other environmental protection measures, but also an important resource in food and pharmaceutical industries. However, the diversity of the macrofungal community in the core habitat of the giant panda in Bifeng Gorge, China is still inadequate. In the ...

Reconfiguration in FPGA-Based Multi-Core Platforms for Hard Real-Time Applications

DEFF Research Database (Denmark)

Pezzarossa, Luca; Schoeberl, Martin; Sparsø, Jens

2016-01-01

-case execution-time of tasks of an application that determines the systems ability to respond in time. To support this focus, the platform must provide service guarantees for both communication and computation resources. In addition, many hard real-time applications have multiple modes of operation, and each......In general-purpose computing multi-core platforms, hardware accelerators and reconfiguration are means to improve performance; i.e., the average-case execution time of a software application. In hard real-time systems, such average-case speed-up is not in itself relevant - it is the worst...... mode has specific requirements. An interesting perspective on reconfigurable computing is to exploit run-time reconfiguration to support mode changes. In this paper we explore approaches to reconfiguration of communication and computation resources in the T-CREST hard real-time multi-core platform...

Status of core nuclear design technology for future fuel

International Nuclear Information System (INIS)

Joo, Hyung Kook; Jung, Hyung Guk; Noh, Jae Man; Kim, Yeong Il; Kim, Taek Kyum; Gil, Choong Sup; Kim, Jung Do; Kim, Young Jin; Sohn, Dong Seong

1997-01-01

The effective utilization of nuclear resource is more important factor to be considered in the design of next generation PWR in addition to the epochal consideration on economics and safety. Assuming that MOX fuel can be considered as one of the future fuel corresponding to the above request, the establishment of basic technology for the MOX core design has been performed : : the specification of the technical problem through the preliminary core design and nuclear characteristic analysis of MOX, the development and verification of the neutron library for lattice code, and the acquisition of data to be used for verification of lattice and core analysis codes. The following further studies will be done in future: detailed verification of library E63LIB/A, development of the spectral history effect treatment module, extension of decay chain, development of new homogenization for the MOX fuel assembly. (author). 6 refs., 7 tabs., 2 figs

A database of paleoceanographic sediment cores from the North Pacific, 1951-2016

Science.gov (United States)

Borreggine, Marisa; Myhre, Sarah E.; Mislan, K. Allison S.; Deutsch, Curtis; Davis, Catherine V.

2017-09-01

We assessed sediment coring, data acquisition, and publications from the North Pacific (north of 30° N) from 1951 to 2016. There are 2134 sediment cores collected by American, French, Japanese, Russian, and international research vessels across the North Pacific (including the Pacific subarctic gyre, Alaskan gyre, Japan margin, and California margin; 1391 cores), the Sea of Okhotsk (271 cores), the Bering Sea (123 cores), and the Sea of Japan (349 cores) reported here. All existing metadata associated with these sediment cores are documented here, including coring date, location, core number, cruise number, water depth, vessel metadata, and coring technology. North Pacific sediment core age models are built with isotope stratigraphy, radiocarbon dating, magnetostratigraphy, biostratigraphy, tephrochronology, % opal, color, and lithological proxies. Here, we evaluate the iterative generation of each published age model and provide comprehensive documentation of the dating techniques used, along with sedimentation rates and age ranges. We categorized cores according to the availability of a variety of proxy evidence, including biological (e.g., benthic and planktonic foraminifera assemblages), geochemical (e.g., major trace element concentrations), isotopic (e.g., bulk sediment nitrogen, oxygen, and carbon isotopes), and stratigraphic (e.g., preserved laminations) proxies. This database is a unique resource to the paleoceanographic and paleoclimate communities and provides cohesive accessibility to sedimentary sequences, age model development, and proxies. The data set is publicly available through PANGAEA at PANGAEA.875998" target="_blank">https://doi.org/10.1594/PANGAEA.875998.

Analysis Of Core Management For The Transition Cores Of RSG-GAS Reactor To Full-Silicide Core

International Nuclear Information System (INIS)

Malem Sembiring, Tagor; Suparlina, Lily; Tukiran

2001-01-01

The core conversion of RSG-GAS reactor from oxide to silicide core with meat density of 2.96 g U/cc is still doing. At the end of 2000, the reactor has been operated for 3 transition cores which is the mixed core of oxide-silicide. Based on previous work, the calculated core parameter for the cores were obtained and it is needed 10 transition cores to achieve a full-silicide core. The objective of this work is to acquire the effect of the increment of the number of silicide fuel on the core parameters such as excess reactivity and shutdown margin. The measurement of the core parameters was carried out using the method of compensation of couple control rods. The experiment shows that the excess reactivity trends lower with the increment of the number of silicide fuel in the core. However, the shutdown margin is not change with the increment of the number of silicide fuel. Therefore, the transition cores can be operated safety to a full-silicide core

Core-to-core uniformity improvement in multi-core fiber Bragg gratings

Science.gov (United States)

Lindley, Emma; Min, Seong-Sik; Leon-Saval, Sergio; Cvetojevic, Nick; Jovanovic, Nemanja; Bland-Hawthorn, Joss; Lawrence, Jon; Gris-Sanchez, Itandehui; Birks, Tim; Haynes, Roger; Haynes, Dionne

2014-07-01

Multi-core fiber Bragg gratings (MCFBGs) will be a valuable tool not only in communications but also various astronomical, sensing and industry applications. In this paper we address some of the technical challenges of fabricating effective multi-core gratings by simulating improvements to the writing method. These methods allow a system designed for inscribing single-core fibers to cope with MCFBG fabrication with only minor, passive changes to the writing process. Using a capillary tube that was polished on one side, the field entering the fiber was flattened which improved the coverage and uniformity of all cores.

Resource-aware complexity scalability for mobile MPEG encoding

NARCIS (Netherlands)

Mietens, S.O.; With, de P.H.N.; Hentschel, C.; Panchanatan, S.; Vasudev, B.

2004-01-01

Complexity scalability attempts to scale the required resources of an algorithm with the chose quality settings, in order to broaden the application range. In this paper, we present complexity-scalable MPEG encoding of which the core processing modules are modified for scalability. Scalability is

The Resource Manager the ATLAS Trigger and Data Acquisition System

CERN Document Server

Aleksandrov, Igor; The ATLAS collaboration; Lehmann Miotto, Giovanna; Soloviev, Igor

2016-01-01

The Resource Manager of the ATLAS Trigger and Data Acquisition system The Resource Manager is one of the core components of the Data Acquisition system of the ATLAS experiment at the LHC. The Resource Manager marshals the right for applications to access resources which may exist in multiple but limited copies, in order to avoid conflicts due to program faults or operator errors. The access to resources is managed in a manner similar to what a lock manager would do in other software systems. All the available resources and their association to software processes are described in the Data Acquisition configuration database. The Resource Manager is queried about the availability of resources every time an application needs to be started. The Resource Manager’s design is based on a client-server model, hence it consists of two components: the Resource Manager "server" application and the "client" shared library. The Resource Manager server implements all the needed functionalities, while the Resource Manager c...

Coupling between core and cladding modes in a helical core fiber with large core offset

International Nuclear Information System (INIS)

Napiorkowski, Maciej; Urbanczyk, Waclaw

2016-01-01

We analyzed the effect of resonant coupling between core and cladding modes in a helical core fiber with large core offset using the fully vectorial method based on the transformation optics formalism. Our study revealed that the resonant couplings to lower order cladding modes predicted by perturbative methods and observed experimentally in fibers with small core offsets are in fact prohibited for larger core offsets. This effect is related to the lack of phase matching caused by elongation of the optical path of the fundamental modes in the helical core. Moreover, strong couplings to the cladding modes of the azimuthal modal number much higher than predicted by perturbative methods may be observed for large core offsets, as the core offset introduces higher order angular harmonics in the field distribution of the fundamental modes. Finally, in contrast to previous studies, we demonstrate the existence of spectrally broad polarization sensitive couplings to the cladding modes suggesting that helical core fibers with large core offsets may be used as broadband circular polarizers. (paper)

Evaluation of In-Core Fuel Management for the Transition Cores of RSG-GAS Reactor to Full-Silicide Core

International Nuclear Information System (INIS)

S, Tukiran; MS, Tagor; P, Surian

2003-01-01

The core conversion of RSG-GAS reactor from oxide to silicide core with meat density of 2.96 gU/cc has been done. The core-of RSG-GAS reactor has been operated full core of silicide fuels which is started with the mixed core of oxide-silicide start from core 36. Based on previous work, the calculated core parameter for the cores were obtained and it is needed 9 transition cores (core 36 - 44) to achieve a full-silicide core (core 45). The objective of this work is to acquire the effect of the increment of the number of silicide fuel on the core parameters. Conversion core was achieved by transition cores mixed oxide-silicide fuels. Each transition core is calculated and measured core parameter such as, excess reactivity and shutdown margin. Calculation done by Batan-EQUIL-2D code and measurement of the core parameters was carried out using the method of compensation of couple control rods. The results of calculation and experiment shows that the excess reactivity trends lower with the increment of the number of silicide fuel in the core. However, the shutdown margin is not change with the increment of the number of silicide fuel. Therefore, the transition cores can be operated safely to a full-silicide core

PWR core design, neutronics evaluation and fuel cycle analysis for thorium-uranium breeding recycle

International Nuclear Information System (INIS)

Bi, G.; Liu, C.; Si, S.

2012-01-01

with reference full UOX core. The fuel cycle analysis has shown that 233 U mono-recycling with U 3 ThOX fuel could save 13% of natural uranium resource compared with UOX once through fuel cycle, slightly more than that of Plutonium single-recycling with MOX fuel. If 233 U multi-recycling with U 3 ThOX fuel is implemented, more natural uranium resource would be saved. (authors)

The Resource Manager the ATLAS Trigger and Data Acquisition System

CERN Document Server

AUTHOR|(INSPIRE)INSPIRE-00210579; The ATLAS collaboration; Avolio, Giuseppe; Lehmann Miotto, Giovanna; Soloviev, Igor

2017-01-01

The Resource Manager is one of the core components of the Data Acquisition system of the ATLAS experiment at the LHC. The Resource Manager marshals the right for applications to access resources which may exist in multiple but limited copies, in order to avoid conflicts due to program faults or operator errors. The access to resources is managed in a manner similar to what a lock manager would do in other software systems. All the available resources and their association to software processes are described in the Data Acquisition configuration database. The Resource Manager is queried about the availability of resources every time an application needs to be started. The Resource Manager’s design is based on a client-server model, hence it consists of two components: the Resource Manager “server” application and the “client” shared library. The Resource Manager server implements all the needed functionalities, while the Resource Manager client library provides remote access to the “server” (i.e....

Core exit thermocouple upgrade at Zion station

International Nuclear Information System (INIS)

Ulinski, T.M.; Ferg, D.A.

1989-01-01

Following the Three Mile Island accident, the ability of the core exit thermocouple (CET) system to monitor reactor core conditions and core cooling status became a requirement of the U.S. Nuclear Regulatory Commission (NRC). Since the thermocouple system at Zion station was not originally required for postaccident monitoring, Commonwealth Edison Company (CECo) committed to upgrading the CET system and to installing a subcooling margin monitoring (SMM) system. The significance of this commitment was that CECo proposed to accomplish the upgrade effort using internal resources and by developing the required in-house expertise instead of procuring integrated packages from several nuclear steam supply system vendors. The result was that CECo was able to demonstrate a number of new capabilities and unique design features with a significant cost savings. These included a qualified connector with an integral thermocouple cold-reference junction temperature compensation; the design, assembly, testing, and installation of a seismically qualified class 1E microprocessor; a commercial-grade dedication/upgrade process for safety-related hardware; a human factors review capability, and a verification and validation program for safety-related software. A discussion of these new capabilities and details of the design features is presented in this paper

Turnover Intentions of Employees With Informal Eldercare Responsibilities: The Role of Core Self-Evaluations and Supervisor Support.

Science.gov (United States)

Greaves, Claire E; Parker, Stacey L; Zacher, Hannes; Jimmieson, Nerina L

2015-12-01

As longevity increases, so does the need for care of older relatives by working family members. This research examined the interactive effect of core self-evaluations and supervisor support on turnover intentions in two samples of employees with informal caregiving responsibilities. Data were obtained from 57 employees from Australia (Study 1) and 66 employees from the United States and India (Study 2). Results of Study 1 revealed a resource compensation effect, that is, an inverse relationship between core self-evaluations and turnover intentions when supervisor care support was low. Results of Study 2 extended these findings by demonstrating resource boosting effects. Specifically, there was an inverse relationship between core self-evaluations and subsequent turnover intentions for those with high supervisor work and care support. In addition, employees' satisfaction and emotional exhaustion from their work mediated the inverse relationship between core self-evaluations and subsequent turnover intentions when supervisor work support and care support were high. Overall, these findings highlight the importance of employee- and supervisor-focused intervention strategies in organizations to support informal caregivers. © The Author(s) 2016.

Earth's inner core: Innermost inner core or hemispherical variations?

NARCIS (Netherlands)

Lythgoe, K. H.; Deuss, A.|info:eu-repo/dai/nl/412396610; Rudge, J. F.; Neufeld, J. A.

2014-01-01

The structure of Earth's deep inner core has important implications for core evolution, since it is thought to be related to the early stages of core formation. Previous studies have suggested that there exists an innermost inner core with distinct anisotropy relative to the rest of the inner core.

Dependence of Core and Extended Flux on Core Dominance ...

Indian Academy of Sciences (India)

Abstract. Based on two extragalactic radio source samples, the core dominance parameter is calculated, and the correlations between the core/extended flux density and core dominance parameter are investi- gated. When the core dominance parameter is lower than unity, it is linearly correlated with the core flux density, ...

Leveraging Online Learning Resources to Teach Core Research Skills to Undergraduates at a Diverse Research University.

Science.gov (United States)

McFARLIN, Brian K; Breslin, Whitney L; Carpenter, Katie C; Strohacker, Kelley; Weintraub, Randi J

2010-01-01

Today's students have unique learning needs and lack knowledge of core research skills. In this program report, we describe an online approach that we developed to teach core research skills to freshman and sophomore undergraduates. Specifically, we used two undergraduate kinesiology (KIN) courses designed to target students throughout campus (KIN1304: Public Health Issues in Physical Activity and Obesity) and specifically kinesiology majors (KIN1252: Foundations of Kinesiology). Our program was developed and validated at the 2 nd largest ethnically diverse research university in the United States, thus we believe that it would be effective in a variety of student populations.

On-line core monitoring with CORE MASTER / PRESTO

International Nuclear Information System (INIS)

Lindahl, S.O.; Borresen, S.; Ovrum, S.

1986-01-01

Advanced calculational tools are instrumental in improving reactor plant capacity factors and fuel utilization. The computer code package CORE MASTER is an integrated system designed to achieve this objective. The system covers all main activities in the area of in-core fuel management for boiling water reactors; design, operation support, and on-line core monitoring. CORE MASTER operates on a common data base, which defines the reactor and documents the operating history of the core and of all fuel bundles ever used

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.

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

Science.gov (United States)

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

2015-11-01

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

Performance modeling and analysis of parallel Gaussian elimination on multi-core computers

Directory of Open Access Journals (Sweden)

Fadi N. Sibai

2014-01-01

Full Text Available Gaussian elimination is used in many applications and in particular in the solution of systems of linear equations. This paper presents mathematical performance models and analysis of four parallel Gaussian Elimination methods (precisely the Original method and the new Meet in the Middle –MiM– algorithms and their variants with SIMD vectorization on multi-core systems. Analytical performance models of the four methods are formulated and presented followed by evaluations of these models with modern multi-core systems’ operation latencies. Our results reveal that the four methods generally exhibit good performance scaling with increasing matrix size and number of cores. SIMD vectorization only makes a large difference in performance for low number of cores. For a large matrix size (n ⩾ 16 K, the performance difference between the MiM and Original methods falls from 16× with four cores to 4× with 16 K cores. The efficiencies of all four methods are low with 1 K cores or more stressing a major problem of multi-core systems where the network-on-chip and memory latencies are too high in relation to basic arithmetic operations. Thus Gaussian Elimination can greatly benefit from the resources of multi-core systems, but higher performance gains can be achieved if multi-core systems can be designed with lower memory operation, synchronization, and interconnect communication latencies, requirements of utmost importance and challenge in the exascale computing age.

MCSE Core Elective Exams in a Nutshell Covers exams 70-270, 70-297, and 70-298

CERN Document Server

Bhardwaj, Pawan

2006-01-01

For Windows XP and Windows Server 2003 administrators preparing forMicrosoft Certified Systems Engineer (MCSE) core exam 70-270, and core exams 70-297, and 70-298, this book is invaluable. Not only does it provide the resources you need to succeed on the exams, but to succeed in the real world as well. Think of this book as the notes you would have taken if you were to capture every essential nugget of information related to the skills measured in the core elective exams. To begin with, MCSE Core Elective Exams in a Nutshell allows you to see all of the topics expected for mastery in each

The caCORE Software Development Kit: Streamlining construction of interoperable biomedical information services

Directory of Open Access Journals (Sweden)

Warzel Denise

2006-01-01

Full Text Available Abstract Background Robust, programmatically accessible biomedical information services that syntactically and semantically interoperate with other resources are challenging to construct. Such systems require the adoption of common information models, data representations and terminology standards as well as documented application programming interfaces (APIs. The National Cancer Institute (NCI developed the cancer common ontologic representation environment (caCORE to provide the infrastructure necessary to achieve interoperability across the systems it develops or sponsors. The caCORE Software Development Kit (SDK was designed to provide developers both within and outside the NCI with the tools needed to construct such interoperable software systems. Results The caCORE SDK requires a Unified Modeling Language (UML tool to begin the development workflow with the construction of a domain information model in the form of a UML Class Diagram. Models are annotated with concepts and definitions from a description logic terminology source using the Semantic Connector component. The annotated model is registered in the Cancer Data Standards Repository (caDSR using the UML Loader component. System software is automatically generated using the Codegen component, which produces middleware that runs on an application server. The caCORE SDK was initially tested and validated using a seven-class UML model, and has been used to generate the caCORE production system, which includes models with dozens of classes. The deployed system supports access through object-oriented APIs with consistent syntax for retrieval of any type of data object across all classes in the original UML model. The caCORE SDK is currently being used by several development teams, including by participants in the cancer biomedical informatics grid (caBIG program, to create compatible data services. caBIG compatibility standards are based upon caCORE resources, and thus the caCORE SDK has

A database of paleoceanographic sediment cores from the North Pacific, 1951–2016

Directory of Open Access Journals (Sweden)

M. Borreggine

2017-09-01

Full Text Available We assessed sediment coring, data acquisition, and publications from the North Pacific (north of 30° N from 1951 to 2016. There are 2134 sediment cores collected by American, French, Japanese, Russian, and international research vessels across the North Pacific (including the Pacific subarctic gyre, Alaskan gyre, Japan margin, and California margin; 1391 cores, the Sea of Okhotsk (271 cores, the Bering Sea (123 cores, and the Sea of Japan (349 cores reported here. All existing metadata associated with these sediment cores are documented here, including coring date, location, core number, cruise number, water depth, vessel metadata, and coring technology. North Pacific sediment core age models are built with isotope stratigraphy, radiocarbon dating, magnetostratigraphy, biostratigraphy, tephrochronology, % opal, color, and lithological proxies. Here, we evaluate the iterative generation of each published age model and provide comprehensive documentation of the dating techniques used, along with sedimentation rates and age ranges. We categorized cores according to the availability of a variety of proxy evidence, including biological (e.g., benthic and planktonic foraminifera assemblages, geochemical (e.g., major trace element concentrations, isotopic (e.g., bulk sediment nitrogen, oxygen, and carbon isotopes, and stratigraphic (e.g., preserved laminations proxies. This database is a unique resource to the paleoceanographic and paleoclimate communities and provides cohesive accessibility to sedimentary sequences, age model development, and proxies. The data set is publicly available through PANGAEA at https://doi.org/10.1594/PANGAEA.875998.

Restraint system for core elements of a reactor core

International Nuclear Information System (INIS)

Class, G.

1975-01-01

In a nuclear reactor, a core element bundle formed of a plurality of side-by-side arranged core elements is surrounded by restraining elements that exert a radially inwardly directly restraining force generating friction forces between the core elements in a restraining plane that is transverse to the core element axes. The adjoining core elements are in rolling contact with one another in the restraining plane by virtue of rolling-type bearing elements supported in the core elements. (Official Gazette)

Construction of Core Collections Suitable for Association Mapping to Optimize Use of Mediterranean Olive (Olea europaea L.) Genetic Resources

Science.gov (United States)

El Bakkali, Ahmed; Haouane, Hicham; Moukhli, Abdelmajid; Costes, Evelyne; Van Damme, Patrick; Khadari, Bouchaib

2013-01-01

Phenotypic characterisation of germplasm collections is a decisive step towards association mapping analyses, but it is particularly expensive and tedious for woody perennial plant species. Characterisation could be more efficient if focused on a reasonably sized subset of accessions, or so-called core collection (CC), reflecting the geographic origin and variability of the germplasm. The questions that arise concern the sample size to use and genetic parameters that should be optimized in a core collection to make it suitable for association mapping. Here we investigated these questions in olive (Olea europaea L.), a perennial fruit species. By testing different sampling methods and sizes in a worldwide olive germplasm bank (OWGB Marrakech, Morocco) containing 502 unique genotypes characterized by nuclear and plastid loci, a two-step sampling method was proposed. The Shannon-Weaver diversity index was found to be the best criterion to be maximized in the first step using the Core Hunter program. A primary core collection of 50 entries (CC50) was defined that captured more than 80% of the diversity. This latter was subsequently used as a kernel with the Mstrat program to capture the remaining diversity. 200 core collections of 94 entries (CC94) were thus built for flexibility in the choice of varieties to be studied. Most entries of both core collections (CC50 and CC94) were revealed to be unrelated due to the low kinship coefficient, whereas a genetic structure spanning the eastern and western/central Mediterranean regions was noted. Linkage disequilibrium was observed in CC94 which was mainly explained by a genetic structure effect as noted for OWGB Marrakech. Since they reflect the geographic origin and diversity of olive germplasm and are of reasonable size, both core collections will be of major interest to develop long-term association studies and thus enhance genomic selection in olive species. PMID:23667437

Structure and mechanism of diet specialisation: testing models of individual variation in resource use with sea otters

Science.gov (United States)

Tinker, M. Tim; Guimarães, Paulo R.; Novak, Mark; Marquitti, Flavia Maria Darcie; Bodkin, James L.; Staedler, Michelle; Bentall, Gena B.; Estes, James A.

2012-01-01

Studies of consumer-resource interactions suggest that individual diet specialisation is empirically widespread and theoretically important to the organisation and dynamics of populations and communities. We used weighted networks to analyze the resource use by sea otters, testing three alternative models for how individual diet specialisation may arise. As expected, individual specialisation was absent when otter density was low, but increased at high-otter density. A high-density emergence of nested resource-use networks was consistent with the model assuming individuals share preference ranks. However, a density-dependent emergence of a non-nested modular network for ‘core’ resources was more consistent with the ‘competitive refuge’ model. Individuals from different diet modules showed predictable variation in rank-order prey preferences and handling times of core resources, further supporting the competitive refuge model. Our findings support a hierarchical organisation of diet specialisation and suggest individual use of core and marginal resources may be driven by different selective pressures.

ABR Core examination preparation: results of a survey of fourth-year radiology residents who took the 2013 examination.

Science.gov (United States)

Shetty, Anup S; Grajo, Joseph R; Decker, Summer; Heitkamp, Darel E; DeStigter, Kristen K; Mezwa, Duane G; Deitte, Lori

2015-01-01

A survey was administered to fourth-year radiology residents after receiving their results from the first American Board of Radiology (ABR) Core examination in 2013. The purpose was to gather information regarding resources and study strategies to share with program directors and future resident classes. An online survey was distributed to examinees nationwide. The survey included free-response and multiple choice questions that covered examination results, perceived value of enumerated study resources, case-based and didactic teaching conferences, board reviews, study materials for noninterpretive skills, multidisciplinary conference attendance, and free-form comments. Two hundred sixty-six of 1186 residents who took the Core examination responded to the survey. Some resources demonstrated a significant difference in perceived value between residents who passed the examination and residents who failed, including internal board reviews (1.10, P multiple choice questions, audience response, and integration of clinical physics and patient safety topics compared to residents who failed. Radiology residents and residency programs have adapted their preparations for the ABR Core examination in a variety of ways. Certain practices and study tools, including daily conferences and internal board reviews, had greater perceived value by residents who passed the examination than by residents who failed. This survey provides insights that can be used to assess and modify current preparation strategies for the ABR Core examination. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Real-time resource availability signalling in IMS-based networks

NARCIS (Netherlands)

Ozcelebi, T.; Radovanovic, I.; Lukkien, J.J.

2007-01-01

The emerging converged IP multimedia subsystem (IMS) allows the use of unlicensed, nondedicated and nondeterministic computer access networks for delivering IP multimedia services. To provide end-to-end quality-of-service (QoS) over such networks combined with the IMS core network, for resource

Interrelationship between core interventions and core competencies of forensic psychiatric nursing in Finland.

Science.gov (United States)

Tenkanen, Helena; Tiihonen, Jari; Repo-Tiihonen, Eila; Kinnunen, Juha

2011-03-01

The importance of core competencies (CC) and their relationship to core interventions in clinical practice guidelines on schizophrenia (CPGS), and the abilities to master these competencies were studied among registered nurses (RN) and practical mental nurses (PMN) in a forensic psychiatric setting. Data were collected from RNs, PMNs, and managers of all five forensic psychiatric facilities in Finland. The research material was obtained by using a 360-degree feedback method. The response rate was 68% (N = 428). The differences between the nurse groups were statistically significant (p ≤ 0.05) regarding the importance of and ability to master the following CCs: (1) pharmacotherapy, (2) knowledge in forensic psychiatry and violent behavior, (3) the treatment of violent patients, (4) processing patient's and own emotion, and (5) need-adapted treatment of the patient. Overall, RNs exceeded PMNs in mastering the CCs, however the principles of the CPGS were not achieved within the current resources in Finland. In summary, RNs, rather than PMNs, should be recruited for work in forensic psychiatric nursing, although a considerable amount of specific training would still be required to achieve competence. Implications of our research indicate that all nurses working in this area need to receive further education in forensic psychiatry and in forensic psychiatric nursing. © 2011 International Association of Forensic Nurses.

Multi-core job submission and grid resource scheduling for ATLAS AthenaMP

CERN Multimedia

CERN. Geneva

2012-01-01

A study into the effectiveness and scalability of AthenaMP in a production environment will be presented. Submitting AthenaMP tasks to the Tier-0 and candidate Tier-2 sites will allow detailed measurement of worker node performance and also highlight the relative performance of local resource management system...

The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition.

Science.gov (United States)

Varano, Gabriele; Raffel, Simon; Sormani, Martina; Zanardi, Federica; Lonardi, Silvia; Zasada, Christin; Perucho, Laura; Petrocelli, Valentina; Haake, Andrea; Lee, Albert K; Bugatti, Mattia; Paul, Ulrike; Van Anken, Eelco; Pasqualucci, Laura; Rabadan, Raul; Siebert, Reiner; Kempa, Stefan; Ponzoni, Maurilio; Facchetti, Fabio; Rajewsky, Klaus; Casola, Stefano

2017-06-08

Similar to resting mature B cells, where the B-cell antigen receptor (BCR) controls cellular survival, surface BCR expression is conserved in most mature B-cell lymphomas. The identification of activating BCR mutations and the growth disadvantage upon BCR knockdown of cells of certain lymphoma entities has led to the view that BCR signalling is required for tumour cell survival. Consequently, the BCR signalling machinery has become an established target in the therapy of B-cell malignancies. Here we study the effects of BCR ablation on MYC-driven mouse B-cell lymphomas and compare them with observations in human Burkitt lymphoma. Whereas BCR ablation does not, per se, significantly affect lymphoma growth, BCR-negative (BCR - ) tumour cells rapidly disappear in the presence of their BCR-expressing (BCR + ) counterparts in vitro and in vivo. This requires neither cellular contact nor factors released by BCR + tumour cells. Instead, BCR loss induces the rewiring of central carbon metabolism, increasing the sensitivity of receptor-less lymphoma cells to nutrient restriction. The BCR attenuates glycogen synthase kinase 3 beta (GSK3β) activity to support MYC-controlled gene expression. BCR - tumour cells exhibit increased GSK3β activity and are rescued from their competitive growth disadvantage by GSK3β inhibition. BCR - lymphoma variants that restore competitive fitness normalize GSK3β activity after constitutive activation of the MAPK pathway, commonly through Ras mutations. Similarly, in Burkitt lymphoma, activating RAS mutations may propagate immunoglobulin-crippled tumour cells, which usually represent a minority of the tumour bulk. Thus, while BCR expression enhances lymphoma cell fitness, BCR-targeted therapies may profit from combinations with drugs targeting BCR - tumour cells.

Using the CMS high level trigger as a cloud resource

International Nuclear Information System (INIS)

Colling, David; Huffman, Adam; Bauer, Daniela; McCrae, Alison; Cinquilli, Mattia; Gowdy, Stephen; Coarasa, Jose Antonio; Ozga, Wojciech; Chaze, Olivier; Lahiff, Andrew; Grandi, Claudio; Tiradani, Anthony; Sgaravatto, Massimo

2014-01-01

The CMS High Level Trigger is a compute farm of more than 10,000 cores. During data taking this resource is heavily used and is an integral part of the experiment's triggering system. However, outside of data taking periods this resource is largely unused. We describe why CMS wants to use the HLT as a cloud resource (outside of data taking periods) and how this has been achieved. In doing this we have turned a single-use cluster into an agile resource for CMS production computing. While we are able to use the HLT as a production cloud resource, there is still considerable further work that CMS needs to carry out before this resource can be used with the desired agility. This report, therefore, represents a snapshot of this activity at the time of CHEP 2013.

Synthetic Aperture Radar Data Processing on an FPGA Multi-Core System

DEFF Research Database (Denmark)

Schleuniger, Pascal; Kusk, Anders; Dall, Jørgen

2013-01-01

on an FPGA. The fabric consisting of 64 processor cores and 2D mesh interconnect utilizes 60% of the hardware resources of a Xilinx Virtex-7 device with 550 thousand logic cells and consumes about 10 watt. We apply software pipelining to hide memory latency and reduce the hardware footprint by 14%. We show...

A Case for Common Core State Standards: Gifted Curriculum 3.0

Science.gov (United States)

VanTassel-Baska, Joyce

2012-01-01

The Common Core State Standards (CCSS) is the most successful attempt to gain consensus across states for 21st century standards in language arts and mathematics. So far, 46 states have accepted these standards, with two consortia organized to translate them into resources and sample activities. A consultant firm has been hired to develop the…

Biological Data Resources at the EMBL-EBI

Directory of Open Access Journals (Sweden)

Rodrigo Lopez

2008-07-01

Full Text Available The European Bioinformatics Institute (EBI is an Outstation of the European Molecular Biology Laboratory (EMBL. These are Europe’s flagships in bioinforma­tics and basic research in molecular biology. The EBI has been maintaining core data resources in molecular biology for 15 years and is notionally custodian to the largest collection of databases and services in Life Sciences in Europe. EBI provides access in a free and unrestricted fashion to these resources to the international research community. The data resources at the EBI are divided into thematic categories. Each represents a special knowledge domain where one or several databases are maintai­ned. The aims of this note are to introduce the reader to these resources and briefly outline training and education activities which may be of interest to students as well as academic staff in general. The web portal for the EBI can be found at http://www.ebi.ac.uk/ and represents a single entry point for all data resources and activities described below.

A "Common" Vision of Instruction? An Analysis of English/Language Arts Professional Development Materials Related to the Common Core State Standards

Science.gov (United States)

Hodge, Emily; Benko, Susanna L.

2014-01-01

The purpose of this article is to describe the stances put forward by a selection of professional development resources interpreting the Common Core State Standards for English Language Arts (ELA) teachers, and to analyse where these resources stand in relation to research in ELA. Specifically, we analyse resources written by English educators…

Globex Resources Ltd. : annual report 2000

International Nuclear Information System (INIS)

2001-01-01

Financial information from Globex Resources Ltd. was presented and a review of their 2000 operations was made available for the benefit of shareholders. The company's core oil and gas business activities include exploration, development and production of crude oil and natural gas in Western Canada. The company plans to continue to increase its reserves and production base in Canada through exploration and development drilling and through strategic acquisitions. Globex is also planning a high impact project in Atlantic Canada, in New Brunswick for the medium- to long-term. In 2000, revenues more than doubled and cash flow tripled to $4.1 million. Earnings also increased nearly 8 times to $2.4 million. Net asset value per share also doubled and production increased by 16 per cent to 713 boe/day. In 2000, Globex Resources acquired 5 per cent of Corridor Resources Inc. This report summarized the company's energy resource activities and presented an operations review as well as consolidated financial statements, and common share information. Revenue and expenditure statements were summarized by source. tabs., figs

Exploitation of heterogeneous resources for ATLAS Computing

CERN Document Server

Chudoba, Jiri; The ATLAS collaboration

2018-01-01

LHC experiments require significant computational resources for Monte Carlo simulations and real data processing and the ATLAS experiment is not an exception. In 2017, ATLAS exploited steadily almost 3M HS06 units, which corresponds to about 300 000 standard CPU cores. The total disk and tape capacity managed by the Rucio data management system exceeded 350 PB. Resources are provided mostly by Grid computing centers distributed in geographically separated locations and connected by the Grid middleware. The ATLAS collaboration developed several systems to manage computational jobs, data files and network transfers. ATLAS solutions for job and data management (PanDA and Rucio) were generalized and now are used also by other collaborations. More components are needed to include new resources such as private and public clouds, volunteers' desktop computers and primarily supercomputers in major HPC centers. Workflows and data flows significantly differ for these less traditional resources and extensive software re...

Developing a virtual community for health sciences library book selection: Doody's Core Titles.

Science.gov (United States)

Shedlock, James; Walton, Linda J

2006-01-01

The purpose of this article is to describe Doody's Core Titles in the Health Sciences as a new selection guide and a virtual community based on an effective use of online systems and to describe its potential impact on library collection development. The setting is the availability of health sciences selection guides. Participants include Doody Enterprise staff, Doody's Library Board of Advisors, content specialists, and library selectors. Resources include the online system used to create Doody's Core Titles along with references to complementary databases. Doody's Core Titles is described and discussed in relation to the literature of selection guides, especially in comparison to the Brandon/Hill selected lists that were published from 1965 to 2003. Doody's Core Titles seeks to fill the vacuum created when the Brandon/Hill lists ceased publication. Doody's Core Titles is a unique selection guide based on its method of creating an online community of experts to identify and score a core list of titles in 119 health sciences specialties and disciplines. The result is a new selection guide, now available annually, that will aid health sciences librarians in identifying core titles for local collections. Doody's Core Titles organizes the evaluation of core titles that are identified and recommended by content specialists associated with Doody's Book Review Service and library selectors. A scoring mechanism is used to create the selection of core titles, similar to the star rating system employed in other Doody Enterprise products and services.

Resource categories and performance in Portuguese non-profit sports clubs

Directory of Open Access Journals (Sweden)

Marco Arraya

2016-01-01

Full Text Available The resource-based view (RBV explores the role of key resources identified as tangible, personnel-based, and intangible resources in creating superior organizational performance. The RBV posits that an organization’s success is mainly driven by resources that possess Barney’s VRIO (valuable, rare, inimitable, and organized framework. The purpose of this study is to demonstrate the relationship between the three categories of resources and organizational performance. The data was analyzed with a two-stage structural equation modelling approach. The sample included Portuguese sports management staff from non-profit clubs which composed of 375 men and 102 women. The results of the structural model demonstrated that, intangible resources can significantly influence organizational performance while, personnel-based resources influence tangible and intangible resources. The results show that “staff competence”, “reputation”, and “financial capital” were the most essential resources, and that is core for non-profit clubs and their strategy to recognize, develop, and leverage VRIO resources. These findings also have considerable implications for sport managers, and suggestions for possible future research were given.

Core lifter

Energy Technology Data Exchange (ETDEWEB)

Pavlov, N G; Edel' man, Ya A

1981-02-15

A core lifter is suggested which contains a housing, core-clamping elements installed in the housing depressions in the form of semirings with projections on the outer surface restricting the rotation of the semirings in the housing depressions. In order to improve the strength and reliability of the core lifter, the semirings have a variable transverse section formed from the outside by the surface of the rotation body of the inner arc of the semiring aroung the rotation axis and from the inner a cylindrical surface which is concentric to the outer arc of the semiring. The core-clamping elements made in this manner have the possibility of freely rotating in the housing depressions under their own weight and from contact with the core sample. These semirings do not have weakened sections, have sufficient strength, are inserted into the limited ring section of the housing of the core lifter without reduction in its through opening and this improve the reliability of the core lifter in operation.

Side core lifter

Energy Technology Data Exchange (ETDEWEB)

Edelman, Ya A

1982-01-01

A side core lifter is proposed which contains a housing with guide slits and a removable core lifter with side projections on the support section connected to the core receiver. In order to preserve the structure of the rock in the core sample by means of guaranteeing rectilinear movement of the core lifter in the rock, the support and core receiver sections are hinged. The device is equipped with a spring for angular shift in the core-reception part.

Core mechanics and configuration behavior of advanced LMFBR core restraint concepts

International Nuclear Information System (INIS)

Fox, J.N.; Wei, B.C.

1978-02-01

Core restraint systems in LMFBRs maintain control of core mechanics and configuration behavior. Core restraint design is complex due to the close spacing between adjacent components, flux and temperature gradients, and irradiation-induced material property effects. Since the core assemblies interact with each other and transmit loads directly to the core restraint structural members, the core assemblies themselves are an integral part of the core restraint system. This paper presents an assessment of several advanced core restraint system and core assembly concepts relative to the expected performance of currently accepted designs. A recommended order for the development of the advanced concepts is also presented

Towards the Sigma Online Learning Model for crowdsourced recommendations of good web-based learning resources

OpenAIRE

Aaberg, Robin Garen

2016-01-01

The web based learning resources is believed to be playing an active role in the learning environment of higher education today. This qualitative study is exploring how students at Bergen University College incorporate web-based learning resources in their learning activities. At the core of this research is the problem of retrieving good web-resources after their first discovery. Usefull and knowledge granting web-resources are discovered within a context of topics, objectives. It is here ar...

77 FR 23766 - Advisory Committee for Education and Human Resources; Notice of Meeting

Science.gov (United States)

2012-04-20

...'s science, technology, engineering, and mathematics (STEM) education and human resources programming. Agenda May 9, 2012 Morning Refreshments/Introductions, 2013 Budget and Planning, EHR's R&D Core Launch...

Quality and Safety as a Core Leadership Competency.

Science.gov (United States)

Bleich, Michael R

2018-05-01

A leader's toolbox of competencies comprises knowledge, skills, and abilities in clinical care, finance, human resource management, and more. As essential as these are, a strong command of quality and safety competencies is sovereign in leading and managing, ensuring an optimal patient experience. Four core areas of quality and safety competencies are presented: systems science, knowledge workers, implementation science and big data, and quality safety tools and techniques. J Contin Educ Nurs. 2018;49(5):200-202. Copyright 2018, SLACK Incorporated.

How cores grow by pebble accretion. I. Direct core growth

Science.gov (United States)

Brouwers, M. G.; Vazan, A.; Ormel, C. W.

2018-03-01

Context. Planet formation by pebble accretion is an alternative to planetesimal-driven core accretion. In this scenario, planets grow by the accretion of cm- to m-sized pebbles instead of km-sized planetesimals. One of the main differences with planetesimal-driven core accretion is the increased thermal ablation experienced by pebbles. This can provide early enrichment to the planet's envelope, which influences its subsequent evolution and changes the process of core growth. Aims: We aim to predict core masses and envelope compositions of planets that form by pebble accretion and compare mass deposition of pebbles to planetesimals. Specifically, we calculate the core mass where pebbles completely evaporate and are absorbed before reaching the core, which signifies the end of direct core growth. Methods: We model the early growth of a protoplanet by calculating the structure of its envelope, taking into account the fate of impacting pebbles or planetesimals. The region where high-Z material can exist in vapor form is determined by the temperature-dependent vapor pressure. We include enrichment effects by locally modifying the mean molecular weight of the envelope. Results: In the pebble case, three phases of core growth can be identified. In the first phase (Mcore mixes outwards, slowing core growth. In the third phase (Mcore > 0.5M⊕), the high-Z inner region expands outwards, absorbing an increasing fraction of the ablated material as vapor. Rainout ends before the core mass reaches 0.6 M⊕, terminating direct core growth. In the case of icy H2O pebbles, this happens before 0.1 M⊕. Conclusions: Our results indicate that pebble accretion can directly form rocky cores up to only 0.6 M⊕, and is unable to form similarly sized icy cores. Subsequent core growth can proceed indirectly when the planet cools, provided it is able to retain its high-Z material.

ASER core curriculum illustration project: aortic intramural hematoma (IMH).

Science.gov (United States)

Perez-Girbes, Alexandre; Dunham, Gregor M; Linnau, Ken F

2017-04-01

This is the 23rd installment of a series that will highlight one case per publication issue from the bank of cases available online as part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online, please visit the ASER Core Curriculum and Recommendations for Study online at http://www.aseronline.org/curriculum/toc.htm .

Personality Model in Human Resources Management

OpenAIRE

Jovan Zubovic

2008-01-01

This paper presents the new „Personality model” of managing human resources in an organisation. The model analyses administrative personnel (usually called management) in an organisation and divides them into three core categories: managers, executives and advisors. Unlike traditional models which do not recognise advisors as part of an organisation, this model gives to advisors the same ranking as managers and executives. Model traces 11 categories of personality traits for every employee, r...

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

DEFF Research Database (Denmark)

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

2013-01-01

The BCR-ABL T315I mutation confers resistance to currently licensed tyrosine kinase inhibitors in chronic myelogenous leukemia. However, the impact of this mutation on survival in early stages of disease, in chronic phase, has never been detailed. Using matched pair analysis, a cohort of 64...... patients with chronic phase chronic myelogenous leukemia harboring a T315I mutation and resistant to imatinib mesylate was compared to a similar cohort of 53 chronic phase patients resistant to imatinib, but with no detectable T315I mutation, in the pre-ponatinib era. These patients were matched according...... to age at diagnosis, interval between disease diagnosis and start of imatinib treatment, and duration of imatinib therapy. Kaplan-Meier survival analyses demonstrated the significant negative impact of the presence of the T315I mutation on overall survival (since imatinib-resistance: 48.4 months for T315...

Multimedia adaptation with SIP resource availability signalling in IMS-networks

NARCIS (Netherlands)

Ozcelebi, T.; Radovanovic, I.

2007-01-01

Unlicensed, nondedicated and nondeterministic computer access networks are included in IP multimedia subsystem (IMS) in addition to the operator core network, which arises new end-to-end quality-of-service (QoS) issues for multimedia streaming. The resource availability of the network and the

Comparison of facility characteristics between SCTF Core-I and Core-II

International Nuclear Information System (INIS)

Adachi, Hiromichi; Iwamura, Takamichi; Sobajima, Makoto; Ohnuki, Akira; Abe, Yutaka; Murao, Yoshio.

1990-08-01

The Slab Core Test Facility (SCTF) was constructed to investigate two-dimensional thermal-hydraulics in the core and fluid behavior of carryover water out of the core including its feed-back effect to the core behavior mainly during the reflood phase of a large break loss-of-coolant accident (LOCA) of a pressurized water reactor (PWR). Since three simulated cores are used in the SCTF Test Program and the design of these three cores are slightly different one by one, repeatability test is required to justify a direct comparison of data obtained with different cores. In the present report, data of Test S2-13 (Run 618) obtained with SCTF Core-II were compared with those of Test S1-05 (Run 511) obtained with the Core-I, which were performed under the forced-flooding condition. Thermal-hydraulic behaviors in these two tests showed quite similar characteristics of both system behavior and two-dimensional core behaviors. Therefore, the test data obtained from the two cores can be compared directly with each other. After the turnaround of clad temperatures, however, some differences were found in upper plenum water accumulation and resultant two-dimensional core cooling behaviors such as quench front propagation from bottom to top of the core. (author)

Temporal Change of Seismic Earth's Inner Core Phases: Inner Core Differential Rotation Or Temporal Change of Inner Core Surface?

Science.gov (United States)

Yao, J.; Tian, D.; Sun, L.; Wen, L.

2017-12-01

Since Song and Richards [1996] first reported seismic evidence for temporal change of PKIKP wave (a compressional wave refracted in the inner core) and proposed inner core differential rotation as its explanation, it has generated enormous interests in the scientific community and the public, and has motivated many studies on the implications of the inner core differential rotation. However, since Wen [2006] reported seismic evidence for temporal change of PKiKP wave (a compressional wave reflected from the inner core boundary) that requires temporal change of inner core surface, both interpretations for the temporal change of inner core phases have existed, i.e., inner core rotation and temporal change of inner core surface. In this study, we discuss the issue of the interpretation of the observed temporal changes of those inner core phases and conclude that inner core differential rotation is not only not required but also in contradiction with three lines of seismic evidence from global repeating earthquakes. Firstly, inner core differential rotation provides an implausible explanation for a disappearing inner core scatterer between a doublet in South Sandwich Islands (SSI), which is located to be beneath northern Brazil based on PKIKP and PKiKP coda waves of the earlier event of the doublet. Secondly, temporal change of PKIKP and its coda waves among a cluster in SSI is inconsistent with the interpretation of inner core differential rotation, with one set of the data requiring inner core rotation and the other requiring non-rotation. Thirdly, it's not reasonable to invoke inner core differential rotation to explain travel time change of PKiKP waves in a very small time scale (several months), which is observed for repeating earthquakes in Middle America subduction zone. On the other hand, temporal change of inner core surface could provide a consistent explanation for all the observed temporal changes of PKIKP and PKiKP and their coda waves. We conclude that

Core competency requirements among extension workers in peninsular Malaysia: Use of Borich's needs assessment model.

Science.gov (United States)

Umar, Sulaiman; Man, Norsida; Nawi, Nolila Mohd; Latif, Ismail Abd; Samah, Bahaman Abu

2017-06-01

The study described the perceived importance of, and proficiency in core agricultural extension competencies among extension workers in Peninsular Malaysia; and evaluating the resultant deficits in the competencies. The Borich's Needs Assessment Model was used to achieve the objectives of the study. A sample of 298 respondents was randomly selected and interviewed using a pre-tested structured questionnaire. Thirty-three core competency items were assessed. Instrument validity and reliability were ensured. The cross-sectional data obtained was analysed using SPSS for descriptive statistics including mean weighted discrepancy score (MWDS). Results of the study showed that on a scale of 5, the most important core extension competency items according to respondents' perception were: "Making good use of information and communication technologies/access and use of web-based resources" (M=4.86, SD=0.23); "Conducting needs assessments" (M=4.84, SD=0.16); "organizing extension campaigns" (M=4.82, SD=0.47) and "Managing groups and teamwork" (M=4.81, SD=0.76). In terms of proficiency, the highest competency identified by the respondents was "Conducting farm and home visits (M=3.62, SD=0.82) followed by 'conducting meetings effectively' (M=3.19, SD=0.72); "Conducting focus group discussions" (M=3.16, SD=0.32) and "conducting community forums" (M=3.13, SD=0.64). The discrepancies implying competency deficits were widest in "Acquiring and allocating resources" (MWDS=12.67); use of information and communication technologies (ICTs) and web-based resources in agricultural extension (MWDS=12.59); and report writing and sharing the results and impacts (MWDS=11.92). It is recommended that any intervention aimed at developing the capacity of extension workers in Peninsular Malaysia should prioritize these core competency items in accordance with the deficits established in this study. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fe-based nanocrystalline powder cores with ultra-low core loss

Energy Technology Data Exchange (ETDEWEB)

Wang, Xiangyue, E-mail: wangxiangyue1986@163.com [China Iron and Steel Research Institute Group, Beijing 100081 (China); Center of Advanced Technology and Materials Co., Ltd., Beijing 100081 (China); Lu, Zhichao; Lu, Caowei; Li, Deren [China Iron and Steel Research Institute Group, Beijing 100081 (China); Center of Advanced Technology and Materials Co., Ltd., Beijing 100081 (China)

2013-12-15

Melt-spun amorphous Fe{sub 73.5}Cu{sub 1}Nb{sub 3}Si{sub 15.5}B{sub 7} alloy strip was crushed to make flake-shaped fine powders. The passivated powders by phosphoric acid were mixed with organic and inorganic binder, followed by cold compaction to form toroid-shaped bonded powder-metallurgical magnets. The powder cores were heat-treated to crystallize the amorphous structure and to control the nano-grain structure. Well-coated phosphate-oxide insulation layer on the powder surface decreased the the core loss with the insulation of each powder. FeCuNbSiB nanocrystalline alloy powder core prepared from the powder having phosphate-oxide layer exhibits a stable permeability up to high frequency range over 2 MHz. Especially, the core loss could be reduced remarkably. At the other hand, the softened inorganic binder in the annealing process could effectively improve the intensity of powder cores. - Highlights: • Fe-based nanocrystalline powder cores were prepared with low core loss. • Well-coated phosphate-oxide insulation layer on the powder surface decreased the core loss. • Fe-based nanocrystalline powder cores exhibited a stable permeability up to high frequency range over 2 MHz. • The softened inorganic binder in the annealing process could effectively improve the intensity of powder cores.

Developing the Clarity and Openness in Reporting: E3-based (CORE) Reference user manual for creation of clinical study reports in the era of clinical trial transparency.

Science.gov (United States)

Hamilton, Samina; Bernstein, Aaron B; Blakey, Graham; Fagan, Vivien; Farrow, Tracy; Jordan, Debbie; Seiler, Walther; Shannon, Anna; Gertel, Art

2016-01-01

Interventional clinical studies conducted in the regulated drug research environment are reported using International Council for Harmonisation (ICH) regulatory guidance documents: ICH E3 on the structure and content of clinical study reports (CSRs) published in 1995 and ICH E3 supplementary Questions & Answers (Q & A) published in 2012.Since the ICH guidance documents were published, there has been heightened awareness of the importance of disclosure of clinical study results. The use of the CSR as a key source document to fulfil emerging obligations has resulted in a re-examination of how ICH guidelines are applied in CSR preparation. The dynamic regulatory and modern drug development environments create emerging reporting challenges. Regulatory medical writing and statistical professionals developed Clarity and Openness in Reporting: E3-based (CORE) Reference over a 2-year period. Stakeholders contributing expertise included a global industry association, regulatory agency, patient advocate, academic and Principal Investigator representatives. CORE Reference should help authors navigate relevant guidelines as they create CSR content relevant for today's studies. It offers practical suggestions for developing CSRs that will require minimum redaction and modification prior to public disclosure.CORE Reference comprises a Preface, followed by the actual resource. The Preface clarifies intended use and underlying principles that inform resource utility. The Preface lists references contributing to development of the resource, which broadly fall into 'regulatory' and 'public disclosure' categories. The resource includes ICH E3 guidance text, ICH E3 Q & A 2012-derived guidance text and CORE Reference text, distinguished from one another through the use of shading. Rationale comments are used throughout for clarification purposes.A separate mapping tool comparing ICH E3 sectional structure and CORE Reference sectional structure is also provided.Together, CORE Reference

Opportunistic Computing with Lobster: Lessons Learned from Scaling up to 25k Non-Dedicated Cores

Science.gov (United States)

Wolf, Matthias; Woodard, Anna; Li, Wenzhao; Hurtado Anampa, Kenyi; Yannakopoulos, Anna; Tovar, Benjamin; Donnelly, Patrick; Brenner, Paul; Lannon, Kevin; Hildreth, Mike; Thain, Douglas

2017-10-01

We previously described Lobster, a workflow management tool for exploiting volatile opportunistic computing resources for computation in HEP. We will discuss the various challenges that have been encountered while scaling up the simultaneous CPU core utilization and the software improvements required to overcome these challenges. Categories: Workflows can now be divided into categories based on their required system resources. This allows the batch queueing system to optimize assignment of tasks to nodes with the appropriate capabilities. Within each category, limits can be specified for the number of running jobs to regulate the utilization of communication bandwidth. System resource specifications for a task category can now be modified while a project is running, avoiding the need to restart the project if resource requirements differ from the initial estimates. Lobster now implements time limits on each task category to voluntarily terminate tasks. This allows partially completed work to be recovered. Workflow dependency specification: One workflow often requires data from other workflows as input. Rather than waiting for earlier workflows to be completed before beginning later ones, Lobster now allows dependent tasks to begin as soon as sufficient input data has accumulated. Resource monitoring: Lobster utilizes a new capability in Work Queue to monitor the system resources each task requires in order to identify bottlenecks and optimally assign tasks. The capability of the Lobster opportunistic workflow management system for HEP computation has been significantly increased. We have demonstrated efficient utilization of 25 000 non-dedicated cores and achieved a data input rate of 30 Gb/s and an output rate of 500GB/h. This has required new capabilities in task categorization, workflow dependency specification, and resource monitoring.

Discontinuous Galerkin Dynamical Core in HOMME

Energy Technology Data Exchange (ETDEWEB)

Nair, R. D. [Univ. of Colorado, Boulder, CO (United States); Tufo, Henry [Univ. of Colorado, Boulder, CO (United States)

2012-08-14

Atmospheric numerical modeling has been going through radical changes over the past decade. One major reason for this trend is due to the recent paradigm change in scientific computing , triggered by the arrival of petascale computing resources with core counts in the tens of thousands to hundreds of thousands range. Modern atmospheric modelers must adapt grid systems and numerical algorithms to facilitate an unprecedented levels of scalability on these modern highly parallel computer architectures. The numerical algorithms which can address these challenges should have the local properties such as high on-processor floating-point operation count to bytes moved and minimum parallel communication overhead.

In-core Instrument Subcritical Verification (INCISV) - Core Design Verification Method - 358

International Nuclear Information System (INIS)

Prible, M.C.; Heibel, M.D.; Conner, S.L.; Sebastiani, P.J.; Kistler, D.P.

2010-01-01

According to the standard on reload startup physics testing, ANSI/ANS 19.6.1, a plant must verify that the constructed core behaves sufficiently close to the designed core to confirm that the various safety analyses bound the actual behavior of the plant. A large portion of this verification must occur before the reactor operates at power. The INCISV Core Design Verification Method uses the unique characteristics of a Westinghouse Electric Company fixed in-core self powered detector design to perform core design verification after a core reload before power operation. A Vanadium self powered detector that spans the length of the active fuel region is capable of confirming the required core characteristics prior to power ascension; reactivity balance, shutdown margin, temperature coefficient and power distribution. Using a detector element that spans the length of the active fuel region inside the core provides a signal of total integrated flux. Measuring the integrated flux distributions and changes at various rodded conditions and plant temperatures, and comparing them to predicted flux levels, validates all core necessary core design characteristics. INCISV eliminates the dependence on various corrections and assumptions between the ex-core detectors and the core for traditional physics testing programs. This program also eliminates the need for special rod maneuvers which are infrequently performed by plant operators during typical core design verification testing and allows for safer startup activities. (authors)

[Application of digital earth technology in research of traditional Chinese medicine resources].

Science.gov (United States)

Liu, Jinxin; Liu, Xinxin; Gao, Lu; Wei, Yingqin; Meng, Fanyun; Wang, Yongyan

2011-02-01

This paper describes the digital earth technology and its core technology-"3S" integration technology. The advance and promotion of the "3S" technology provide more favorable means and technical support for Chinese medicine resources survey, evaluation and appropriate zoning. Grid is a mature and popular technology that can connect all kinds of information resources. The author sums up the application of digital earth technology in the research of traditional Chinese medicine resources in recent years, and proposes the new method and technical route of investigation in traditional Chinese medicine resources, traditional Chinese medicine zoning and suitability assessment by combining the digital earth technology and grid.

Waves in the core and mechanical core-mantle interactions

DEFF Research Database (Denmark)

Jault, D.; Finlay, Chris

2015-01-01

This Chapter focuses on time-dependent uid motions in the core interior, which can beconstrained by observations of the Earth's magnetic eld, on timescales which are shortcompared to the magnetic diusion time. This dynamics is strongly inuenced by the Earth's rapid rotation, which rigidies...... the motions in the direction parallel to the Earth'srotation axis. This property accounts for the signicance of the core-mantle topography.In addition, the stiening of the uid in the direction parallel to the rotation axis gives riseto a magnetic diusion layer attached to the core-mantle boundary, which would...... otherwisebe dispersed by Alfven waves. This Chapter complements the descriptions of large-scaleow in the core (8.04), of turbulence in the core (8.06) and of core-mantle interactions(8.12), which can all be found in this volume. We rely on basic magnetohydrodynamictheory, including the derivation...

A core design study for 'zero-sodium-void-worth' cores

International Nuclear Information System (INIS)

Kawashima, Masatoshi; Suzuki, Masao; Hill, R.N.

1992-01-01

Recently, a number of low sodium-void-worth metal-fueled core design concepts have been proposed; to provide for flexibility in transuranic nuclide management strategy, core designs which exhibit a wide range of breeding characteristics have been developed. Two core concepts, a flat annular (transuranic burning) core and an absorber-type parfait (transuranic self-sufficient) core, are selected for this study. In this paper, the excess reactivity management schemes applied in the two designs are investigated in detail. In addition, the transient effect of reactivity insertions on the parfait core design is assessed. The upper and lower core regions in the parfait design are neutronically decoupled; however, the common coolant channel creates thermalhydraulic coupling. This combination of neutronic and thermalhydraulic characteristics leads to unique behavior in anticipated transient overpower events. (author)

A multipurpose computing center with distributed resources

Science.gov (United States)

Chudoba, J.; Adam, M.; Adamová, D.; Kouba, T.; Mikula, A.; Říkal, V.; Švec, J.; Uhlířová, J.; Vokáč, P.; Svatoš, M.

2017-10-01

The Computing Center of the Institute of Physics (CC IoP) of the Czech Academy of Sciences serves a broad spectrum of users with various computing needs. It runs WLCG Tier-2 center for the ALICE and the ATLAS experiments; the same group of services is used by astroparticle physics projects the Pierre Auger Observatory (PAO) and the Cherenkov Telescope Array (CTA). OSG stack is installed for the NOvA experiment. Other groups of users use directly local batch system. Storage capacity is distributed to several locations. DPM servers used by the ATLAS and the PAO are all in the same server room, but several xrootd servers for the ALICE experiment are operated in the Nuclear Physics Institute in Řež, about 10 km away. The storage capacity for the ATLAS and the PAO is extended by resources of the CESNET - the Czech National Grid Initiative representative. Those resources are in Plzen and Jihlava, more than 100 km away from the CC IoP. Both distant sites use a hierarchical storage solution based on disks and tapes. They installed one common dCache instance, which is published in the CC IoP BDII. ATLAS users can use these resources using the standard ATLAS tools in the same way as the local storage without noticing this geographical distribution. Computing clusters LUNA and EXMAG dedicated to users mostly from the Solid State Physics departments offer resources for parallel computing. They are part of the Czech NGI infrastructure MetaCentrum with distributed batch system based on torque with a custom scheduler. Clusters are installed remotely by the MetaCentrum team and a local contact helps only when needed. Users from IoP have exclusive access only to a part of these two clusters and take advantage of higher priorities on the rest (1500 cores in total), which can also be used by any user of the MetaCentrum. IoP researchers can also use distant resources located in several towns of the Czech Republic with a capacity of more than 12000 cores in total.

k-core covers and the core

NARCIS (Netherlands)

Sanchez-Rodriguez, E.; Borm, Peter; Estevez-Fernandez, A.; Fiestras-Janeiro, G.; Mosquera, M.A.

This paper extends the notion of individual minimal rights for a transferable utility game (TU-game) to coalitional minimal rights using minimal balanced families of a specific type, thus defining a corresponding minimal rights game. It is shown that the core of a TU-game coincides with the core of

Decision support for natural resource management; models and evaluation methods

NARCIS (Netherlands)

Wessels, J.; Makowski, M.; Nakayama, H.

2001-01-01

When managing natural resources or agrobusinesses, one always has to deal with autonomous processes. These autonomous processes play a core role in designing model-based decision support systems. This chapter tries to give insight into the question of which types of models might be used in which

78 FR 31563 - Ryan White HIV/AIDS Program Core Medical Services Waiver; Application Requirements

Science.gov (United States)

2013-05-24

... HIV/AIDS Program Core Medical Services Waiver; Application Requirements AGENCY: Health Resources and... Public Health Service Act, as amended by the Ryan White HIV/AIDS Treatment Extension Act of 2009 (Ryan... medical services, including antiretroviral drugs, for individuals with HIV/AIDS identified and eligible...

[Construction of the addiction prevention core competency model for preventing addictive behavior in adolescents].

Science.gov (United States)

Park, Hyun Sook; Jung, Sun Young

2013-12-01

This study was done to provide fundamental data for the development of competency reinforcement programs to prevent addictive behavior in adolescents through the construction and examination of an addiction prevention core competency model. In this study core competencies for preventing addictive behavior in adolescents through competency modeling were identified, and the addiction prevention core competency model was developed. It was validated methodologically. Competencies for preventing addictive behavior in adolescents as defined by the addiction prevention core competency model are as follows: positive self-worth, self-control skill, time management skill, reality perception skill, risk coping skill, and positive communication with parents and with peers or social group. After construction, concurrent cross validation of the addiction prevention core competency model showed that this model was appropriate. The study results indicate that the addiction prevention core competency model for the prevention of addictive behavior in adolescents through competency modeling can be used as a foundation for an integral approach to enhance adolescent is used as an adjective and prevent addictive behavior. This approach can be a school-centered, cost-efficient strategy which not only reduces addictive behavior in adolescents, but also improves the quality of their resources.

Nurture of human resources for geological repository program

International Nuclear Information System (INIS)

Fujiwara, A.

2004-01-01

The Japanese geological repository program entered the implementing stage in 2002. At the implementing stage of the program, different sectors need various human resources to conduct their functions. This paper discusses a suitable framework of nurture of the human resources to progress the geological repository program. The discussion is based on considering of specific characters involved in the program and of the multidisciplinary knowledge related to geological disposal. Considering the specific characters of the project, two types of the human resources need to be nurtured. First type is the core persons with the highest knowledge on geological disposal. They are expected to communicate with the various stakeholders and pass down the whole knowledge of the project to the next generation. Another is to conduct the project as the managers, the engineers and the workers. The former human resources can be developed through the broad practice and experience in each sector. The latter human resources can be effectively developed by training of the fundamental knowledge on geological disposal at training centers as well as by conventional on-the-job training. The sectors involved in the program need to take their own roles in the nurture of these human resources. (author)

An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

Science.gov (United States)

Steegmann, Juan Luis; Colomer, Dolors; Gómez-Casares, Maria-Teresa; García-Gutiérrez, Valentín; Ortí, Guillermo; Ramírez-Payer, Angel; Olavarria, Eduardo; Vall-Llovera, Ferrán; Giraldo, Pilar; Conde, Eulogio; Vallansot, Rolando; López-Lorenzo, Jose Luis; Palomera, Luis; Álvarez-Larrán, Alberto; Conesa, Venancio; Bautista, Guiomar; Casas, Laura; Giles, Frank; Hochhaus, Andreas; Casado-Montero, Luis Felipe

2017-10-01

This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter. This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter). The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months. The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

Core catcher for nuclear reactor core meltdown containment

International Nuclear Information System (INIS)

Driscoll, M.J.; Bowman, F.L.

1978-01-01

A bed of graphite particles is placed beneath a nuclear reactor core outside the pressure vessel but within the containment building to catch the core debris in the event of failure of the emergency core cooling system. Spray cooling of the debris and graphite particles together with draining and flooding of coolant fluid of the graphite bed is provided to prevent debris slump-through to the bottom of the bed

A pressure core ultrasonic test system for on-board analysis of gas hydrate-bearing sediments under in situ pressures.

Science.gov (United States)

Yang, Lei; Zhou, Weihua; Xue, Kaihua; Wei, Rupeng; Ling, Zheng

2018-05-01

The enormous potential as an alternative energy resource has made natural gas hydrates a material of intense research interest. Their exploration and sample characterization require a quick and effective analysis of the hydrate-bearing cores recovered under in situ pressures. Here a novel Pressure Core Ultrasonic Test System (PCUTS) for on-board analysis of sediment cores containing gas hydrates at in situ pressures is presented. The PCUTS is designed to be compatible with an on-board pressure core transfer device and a long gravity-piston pressure-retained corer. It provides several advantages over laboratory core analysis including quick and non-destructive detection, in situ and successive acoustic property acquisition, and remission of sample storage and transportation. The design of the unique assembly units to ensure the in situ detection is demonstrated, involving the U-type protecting jackets, transducer precession device, and pressure stabilization system. The in situ P-wave velocity measurements make the detection of gas hydrate existence in the sediments possible on-board. Performance tests have verified the feasibility and sensitivity of the ultrasonic test unit, showing the dependence of P-wave velocity on gas hydrate saturation. The PCUTS has been successfully applied for analysis of natural samples containing gas hydrates recovered from the South China Sea. It is indicated that on-board P-wave measurements could provide a quick and effective understanding of the hydrate occurrence in natural samples, which can assist further resource exploration, assessment, and subsequent detailed core analysis.

A pressure core ultrasonic test system for on-board analysis of gas hydrate-bearing sediments under in situ pressures

Science.gov (United States)

Yang, Lei; Zhou, Weihua; Xue, Kaihua; Wei, Rupeng; Ling, Zheng

2018-05-01

The enormous potential as an alternative energy resource has made natural gas hydrates a material of intense research interest. Their exploration and sample characterization require a quick and effective analysis of the hydrate-bearing cores recovered under in situ pressures. Here a novel Pressure Core Ultrasonic Test System (PCUTS) for on-board analysis of sediment cores containing gas hydrates at in situ pressures is presented. The PCUTS is designed to be compatible with an on-board pressure core transfer device and a long gravity-piston pressure-retained corer. It provides several advantages over laboratory core analysis including quick and non-destructive detection, in situ and successive acoustic property acquisition, and remission of sample storage and transportation. The design of the unique assembly units to ensure the in situ detection is demonstrated, involving the U-type protecting jackets, transducer precession device, and pressure stabilization system. The in situ P-wave velocity measurements make the detection of gas hydrate existence in the sediments possible on-board. Performance tests have verified the feasibility and sensitivity of the ultrasonic test unit, showing the dependence of P-wave velocity on gas hydrate saturation. The PCUTS has been successfully applied for analysis of natural samples containing gas hydrates recovered from the South China Sea. It is indicated that on-board P-wave measurements could provide a quick and effective understanding of the hydrate occurrence in natural samples, which can assist further resource exploration, assessment, and subsequent detailed core analysis.

Characterization of chickpea germplasm conserved in the Indian National Genebank and development of a core set using qualitative and quantitative trait data

Directory of Open Access Journals (Sweden)

Sunil Archak

2016-10-01

Full Text Available Chickpea is the third most important pulse crop as a source of dietary protein. Ever-increasing demand in Asian countries calls for breeding superior desi-type varieties, in turn necessitating the availability of characterized germplasm to breeders. The Indian National Genebank, located at the National Bureau of Plant Genetic Resources, New Delhi, conserves 14,651 accessions of chickpea. The entire set was characterized in a single large-scale experiment. High variation was observed for eight quantitative and 12 qualitative agro-morphological traits. Allelic richness procedure was employed to assemble a core set comprising 1103 accessions, 70.0% of which were of Indian origin. Comparable values of total variation explained by the first three principal components in the entire collection (51.1% and the core (52.4% together with conservation of nine pairwise r values among quantitative traits in the core collection and a coincidence rate around 99.7% indicated that the chickpea core was indeed an excellent representation of the entire chickpea collection in the National Genebank. The chickpea core exhibited greater diversity than the entire collection in agro-morphological traits, as assessed by higher variance and Shannon–Weaver diversity indices, indicating that the chickpea core maximized the phenotypic diversity available in the Indian chickpea germplasm. The chickpea core, comprising mainly indigenous desi genotypes, is expected to be an excellent resource for chickpea breeders. Information on the chickpea core can be accessed at http://www.nbpgr.ernet.in/pgrportal.

Human resource management in the Georgian National Immunization Program: a baseline assessment

OpenAIRE

Cohen-Kohler Jillian; Esmail Laura C; Djibuti Mamuka

2007-01-01

Abstract Background Georgia's health care system underwent dramatic reform after gaining independence in 1991. The decentralization of the health care system was one of the core elements of health care reform but reports suggest that human resource management issues were overlooked. The Georgian national immunization program was affected by these reforms and is not functioning at optimum levels. This paper describes the state of human resource management practices within the Georgian national...

A study on literature obsolescence and core journals' cost-benefit in citations of the 'Scientific Medical Journal of Ahwaz'.

Science.gov (United States)

Zare-Farashbandi, Firoozeh; Mohammadi, Parastoo Parsaei

2014-01-01

One of the methods of identifying core and popular resources is by citation evaluation. Using citation evaluation, the librarians of the Acquisition Department can use quantitative methods to indentify core and popular resources among numerous information resources and make serious savings in the library's budget, by acquiring these core resources and eliminating useless ones. The aim of this study is assessing literature obsolescence and core journals' cost-benefit in citations of the 'Scientific Medical Journal of Ahwaz'. This study is a descriptive and cross-sectional survey that uses citation analysis. Sampling is objective sampling from all documents from years 1364 (1985) to 1385 (2006), and the population comprises of 6342 citations of the articles published in 'Scientific Medical Journal of Ahwaz'. Data collection is done through referring to the original documents and the data is analyzed using the Excel software, and for descriptive and analytical statistics the cost-benefit formula and Bradford law formula are used. Findings showed that the average citation for each document in the 'Scientific Medical Journal of Ahwaz' was 15.81. The average citation to international sources was 14.37, and the average citation to national sources was 1.44. The literature obsolescence of Farsi documents in this study was 15 years, while it was equal to 20 years for English documents. The highly cited Farsi journals were (sorted based on citation in descending order): 'Scientific Medical Journal of Ahwaz', 'Daroudarman', 'Nabz,' and 'Journal of Medical School, Shahid Beheshti University of Medical Sciences'. The highly cited English journals were (sorted based on citation in descending order): 'Pediatrics', 'The New England Journal of Medicine', 'Gastroenterology' and 'Medicine'. All of these four journals are part of the ISI database and have good impact factors in the Journal Citation Reports (JCR). Also their cost-benefit was reasonable based on the frequency of their

MOX recycling in GEN 3 + EPR Reactor homogeneous and stable full MOX core

Energy Technology Data Exchange (ETDEWEB)

Arslan, M.; Villele, E. de; Gauthier, J.C.; Marincic, A. [AREVA - Tour AREVA, 1 Place Jean Millier, 92084 Paris La Defense (France)

2013-07-01

In the case of the EPR (European Pressurized Reactor) reactor, 100% MOX core management is possible with simple design adaptations which are not significantly costly. 100% MOX core management offers several highly attractive advantages. First, it is possible to have the same plutonium content in all the rods of a fuel assembly instead of having rods with 3 different plutonium contents, as in MOX assemblies in current PWRs. Secondly, the full MOX core is more homogeneous. Thirdly, the stability of the core is significantly increased due to a large reduction in the Xe effect. Fourthly, there is a potential for the performance of the MOX fuel to match that of new high performance UO{sub 2} fuel (enrichment up to 4.95 %) in terms of increased burn up and cycle length. Fifthly, since there is only one plutonium content, the manufacturing costs are reduced. Sixthly, there is an increase in the operating margins of the reactor, and in the safety margins in accident conditions. The use of 100% MOX core will improve both utilisation of natural uranium resources and reductions in high level radioactive waste inventory.

MOX recycling in GEN 3 + EPR Reactor homogeneous and stable full MOX core

International Nuclear Information System (INIS)

Arslan, M.; Villele, E. de; Gauthier, J.C.; Marincic, A.

2013-01-01

In the case of the EPR (European Pressurized Reactor) reactor, 100% MOX core management is possible with simple design adaptations which are not significantly costly. 100% MOX core management offers several highly attractive advantages. First, it is possible to have the same plutonium content in all the rods of a fuel assembly instead of having rods with 3 different plutonium contents, as in MOX assemblies in current PWRs. Secondly, the full MOX core is more homogeneous. Thirdly, the stability of the core is significantly increased due to a large reduction in the Xe effect. Fourthly, there is a potential for the performance of the MOX fuel to match that of new high performance UO 2 fuel (enrichment up to 4.95 %) in terms of increased burn up and cycle length. Fifthly, since there is only one plutonium content, the manufacturing costs are reduced. Sixthly, there is an increase in the operating margins of the reactor, and in the safety margins in accident conditions. The use of 100% MOX core will improve both utilisation of natural uranium resources and reductions in high level radioactive waste inventory

Permeability of sediment cores from methane hydrate deposit in the Eastern Nankai Trough, Japan

Science.gov (United States)

Konno, Y.; Yoneda, J.; Egawa, K.; Ito, T.; Jin, Y.; Kida, M.; Suzuki, K.; Nakatsuka, Y.; Nagao, J.

2013-12-01

Effective and absolute permeability are key parameters for gas production from methane-hydrate-bearing sandy sediments. Effective and/or absolute permeability have been measured using methane-hydrate-bearing sandy cores and clayey and silty cores recovered from Daini Atsumi Knoll in the Eastern Nankai Trough during the 2012 JOGMEC/JAPEX Pressure coring operation. Liquid-nitrogen-immersed cores were prepared by rapid depressurization of pressure cores recovered by a pressure coring system referred to as the Hybrid PCS. Cores were shaped cylindrically on a lathe with spraying of liquid nitrogen to prevent hydrate dissociation. Permeability was measured by a flooding test or a pressure relaxation method under near in-situ pressure and temperature conditions. Measured effective permeability of hydrate-bearing sediments is less than tens of md, which are order of magnitude less than absolute permeability. Absolute permeability of clayey cores is approximately tens of μd, which would perform a sealing function as cap rocks. Permeability reduction due to a swelling effect was observed for a silty core during flooding test of pure water mimicking hydrate-dissociation-water. Swelling effect may cause production formation damage especially at a later stage of gas production from methane hydrate deposits. This study was financially supported by the Research Consortium for Methane Hydrate Resources in Japan (MH21 Research Consortium) that carries out Japan's Methane Hydrate R&D Program conducted by the Ministry of Economy, Trade and Industry (METI).

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-08-15

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

Development of RBWR (Resource-renewable BWR) for environmental burden reduction of radioactive wastes

International Nuclear Information System (INIS)

Hino, Tetsushi; Ohtsuka, Masaya; Moriya, Kumiaki; Matsuura, Masayoshi

2014-01-01

Accumulation of long-life transuranium elements produced as by-products with uranium fuel burning became an issue of nuclear power. Hitachi had been developing the reactor with transuranium elements burning as fuels based on BWR type reactors successfully used as commercial reactors: RBWR (Resource-renewable BWR). Efficient transmutation and fissioning of transuranium elements needed adjustment of in-core neutron energy spectra distribution better for nuclear reaction of transuranium elements. Taking advantage of characteristics of BWR type reactors with neutron spectra hardening more easily adjustable than other type of reactors, multiple recycling and fissioning transuranium elements as fuels could make environmental burden reduction of radioactive wastes and efficient use of resources compatible. This article described the concept and history of RBWR and showed its specifications and reactor core characteristics. (T. Tanaka)

Core issues of a water resource management. A review of literature

International Nuclear Information System (INIS)

Chavarro Velandia, Andres

2011-01-01

Water becomes recently scarce in many developing countries. Colombia is one of these if it takes into account the warnings included in the last national water research. Therefore is urgent debate about which are the options to achieve a sustainable management of water. So, the objective of the present paper is to explore the core issues to be considered in order to discuss the problematic of the water management for Colombia. The paper is a review of literature from 5 date bases internationally recognized. From the review it found the management of water is more than the mere use of mechanisms but it implies consider topics like governance, solid knowledge about who and how use the water and then yet the options to manage it. In addition it found that market based perspectives tend to work isolated compare to the rest of alternatives which are multi-disciplinary and multi-dimensional. Finally, stand out the fact that the non-market management tools tends to be integrated management water models (it includes multiple sources, actors and different applications)

Conceptualising 'knowledge management' in the context of library and information science using the core/periphery model

Directory of Open Access Journals (Sweden)

O.B. Onyancha

2009-04-01

Full Text Available This study took cognisance of the fact that the term 'knowledge management' lacks a universally accepted definition, and consequently sought to describe the term using the most common co-occurring terms in knowledge management (KM literature as indexed in the Library, Information Science and Technology Abstracts (LISTA database. Using a variety of approaches and analytic techniques (e.g. core/periphery analysis and co-occurrence of words as subject terms, data were analysed using the core/periphery model and social networks through UCINET for Windows, TI, textSTAT and Bibexcel computer-aided software. The study identified the following as the compound terms with which KM co-occurs most frequently: information resources management, information science, information technology, information services, information retrieval, library science, management information systems and libraries. The core single subject terms with which KM can be defined include resources, technology, libraries, systems, services, retrieval, storage, data and computers. The article concludes by offering the library and information science (LIS professionals' general perception of KM based on their use of terms, through which KM can be defined within the context of LIS.

World resources 1992-93

International Nuclear Information System (INIS)

Anon.

1992-01-01

The World Resources series is intended to meet the critical need for accessible, accurate information on some of the most pressing issues of our time. Wise management of natural resources and protection of the global environment are essential to achieve sustainable economic development and hence to alleviate poverty, improve the human condition, and preserve the biological systems on which all life depends. This volume has a special focus on sustainable development, in support of the upcoming 1992 United Nations Conference on Environment and Development (UNCED). Part 1 consists of four special chapters on sustainable development: an overview chapter and three case studies of what sustainable development might mean in industrial countries, low-income countries, and rapidly industrializing countries. Additional material pertinent to this topic is found throughout the volume. Part 2 continues the tradition of examining in each volume a particular region in more detail - in this case, an overview of the severe environmental and resource problems faced by Central Europe as that region makes a difficult transition to more democratic governments and more market-oriented economies. Part 3 reports on basic conditions and trends, key issues, major problems and efforts to resolve them, and recent developments in each of the major resource categories, from population and human development to energy to atmosphere and climate. Where data exist, the chapters give a 20-year perspective on trends in the physical environment - spanning the time between the first United Nations Conference on the Environment and UNCED. Supporting data, as well as the core data tables from the World Resources Data Base, are found in Part 4. Chapters have been processed separately for inclusion on the data base

Core Skills for Effective Science Communication: A Teaching Resource for Undergraduate Science Education

Science.gov (United States)

Mercer-Mapstone, Lucy; Kuchel, Louise

2017-01-01

Science communication is a diverse and transdisciplinary field and is taught most effectively when the skills involved are tailored to specific educational contexts. Few academic resources exist to guide the teaching of communication with non-scientific audiences for an undergraduate science context. This mixed methods study aimed to explore what…

Drilling equipment for difficult coring conditions: a new type of core lifter and triple tube core barrel

Energy Technology Data Exchange (ETDEWEB)

Robinson, J B

1968-08-01

Although considerable improvements in diamond drilling equipment have been made since the early 1950's, deficiencies in existing equipment led to the development of a new type core lifter and special 20 ft triple tube core barrel designed to operate in bad coring conditions. It is claimed that although developed essentially for coal drilling, the new equipment could be adapted to other fields of diamond drilling with the cost advantage of increased life of the core lifter.

A General Water Resources Regulation Software System in China

Science.gov (United States)

LEI, X.

2017-12-01

To avoid iterative development of core modules in water resource normal regulation and emergency regulation and improve the capability of maintenance and optimization upgrading of regulation models and business logics, a general water resources regulation software framework was developed based on the collection and analysis of common demands for water resources regulation and emergency management. It can provide a customizable, secondary developed and extensible software framework for the three-level platform "MWR-Basin-Province". Meanwhile, this general software system can realize business collaboration and information sharing of water resources regulation schemes among the three-level platforms, so as to improve the decision-making ability of national water resources regulation. There are four main modules involved in the general software system: 1) A complete set of general water resources regulation modules allows secondary developer to custom-develop water resources regulation decision-making systems; 2) A complete set of model base and model computing software released in the form of Cloud services; 3) A complete set of tools to build the concept map and model system of basin water resources regulation, as well as a model management system to calibrate and configure model parameters; 4) A database which satisfies business functions and functional requirements of general water resources regulation software can finally provide technical support for building basin or regional water resources regulation models.

Financial development and oil resource abundance-growth relations: evidence from panel data.

Science.gov (United States)

Law, Siong Hook; Moradbeigi, Maryam

2017-10-01

This study investigates whether financial development dampens the negative impact of oil resource abundance on economic growth. Because of substantial cross-sectional dependence in our data, which contain a core sample of 63 oil-producing countries from 1980 through 2010, we use the common correlated effect mean group (CCEMG) estimator to account for the high degree of heterogeneity and drop the outlier countries. The empirical results reveal that oil resource abundance affects the growth rate in output contingent on the degree of development in financial markets. More developed financial markets can channel the revenues from oil into more productive activities and thus offset the negative effects of oil resource abundance on economic growth. Thus, better financial development can reverse resource curse or enhance resource blessing in oil-rich economies.

Analyses of resource reservation schemes for optical burst switching networks

Science.gov (United States)

Solanska, Michaela; Scholtz, Lubomir; Ladanyi, Libor; Mullerova, Jarmila

2017-12-01

With growing demands of Internet Protocol services for transmission capacity and speed, the Optical Burst Switching presents the solution for future high-speed optical networks. Optical Burst Switching is a technology for transmitting large amounts of data bursts through a transparent optical switching network. To successfully transmit bursts over OBS network and reach the destination node, resource reservation schemes have to be implemented to allocate resources and configure optical switches for that burst at each node. The one-way resource reservation schemes and the performance evaluation of reservation schemes are presented. The OBS network model is performed using OMNeT++ simulation environment. During the reservation of network resources, the optical cross-connect based on semiconductor optical amplifier is used as the core node. Optical switches based on semiconductor optical amplifiers are a promising technology for high-speed optical communication networks.

Keeping Dublin Core Simple: Cross-Domain Discovery or Resource Description?; First Steps in an Information Commerce Economy: Digital Rights Management in the Emerging E-Book Environment; Interoperability: Digital Rights Management and the Emerging EBook Environment; Searching the Deep Web: Direct Query Engine Applications at the Department of Energy.

Science.gov (United States)

Lagoze, Carl; Neylon, Eamonn; Mooney, Stephen; Warnick, Walter L.; Scott, R. L.; Spence, Karen J.; Johnson, Lorrie A.; Allen, Valerie S.; Lederman, Abe

2001-01-01

Includes four articles that discuss Dublin Core metadata, digital rights management and electronic books, including interoperability; and directed query engines, a type of search engine designed to access resources on the deep Web that is being used at the Department of Energy. (LRW)

Meeting the coming organizational risk challenges in human resources

Directory of Open Access Journals (Sweden)

Zakić Nebojša

2016-01-01

Full Text Available The research presented in this paper concerns challenges of organizational risk in the field of human resources. Research goals are to determine the degree of importance and influence of human risks in order to achieve a more favorable environment for successful business. The empirical research has been conducted in Serbia during 2015, with a sample of 43 companies from the Processing industry. There were mathematical and statistical methods, multiple regression analysis and logistic regression used. Group's core results showed that over 80% of production companies are aware of the human resources risks and their importance for the business. The contribution of this paper is to prove the scientific significance of the upcoming risks of human resources establishing theoretical and empirical knowledge about the need to improve organization approach to managing these risks.

Adaptive Immunity to Leukemia Is Inhibited by Cross-Reactive Induced Regulatory T Cells.

Science.gov (United States)

Manlove, Luke S; Berquam-Vrieze, Katherine E; Pauken, Kristen E; Williams, Richard T; Jenkins, Marc K; Farrar, Michael A

2015-10-15

BCR-ABL(+) acute lymphoblastic leukemia patients have transient responses to current therapies. However, the fusion of BCR to ABL generates a potential leukemia-specific Ag that could be a target for immunotherapy. We demonstrate that the immune system can limit BCR-ABL(+) leukemia progression although ultimately this immune response fails. To address how BCR-ABL(+) leukemia escapes immune surveillance, we developed a peptide: MHC class II tetramer that labels endogenous BCR-ABL-specific CD4(+) T cells. Naive mice harbored a small population of BCR-ABL-specific T cells that proliferated modestly upon immunization. The small number of naive BCR-ABL-specific T cells was due to negative selection in the thymus, which depleted BCR-ABL-specific T cells. Consistent with this observation, we saw that BCR-ABL-specific T cells were cross-reactive with an endogenous peptide derived from ABL. Despite this cross-reactivity, the remaining population of BCR-ABL reactive T cells proliferated upon immunization with the BCR-ABL fusion peptide and adjuvant. In response to BCR-ABL(+) leukemia, BCR-ABL-specific T cells proliferated and converted into regulatory T (Treg) cells, a process that was dependent on cross-reactivity with self-antigen, TGF-β1, and MHC class II Ag presentation by leukemic cells. Treg cells were critical for leukemia progression in C57BL/6 mice, as transient Treg cell ablation led to extended survival of leukemic mice. Thus, BCR-ABL(+) leukemia actively suppresses antileukemia immune responses by converting cross-reactive leukemia-specific T cells into Treg cells. Copyright © 2015 by The American Association of Immunologists, Inc.

Characterizing the Core via K-Core Covers

NARCIS (Netherlands)

Sanchez, S.M.; Borm, P.E.M.; Estevez, A.

2013-01-01

This paper extends the notion of individual minimal rights for a transferable utility game (TU-game) to coalitional minimal rights using minimal balanced families of a specific type, thus defining a corresponding minimal rights game. It is shown that the core of a TU-game coincides with the core of

Determination of PWR core water level using ex-core detectors signals

International Nuclear Information System (INIS)

Bernal, Alvaro; Abarca, Agustin; Miro, Rafael; Verdu, Gumersindo

2013-01-01

The core water level provides relevant neutronic and thermalhydraulic information of the reactor such as power, k eff and cooling ability; in fact, core water level monitoring could be used to predict LOCA and cooling reduction which may deal with core damage. Although different detection equipment is used to monitor several parameters such as the power, core water level monitoring is not an evident task. However, ex-core detectors can measure the fast neutrons leaking the core and several studies demonstrate the existence of a relationship between fast neutron leakage and core water level due to the shielding effect of the water. In addition, new ex-core detectors are being developed, such as silicon carbide semiconductor radiation detectors, monitoring the neutron flux with higher accuracy and in higher temperatures conditions. Therefore, a methodology to determine this relationship has been developed based on a Monte Carlo calculation using MCNP code and applying variance reduction with adjoint functions based on the adjoint flux obtained with the discrete ordinates code TORT. (author)

HYDRATE CORE DRILLING TESTS

Energy Technology Data Exchange (ETDEWEB)

John H. Cohen; Thomas E. Williams; Ali G. Kadaster; Bill V. Liddell

2002-11-01

The ''Methane Hydrate Production from Alaskan Permafrost'' project is a three-year endeavor being conducted by Maurer Technology Inc. (MTI), Noble, and Anadarko Petroleum, in partnership with the U.S. DOE National Energy Technology Laboratory (NETL). The project's goal is to build on previous and ongoing R&D in the area of onshore hydrate deposition. The project team plans to design and implement a program to safely and economically drill, core and produce gas from arctic hydrates. The current work scope includes drilling and coring one well on Anadarko leases in FY 2003 during the winter drilling season. A specially built on-site core analysis laboratory will be used to determine some of the physical characteristics of the hydrates and surrounding rock. Prior to going to the field, the project team designed and conducted a controlled series of coring tests for simulating coring of hydrate formations. A variety of equipment and procedures were tested and modified to develop a practical solution for this special application. This Topical Report summarizes these coring tests. A special facility was designed and installed at MTI's Drilling Research Center (DRC) in Houston and used to conduct coring tests. Equipment and procedures were tested by cutting cores from frozen mixtures of sand and water supported by casing and designed to simulate hydrate formations. Tests were conducted with chilled drilling fluids. Tests showed that frozen core can be washed out and reduced in size by the action of the drilling fluid. Washing of the core by the drilling fluid caused a reduction in core diameter, making core recovery very difficult (if not impossible). One successful solution was to drill the last 6 inches of core dry (without fluid circulation). These tests demonstrated that it will be difficult to capture core when drilling in permafrost or hydrates without implementing certain safeguards. Among the coring tests was a simulated hydrate

Multi-objective and multi-physics optimization methodology for SFR core: application to CFV concept

International Nuclear Information System (INIS)

Fabbris, Olivier

2014-01-01

Nuclear reactor core design is a highly multidisciplinary task where neutronics, thermal-hydraulics, fuel thermo-mechanics and fuel cycle are involved. The problem is moreover multi-objective (several performances) and highly dimensional (several tens of design parameters).As the reference deterministic calculation codes for core characterization require important computing resources, the classical design method is not well suited to investigate and optimize new innovative core concepts. To cope with these difficulties, a new methodology has been developed in this thesis. Our work is based on the development and validation of simplified neutronics and thermal-hydraulics calculation schemes allowing the full characterization of Sodium-cooled Fast Reactor core regarding both neutronics performances and behavior during thermal hydraulic dimensioning transients.The developed methodology uses surrogate models (or meta-models) able to replace the neutronics and thermal-hydraulics calculation chain. Advanced mathematical methods for the design of experiment, building and validation of meta-models allows substituting this calculation chain by regression models with high prediction capabilities.The methodology is applied on a very large design space to a challenging core called CFV (French acronym for low void effect core) with a large gain on the sodium void effect. Global sensitivity analysis leads to identify the significant design parameters on the core design and its behavior during unprotected transient which can lead to severe accidents. Multi-objective optimizations lead to alternative core configurations with significantly improved performances. Validation results demonstrate the relevance of the methodology at the pre-design stage of a Sodium-cooled Fast Reactor core. (author) [fr

Rotary core drills

Energy Technology Data Exchange (ETDEWEB)

1967-11-30

The design of a rotary core drill is described. Primary consideration is given to the following component parts of the drill: the inner and outer tube, the core bit, an adapter, and the core lifter. The adapter has the form of a downward-converging sleeve and is mounted to the lower end of the inner tube. The lifter, extending from the adapter, is split along each side so that it can be held open to permit movement of a core. It is possible to grip a core by allowing the lifter to assume a closed position.

Metallic nanoshells with semiconductor cores: optical characteristics modified by core medium properties.

Science.gov (United States)

Bardhan, Rizia; Grady, Nathaniel K; Ali, Tamer; Halas, Naomi J

2010-10-26

It is well-known that the geometry of a nanoshell controls the resonance frequencies of its plasmon modes; however, the properties of the core material also strongly influence its optical properties. Here we report the synthesis of Au nanoshells with semiconductor cores of cuprous oxide and examine their optical characteristics. This material system allows us to systematically examine the role of core material on nanoshell optical properties, comparing Cu(2)O core nanoshells (ε(c) ∼ 7) to lower core dielectric constant SiO(2) core nanoshells (ε(c) = 2) and higher dielectric constant mixed valency iron oxide nanoshells (ε(c) = 12). Increasing the core dielectric constant increases nanoparticle absorption efficiency, reduces plasmon line width, and modifies plasmon energies. Modifying the core medium provides an additional means of tailoring both the near- and far-field optical properties in this unique nanoparticle system.

Models of resource planning during formation of calendar construction plans for erection of high-rise buildings

Science.gov (United States)

Pocebneva, Irina; Belousov, Vadim; Fateeva, Irina

2018-03-01

This article provides a methodical description of resource-time analysis for a wide range of requirements imposed for resource consumption processes in scheduling tasks during the construction of high-rise buildings and facilities. The core of the proposed approach and is the resource models being determined. The generalized network models are the elements of those models, the amount of which can be too large to carry out the analysis of each element. Therefore, the problem is to approximate the original resource model by simpler time models, when their amount is not very large.

Genetic resources in maize breeding

Directory of Open Access Journals (Sweden)

Anđelković Violeta

2017-01-01

Full Text Available Maize, wheat and rice are the most important cereals grown in the world. It is predicted that by 2025 maize is likely to become the crop with the greatest production globally. Conservation of maize germplasm provides the main resources for increased food and feed production. Conservation in gene banks (ex-situ is dominant strategy for maize conservation. More than 130 000 maize accessions, e.g. about 40% of total number, are stored in ten largest gene banks worldwide and Maize Research Institute Zemun Polje (MRIZP gene bank, with about 6000 accessions, is among them. Organized collecting missions started in 1961. in the former Yugoslavian territory, and up today, more than 2000 local maize landraces were stored. Pre-breeding activities that refer to identification of desirable traits from unadapted germplasm within genebank, result in materials expected to be included in breeding programs. Successful examples are LAMP, GEM and GENRES projects. At the end of XX century, at MRIZP genebank two pre-breeding activities were undertaken: eco-core and elite-core collections were created and landraces fulfilled particular criteria were chosen. In the last decade, MRIZP genebank collection was used for identification of sources for drought tolerance and improved grain quality. According to agronomic traits and general combining ability, two mini-core collections were created and included in commercial breeding programs.

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

Science.gov (United States)

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

2015-10-01

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

A core performance study on an actinide recycling 'zero-sodium-void worth' core

International Nuclear Information System (INIS)

Kawashima, M.; Nakagawa, M.; Yamaoka, M.; Kasahara, F.

1994-01-01

A core performance study was made for an absorber-type parfait core (A-APC) as one of 'Zero-sodium-void-worth' core concepts. This evaluation study pursued different two aspects; one for transuranic (TRU) management strategy, and another for a loss-of-coolant anticipated transient behavior considering the unique core configuration. The results indicated that this core has a large flexibility for actinide recycling in terms of self-sufficiency and minor actinide burning. The result also showed that this core has kept a large mitigation potential for ULOF events as well as a simple flat core concept, reflecting detailed three dimensional core bowing behavior for the A-APC configuration. (author)

Preliminaries on core image analysis using fault drilling samples; Core image kaiseki kotohajime (danso kussaku core kaisekirei)

Energy Technology Data Exchange (ETDEWEB)

Miyazaki, T; Ito, H [Geological Survey of Japan, Tsukuba (Japan)

1996-05-01

This paper introduces examples of image data analysis on fault drilling samples. The paper describes the following matters: core samples used in the analysis are those obtained from wells drilled piercing the Nojima fault which has moved in the Hygoken-Nanbu Earthquake; the CORESCAN system made by DMT Corporation, Germany, used in acquiring the image data consists of a CCD camera, a light source and core rotation mechanism, and a personal computer, its resolution being about 5 pixels/mm in both axial and circumferential directions, and 24-bit full color; with respect to the opening fractures in core samples collected by using a constant azimuth coring, it was possible to derive values of the opening width, inclination angle, and travel from the image data by using a commercially available software for the personal computer; and comparison of this core image with the BHTV record and the hydrophone VSP record (travel and inclination obtained from the BHTV record agree well with those obtained from the core image). 4 refs., 4 figs.

Learning experiences in population education: proposed guidelines and core messages.

Science.gov (United States)

1984-01-01

As a result of the 1984 Regional Workshop for the Development of Packages of Adequate Learning Requirements in Population Education, the participants tackled the problem of non-institutionalization of population education into the formal and non-formal educational curricula in their countries. Based on their deliberations, several sets of guidelines and core messages were formulated to provide countries with a more definite direction that will hopefully ensure the functional and effective integration of population education in their respective national school and out-of-school curriculum system. Useful packages of learning materials in population education should help realize the country's population policy and goals within the broader framework of socioeconomic development, and the content of the package should comprehensively cover the core messages of the country's Population Information, Education and Communication (IEC) Program. The population knowledge base of the package should be accurate and relevant; the package should provide for graphic and visual presentation and for assessment of effects on the target groups. Proposed core messages in population education discuss the advantages of small family size and delayed marriage, and aspects of responsible parenthood. Other messages discuss population resource development and population-related beliefs and values.

Using the GlideinWMS System as a Common Resource Provisioning Layer in CMS

Energy Technology Data Exchange (ETDEWEB)

Balcas, J. [Vilnius U.; Belforte, S. [Trieste U.; Bockelman, B. [Nebraska U.; Colling, D. [Imperial Coll., London; Gutsche, O. [Fermilab; Hufnagel, D. [Fermilab; Khan, F. [Quaid-i-Azam U.; Larson, K. [Fermilab; Letts, J. [UC, San Diego; Mascheroni, M. [Milan Bicocca U.; Mason, D. [Fermilab; McCrea, A. [UC, San Diego; Piperov, S. [Brown U.; Saiz-Santos, M. [UC, San Diego; Sfiligoi, I. [UC, San Diego; Tanasijczuk, A. [UC, San Diego; Wissing, C. [DESY

2015-12-23

CMS will require access to more than 125k processor cores for the beginning of Run 2 in 2015 to carry out its ambitious physics program with more and higher complexity events. During Run1 these resources were predominantly provided by a mix of grid sites and local batch resources. During the long shut down cloud infrastructures, diverse opportunistic resources and HPC supercomputing centers were made available to CMS, which further complicated the operations of the submission infrastructure. In this presentation we will discuss the CMS effort to adopt and deploy the glideinWMS system as a common resource provisioning layer to grid, cloud, local batch, and opportunistic resources and sites. We will address the challenges associated with integrating the various types of resources, the efficiency gains and simplifications associated with using a common resource provisioning layer, and discuss the solutions found. We will finish with an outlook of future plans for how CMS is moving forward on resource provisioning for more heterogenous architectures and services.

What successful math teachers do, grades 6-12 80 research-based strategies for the common core-aligned classroom

CERN Document Server

Posamentier, Alfred S (Steven); Jaye, Daniel I

2013-01-01

The math teacher's go-to resource-now updated for the Common Core! What works in math and why has never been the issue; the research is all out there. Where teachers struggle is the "how." That's the big service What Successful Math Teachers Do provides.  It's a powerful portal to what the best research looks like in practice strategy by strategy-now aligned to both the Common Core and the NCTM Standards. For each of the book's 80 strategies, the authors present A brief description A summary of supporting research The corresponding NCTM and Common Core Standards Classroom applications Possible pitfalls Recommended reading and research.

Type i CD20 antibodies recruit the B cell receptor for complement-dependent lysis of malignant B cells

DEFF Research Database (Denmark)

Engelberts, P. J.; Voorhorst, M.; Schuurman, J.

2016-01-01

. We hypothesized that CD20 Ab-induced clustering of the IgM or IgG BCR was involved in accessory CDC. Indeed, accessory CDC was consistently observed in B cell lines expressing an IgM BCR and in some cell lines expressing an IgG BCR, but it was absent in BCR- B cell lines. A direct relationship...... between BCR expression and accessory CDC was established by transfecting the BCR into CD20+ cells: OFA-F(ab')2 fragments were able to induce CDC in the CD20+BCR+ cell population, but not in the CD20+BCR- population. Importantly, OFA-F(ab')2 fragments were able to induce CDC ex vivo in malignant B cells...... isolated from patients with mantle cell lymphoma and Waldenström macroglobulinemia. In summary, accessory CDC represents a novel effector mechanism that is dependent on type I CD20 Ab-induced BCR clustering. Accessory CDC may contribute to the excellent capacity of type I CD20 Abs to induce CDC...

Sidewall coring shell

Energy Technology Data Exchange (ETDEWEB)

Edelman, Ya A; Konstantinov, L P; Martyshin, A N

1966-12-12

A sidewall coring shell consists of a housing and a detachable core catcher. The core lifter is provided with projections, the ends of which are situated in another plane, along the longitudinal axis of the lifter. The chamber has corresponding projections.

Leading Change for the Implementation of Common Core State Standards in Rural School Districts

Science.gov (United States)

Lopez, Paul; Wise, Donald

2015-01-01

Rural school districts across the nation, with their limited resources, face daunting challenges posed by the implementation of the Common Core State Standards. This article presents a recent study of 13 rural school districts in the Central Valley of California and how these districts are responding to those challenges. A total of 352 teachers…

Electromagnetically driven westward drift and inner-core superrotation in Earth's core.

Science.gov (United States)

Livermore, Philip W; Hollerbach, Rainer; Jackson, Andrew

2013-10-01

A 3D numerical model of the earth's core with a viscosity two orders of magnitude lower than the state of the art suggests a link between the observed westward drift of the magnetic field and superrotation of the inner core. In our model, the axial electromagnetic torque has a dominant influence only at the surface and in the deepest reaches of the core, where it respectively drives a broad westward flow rising to an axisymmetric equatorial jet and imparts an eastward-directed torque on the solid inner core. Subtle changes in the structure of the internal magnetic field may alter not just the magnitude but the direction of these torques. This not only suggests that the quasi-oscillatory nature of inner-core superrotation [Tkalčić H, Young M, Bodin T, Ngo S, Sambridge M (2013) The shuffling rotation of the earth's inner core revealed by earthquake doublets. Nat Geosci 6:497-502.] may be driven by decadal changes in the magnetic field, but further that historical periods in which the field exhibited eastward drift were contemporaneous with a westward inner-core rotation. The model further indicates a strong internal shear layer on the tangent cylinder that may be a source of torsional waves inside the core.

Improving the calculated core stability by the core nuclear design optimization

International Nuclear Information System (INIS)

Partanen, P.

1995-01-01

Three different equilibrium core loadings for TVO II reactor have been generated in order to improve the core stability properties at uprated power level. The reactor thermal power is assumed to be uprated from 2160 MW th to 2500 MW th , which moves the operating point after a rapid pump rundown where the core stability has been calculated from 1340 MW th and 3200 kg/s to 1675 MW th and 4000 kg/s. The core has been refuelled with ABB Atom Svea-100 -fuel, which has 3,64% w/o U-235 average enrichment in the highly enriched zone. PHOENIX lattice code has been used to provide the homogenized nuclear constants. POLCA4 static core simulator has been used for core loadings and cycle simulations and RAMONA-3B program for simulating the dynamic response to the disturbance for which the stability behaviour has been evaluated. The core decay ratio has been successfully reduced from 0,83 to 0,55 mainly by reducing the power peaking factors. (orig.) (7 figs., 1 tab.)

Geothermal alteration of basaltic core from the Snake River Plain, Idaho

Science.gov (United States)

Sant, Christopher J.

The Snake River Plain is located in the southern part of the state of Idaho. The eastern plain, on which this study focuses, is a trail of volcanics from the Yellowstone hotspot. Three exploratory geothermal wells were drilled on the Snake River Plain. This project analyzes basaltic core from the first well at Kimama, north of Burley, Idaho. The objectives of this project are to establish zones of geothermal alteration and analyze the potential for geothermal power production using sub-aquifer resources on the axial volcanic zone of the Snake River Plain. Thirty samples from 1,912 m of core were sampled and analyzed for clay content and composition using X-ray diffraction. Observations from core samples and geophysical logs are also used to establish alteration zones. Mineralogical data, geophysical log data and physical characteristics of the core suggest that the base of the Snake River Plain aquifer at the axial zone is located 960 m below the surface, much deeper than previously suspected. Swelling smectite clay clogs pore spaces and reduces porosity and permeability to create a natural base to the aquifer. Increased temperatures favor the formation of smectite clay and other secondary minerals to the bottom of the hole. Below 960 m the core shows signs of alteration including color change, formation of clay, and filling of other secondary minerals in vesicles and fractured zones of the core. The smectite clay observed is Fe-rich clay that is authigenic in some places. Geothermal power generation may be feasible using a low temperature hot water geothermal system if thermal fluids can be attained near the bottom of the Kimama well.

Space Resources Roundtable 2

Science.gov (United States)

Ignatiev, A.

2000-01-01

Contents include following: Developing Technologies for Space Resource Utilization - Concept for a Planetary Engineering Research Institute. Results of a Conceptual Systems Analysis of Systems for 200 m Deep Sampling of the Martian Subsurface. The Role of Near-Earth Asteroids in Long-Term Platinum Supply. Core Drilling for Extra-Terrestrial Mining. Recommendations by the "LSP and Manufacturing" Group to the NSF-NASA Workshop on Autonomous Construction and Manufacturing for Space Electrical Power Systems. Plasma Processing of Lunar and Planetary Materials. Percussive Force Magnitude in Permafrost. Summary of the Issues Regarding the Martian Subsurface Explorer. A Costing Strategy for Manufacturing in Orbit Using Extraterrestrial Resources. Mine Planning for Asteroid Orebodies. Organic-based Dissolution of Silicates: A New Approach to Element Extraction from LunarRegohth. Historic Frontier Processes Active in Future Space-based Mineral Extraction. The Near-Earth Space Surveillance (NIESS) Mission: Discovery, Tracking, and Characterization of Asteroids, Comets, and Artificial Satellites with a microsatellite. Privatized Space Resource Property Ownership. The Fabrication of Silicon Solar Cells on the Moon Using In-Situ Resources. A New Strategy for Exploration Technology Development: The Human Exploration and Development of Space (HEDS) Exploratiori/Commercialization Technology Initiative. Space Resources for Space Tourism. Recovery of Volatiles from the Moon and Associated Issues. Preliminary Analysis of a Small Robot for Martian Regolith Excavation. The Registration of Space-based Property. Continuous Processing with Mars Gases. Drilling and Logging in Space; An Oil-Well Perspective. LORPEX for Power Surges: Drilling, Rock Crushing. An End-To-End Near-Earth Asteroid Resource Exploitation Plan. An Engineering and Cost Model for Human Space Settlement Architectures: Focus on Space Hotels and Moon/Mars Exploration. The Development and Realization of a Silicon-60-based

Bringing ATLAS production to HPC resources. A case study with SuperMuc and Hydra

Energy Technology Data Exchange (ETDEWEB)

Duckeck, Guenter; Walker, Rodney [LMU Muenchen (Germany); Kennedy, John; Mazzaferro, Luca [RZG Garching (Germany); Kluth, Stefan [Max-Planck-Institut fuer Physik, Muenchen (Germany); Collaboration: ATLAS-Collaboration

2015-07-01

The possible usage of Supercomputer systems or HPC resources by ATLAS is now becoming viable due to the changing nature of these systems and it is also very attractive due to the need for increasing amounts of simulated data. The ATLAS experiment at CERN will begin a period of high luminosity data taking in 2015. The corresponding need for simulated data might potentially exceed the capabilities of the current Grid infrastructure. ATLAS aims to address this need by opportunistically accessing resources such as cloud and HPC systems. This contribution presents the results of two projects undertaken by LMU/LRZ and MPP/RZG to use the supercomputer facilities SuperMuc (LRZ) and Hydra (RZG). Both are Linux based supercomputers in the 100 k CPU-core category. The integration of such HPC resources into the ATLAS production system poses many challenges. Firstly, established techniques and features of standard WLCG operation are prohibited or much restricted on HPC systems, e.g. Grid middleware, software installation, outside connectivity, etc. Secondly, efficient use of available resources requires massive multi-core jobs, back-fill submission and check-pointing. We discuss the customization of these components and the strategies for HPC usage as well as possibilities for future directions.

Core Values | NREL

Science.gov (United States)

Core Values Core Values NREL's core values are rooted in a safe and supportive work environment guide our everyday actions and efforts: Safe and supportive work environment Respect for the rights physical and social environment Integrity Maintain the highest standard of ethics, honesty, and integrity

Concentrations and human health implications of heavy metals in wild aquatic organisms captured from the core area of Daya Bay's Fishery Resource Reserve, South China Sea.

Science.gov (United States)

Gu, Yang-Guang; Huang, Hong-Hui; Lin, Qin

2016-07-01

Heavy metal concentrations in edible organisms from the core area of Daya Bay's Fishery Resource Reserve, South China Sea, were determined. Samples of 14 crustacean, fish, and shellfish species were collected and analyzed. The As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn concentrations were 0.18-1.16, 0.002-0.919, 0.40-2.85, 0.07-4.10, 0.004-0.055, 0.14-1.19, 0.014-0.070, and 4.57-15.94μg/g wet weight, respectively. The As concentrations were higher than the Chinese maximum permissible levels in all of the fish and shellfish species and two crustacean species, indicating that consumption of these wild species by humans may pose health risks. However, calculations of the health risks posed to humans indicated that no significant adverse health effects would be associated with consuming these species. Copyright © 2016 Elsevier B.V. All rights reserved.

Resource Symmetric Dispatch Model for Internet of Things on Advanced Logistics

Directory of Open Access Journals (Sweden)

Guofeng Qin

2016-04-01

Full Text Available Business applications in advanced logistics service are highly concurrent. In this paper, we propose a resource symmetric dispatch model for the concurrent and cooperative tasks of the Internet of Things. In the model, the terminals receive and deliver commands, data, and information with mobile networks, wireless networks, and sensor networks. The data and information are classified and processed by the clustering servers in the cloud service platform. The cluster service, resource dispatch, and load balance are cooperative for management and monitoring of every application case during the logistics service lifecycle. In order to support the high performance of cloud service, resource symmetric dispatch algorithm among clustering servers and load balancing method among multi-cores in one server, including NIO (Non-blocking Input/Output and RMI (Remote Method Invocation are utilized to dispatch the cooperation of computation and service resources.

Seismic core shroud

International Nuclear Information System (INIS)

Puri, A.; Mullooly, J.F.

1981-01-01

A core shroud is provided, comprising: a coolant boundary, following the shape of the core boundary, for channeling the coolant through the fuel assemblies; a cylindrical band positioned inside the core barrel and surrounding the coolant boundary; and support members extending from the coolant boundary to the band, for transferring load from the coolant boundary to the band. The shroud may be assembled in parts using automated welding techniques, and it may be adjusted to fit the reactor core easily

Integrated Water Resources Management: contrasting principles, policy, and practice, Awash River Basin, Ethiopia

NARCIS (Netherlands)

Mersha, A.; Fraiture, de C.M.S.; Mehari, Alem; Masih, I.; Alamirew, T.

2016-01-01

Integrated Water Resources Management (IWRM) has been a dominant paradigm for water sector reform worldwide over the past two decades. Ethiopia, among early adopters, has developed a water policy, legislations, and strategy per IWRM core principles. However, considerable constraints are still in its

Need Assessment of the Digital Archives Industry Human Resources in Taiwan

Directory of Open Access Journals (Sweden)

Hsueh-Hua Chen

2005-03-01

Full Text Available For an industry to develop successfully, one of the most important factors is to have sufficient and high quality human resources. Digital archives industry will be one of the major industries in Taiwan. We need sufficient human resources in different areas, therefore the job categories, job descriptions, and core technologies of these human resources shall be closely tightened to the need of digital content industry in different development stages. The purpose of this study is to investigate the present status and issues of human resource development of the digital archives industry. It then will study the planning of learning map of the digital archives industry to serve as guideline for Digital Content Institute, educational training and enterprise personnel recruitment. To achieve the above objectives, the method of depth interview is used in this study. We also try to design modular training courses for human resource development of the digital archives industry. [Article Content in Chinese

Using "The Joy Luck Club" to Teach Core Standards and 21st Century Literacies

Science.gov (United States)

Burns, Leslie David; Botzakis, Stergios G.

2012-01-01

In this article the authors illustrate an instructional unit based on a Common Core grades 9-10 illustrative text--Amy Tan's "Two Kinds" from "The Joy Luck Club." They demonstrate how teachers can meet the new standards "and" respond to students' 21st-century needs by using this modern classic along with other traditional and new media resources.…

Party rules, party resources and the politics of parliamentary democracies

DEFF Research Database (Denmark)

Poguntke, Thomas; Scarrow, Susan; Webb, Paul

2016-01-01

, then investigate what it tells us about contemporary party organization in these countries, focusing on parties’ resources, structures and internal decision-making. We examine organizational patterns by country and party family, and where possible we make temporal comparisons with older data sets. Our analyses...... suggest a remarkable coexistence of uniformity and diversity. In terms of the major organizational resources on which parties can draw, such as members, staff and finance, the new evidence largely confirms the continuation of trends identified in previous research: that is, declining membership......, but enhanced financial resources and more paid staff. We also find remarkable uniformity regarding the core architecture of party organizations. At the same time, however, we find substantial variation between countries and party families in terms of their internal processes, with particular regard to how...

Diversity analysis and establishment of core subsets of hyacinth bean collection of bangladesh

International Nuclear Information System (INIS)

Islam, M.N.

2014-01-01

Plant Genetic Resource Centre, Bangladesh Agricultural Research Institute, Gazipur, Bangladesh, maintained 484 hyacinth bean (Lablab purpureusL.) accessions. Distribution of vine colors, flower and pod colors, pod curvature and beak position on pod noticed the presence of substantial variation in the collection. Shannon Diversity Index also revealed high phenotypic diversity in vine and pod characters. High diversities were estimated in quantitative characters of inflorescence and pod characters. Considering a core collection strategy, the accessions were stratified into two groups based on vine colors: green and purple. Maximum genotypes of the collection were of green vine. Each of two subgroups were divided into three groups according to colors of pod i.e., green, white and red. Each group again divided itself into two according to beak position as central and marginal of pod. High diversity was also found regarding pod curvature and beak position on it. Strategically, a core subset consisting of 36 accessions out of 484 accessions was determined. Diversity Indices of different characters of the core accessions were of equal or higher magnitudes to the respective characters of base collection indicating the better representation of core to the original collection. (author)

Analysis of core and core barrel heat-up under conditions simulating severe reactor accidents

International Nuclear Information System (INIS)

Chellaiah, S.; Viskanta, R.; Ranganathan, P.; Anand, N.K.

1987-01-01

This paper reports on the development of a model for estimating the temperature distributions in the reactor core, core barrel, thermal shield and reactor pressure vessel of a PWR during an undercooling transient. A number of numerical calculations simulating the core uncovering of the TMI-2 reactor and the subsequent heat-up of the core have been performed. The results of the calculations show that the exothermic heat release due to Zircaloy oxidation contributes to the sharp heat-up of the core. However, the core barrel temperature rise which is driven by the temperature increase of the edge of the core (e.g., the core baffle) is very modest. The maximum temperature of the core barrel never exceeded 610 K (at a system pressure of 68 bar) after a 75 minute simulation following the start of core uncovering

Improvement of Axial Reflector Cross Section Generation Model for PWR Core Analysis

Energy Technology Data Exchange (ETDEWEB)

Shim, Cheon Bo; Lee, Kyung Hoon; Cho, Jin Young [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

This paper covers the study for improvement of axial reflector XS generation model. In the next section, the improved 1D core model is represented in detail. Reflector XS generated by the improved model is compared to that of the conventional model in the third section. Nuclear design parameters generated by these two XS sets are also covered in that section. Significant of this study is discussed in the last section. Two-step procedure has been regarded as the most practical approach for reactor core designs because it offers core design parameters quite rapidly within acceptable range. Thus this approach is adopted for SMART (System-integrated Modular Advanced Reac- Tor) core design in KAERI with the DeCART2D1.1/ MASTER4.0 (hereafter noted as DeCART2D/ MASTER) code system. Within the framework of the two-step procedure based SMART core design, various researches have been studied to improve the core design reliability and efficiency. One of them is improvement of reflector cross section (XS) generation models. While the conventional FA/reflector two-node model used for most core designs to generate reflector XS cannot consider the actual configuration of fuel rods that intersect at right angles to axial reflectors, the revised model reflects the axial fuel configuration by introducing the radially simplified core model. The significance of the model revision is evaluated by observing HGC generated by DeCART2D, reflector XS, and core design parameters generated by adopting the two models. And it is verified that about 30 ppm CBC error can be reduced and maximum Fq error decreases from about 6 % to 2.5 % by applying the revised model. Error of AO and axial power shapes are also reduced significantly. Therefore it can be concluded that the simplified 1D core model improves the accuracy of the axial reflector XS and leads to the two-step procedure reliability enhancement. Since it is hard for core designs to be free from the two-step approach, it is necessary to find

Overview of core designs and requirements/criteria for core restraint systems

International Nuclear Information System (INIS)

Sutherland, W.H.

1984-09-01

The requirements and lifetime criteria for the design of a Liquid Metal Fast Breeder Reactor (LMFBR) Core Restraint System are presented. A discussion of the three types of core restraint systems used in LMFBR core design is given. Details of the core restraint system selected for FFTF are presented and the reasons for this selection given. Structural analysis procedures being used to manage the FFTF assembly irradiations are discussed. Efforts that are ongoing to validate the calculational methods and lifetime criteria are presented

A Public Database of Memory and Naive B-Cell Receptor Sequences.

Directory of Open Access Journals (Sweden)

William S DeWitt

Full Text Available The vast diversity of B-cell receptors (BCR and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

A Public Database of Memory and Naive B-Cell Receptor Sequences.

Science.gov (United States)

DeWitt, William S; Lindau, Paul; Snyder, Thomas M; Sherwood, Anna M; Vignali, Marissa; Carlson, Christopher S; Greenberg, Philip D; Duerkopp, Natalie; Emerson, Ryan O; Robins, Harlan S

2016-01-01

The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

Theoretical Investigation of Inter-core Crosstalk Properties in Homogeneous Trench-Assisted Multi-Core Fibers

DEFF Research Database (Denmark)

Ye, Feihong; Morioka, Toshio; Tu, Jiajing

2014-01-01

We derive analytical expressions for inter-core crosstalk, its dependence on core pitch and wavelength in homogeneous trench-assisted multi-core fibers. They are in excellent agreement with numerical simulation results.......We derive analytical expressions for inter-core crosstalk, its dependence on core pitch and wavelength in homogeneous trench-assisted multi-core fibers. They are in excellent agreement with numerical simulation results....

Fast data reconstructed method of Fourier transform imaging spectrometer based on multi-core CPU

Science.gov (United States)

Yu, Chunchao; Du, Debiao; Xia, Zongze; Song, Li; Zheng, Weijian; Yan, Min; Lei, Zhenggang

2017-10-01

Imaging spectrometer can gain two-dimensional space image and one-dimensional spectrum at the same time, which shows high utility in color and spectral measurements, the true color image synthesis, military reconnaissance and so on. In order to realize the fast reconstructed processing of the Fourier transform imaging spectrometer data, the paper designed the optimization reconstructed algorithm with OpenMP parallel calculating technology, which was further used for the optimization process for the HyperSpectral Imager of `HJ-1' Chinese satellite. The results show that the method based on multi-core parallel computing technology can control the multi-core CPU hardware resources competently and significantly enhance the calculation of the spectrum reconstruction processing efficiency. If the technology is applied to more cores workstation in parallel computing, it will be possible to complete Fourier transform imaging spectrometer real-time data processing with a single computer.

Neutronic design of mixed oxide-silicide cores for the core conversion of rsg-gas reactor

International Nuclear Information System (INIS)

Sembiring, Tagor Malem; Tukiran; Pinem surian; Febrianto

2001-01-01

The core conversion of rsg-gas reactor from an all-oxide (U 3 O 8 -Al) core, through a series of mixed oxide-silicide core, to an all-silicide (U 3 Si 2 -Al) core for the same meat density of 2.96 g U/cc is in progress. The conversion is first step of the step-wise conversion and will be followed by the second step that is the core conversion from low meat density of silicide core, through a series of mixed lower-higher density of silicide core, to an all-higher meat density of 3.55 g/cc core. Therefore, the objectives of this work is to design the mixed cores on the neutronic performance to achieve safety a first full-silicide core for the reactor with the low uranium meat density of 2.96gU/cc. The neutronic design of the mixed cores was performed by means of Batan-EQUIL-2D and Batan-3DIFF computer codes for 2 and 3 dimension diffusion calculation, respectively. The result shows that all mixed oxide-silicide cores will be feasible to achieve safety a fist full-silicide core. The core performs the same neutronic core parameters as those of the equilibrium silicide core. Therefore, the reactor availability and utilization during the core conversion is not changed

Resource Utilisation and Curriculum Implementation in Community Colleges in Kenya

Directory of Open Access Journals (Sweden)

Peter Changilwa Kigwilu

2017-12-01

Full Text Available The study investigated how Catholic-sponsored community colleges in Nairobi utilise the existing physical facilities and teaching and learning resources for effective implementation of Artisan and Craft curricula. The study adopted a mixed methods research design. Proportional stratified random sampling was used to sample 172 students and 18 teachers while four directors of community colleges were purposively selected. Questionnaires were administered to students and teachers, while directors were interviewed. Teaching and learning resources, such as workshops, equipment, lecture rooms, laboratories, raw materials for practical training and reference books, were found to be adequate, although underutilised. However, sports grounds, libraries and course texts were inadequate. Resource inadequacies were often mitigated by signing equipment co-sharing agreements with peer institutions and local firms. Teachers rated highly the influence of physical facilities on curriculum implementation. Both students and teachers rated highly the influence of teaching and learning resources on curriculum implementation. The study concludes that, while some physical facilities and teaching and learning resources are adequate, their underutilisation and the inadequacy of other core facilities and resources, such as libraries and course textbooks, hinder effective teaching and learning in these community colleges.

Confirmation study of the effectiveness of prospect techniques for deep geothermal resources. Deep-seated geothermal resources survey report (Fiscal year 1993); 1993 nendo chinetsu tansa gijutsu nado kensho chosa. Shinbu chinetsu shigen chosa

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-03-01

Drilling and survey of deep geothermal exploration wells were conducted in order to grasp the existing situation of deep geothermal resource and the whole image of geothermal systems in the area where geothermal resource was already developed. Following fiscal 1992, the well was drilled in fiscal 1993 down to depths of 605m-1505m, and a 13-3/8 inch casing was inserted down to a depth of 1500m. In the drilling, four cores including oriented cores were sampled, and microscopic observation, X-ray diffraction analysis, fluid inclusion survey, core property test, etc. were conducted. In the FMI logging, detected were 273 bedding planes, 483 fractures, etc. Further made were a velocity structure survey, a gravity survey in the area of 270 km{sup 2} including deep exploration wells, a quality survey of the Kakkonda river water, etc. As to geothermal structure models in the Kakkonda area, results of the drilling were added to prediction models before drilling deep exploration wells, but the revision was not very much. Besides, studies were made of a survey method using microearthquakes, a survey technique using resistivity, etc. 61 refs., 259 figs., 95 tabs.

Overview of core designs and requirements/criteria for core restraint systems

International Nuclear Information System (INIS)

Sutherland, W.H.

1984-01-01

The requirements and lifetime criteria for the design of a Liquid Metal Fast Breeder Reactor (LMFBR) Core Restraint System is presented. A discussion of the three types of core restraint systems used in LMFBR core design is given. Details of the core restraint system selected for FFTF are presented and the reasons for this selection given. Structural analysis procedures being used to manage the FFTF assembly irradiations are discussed. Efforts that are ongoing to validate the calculational methods and lifetime criteria are presented. (author)

Nuclear reactor core flow baffling

International Nuclear Information System (INIS)

Berringer, R.T.

1979-01-01

A flow baffling arrangement is disclosed for the core of a nuclear reactor. A plurality of core formers are aligned with the grids of the core fuel assemblies such that the high pressure drop areas in the core are at the same elevations as the high pressure drop areas about the core periphery. The arrangement minimizes core bypass flow, maintains cooling of the structure surrounding the core, and allows the utilization of alternative beneficial components such as neutron reflectors positioned near the core

Research on SEU hardening of heterogeneous Dual-Core SoC

Science.gov (United States)

Huang, Kun; Hu, Keliu; Deng, Jun; Zhang, Tao

2017-08-01

The implementation of Single-Event Upsets (SEU) hardening has various schemes. However, some of them require a lot of human, material and financial resources. This paper proposes an easy scheme on SEU hardening for Heterogeneous Dual-core SoC (HD SoC) which contains three techniques. First, the automatic Triple Modular Redundancy (TMR) technique is adopted to harden the register heaps of the processor and the instruction-fetching module. Second, Hamming codes are used to harden the random access memory (RAM). Last, a software signature technique is applied to check the programs which are running on CPU. The scheme need not to consume additional resources, and has little influence on the performance of CPU. These technologies are very mature, easy to implement and needs low cost. According to the simulation result, the scheme can satisfy the basic demand of SEU-hardening.

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

Science.gov (United States)

Lestari; Budiyanto, F.; Hindarti, D.

2018-02-01

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

Start-up fuel and power flattening of sodium-cooled candle core

International Nuclear Information System (INIS)

Takaki, Naoyuki; Sagawa, Yu; Umino, Akitake; Sekimoto, Hiroshi

2013-01-01

The hard neutron spectrum and unique power shape of CANDLE enable its distinctive performances such as achieving high burnup more than 30% and exempting necessity of both enrichment and reprocessing. On the other hand, they also cause several challenging problems. One is how the initial fuel can be prepared to start up the first CANDLE reactor because the equilibrium fuel composition that enables stable CANDLE burning is complex both in axial and radial directions. Another prominent problem is high radial power peaking factor that worsens averaged burnup, namely resource utilization factor in once-through mode and shorten the life time of structure materials. The purposes of this study are to solve these two problems. Several ideas for core configurations and startup fuel using single enrichment uranium and iron as a substitute of fission products are studied. As a result, it is found that low enriched uranium is applicable to ignite the core but all concepts examined here exceeded heat limits. Adjustment in enrichment and height of active and burnt zone is opened for future work. Sodium duct assemblies and thorium fuel assemblies loaded in the center region are studied as measures to reduce radial power peaking factor. Replacing 37 fuels by thorium fuel assemblies in the zeroth to third row provides well-balanced performance with flattened radial power distribution. The CANDLE core loaded with natural uranium in the outer and thorium in the center region achieved 35.6% of averaged burnup and 7.0 years of cladding life time owing to mitigated local fast neutron irradiation at the center. Using thorium with natural or depleted uranium in CANDLE reactor is also beneficial to diversifying fission resource and extending available term of fission energy without expansion of needs for enrichment and reprocessing

Adaptation to the International Business Environment: A Resource Advantage Perspective

Directory of Open Access Journals (Sweden)

Manuel Portugal Ferreira

2008-01-01

Full Text Available This paper discusses the importance of the adaptation of the firm to the International Business Environment. Using concepts from the literature on resource advantage, we posit that the firms' adaptation capability to different International Business Environments is a valuable, difficult to imitate, non-tradeable, rare butnot scarce and path dependent resource. We further suggest that adaptation to International Business Environment is a non-substitutable core source of competitive advantage for the multinational enterprises, developed over time through the firms experiences and built into their routines. In line with this argument, some propositions are formulated. We conclude with a broad discussion and suggesting some avenues for future research\\.

Hybrid SDN Architecture for Resource Consolidation in MPLS Networks

OpenAIRE

Katov, Anton Nikolaev; Mihovska, Albena D.; Prasad, Neeli R.

2015-01-01

This paper proposes a methodology for resourceconsolidation towards minimizing the power consumption in alarge network, with a substantial resource overprovisioning. Thefocus is on the operation of the core MPLS networks. Theproposed approach is based on a software defined networking(SDN) scheme with a reconfigurable centralized controller, whichturns off certain network elements. The methodology comprisesthe process of identifying time periods with lower traffic demand;the ranking of the net...

Espaço de cores

Directory of Open Access Journals (Sweden)

Claudia Feitosa-Santana

2006-01-01

Full Text Available O artigo apresenta definições para os termos espaço de cores e sistemas de cores; classifica, de acordo com David Brainard (2003, os sistemas de cores em dois grupos: aparência de cores e diferenças de cores. Dentre os diversos sistemas de cores existentes, o artigo descreve dois deles: o sistema de cores Munsell &– um dos mais utilizados entre os sistemas de aparência de cores &– e a descrição do sistema de cores CIE 1931 &– um dos mais utilizados dentre os sistemas de diferença de cores. Faz-se uma retrospectiva histórica da busca por espaços de cores que representem a percepção de cores humana assim como as diversas reconstruções de espaços de cores por métodos eletrofisiológicos ou psicofísicos. Muitas dessas reconstruções utilizam a escala multidimensional (mds. O artigo também introduz a possibilidade da reconstrução dos espaços de cores de pacientes com discromatopsia adquirida como uma distorção do espaço de indivíduos tricromatas normais.

Core antigen and circulating anti-core antibody in hepatitis B infection

Energy Technology Data Exchange (ETDEWEB)

Howard, C R; Zuckerman, A J [London School of Hygiene and Tropical Medicine (UK)

1977-02-01

Core antigen was obtained from the sera of persistent chronic carriers of hepatitis B virus by centrifugation and treatment with Nonidet P40 and 2-mercaptoethanol. The separated core antigen was radiolabelled and identified as a nucleoprotein structure of buoyant density 1.36 g/cm/sup 3/ and possessing an isoelectric point of 4.4. This material was employed in a radioimmnoassay procedure of high sensitivity for the detection of core antibody. In a series of sera from patients with acute type B hepatitis, core antibody was demonstrated 2 to 3 weeks after the onset of jaundice during the period of surface antigenaemia. The presence of core antibody may therefore provide an accurate serological marker for the detection of active or recent virus replication in future epidemiological studies of hepatitis B infection.

Internal core tightener

International Nuclear Information System (INIS)

Brynsvold, G.V.; Snyder, H.J. Jr.

1976-01-01

An internal core tightener is disclosed which is a linear actuated (vertical actuation motion) expanding device utilizing a minimum of moving parts to perform the lateral tightening function. The key features are: (1) large contact areas to transmit loads during reactor operation; (2) actuation cam surfaces loaded only during clamping and unclamping operation; (3) separation of the parts and internal operation involved in the holding function from those involved in the actuation function; and (4) preloaded pads with compliant travel at each face of the hexagonal assembly at the two clamping planes to accommodate thermal expansion and irradiation induced swelling. The latter feature enables use of a ''fixed'' outer core boundary, and thus eliminates the uncertainty in gross core dimensions, and potential for rapid core reactivity changes as a result of core dimensional change. 5 claims, 12 drawing figures

Using a profile of a modified Brief ICF Core Set for chronic widespread musculoskeletal pain with qualifiers for baseline assessment in interdisciplinary pain rehabilitation

Directory of Open Access Journals (Sweden)

Löfgren M

2013-08-01

Full Text Available Monika Löfgren,1,2 Jan Ekholm,2 Lisbet Broman,3 Philipe Njoo,1 Marie-Louise Schult1–3 1Department of Rehabilitation Medicine Stockholm, Danderyd University Hospital, Sweden; 2Karolinska Institutet, Division of Rehabilitation Medicine, Department of Clinical Sciences, Danderyd University Hospital, Stockholm, Sweden; 3Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden Aim: To describe the use of a “workable” visual profile of function and disability, based on a modified Brief International Classification of Functioning, Disability and Health (ICF Core Set for chronic widespread pain, for initial assessments in a clinical setting of interdisciplinary pain rehabilitation teams. Method: The Brief ICF Core Set was slightly adapted to meet the needs of an interdisciplinary rehabilitation medicine team working in a university outpatient clinic and admitting patients referred from primary care. The Core Set categories were made measurable by means of eg, assessment instruments and clinical investigations. The resulting profile was given a workable shape to facilitate rapid understanding of the initial assessment outcome. Results: Individual patients showed different profiles of problems and resources, which facilitated individual rehabilitation planning. At the level of the study group, the profiles for the Core Set component Body Functions showed that most patients had severe impairment in the sensation of pain and exercise tolerance categories of function, but most had resources in the motivation and memory categories of function. Likewise, for the component Activities, most patients had limitations in lifting and carrying objects and remunerative employment, but most had resources in intimate relationships and family relationships. At first, the use of the modified Brief ICF Core Set in the team conference was rather time consuming, but after a couple of months of experience, the team assessment took

Core competencies for pain management: results of an interprofessional consensus summit.

Science.gov (United States)

Fishman, Scott M; Young, Heather M; Lucas Arwood, Ellyn; Chou, Roger; Herr, Keela; Murinson, Beth B; Watt-Watson, Judy; Carr, Daniel B; Gordon, Debra B; Stevens, Bonnie J; Bakerjian, Debra; Ballantyne, Jane C; Courtenay, Molly; Djukic, Maja; Koebner, Ian J; Mongoven, Jennifer M; Paice, Judith A; Prasad, Ravi; Singh, Naileshni; Sluka, Kathleen A; St Marie, Barbara; Strassels, Scott A

2013-07-01

The objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported. An interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached. The consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain. These competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain. Wiley Periodicals, Inc.

Application Service Providers (ASP Adoption in Core and Non-Core Functions

Directory of Open Access Journals (Sweden)

Aman Y.M. Chan

2009-10-01

Full Text Available With the further improvement in internet bandwidth, connection stability and data transmission security, a new wave of Application Service Providers (ASP is on his way. The recent booming on some models such as Software Application as Service (SaaS and On-Demand in 2008, has led to emergence of ASP model in core business functions. The traditional IS outsourcing covers the non-core business functions that are not critical to business performance and competitive advantages. Comparing with traditional IS outsourcing, ASP is a new phenomenon that can be considered as an emerging innovation as it covers both core and non-core business functions. Most of the executives do not comprehend the difference and similarity between traditional IS outsourcing and ASP mode. Hence, we propose to conduct a research so as to identify the determinants (cost benefit, gap in IS capability complementing the company's strategic goal, and trust to ASP's service and security level and moderating factors (management's attitude in ownership & control, and company aggressiveness of ASP adoption decision in both core and non-core business functions.

Reactor core

International Nuclear Information System (INIS)

Azekura, Kazuo; Kurihara, Kunitoshi.

1992-01-01

In a BWR type reactor, a great number of pipes (spectral shift pipes) are disposed in the reactor core. Moderators having a small moderating cross section (heavy water) are circulated in the spectral shift pipes to suppress the excess reactivity while increasing the conversion ratio at an initial stage of the operation cycle. After the intermediate stage of the operation cycle in which the reactor core reactivity is lowered, reactivity is increased by circulating moderators having a great moderating cross section (light water) to extend the taken up burnup degree. Further, neutron absorbers such as boron are mixed to the moderator in the spectral shift pipe to control the concentration thereof. With such a constitution, control rods and driving mechanisms are no more necessary, to simplify the structure of the reactor core. This can increase the fuel conversion ratio and control great excess reactivity. Accordingly, a nuclear reactor core of high conversion and high burnup degree can be attained. (I.N.)

Electromagnetically driven westward drift and inner-core superrotation in Earth’s core

Science.gov (United States)

Livermore, Philip W.; Hollerbach, Rainer; Jackson, Andrew

2013-01-01

A 3D numerical model of the earth’s core with a viscosity two orders of magnitude lower than the state of the art suggests a link between the observed westward drift of the magnetic field and superrotation of the inner core. In our model, the axial electromagnetic torque has a dominant influence only at the surface and in the deepest reaches of the core, where it respectively drives a broad westward flow rising to an axisymmetric equatorial jet and imparts an eastward-directed torque on the solid inner core. Subtle changes in the structure of the internal magnetic field may alter not just the magnitude but the direction of these torques. This not only suggests that the quasi-oscillatory nature of inner-core superrotation [Tkalčić H, Young M, Bodin T, Ngo S, Sambridge M (2013) The shuffling rotation of the earth’s inner core revealed by earthquake doublets. Nat Geosci 6:497–502.] may be driven by decadal changes in the magnetic field, but further that historical periods in which the field exhibited eastward drift were contemporaneous with a westward inner-core rotation. The model further indicates a strong internal shear layer on the tangent cylinder that may be a source of torsional waves inside the core. PMID:24043841

78 FR 63990 - HIV/AIDS Bureau; Ryan White HIV/AIDS Program Core Medical Services Waiver; Application Requirements

Science.gov (United States)

2013-10-25

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration HIV/AIDS Bureau; Ryan White HIV/AIDS Program Core Medical Services Waiver; Application Requirements AGENCY: Health... Service Act, as amended by the Ryan White HIV/AIDS Treatment Extension Act of 2009 (Ryan White Program or...

Inner Core Rotation from Geomagnetic Westward Drift and a Stationary Spherical Vortex in Earth's Core

Science.gov (United States)

Voorhies, C. V.

1999-01-01

The idea that geomagnetic westward drift indicates convective leveling of the planetary momentum gradient within Earth's core is pursued in search of a differentially rotating mean state, upon which various oscillations and secular effects might be superimposed. The desired state conforms to roughly spherical boundary conditions, minimizes dissipative interference with convective cooling in the bulk of the core, yet may aide core cooling by depositing heat in the uppermost core and lower mantle. The variational calculus of stationary dissipation applied to a spherical vortex within the core yields an interesting differential rotation profile akin to spherical Couette flow bounded by thin Hartmann layers. Four boundary conditions are required. To concentrate shear induced dissipation near the core-mantle boundary, these are taken to be: (i) no-slip at the core-mantle interface; (ii) geomagnetically estimated bulk westward flow at the base of the core-mantle boundary layer; (iii) no-slip at the inner-outer core interface; and, to describe magnetic locking of the inner core to the deep outer core, (iv) hydrodynamically stress-free at the inner-outer core boundary. By boldly assuming the axial core angular momentum anomaly to be zero, the super-rotation of the inner core is calculated to be at most 1.5 degrees per year.

Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach.

Science.gov (United States)

Pulcini, C; Binda, F; Lamkang, A S; Trett, A; Charani, E; Goff, D A; Harbarth, S; Hinrichsen, S L; Levy-Hara, G; Mendelson, M; Nathwani, D; Gunturu, R; Singh, S; Srinivasan, A; Thamlikitkul, V; Thursky, K; Vlieghe, E; Wertheim, H; Zeng, M; Gandra, S; Laxminarayan, R

2018-04-03

With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability. A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with ≥80% agreement; 20 elements and items were rephrased. This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

Implementation of a Shared Resource Financial Management System

Science.gov (United States)

Caldwell, T.; Gerlach, R.; Israel, M.; Bobin, S.

2010-01-01

CF-6 Norris Cotton Cancer Center (NCCC), an NCI-designated Comprehensive Cancer Center at Dartmouth Medical School, administers 12 Life Sciences Shared Resources. These resources are diverse and offer multiple products and services. Previous methods for tracking resource use, billing, and financial management were time consuming, error prone and lacked appropriate financial management tools. To address these problems, we developed and implemented a web-based application with a built-in authorization system that uses Perl, ModPerl, Apache2, and Oracle as the software infrastructure. The application uses a role-based system to differentiate administrative users with those requesting services and includes many features requested by users and administrators. To begin development, we chose a resource that had an uncomplicated service, a large number of users, and required the use of all of the applications features. The Molecular Biology Core Facility at NCCC fit these requirements and was used as a model for developing and testing the application. After model development, institution wide deployment followed a three-stage process. The first stage was to interview the resource manager and staff to understand day-to-day operations. At the second stage, we generated and tested customized forms defining resource services. During the third stage, we added new resource users and administrators to the system before final deployment. Twelve months after deployment, resource administrators reported that the new system performed well for internal and external billing and tracking resource utilization. Users preferred the application's web-based system for distribution of DNA sequencing and other data. The sample tracking features have enhanced day-to-day resource operations, and an on-line scheduling module for shared instruments has proven a much-needed utility. Principal investigators now are able to restrict user spending to specific accounts and have final approval of the

Epistemology and ontology in core ontologies: FOLaw and LRI-Core, two core ontologies for law

NARCIS (Netherlands)

Breukers, J.A.P.J.; Hoekstra, R.J.

2004-01-01

For more than a decade constructing ontologies for legal domains, we, at the Leibniz Center for Law, felt really the need to develop a core ontology for law that would enable us to re-use the common denominator of the various legal domains. In this paper we present two core ontologies for law. The