Sample records for human aml blasts

  1. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia. (United States)

    Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G


    Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL hi blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases. © 2016 by The American Society of Hematology.

  2. Circumvention of ara-C resistance by aphidicolin in blast cells from patients with AML. (United States)

    Sargent, J M; Elgie, A W; Williamson, C J; Lewandowicz, G M; Taylor, C G


    Treatment failure in AML is often attributed to P-glycoprotein-associated multidrug resistance. However, the importance of increased DNA repair in resistant cells is becoming more apparent. In order to investigate the ability of the DNA repair inhibitor aphidicolin to modulate drug resistance, we continually exposed blasts cells, isolated from 22 patients with AML, to a variety of agents +/- 15 microM aphidicolin for 48 hours. Cell survival was measured using the MTT assay. Overall, there was no significant effect of aphidicolin on sensitivity to daunorubicin, doxorubicin, etoposide or fludarabine. However, there was a marked increase in sensitivity to ara-C with a median 4.75-fold increase overall (range 0.8-80-fold;P< 0.005). The effect of aphidicolin was significantly greater in blast cells found resistant in vitro to ara-C (8.9-fold compared to 2.12-fold, P< 0.01). This observation was further validated by the correlation between ara-C LC(50)and extent of modulation effect (P< 0.05). Cells isolated from 10 cord blood samples were also tested in order to establish the haematological toxicity of combining ara-C and aphidicolin. The therapeutic index (LC(50)normal cells/tumour cells) for ara-C + aphidicolin was higher than that for ara-C alone suggesting no increased myelotoxicity for the combination. Increased cytotoxicity without increased haematotoxicity makes the combination of ara-C plus aphidicolin ideal for inclusion in future clinical trials. Copyright 2001 Cancer Research Campaign.

  3. Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients (United States)

    Fucikova, Jitka; Truxova, Iva; Hensler, Michal; Becht, Etienne; Kasikova, Lenka; Moserova, Irena; Vosahlikova, Sarka; Klouckova, Jana; Church, Sarah E.; Cremer, Isabelle; Kepp, Oliver; Kroemer, Guido; Galluzzi, Lorenzo; Salek, Cyril


    Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called “damage-associated molecular patterns,” DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from patients with acute myeloid leukemia (AML) exposed multiple DAMPs, including calreticulin (CRT), heat-shock protein 70 (HSP70), and HSP90 on their plasma membrane irrespective of treatment. In these patients, high levels of surface-exposed CRT correlated with an increased proportion of natural killer cells and effector memory CD4+ and CD8+ T cells in the periphery. Moreover, CRT exposure on the plasma membrane of malignant blasts positively correlated with the frequency of circulating T cells specific for leukemia-associated antigens, indicating that ecto-CRT favors the initiation of anticancer immunity in patients with AML. Finally, although the levels of ecto-HSP70, ecto-HSP90, and ecto-CRT were all associated with improved relapse-free survival, only CRT exposure significantly correlated with superior overall survival. Thus, CRT exposure represents a novel powerful prognostic biomarker for patients with AML, reflecting the activation of a clinically relevant AML-specific immune response. PMID:27802968

  4. Functional analysis of P-glycoprotein and multidrug resistance associated protein related multidrug resistance in AML-blasts. (United States)

    Brügger, D; Herbart, H; Gekeler, V; Seitz, G; Liu, C; Klingebiel, T; Orlikowsky, T; Einsele, H; Denzlinger, C; Bader, P; Niethammer, D; Beck, J F


    Despite the high effectiveness of various P-glycoprotein (P-gp) modulating substances in vitro their clinical value e.g. for combination treatment of acute myelogenous leukemias (AML) remains still unclear. This might be explainable by recent findings that other factors than P-gp (e.g. the multidrug resistance associated protein (MRP)) may also be involved in clinical occurring drug resistance. To study P-gp and MRP mediated MDR in AML blasts from patients with relapses at the functional level we measured rhodamine 123 (RHO) efflux in combination with a P-gp specific (SDZ PSC 833) or a MRP specific (MK571) modulator, respectively. Furthermore, direct antineoplastic drug action was monitored by determination of damaged cell fraction of a blast population using flow cytometry. We generally found strongly modulated RHO efflux by SDZ PSC 833 but slight RHO-efflux modulation by MK571 in blasts from relapsed states of AML expressing MDR1 or MRP mRNA at various levels. We could not demonstrate, though, significant PSC 833 or MK571 mediated modulation of the cytotoxic effects of etoposide. The results point to the possibility that combination of etoposide and a modulator might not improve responses to chemotherapy by targeting P-gp or MRP exclusively.

  5. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy

    DEFF Research Database (Denmark)

    Bruedigam, Claudia; Bagger, Frederik Otzen; Heidel, Florian H.


    (-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia...... progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs....

  6. Early clearance of peripheral blasts measured by flow cytometry during the first week of AML induction therapy as a new independent prognostic factor: a GOELAMS study. (United States)

    Lacombe, F; Arnoulet, C; Maynadié, M; Lippert, E; Luquet, I; Pigneux, A; Vey, N; Casasnovas, O; Witz, F; Béné, M C


    An early appreciation of treatment efficacy could be very useful in acute myeloblastic leukemia (AML), and a prognostic value has been suggested for the morphological assessment of decrease in blasts during induction therapy. More sensitive, multiparametric flow cytometry (FCM) can detect far lower blast counts, allowing for a precise and reliable calculation of blast cell decrease rate (BDR). Such a multiparametric FCM four-colours/single-tube protocol, combining CD11b, CD45-ECD and CD16-PC5, was applied to peripheral blood samples from 130 AML patients, collected daily during induction chemotherapy. Normalized blast cell percentages were used to calculate the relevant decrease slopes. Slope thresholds (-15), or the time required to reach 90% depletion of the peripheral blast load (5 days), was strongly associated with the achievement of complete remission (P<0.0001). Log-rank test and Cox model showed that they also carried high statistical significance (P<0.0001) for disease-free survival. The prognostic value of cytogenetic features, confirmed in this series, was refined by BDR, which allowed to discriminate between good- and poor-risk patients among those with intermediate or normal karyotypes. This simple FCM protocol allows for an accurate prognostic sequential approach adapted to the determination of decrease in peripheral blast cells during induction chemotherapy.

  7. Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods. (United States)

    Kremser, Andreas; Dressig, Julia; Grabrucker, Christine; Liepert, Anja; Kroell, Tanja; Scholl, Nina; Schmid, Christoph; Tischer, Johanna; Kufner, Stefanie; Salih, Helmut; Kolb, Hans Jochem; Schmetzer, Helga


    Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

  8. Transformation from refractory anemia with excess of blasts (RAEB) into acute myeloid leukemia (AML) obserbed in a heavily exposed atomic bomb survivor

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    Iwato, Koji; Kawano, Michio; Kimura, Akiro; Kuramoto, Atsushi; Tanaka, Kimio; Kamada, Nanao


    A heavily exposed atomic bomb survivor, 59-year-old man presented refractory anemia with excess of blasts (RAEB) terminating in acute myeloid leukemia (AML) 38 years after exposure. When he manifested AML, combination chemotherapy was started. But complete remission was not obtained even by B-DOMP regimen. Cytogenetic studies were performed, and their relation to the clinical course was analyzed. Peripheral blood T lymphocytes had 41.9 % non-clonal chromosomal abnormalities suggesting over 400 rad exposure. Bone marrow cells at RAEB exhibited a presence of mosaic clones of normal and abnormal chromosomal pattern, which supported the clinical diagnosis of RAEB and corresponded to the clinical features such as steady state and a low percentage of myeloblasts. At transformation into AML, clonal chromosomal abnormality was seen in bone marrow cells. It may explain a rapid increase of abnormal cells. This abnormal clone showed a little different karyotype seen at RAEB. But it was suspected to derive from a clone at RAEB, because of the same persistent chromosomal abnormalities. Then it aquired an additional chromosomal abnormalities at clinically drug-resistant phase of AML. In vivo selection assay of these leukemic cells revealed that transforming gene took part in this leukemogenesis. These data shown in this paper contribute to investigate a mechanism of leukemogenesis in atomic bomb survivors and establishment of new therapy.

  9. Transformation from refractory anemia with excess of blasts (RAEB) into acute myeloid leukemia (AML) obserbed in a heavily exposed atomic bomb survivor

    International Nuclear Information System (INIS)

    Iwato, Koji; Kawano, Michio; Kimura, Akiro; Kuramoto, Atsushi; Tanaka, Kimio; Kamada, Nanao


    A heavily exposed atomic bomb survivor, 59-year-old man presented refractory anemia with excess of blasts (RAEB) terminating in acute myeloid leukemia (AML) 38 years after exposure. When he manifested AML, combination chemotherapy was started. But complete remission was not obtained even by B-DOMP regimen. Cytogenetic studies were performed, and their relation to the clinical course was analyzed. Peripheral blood T lymphocytes had 41.9 % non-clonal chromosomal abnormalities suggesting over 400 rad exposure. Bone marrow cells at RAEB exhibited a presence of mosaic clones of normal and abnormal chromosomal pattern, which supported the clinical diagnosis of RAEB and corresponded to the clinical features such as steady state and a low percentage of myeloblasts. At transformation into AML, clonal chromosomal abnormality was seen in bone marrow cells. It may explain a rapid increase of abnormal cells. This abnormal clone showed a little different karyotype seen at RAEB. But it was suspected to derive from a clone at RAEB, because of the same persistent chromosomal abnormalities. Then it aquired an additional chromosomal abnormalities at clinically drug-resistant phase of AML. In vivo selection assay of these leukemic cells revealed that transforming gene took part in this leukemogenesis. These data shown in this paper contribute to investigate a mechanism of leukemogenesis in atomic bomb survivors and establishment of new therapy. (author)

  10. Human Injury Criteria for Underwater Blasts.

    Directory of Open Access Journals (Sweden)

    Rachel M Lance

    Full Text Available Underwater blasts propagate further and injure more readily than equivalent air blasts. Development of effective personal protection and countermeasures, however, requires knowledge of the currently unknown human tolerance to underwater blast. Current guidelines for prevention of underwater blast injury are not based on any organized injury risk assessment, human data or experimental data. The goal of this study was to derive injury risk assessments for underwater blast using well-characterized human underwater blast exposures in the open literature. The human injury dataset was compiled using 34 case reports on underwater blast exposure to 475 personnel, dating as early as 1916. Using severity ratings, computational reconstructions of the blasts, and survival information from a final set of 262 human exposures, injury risk models were developed for both injury severity and risk of fatality as functions of blast impulse and blast peak overpressure. Based on these human data, we found that the 50% risk of fatality from underwater blast occurred at 302±16 kPa-ms impulse. Conservatively, there is a 20% risk of pulmonary injury at a kilometer from a 20 kg charge. From a clinical point of view, this new injury risk model emphasizes the large distances possible for potential pulmonary and gut injuries in water compared with air. This risk value is the first impulse-based fatality risk calculated from human data. The large-scale inconsistency between the blast exposures in the case reports and the guidelines available in the literature prior to this study further underscored the need for this new guideline derived from the unique dataset of actual injuries in this study.

  11. KRAS (G12D Cooperates with AML1/ETO to Initiate a Mouse Model Mimicking Human Acute Myeloid Leukemia

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    Shanmin Zhao


    Full Text Available Background/Aims: It has been demonstrated that KRAS mutations represent about 90% of cancer-associated mutations, and that KRAS mutations play an essential role in neoplastic transformation. Cancer-associated RAS mutations occur frequently in acute myeloid leukemia (AML, suggesting a functional role for Ras in leukemogenesis. Methods: We successfully established a mouse model of human leukemia by transplanting bone marrow cells co-transfected with the K-ras (G12D mutation and AML1/ETO fusion protein. Results: Mice transplanted with AML/ETO+KRAS co-transduced cells had the highest mortality rate than mice transplanted with AML/ETO- or KRAS-transduced cells (115d vs. 150d. Upon reaching a terminal disease stage, EGFP-positive cells dominated their spleen, lymph nodes, peripheral blood and central nervous system tissue. Immunophenotyping, cytologic analyses revealed that AML/ETO+KRAS leukemias predominantly contained immature myeloid precursors (EGFP+/c-Kit+/Mac-1-/Gr-1-. Histologic analyses revealed that massive leukemic infiltrations were closely packed in dense sheets that effaced the normal architecture of spleen and thymus in mice transplanted with AML1/ETO + KRAS co-transduced cells. K-ras mRNA and protein expression were upregulated in bone marrow cells of the K-ras group and AML1/ETO + Kras group. The phosphorylation of MEK/ERK was significantly enhanced in the AML1/ETO + Kras group. The similar results of the AML1/ETO + Nras group were consistent with those reported previously. Conclusion: Co-transduction of KrasG12D and AML1/ETO induces acute monoblastic leukemia. Since expression of mutant K-ras alone was insufficient to induce leukemia, this model may be useful for investigating the multi-step leukemogenesis model of human leukemia.

  12. Autonomous growth potential of leukemia blast cells is associated with poor prognosis in human acute leukemias

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    Jakubowski Ann A


    Full Text Available Abstract We have described a severe combined immunodeficiency (SCID mouse model that permits the subcutaneous growth of primary human acute leukemia blast cells into a measurable subcutaneous nodule which may be followed by the development of disseminated disease. Utilizing the SCID mouse model, we examined the growth potential of leukemic blasts from 133 patients with acute leukemia, (67 acute lymphoblastic leukemia (ALL and 66 acute myeloid leukemia (AML in the animals after subcutaneous inoculation without conditioning treatment. The blasts displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor growth". Out of 133 leukemias, 45 (33.8% displayed an aggressive growth pattern, 14 (10.5% displayed an indolent growth pattern and 74 (55.6% did not grow in SCID mice. The growth probability of leukemias from relapsed and/or refractory disease was nearly 3 fold higher than that from patients with newly diagnosed disease. Serial observations found that leukemic blasts from the same individual, which did not initiate tumor growth at initial presentation and/or at early relapse, may engraft and grow in the later stages of disease, suggesting that the ability of leukemia cells for engraftment and proliferation was gradually acquired following the process of leukemia progression. Nine autonomous growing leukemia cell lines were established in vitro. These displayed an aggressive proliferation pattern, suggesting a possible correlation between the capacity of human leukemia cells for autonomous proliferation in vitro and an aggressive growth potential in SCID mice. In addition, we demonstrated that patients whose leukemic blasts displayed an aggressive growth and dissemination pattern in SClD mice had a poor clinical outcome in patients with ALL as well as AML. Patients whose leukemic blasts grew indolently or whose leukemia cells failed to induce growth had a significantly longer DFS and more favorable clinical course.

  13. Impact of baseline cytogenetic findings and cytogenetic response on outcome of high-risk myelodysplastic syndromes and low blast count AML treated with azacitidine. (United States)

    Sébert, Marie; Komrokji, Rami S; Sekeres, Mikkael A; Prebet, Thomas; Cluzeau, Thomas; Santini, Valeria; Gyan, Emmanuel; Sanna, Alessandro; Ali, Najla HAl; Hobson, Sean; Eclache, Virginie; List, Alan; Fenaux, Pierre; Adès, Lionel


    Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype. None of the cytogenetic abnormalities had significant impact on ORR (43.9%) or complete response (15.35%), except 3q abnormalities and complex karyotypes, which were associated with a lower ORR. OS differed significantly across all R-IPSS cytogenetic subgroups (pcytogenetics. CyR was achieved in 32% of the 281 evaluable patients with abnormal cytogenetics, was complete (CCyR) in 71 (25.3%) patients. We found no correlation between hematological response and cytogenetic response and 21% of the patients with CCyR did not achieve morphological response. In the 281 patients, we found no impact of CyR on survival, but when restricting to MDS (ie: <20% marrow blasts) achievement of CCyR was associated with better OS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Modelling human eye under blast loading. (United States)

    Esposito, L; Clemente, C; Bonora, N; Rossi, T


    Primary blast injury (PBI) is the general term that refers to injuries resulting from the mere interaction of a blast wave with the body. Although few instances of primary ocular blast injury, without a concomitant secondary blast injury from debris, are documented, some experimental studies demonstrate its occurrence. In order to investigate PBI to the eye, a finite element model of the human eye using simple constitutive models was developed. The material parameters were calibrated by a multi-objective optimisation performed on available eye impact test data. The behaviour of the human eye and the dynamics of mechanisms occurring under PBI loading conditions were modelled. For the generation of the blast waves, different combinations of explosive (trinitrotoluene) mass charge and distance from the eye were analysed. An interpretation of the resulting pressure, based on the propagation and reflection of the waves inside the eye bulb and orbit, is proposed. The peculiar geometry of the bony orbit (similar to a frustum cone) can induce a resonance cavity effect and generate a pressure standing wave potentially hurtful for eye tissues.

  15. Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts

    International Nuclear Information System (INIS)

    Cartellieri, M; Feldmann, A; Koristka, S; Arndt, C; Loff, S; Ehninger, A; Bonin, M von; Bejestani, E P; Ehninger, G; Bachmann, M P


    The adoptive transfer of CD19-specific chimeric antigen receptor engineered T cells (CAR T cells) resulted in encouraging clinical trials in indolent B-cell malignancies. However, they also show the limitations of this fascinating technology: CAR T cells can lead to even life-threatening off-tumor, on-target side effects if CAR T cells crossreact with healthy tissues. Here, we describe a novel modular universal CAR platform technology termed UniCAR that reduces the risk of on-target side effects by a rapid and reversible control of CAR T-cell reactivity. The UniCAR system consists of two components: (1) a CAR for an inert manipulation of T cells and (2) specific targeting modules (TMs) for redirecting UniCAR T cells in an individualized time- and target-dependent manner. UniCAR T cells can be armed against different tumor targets simply by replacement of the respective TM for (1) targeting more than one antigen simultaneously or subsequently to enhance efficacy and (2) reducing the risk for development of antigen-loss tumor variants under treatment. Here we provide ‘proof of concept' for retargeting of UniCAR T cells to CD33- and/or CD123-positive acute myeloid leukemia blasts in vitro and in vivo

  16. Regulatory T cells-derived IL-35 promotes the growth of adult acute myeloid leukemia blasts. (United States)

    Tao, Qianshan; Pan, Ying; Wang, Yiping; Wang, Huiping; Xiong, Shudao; Li, Qing; Wang, Jia; Tao, Lili; Wang, Zhitao; Wu, Fan; Zhang, Rui; Zhai, Zhimin


    Tumor immune escape mechanism mediated by CD4+CD25+regulatory T cells (Tregs) is a key factor in the pathogenesis of acute myeloid leukemia (AML). IL-35, as a novel inhibitory cytokine, is produced by Tregs specially and regulates functions of Tregs in murine. However, IL-35 expression of Tregs in human is still disputed, and its role in AML is yet to be elucidated. In this study, we found that IL-35 was expressed highly in peripheral blood plasma of adult patients with AML and significantly correlated with the clinical stages of malignancy. Tregs-derived from adult AML patients produced IL-35 in a stimulation-dependent manner. IL-35 promoted AML blasts immune escape by expanding Tregs and inhibiting CD4+CD25-effector T cells (Teffs). Furthermore, IL-35 directly promoted the proliferation of AML blasts and reduced the apoptosis of AML blasts. Together, our study demonstrates that IL-35-derived from Tregs promotes the growth of adult AML blasts, suggesting that IL-35 has an important role in the pathogenesis of AML. © 2015 UICC.

  17. The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from chemotherapy in AML Patients. (United States)

    Dong-Feng, Zeng; Ting, Liu; Yong, Zhang; Cheng, Chang; Xi, Zhang; Pei-Yan, Kong


    Accumulating evidence indicates that the interaction of human LSCs (leukemic stem cells) with the hematopoietic microenvironment, mediated by the thrombopoietin (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle-dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML (acute myelogenous leukemia) chemotherapy resistance hasn't been fully understood. The c-MPL and TPO levels in different AML samples were measured by flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML cell line that had been co-cultured with different BMSC-derived osteoblasts was measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR). The levels of TPO/c-MPL in the initial and relapse AML patients were significantly higher than that in the control (P MPL expression was found in the bone marrow mononuclear cells of the relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived osteoblasts was the highest among all co-culture systems. High level of TPO/c-MPL signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and on their downstream effector molecules that direct the interactions between patient-derived blasts and leukemia repopulating cells need to be further studied.

  18. The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO (United States)

    Chou, Fu-Sheng; Griesinger, Andrea; Wunderlich, Mark; Lin, Shan; Link, Kevin A.; Shrestha, Mahesh; Goyama, Susumu; Mizukawa, Benjamin; Shen, Shuhong; Marcucci, Guido


    AML1-ETO (AE) is a fusion product of translocation (8;21) that accounts for 40% of M2 type acute myeloid leukemia (AML). In addition to its role in promoting preleukemic hematopoietic cell self-renewal, AE represses DNA repair genes, which leads to DNA damage and increased mutation frequency. Although this latter function may promote leukemogenesis, concurrent p53 activation also leads to an increased baseline apoptotic rate. It is unclear how AE expression is able to counterbalance this intrinsic apoptotic conditioning by p53 to promote survival and self-renewal. In this report, we show that Bcl-xL is up-regulated in AE cells and plays an essential role in their survival and self-renewal. Further investigation revealed that Bcl-xL expression is regulated by thrombopoietin (THPO)/MPL-signaling induced by AE expression. THPO/MPL-signaling also controls cell cycle reentry and mediates AE-induced self-renewal. Analysis of primary AML patient samples revealed a correlation between MPL and Bcl-xL expression specifically in t(8;21) blasts. Taken together, we propose that survival signaling through Bcl-xL is a critical and intrinsic component of a broader self-renewal signaling pathway downstream of AML1-ETO–induced MPL. PMID:22337712

  19. Atmospheric Measurements Laboratory (AML) (United States)

    Federal Laboratory Consortium — The Atmospheric Measurements Laboratory (AML) is one of the nation's leading research facilities for understanding aerosols, clouds, and their interactions. The AML...

  20. OSI-211, a novel liposomal topoisomerase I inhibitor, is active in SCID mouse models of human AML and ALL. (United States)

    Tomkinson, Blake; Bendele, Ray; Giles, Francis J; Brown, Eric; Gray, Atherton; Hart, Karen; LeRay, Jeremy D; Meyer, Denny; Pelanne, Michelle; Emerson, David L


    OSI-211 (liposomal lurtotecan), was evaluated using several different dose schedules (1mg/kg, d1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) in severe combined immunodeficient (SCID) mouse models of acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) with early treatment (ET, days 6-8) or late treatment (LT, days 15-19), examining early and advanced disease, respectively. Due to the aggressive nature of the Molt-4 model, the ET and LT were accelerated to day 3 or 4 and day 8 post-implant, respectively. For each model, 2 x 10(7) (KBM-3B) or 1 x 10(7) (Molt-4, HL-60 and CEM) leukemia cells were injected intravenously into the tail vein. Each control and test group consisted of eight animals. All three schedules (1mg/kg qd1-5, 1.75 mg/kg d1, 3, 5 and 6 mg/kg d1, 8) increased the life span of OSI-211 treated animals in each model, with a tendency toward improved efficacy with the 6 mg/kg d1, 8 schedule. As a result, the activity of the 6 mg/kg d1, 8 schedule is detailed for each model. ET significantly (Pmodel with 86% long-term survivors (LTS). Using PRC analysis, human beta-globin gene sequences in one or several tissues were amplified in all but 3 LTS, suggesting minimal residual disease in 26 of the 29 LTS. LT also significantly (Pmodel, with an average ILS=196+/-11% and one LTS. Treatment of HL-60 leukemia animals significantly (Pmodel tested, significantly (Pmodel, ET resulted in a significantly (POSI-211, treatment with DaunoXome, the liposomal formulation of daunorubicin, a drug with clinical efficacy in AML and ALL, had no effect on survival in the KBM-3B, nor Molt-4 A4 leukemia models when administered at its maximum or near maximum tolerated doses of 3mg/kg d1, 8. These data demonstrate that OSI-211 has potent antileukemia activity in preclinical SCID mouse AML and ALL leukemia models, supporting the clinical investigation of OSI-211 for hematological malignancies.

  1. Access/AML - (United States)

    Department of Transportation — The AccessAML is a web-based internet single application designed to reduce the vulnerability associated with several accounts assinged to a single users. This is a...

  2. A computational model of blast loading on the human eye. (United States)

    Bhardwaj, Rajneesh; Ziegler, Kimberly; Seo, Jung Hee; Ramesh, K T; Nguyen, Thao D


    Ocular injuries from blast have increased in recent wars, but the injury mechanism associated with the primary blast wave is unknown. We employ a three-dimensional fluid-structure interaction computational model to understand the stresses and deformations incurred by the globe due to blast overpressure. Our numerical results demonstrate that the blast wave reflections off the facial features around the eye increase the pressure loading on and around the eye. The blast wave produces asymmetric loading on the eye, which causes globe distortion. The deformation response of the globe under blast loading was evaluated, and regions of high stresses and strains inside the globe were identified. Our numerical results show that the blast loading results in globe distortion and large deviatoric stresses in the sclera. These large deviatoric stresses may be indicator for the risk of interfacial failure between the tissues of the sclera and the orbit.

  3. Effects of granulocyte-macrophage colony-stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture. (United States)

    Tsao, C J; Cheng, T Y; Chang, S L; Su, W J; Tseng, J Y


    We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors.

  4. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas


    ) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. RESULTS: Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13......BACKGROUND: Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients...... treated with SCT. MATERIAL AND METHODS: Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17...

  5. Successful treatment of congenital acute myeloid leukemia (AML-M6) in a premature infant. (United States)

    van Dongen, Joyce C A; Dalinghaus, Michiel; Kroon, Andre A; de Vries, Andrica C H; van den Heuvel-Eibrink, Marry M


    Congenital acute myeloid leukemia (AML), and especially AML-M6 is a rare disease with a poor prognosis. Moreover, reports of treatment outcome of congenital AML-M6 in premature infants are not available. We report the first treated case of congenital AML-M6 in a premature girl, who received a full AML protocol. She presented with blueberry-muffin spots, anemia, high white blood cell count, and serious cardiopulmonary distress. Peripheral blood smears showed AML-M6 blasts. After treatment with a sequential low-dose cytarabine after birth and full-dose AML treatment according to the MRC-12 protocol at the age of 2 months, she now is in continuous complete remission for 4 years.

  6. HLA-G Expression on Blasts and Tolerogenic Cells in Patients Affected by Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Grazia Locafaro


    Full Text Available Human Leukocyte Antigen-G (HLA-G contributes to cancer cell immune escape from host antitumor responses. The clinical relevance of HLA-G in several malignancies has been reported. However, the role of HLA-G expression and functions in Acute Myeloid Leukemia (AML is still controversial. Our group identified a subset of tolerogenic dendritic cells, DC-10 that express HLA-G and secrete IL-10. DC-10 are present in the peripheral blood and are essential in promoting and maintaining tolerance via the induction of adaptive T regulatory (Treg cells. We investigated HLA-G expression on blasts and the presence of HLA-G-expressing DC-10 and CD4+ T cells in the peripheral blood of AML patients at diagnosis. Moreover, we explored the possible influence of the 3′ untranslated region (3′UTR of HLA-G, which has been associated with HLA-G expression, on AML susceptibility. Results showed that HLA-G-expressing DC-10 and CD4+ T cells are highly represented in AML patients with HLA-G positive blasts. None of the HLA-G variation sites evaluated was associated with AML susceptibility. This is the first report describing HLA-G-expressing DC-10 and CD4+ T cells in AML patients, suggesting that they may represent a strategy by which leukemic cells escape the host’s immune system. Further studies on larger populations are required to verify our findings.

  7. Computational modeling of blast wave interaction with a human body and assessment of traumatic brain injury (United States)

    Tan, X. G.; Przekwas, A. J.; Gupta, R. K.


    The modeling of human body biomechanics resulting from blast exposure poses great challenges because of the complex geometry and the substantial material heterogeneity. We developed a detailed human body finite element model representing both the geometry and the materials realistically. The model includes the detailed head (face, skull, brain and spinal cord), the neck, the skeleton, air cavities (lungs) and the tissues. Hence, it can be used to properly model the stress wave propagation in the human body subjected to blast loading. The blast loading on the human was generated from a simulated C4 explosion. We used the highly scalable solvers in the multi-physics code CoBi for both the blast simulation and the human body biomechanics. The meshes generated for these simulations are of good quality so that relatively large time-step sizes can be used without resorting to artificial time scaling treatments. The coupled gas dynamics and biomechanics solutions were validated against the shock tube test data. The human body models were used to conduct parametric simulations to find the biomechanical response and the brain injury mechanism due to blasts impacting the human body. Under the same blast loading condition, we showed the importance of inclusion of the whole body.

  8. Brain injuries from blast. (United States)

    Bass, Cameron R; Panzer, Matthew B; Rafaels, Karen A; Wood, Garrett; Shridharani, Jay; Capehart, Bruce


    Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is

  9. Acute myeloid leukemia (AML) - children (United States)

    Acute myeloid leukemia is a cancer of the blood and bone marrow. Bone marrow is the soft tissue inside ... develops quickly. Both adults and children can get acute myeloid leukemia ( AML ). This article is about AML in children.

  10. An antigen shared by human granulocytes, monocytes, marrow granulocyte precursors and leukemic blasts. (United States)

    Shumak, K H; Rachkewich, R A


    An antibody to human granulocytes was raised in rabbits by immunization with granulocytes pretreated with rabbit antibody to contaminating antigens. The antibody reacted not only with granulocytes but also with monocytes and bone marrow granulocyte precursors including colony-forming units in culture (CFU-C). In tests with leukemic cells, the antibody reacted with blasts from most (8 of 9) patients with acute myelomonoblastic leukemia and from some patients with acute myeloblastic leukemia, morphologically undifferentiated acute leukemia and chronic myelogenous leukemia in blast crisis. The antibody did not react with blasts from patients with acute lymphoblastic leukemia nor with leukemic cells from patients with chronic lymphocytic leukemia.

  11. Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML (United States)


    Relapsed Acute Lymphoblastic Leukemia (ALL); Refractory Acute Lymphoblastic Leukemia (ALL); Relapsed Acute Myelogenous Leukemia (AML); Refractory Acute Myelogenous Leukemia (AML); Relapsed Mixed Lineage Leukemia; Refractory Mixed Lineage Leukemia; Relapsed Biphenotypic Leukemia; Refractory Biphenotypic Leukemia; Chronic Myelogenous Leukemia (CML) in Blast Crisis

  12. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients.

    Directory of Open Access Journals (Sweden)

    Virginie Marcel

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML.

  13. Outcome of poor response paediatric AML using early SCT. (United States)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas; Forestier, Erik; Gustafsson, Britt; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Hasle, Henrik


    Children with poor response acute myeloid leukaemia (AML) generally have a very poor outcome. Allogeneic stem cell transplantation (SCT) is often recommended for these children but the benefit is unclear. The aim of this study was to investigate survival for poor response AML patients treated with SCT. Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13, matched sibling donors in 6, cord blood donor in 4, and haploidentical donor in two. The median follow-up for the 31 poor responding patients was 2.6 years (range 0.4 - 8.1 years) and 3-year probability of survival 70% (95% CI 59-77%). The poor responders in the NOPHO-AML 2004 protocol had a favourable prognosis treated with time-intensive induction followed by SCT. © 2012 John Wiley & Sons A/S.

  14. Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123"+/CD131"− phenotype of leukemia stem cells

    International Nuclear Information System (INIS)

    Gao, Catherine; Leyton, Jeffrey V.; Schimmer, Aaron D.; Minden, Mark; Reilly, Raymond M.


    Chimeric IgG_1 monoclonal antibody CSL360 recognizes the CD123"+/CD131"− phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting "1"1"1In-DTPA-NLS-CSL360 radioimmunoconjugates incorporating nuclear translocation sequence (NLS) peptides bound specifically to Raji cells transfected with CD123 and exhibited a K_D of 11 nmols/L in a competition receptor-binding assay using CD123-transfected CHO cells. "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and transported to the nucleus of human AML-5 myeloid leukemia cells. The clonogenic survival of AML-5 cells was reduced by "1"1"1In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control "1"1"1In-DTPA-chIgG_1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free "1"1"1In acetate did not decrease cell survival. These results are promising for further evaluation of "1"1"1In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation. - Highlights: • "1"1"1In-DTPA-NLS-CSL360 the CD123"+/CD131"− phenotype of leukemic stem cells (LSC). • "1"1"1In-DTPA-NLS-CSL360 was bound, internalized and imported into the nucleus of AML-5 leukemia cells. • "1"1"1In-DTPA-NLS-CSL360 reduced the clonogenic survival of AML-5 leukemia cells by 4-fold.

  15. Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group. (United States)

    Barnard, Dorothy R; Alonzo, Todd A; Gerbing, Robert B; Lange, Beverly; Woods, William G


    Myelodysplastic syndromes (MDS), acute erythroleukemia (FAB M6), and acute megakaryocytic leukemia (FAB M7) have overlapping features. Children without Down syndrome or acute promyelocytic leukemia who were newly diagnosed with primary myelodysplastic syndrome or acute myeloid leukemia (AML) M6 or M7 were compared to children with de novo AML M0-M5. All children were entered on the Children's Cancer Group therapeutic research study CCG 2891. The presentation and outcomes of the 132 children diagnosed with MDS (60 children), AML FAB M6 (19 children), or AML FAB M7 (53 children) were similar. Children with AML FAB M7 were diagnosed at a significantly younger age (P = 0.001). Children with MDS, M6, or M7 had significantly lower white blood cell (WBC) counts (P = 0.001), lower peripheral blast counts (P M6 and AML M7 resemble MDS in presentation, poor induction success rates, and outcomes.

  16. Blast management


    Shouraki, Mohammad Kargar; Naserkheil, Ali Asghar


    Blast Management (BM) is composed of the combination of human resources management (HRM) principles and concepts and various methods of quality management (QM) with a financial approach. BM is made up of three aspects: hard, soft and concept and BLAST means an explosive shift in organization's mindset and thought and rapid action against it. The first aspect, hard, includes a set of managerial toots and philosophies to improve the quality and productivity with a financial approach.

  17. Genome-wide analysis of histone H3 acetylation patterns in AML identifies PRDX2 as an epigenetically silenced tumor suppressor gene

    DEFF Research Database (Denmark)

    Agrawal-Singh, Shuchi; Isken, Fabienne; Agelopoulos, Konstantin


    to have lower H3Ac levels in AML compared with progenitor cells, which suggested that a large number of genes are epigenetically silenced in AML. Intriguingly, we identified peroxiredoxin 2 (PRDX2) as a novel potential tumor suppressor gene in AML. H3Ac was decreased at the PRDX2 gene promoter in AML......With the use of ChIP on microarray assays in primary leukemia samples, we report that acute myeloid leukemia (AML) blasts exhibit significant alterations in histone H3 acetylation (H3Ac) levels at > 1000 genomic loci compared with CD34+ progenitor cells. Importantly, core promoter regions tended......, which correlated with low mRNA and protein expression. We also observed DNA hypermethylation at the PRDX2 promoter in AML. Low protein expression of the antioxidant PRDX2 gene was clinically associated with poor prognosis in patients with AML. Functionally, PRDX2 acted as inhibitor of myeloid cell...

  18. An Animal-to-Human Scaling Law for Blast-Induced Traumatic Brain Injury Risk Assessment (United States)


    human injury risk would be of critical importance for guiding the design of blast- protective helmets and face shields. Materials and Methods ...Biomedical Imaging (IEEE, Piscataway, NJ), Vol 53, pp 1142–1145. 39. Prevost TP, Balakrishnan A, Suresh S, Socrate S (2011) Biomechanics of brain tissue. Acta...3006–3012. 51. El Sayed T, Mota A, Fraternali F, Ortiz M (2008) Biomechanics of traumatic brain in- jury. Comput Methods Appl Mech Eng 197(51–52):4692

  19. The Proteasome Inhibitor Bortezomib Sensitizes AML with Myelomonocytic Differentiation to TRAIL Mediated Apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Marianne van; Murphy, Eoin [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); Morrell, Ruth [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Knapper, Steven [Department of Haematology, School of Medicine, Cardiff University, Heath Park, CF14 4XN Cardiff (United Kingdom); O' Dwyer, Michael [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Medicine, National University of Ireland, University Road, Galway (Ireland); Samali, Afshin; Szegezdi, Eva, E-mail: [Apoptosis Research Center, National University of Ireland, University Road, Galway (Ireland); School of Natural Sciences, National University of Ireland, University Road, Galway (Ireland)


    Acute myeloid leukemia (AML) is an aggressive stem cell malignancy that is difficult to treat. There are limitations to the current treatment regimes especially after disease relapse, and therefore new therapeutic agents are urgently required which can overcome drug resistance whilst avoiding unnecessary toxicity. Among newer targeted agents, both tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and proteasome inhibitors show particular promise. In this report we show that a combination of the proteasome inhibitor bortezomib and TRAIL is effective against AML cell lines, in particular, AML cell lines displaying myelomonocytic/monocytic phenotype (M4/M5 AML based on FAB classification), which account for 20-30% of AML cases. We show that the underlying mechanism of sensitization is at least in part due to bortezomib mediated downregulation of c-FLIP and XIAP, which is likely to be regulated by NF-κB. Blockage of NF-κB activation with BMS-345541 equally sensitized myelomonocytic AML cell lines and primary AML blasts to TRAIL.

  20. Brain response to primary blast wave using validated finite element models of human head and advanced combat helmet

    Directory of Open Access Journals (Sweden)

    Liying eZhang


    Full Text Available Blast-induced traumatic brain injury has emerged as a signature injury in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH, a finite element (FE study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27-0.66 MPa from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP in the head ranged from 0.68-1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10-35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44% was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%. The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence "iso-damage" curves for brain injury are likely different than the Bowen curves

  1. AML (Logistics Center) Local Area Network - (United States)

    Department of Transportation — The AML LAN is designed to facilitate the services and resources needed to support the operations of the FAA Logistics Center users. The AML LAN provides support for...

  2. Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AML)

    International Nuclear Information System (INIS)

    Tang, Ruoping; Faussat, Anne-Marie; Perrot, Jean-Yves; Marjanovic, Zora; Cohen, Simy; Storme, Thomas; Morjani, Hamid; Legrand, Ollivier; Marie, Jean-Pierre


    Chemotherapeutic drug efflux via the P-glycoprotein (P-gp) transporter encoded by the MDR1/ABCB1 gene is a significant cause of drug resistance in numerous malignancies, including acute leukemias, especially in older patients with acute myeloid leukemia (AML). Therefore, the P-gp modulators that block P-gp-mediated drug efflux have been developed, and used in combination with standard chemotherapy. In this paper, the capacity of zosuquidar, a specific P-gp modulator, to reverse chemoresistance was examined in both leukemia cell lines and primary AML blasts. The transporter protein expressions were analyzed by flow cytometry using their specific antibodies. The protein functionalities were assessed by the uptake of their fluorescence substrates in presence or absence their specific modulators. The drug cytotoxicity was evaluated by MTT test. Zosuquidar completely or partially restored drug sensitivity in all P-gp-expressing leukemia cell lines tested and enhanced the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AML blasts with active P-gp. In addition, P-gp inhibition by zosuquidar was found to be more potent than cyclosporine A in cells with highly active P-gp. These in vitro studies suggest that zosuquidar may be an effective adjunct to cytotoxic chemotherapy for AML patients whose blasts express P-gp, especially for older patients

  3. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    International Nuclear Information System (INIS)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.


    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of 3 H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes

  4. Monoclonal antibodies to antigens on human neutrophils, activated T lymphocytes, and acute leukemia blast cells

    Energy Technology Data Exchange (ETDEWEB)

    Miterev, G.Yu.; Burova, G.F.; Puzhitskaya, M.S.; Danilevich, S.V.; Bulycheva, T.I.


    The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.

  5. Initiation of MLL-rearranged AML is dependent on C/EBPα

    DEFF Research Database (Denmark)

    Ohlsson, Ewa; Hasemann, Marie Sigurd; Willer, Anton


    have compared gene expression profiles from human MLL-rearranged AML to normal progenitors and identified the myeloid tumor suppressor C/EBPα as a putative collaborator in MLL-rearranged AML. Interestingly, we find that deletion of Cebpa rendered murine hematopoietic progenitors completely resistant...

  6. A radiolabeled antibody targeting CD123+ leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

    Directory of Open Access Journals (Sweden)

    Jeffrey V. Leyton


    Full Text Available Radioimmunotherapy (RIT with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS peptides and labeled with the Auger electron-emitter, 111In (111In-NLS-CSL360 was studied in the prevalent NOD/SCID mouse AML engraftment assay. Significant decreases in CD123+ leukemic cells and impairment of leukemic stem cell self-renewal were achieved with high doses of RIT. However, NOD/SCID mice were very radiosensitive to these doses. At low non-toxic treatment doses, 111In-NLS-CSL360 demonstrated a trend towards improved survival associated with decreased spleen/body weight ratio, an indicator of leukemia burden, and almost complete eradication of leukemia from the bone marrow in some mice.

  7. Primary Blast Injury Criteria for Animal/Human TBI Models using Field Validated Shock Tubes (United States)


    acute hemorrhage characterized by partial filling of small groups of alveoli by blood . 240 kPa: Mild multifocal pools of acute hemorrhage which...Neurotrauma, Blast TBI, Primary blast brain injury, Blast overpressure, Blood -brain barrier, Neuroinflammation, Oxidative stress, Neuroproteomics 16...stress, neuroinflammation and BBB damage as a result of blast overpressure in the acute phase (0, 4 and 24 hours post-exposure). Our group

  8. Functionally deregulated AML1/RUNX1 cooperates with BCR-ABL to induce a blastic phase-like phenotype of chronic myelogenous leukemia in mice.

    Directory of Open Access Journals (Sweden)

    Kiyoko Yamamoto

    Full Text Available Patients in the chronic phase (CP of chronic myelogenous leukemia (CML have been treated successfully following the advent of ABL kinase inhibitors, but once they progress to the blast crisis (BC phase the prognosis becomes dismal. Although mechanisms underlying the progression are largely unknown, recent studies revealed the presence of alterations of key molecules for hematopoiesis, such as AML1/RUNX1. Our analysis of 13 BC cases revealed that three cases had AML1 mutations and the transcript levels of wild-type (wt. AML1 were elevated in BC compared with CP. Functional analysis of representative AML1 mutants using mouse hematopoietic cells revealed the possible contribution of some, but not all, mutants for the BC-phenotype. Specifically, K83Q and R139G, but neither R80C nor D171N mutants, conferred upon BCR-ABL-expressing cells a growth advantage over BCR-ABL-alone control cells in cytokine-free culture, and the cells thus grown killed mice upon intravenous transfer. Unexpectedly, wt.AML1 behaved similarly to K83Q and R139G mutants. In a bone marrow transplantation assay, K83Q and wt.AML1s induced the emergence of blast-like cells. The overall findings suggest the roles of altered functions of AML1 imposed by some, but not all, mutants, and the elevated expression of wt.AML1 for the disease progression of CML.

  9. Membranes replace irradiated blast cells as growth requirement for leukemic blast progenitors in suspension culture

    International Nuclear Information System (INIS)

    Nara, N.; McCulloch, E.A.


    The blast cells of acute myeloblastic leukemia (AML) may be considered as a renewal population, maintained by blast stem cells capable of both self-renewal and the generation of progeny with reduced or absent proliferative potential. This growth requires that two conditions be met: first, the cultures must contain growth factors in media conditioned either by phytohemagglutinin (PHA)-stimulated mononuclear leukocytes (PHA-LCM), or by cells of the continuous bladder carcinoma line HTB9 (HTB9-CM). Second, the cell density must be maintained at 10(6) blasts/ml; this may be achieved by adding irradiated cells to smaller numbers of intact blasts. The authors are concerned with the mechanism of the feeding function. They present evidence that (a) cell-cell contact is required. (b) Blasts are heterogeneous in respect to their capacity to support growth. (c) Fractions containing membranes from blast cells will substitute for intact cells in promoting the generation of new blast progenitors in culture. (d) This membrane function may be specific for AML blasts, since membranes from blasts of lymphoblastic leukemia or normal marrow cells were inactive

  10. Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1.

    Directory of Open Access Journals (Sweden)

    Shinobu Tsuzuki


    Full Text Available AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo.The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo.These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood

  11. Perspectives on repeated low-level blast and the measurement of neurotrauma in humans as an occupational exposure risk (United States)

    Carr, W.; Dell, K. C.; Yanagi, M. A.; Hassan, D. M.; LoPresti, M. L.


    A pressing question in military medical research is the nature and degree of effects on the human brain from occupational repeated exposure to low-level explosive blast, but reliable and effective means to objectively measure such effects remain elusive. In survey results, headache, difficulty sleeping, irritability, cognitive impairment, and a variety of other symptoms consistent with post-concussive syndrome have been reported by those exposed to blast and there was positive correlation between degree of blast exposure and degree of symptomology, but an important goal is to obtain more objective evidence of an effect than self-report alone. This review reflects recent efforts to measure and evaluate such hypothesized effects and current recommendations for ongoing study. Optimal measures are likely those with sensitivity and specificity to systemic effects in mild neurotrauma, that have minimal to no volitional component, and that can be sampled relatively quickly with minimal intrusion in prospective, observational field studies during routine training with explosives. An understanding of an association between parameters of exposure to repeated low-level blast and negative neurologic effects would support the evaluation of clinical implications and development of protective equipment and surveillance protocols where warranted. At present, low-level blast exposure surveillance measurements do not exist as a systematic record for any professional community.

  12. Clinical impact of leukemic blast heterogeneity at diagnosis in cytogenetic intermediate-risk acute myeloid leukemia

    DEFF Research Database (Denmark)

    Hoffmann, Marianne Hutchings; Klausen, Tobias Wirenfeldt; Boegsted, Martin


    Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact.......Individual cellular heterogeneity within the acute myeloid leukemia (AML) bone marrow samples can be observed by multi parametric flow cytometry analysis (MFC) indicating that immunophenotypic screening for leukemic blast subsets may have prognostic impact....

  13. Targeted immunotherapy in acute myeloblastic leukemia: from animals to humans. (United States)

    Robin, Marie; Schlageter, Marie-Hélène; Chomienne, Christine; Padua, Rose-Ann


    Immunity against acute myeloid leukemia (AML) is demonstrated in humans by the graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation. Specific leukemic antigens have progressively been discovered and circulating specific T lymphocytes against Wilms tumor antigen, proteinase peptide or fusion-proteins produced from aberrant oncogenic chromosomal translocations have been detected in leukemic patients. However, due to the fact that leukemic blasts develop various escape mechanisms, antileukemic specific immunity is not able to control leukemic cell proliferation. The aim of immunotherapy is to overcome tolerance and boost immunity to elicit an efficient immune response against leukemia. We review different immunotherapy strategies tested in preclinical animal models of AML and the human trials that spurred from encouraging results obtained in animal models, demonstrate the feasibility of immunotherapy in AML patients.

  14. Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI) (United States)


    Andersson G (2009) The role of anxiety sensitivity and behavioral avoidance in tinnitus disability. IntJAudiol 48:295-299. Hiller W, Goebel G (1999...Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI) PRINCIPAL INVESTIGATOR...Induced Tinnitus and Related Traumatic Brain Injury (TBI) 5b. GRANT NUMBER W81XWH-11-2-0031 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  15. Osteolytic Bone Lesions - A Rare Presentation of AML M6. (United States)

    Geetha, N; Sreelesh, K P; Priya, M J; Lali, V S; Rekha, N


    Acute myeloid leukemia (AML) M6 is a rare form of AML accounting for M6 before. We discuss the case of a 17 year old boy with AML M6, who presented with osteolytic lesion of right humerus. He was treated with induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  16. Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6. (United States)

    Hasserjian, R P; Howard, J; Wood, A; Henry, K; Bain, B


    Classic erythroleukaemia (acute myeloid leukaemia M6, or M6 AML) is defined as an excess of myeloblasts in an erythroid predominant background. Leukaemia variants in which the primitive blast cells are demonstrably erythroid are extremely rare and poorly characterised. Variably referred to as "true erythroleukaemia" or "acute erythremic myelosis", they are often included within the M6 AML category even though they do not meet strict criteria for this type of AML. Two cases of acute erythroid neoplasia are presented with clinical, morphological, immunophenotypic, and cytogenetic analysis. Both patients presented with profound anaemia, one in a setting of long standing myelodysplasia. Bone marrow examination revealed a predominant population of highly dysplastic erythroid cells in both cases. In one case, the liver was infiltrated by neoplastic erythroid cells. Both patients died within four months of diagnosis. This report illustrates that cases of acute leukaemia occur in which the dominant neoplastic cell is a primitive erythroid cell without an accompanying increase in myeloblasts. This does not preclude the neoplastic clone originating in a multipotent haemopoietic stem cell, as suggested by cases arising in patients with myelodysplasia. Acute erythremic myelosis should be recognised as a distinct variant of M6 AML.

  17. The MDM-2 Antagonist Nutlin-3 Promotes the Maturation of Acute Myeloid Leukemic Blasts

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    Paola Secchiero


    Full Text Available The small-molecule inhibitor of murine double minute (MDM-2, Nutlin-3, induced variable apoptosis in primary acute myeloid leukemia (AML blasts, promoted myeloid maturation of surviving cells, as demonstrated by analysis of CD11 b, CD14 surface antigens, by morphologic examination. Although the best-characterized activity of Nutlin-3 is activation of the p53 pathway, Nutlin-3 induced maturation also in one AML sample characterized by p53 deletion, as well as in the p53-/- human myeloblastic HL-60 cell line. At the molecular level, the maturational activity of Nutlin-3 in HL-60 cells was accompanied by the induction of E2F1 transcription factor, it was significantly counteracted by specific gene knockdown with small interfering RNA for E2F1. Moreover, Nutlin-3, as well as tumor necrosis factor (TNF α, potentiated the maturational activity of recombinant TNF-related apoptosis-inducing lig, (TRAIL in HL-60 cells. However, although TNF-α significantly counteracted the proapoptotic activity of TRAIL, Nutlin-3 did not interfere with the proapoptotic activity of TRAIL. Taken together, these data disclose a novel, potentially relevant therapeutic role for Nutlin-3 in the treatment of both p53 wild-type, p53-/- AML, possibly in association with recombinant TRAIL.

  18. Targeting Human C-Type Lectin-Like Molecule-1 (CLL1) with a Bispecific Antibody for Acute Myeloid Leukemia Immunotherapy**


    Lu, Hua; Zhou, Quan; Deshmukh, Vishal; Phull, Hardeep; Ma, Jennifer; Tardif, Virginie; Naik, Rahul R.; Bouvard, Claire; Zhang, Yong; Choi, Seihyun; Lawson, Brian R.; Zhu, Shoutian; Kim, Chan Hyuk; Schultz, Peter G.


    Acute myeloid leukemia (AML), the most common acute adult leukemia and the second most common pediatric leukemia, still has a poor prognosis. Human C-type lectin-like molecule-1 (CLL1) is a recently identified myeloid lineage restricted cell surface marker, which is overexpressed in over 90% of AML patient myeloid blasts and in leukemic stem cells. Here, we describe the synthesis of a novel bispecific antibody, αCLL1-αCD3, using the genetically encoded unnatural amino acid, p-acetylphenylalan...


    Directory of Open Access Journals (Sweden)

    Robert Gale


    Full Text Available Therapy-related leukemia or therapy-related myeloid neoplasm are widely-used terms to designate leukemia developing in persons who previously received anti-cancer therapy (for example, see references 1, 2, especially if the prior anti-cancer therapy included drugs such as alkylators, DNA-intercalators, topoisomerase-2-inhibitors, purines and/or ionizing radiations.   Sometimes specific genes such as AML1, EVI1, NRAS or MLL are mutated by therapy or gene variants are produced which activate mutagens or interfere with DNA repair, such FANC, NQ01 or AML2. 3-5   But how can we know if AML in someone is a therapy-related? Keywords: Therapy-related leukemia; alkylators; ionizing radiations; Topoisomerase Inhibitors; DNA Repair

  20. Age-related epigenetic drift in the pathogenesis of MDS and AML. (United States)

    Maegawa, Shinji; Gough, Sheryl M; Watanabe-Okochi, Naoko; Lu, Yue; Zhang, Nianxiang; Castoro, Ryan J; Estecio, Marcos R H; Jelinek, Jaroslav; Liang, Shoudan; Kitamura, Toshio; Aplan, Peter D; Issa, Jean-Pierre J


    The myelodysplastic syndrome (MDS) is a clonal hematologic disorder that frequently evolves to acute myeloid leukemia (AML). Its pathogenesis remains unclear, but mutations in epigenetic modifiers are common and the disease often responds to DNA methylation inhibitors. We analyzed DNA methylation in the bone marrow and spleen in two mouse models of MDS/AML, the NUP98-HOXD13 (NHD13) mouse and the RUNX1 mutant mouse model. Methylation array analysis showed an average of 512/3445 (14.9%) genes hypermethylated in NHD13 MDS, and 331 (9.6%) genes hypermethylated in RUNX1 MDS. Thirty-two percent of genes in common between the two models (2/3 NHD13 mice and 2/3 RUNX1 mice) were also hypermethylated in at least two of 19 human MDS samples. Detailed analysis of 41 genes in mice showed progressive drift in DNA methylation from young to old normal bone marrow and spleen; to MDS, where we detected accelerated age-related methylation; and finally to AML, which markedly extends DNA methylation abnormalities. Most of these genes showed similar patterns in human MDS and AML. Repeat element hypomethylation was rare in MDS but marked the transition to AML in some cases. Our data show consistency in patterns of aberrant DNA methylation in human and mouse MDS and suggest that epigenetically, MDS displays an accelerated aging phenotype.

  1. AML (Advanced Mud Logging: First Among Equals

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    T. Loermans


    Full Text Available During the past ten years an enormous development in mud logging technology has been made. Traditional mud logging was only qualitative in nature, and mudlogs could not be used for the petrophysical well evaluations which form the basis for all subsequent activities on wells and fields. AML however can provide quantitative information, logs with a reliability, trueness and precision like LWD and WLL. Hence for well evaluation programmes there are now three different logging methods available, each with its own pros and cons on specific aspects: AML, LWD and WLL. The largest improvements have been made in mud gas analysis and elemental analysis of cuttings. Mud gas analysis can yield hydrocarbon fluid composition for some components with a quality like PVT analysis, hence not only revolutionising the sampling programme so far done with only LWD/WLL, but also making it possible to geosteer on fluid properties. Elemental analysis of cuttings, e.g. with XRF, with an ability well beyond the capabilities of the spectroscopy measurements possible earlier with LWD/WLL tools, is opening up improved ways to evaluate formations, especially of course where the traditional methods are falling short of requirements, such as in unconventional reservoirs. An overview and specific examples of these AML logs is given, from which it may be concluded that AML now ought to be considered as “first among its equals”.

  2. The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. (United States)

    van Rhenen, Anna; van Dongen, Guus A M S; Kelder, Angèle; Rombouts, Elwin J; Feller, Nicole; Moshaver, Bijan; Stigter-van Walsum, Marijke; Zweegman, Sonja; Ossenkoppele, Gert J; Jan Schuurhuis, Gerrit


    In CD34(+) acute myeloid leukemia (AML), the malignant stem cells reside in the CD38(-) compartment. We have shown before that the frequency of such CD34(+)CD38(-) cells at diagnosis correlates with minimal residual disease (MRD) frequency after chemotherapy and with survival. Specific targeting of CD34(+)CD38(-) cells might thus offer therapeutic options. Previously, we found that C-type lectin-like molecule-1 (CLL-1) has high expression on the whole blast compartment in the majority of AML cases. We now show that CLL-1 expression is also present on the CD34(+)CD38(-) stem- cell compartment in AML (77/89 patients). The CD34(+)CLL-1(+) population, containing the CD34(+)CD38(-)CLL-1(+) cells, does engraft in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with outgrowth to CLL-1(+) blasts. CLL-1 expression was not different between diagnosis and relapse (n = 9). In remission, both CLL-1(-) normal and CLL-1(+) malignant CD34(+)CD38(-) cells were present. A high CLL-1(+) fraction was associated with quick relapse. CLL-1 expression is completely absent both on CD34(+)CD38(-) cells in normal (n = 11) and in regenerating bone marrow controls (n = 6). This AML stem-cell specificity of the anti-CLL-1 antibody under all conditions of disease and the leukemia-initiating properties of CD34(+)CLL-1(+) cells indicate that anti-CLL-1 antibody enables both AML-specific stem-cell detection and possibly antigen-targeting in future.

  3. A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience. (United States)

    Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen


    To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

  4. Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies. (United States)

    Graf, Michaela; Hecht, Karin; Reif, Susanne; Pelka-Fleischer, Renate; Pfister, Karin; Schmetzer, Helga


    Hemopoietic cytokines regulate hemopoietic cell functions via specific cell surface receptors. There is evidence to suggest, that those receptors (R) could play a role in leukemia with respect to cell differentiations and its regulation, prognosis, and pathobiology. Knowledge of individual cytokine receptor (CKR) profiles could provide new discoveries about CKR-supported therapeutic considerations. We have studied the expression of CKR on mononuclear bone marrow (BM) cells of 89 patients with acute myeloid leukemia (AML) at first diagnosis, three patients at relapse or with persisting AML and eight healthy probands by fluorescence-activated cell sorting (FACS) analysis using directly fluorescein-conjugated antibodies: CD114 (hG-CSF-R), CD116 (hGM-CSF-R), CD117 (hSCF-R), CD123 (hIL-3-R), CD130 (gp130subunit), CD135 (hFL-R). A case was defined as positive, if more than 20% of the cells expressed the regarding CKR. All investigated CKR were more frequently expressed in AML-samples than in healthy BM-samples, except CD130, which was only expressed on 5-6% of AML-blasts in all and with only one healthy BM-sample being CD130(+). Within the French-American-British (FAB) types we observed a maturation- and lineage (granulocytic/monocytic)-committed expression profile. Monocytic subtypes (FAB-type M4/M5) showed significantly more GM-CSF-R(+) (P = 0.001) and FL-R(+) (P = 0.001) and significantly less stem cell factor-R (SCF-R(+)) (P = 0.02) cases. Highest proportions of G-CSF-R(+) blasts were observed in FAB-type M3. In undifferentiated leukemias (FAB-type M1, M2) high amounts of SCF-R(+), IL-3-R(+), and FL-R(+) blasts could be detected. FL-R was the only CKR, which was positive in FAB-type M0 (n = 2). No differences in CKR-expression were detected between primary (p) and secondary (s). Separating our patient cohorts in cytogenetic risk groups we could detect a significant higher proportion of G-CSF-R(+) blasts in the cytogenetic good risk group than in the bad risk group (P

  5. CD117 expression on blast cells in acute myeloid leukemia

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    Goryainova N.V.


    Full Text Available The aim of the present work was to analyze the frequency of CD117 (c-KIT antigen expression on the blast cells in acute myeloid leukemia (AML, evaluation of the presence of the relationship between the expression of the c-KIT and leukemia according to the FAB classification and definition of co-expression of the antigen CD117, antigens CD33 and CD34. The data of 47 patients with AML were diagnosed. M0 AML variant was established in 3 (6% patients, M1 – in 2 (4%, M2 – in 9 (20%, M4 – in 22 (47% and M5 – in 11 (23%. For immunophenotypic stu¬dies monoclonal antibodies (mAb that detect antigens of anti-CD34, anti-CD33 and anti-CD117 (Becton Dickinson, USA were used. The presence of the antigen CD117 was detected in 39 people, accounting for 83% of all surveyed. Antigen c-KIT was present in 48.117.0% cells on average: in all 3 cases – AML M0, in2 cases of AML M1, in 6 cases – AML M2, 20 of 22 cases – AML M4 and in 8 of 11 AML M5 cases. Average levels of CD117 in investigated leukemia cases statistically differed significantly (p=0.0067. Among 39 CD117- positive patients in 25 (53% co-expression of CD117+/CD34+ was revealed. Expression of CD117+/CD34- was observed in 14 cases (30%, CD117-/CD34+ – in 4 cases (8,5%, CD117-/CD34- – in 4 cases (8.5%. CD34 had of 64% of cells of myeloid origin. A high positive cor¬relation between expression of CD117 and CD34 (r=+0,5169 was determined, being statistically significant (p0,0067.

  6. Osteoblasts Protect AML Cells from SDF-1-Induced Apoptosis (United States)

    Kremer, Kimberly N.; Dudakovic, Amel; McGee-Lawrence, Meghan E.; Philips, Rachael L.; Hess, Allan D.; Smith, B. Douglas; van Wijnen, Andre J.; Karp, Judith E.; Kaufmann, Scott H.; Westendorf, Jennifer J.; Hedin, Karen E.


    The bone marrow provides a protective environment for acute myeloid leukemia (AML) cells that often allows leukemic stem cells to survive standard chemotherapeutic regimens. Targeting these leukemic stem cells within the bone marrow is critical for preventing relapse. We recently demonstrated that SDF-1, a chemokine abundant in the bone marrow, induces apoptosis in AML cell lines and in patient samples expressing high levels of its receptor, CXCR4. Here we show that a subset of osteoblast lineage cells within the bone marrow can protect AML cells from undergoing apoptosis in response to the SDF-1 naturally present in that location. In co-culture systems, osteoblasts at various stages of differentiation protected AML cell lines and patient isolates from SDF-1-induced apoptosis. The differentiation of the osteoblast cell lines, MC3T3 and W-20-17, mediated this protection via a cell contact-independent mechanism. In contrast, bone marrow-derived mesenchymal cells, the precursors of osteoblasts, induced apoptosis in AML cells via a CXCR4-dependent mechanism and failed to protect AML cells from exogenously added SDF-1. These results indicate that osteoblasts in the process of differentiation potently inhibit the SDF-1-driven apoptotic pathway of CXCR4-expressing AML cells residing in the bone marrow. Drugs targeting this protective mechanism could potentially provide a new approach to treating AML by enhancing the SDF-1-induced apoptosis of AML cells residing within the bone marrow microenvironment. PMID:24851270

  7. Low-dose total body irradiation and G-CSF without hematopoietic stem cell support in the treatment of relapsed or refractory acute myelogenous leukemia (AML), or AML in second or subsequent remission

    International Nuclear Information System (INIS)

    Shulman, Lawrence N.; Tarbell, Nancy J.; Storen, Elizabeth; Marcus, Karen; Mauch, Peter M.


    Purpose: Patients with relapsed acute myelogenous leukemia (AML), who are not eligible for bone marrow transplantation, have a poor prognosis when treated with chemotherapy alone. Total body irradiation (TBI) is an effective modality against AML when used in doses of 1000-1400 cGy with hematopoietic stem cell support. We undertook a phase I study of TBI with granulocyte-colony-stimulating factor (G-CSF) support, without stem cell support in patients with AML either in relapse or second or subsequent remission. Methods and Materials: Patients with relapsed AML, or AML in second or subsequent remission were treated in a phase I study of TBI followed by G-CSF. The first dose level was 200 cGy. After the initial cohort of patients it was clear that patients with overt leukemia did not benefit from this treatment, and subsequent patients were required to be in remission at the time of TBI. Results: Eleven patients were treated, 4 in overt relapse, and 7 in remission. 200 cGy was used in all, and dose escalation was not possible due to prolonged thrombocytopenia in all patients but one. Neutrophil recovery was adequate in those patients who remained in remission after TBI. Patients with overt leukemia had transient reduction in blast counts, but rapid recurrence of their leukemia. Patients treated in remission had short remissions, with the exception of one patient who is in remission 32 months after treatment. Conclusion: There is some antileukemic effect of TBI even at 200 cGy, though this dose appears to be too low to help a significant number of patients. If TBI is to be escalated without stem cell support, then a thrombopoietic agent will need to be used

  8. Proteasome inhibition enhances the efficacy of volasertib-induced mitotic arrest in AML in vitro and prolongs survival in vivo. (United States)

    Schnerch, Dominik; Schüler, Julia; Follo, Marie; Felthaus, Julia; Wider, Dagmar; Klingner, Kathrin; Greil, Christine; Duyster, Justus; Engelhardt, Monika; Wäsch, Ralph


    Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B. Therefore, we tested whether interfering with mitotic slippage through proteasome inhibition arrests and kills AML cells more efficiently during mitosis. We show that therapeutic doses of bortezomib block the slow degradation of cyclin B during a volasertib-induced mitotic arrest in AML cell lines and patient-derived primary AML cells. In a xenotransplant mouse model of human AML, mice receiving volasertib in combination with bortezomib showed superior disease control compared to mice receiving volasertib alone, highlighting the potential therapeutic impact of this drug combination.

  9. Examination of the protective roles of helmet/faceshield and directionality for human head under blast waves. (United States)

    Sarvghad-Moghaddam, Hesam; Jazi, Mehdi Salimi; Rezaei, Asghar; Karami, Ghodrat; Ziejewski, Mariusz


    A parametric study was conducted to delineate the efficacy of personal protective equipment (PPE), such as ballistic faceshields and advanced combat helmets, in the case of a blast. The propagations of blast waves and their interactions with an unprotected head, a helmeted one, and a fully protected finite element head model (FEHM) were modeled. The biomechanical parameters of the brain were recorded when the FEHM was exposed to shockwaves from the front, back, top, and bottom. The directional dependent tissue response of the brain and the variable efficiency of PPE with respect to the blast orientation were two major results of this study.

  10. Nassi-Schneiderman Diagram in HTML Based on AML (United States)

    Menyhárt, László


    In an earlier work I defined an extension of XML called Algorithm Markup Language (AML) for easy and understandable coding in an IDE which supports XML editing (e.g. NetBeans). The AML extension contains annotations and native language (English or Hungarian) tag names used when coding our algorithm. This paper presents a drawing tool with which…

  11. MRD in AML: it is time to change the definition of remission. (United States)

    Ossenkoppele, Gert J; Schuurhuis, Gerrit Jan


    The possibility of defining residual disease far below the morphological level of 5% blast cells is changing the landscape of risk classification in acute myeloid leukemia (AML). The so-called minimal residual disease (MRD) approach at this time can establish the presence of leukemia cells down to levels of 1:1000-1:10(6) white blood cells, compared to 1:20 for morphology. Availability of the newer and more sensitive technology to quantify the level of leukemic burden raises the issue of whether MRD should emerge as a new definition of complete response. This paper explores some of the issues surrounding such a change in definition. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Paclitaxel Induced MDS and AML: A Case Report and Literature Review

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    Udit Bhaskar Bhatnagar


    Full Text Available Therapy related acute myelogenous leukemia (AML and myelodysplastic syndromes (MDS have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies.

  13. The CNGRC-GG-D(KLAKLAK)2 peptide induces a caspase-independent, Ca2+-dependent death in human leukemic myeloid cells by targeting surface aminopeptidase N/CD13. (United States)

    Bouchet, Sandrine; Tang, Ruoping; Fava, Fanny; Legrand, Ollivier; Bauvois, Brigitte


    The CD13 antigen's binding site for the Asn-Gly-Arg (NGR) motif enables NGR-containing chemotherapeutic drugs to be delivered to CD13-positive tumours. Human CD13-positive acute myeloid leukemia (AML) cells proliferate abnormally and escape death. Here, we show that the CNGRC-GG-D(KLAKLAK)2 peptide induces death in AML cell lines (U937, THP-1, NB4, HL-60) and primary blood cells from AML patients. Cell death was characterized as a caspase-independent mechanism, without DNA fragmentation, but phosphatidylserine externalization and membrane disruption. Our results demonstrate in U937 cells that (i) the NGR-peptide triggers the loss of mitochondrial potential(ΔΨm) and generates superoxide anion (O2-), (ii) N-acetyl-L-cysteine (NAC) and extra/intracellular Ca2+ chelators (BAPTA) prevent both O2- production and cell death, (iii) the Ca2+-channel blocker nifedipine prevents cell death (indicating that Ca2+ influx is the initial death trigger), and (iv) BAPTA, but not NAC, prevents ΔΨm loss (suggesting O2- is a mitochondrial downstream effector). AML cell lines and primary blasts responding to the lethal action of NGR-peptide express promatrix metalloproteinase-12 (proMMP-12) and its substrate progranulin (an 88 kDa cell survival factor). A cell-free assay highlighted proMMP-12 activation by O2-. Accordingly, NGR-peptide's downregulation of 88 kDa progranulin protein was prevented by BAPTA and NAC. Conversely, AML blast resistance to NGR-peptide is associated with the expression of a distinct, 105 kDa progranulin isoform. These results indicate that CNGRC-GG-D(KLAKLAK)2 induces death in AML cells through the Ca2+-mitochondria-O2.-pathway, and support the link between proMMP-12 activation and progranulin cleavage during cell death. Our findings may have implications for the understanding of tumour biology and treatment.

  14. Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

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    Lisa Pleyer


    Full Text Available We recently published a clinically-meaningful improvement in median overall survival (OS for patients with acute myeloid leukaemia (AML, >30% bone marrow (BM blasts and white blood cell (WBC count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010. As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012 and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214 with AAR patients meeting the same inclusion criteria (“AAR (001-like” cohort; n = 95. The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616 for “AML-001” versus “AAR (001-like” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309 and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6 months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95 versus all AAR patients with World Health Organization (WHO-defined AML (

  15. Assessment of the Effects of Acute and Repeated Exposure to Blast Overpressure in Rodents: Towards a Greater Understanding of Blast and the Potential Ramifications for Injury in Humans Exposed to Blast

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    Stephen Thomas Ahlers


    Full Text Available Mild traumatic brain injury (mTBI resulting from exposure to improvised explosive devices (IEDs has fueled a requirement to develop animals models that mirror this condition using exposure to blast overpressure (BOP. En route to developing a model of repeated exposure to BOP we sought to initially characterize the effects of acute BOP exposure in rodents, focusing specifically on the levels of BOP exposure that produced clinical mTBI symptoms. We first measured BOP effects on gross motor function on a balance beam. Separate groups of unanesthetized rats were exposed (in different orientations to 40 kPa, 75 kPa and 120 kPa BOP exposure inside a pneumatically driven shock tube. Results demonstrated that rats exposed to 120 kPa demonstrated transient alterations or loss of consciousness indicated by a transient loss of righting and by increased latencies on the balance beam. The 120 kPa exposure was the threshold for overt pathology for acute BOP exposure with approximately 30% of rats presenting with evidence of subdural hemorrhage and cortical contusions. All animals exposed to 120 kPa BOP manifested evidence of significant pulmonary hemorrhage. Anterograde memory deficits were observed in rats exposed to 75 kPa facing the BOP wave and rats exposed to 120 kPa in the lateral (side orientation. We next assessed repeated exposure to either lateral or frontal 40 kPa BOP in anesthetized rats, once per day for 12 days. Results showed that repeated exposure in the frontal, but not side, orientation to the BOP wave produced a transitory learning deficit on a Morris water maze (MWM task as shown by significantly longer latencies to reach the submerged platform in the second and third blocks of a four block session. Implications of these data are discussed in relation to the manifestation of mTBI in military personnel exposed to IEDs. Finally, we suggest that there are multiple types of brain injury from blast.

  16. The applicability of the WHO classification in paediatric AML. A NOPHO-AML study

    DEFF Research Database (Denmark)

    Sandahl, Julie D; Kjeldsen, Eigil; Abrahamsson, Jonas


    The World Health Organization (WHO) classification of myeloid leukaemia was revised in 2008. It incorporates newly recognized entities and emphasizes the pivotal role of cytogenetic abnormalities. The aim of this study was to evaluate the usability of the WHO classification when applied to a large......(7q) into one group. We found that -7 (n = 14) had significantly poorer outcome than del(7q) (n = 11); 5-year event-free survival 26% vs. 67%, (P = 0·02), and 5-year overall survival 51% vs. 90%, (P = 0·04). The largest group was the highly heterogeneous AML not otherwise specified (NOS) (n = 280...

  17. CNS Involvement in AML Patient Treated with 5-Azacytidine

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    Diamantina Vasilatou


    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  18. Trisomy 8 in Pediatric Acute Myeloid Leukemia. A NOPHO-AML Study

    DEFF Research Database (Denmark)

    Laursen, Anne Cathrine Lund; Sandahl, Julie Damgaard; Kjeldsen, Eigil


    Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML...

  19. Direct Comparison of the Primary Blast Response of a Physical Head Model with Post-mortem Human Subjects (United States)


    quantitatively the effect of protective headwear. The following article discusses the validation of the BI2PED (Blast-Induced Brain Injury Protection...shots using rget locatio classic sho long positiv order of ith its cu , the current b e to generat ark. In order rated shock an operationa rom free

  20. Hif-1α and Hif-2α synergize to suppress AML development but are dispensable for disease maintenance. (United States)

    Vukovic, Milica; Guitart, Amelie V; Sepulveda, Catarina; Villacreces, Arnaud; O'Duibhir, Eoghan; Panagopoulou, Theano I; Ivens, Alasdair; Menendez-Gonzalez, Juan; Iglesias, Juan Manuel; Allen, Lewis; Glykofrydis, Fokion; Subramani, Chithra; Armesilla-Diaz, Alejandro; Post, Annemarie E M; Schaak, Katrin; Gezer, Deniz; So, Chi Wai Eric; Holyoake, Tessa L; Wood, Andrew; O'Carroll, Dónal; Ratcliffe, Peter J; Kranc, Kamil R


    Leukemogenesis occurs under hypoxic conditions within the bone marrow (BM). Knockdown of key mediators of cellular responses to hypoxia with shRNA, namely hypoxia-inducible factor-1α (HIF-1α) or HIF-2α, in human acute myeloid leukemia (AML) samples results in their apoptosis and inability to engraft, implicating HIF-1α or HIF-2α as therapeutic targets. However, genetic deletion of Hif-1α has no effect on mouse AML maintenance and may accelerate disease development. Here, we report the impact of conditional genetic deletion of Hif-2α or both Hif-1α and Hif-2α at different stages of leukemogenesis in mice. Deletion of Hif-2α accelerates development of leukemic stem cells (LSCs) and shortens AML latency initiated by Mll-AF9 and its downstream effectors Meis1 and Hoxa9. Notably, the accelerated initiation of AML caused by Hif-2α deletion is further potentiated by Hif-1α codeletion. However, established LSCs lacking Hif-2α or both Hif-1α and Hif-2α propagate AML with the same latency as wild-type LSCs. Furthermore, pharmacological inhibition of the HIF pathway or HIF-2α knockout using the lentiviral CRISPR-Cas9 system in human established leukemic cells with MLL-AF9 translocation have no impact on their functions. We therefore conclude that although Hif-1α and Hif-2α synergize to suppress the development of AML, they are not required for LSC maintenance. © 2015 Vukovic et al.

  1. Transglutaminase 2 expression in acute myeloid leukemia: Association with adhesion molecule expression and leukemic blast motility (United States)

    Meyer, Stefan; Ravandi-Kashani, Farhad; Borthakur, Gautam; Coombes, Kevin R.; Zhang, Nianxiang; Kornblau, Steven


    Acute myeloid leukemia (AML) is a heterogenous disease with differential oncogene association, outcome and treatment regimens. Treatment strategies for AML have improved outcome but despite increased molecular biological information AML is still associated with poor prognosis. Proteomic analysis on the effects of a range of leukemogenic oncogenes showed that the protein transglutaminase 2 (TG2) is expressed at greater levels as a consequence of oncogenic transformation. Further analysis of this observation was performed with 511 AML samples using reverse phase proteomic arrays, demonstrating that TG2 expression was higher at relapse than diagnosis in many cases. In addition elevated TG2 expression correlated with increased expression of numerous adhesion proteins and many apoptosis regulating proteins, two processes related to leukemogenesis. TG2 has previously been linked to drug resistance in cancer and given the negative correlation between TG2 levels and peripheral blasts observed increased TG2 levels may lead to the protection of the leukemic stem cell due to increased adhesion/reduced motility. TG2 may therefore form part of a network of proteins that define poor outcome in AML patients and potentially offer a target to sensitize AML stem cells to drug treatment. PMID:23576428

  2. The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs

    NARCIS (Netherlands)

    Mandoli, Amit; Singh, Abhishek A.; Prange, Koen H. M.; Tijchon, Esther; Oerlemans, Marjolein; Dirks, Rene; Ter Huurne, Menno; Wierenga, Albertus T. J.; Janssen-Megens, Eva M.; Berentsen, Kim; Sharifi, Nilofar; Kim, Bowon; Matarese, Filomena; Nguyen, Luan N.; Hubner, Nina C.; Rao, Nagesha A.; van den Akker, Emile; Altucci, Lucia; Vellenga, Edo; Stunnenberg, Hendrik G.; Martens, Joost H. A.


    The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels

  3. Cytogenetic findings in adult secondary acute myeloid leukemia (AML): frequency of favorable and adverse chromosomal aberrations do not differ from adult de novo AML

    DEFF Research Database (Denmark)

    Preiss, Birgitte S; Bergman, Olav J; Friis, Lone S


    During a 15-year period, 161 adult patients were diagnosed with secondary acute myeloid leukemia (s-AML) in the region of Southern Denmark. In 73 patients, the AML diagnosis was preceded by myelodysplastic syndrome (MDS-AML), in 31 patients by an antecedent hematologic disease, and in 57 patients...

  4. Basic Local Alignment Search Tool (BLAST) (United States)

    U.S. Department of Health & Human Services — BLAST finds regions of similarity between biological sequences. The program compares nucleotide or protein sequences to sequence databases and calculates the...

  5. Shear Forces during Blast, Not Abrupt Changes in Pressure Alone, Generate Calcium Activity in Human Brain Cells (United States)


    8217[-·:’ 50 100 150 200 250 300 Time (sec) Mean Peak Shear Stress (Pa) 0.6 ɘ.0001 200 250 300 350 400 Fluid Volume (I- LL ) lack of correlation to...Blood Flow Metab 30: 255–266. 5. Nakagawa A, Manley GT, Gean AD, Ohtani K, Armonda R, et al. (2011) Mechanisms of primary blast-induced traumatic brain

  6. The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation. (United States)

    de Laurentiis, A; Hiscott, J; Alcalay, M


    The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene. Many studies on TEL-AML1 describe specific properties of the fusion protein, but a thorough understanding of its function is lacking. We exploited a pluripotent hematopoietic stem/progenitor cell line, EML1, and generated a cell line (EML-TA) stably expressing the TEL-AML1 fusion protein. EML1 cells differentiate to mature B-cells following treatment with IL7; whereas EML-TA display an impaired differentiation capacity and remain blocked at an early stage of maturation. Global gene expression profiling of EML1 cells at different stages of B-lymphoid differentiation, compared with EML-TA, identified the interferon (IFN)α/β pathway as a primary target of repression by TEL-AML1. In particular, expression and phosphorylation of interferon-regulatory factor 3 (IRF3) was decreased in EML-TA cells; strikingly, stable expression of IRF3 restored the capacity of EML-TA cells to differentiate into mature B-cells. Similarly, IRF3 silencing in EML1 cells by siRNA was sufficient to block B-lymphoid differentiation. The ability of TEL-AML1 to block B-cell differentiation and downregulate the IRF3-IFNα/β pathway was confirmed in mouse and human primary hematopoietic precursor cells (Lin- and CD34+ cells, respectively), and in a patient-derived cell line expressing TEL-AML1 (REH). Furthermore, treatment of TEL-AML1 expressing cells with IFNα/β was sufficient to overcome the maturation block. Our data provide new insight on TEL-AML1 function and may offer a new therapeutic opportunity for B-ALL.

  7. SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. (United States)

    Kung Sutherland, May S; Walter, Roland B; Jeffrey, Scott C; Burke, Patrick J; Yu, Changpu; Kostner, Heather; Stone, Ivan; Ryan, Maureen C; Sussman, Django; Lyon, Robert P; Zeng, Weiping; Harrington, Kimberly H; Klussman, Kerry; Westendorf, Lori; Meyer, David; Bernstein, Irwin D; Senter, Peter D; Benjamin, Dennis R; Drachman, Jonathan G; McEarchern, Julie A


    Outcomes in acute myeloid leukemia (AML) remain unsatisfactory, and novel treatments are urgently needed. One strategy explores antibodies and their drug conjugates, particularly those targeting CD33. Emerging data with gemtuzumab ozogamicin (GO) demonstrate target validity and activity in some patients with AML, but efficacy is limited by heterogeneous drug conjugation, linker instability, and a high incidence of multidrug resistance. We describe here the development of SGN-CD33A, a humanized anti-CD33 antibody with engineered cysteines conjugated to a highly potent, synthetic DNA cross-linking pyrrolobenzodiazepine dimer via a protease-cleavable linker. The use of engineered cysteine residues at the sites of drug linker attachment results in a drug loading of approximately 2 pyrrolobenzodiazepine dimers per antibody. In preclinical testing, SGN-CD33A is more potent than GO against a panel of AML cell lines and primary AML cells in vitro and in xenotransplantation studies in mice. Unlike GO, antileukemic activity is observed with SGN-CD33A in AML models with the multidrug-resistant phenotype. Mechanistic studies indicate that the cytotoxic effects of SGN-CD33A involve DNA damage with ensuing cell cycle arrest and apoptotic cell death. Together, these data suggest that SGN-CD33A has CD33-directed antitumor activity and support clinical testing of this novel therapeutic in patients with AML.

  8. PD-1 signaling and inhibition in AML and MDS. (United States)

    Haroun, Faysal; Solola, Sade A; Nassereddine, Samah; Tabbara, Imad


    Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.


    Directory of Open Access Journals (Sweden)

    Francesco D'Alò


    Full Text Available Acute myeloid leukemia (AML is a clonal disorder of the hematopoietic stem cell, typical of the elderly, with a median age of over 60 years at diagnosis. In AML, older age is one of the strongest independent adverse prognostic factor, associated with decreased complete response rate, worse disease-free and overall survival, with highest rates of treatment related mortality, resistant disease and relapse, compared to younger patients. While clinical risk factors do not significantly differ between older and younger patients, outcomes are compromised in elderly patients not only by increased comorbidities and susceptibility to toxicity from therapy, but it is now recognized that elderly AML represents a biologically distinct disease, that is itself more aggressive and less responsive to therapy. In elderly individuals prolonged exposure to environmental carcinogens may be the basis for the aggressive biology of the disease. This may also be the basis for similarities between elderly AML and therapy-related myeloid malignancies, mimicking toxic effects of previous cytotoxic treatments on hematopoietic stem cells. Age is itself a risk factor for t-MN, which are more frequent in elderly patients, where also a shorter latency between treatment of primary tumor and t-MN has been reported. Similarities between therapy-related malignancies and elderly AML include morphological aspects, as the presence of multilineage dysplasia preceding and/or concomitant to the development of leukemia, and adverse cytogenetics, including poor karyotype and chromosome 5 and/or 7 abnormalities. Looking at molecular prognosticators in elderly AML, similar to t-MN,  reduced frequency of favorable factors, as reduced number of NPM1 and CEBPA mutated cases has been observed, together with increased incidence of negative factors, as increased MDR1 expression, accelerated telomere shortening  and frequency of methylation changes. Given the unfavorable prognosis of elderly and

  10. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.


    chromosomal structural rearrangements and single nucleotide variants (SNVs). Conventional AML diagnostics and recent seminal next-generation sequencing (NGS) studies have identified more than 200 recurrent genetic aberrations presenting in various combinations in individual patients. Significantly, many...... of these aberrations occur in normal hematopoietic stem and progenitor cells (HSCs/HPCs) before definitive leukemic transformation through additional acquisition of a few (that is, mostly 1 or 2) leukemia-promoting driver aberrations. NGS studies on sorted bone marrow (BM) populations of AML patients with a normal...

  11. Blast noise classification with common sound level meter metrics. (United States)

    Cvengros, Robert M; Valente, Dan; Nykaza, Edward T; Vipperman, Jeffrey S


    A common set of signal features measurable by a basic sound level meter are analyzed, and the quality of information carried in subsets of these features are examined for their ability to discriminate military blast and non-blast sounds. The analysis is based on over 120 000 human classified signals compiled from seven different datasets. The study implements linear and Gaussian radial basis function (RBF) support vector machines (SVM) to classify blast sounds. Using the orthogonal centroid dimension reduction technique, intuition is developed about the distribution of blast and non-blast feature vectors in high dimensional space. Recursive feature elimination (SVM-RFE) is then used to eliminate features containing redundant information and rank features according to their ability to separate blasts from non-blasts. Finally, the accuracy of the linear and RBF SVM classifiers is listed for each of the experiments in the dataset, and the weights are given for the linear SVM classifier.

  12. Calculation of driling and blasting parameters in blasting performance


    Dambov, Risto; Karanakova Stefanovska, Radmila; Dambov, Ilija


    In all mining technology drilling and blasting parameters and works are one of the main production processes at each mine. The parameters of drilling and blasting and explosives consumption per ton of blasting mass are define economic indicators of any blasting no matter for what purpose and where mining is performed. The calculation of rock blasting should always have in mind that the methodology of calculation of all drilling and blasting parameters in blasting performance are performed for...

  13. Gene expression profiling of acute myeloid leukemia samples from adult patients with AML-M1 and -M2 through boutique microarrays, real-time PCR and droplet digital PCR. (United States)

    Handschuh, Luiza; Kaźmierczak, Maciej; Milewski, Marek C; Góralski, Michał; Łuczak, Magdalena; Wojtaszewska, Marzena; Uszczyńska-Ratajczak, Barbara; Lewandowski, Krzysztof; Komarnicki, Mieczysław; Figlerowicz, Marek


    Acute myeloid leukemia (AML) is the most common and severe form of acute leukemia diagnosed in adults. Owing to its heterogeneity, AML is divided into classes associated with different treatment outcomes and specific gene expression profiles. Based on previous studies on AML, in this study, we designed and generated an AML-array containing 900 oligonucleotide probes complementary to human genes implicated in hematopoietic cell differentiation and maturation, proliferation, apoptosis and leukemic transformation. The AML-array was used to hybridize 118 samples from 33 patients with AML of the M1 and M2 subtypes of the French-American‑British (FAB) classification and 15 healthy volunteers (HV). Rigorous analysis of the microarray data revealed that 83 genes were differentially expressed between the patients with AML and the HV, including genes not yet discussed in the context of AML pathogenesis. The most overexpressed genes in AML were STMN1, KITLG, CDK6, MCM5, KRAS, CEBPA, MYC, ANGPT1, SRGN, RPLP0, ENO1 and SET, whereas the most underexpressed genes were IFITM1, LTB, FCN1, BIRC3, LYZ, ADD3, S100A9, FCER1G, PTRPE, CD74 and TMSB4X. The overexpression of the CPA3 gene was specific for AML with mutated NPM1 and FLT3. Although the microarray-based method was insufficient to differentiate between any other AML subgroups, quantitative PCR approaches enabled us to identify 3 genes (ANXA3, S100A9 and WT1) whose expression can be used to discriminate between the 2 studied AML FAB subtypes. The expression levels of the ANXA3 and S100A9 genes were increased, whereas those of WT1 were decreased in the AML-M2 compared to the AML-M1 group. We also examined the association between the STMN1, CAT and ABL1 genes, and the FLT3 and NPM1 mutation status. FLT3+/NPM1- AML was associated with the highest expression of STMN1, and ABL1 was upregulated in FLT3+ AML and CAT in FLT3- AML, irrespectively of the NPM1 mutation status. Moreover, our results indicated that CAT and WT1

  14. Resistance of some leukemic blasts to lysis by lymphokine activated killer (LAK) cells

    Energy Technology Data Exchange (ETDEWEB)

    Panayotides, P; Sjoegren, A -M; Reizenstein, P; Porwit, A. Immunopathology Lab., Dept. of Pathology, Karolinska Hospital, Stockholm; Wasserman, J


    Peripheral blood mononuclear cells (PBMC) from healthy donors and AML patients in remission were stimulated with phytohemagglutinin (PHA) and recombinant interleukin-2 (IL-2). These stimulated cells (lymphokine activated killer (LAK) cells) showed increased DNA synthesis as measured by /sup 3/H-Thymidine uptake. A synergistic effect of PHA and IL-2 was found. LAK cells' ability to kill acute myeloid leukemia (AML) blasts was investigated by the /sup 51/Cr release assay. LAK cells showed a cytotoxicity (over 10% specific /sup 51/Cr release) against 9/12 leukemic blasts, even at effector/target (E/T) ratios as low as 5:1. However, on average only 22.2% (SD 11.8) and 36.5% (SD 12.5) /sup 51/Cr release were obtained in 4- and 18-hour cytotoxicity assays, respectively, at an E/T ratio of 20:1. Leukemic blasts in 3/12 AML cases and normal PBMC were entirely resistant to lysis, even at an E/T ratio of 80:1. Susceptibility to lysis was not correlated to peanut-agglutinin receptor expression. LAK cells were more cytotoxic towards the K-562 cell line (natural killer activity) than unstimulated PBMC.

  15. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element. (United States)

    Fukunaga, Junichi; Nomura, Yusuke; Tanaka, Yoichiro; Amano, Ryo; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Sakamoto, Taiichi; Kozu, Tomoko


    AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5'-NNCCAC-3' and 5'-GCGMGN'N'-3' (M:A or C; N and N' form Watson-Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.

  16. Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

    DEFF Research Database (Denmark)

    Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E


    During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

  17. Consecutive epigenetically-active agent combinations act in ID1-RUNX3-TET2 and HOXA pathways for Flt3ITD+ve AML. (United States)

    Sayar, Hamid; Liu, Yan; Gao, Rui; Zaid, Mohammad Abu; Cripe, Larry D; Weisenbach, Jill; Sargent, Katie J; Nassiri, Mehdi; Li, Lang; Konig, Heiko; Suvannasankha, Attaya; Pan, Feng; Shanmugam, Rajasubramaniam; Goswami, Chirayu; Kapur, Reuben; Xu, Mingjiang; Boswell, H Scott


    Co-occurrence of Flt3ITD and TET2 mutations provoke an animal model of AML by epigenetic repression of Wnt pathway antagonists, including RUNX3, and by hyperexpression of ID1, encoding Wnt agonist. These affect HOXA over-expression and treatment resistance. A comparable epigenetic phenotype was identified among adult AML patients needing novel intervention. We chose combinations of targeted agents acting on distinct effectors, at the levels of both signal transduction and chromatin remodeling, in relapsed/refractory AML's, including Flt3ITD+ve, described with a signature of repressed tumor suppressor genes, involving Wnt antagonist RUNX3 , occurring along with ID1 and HOXA over-expressions. We tracked patient response to combination of Flt3/Raf inhibitor, Sorafenib, and Vorinostat, pan-histone deacetylase inhibitor, without or with added Bortezomib, in consecutive phase I trials. A striking association of rapid objective remissions (near-complete, complete responses) was noted to accompany induced early pharmacodynamic changes within patient blasts in situ, involving these effectors, significantly linking RUNX3 /Wnt antagonist de-repression (80%) and ID1 downregulation (85%), to a response, also preceded by profound HOXA9 repression. Response occurred in context of concurrent TET2 mutation/hypomorphy and Flt3ITD+ve mutation (83% of complete responses). Addition of Bortezomib to the combination was vital to attainment of complete response in Flt3ITD+ve cases exhibiting such Wnt pathway dysregulation.

  18. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Buchmann, I.


    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90 Y, 188 Re and 131 I are the most frequently used β - -particles. Of these, 90 Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90 Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90 Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90 Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of

  19. Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML. (United States)

    Zampini, Matteo; Tregnago, Claudia; Bisio, Valeria; Simula, Luca; Borella, Giulia; Manara, Elena; Zanon, Carlo; Zonta, Francesca; Serafin, Valentina; Accordi, Benedetta; Campello, Silvia; Buldini, Barbara; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe; Pigazzi, Martina


    The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.

  20. Osteolytic bone lesions – A rare presentation of AML M6.

    Directory of Open Access Journals (Sweden)

    Geetha N.


    Full Text Available Acute myeloid leukemia (AML M6 is a rare form of AML  accounting  for < 5 % of all AML.  Extramedullary involvement  is very rarely seen in this entity.  Skeletal lesion has not been described in AML M6 before. We discuss the case of  a 17 year old boy with AML M6 who presented with  osteolytic lesion of right humerus.  He was treated with  induction and consolidation chemotherapy. The present case is the first report in literature of AML M6 presenting with skeletal lesions.

  1. Physical properties of Kentucky's AML landslides: Case studies analyzed

    International Nuclear Information System (INIS)

    Iannacchione, A.T.; Vallejo, L.E.


    Once an abandoned mined land (AML) landslide occurs and is identified as an emergency, engineers must rapidly implement a slope stabilization design. Correct slope remediation solutions are generally derived from well-executed geotechnical examinations. This paper summarizes a large body of geotechnical data compiled by the US office of Surface Mining Reclamation and Enforcement (OSM) from AML landslides in eastern Kentucky. Special attention is placed on the examination of subsurface failures, phreatic water levels, soil profiles, and soil composition information from numerous borehole exploration programs. Strength properties calculated from laboratory procedures and stability analysis techniques were also reviewed. Laboratory-determined soil shear strength values were found to be higher than those inferred from stability analysis. This suggests that postfailure determinations of the phreatic surface may be largely inappropriate when used in stability analysis or that laboratory-measured shear strengths are ineffective in replicating in situ colluvium/spoil slope properties

  2. Socioeconomic Status (SES) and Childhood Acute Myeloid Leukemia (AML) Mortality (United States)

    Knoble, Naomi B.; Alderfer, Melissa A.; Hossain, Md Jobayer


    Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3,651 pediatric AML patients, aged 0–19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02–1.12) and 1.05(1.00–1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1: (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3: (high economic/educational disadvantage, high-mobility) and Cluster 6: (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI) = 1.19(1.0–1.4) and 1.23 (1.1–1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features. PMID:27543948

  3. Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)


    Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and

  4. A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML

    DEFF Research Database (Denmark)

    Knapper, Steven; Russell, Nigel; Gilkes, Amanda


    The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activ...

  5. Myeloperoxidase mRNA detection for lineage determination of leukemic blasts: retrospective analysis. (United States)

    Crisan, D; Anstett, M J


    Myeloperoxidase (MPO) mRNA is an early myeloid marker; its detection in the morphologically and immunophenotypically primitive blasts of acute undifferentiated leukemia (AUL) establishes myeloid lineage and allows reclassification as acute myelogenous leukemia with minimal differentiation (AML-MO). We have previously reported a procedure for MPO mRNA detection by RT-PCR (reverse transcription-polymerase chain reaction) and an adaptation for use of routine hematology smears. This variant procedure allows retrospective analysis of mRNA and is used in the present study to evaluate the lineage of leukemic blasts in seven cases with morphology and cytochemistry consistent with AUL. All hematology smears used in this study were air-dried, unstained or Wright-stained and stored at room temperature for periods varying between 3 days and 2 years. MPO mRNA was detected in six cases, establishing the myeloid lineage of the blasts and the diagnosis of AML-MO. In the remaining case, the blasts were MPO mRNA negative, confirming the diagnosis of AUL. The RT-PCR procedure for retrospective mRNA analysis is useful in the clinical setting, due to its high specificity and sensitivity, speed (less than 24 h), safety (no radioactivity) and convenient use of routine hematology smears; it is particularly attractive in clinical situations when fresh or frozen specimens are no longer available at the time when the need for molecular diagnostics becomes apparent.

  6. Transcriptome Profiling of Pediatric Core Binding Factor AML.

    Directory of Open Access Journals (Sweden)

    Chih-Hao Hsu

    Full Text Available The t(8;21 and Inv(16 translocations disrupt the normal function of core binding factors alpha (CBFA and beta (CBFB, respectively. These translocations represent two of the most common genomic abnormalities in acute myeloid leukemia (AML patients, occurring in approximately 25% pediatric and 15% of adult with this malignancy. Both translocations are associated with favorable clinical outcomes after intensive chemotherapy, and given the perceived mechanistic similarities, patients with these translocations are frequently referred to as having CBF-AML. It remains uncertain as to whether, collectively, these translocations are mechanistically the same or impact different pathways in subtle ways that have both biological and clinical significance. Therefore, we used transcriptome sequencing (RNA-seq to investigate the similarities and differences in genes and pathways between these subtypes of pediatric AMLs. Diagnostic RNA from patients with t(8;21 (N = 17, Inv(16 (N = 14, and normal karyotype (NK, N = 33 were subjected to RNA-seq. Analyses compared the transcriptomes across these three cytogenetic subtypes, using the NK cohort as the control. A total of 1291 genes in t(8;21 and 474 genes in Inv(16 were differentially expressed relative to the NK controls, with 198 genes differentially expressed in both subtypes. The majority of these genes (175/198; binomial test p-value < 10(-30 are consistent in expression changes among the two subtypes suggesting the expression profiles are more similar between the CBF cohorts than in the NK cohort. Our analysis also revealed alternative splicing events (ASEs differentially expressed across subtypes, with 337 t(8;21-specific and 407 Inv(16-specific ASEs detected, the majority of which were acetylated proteins (p = 1.5 x 10(-51 and p = 1.8 x 10(-54 for the two subsets. In addition to known fusions, we identified and verified 16 de novo fusions in 43 patients, including three fusions involving NUP98 in six

  7. The role of therapeutic leukapheresis in hyperleukocytotic AML.

    Directory of Open Access Journals (Sweden)

    Friederike Pastore

    Full Text Available Hyperleukocytosis in AML with leukostasis is a serious life-threatening condition leading to a high early mortality which requires immediate cytoreductive therapy. Therapeutic leukapheresis is currently recommended by the American Society of Apheresis in patients with a WBC>100 G/l with signs of leukostasis, but the role of prophylactic leukapheresis before clinical signs of leukostasis occur is unclear.We retrospectively analyzed the role of leukapheresis in 52 patients (median age 60 years with hyperleukocytotic AML with and without clinical signs of leukostasis. Since leukapheresis was performed more frequently in patients with signs of leukostasis due to the therapeutic policy in our hospital, we developed a risk score for early death within seven days after start of therapy (EDd7 to account for this selection bias and to independently measure the effect of leukapheresis on EDd7.20 patients received leukapheresis in combination to chemotherapy compared to 32 patients who received chemotherapy only. In a multivariate logistic regression model for the estimation of the probability of EDd7 thromboplastin time and creatinine remained as independent significant parameters and were combined to create an EDd7 risk score. The effect of leukapheresis on EDd7 was evaluated in a bivariate logistic regression together with the risk score. Leukapheresis did not significantly change early mortality in all patients with a WBC≥100 G/l.Prophylactic leukapheresis in hyperleukocytotic patients with and without leukostasis did not improve early mortality in our retrospective study. Larger and prospective clinical trials are needed to validate the risk score and to further explore the role of leukapheresis in AML with hyperleukocytosis.

  8. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML. (United States)

    Swords, Ronan T; Coutre, Steven; Maris, Michael B; Zeidner, Joshua F; Foran, James M; Cruz, Jose; Erba, Harry P; Berdeja, Jesus G; Tam, Wayne; Vardhanabhuti, Saran; Pawlikowska-Dobler, Iwona; Faessel, Hélène M; Dash, Ajeeta B; Sedarati, Farhad; Dezube, Bruce J; Faller, Douglas V; Savona, Michael R


    Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We performed a phase 1b study of pevonedistat (PEV) with azacitidine (AZA) based on synergistic activity seen preclinically. Primary objectives included safety and tolerability, and secondary objectives included pharmacokinetics (PK) and disease response. Patients ≥60 years with treatment-naive AML (unfit for standard induction therapy) received PEV 20 or 30 mg/m 2 IV on days 1, 3, and 5 combined with fixed-dose AZA (75 mg/m 2 IV/subcutaneously) on days 1 to 5, 8, and 9, every 28 days. The most common treatment-emergent adverse events were constipation (48%), nausea (42%), fatigue (42%), and anemia (39%). In total, 11 deaths were observed and considered unrelated to study therapy by the investigators. Transient elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were dose limiting. The recommended phase 2 dose (RP2D) of PEV in this combination is 20 mg/m 2 PEV PK was not altered by the addition of AZA. Overall response rate (ORR) based on an intent-to-treat analysis was 50% (20 complete remissions [CRs], 5 complete remission with incomplete peripheral count recovery, 7 partial remissions [PRs]), with an 8.3-month median duration of remission. In patients receiving ≥6 cycles of therapy (n = 23, 44%), ORR was 83%. In patients with TP53 mutations, the composite CR/PR rate was 80% (4/5). Two of these patients stayed on study for >10 cycles. Baseline bone marrow blast percentage or cytogenetic/molecular risk did not influence ORR. This study was registered at as #NCT01814826. © 2018 by The American Society of Hematology.

  9. Identification of the Molecular Mechanisms Responsible for the Inhibition of Homing of AML Cells Triggered by CD44-Ligation

    KAUST Repository

    Al-Jifri, Ablah


    Acute Myeloid Leukemia (AML) is a cancerous disease that is defined by the inability to produce functional and mature blood cells, as well as the uncontrolled proliferation due to failure to undergo apoptosis of abnormal cells. The most common therapy for Leukemia, chemotherapy, has proven only to be partially efficient since it does not target the leukemic stem cells (LSCs) that have a high self-renewal and repopulation capacity and result in remission of the disease. Therefore targeting LSCs will provide more efficient therapy. One way to achieve this would be to inhibit their homing capability to the bone marrow. It has recently been shown that CD44, an adhesive molecule, plays a crucial role in cell trafficking and lodgement of both normal and leukemic stem cells. More importantly anti-CD44 monoclonal antibodies, along with its ability to induce differentiation of leukemic blasts, it inhibits specifically the homing capacity of LSCs to their micro-environmental niches. However, these molecular mechanisms that underlie the inhibition of homing have yet to be determined. To address these questions we conducted in vitro adhesion and blot-rolling assays to analyze the adherence and rolling capacity of these LSCs before and after treatment with anti-CD44 monoclonal antibody (mAb). Since glycosyltransferases play a crucial role in post translational carbohydrate decoration on adhesion molecules, we analyzed the expression (using quantitative PCR) of the different glycosyltransferases expressed in LSC\\'s before and after CD44 ligation (mAb treatment). Furthermore, we analyzed differentiation by flow cytometric analysis of treated and non-treated LSC\\'s. We anticipate that our results will set forth new insights into targeted therapies for AML.

  10. AML with t(7;12)(q36;p13) is associated with infancy and trisomy 19. Data from NOPHO-AML and review of the literature

    DEFF Research Database (Denmark)

    Espersen, Anne Dorte Lerche; Noren-Nyström, Ulrika; Abrahamsson, Jonas


    The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children ...). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation...

  11. A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML) (United States)

    Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott


    Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

  12. CD4(+)and CD8(+)T-cell reactions against leukemia-associated- or minor-histocompatibility-antigens in AML-patients after allogeneic SCT. (United States)

    Steger, Brigitte; Milosevic, Slavoljub; Doessinger, Georg; Reuther, Susanne; Liepert, Anja; Braeu, Marion; Schick, Julia; Vogt, Valentin; Schuster, Friedhelm; Kroell, Tanja; Busch, Dirk H; Borkhardt, Arndt; Kolb, Hans-Jochem; Tischer, Johanna; Buhmann, Raymund; Schmetzer, Helga


    T-cells play an important role in the remission-maintenance in AML-patients (pts) after SCT, however the role of LAA- (WT1, PR1, PRAME) or minor-histocompatibility (mHag, HA1) antigen-specific CD4(+) and CD8(+)T-cells is not defined. A LAA/HA1-peptide/protein stimulation, cloning and monitoring strategy for specific CD8(+)/CD4(+)T-cells in AML-pts after SCT is given. Our results show that (1) LAA-peptide-specific CD8+T-cells are detectable in every AML-pt after SCT. CD8(+)T-cells, recognizing two different antigens detectable in 5 of 7 cases correlate with long-lasting remissions. Clonal TCR-Vβ-restriction exemplarily proven by spectratyping in PRAME-specific CD8(+)T-cells; high PRAME-peptide-reactivity was CD4(+)-associated, as shown by IFN-γ-release. (2) Two types of antigen-presenting cells (APCs) were tested for presentation of LAA/HA1-proteins to CD4(+)T-cells: miniEBV-transduced lymphoblastoid cells (B-cell-source) and CD4-depleted MNC (source for B-cell/monocyte/DC). We provide a refined cloning-system for proliferating, CD40L(+)CD4(+)T-cells after LAA/HA1-stimulation. CD4(+)T-cells produced cytokines (GM-CSF, IFN-γ) upon exposure to LAA/HA1-stimulation until after at least 7 restimulations and demonstrated cytotoxic activity against naive blasts, but not fibroblasts. Antileukemic activity of unstimulated, stimulated or cloned CD4(+)T-cells correlated with defined T-cell-subtypes and the clinical course of the disease. In conclusion we provide immunological tools to enrich and monitor LAA/HA1-CD4(+)- and CD8(+)T-cells in AML-pts after SCT and generate data with relevant prognostic value. We were able to demonstrate the presence of LAA-peptide-specific CD8(+)T-cell clones in AML-pts after SCT. In addition, we were also able to enrich specific antileukemic reactive CD4(+)T-cells without GvH-reactivity upon repeated LAA/HA1-protein stimulation and limiting dilution cloning. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. Asymptotically Matched Layer (AML) for transient wave propagation in a moving frame of reference

    DEFF Research Database (Denmark)

    Madsen, Stine Skov; Krenk, Steen


    The paper presents an Asymptotically Matched Layer (AML) formulation in a moving frame of reference for transient dynamic response of a multi-layer 2D half-space. A displacement based finite element formulation of the convected domain problem is presented together with the AML formulation in whic...

  14. IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells. (United States)

    Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit


    Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

  15. Effectiveness of eye armor during blast loading. (United States)

    Bailoor, Shantanu; Bhardwaj, Rajneesh; Nguyen, Thao D


    Ocular trauma is one of the most common types of combat injuries resulting from the interaction of military personnel with improvised explosive devices. Ocular blast injury mechanisms are complex, and trauma may occur through various injury mechanisms. However, primary blast injuries (PBI) are an important cause of ocular trauma that may go unnoticed and result in significant damage to internal ocular tissues and visual impairment. Further, the effectiveness of commonly employed eye armor, designed for ballistic and laser protection, in lessening the severity of adverse blast overpressures (BOP) is unknown. In this paper, we employed a three-dimensional (3D) fluid-structure interaction computational model for assessing effectiveness of the eye armor during blast loading on human eyes and validated results against free field blast measurements by Bentz and Grimm (2013). Numerical simulations show that the blast waves focused on the ocular region because of reflections from surrounding facial features and resulted in considerable increase in BOP. We evaluated the effectiveness of spectacles and goggles in mitigating the pressure loading using the computational model. Our results corroborate experimental measurements showing that the goggles were more effective than spectacles in mitigating BOP loading on the eye. Numerical results confirmed that the goggles significantly reduced blast wave penetration in the space between the armor and the eyes and provided larger clearance space for blast wave expansion after penetration than the spectacles. The spectacles as well as the goggles were more effective in reducing reflected BOP at higher charge mass because of the larger decrease in dynamic pressures after the impact. The goggles provided greater benefit of reducing the peak pressure than the spectacles for lower charge mass. However, the goggles resulted in moderate, sustained elevated pressure loading on the eye, that became 50-100% larger than the pressure loading

  16. Development of an Anatomically Accurate Finite Element Human Ocular Globe Model for Blast-Related Fluid-Structure Interaction Studies (United States)


    nucleus green ) is attached to the shell of the eye via the zonule fibers (orange) and the ciliary body (pink). The zonule fibers are approximated in shown in the literature.13,24 (a and b) A study conducted by Norman et al.24 with images from normal human subjects sectioned into 15 equal...Fig. 13 Scleral thickness variation procedure in the model: a) scleral thickness variation contours with thickness values noted from Norman et al

  17. [Initial subretinal localization of acute myeloblastic leukemia (AML5) recurrence]. (United States)

    Le Gall, S; François, S; Urier, N; Genevieve, F; d'Hermies, F; Rachieru, P; Ifrah, N


    Reduced visual acuity in patients with acute leucemia can result from many causes including an ocular localization. A patient previously treated for acute myeloblastic leucemia-5 (AML5) developed bilateral vision impairment related to a subretinal localization of the leucemia. Meningeal and bone marrow relapse followed. The subretinal localization responded only to massive systemic steroid treatment. Although asymptomatic, ocular localizations are frequent in leucemia. Their prognostic impact depends on the ocular structure involved and on the chronology of onset--early or late in the leucemia course. The underlying pathophysiological mechanism of ocular involvement remains unexplained but hyperleucocytosis at presentation may be a risk factor and would justify at least systematic specialized examinations and discussion of prophylactic treatment.

  18. American experience in the implementation of AML / CFT system

    Directory of Open Access Journals (Sweden)

    Larin Dmitry


    Full Text Available This article presents a research into very specific matters and issues of creating and further improvement of Anti-Money Laundering and Combating the Financing of Terrorism system (abbreviated as AML/CFT in the USA. In contains a precise analysis of key elements of this system, as well as a deep look into the nature and purposes of financial intelligence “FinCEN”. Strong emphasis is laid on The US Foreign Account Tax Compliance Act (FATCA for the reason that, according to this Act, any foreign financial institution is legitimately forced to sign a special agreement with The US Internal Revenue Service (IRS, giving the Service power to maintain control over any American asset within its equity. The latter is understood as a legal right to investigate not only the accounts and property of American taxpayers, but to investigate any account or capital of any foreign institution having American shares or stocks.

  19. Prenatal origin of childhood AML occurs less frequently than in childhood ALL

    International Nuclear Information System (INIS)

    Burjanivova, Tatiana; Zuna, Jan; Madzo, Jozef; Muzikova, Katerina; Meyer, Claus; Schneider, Bjoern; Votava, Felix; Marschalek, Rolf; Stary, Jan; Trka, Jan


    While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

  20. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. (United States)

    Wong, Terrence N; Miller, Christopher A; Klco, Jeffery M; Petti, Allegra; Demeter, Ryan; Helton, Nichole M; Li, Tiandao; Fulton, Robert S; Heath, Sharon E; Mardis, Elaine R; Westervelt, Peter; DiPersio, John F; Walter, Matthew J; Welch, John S; Graubert, Timothy A; Wilson, Richard K; Ley, Timothy J; Link, Daniel C


    There is interest in using leukemia-gene panels and next-generation sequencing to assess acute myelogenous leukemia (AML) response to induction chemotherapy. Studies have shown that patients with AML in morphologic remission may continue to have clonal hematopoiesis with populations closely related to the founding AML clone and that this confers an increased risk of relapse. However, it remains unknown how induction chemotherapy influences the clonal evolution of a patient's nonleukemic hematopoietic population. Here, we report that 5 of 15 patients with genetic clearance of their founding AML clone after induction chemotherapy had a concomitant expansion of a hematopoietic population unrelated to the initial AML. These populations frequently harbored somatic mutations in genes recurrently mutated in AML or myelodysplastic syndromes and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that nonleukemic hematopoietic stem and progenitor cells, harboring specific aging-acquired mutations, may have a competitive fitness advantage after induction chemotherapy, expand, and persist long after the completion of chemotherapy. Although the clinical importance of these "rising" clones remains to be determined, it will be important to distinguish them from leukemia-related populations when assessing for molecular responses to induction chemotherapy. © 2016 by The American Society of Hematology.

  1. [Application of Next Generation Sequencing for AML/MDS Diagnosis and Treatment]. (United States)

    Cheng, Huan-Chen; Liu, Sheng-Wei; Liu, Yu; Zhao, Xue-Fei; Li, Wei; Qiu, Lin; Ma, Jun


    To detect the mutations of AML/MDS- related genes by using next generation sequencing (NGS), to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS, and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases. The specimens were collected from primary AML (68 cases) and MDS (57 cases) patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips. TET2 gene showed the highest mutation rate in AML (55.9%) and MDS (56.1%). The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3, C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack, but the mutation rate of TET2 gene was not obviously changed, whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression, but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission. Both AML and MDS have their own specific mutated genes and sites. Some gene mutations, such as CEBPA, can be used as an effective indicator to monitoring MRD in AML patients, but those only used for the evaluation of the disease progression and prognosis in MDS patients.

  2. High Frequency of AML1/RUNX1 Point Mutations in Radiation-Associated Myelodysplastic Syndrome Around Semipalatinsk Nuclear Test Site


    Dinara, ZHARLYGANOVA; Hironori, HARADA; Yuka, HARADA; Sergey, SHINKAREV; Zhaxybay, ZHUMADILOV; Aigul, ZHUNUSOVA; Naylya J., TCHAIZHUNUSOVA; Kazbek N., APSALIKOV; Vadim, KEMAIKIN; Kassym, ZHUMADILOV; Noriyuki, KAWANO; Akiro, KIMURA; Masaharu, HOSHI; Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University; Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University


    It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients wi...

  3. The BLAST experiment

    NARCIS (Netherlands)

    Hasell, D.; Botto, T.; van den Brand, J.F.J.


    The Bates large acceptance spectrometer toroid (BLAST) experiment was operated at the MIT-Bates Linear Accelerator Center from 2003 until 2005. The detector and experimental program were designed to study, in a systematic manner, the spin-dependent electromagnetic interaction in few-nucleon systems.

  4. Safety and Pharmacokinetics of the Antisense Oligonucleotide (ASO) LY2181308 as a Single-Agent or in Combination with Idarubicin and Cytarabine in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML) (United States)

    Erba, Harry P.; Sayar, Hamid; Juckett, Mark; Lahn, Michael; Andre, Valerie; Callies, Sophie; Schmidt, Shelly; Kadam, Sunil; Brandt, John T.; Van Bockstaele, Dirk; Andreeff, Michael


    Summary Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. Methods In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n=8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n=16). LY2181308 was administered with a loading dosage of 3 consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m2 was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m2 was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Results Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). Conclusions LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials. PMID:23397500

  5. The emerging role of immune checkpoint based approaches in AML and MDS. (United States)

    Boddu, Prajwal; Kantarjian, Hagop; Garcia-Manero, Guillermo; Allison, James; Sharma, Padmanee; Daver, Naval


    The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases. CTLA-4 inhibition may be especially effective in treating late post-allogeneic stem cell transplant relapse of AML in patients with limited or no graft versus host disease. Immune checkpoint inhibition, specifically PD-1 inhibition, demonstrated limited single agent efficacy in patients with relapsed AML and with MDS post-hypomethylating therapy. Rationally designed combinations of PD-1 inhibitors with standard anti-leukemic therapy are needed. Hypomethylating agents such as azacitidine, up-regulate PD-1, PD-L1, and PD-L2 in patients with AML/MDS and up-regulation of these genes was associated with the emergence of resistance. The combination of azacitidine and PD-1/PD-L1 inhibition may be a potential mechanism to prevent or overcome resistance to 5-azacitidine. A number of such combinations are being evaluated in clinical trials with early encouraging results. Immune checkpoint inhibition is also an attractive option to improve relapse-free survival or eliminate minimal residual disease post induction and consolidation by enhancing T-cell surveillance in patients with high-risk AML. The ongoing clinical trials with checkpoint inhibitors in AML/MDS will improve our understanding of the immunobiology of these diseases and guide us to the most appropriate application of these agents in the therapy of AML/MDS.

  6. Focal Adhesion Kinase as a Potential Target in AML and MDS. (United States)

    Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng; Yang, Hui; Garcia-Manero, Guillermo; Mak, Duncan H; Mu, Hong; Ruvolo, Vivian R; Qiu, Yihua; Coombes, Kevin; Zhang, Nianxiang; Ragon, Brittany; Weaver, David T; Pachter, Jonathan A; Kornblau, Steven; Andreeff, Michael


    Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics ( P = 2 × 10 -4 ) and relapse ( P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3 -ITD ( P = 0.0024) or RAS ( P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34 + ( P = 5.42 × 10 -20 ) and CD34 + CD38 - MDS ( P = 7.62 × 10 -9 ) cells compared with normal CD34 + cells. MDS patients with higher FAK in CD34 + cells tended to have better overall survival ( P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133-44. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Patient-derived acute myeloid leukemia (AML) bone marrow cells display distinct intracellular kinase phosphorylation patterns

    International Nuclear Information System (INIS)

    Shults, Keith; Flye, Leanne; Green, Lisa; Daly, Thomas; Manro, Jason R; Lahn, Michael


    Multiparametric analyses of phospho-protein activation in patients with acute myeloid leukemia (AML) offers a quantitative measure to monitor the activity of novel intracellular kinase (IK) inhibitors. As recent clinical investigation with FMS-like tyrosine-3 inhibitors demonstrated, targeting IK with selective inhibitors can have a modest clinical benefit. Because multiple IKs are active in patients with AML, multikinase inhibitors may provide the necessary inhibition profile to achieve a more sustained clinical benefit. We here describe a method of assessing the activation of several IKs by flow cytometry. In 40 different samples of patients with AML we observed hyper-activated phospho-proteins at baseline, which is modestly increased by adding stem cell factor to AML cells. Finally, AML cells had a significantly different phospho-protein profile compared with cells of the lymphocyte gate. In conclusion, our method offers a way to determine the activation status of multiple kinases in AML and hence is a reliable assay to evaluate the pharmacodynamic activity of novel multikinase inhibitors

  8. Therapy-related AML/MDS after treatment of low-grade B-cell lymphoma

    International Nuclear Information System (INIS)

    Yanada, Masamitsu


    Described is the therapy-related AML (acute myelogenetic leukemia)/MDS (myelo-dysplasia syndrome), which is manifested after various treatments of low-grade B-cell lymphoma and has strongly attracted attention because of the markedly improved prognosis due to recent advantages of the therapy for the disease. AML/MDS occurs several years after chemotherapy and/or radiation therapy which cause DNA damage in hematopoietic cells, and the AML/MDS risk is known increased in patients undergone especially with autologous transplantation of those cells. AML/MDS has the feature similar to that caused either by alkylating agent or by topoisomerase-2 inhibitor, and the disease by radiation belong to the former. Yet unclear is the problem whether malignant cells causing the disease after therapy are derived from the remaining cells in the graft or in the body. Although irradiations of total body and total lymphaden as well as chemotherapy are said to be related to AML/MDS and local irradiation does not contribute to its risk, the most important factor for the disease is considered to be the autotransplantation as the recurrence occurs in 50% after it. Thus the treatment history should be taken into consideration for suppressing AML/MDS, for which follow up with consideration for the disease is required particularly after autotransplantation. (R.T.)

  9. Acceleration-based methodology to assess the blast mitigation performance of explosive ordnance disposal helmets (United States)

    Dionne, J. P.; Levine, J.; Makris, A.


    To design the next generation of blast mitigation helmets that offer increasing levels of protection against explosive devices, manufacturers must be able to rely on appropriate test methodologies and human surrogates that will differentiate the performance level of various helmet solutions and ensure user safety. Ideally, such test methodologies and associated injury thresholds should be based on widely accepted injury criteria relevant within the context of blast. Unfortunately, even though significant research has taken place over the last decade in the area of blast neurotrauma, there currently exists no agreement in terms of injury mechanisms for blast-induced traumatic brain injury. In absence of such widely accepted test methods and injury criteria, the current study presents a specific blast test methodology focusing on explosive ordnance disposal protective equipment, involving the readily available Hybrid III mannequin, initially developed for the automotive industry. The unlikely applicability of the associated brain injury criteria (based on both linear and rotational head acceleration) is discussed in the context of blast. Test results encompassing a large number of blast configurations and personal protective equipment are presented, emphasizing the possibility to develop useful correlations between blast parameters, such as the scaled distance, and mannequin engineering measurements (head acceleration). Suggestions are put forward for a practical standardized blast testing methodology taking into account limitations in the applicability of acceleration-based injury criteria as well as the inherent variability in blast testing results.

  10. Blasting agents and initiation systems

    Energy Technology Data Exchange (ETDEWEB)

    Fiscor, S.


    Although blasting differs between and within each industry, as a whole, the mines and quarries are making a shift from a purely ammonium nitrate/fuel oil (ANFO) mixture to a blend of emulsion and ANFO on a straight emulsion. Non-electric (shock tube) initiation systems have provided a viable alternative to the electric detonator (blasting cap). Explosives manufacturers are seeing their roles changes to being blasting contractors or consultants rather than just suppliers. The article discusses these trends and gives examples of typical blasting techniques and amounts of blasting agent used at large USA surface coal mines. Electric caps are still used in blasting underground coal. The Ensign Bickford Co. (EBCo) is developing electronic detonators and has been field testing an electronic initiator, the DIGIDET detonator, for the last four years. When commercially available, electronic detonators will be accurate but will come with a hefty price tag. 2 photos.

  11. c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

    International Nuclear Information System (INIS)

    Gao Fenghou; Wang Qiong; Wu Yingli; Li Xi; Zhao Kewen; Chen Guoqiang


    AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

  12. Blasting agent package

    Energy Technology Data Exchange (ETDEWEB)

    Fox, R.


    A protected preassembled package for blasting agents susceptible to desensitization by water consists of, in combination: (1) an inner rigid and self-supporting tube, the upper end of which is suited to be connected, or attached, to the discharge end of a loading hose for a blasting agent and the lower end of which is open; and (2) a flexible tubular liner made of water-resistant film, having a diameter greater than that of the inner tube and a length at least equal to the desired depth of its insertion into the borehole, the liner being sleeved over the length of the inner tube, the upper end of the liner being attached to the inner tube and the lower end of the liner being closed so as to prevent substantial discharge of the explosive mixture therefrom when the latter is pumped into it. (24 claims)

  13. Tunnel blasting - recent developments

    Energy Technology Data Exchange (ETDEWEB)

    White, T.E.


    While tunnelling machines are more efficient than previously, there are still areas where blasting is a more efficient method of advance. Drilling and design methods are increasingly sophisticated, as is choice of explosive. Explosive deployment must be carefully calculated so as to avoid desensitisation. Nitroglycerine may be used as slurries; bulk mixing on site of ANFO is also practised in mining in the UK. Electric detonators, Nonel tubes, and electronic detonators are also increasingly employed.

  14. Blasting technology advances

    Energy Technology Data Exchange (ETDEWEB)


    Nitroglycerine explosives are increasingly giving way to emulsions and low cost Anfo compositions, the latter sometimes incorporating emulsion in order to improve water resistance and performance. The aim is to produce an explosive which is extremely efficient, relatively safe and can be tailored to meet user requirements. Discussion is presented of emulsion delivery systems, initiation systems, electronic detonators, computer blast modelling, directional explosives, underground automation, and the development of Soviet explosives. 3 refs., 4 figs.

  15. Immunophenotype of leukemic blasts with small peroxidase-positive granules detected by electron microscopy. (United States)

    Vainchenker, W; Villeval, J L; Tabilio, A; Matamis, H; Karianakis, G; Guichard, J; Henri, A; Vernant, J P; Rochant, H; Breton-Gorius, J


    Forty-three cases of undifferentiated leukemias by light microscopy examination were diagnosed as acute myeloblastic leukemias by ultrastructural revelation of peroxidase and were subsequently studied by immunological markers. In 41 of these cases, blasts were labeled by at least one of the antimyeloid MoAbs (My 7, My 9, and 80H5). An antimyeloperoxidase polyclonal antibody was used in 23 cases and was clearly positive in 11 of them, while cytochemistry by light microscopy was negative. These myeloblasts were frequently mixed with a minority of blasts from other lineages especially promegakaryoblasts. It is noteworthy that in 6 cases myeloid and lymphoid markers (E rosette receptor, common acute lymphoblastic leukemia antigen (cALLA), CD 9, CD 19 antigens (anti-B4 MoAb] were detected on a fraction of blast cells, suggesting a bilineage leukemia. However, in double labeling experiments, blasts with myeloperoxidase coexpressed lymphoid and myeloid markers including cALLA and CD 19 antigen. In one case, blasts had a typical non-B, non-T acute lymphoblastic leukemia phenotype (HLA-DR, CD 9, CD 19, cALLA positive) without staining by any of the antimyeloid MoAbs. However, 70% of the blasts were labeled by the antimyeloperoxidase antibody and expressed peroxidase-positive granules at ultrastructural level. In conclusion, most of the AML undiagnosed by optical cytochemistry are identified by antimyeloid antibodies. Some of these cases are also stained by some antilymphoid MoAbs. Use of antibodies against myeloperoxidase may improve the diagnosis of difficult cases of acute myeloblastic leukemia.

  16. Effects of low-level blast exposure on the nervous system: Is there really a controversy?

    Directory of Open Access Journals (Sweden)

    Gregory A Elder


    Full Text Available High-pressure blast waves can cause extensive CNS injury in humans. However, in combat settings such as Iraq and Afghanistan, lower level exposures associated with mild TBI (mTBI or subclinical exposure have been much more common. Yet controversy exists concerning what traits can be attributed to low-level blast, in large part due to the difficulty of distinguishing blast-related mTBI from post-traumatic stress disorder (PTSD. We describe how TBI is defined in humans and the problems posed in using current definitions to recognize blast-related mTBI. We next consider the problem of applying definitions of human mTBI to animal models, in particular that TBI severity in humans is defined in relation to alteration of consciousness at the time of injury, which typically cannot be assessed in animals. However, based on outcome assessments a condition of low-level blast exposure can be defined in animals that likely approximates human mTBI or subclinical exposure. We review blast injury modeling in animals noting that inconsistencies in experimental approach have contributed to uncertainty over the effects of low-level blast. Yet animal studies show that low-level blast pressure waves are transmitted to the brain. In brain low-level blast exposures cause behavioral, biochemical, pathological and physiological effects on the nervous system including the induction of PTSD-related behavioral traits in the absence of a psychological stressor. We review the relationship of blast exposure to chronic neurodegenerative diseases noting the paradoxical lowering of Abeta by blast, which along with other observations suggest that blast-related TBI is pathophysiologically distinct from non-blast TBI. Human neuroimaging studies show that blast-related mTBI is associated with a variety of chronic effects that are unlikely to be explained by co-morbid PTSD. We conclude that abundant evidence supports low-level blast as having long-term effects on the nervous system.

  17. Computational modeling of blast induced whole-body injury: a review. (United States)

    Chanda, Arnab; Callaway, Christian


    Blast injuries affect millions of lives across the globe due to its traumatic after effects on the brain and the whole body. To date, military grade armour materials are designed to mitigate ballistic and shrapnel attacks but are less effective in resisting blast impacts. In order to improve blast absorption characteristics of armours, the first key step is thoroughly understands the effects of blasts on the human body itself. In the last decade, a plethora of experimental and computational work has been carried out to investigate the mechanics and pathophysiology of Traumatic Brain Injury (TBI). However, very few attempts have been made so far to study the effect of blasts on the various other parts of the body such as the sensory organs (eyes and ears), nervous system, thorax, extremities, internal organs (such as the lungs) and the skeletal system. While an experimental evaluation of blast effects on such physiological systems is difficult, developing finite element (FE) models could allow the recreation of realistic blast scenarios on full scale human models and simulate the effects. The current article reviews the state-of-the-art in computational research in blast induced whole-body injury modelling, which would not only help in identifying the areas in which further research is required, but would also be indispensable for understanding body location specific armour design criteria for improved blast injury mitigation.

  18. Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial. (United States)

    Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, Maria C; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco


    Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to primary resistance to chemotherapy account for a significant proportion of cases and have a particularly dismal prognosis. We report the clinical and biological data, and final outcome of 48 paediatric patients with primary-resistant AML enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 clinical trial. These patients had a significantly higher white blood cell count at diagnosis compared to other AML patients. Cytogenetic and molecular features did not differ between patients with primary induction failure and patients allocated to the high-risk group. For the whole patient population, the probability of overall survival, event-free survival (EFS) and disease-free survival (DFS) was 21·8% ± 6·2, 20·4% ± 5·9, and 49·5% ± 11·3, respectively. Twenty-eight (58%) patients received haematopoietic stem cell transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who underwent HSCT had improved EFS (31·2% vs. 5%, P < 0·0001). Only one of the 20 patients who did not receive HSCT is alive and disease free. The 19 patients in complete remission at time of HSCT showed significantly better DFS than the 9 with active disease (46% vs. 0%, P = 0·02). This study represents one of the largest series with long-term follow up of paediatric AML patients with primary refractory disease. Children who underwent transplantation had an encouraging long-term outcome. Disease recurrence remains the major cause of treatment failure; a better understanding of the disease biology is desirable to develop more effective treatment strategies. © 2015 John Wiley & Sons Ltd.

  19. Investigations of primary blast-induced traumatic brain injury (United States)

    Sawyer, T. W.; Josey, T.; Wang, Y.; Villanueva, M.; Ritzel, D. V.; Nelson, P.; Lee, J. J.


    The development of an advanced blast simulator (ABS) has enabled the reproducible generation of single-pulse shock waves that simulate free-field blast with high fidelity. Studies with rodents in the ABS demonstrated the necessity of head restraint during head-only exposures. When the head was not restrained, violent global head motion was induced by pressures that would not produce similar movement of a target the size and mass of a human head. This scaling artefact produced changes in brain function that were reminiscent of traumatic brain injury (TBI) due to impact-acceleration effects. Restraint of the rodent head eliminated these, but still produced subtle changes in brain biochemistry, showing that blast-induced pressure waves do cause brain deficits. Further experiments were carried out with rat brain cell aggregate cultures that enabled the conduct of studies without the gross movement encountered when using rodents. The suspension nature of this model was also exploited to minimize the boundary effects that complicate the interpretation of primary blast studies using surface cultures. Using this system, brain tissue was found not only to be sensitive to pressure changes, but also able to discriminate between the highly defined single-pulse shock waves produced by underwater blast and the complex pressure history exposures experienced by aggregates encased within a sphere and subjected to simulated air blast. The nature of blast-induced primary TBI requires a multidisciplinary research approach that addresses the fidelity of the blast insult, its accurate measurement and characterization, as well as the limitations of the biological models used.

  20. Numerical simulation of muzzle blast

    NARCIS (Netherlands)

    Tyler-Street, M.


    Structural design methods for naval ships include environmental, operational and military load cases. One of the operational loads acting on a typical naval vessel is the muzzle blast from a gun. Simulating the muzzle blast load acting on a ship structure with CFD and ALE methods leads to large

  1. Control blasting of reinforced concrete

    International Nuclear Information System (INIS)

    Nagase, Tetsuo


    With the need of decommissioning nuclear power plants, it is urgently required to establish its methods and standards. In Shimizu Construction Co., Ltd., experimental feasibility studies have been made on explosive demolition method i.e. the controlled blasting for the massive concrete structures peculiar to nuclear power plants, considering low radiation exposure, safety and high efficiency. As such, four techniques of line drilling, cushion blasting, pre-splitting and guide hole blasting, respectively, are described with photographs. Assuming the selective demolition of activated concrete structures, the series of experiments showed the good results of clear-cut surfaces and the effect of blasting was confined properly. Moreover, the scattering of debris in blasting was able to be entirely prevented by the use of rubber belts. The generation of gas and dust was also little due to the small amount of the charge used. (J.P.N.)

  2. NCBI BLAST+ integrated into Galaxy. (United States)

    Cock, Peter J A; Chilton, John M; Grüning, Björn; Johnson, James E; Soranzo, Nicola


    The NCBI BLAST suite has become ubiquitous in modern molecular biology and is used for small tasks such as checking capillary sequencing results of single PCR products, genome annotation or even larger scale pan-genome analyses. For early adopters of the Galaxy web-based biomedical data analysis platform, integrating BLAST into Galaxy was a natural step for sequence comparison workflows. The command line NCBI BLAST+ tool suite was wrapped for use within Galaxy. Appropriate datatypes were defined as needed. The integration of the BLAST+ tool suite into Galaxy has the goal of making common BLAST tasks easy and advanced tasks possible. This project is an informal international collaborative effort, and is deployed and used on Galaxy servers worldwide. Several examples of applications are described here.

  3. Allo-SCT for  Philadelphia-negative myeloproliferative neoplasms in blast phase: a study from the Societe Française de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC). (United States)

    Cahu, X; Chevallier, P; Clavert, A; Suarez, F; Michallet, M; Vincent, L; Vigouroux, S; Blaise, D; Mariette, C; Bilger, K; Robin, M; Yakoub-Agha, I; Peffault de Latour, R; Mohty, M


    Progression of Philadelphia-negative myeloproliferative (MPN) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) to acute myeloid leukemia (AML) is an adverse event in the course of the disease. Although allogeneic hematopoietic SCT (allo-SCT) is considered as the only curative therapy, few data exist on the outcome of patients with Philadelphia-negative MPN or MDS/MPN in blast phase who received an allo-SCT. Sixty patients were included in this retrospective study. AML was secondary to an MPN in 43 cases, whereas AML evolved from an MDS/MPN in 17 cases. Patients received allo-SCT in CR or advanced disease in 26 cases and 34 cases, respectively. With a median follow-up of 31 months (range, 25-44), OS and leukemia-free survival (LFS) were, respectively, 18% and 9% at 3 years. CR at transplant was associated with an improved LFS in univariate and multivariate analysis. The 3-year LFS was 18% for patients undergoing allo-SCT in CR versus 3% in advanced disease (P=0.008). Absence of thrombosis and an intermediate or favorable AML karyotype were associated with an improved outcome for patients who received allo-SCT in CR. New strategies are needed to improve the outcome of patients with MPN-MDS/MPN in blast phase.

  4. Blast from the past (United States)

    Carlowicz, Michael


    Forget dynamite or hydraulic and mechanical drills. Industrial and federal researchers have started boring holes with rocket fuel. In a cooperative arrangement between Sandia National Laboratory, Global Environmental Solutions, and Universal Tech Corp., scientists and engineers extracted fuel from 200 rocket motors and used it as a mining explosive. In a demonstration completed last fall, researchers used 4950 kg of solid rocket propellant to move more than 22,500 metric tons of rock from the Lone Star Quarry in Prairie, Oklahoma. They found that the fuel improved blast energy and detonation velocity over traditional explosives, and it required fewer drill holes.

  5. Trouble shooting problem blasts

    Energy Technology Data Exchange (ETDEWEB)

    Konya, K.D. [Society of Explosive Engineers, Montville, OH (United States)


    There have been many occurrences of water-gel or emulsion explosives or heavy Anfo`s (ammonium nitrate and fuel oil) either not detonating in some blast holes in surface coal mining operations, or producing yellow or reddish-brown fumes upon reaction. The explosives rely on entrapped gas to detonate properly. It is important to control the size of the bubble and the dispersion of gas bubbles throughout the explosive. The article discusses and compares the use of microspheres and of gassing agents for detonation control.

  6. Dismounted Complex Blast Injury. (United States)

    Andersen, Romney C; Fleming, Mark; Forsberg, Jonathan A; Gordon, Wade T; Nanos, George P; Charlton, Michael T; Ficke, James R


    The severe Dismounted Complex Blast Injury (DCBI) is characterized by high-energy injuries to the bilateral lower extremities (usually proximal transfemoral amputations) and/or upper extremity (usually involving the non-dominant side), in addition to open pelvic injuries, genitourinary, and abdominal trauma. Initial resuscitation and multidisciplinary surgical management appear to be the keys to survival. Definitive treatment follows general principals of open wound management and includes decontamination through aggressive and frequent debridement, hemorrhage control, viable tissue preservation, and appropriate timing of wound closure. These devastating injuries are associated with paradoxically favorable survival rates, but associated injuries and higher amputation levels lead to more difficult reconstructive challenges.

  7. The use of computer blast simulations to improve blast quality

    International Nuclear Information System (INIS)

    Favreau, R.F.; Kuzyk, G.W.; Babulic, P.J.; Tienkamp, N.J.


    Atomic Energy of Canada Limited is constructing an Underground Research Laboratory (URL) as part of a comprehensive program to evaluate the concept of nuclear fuel waste disposal deep in crystalline rock formations. Careful blasting methods have been used to minimize damage to the excavation surfaces. Good wall quality is desirable in any excavation. In excavations required for nuclear waste disposal, the objective will be to minimize blast-induced fractures which may complicate the sealing requirements necessary to control subsequent movement of groundwater around a sealed disposal vault. The construction of the URL has provided an opportunity for the development of controlled blasting methods, especially for drilling accuracy and optimization of explosive loads in the perimeter and cushion holes. The work has been assisted by the use of blast simulations with the mathematical model Blaspa. This paper reviews the results of a recent project to develop a controlled method of full-face blasting, and compares the observed field results with the results of a blast simulator called Blaspa. Good agreement is found between the two, and the Blaspa results indicate quantitatively how the blasting may induce damage in the final excavation surface. In particular, the rock in the final wall may be stressed more severely by the cushion holes than by the perimeter holes. Bootleg of the rock between the perimeter and cushion rows occurs when the burst-out velocity imparted to it by the explosive loads in the perimeter holes is inadequate. In practice, these findings indicate that quantitative rock stress and rock burst-out velocity criteria can be established to minimize wall damage and bootleg. Thus, blast simulations become an efficient way to design controlled blasting and to optimize quality of the excavation surface


    International Nuclear Information System (INIS)

    McPhee, William S.


    The objective of this project is to improve the productivity and lower the expense of existing vacuum blasting technology. This technology is used to remove radioactive contamination, PCBs, and lead-based paint and provides worker protection by continuously recycling the material and dust for the decontamination tasks. The proposed work would increase the cleaning rate and provide safe and cost-effective decontamination of the DOE sites. This work focuses on redesigning and improving existing vacuum blasting technology including blast head nozzles, ergonomic handling of the blast head by reducing its weight; brush-ring design, vacuum level regulator, efficiency of the dust separator, and operational control sensors. The redesign is expected to enhance the productivity and economy of the vacuum blasting system by at least 50% over current vacuum blasting systems. There are three phases in the project. Phase I consists of developing and testing mathematical models. Phase II consists of pre-prototype design and fabrication and pre-prototype unit testing. Phase III consists of prototype design and field verification testing. In phase I, mathematical models are developed and analyzed for the nozzle, blast head, wind curtain, and dust separator, first as individual devices and then combined as an integrated model. This allows study of respective airflow and design parameters. The Contractor shall, based on the results of the mathematical modeling studies, design experimental models of the components and test these models. In addition, the Contractor shall develop sensors to detect the relationship of the blast head to the blast surfaces and controls to minimize the dependency on an operator's skill and judgment to obtain optimum positioning, as well as real-time characterization sensors to determine as the blast head is moving the depth to which coatings must be removed, thereby improving production and minimizing waste. In phase II, the Contractor shall design and

  9. Azacitidine in the 'real-world': an evaluation of 1101 higher-risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada. (United States)

    Mozessohn, Lee; Cheung, Matthew C; Fallahpour, Saber; Gill, Tripat; Maloul, Asmaa; Zhang, Liying; Lau, Olivia; Buckstein, Rena


    The outcome of myelodysplastic syndrome (MDS) patients with uniformly higher-risk disease treated with azacitidine (AZA) in the 'real-world' remains largely unknown. We evaluated 1101 consecutive higher-risk MDS patients (International Prognostic Scoring System intermediate-2/high) and low-blast count acute myeloid leukaemia (AML; 21-30% blasts) patients treated in Ontario, Canada. By dosing schedule, 24·7% received AZA for seven consecutive days, 12·4% for six consecutive days and 62·9% by 5-2-2. Overall, median number of cycles was 6 (range 1-67) and 8 (range 6-14) when restricted to the 692 (63%) patients who received at least 4 cycles. The actuarial median survival was 11·6 months [95% confidence interval (CI) 10·7-12·4) for the entire cohort and 18·0 months (landmark analysis; 95% CI 16·6-19·1 months) for those receiving at least 4 cycles. There was no difference in overall survival (OS) between the 3 dosing schedules (P = 0·87). In our large 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML, we demonstrated a lower than expected OS. Reassuringly, survival did not differ by dosing schedules. The OS was higher in the 2/3 of patients who received at least 4 cycles of treatment, reinforcing the necessity of sustained administration until therapeutic benefits are realised. This represents the largest 'real-world' evaluation of AZA in higher-risk MDS/low-blast count AML. © 2018 John Wiley & Sons Ltd.

  10. Myeloid Sarcoma Predicts Superior Outcome in Pediatric AML; Can Cytogenetics Solve the Puzzle? (United States)

    Pramanik, Raja; Tyagi, Anudishi; Chopra, Anita; Kumar, Akash; Vishnubhatla, Sreenivas; Bakhshi, Sameer


    The purpose of our study was to evaluate the clinical, cytogenetic, and molecular features, and survival outcomes in patients with acute myeloid leukemia (AML) with myeloid sarcoma (MS) and compare them with patients with AML without MS. This was a retrospective analysis of de novo pediatric AML patients with or without MS diagnosed at our cancer center between June 2003 and June 2016. MS was present in 121 of 570 (21.2%), the most frequent site being the orbit. Patients with MS had a younger median age (6 years vs. 10 years) and presented with higher hemoglobin and platelet but lower white blood cell count compared with patients without MS. Further, t (8; 21) (P < .01), loss of Y chromosome (P < .01), and deletion 9q (P = .03) were significantly higher in patients with AML with MS. Event-free survival (EFS; P = .003) and overall survival (OS; P = .001) were better among patients with AML with MS (median EFS 21.0 months and median OS 37.1 months) compared with those with AML without MS (median EFS 11.2 months and median OS 16.2 months). The t (8; 21) was significantly associated with MS (odds ratio, 3.92). In a comparison of the 4 groups divided according to the presence or absence of MS and t (8; 21), the subgroup of patients having MS without concomitant t (8; 21) was the only group to have a significantly better OS (hazard ratio, 0.53; 95% confidence interval, 0.34-0.82; P = .005). Although t (8; 21) was more frequently associated with MS, it did not appear to be the reason for better outcome. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer. (United States)

    Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia


    The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

  12. Centrifugal shot blast system

    International Nuclear Information System (INIS)


    This report describes a demonstration of Concrete cleaning, Inc., modified centrifugal shot blast technology to remove the paint coating from concrete flooring. This demonstration is part of the Chicago Pile-5 (CP-5) Large-Scale Demonstration Project (LSDP) sponsored by the US Department of Energy (DOE), office of Science and Technology (OST), Deactivation and Decommissioning Focus Area (DDFA). The objective of the LSDP is to select and demonstrate potentially beneficial technologies at the Argonne National Laboratory-East (ANL) CP-5 Research Reactor. The purpose of the LSDP is to demonstrate that using innovative and improved decontamination and decommissioning (D and D) technologies from various sources can result in significant benefits, such as decreased cost and increased health and safety, as compared with baseline D and D technologies. Potential markets exist for the innovative centrifugal shot blast system at the following sites: Fernald Environmental Management Project, Los Alamos, Nevada, Oak Ridge Y-12 and K-25, Paducah, Portsmouth Gaseous Diffusion site, and the Savannah River Site. This information is based on a revision to the OST Linkage Tables dated August 4, 1997

  13. Disease evolution and outcomes in familial AML with germline CEBPA mutations

    DEFF Research Database (Denmark)

    Tawana, Kiran; Wang, Jun; Renneville, Aline


    collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant......, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course...

  14. Gene expression profiling in MDS and AML: potential and future avenues

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, K; Boultwood, J; Ferrari, S


    Today, the classification systems for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) already incorporate cytogenetic and molecular genetic aberrations in an attempt to better reflect disease biology. However, in many MDS/AML patients no genetic aberrations have been identified yet...... with regard to diagnosis, prediction of clinical outcome, discovery of novel subclasses and identification of novel therapeutic targets and novel drugs. As many challenges remain ahead, we discuss the pitfalls of this technology and its potential including future integrative studies with other genomics...

  15. CO2 pellet blasting studies

    International Nuclear Information System (INIS)

    Archibald, K.E.


    Initial tests with CO 2 pellet blasting as a decontamination technique were completed in 1993 at the Idaho Chemical Processing Plant (ICPP) at the Idaho National Engineering Laboratory (INEL). During 1996, a number of additional CO 2 pellet blasting studies with Alpheus Cleaning Technologies, Oak Ridge National Laboratory, and Pennsylvania State University were conducted. After the testing with Alpheus was complete, an SDI-5 shaved CO 2 blasting unit was purchased by the ICPP to test and determine its capabilities before using in ICPP decontamination efforts. Results of the 1996 testing will be presented in this report

  16. Enumerating bone marrow blasts from nonerythroid cellularity improves outcome prediction in myelodysplastic syndromes and permits a better definition of the intermediate risk category of the Revised International Prognostic Scoring System (IPSS-R). (United States)

    Calvo, Xavier; Arenillas, Leonor; Luño, Elisa; Senent, Leonor; Arnan, Montserrat; Ramos, Fernando; Pedro, Carme; Tormo, Mar; Montoro, Julia; Díez-Campelo, María; Blanco, María Laura; Arrizabalaga, Beatriz; Xicoy, Blanca; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Meritxell; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes


    The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E). We assessed if calculating IPSS-R by enumerating blasts from NECs improves prognostication of MDS. Twenty-four percent of patients classified into the intermediate category were reclassified into higher-risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower-risk patients showed longer survivals than previously whereas higher-risk ones maintained the outcome expected in this poor prognostic group (median OS < 20 months). Furthermore, our approach was particularly useful for detecting patients at risk of dying with AML. Regarding MDS-E, 51% patients classified into the intermediate category were reclassified into higher-risk ones and showed shorter OS and time to AML. In this subgroup of MDS, IPSS-R was capable of splitting our series in five groups with significant differences in OS only when blasts were assessed from NECs. In conclusion, our easy-applicable approach improves prognostic assessment of MDS patients. © 2017 Wiley Periodicals, Inc.

  17. Use of G-CSF to hasten neutrophil recovery after auto-SCT for AML is not associated with increased relapse incidence: a report from the Acute Leukemia Working Party of the EBMT. (United States)

    Czerw, T; Labopin, M; Gorin, N-C; Giebel, S; Blaise, D; Dumas, P-Y; Foa, R; Attal, M; Schaap, N; Michallet, M; Bonmati, C; Veelken, H; Mohty, M


    Application of G-CSF in AML is controversial as leukemic blasts may express receptors interacting with the cytokine, which may stimulate leukemia growth. We retrospectively analyzed the impact of G-CSF use to accelerate neutrophil recovery after auto-SCT on outcome. Adults with AML in first CR autografted between 1994 and 2010 were included. Nine hundred and seventy two patients were treated with G-CSF after auto-SCT whereas 1121 were not. BM and PB were used as a source of stem cells in 454 (22%) and 1639 (78%) cases, respectively. The incidence of relapse at 5 years in the BM-auto-SCT group was 38% for patients receiving post-transplant G-CSF and 43% for those not treated with G-CSF, P=0.46. In the PB-auto-SCT cohort, respective probabilities were 48% and 49%, P=0.49. No impact of the use of G-CSF could be demonstrated with respect to the probability of leukemia-free survival: in the BM-auto-SCT group, 51% for G-CSF(+) and 48% for G-CSF(-), P=0.73; in PB-auto-SCT group, 42% for G-CSF(+) and 43% for G-CSF(-), P=0.83. Although G-CSF administration significantly shortened the neutropenic phase, no beneficial effect was observed with regard to non-relapse mortality. In patients with AML, the use of G-CSF after auto-SCT is not associated with increased risk of relapse irrespective of the source of stem cells used.

  18. The TAK1-NF-κB axis as therapeutic target for AML

    NARCIS (Netherlands)

    Bosman, Matthieu Cornelis Johannes; Schepers, Hein; Jaques, Jennifer; Vos, Annet; Quax, Wim Johannes; Schuringa, Jan Jacob; Vellenga, Edo


    Development and maintenance of leukemia can partially be attributed to alterations in (anti) apoptotic gene expression. Genome-wide transcriptome analyses revealed that 89 apoptosis-associated genes were differentially expressed between patient acute myeloid leukemia (AML) CD34(+) cells and normal

  19. Genetic and epigenetic similarities and differences between childhood and adult AML

    DEFF Research Database (Denmark)

    Juhl-Christensen, Caroline; Ommen, Hans Beier; Aggerholm, Anni


    The biology of acute myeloid leukemia (AML) is complex and includes both genetic and epigenetic aberrations. We addressed the combined consequences of promoter hypermethylation of p15, CDH1, ER, MDR1, and RARB2 and mutation of NPM1, CEBPA, FLT3, and WT1 in a Danish cohort of 70 pediatric and 383...

  20. Prognostic Value of RUNX1 Mutations in AML: A Meta-Analysis (United States)

    Jalili, Mahdi; Yaghmaie, Marjan; Ahmadvand, Mohammad; Alimoghaddam, Kamran; Mousavi, Seyed Asadollah; Vaezi, Mohammad; Ghavamzadeh, Ardeshir


    The RUNX1 (AML1) gene is a relatively infrequent mutational target in cases of acute myeloid leukemia (AML). Previous work indicated that RUNX1 mutations can have pathological and prognostic implications. To evaluate prognostic value, we conducted a meta-analysis of 4 previous published works with data for survival according to RUNX1 mutation status. Pooled hazard ratios for overall survival and disease-free survival were 1.55 (95% confidence interval (CI) = 1.11–2.15; p-value = 0.01) and 1.76 (95% CI = 1.24–2.52; p-value = 0.002), respectively, for cases positive for RUNX1 mutations. This evidence supports clinical implications of RUNX1 mutations in the development and progression of AML cases and points to the possibility of a distinct category within the newer WHO classification. Though it must be kept in mind that the present work was based on data extracted from observational studies, the findings suggest that the RUNX1 status can contribute to risk-stratification and decision-making in management of AML. Creative Commons Attribution License

  1. BLAST and FASTA similarity searching for multiple sequence alignment. (United States)

    Pearson, William R


    BLAST, FASTA, and other similarity searching programs seek to identify homologous proteins and DNA sequences based on excess sequence similarity. If two sequences share much more similarity than expected by chance, the simplest explanation for the excess similarity is common ancestry-homology. The most effective similarity searches compare protein sequences, rather than DNA sequences, for sequences that encode proteins, and use expectation values, rather than percent identity, to infer homology. The BLAST and FASTA packages of sequence comparison programs provide programs for comparing protein and DNA sequences to protein databases (the most sensitive searches). Protein and translated-DNA comparisons to protein databases routinely allow evolutionary look back times from 1 to 2 billion years; DNA:DNA searches are 5-10-fold less sensitive. BLAST and FASTA can be run on popular web sites, but can also be downloaded and installed on local computers. With local installation, target databases can be customized for the sequence data being characterized. With today's very large protein databases, search sensitivity can also be improved by searching smaller comprehensive databases, for example, a complete protein set from an evolutionarily neighboring model organism. By default, BLAST and FASTA use scoring strategies target for distant evolutionary relationships; for comparisons involving short domains or queries, or searches that seek relatively close homologs (e.g. mouse-human), shallower scoring matrices will be more effective. Both BLAST and FASTA provide very accurate statistical estimates, which can be used to reliably identify protein sequences that diverged more than 2 billion years ago.

  2. Blast wave injury prediction models for complex scenarios

    NARCIS (Netherlands)

    Teland, J.A.; Doormaal, J.C.A.M. van


    Blast waves from explosions can cause lethal injuries to humans. Development of injury criteria has been ongoing for many years, but with the main focus on free field conditions. However, with terrorist actions as a new threat, explosions in urban areas have become of much more interest. Urban areas

  3. 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group. (United States)

    Büchner, Thomas; Hiddemann, Wolfgang; Berdel, Wolfgang E; Wörmann, Bernhard; Schoch, Claudia; Fonatsch, Christa; Löffler, Helmut; Haferlach, Torsten; Ludwig, Wolf-Dieter; Maschmeyer, Georg; Staib, Peter; Aul, Carlo; Gruneisen, Andreas; Lengfelder, Eva; Frickhofen, Norbert; Kern, Wolfgang; Serve, Hubert L; Mesters, Rolf M; Sauerland, Maria Cristina; Heinecke, Achim


    To examine the efficacy of prolonged maintenance chemotherapy versus intensified consolidation therapy for patients with acute myeloid leukemia (AML). Eight hundred thirty-two patients (median age, 54 years; range, 16 to 82 years) with de novo AML were randomly assigned to receive 6-thioguanine, cytarabine, and daunorubicin (TAD) plus cytarabine and mitoxantrone (HAM; cytarabine 3 g/m2 [age or = 60 years] x 6) induction, TAD consolidation, and monthly modified TAD maintenance for 3 years, or TAD-HAM-TAD and one course of intensive consolidation with sequential HAM (S-HAM) with cytarabine 1 g/m2 (age or = 60 years) x 8 instead of maintenance. A total of 69.2% patients went into complete remission (CR). Median relapse-free survival (RFS) was 19 months for patients on the maintenance arm, with 31.4% of patients relapse-free at 5 years, versus 12 months for patients on the S-HAM arm, with 24.7% of patients relapse-free at 5 years (P =.0118). RFS from maintenance was superior in patients with poor risk by unfavorable karyotype, age > or = 60 years, lactate dehydrogenase level greater than 700 U/L, or day 16 bone marrow blasts greater than 40% (P =.0061) but not in patients with good risk by complete absence of any poor risk factors. Although a survival benefit in the CR patients is not significant (P =.085), more surviving patients in the maintenance than in the S-HAM arm remain in first CR (P =.026). We conclude that TAD-HAM-TAD-maintenance first-line treatment has a higher curative potential than TAD-HAM-TAD-S-HAM and improves prognosis even among patients with poor prognosis.

  4. Model for small arms fire muzzle blast wave propagation in air (United States)

    Aguilar, Juan R.; Desai, Sachi V.


    Accurate modeling of small firearms muzzle blast wave propagation in the far field is critical to predict sound pressure levels, impulse durations and rise times, as functions of propagation distance. Such a task being relevant to a number of military applications including the determination of human response to blast noise, gunfire detection and localization, and gun suppressor design. Herein, a time domain model to predict small arms fire muzzle blast wave propagation is introduced. The model implements a Friedlander wave with finite rise time which diverges spherically from the gun muzzle. Additionally, the effects in blast wave form of thermoviscous and molecular relaxational processes, which are associated with atmospheric absorption of sound were also incorporated in the model. Atmospheric absorption of blast waves is implemented using a time domain recursive formula obtained from numerical integration of corresponding differential equations using a Crank-Nicholson finite difference scheme. Theoretical predictions from our model were compared to previously recorded real world data of muzzle blast wave signatures obtained by shooting a set different sniper weapons of varying calibers. Recordings containing gunfire acoustical signatures were taken at distances between 100 and 600 meters from the gun muzzle. Results shows that predicted blast wave slope and exponential decay agrees well with measured data. Analysis also reveals the persistency of an oscillatory phenomenon after blast overpressure in the recorded wave forms.

  5. Peptide microarray profiling identifies phospholipase C gamma 1 (PLC-γ1) as a potential target for t(8;21) AML

    NARCIS (Netherlands)

    Mahmud, Hasan; Scherpen, Frank J. G.; Meeuwsen de Boer, Tiny; Lourens, Harm-Jan; Schoenherr, Caroline; Eder, Matthias; Scherr, Michaela; Guryev, Victor; de Bont, Eveline S.


    The t(8;21) (q22;q22) chromosomal translocation is one of the most frequent genetic alterations in acute myeloid leukemia (AML) which has a need for improved therapeutic strategies. We found PLC-γ1 as one of the highest phosphorylated peptides in t(8;21) AML samples compared to NBM or CN-AML in our

  6. Proliferative status of primitive hematopoietic progenitors from patients with acute myelogenous leukemia (AML). (United States)

    Guan, Y; Hogge, D E


    One possible explanation for the competitive advantage that malignant cells in patients with acute myelogenous leukemia (AML) appear to have over normal hematopoietic elements is that leukemic progenitors proliferate more rapidly than their normal progenitor cell counterparts. To test this hypothesis, an overnight 3H-thymidine (3H-Tdr) suicide assay was used to analyze the proliferative status of malignant progenitors detected in both colony-forming cell (CFC) and long-term culture initiating cell (LTC-IC) assays from the peripheral blood of nine patients with newly diagnosed AML. Culture of AML cells in serum-free medium with 100 ng/ml Steel factor (SF), 20 ng/ml interleukin 3 (IL-3) and 20 ng/ml granulocyte colony-stimulating factor (G-CSF) for 16-24 h maintained the number of AML-CFC and LTC-IC at near input values (mean % input +/- s.d. for CFC and LTC-IC were 78 +/- 33 and 126 +/- 53, respectively). The addition of 20 muCi/ml high specific activity 3H-Tdr to these cultures reduced the numbers of both progenitor cell types from most of the patient samples substantially: mean % kill +/- s.d. for AML-CFC and LTC-IC were 64 +/- 27 and 82 +/- 16, respectively, indicating that a large proportion of both progenitor populations were actively cycling. FISH analysis of colonies from CFC and LTC-IC assays confirmed that most cytogenetically abnormal CFC and LTC-IC were actively cycling (mean % kill +/- s.d.: 68 +/- 26 and 85 +/- 13, respectively). Interestingly, in six patient samples where a significant number of cytogenetically normal LTC-ICs were detected, the % kill of these cells (74 +/- 20) was similar to that of the abnormal progenitors. These data contrast with the predominantly quiescent cell cycle status of CFC and LTC-IC previously observed in steady-state peripheral blood from normal individuals but also provide evidence that a significant proportion of primitive malignant progenitors from AML patients are quiescent and therefore may be resistant to standard

  7. The use of computer blast simulations to improve blast quality

    International Nuclear Information System (INIS)

    Favreau, R.F.; Kuzzyk, G.W.; Babulic, P.J.; Morin, R.A.; Tienkamp, N.J.


    An underground research laboratory (URL) has been constructed as part of a comprehensive program to evaluate the concept of nuclear fuel waste disposal in deep crystalline rock formations. Careful blasting methods have been used to minimize damage to the excavation surfaces. This paper reviews the results of the program to develop controlled blasting for the full-face method, comparing the field observed results achieved with the simulated theoretical results. The simulated results indicate how the blasting may damage the excavation surface. Results suggest that the rock around the final wall is stressed more severely by the cushion holes than by the perimeter holes and that bootleg of the rock between the perimeter and cushion rows occurs when the burst-out velocity imparted to it by the explosive loads in the perimeter holes is inadequate

  8. [Detection of heterogeneity and evolution of subclones in t(8;21) AML by QM-FISH]. (United States)

    Wang, Ying-chan; Hu, Lin-ping; Lin, Dong; Li, Cheng-wen; Yuan, Tian; Jia, Yu-jiao; Tian, Zheng; Tang, Ke-jing; Wang, Min; Wang, Jian-xiang


    To explore the heterogeneous subclones in acute myeloid leukemia (AML) with t(8;21) by quantitative multicolor- fluorescence in situ hybridization (QM-FISH), and to figure out whether there is putative ancestral relationship among different subclones. Bacterial artificial chromosomes (BAC) clones that contain the targeted genes including AML1, ETO, WT1, p27 and c-kit were searched in the data base UCSC Genome Bioinformatics. Multicolor FISH probes were prepared by linking fluorescein labeled dUTP or dCTP to targeted genes by nick translation. Bone marrow mononuclear cells from t (8;21) AML patients are dropped on to the wet surface of glass slides after hypotonic treatment and fixation. After hybridization, the fluorescence signals were captured by Zeiss fluorescence microscope. The copy number of AML1, ETO, WT1, p27, c- kit and the AML1-ETO fusion gene in AML1-ETO positive cells was counted. The cells with same signals were defined as a subclone. Various subclones were recorded and their proportions were calculated, and their evolutionary relationship was deduced. The subclones in matched primary and relapsed samples were compared, the evolution of dominant clones were figured out and the genomic abnormality that is associated with relapse and drug resistance were speculated. In this study, 36 primary AML with t(8;21) cases and 1 relapsed case paired with the primary case were detected. In these 36 primary cases, 4 cases (11.1%) acquired additional AML1-ETO fusion signal, 3(8.3%) had additional AML1 signal, 4(11.1%) had additional ETO signal, 20(55.6%) had additional WT1 signal, 15(41.7%) had additional p27 signal and 14(38.9%) had additional c-kit signal. In addition, 10(27.8%) displayed AML1 signal deletion, and such an aberration represents statistic significance in male patients. It seems that male patients usually accompany AML1 signal deletion. Of 36 cases, 28(77.8 %) harbored at least 2 subclones (ranged from 2 to 10). According to the genetic signature of

  9. Simulating geometrically complex blast scenarios

    Directory of Open Access Journals (Sweden)

    Ian G. Cullis


    Full Text Available The effects of blast waves generated by energetic and non-energetic sources are of continuing interest to the ballistics research community. Modern conflicts are increasingly characterised by asymmetric urban warfare, with improvised explosive devices (IEDs often playing a dominant role on the one hand and an armed forces requirement for minimal collateral effects from their weapons on the other. These problems are characterised by disparate length- and time-scales and may also be governed by complex physics. There is thus an increasing need to be able to rapidly assess and accurately predict the effects of energetic blast in topologically complex scenarios. To this end, this paper presents a new QinetiQ-developed advanced computational package called EAGLE-Blast, which is capable of accurately resolving the generation, propagation and interaction of blast waves around geometrically complex shapes such as vehicles and buildings. After a brief description of the numerical methodology, various blast scenario simulations are described and the results compared with experimental data to demonstrate the validation of the scheme and its ability to describe these complex scenarios accurately and efficiently. The paper concludes with a brief discussion on the use of the code in supporting the development of algorithms for fast running engineering models.

  10. Rock fragmentation control in opencast blasting

    Directory of Open Access Journals (Sweden)

    P.K. Singh


    Full Text Available The blasting operation plays a pivotal role in the overall economics of opencast mines. The blasting sub-system affects all the other associated sub-systems, i.e. loading, transport, crushing and milling operations. Fragmentation control through effective blast design and its effect on productivity are the challenging tasks for practicing blasting engineer due to inadequate knowledge of actual explosive energy released in the borehole, varying initiation practice in blast design and its effect on explosive energy release characteristic. This paper describes the result of a systematic study on the impact of blast design parameters on rock fragmentation at three mines in India. The mines use draglines and shovel–dumper combination for removal of overburden. Despite its pivotal role in controlling the overall economics of a mining operation, the expected blasting performance is often judged almost exclusively on the basis of poorly defined parameters such as powder factor and is often qualitative which results in very subjective assessment of blasting performance. Such an approach is very poor substitutes for accurate assessment of explosive and blasting performance. Ninety one blasts were conducted with varying blast designs and charging patterns, and their impacts on the rock fragmentation were documented. A high-speed camera was deployed to record the detonation sequences of the blasts. The efficiency of the loading machines was also correlated with the mean fragment size obtained from the fragmentation analyses.

  11. BLEVE blast by expansion-controlled evaporation

    NARCIS (Netherlands)

    Berg, A.C. van den; Voort, M.M. van der; Weerheijm, J.; Versloot, N.H.A.


    This report presents a new method to calculate the blast effects originating from an exploding vessel of liquefied gas. Adequate blast calculation requires full knowledge of the blast source characteristics, that is, the release and subsequent evaporation rate of the flashing liquid. Because the

  12. 30 CFR 75.1323 - Blasting circuits. (United States)


    ...) Blasting circuits shall be protected from sources of stray electric current. (b) Detonators made by different manufacturers shall not be combined in the same blasting circuit. (c) Detonator leg wires shall be... used between the blasting cable and detonator circuitry shall— (1) Be undamaged; (2) Be well insulated...

  13. Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models. (United States)

    Portwood, Scott; Lal, Deepika; Hsu, Yung-Chun; Vargas, Rodrigo; Johnson, Megan K; Wetzler, Meir; Hart, Charles P; Wang, Eunice S


    Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. ©2013 AACR.

  14. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. (United States)

    Döhner, Hartmut; Estey, Elihu; Grimwade, David; Amadori, Sergio; Appelbaum, Frederick R; Büchner, Thomas; Dombret, Hervé; Ebert, Benjamin L; Fenaux, Pierre; Larson, Richard A; Levine, Ross L; Lo-Coco, Francesco; Naoe, Tomoki; Niederwieser, Dietger; Ossenkoppele, Gert J; Sanz, Miguel; Sierra, Jorge; Tallman, Martin S; Tien, Hwei-Fang; Wei, Andrew H; Löwenberg, Bob; Bloomfield, Clara D


    The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease. © 2017 by The American Society of Hematology.

  15. High frequency of streptococcal bacteraemia during childhood AML therapy irrespective of dose of cytarabine

    DEFF Research Database (Denmark)

    Johannsen, Katrine Helle; Handrup, Mette Møller; Lausen, Birgitte Frederiksen


    of cytarabine and more chemotherapy series (n = 6) than other protocols with the potential increased risk of severe VGS infections. PROCEDURE: Medical records of all Danish children enrolled on the NOPHO-AML-2004 protocol between January 2004 and September 2011 (n = 45) were retrospectively reviewed and all...... rate of VGS seemed independent of high-dose cytarabine but was more likely caused by the intensive chemotherapy treatment leading to severe mucositis and neutropenia....

  16. Socioeconomic status (SES) and childhood acute myeloid leukemia (AML) mortality risk: Analysis of SEER data. (United States)

    Knoble, Naomi B; Alderfer, Melissa A; Hossain, Md Jobayer


    Socioeconomic status (SES) is a complex construct of multiple indicators, known to impact cancer outcomes, but has not been adequately examined among pediatric AML patients. This study aimed to identify the patterns of co-occurrence of multiple community-level SES indicators and to explore associations between various patterns of these indicators and pediatric AML mortality risk. A nationally representative US sample of 3651 pediatric AML patients, aged 0-19 years at diagnosis was drawn from 17 Surveillance, Epidemiology, and End Results (SEER) database registries created between 1973 and 2012. Factor analysis, cluster analysis, stratified univariable and multivariable Cox proportional hazards models were used. Four SES factors accounting for 87% of the variance in SES indicators were identified: F1) economic/educational disadvantage, less immigration; F2) immigration-related features (foreign-born, language-isolation, crowding), less mobility; F3) housing instability; and, F4) absence of moving. F1 and F3 showed elevated risk of mortality, adjusted hazards ratios (aHR) (95% CI): 1.07(1.02-1.12) and 1.05(1.00-1.10), respectively. Seven SES-defined cluster groups were identified. Cluster 1 (low economic/educational disadvantage, few immigration-related features, and residential-stability) showed the minimum risk of mortality. Compared to Cluster 1, Cluster 3 (high economic/educational disadvantage, high-mobility) and Cluster 6 (moderately-high economic/educational disadvantages, housing-instability and immigration-related features) exhibited substantially greater risk of mortality, aHR(95% CI)=1.19(1.0-1.4) and 1.23 (1.1-1.5), respectively. Factors of correlated SES-indicators and their pattern-based groups demonstrated differential risks in the pediatric AML mortality indicating the need of special public-health attention in areas with economic-educational disadvantages, housing-instability and immigration-related features. Copyright © 2016 Elsevier Ltd. All

  17. Control buildings for blast resistance

    Energy Technology Data Exchange (ETDEWEB)

    Brown, G.A.


    Offers advice on interior design for blast-resistant control buildings. Suggests that for the comfort and safety of occupants, special attention must be paid to internal finishes and color schemes. Considers external treatment (e.g. panels, cladding fixings, thermal insulation), air intakes and exhausts, internal finishes (e.g. stud lining method), and internal walls and partitions. Presents diagrams showing construction method for a control building; elimination of ''cold bridge'' at eaves level; staggering door openings to minimize blast effects; and flexure of concrete walls without affecting the inner lining.

  18. Porcine head response to blast. (United States)

    Shridharani, Jay K; Wood, Garrett W; Panzer, Matthew B; Capehart, Bruce P; Nyein, Michelle K; Radovitzky, Raul A; Bass, Cameron R 'dale'


    Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposes porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110 to 740 kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. Instrumentation was placed on the porcine head to measure bulk acceleration, pressure at the surface of the head, and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within 30 s and the remaining two recovered within 8 min following respiratory assistance and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300-2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G's and were well correlated with peak incident overpressure (R(2) = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are

  19. Water in the blast hole

    Energy Technology Data Exchange (ETDEWEB)

    Pilshaw, S.R. [Pilshaw Associates, KS (United States)


    Water in the blast area is a considerable problem in US opencast coal mining. While gelatin dynamite was reasonably water resistant, Anfo is not. All potential solutions to this problem: the use of Anfo and emulsion (Heavy Anfo), pumping, draining, and the use of water bags, involve considerable extra cost. With small amounts of water an alternative solution has been formulated: the use of a self inflating gas bag to exclude water, and loading the Anfo from the water line up to the stemming level of the blasthole. Quite substantial water columns may be sealed off in this manner, with little or no deleterious effect on blast effects.

  20. Problems getting from the laboratory to the field: Reclamation of an AML site

    International Nuclear Information System (INIS)

    Dick, W.A.; Stehouwer, R.C.


    Acid and toxic abandoned mineland sites provide an opportunity whereby flue gas desulfurization (FGD) by-product can be beneficially used as a reclamation amendment material. Studies are needed to compare the effectiveness of FGD by-product, as compared with resoil, for reclamation purposes. Initial studies provided information about the chemical and physical properties of the FGD by-product and how to transport and blend the FGD by-product with yard waste compost. Greenhouse studies indicated that rates of 125 dry tons/acre of FGD and 50 dry tons/acre of yard waste compost would provide optimum results for reclamation of acid and toxic spoil contained at the Fleming abandoned mineland (AML) site. Their results showed that heavy metal loading rates were much lower using the FGD/compost mixture than using resoil material. Dioxin in the mixture was also less than the 5 ppt level considered as normal background. The technical problems of using FGD by-product for reclamation of an AML site were solved. However, considerable efforts to educate the public about the merits of reclaiming the Fleming AML site using this FGD/compost mixture were required before initiating field reclamation activities. Education efforts must continue if FGD by-products are to achieve general acceptance as a reclamation alternative to resoil in cases where resoil is of scarce supply

  1. A multigene array for measurable residual disease detection in AML patients undergoing SCT (United States)

    Goswami, M; McGowan, K S; Lu, K; Jain, N; Candia, J; Hensel, N F; Tang, J; Calvo, K R; Battiwalla, M; Barrett, A J; Hourigan, C S


    AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ–PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994–2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ–PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection. PMID:25665046

  2. Blast wave parameters at diminished ambient pressure (United States)

    Silnikov, M. V.; Chernyshov, M. V.; Mikhaylin, A. I.


    Relation between blast wave parameters resulted from a condensed high explosive (HE) charge detonation and a surrounding gas (air) pressure has been studied. Blast wave pressure and impulse differences at compression and rarefaction phases, which traditionally determine damage explosive effect, has been analyzed. An initial pressure effect on a post-explosion quasi-static component of the blast load has been investigated. The analysis is based on empirical relations between blast parameters and non-dimensional similarity criteria. The results can be directly applied to flying vehicle (aircraft or spacecraft) blast safety analysis.

  3. Leucemia mielóide aguda Ph1-positivo de novo ou crise blástica de leucemia mielóide crônica? Análise molecular e evolução clínica de um caso Molecular analysis and clinical evolution of one case of Ph1-positive acute myeloid leukemia (AML

    Directory of Open Access Journals (Sweden)

    G.W.B. Colleoni


    Full Text Available Os autores relatam um caso de leucemia mielóide aguda (LMA que apresentava, ao diagnóstico, basofilia no sangue periférico e cariótipo com presença do cromossomo Filadélfia (Ph1. Após um ano de tratamento com quimioterapia intensiva e em fase de remissão clínica e hematológica, a análise molecular pela técnica da reação em cadeia da polimerase-transcriptase reversa (RT-PCR revelou presença de doença residual (rearranjo b2-a2. A seguir, o paciente apresentou primeira recidiva como LMA e, após a remissão, evoluiu com quadro hematológico sugestivo de leucemia mielóide crônica (LMC em fase crônica. Após dez meses, apresentou nova recidiva da LMA. Os autores discutem a dificuldade do diagnóstico diferencial entre LMA Ph1-positivo de novo e crise blástica mielóide como primeira manifestação clínica da LMC, baseados nos aspectos clínicos e moleculares.A case of AML presented with basophilia in peripheral blood and Ph1 chromosome in karyotype analysis is reported. After one year of treatment with intensive chemoterapy and clinical and hematological remission, molecular analysis (RT-PCR detected minimal residual disease (b2-a2 rearrangement. Thus, the patient relapsed as AML and, after second remission, he developed a hematological picture of chronic CML. Ten months later, he relapsed again as AML. The difficulties of diagnosis between AML Ph1-positive de novo and myeloid blast crisis of CML, as the first manifestation of disease, based on clinical and molecular aspects are discussed.

  4. Distinct patterns of DNA damage response and apoptosis correlate with Jak/Stat and PI3kinase response profiles in human acute myelogenous leukemia.

    Directory of Open Access Journals (Sweden)

    David B Rosen

    Full Text Available BACKGROUND: Single cell network profiling (SCNP utilizing flow cytometry measures alterations in intracellular signaling responses. Here SCNP was used to characterize Acute Myeloid Leukemia (AML disease subtypes based on survival, DNA damage response and apoptosis pathways. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty four diagnostic non-M3 AML samples from patients with known clinical outcome were treated with a panel of myeloid growth factors and cytokines, as well as with apoptosis-inducing agents. Analysis of induced Jak/Stat and PI3K pathway responses in blasts from individual patient samples identified subgroups with distinct signaling profiles that were not seen in the absence of a modulator. In vitro exposure of patient samples to etoposide, a DNA damaging agent, revealed three distinct "DNA damage response (DDR/apoptosis" profiles: 1 AML blasts with a defective DDR and failure to undergo apoptosis; 2 AML blasts with proficient DDR and failure to undergo apoptosis; 3 AML blasts with proficiency in both DDR and apoptosis pathways. Notably, AML samples from clinical responders fell within the "DDR/apoptosis" proficient profile and, as well, had low PI3K and Jak/Stat signaling responses. In contrast, samples from clinical non responders had variable signaling profiles often with in vitro apoptotic failure and elevated PI3K pathway activity. Individual patient samples often harbored multiple, distinct, leukemia-associated cell populations identifiable by their surface marker expression, functional performance of signaling pathway in the face of cytokine or growth factor stimulation, as well as their response to apoptosis-inducing agents. CONCLUSIONS AND SIGNIFICANCE: Characterizing and tracking changes in intracellular pathway profiles in cell subpopulations both at baseline and under therapeutic pressure will likely have important clinical applications, potentially informing the selection of beneficial targeted agents, used either alone or in

  5. A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

    International Nuclear Information System (INIS)

    Saland, E; Boutzen, H; Castellano, R; Pouyet, L; Griessinger, E; Larrue, C; Toni, F de; Scotland, S; David, M; Danet-Desnoyers, G; Vergez, F; Barreira, Y; Collette, Y; Récher, C; Sarry, J-E


    Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγ c null mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies

  6. Caspase-3 controls AML1-ETO-driven leukemogenesis via autophagy modulation in a ULK1-dependent manner. (United States)

    Man, Na; Tan, Yurong; Sun, Xiao-Jian; Liu, Fan; Cheng, Guoyan; Greenblatt, Sarah M; Martinez, Camilo; Karl, Daniel L; Ando, Koji; Sun, Ming; Hou, Dan; Chen, Bingyi; Xu, Mingjiang; Yang, Feng-Chun; Chen, Zhu; Chen, Saijuan; Nimer, Stephen D; Wang, Lan


    AML1-ETO (AE), a fusion oncoprotein generated by t(8;21), can trigger acute myeloid leukemia (AML) in collaboration with mutations including c-Kit, ASXL1/2, FLT3, N-RAS, and K-RAS. Caspase-3, a key executor among its family, plays multiple roles in cellular processes, including hematopoietic development and leukemia progression. Caspase-3 was revealed to directly cleave AE in vitro, suggesting that AE may accumulate in a Caspase-3-compromised background and thereby accelerate leukemogenesis. Therefore, we developed a Caspase-3 knockout genetic mouse model of AML and found that loss of Caspase-3 actually delayed AML1-ETO9a (AE9a)-driven leukemogenesis, indicating that Caspase-3 may play distinct roles in the initiation and/or progression of AML. We report here that loss of Caspase-3 triggers a conserved, adaptive mechanism, namely autophagy (or macroautophagy), which acts to limit AE9a-driven leukemia. Furthermore, we identify ULK1 as a novel substrate of Caspase-3 and show that upregulation of ULK1 drives autophagy initiation in leukemia cells and that inhibition of ULK1 can rescue the phenotype induced by Caspase-3 deletion in vitro and in vivo. Collectively, these data highlight Caspase-3 as an important regulator of autophagy in AML and demonstrate that the balance and selectivity between its substrates can dictate the pace of disease. © 2017 by The American Society of Hematology.

  7. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    LENUS (Irish Health Repository)

    Rishi, Loveena


    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C\\/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C\\/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C\\/EBPα-p42, and in normal granulocyte\\/macrophage progenitor cells, we detect C\\/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C\\/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis.

  8. Fragment Size Distribution of Blasted Rock Mass (United States)

    Jug, Jasmin; Strelec, Stjepan; Gazdek, Mario; Kavur, Boris


    Rock mass is a heterogeneous material, and the heterogeneity of rock causes sizes distribution of fragmented rocks in blasting. Prediction of blasted rock mass fragmentation has a significant role in the overall economics of opencast mines. Blasting as primary fragmentation can significantly decrease the cost of loading, transport, crushing and milling operations. Blast fragmentation chiefly depends on the specific blast design (geometry of blast holes drilling, the quantity and class of explosive, the blasting form, the timing and partition, etc.) and on the properties of the rock mass (including the uniaxial compressive strength, the rock mass elastic Young modulus, the rock discontinuity characteristics and the rock density). Prediction and processing of blasting results researchers can accomplish by a variety of existing software’s and models, one of them is the Kuz-Ram model, which is possibly the most widely used approach to estimating fragmentation from blasting. This paper shows the estimation of fragmentation using the "SB" program, which was created by the authors. Mentioned program includes the Kuz-Ram model. Models of fragmentation are confirmed and calibrated by comparing the estimated fragmentation with actual post-blast fragmentation from image processing techniques. In this study, the Kuz-Ram fragmentation model has been used for an open-pit limestone quarry in Dalmatia, southern Croatia. The resulting calibrated value of the rock factor enables the quality prognosis of fragmentation in further blasting works, with changed drilling geometry and blast design parameters. It also facilitates simulation in the program to optimize blasting works and get the desired fragmentations of the blasted rock mass.

  9. NOBLAST and JAMBLAST: New Options for BLAST and a Java Application Manager for BLAST results. (United States)

    Lagnel, Jacques; Tsigenopoulos, Costas S; Iliopoulos, Ioannis


    NOBLAST (New Options for BLAST) is an open source program that provides a new user-friendly tabular output format for various NCBI BLAST programs (Blastn, Blastp, Blastx, Tblastn, Tblastx, Mega BLAST and Psi BLAST) without any use of a parser and provides E-value correction in case of use of segmented BLAST database. JAMBLAST using the NOBLAST output allows the user to manage, view and filter the BLAST hits using a number of selection criteria. A distribution package of NOBLAST and JAMBLAST including detailed installation procedure is freely available from and Supplementary data are available at Bioinformatics online.



    Kashuba, Oleh Ivanovych; Skliarov, L I; Skliarov, A L


    The problems of improving reliability of an electric blasting method using electric detonators with nichrome filament bridges. It was revealed that in the calculation of the total resistance of the explosive network it is necessary to increase to 24% of the nominal value

  11. Blast Shock Wave Mitigation Using the Hydraulic Energy Redirection and Release Technology (United States)

    Chen, Yun; Huang, Wei; Constantini, Shlomi


    A hydraulic energy redirection and release technology has been developed for mitigating the effects of blast shock waves on protected objects. The technology employs a liquid-filled plastic tubing as a blast overpressure transformer to transfer kinetic energy of blast shock waves into hydraulic energy in the plastic tubings. The hydraulic energy is redirected through the plastic tubings to the openings at the lower ends, and then is quickly released with the liquid flowing out through the openings. The samples of the specifically designed body armor in which the liquid-filled plastic tubings were installed vertically as the outer layer of the body armor were tested. The blast test results demonstrated that blast overpressure behind the body armor samples was remarkably reduced by 97% in 0.2 msec after the liquid flowed out of its appropriate volume through the openings. The results also suggested that a volumetric liquid surge might be created when kinetic energy of blast shock wave was transferred into hydraulic energy to cause a rapid physical movement or displacement of the liquid. The volumetric liquid surge has a strong destructive power, and can cause a noncontact, remote injury in humans (such as blast-induced traumatic brain injury and post-traumatic stress disorder) if it is created in cardiovascular system. The hydraulic energy redirection and release technology can successfully mitigate blast shock waves from the outer surface of the body armor. It should be further explored as an innovative approach to effectively protect against blast threats to civilian and military personnel. PMID:22745740

  12. An analysis of the heap construction by long hole blasting for in-situ leaching of blasted ore

    International Nuclear Information System (INIS)

    Yang Shijiao


    The author establishes specific requirements for heap construction by blasting on the basis of the mechanism for in situ leaching of blasted ore, analyses the feasibility of heap construction by long hole blasting, selection of the blast plan and the relevant technological problems, and gives a case of heap construction by long hole blasting in Renhua uranium mine

  13. Role of the Phosphorylation of mTOR in the Differentiation of AML Cells Triggered with CD44 Antigen

    KAUST Repository

    Darwish, Manar M


    Acute myeloid leukemia (AML) is a hematological disorder characterized by blockage of differentiation of myeloblasts. To date, the main therapy for AML is chemotherapy. Yet, studies are seeking a better treatment to enhance the survival rate of patients and minimize the relapsing of the disease. Since the major problem in these cells is that they are arrested in cellular differentiation, drugs that could induce their differentiation have proven to be efficient and of major interest for AML therapy. CD44 triggering appeared as a promising target for AML therapy as it has been shown that specific monoclonal antibodies, such as A3D8 and H90, reversed the blockage of differentiation, inhibited the proliferation of all AML subtypes, and in some cases, induced cell apoptosis. Studies conducted in our laboratory have added strength to these antibodies as potential treatment for AML. Indeed, our laboratory found that treating HL60 cells with A3D8 shows a decrease in the phosphorylation of the mammalian target of Rapamycin (mTOR) kinase correlated with the inhibition of proliferation/induction of differentiation of AML cells.The relationship between the induction of differentiation and the inhibition of proliferation and the decrease of mTOR phosphorylation remains to be clarified. To study the importance of the de-phosphorylation of mTOR and the observed effect of CD44 triggering on differentiation and/or proliferation, we sought to prepare phospho-mimic mutants of the mTOR kinase that will code for a constitutively phosphorylated form of mTOR and used two main methods to express this mutant in HL60 cells: lentiviral and simple transfection (cationic-liposomal transfection).

  14. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study. (United States)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders; Glosli, Heidi; Jahnukainen, Kirsi; Jarfelt, Marianne; Jónmundsson, Guðmundur K; Malmros, Johan; Nysom, Karsten; Hasle, Henrik


    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings. We included 137 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, who were alive by June 2007. Patients with relapse or treated with HSCT were excluded. AML survivors participated in a physical and biochemical examination (n = 102) and completed a questionnaire (n = 101). One of their siblings completed an identical questionnaire (n = 84). At a median follow-up of 11 years (range 5-25) after diagnosis of AML the survivors (median age 16 years, range 5-36) were either prepubertal or had entered puberty normally. Serum levels of FSH, LH, testosterone, estradiol, sex hormone binding globulin (SHBG), inhibin A and B, and testicular volumes were within normal ranges. Anti-Müllerian hormone (AMH) levels were decreased in 5 of 40 postpubertal females. Mean reported age at menarche was 13.1 (range 11-17) years. Among survivors 15 years of age or older 31% of females reported pregnancies and 9% of males reported pregnancies in their partners, rates comparable with the frequency reported by their siblings. Most AML survivors treated with chemotherapy had normal pubertal development and fertility, however, AMH levels were decreased in 13% of postpubertal females. Longer follow-up is necessary to evaluate possible risk of premature ovarian failure. © 2013 Wiley Periodicals, Inc.

  15. Therapy Related AML/MDS Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India. (United States)

    Vyas, Chintan; Jain, Sandeep; Kapoor, Gauri


    Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating late effect of cancer treatment. There is limited data on incidence of t-AML/MDS from India. We retrospectively studied pediatric t AML/MDS at our institute between January 1996 and December 2015. Among 1285 children, 8 patients developed t-AML with a median age of 15.5 years. Overall incidence of t-AML/MDS was 0.62% [0.99% (4/402) in solid tumours and 0.45% (4/883) in leukemia/lymphoma, P  = 0.26] with 6390 patient years of follow up. Primary malignancy included sarcoma [bone (2), soft tissue (2)], B-non-Hodgkin lymphoma (2) and acute lymphoblastic leukemia (2). The median cumulative equivalent doses of cyclophosphamide, doxorubicin and etoposide were 6.8, 270 and 2.5 gm/m 2 respectively. Two patients received radiotherapy [rhabdomyosarcoma (50 Gy), synovial sarcoma (45 Gy)]. The median latency period to develop t-AML/MDS was 24 months (range 16.5-62 months). Most common FAB morphology was M4/M5 (7/8) and cytogenetic abnormality was MLL rearrangement (4/8). Five patients opted for treatment, 4 achieved remission out of which 2 patients are alive and disease free. Short latency periods, absence of pre-leukemic phase and 11q23 translocations were characteristic in the patients with t-AML/MDS. In view of poor outcome with conventional therapy, novel strategies and prevention need to be considered.

  16. Development of a Strategy for Simulating Blast-Vehicle Interactions (United States)


    Magnus effect . Although large rotational speeds were measured, it was concluded that the Magnus force had little influence and did not significantly...CHEM (rigid flat-plate). 104 Figure 5.3: Geometry used for blast wave interacting with a cylinder (Ofengeim and Drikakis 1997). 105 Figure 5.4: CFD...their effects on vehicles and their human occupants. The framework couples the MPMICE CFD code with DYNA3D and LS-DYNA finite element codes

  17. Design of the randomized, Phase III, QUAZAR AML Maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia. (United States)

    Roboz, Gail J; Montesinos, Pau; Selleslag, Dominik; Wei, Andrew; Jang, Jun-Ho; Falantes, Jose; Voso, Maria T; Sayar, Hamid; Porkka, Kimmo; Marlton, Paula; Almeida, Antonio; Mohan, Sanjay; Ravandi, Farhad; Garcia-Manero, Guillermo; Skikne, Barry; Kantarjian, Hagop


    Older patients with acute myeloid leukemia (AML) have worse rates of complete remission and shorter overall survival than younger patients. The epigenetic modifier CC-486 is an oral formulation of azacitidine with promising clinical activity in patients with AML in Phase I studies. The Phase III, randomized, double-blind, placebo-controlled QUAZAR AML Maintenance trial (CC-486-AML-001) examines CC-486 maintenance therapy (300 mg/day for 14 days of 28-day treatment cycles) for patients aged ≥55 years with AML in first complete remission. The primary end point is overall survival. Secondary end points include relapse-free survival, safety, health-related quality of life and healthcare resource utilization. This trial will investigate whether CC-486 maintenance can prolong remission and improve survival for older patients with AML.

  18. Blast-Induced Acceleration in a Shock Tube: Distinguishing Primary and Tertiary Blast Injury (United States)


    injury conditions (blast and acceleration vs acceleration alone) undergo neurobehavioral and histopathological assessments to comprehensively... reversal . To facilitate mid-air blasts, a release mechanism was devised. Balls were attached to the bail of the mechanism. The blast wave would cause

  19. CrocoBLAST: Running BLAST efficiently in the age of next-generation sequencing. (United States)

    Tristão Ramos, Ravi José; de Azevedo Martins, Allan Cézar; da Silva Delgado, Gabrielle; Ionescu, Crina-Maria; Ürményi, Turán Peter; Silva, Rosane; Koca, Jaroslav


    CrocoBLAST is a tool for dramatically speeding up BLAST+ execution on any computer. Alignments that would take days or weeks with NCBI BLAST+ can be run overnight with CrocoBLAST. Additionally, CrocoBLAST provides features critical for NGS data analysis, including: results identical to those of BLAST+; compatibility with any BLAST+ version; real-time information regarding calculation progress and remaining run time; access to partial alignment results; queueing, pausing, and resuming BLAST+ calculations without information loss. CrocoBLAST is freely available online, with ample documentation ( No installation or user registration is required. CrocoBLAST is implemented in C, while the graphical user interface is implemented in Java. CrocoBLAST is supported under Linux and Windows, and can be run under Mac OS X in a Linux virtual machine. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:

  20. Pressurized grout remote backfilling at AML sites near Beulah and Zap, North Dakota

    International Nuclear Information System (INIS)

    Weiner, E.J.; Dodd, W.E.


    The Abandoned Mine Lands (AML) Division of the North Dakota Public Service Commission (PSC) is charged with the reclamation of hazardous abandoned mine sites in North Dakota. Several underground lignite coalmines were operated near the cities of Beulah and Zap, North Dakota, from the early 1900's until about 1955. Coal seams in this area were relatively thick and the overburden generally shallow. As these mines have deteriorated with time, deep collapse features, or sinkholes, have surfaced in many areas. These features are very dangerous, especially when they occur at or near residential and commercial areas and public roads. In the past five years, sinkholes have surfaced beneath a commercial building (boat dealership, lounge, and gas station) and beneath a nearby occupied mobile home north of Beulah. sinkholes have also surfaced near KHOL Radio Station in Beulah and in the right of way of a public road south of Zap. The AML Division has conducted several emergency sinkhole-filling projects in these areas. In 1995--97, the AML Division conducted exploratory drilling which confirmed the presence of collapsing underground mines at these sites. The remediation of these sites around Beulah/Zap will take place over several years and involve three or more separate contracts due to budget considerations. In 1997, the AML Division began reclamation at these sties utilizing pressurized grout remote backfilling. In this technique, a cementitious grout is pumped through cased drill holes directly into the mine cavities to fill them and thereby stabilize the surface from collapse. The successful contractor for Phase One of the project was The Concrete Doctor, Inc. (TCDI). This paper will concentrate on Phase One of this work performed from June through September 1997. This project is especially interesting because grout was pumped through holes drilled inside the occupied commercial building. Grout was also pumped through angled holes that intercepted mined workings directly

  1. Pressurized grout remote backfilling at AML sites near Beulah and Zap, North Dakota

    Energy Technology Data Exchange (ETDEWEB)

    Weiner, E.J.; Dodd, W.E.


    The Abandoned Mine Lands (AML) Division of the North Dakota Public Service Commission (PSC) is charged with the reclamation of hazardous abandoned mine sites in North Dakota. Several underground lignite coalmines were operated near the cities of Beulah and Zap, North Dakota, from the early 1900's until about 1955. Coal seams in this area were relatively thick and the overburden generally shallow. As these mines have deteriorated with time, deep collapse features, or sinkholes, have surfaced in many areas. These features are very dangerous, especially when they occur at or near residential and commercial areas and public roads. In the past five years, sinkholes have surfaced beneath a commercial building (boat dealership, lounge, and gas station) and beneath a nearby occupied mobile home north of Beulah. sinkholes have also surfaced near KHOL Radio Station in Beulah and in the right of way of a public road south of Zap. The AML Division has conducted several emergency sinkhole-filling projects in these areas. In 1995--97, the AML Division conducted exploratory drilling which confirmed the presence of collapsing underground mines at these sites. The remediation of these sites around Beulah/Zap will take place over several years and involve three or more separate contracts due to budget considerations. In 1997, the AML Division began reclamation at these sties utilizing pressurized grout remote backfilling. In this technique, a cementitious grout is pumped through cased drill holes directly into the mine cavities to fill them and thereby stabilize the surface from collapse. The successful contractor for Phase One of the project was The Concrete Doctor, Inc. (TCDI). This paper will concentrate on Phase One of this work performed from June through September 1997. This project is especially interesting because grout was pumped through holes drilled inside the occupied commercial building. Grout was also pumped through angled holes that intercepted mined workings

  2. Tumor Lysis Syndrome (TLS following intrathecal chemotherapy in a child with acute myelogenous leukemia (AML

    Directory of Open Access Journals (Sweden)

    Chana L. Glasser, MD


    Full Text Available Tumor Lysis Syndrome (TLS is a well-known complication of induction therapy for hematologic malignancies. It is characterized by rapid breakdown of malignant white blood cells (WBCs leading to metabolic derangements and serious morbidity if left untreated. Most commonly, TLS is triggered by systemic chemotherapy, however, there have been case reports of TLS following intrathecal (IT chemotherapy, all in patients with acute lymphoblastic leukemia (ALL/lymphoma. Here, we report the first case of a patient with acute myelogenous leukemia (AML who developed TLS following a single dose of IT cytosine arabinoside (Ara-C.

  3. Sequential Use of Second-Generation Tyrosine Kinase Inhibitor Treatment and Intensive Chemotherapy Induced Long-Term Complete Molecular Response in Imatinib-Resistant CML Patient Presenting as a Myeloid Blast Crisis

    Directory of Open Access Journals (Sweden)

    Masaaki Tsuji


    Full Text Available Myeloid blast crisis of chronic myeloid leukemia (CML-MBC is rarely seen at presentation and has a poor prognosis. There is no standard therapy for CML-MBC. It is often difficult to distinguish CML-MBC from acute myeloid leukemia expressing the Philadelphia chromosome (Ph+ AML. We present a case in which CML-MBC was seen at the initial presentation in a 75-year-old male. He was treated with conventional AML-directed chemotherapy followed by imatinib mesylate monotherapy, which failed to induce response. However, he achieved long-term complete molecular response after combination therapy involving dasatinib, a second-generation tyrosine kinase inhibitor, and conventional chemotherapy.

  4. Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    KAUST Repository

    Aldehaiman, Mansour M.


    Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature nonfunctional highly proliferative hematopoietic cells in the blood, due to a blockage in myeloid differentiation at various stages. Since the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell (LSC). CD44 is a cell surface receptor that is over-expressed on AML cells. When bound to anti-CD44 monoclonal antibodies (mAbs), this differentiation block is relieved in AML cells and their proliferation is reduced. The molecular mechanisms that AML cells undergo to achieve this reversal of their apparent phenotype is not fully understood. To this end, we designed a study using quantitative phosphoproteomics approaches aimed at identifying differences in phosphorylation found on proteins involved in signaling pathways post-treatment with CD44-mAbs. The Rho family of GTPases emerged as one of the most transformed pathways following the treatment with CD44-mAbs. The P21 activated kinase 2(PAK2), a target of the Rho family of GTPases, was found to be differentially phosphorylated in AML cells post-treatment with CD44-mAbs. This protein has been found to possess a role similar to that of a switch that determines whether the cell survives or undergoes apoptosis. Beyond confirming these results by various biochemical approaches, our study aimed to determine the effect of knock down of PAK2 on AML cell proliferation and differentiation. In addition, over-expression of PAK2 mutants using plasmid cloning was also explored to fully understand how levels of PAK2 as well as the alteration of specific phospohorylation sites could alter AML cell responses to CD44-mAbs. Results from this study will be important in determining whether PAK2 could be used as a potential therapeutic target

  5. Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study. (United States)

    Steensma, David P; Abedi, Medrdad; Bejar, Rafael; Cogle, Christopher R; Foucar, Kathryn; Garcia-Manero, Guillermo; George, Tracy I; Grinblatt, David; Komrokji, Rami; Ma, Xiaomei; Maciejewski, Jaroslaw; Pollyea, Daniel A; Savona, Michael R; Scott, Bart; Sekeres, Mikkael A; Thompson, Michael A; Swern, Arlene S; Nifenecker, Melissa; Sugrue, Mary M; Erba, Harry


    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are myeloid neoplasms in which outgrowth of neoplastic clones disrupts normal hematopoiesis. Some patients with unexplained persistent cytopenias may not meet minimal diagnostic criteria for MDS but an alternate diagnosis is not apparent; the term idiopathic cytopenia of undetermined significance (ICUS) has been used to describe this state. MDS and AML occur primarily in older patients who are often treated outside the clinical trial setting. Consequently, our understanding of the patterns of diagnostic evaluation, management, and outcomes of these patients is limited. Furthermore, there are few natural history studies of ICUS. To better understand how patients who have MDS, ICUS, or AML are managed in the routine clinical setting, the Connect MDS/AML Disease Registry, a multicenter, prospective, observational cohort study of patients newly diagnosed with these conditions has been initiated. The Connect MDS/AML Disease Registry will capture diagnosis, risk assessment, treatment, and outcomes data for approximately 1500 newly diagnosed patients from approximately 150 community and academic sites in the United States in 4 cohorts: (1) lower-risk MDS (International Prognostic Scoring System [IPSS] low and intermediate-1 risk), with and without del(5q); (2) higher-risk MDS (IPSS intermediate-2 and high risk); (3) ICUS; and (4) AML in patients aged ≥ 55 years (excluding acute promyelocytic leukemia). Diagnosis will be confirmed by central review. Baseline patient characteristics, diagnostic patterns, treatment patterns, clinical outcomes, health economics outcomes, and patient-reported health-related quality of life will be entered into an electronic data capture system at enrollment and quarterly for 8 years. A tissue substudy to explore the relationship between karyotypes, molecular markers, and clinical outcomes will be conducted, and is optional for patients. The Connect MDS/AML Disease


    International Nuclear Information System (INIS)

    McPhee, William S.


    The Department of Energy (DOE) needs improved technologies to decontaminate large areas of both concrete and steel surfaces. The technology should have high operational efficiency, minimize exposures to workers, and produce low levels of secondary waste. In order to meet the DOE's needs, an applied research and development project for the improvement of a current decontamination technology, Vacuum Blasting, is proposed. The objective of this project is to improve the productivity and lower the expense of the existing vacuum blasting technology which has been widely used in DOE sites for removing radioactive contamination, PCBs, and lead-based paint. The proposed work would increase the productivity rate and provide safe and cost-effective decontamination of the DOE sites

  7. Alkaline carbonates in blast furnace process

    Directory of Open Access Journals (Sweden)

    P. Besta


    Full Text Available The production of iron in blast furnaces is a complex of physical, chemical and mechanical processes. The input raw materials contain not only metallic components, but also a number of negative elements. The most important negative elements include alkaline carbonates. They can significantly affect the course of the blast furnace process and thus the overall performance of the furnace. As a result of that, it is essential to accurately monitor the alkali content in the blast furnace raw materials. The article analyzes the alkali content in input and output raw materials and their impact on the blast furnace process.

  8. RUNX1/AML1 point mutations take part in the pathogenesis of radiation-and therapy-related myeloid neoplasms

    International Nuclear Information System (INIS)

    Harada, Yuka; Kimura, Akiro; Harada, Hironori


    High frequency of myelodysplastic syndrome (MDS) has been reported in Hiroshima A-bomb exposed survivors, in resident around Semipalatinsk Nuclear Laboratory and in exposed people by Chernobyl Nuclear Power Station Accident. MDS/acute myeloid leukemia (AML) is thought to be caused by mutation of runt-related transcription factor 1 (RUNX1) gene after a long time post exposure to relatively low dose radiation. In this study, participation of RUNX1/AML1 point mutations was examined in pathogenesis of the title neoplasms experienced in authors' facility. Subjects were 18/417 cases in whom myeloproliferative neoplasms (MPN) had switched to MDS or AML in the follow-up period of 1-25 years, and 11/124 cases in whom t-MN (therapy-related myeloid neoplasms) had developed during the remission of acute promyelocytic leukemia (APL) in the 1-9.7 years follow up. Point mutations were analyzed by PCR-single strand conformation polymorphism (PCR-SSCP) followed by base sequencing. In the former cases above, RUNX1 point mutation was found in 5/18 cases and in the latter, 4/11. When patients with persistent decrease of blood cells post therapy of APL were followed up for mutation, their RUNX1 point mutation was detected before they were diagnosed to be morbid of MDS/AML. The point mutation was thus a biomarker of myelo-hematogenic cancer, and was thought useful for early diagnosis of MDS and AML. (T.T.)

  9. Design and kinetic analysis of hammerhead ribozyme and DNAzyme that specifically cleave TEL-AML1 chimeric mRNA

    International Nuclear Information System (INIS)

    Choi, Woo-Hyung; Choi, Bo-Ra; Kim, Jae Hyun; Yeo, Woon-Seok; Oh, Sangtaek; Kim, Dong-Eun


    In order to develop the oligonucleotides to abolish an expression of TEL-AML1 chimeric RNA, which is a genetic aberration that causes the acute lymphoblastic leukemia (ALL), hammerhead ribozymes and deoxyoligoribozymes that can specifically cleave TEL-AML1 fusion RNA were designed. Constructs of the deoxyribozyme with an asymmetric substrate binding arm (Dz26) and the hammerhead ribozyme with a 4 nt-bulged substrate binding arm in the stem III (buRz28) were able to cleave TEL-AML1 chimeric RNA specifically at sites close to the junction in vitro, without cleaving the normal TEL and AML1 RNA. Single-turnover kinetic analysis under enzyme-excess condition revealed that the buRz28 is superior to the Dz26 in terms of substrate binding and RNA-cleavage. In conjunction with current progress in a gene-delivery technology, the designed oligonucleotides that specifically cleave the TEL-AML1 chimeric mRNA are hoped to be applicable for the treatment of ALL in vivo

  10. Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission

    Directory of Open Access Journals (Sweden)

    Merk Martina


    Full Text Available Abstract Background Active dendritic cell (DC immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML. Here we present for the first time a GMP-compliant 3-day protocol for generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR agonists in intensively pretreated patients with AML. Methods Four different maturation cocktails were compared for their impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation in 20 AML patients and 25 healthy controls. Results Maturation cocktails containing the TLR7/8 agonists R848 or CL075, with and without the addition of the TLR3 agonist poly(I:C, induced DCs that had a positive costimulatory profile, secreted high levels of IL-12(p70, showed chemotaxis to CCR7 ligands, had the ability to activate NK cells, and efficiently stimulated antigen-specific CD8+ T cells. Conclusions Our results demonstrate that this approach translates into biologically improved DCs, not only in healthy controls but also in AML patients. This data supports the clinical application of TLR-matured DCs in patients with AML for activation of innate and adaptive immune responses.

  11. Interspecies Scaling in Blast Neurotrauma (United States)


    and services to assist recovery . Santa Monica, CA: Rand Corporation. Taylor, PA and Ford, CC. 2009. "Simulation of Blast-Induced Early-Time...reducing this burden, to Washington Headquarters Services , Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite... Warden 2006). As of 2008 it was estimated that approximately 19% or 320,000 OIF/OEF veterans had sustained a TBI (Tanielian et al. 2008). In 2011 a

  12. Water in blast holes can improve blasting efficiency and cut costs

    Energy Technology Data Exchange (ETDEWEB)

    O' Regan, G.


    Water in blast holes has been a traditional problem faced by blasting engineers and foremen in surface mining. Presently accepted techniques for blasting in water-filled holes include the use of more expensive water-gel explosives which are denser than water, dewatering of holes by pumping, and blowing out the water with a small charge before loading the main ANFO charge column. These methods involve considerable expense and delay to the normal charge-loading procedure. The author describes a method of using the water in blast holes to improve blasting efficiency and reduce the consumption of explosive.

  13. Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate. (United States)

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


    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.

  14. Development of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Eduardo Laborda


    Full Text Available The treatment of patients with acute myeloid leukemia (AML with targeted immunotherapy is challenged by the heterogeneity of the disease and a lack of tumor-exclusive antigens. Conventional immunotherapy targets for AML such as CD33 and CD123 have been proposed as targets for chimeric antigen receptor (CAR-engineered T-cells (CAR-T-cells, a therapy that has been highly successful in the treatment of B-cell leukemia and lymphoma. However, CD33 and CD123 are present on hematopoietic stem cells, and targeting with CAR-T-cells has the potential to elicit long-term myelosuppression. C-type lectin-like molecule-1 (CLL1 or CLEC12A is a myeloid lineage antigen that is expressed by malignant cells in more than 90% of AML patients. CLL1 is not expressed by healthy Hematopoietic Stem Cells (HSCs, and is therefore a promising target for CAR-T-cell therapy. Here, we describe the development and optimization of an anti-CLL1 CAR-T-cell with potent activity on both AML cell lines and primary patient-derived AML blasts in vitro while sparing healthy HSCs. Furthermore, in a disseminated mouse xenograft model using the CLL1-positive HL60 cell line, these CAR-T-cells completely eradicated tumor, thus supporting CLL1 as a promising target for CAR-T-cells to treat AML while limiting myelosuppressive toxicity.

  15. Cellular intrinsic mechanism affecting the outcome of AML treated with Ara-C in a syngeneic mouse model.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhao

    Full Text Available The mechanisms underlying acute myeloid leukemia (AML treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C.

  16. An AML1-ETO/miR-29b-1 regulatory circuit modulates phenotypic properties of acute myeloid leukemia cells. (United States)

    Zaidi, Sayyed K; Perez, Andrew W; White, Elizabeth S; Lian, Jane B; Stein, Janet L; Stein, Gary S


    Acute myeloid leukemia (AML) is characterized by an aggressive clinical course and frequent cytogenetic abnormalities that include specific chromosomal translocations. The 8;21 chromosomal rearrangement disrupts the key hematopoietic RUNX1 transcription factor, and contributes to leukemia through recruitment of co-repressor complexes to RUNX1 target genes, altered subnuclear localization, and deregulation of the myeloid gene regulatory program. However, a role of non-coding microRNAs (miRs) in t(8;21)-mediated leukemogenesis is minimally understood. We present evidence of an interplay between the tumor suppressor miR-29b-1 and the AML1-ETO (also designated RUNX1-RUNX1T1) oncogene that is encoded by the t(8;21). We find that AML1-ETO and corepressor NCoR co-occupy the miR-29a/b-1 locus and downregulate its expression in leukemia cells. Conversely, re-introduction of miR-29b-1 in leukemia cells expressing AML1-ETO causes significant downregulation at the protein level through direct targeting of the 3' untranslated region of the chimeric transcript. Restoration of miR-29b-1 expression in leukemia cells results in decreased cell growth and increased apoptosis. The AML1-ETO-dependent differentiation block and transcriptional program are partially reversed by miR-29b-1. Our findings establish a novel regulatory circuit between the tumor-suppressive miR-29b-1 and the oncogenic AML1-ETO that controls the leukemic phenotype in t(8;21)-carrying acute myeloid leukemia.

  17. The use of blast furnace slag

    Directory of Open Access Journals (Sweden)

    V. Václavík


    Full Text Available The paper presents the results of experimental research that dealt with the substitution of finely ground blast furnace slag for Portland cement in the course of simple concrete manufacturing. Physical and mechanical properties of experimental concrete mixtures based on finely ground blast furnace slag were observed.

  18. Blast mitigation experimental and numerical studies

    CERN Document Server


    Presents experimental methods of material and structural response to dynamic blast loads Includes computational analysis of material and structural response to dynamic blast loads Offers mitigation measures for structures in various environments Relates lab experiments to larger field tests Features more than 150 illustrations

  19. Blast resistance behaviour of steel frame structrures

    NARCIS (Netherlands)

    Mediavilla Varas, J.; Soetens, F.


    The effect of a blast explosion on a typical steel frame building is investigated by means of computer simulations. The simulations help to identify possible hot spots that may lead to local or global failure. Since the blast energy is transferred to the structure by means of the façade, it is

  20. Blast resistance behaviour of steel frame structures

    NARCIS (Netherlands)

    Varas, J.M.; Soetens, F.


    The effect of a blast explosion on a typical steel frame building is investigated by means of computer simulations. The simulations help to identify possible hot spots that may lead to local or global failure. The blast energy is transferred to the structure by means of the façade. In particular

  1. 30 CFR 56.6312 - Secondary blasting. (United States)


    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Explosives Use § 56.6312 Secondary blasting. Secondary blasts fired at the same time in the same work area shall be initiated from...

  2. Co-culture with podoplanin+ cells protects leukemic blast cells with leukemia-associated antigens in the tumor microenvironment. (United States)

    Lee, Ji Yoon; Han, A-Reum; Lee, Sung-Eun; Min, Woo-Sung; Kim, Hee-Je


    Podoplanin+ cells are indispensable in the tumor microenvironment. Increasing evidence suggests that podoplanin may support the growth and metastasis of solid tumors; however, to the best of our knowledge no studies have determined whether or not podoplanin serves a supportive role in acute myeloid leukemia (AML). The effects of co‑culture with podoplanin+ cells on the cellular activities of the leukemic cells, such as apoptosis and cell proliferation, in addition to the expression of podoplanin in leukemic cells, were investigated. Due to the fact that genetic abnormalities are the primary cause of leukemogenesis, the overexpression of the fibromyalgia‑like tyrosine kinase‑3 gene in colony forming units was also examined following cell sorting. Podoplanin+ cells were found to play a protective role against apoptosis in leukemic cells and to promote cell proliferation. Tumor‑associated antigens, including Wilms' tumor gene 1 and survivin, were increased when leukemic cells were co‑cultured with podoplanin+ cells. In combination, the present results also suggest that podoplanin+ cells can function as stromal cells for blast cell retention in the AML tumor microenvironment.

  3. Condition for Contur Blasting use on Openpit Mines


    Krsmanovic, I; Dambov, Risto


    For purpose of obtaining a stable final slope in open pit mines practice, the most common approach is the contour blasting method and investigation of possible applications of various primary blasting methods for purpose of gaining the optimal techno-economical effects. This paper presents one of the contour blasting methods, drilling and blasting parameters, construction of explosive charges and method of initiation.

  4. 30 CFR 780.13 - Operation plan: Blasting. (United States)


    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Operation plan: Blasting. 780.13 Section 780.13... SURFACE MINING PERMIT APPLICATIONS-MINIMUM REQUIREMENTS FOR RECLAMATION AND OPERATION PLAN § 780.13 Operation plan: Blasting. (a) Blasting plan. Each application shall contain a blasting plan for the proposed...

  5. Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Glosli, Heidi; Jahnukainen, Kirsi


    BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society...

  6. The impact of TEL-AML1 (ETV6-RUNX1) expression in precursor B cells and implications for leukaemia using three different genome-wide screening methods

    International Nuclear Information System (INIS)

    Linka, Y; Ginzel, S; Krüger, M; Novosel, A; Gombert, M; Kremmer, E; Harbott, J; Thiele, R; Borkhardt, A; Landgraf, P


    The reciprocal translocation t(12;21)(p13;q22), the most common structural genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children, results in a chimeric transcription factor TEL-AML1 (ETV6-RUNX1). We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture, we identified 217 directly and 118 indirectly regulated targets of the TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were enriched in AML1-binding sites. The majority of promoter regions were specific for the fusion protein and not bound by native AML1 or TEL. Comparison with gene expression profiles from TEL-AML1-positive patients identified 56 concordantly misregulated genes with negative effects on proliferation and cellular transport mechanisms and positive effects on cellular migration, and stress responses including immunological responses. In summary, this work for the first time gives a comprehensive insight into how TEL-AML1 expression may directly and indirectly contribute to alter cells to become prone for leukemic transformation

  7. Anorectal injury in pelvic blast. (United States)

    Brogden, Tom G; Garner, J P


    The signature injury of the Afghanistan campaign has, amongst other things, included an increased incidence of destructive anorectal injury. There is no significant body of evidence about this type of injury on which to base management strategies. This review examines the historical military data, later civilian reports, many of which have challenged the military dogmas of Vietnam, and the spartan contemporaneous military data which does not particularly address pelviperineal blast injury. There is no evidence to support a move away from the doctrine of the four D's (diversion, distal washout, drainage and direct repair), but sound surgical judgement remains the mainstay of managing these challenging and highly morbid injuries.

  8. Human Injury Criteria for Underwater Blasts (United States)


    further underscored the need for this new guideline based on injury data. Conference Name: Personal Armour Systems Symposium Conference Date...29.  Cole, R., Underwater Explosion. (Dover Publications, Inc ., New York, N.Y., 1948) 30.  Nakahara, M., Nagayama, K, Mori, Y, Japanese Journal...Abstract of the Undersea and Hyperbaric Medical Society, Inc . Annual Scientific Meeting, (1976).

  9. The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells. (United States)

    Matsumura, I; Kanakura, Y; Kato, T; Ikeda, H; Horikawa, Y; Ishikawa, J; Kitayama, H; Nishiura, T; Tomiyama, Y; Miyazaki, H; Matsuzawa, Y


    Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.

  10. ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia

    NARCIS (Netherlands)

    Martens, Joost H. A.; Mandoli, Amit; Simmer, Femke; Wierenga, Bart-Jan; Saeed, Sadia; Singh, Abhishek A.; Altucci, Lucia; Vellenga, Edo; Stunnenberg, Hendrik G.


    ERG and FLI1 are closely related members of the ETS family of transcription factors and have been identified as essential factors for the function and maintenance of normal hematopoietic stem cells. Here genome-wide analysis revealed that both ERG and FLI1 occupy similar genomic regions as AML1-ETO

  11. Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

    KAUST Repository

    Aldehaiman, Mansour M.


    the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell

  12. Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation

    NARCIS (Netherlands)

    Radivoyevitch, T.; Sachs, R. K.; Gale, R. P.; Molenaar, R. J.; Brenner, D. J.; Hill, B. T.; Kalaycio, M. E.; Carraway, H. E.; Mukherjee, S.; Sekeres, M. A.; Maciejewski, J. P.


    Risks of acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) are known to increase after cancer treatments. Their rise-and-fall dynamics and their associations with radiation have, however, not been fully characterized. To improve risk definition we developed SEERaBomb R software for

  13. LTC vacuum blasting machine (concrete): Baseline report

    International Nuclear Information System (INIS)


    The LTC shot blast technology was tested and is being evaluated at Florida International University (FIU) as a baseline technology. In conjunction with FIU's evaluation of efficiency and cost, this report covers the evaluation conducted for safety and health issues. It is a commercially available technology and has been used for various projects at locations throughout the country. The LTC 1073 Vacuum Blasting Machine uses a high-capacity, direct-pressure blasting system which incorporates a continuous feed for the blast media. The blast media cleans the surface within the contained brush area of the blast. It incorporates a vacuum system which removes dust and debris from the surface as it is blasted. The safety and health evaluation during the testing demonstration focused on two main areas of exposure: dust and noise. Dust exposure during maintenance activities was minimal, but due to mechanical difficulties dust monitoring could not be conducted during operation. Noise exposure was significant. Further testing for each of these exposures is recommended because of the outdoor environment where the testing demonstration took place. This may cause the results to be inaccurate. It is feasible that the dust and noise levels will be higher in an enclosed environment. In addition, other safety and health issues found were ergonomics, heat stress, tripping hazards, electrical hazards, lockout/tagout, and arm-hand vibration

  14. Analysis of the Blasting Effect on the Environment around Blasting Areas at Pt. Semen Baturaja Persero, Tbk.

    Directory of Open Access Journals (Sweden)

    Jihan Farhan Lubis


    Full Text Available • Semen Baturaja Persero, Tbk is one of the companies engaged in the production of cement that takes raw materials through limestone mining process located in Baturaja City, OKU Regency, South Sumatera Province. Limestone mining activities use blasting activity that produces blasting effects and flyrock. Measurements of vibration and flyrock frequencies obtained a maximum value for vibration of 4.66 mm/s and predicted farthest distance of flyrock above 170 m when powder factor exceeds 0.1 kg/m3. The results of the data show that the level of emission has exceeded the standard limits for second class buildings (3 mm/s based on (SNI 7571: 2010. Blasting just 175-300 m from the nearest settlement and already exceed the save distance for equipment 300m and 500m for human activity based on USBM (United States Bureau of Mines. To reduce the vibration level, the maximum number of mass per delay is 43 kg/delay with PPV parameter 3 mm/s at 170m distance. Actual factor powder should not exceed 0.1 kg / m3 to minimize flyovers in safe zones not exceeding 150 m.

  15. Primary blast survival and injury risk assessment for repeated blast exposures. (United States)

    Panzer, Matthew B; Bass, Cameron R Dale; Rafaels, Karin A; Shridharani, Jay; Capehart, Bruce P


    The widespread use of explosives by modern insurgents and terrorists has increased the potential frequency of blast exposure in soldiers and civilians. This growing threat highlights the importance of understanding and evaluating blast injury risk and the increase of injury risk from exposure to repeated blast effects. Data from more than 3,250 large animal experiments were collected from studies focusing on the effects of blast exposure. The current study uses 2,349 experiments from the data collection for analysis of the primary blast injury and survival risk for both long- and short-duration blasts, including the effects from repeated exposures. A piecewise linear logistic regression was performed on the data to develop survival and injury risk assessment curves. New injury risk assessment curves uniting long- and short-duration blasts were developed for incident and reflected pressure measures and were used to evaluate the risk of injury based on blast over pressure, positive-phase duration, and the number of repeated exposures. The risk assessments were derived for three levels of injury severity: nonauditory, pulmonary, and fatality. The analysis showed a marked initial decrease in injury tolerance with each subsequent blast exposure. This effect decreases with increasing number of blast exposures. The new injury risk functions showed good agreement with the existing experimental data and provided a simplified model for primary blast injury risk. This model can be used to predict blast injury or fatality risk for single exposure and repeated exposure cases and has application in modern combat scenarios or in setting occupational health limits. .Copyright © 2012 by Lippincott Williams & Wilkins

  16. Exposure to a predator scent induces chronic behavioral changes in rats previously exposed to low-level blast: Implications for the relationship of blast-related TBI to PTSD

    Directory of Open Access Journals (Sweden)

    Georgina Perez-Garcia


    Full Text Available Blast-related mild traumatic brain injury (mTBI has been unfortunately common in veterans who served in the recent conflicts in Iraq and Afghanistan. The postconcussion syndrome associated with these mTBIs has frequently appeared in combination with post-traumatic stress disorder (PTSD. The presence of PTSD has complicated diagnosis since clinically PTSD and the postconcussion syndrome of mTBI have many overlapping symptoms. In particular establishing how much of the symptom complex can be attributed to the psychological trauma associated with PTSD in contrast to the physical injury of TBI has proven difficult. Indeed some have suggested that much of what is now being called blast-related postconcussion syndrome is better explained by PTSD. The relationship between the postconcussion syndrome of mTBI and PTSD is complex. Association of the two disorders might be viewed as additive effects of independent psychological and physical traumas suffered in a war zone. However we previously found that rats exposed to repetitive low-level blast exposure in the absence of a psychological stressor developed a variety of anxiety and PTSD-related behavioral traits that were present months following the last blast exposure. Here we show that a single predator scent challenge delivered 8 months after the last blast exposure induces chronic anxiety related changes in blast-exposed rats that are still present 45 days later. These observations suggest that in addition to independently inducing PTSD-related traits, blast exposure sensitizes the brain to react abnormally to a subsequent psychological stressor. These studies have implications for conceptualizing the relationship between blast-related mTBI and PTSD and suggest that blast-related mTBI in humans may predispose to the later development of PTSD in reaction to subsequent psychological stressors.

  17. A Blast Wave Model With Viscous Corrections (United States)

    Yang, Z.; Fries, R. J.


    Hadronic observables in the final stage of heavy ion collision can be described well by fluid dynamics or blast wave parameterizations. We improve existing blast wave models by adding shear viscous corrections to the particle distributions in the Navier-Stokes approximation. The specific shear viscosity η/s of a hadron gas at the freeze-out temperature is a new parameter in this model. We extract the blast wave parameters with viscous corrections from experimental data which leads to constraints on the specific shear viscosity at kinetic freeze-out. Preliminary results show η/s is rather small.

  18. Behavior of coke in large blast furnaces

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, N


    Three blast furnaces were quenched in operation and the contents were examined; the temperature distribution was also measured, using Tempil pellets. The furnaces examined included a low productivity one, which was examined to see what was wrong. Changes in the quality of coke as it descends in the furnace, and coke behavior in the raceway and hearth are reported. The functions required of coke, and the effects of poor coke quality, are explained, together with the coke quality required in large blast furnaces. A theoretical study of the role of coke in large blast furnaces is included.

  19. A Blast Wave Model With Viscous Corrections

    International Nuclear Information System (INIS)

    Yang, Z; Fries, R J


    Hadronic observables in the final stage of heavy ion collision can be described well by fluid dynamics or blast wave parameterizations. We improve existing blast wave models by adding shear viscous corrections to the particle distributions in the Navier-Stokes approximation. The specific shear viscosity η/s of a hadron gas at the freeze-out temperature is a new parameter in this model. We extract the blast wave parameters with viscous corrections from experimental data which leads to constraints on the specific shear viscosity at kinetic freeze-out. Preliminary results show η/s is rather small. (paper)

  20. Blast casting requires fresh assessment of methods

    Energy Technology Data Exchange (ETDEWEB)

    Pilshaw, S.R.


    The article discusses the reasons why conventional blasting operations, mainly that of explosive products, drilling and initiation methods are inefficient, and suggests new methods and materials to overcome the problems of the conventional operations. The author suggests that the use of bulk ANFO for casting, instead of high energy and density explosives with high velocity detonation is more effective in producing heave action results. Similarly the drilling of smaller blast holes than is conventional allows better loading distribution of explosives in the rock mass. The author also suggests that casting would be more efficient if the shot rows were loaded differently to produce a variable burden blasting pattern.

  1. The peripheral cannabinoid receptor Cb2, frequently expressed on AML blasts, either induces a neutrophilic differentiation block or confers abnormal migration properties in a ligand-dependent manner

    NARCIS (Netherlands)

    M. Alberich-Jorda (Meritxell); N. Rayman (Nazik); M. Tas (Marjolein); S.E. Verbakel (Sandra); N. Battista (Natalia); K. van Lom (Kirsten); B. Löwenberg (Bob); M. Maccarrone (Mauro); H.R. Delwel (Ruud)


    textabstractCb2, the gene encoding the peripheral cannabinoid receptor, is located in a common virus integration site and is overex-pressed in retrovirally induced murine myeloid leukemias. Here we show that this G protein-coupled receptor (GPCR) is also aberrantly expressed in a

  2. Biology and relevance of human acute myeloid leukemia stem cells. (United States)

    Thomas, Daniel; Majeti, Ravindra


    Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research. © 2017 by The American Society of Hematology.

  3. Ibrutinib synergizes with poly(ADP-ribose) glycohydrolase inhibitors to induce cell death in AML cells via a BTK-independent mechanism. (United States)

    Rotin, Lianne E; Gronda, Marcela; MacLean, Neil; Hurren, Rose; Wang, XiaoMing; Lin, Feng-Hsu; Wrana, Jeff; Datti, Alessandro; Barber, Dwayne L; Minden, Mark D; Slassi, Malik; Schimmer, Aaron D


    Targeting Bruton's tyrosine kinase (BTK) with the small molecule BTK inhibitor ibrutinib has significantly improved patient outcomes in several B-cell malignancies, with minimal toxicity. Given the reported expression and constitutive activation of BTK in acute myeloid leukemia (AML) cells, there has been recent interest in investigating the anti-AML activity of ibrutinib. We noted that ibrutinib had limited single-agent toxicity in a panel of AML cell lines and primary AML samples, and therefore sought to identify ibrutinib-sensitizing drugs. Using a high-throughput combination chemical screen, we identified that the poly(ADP-ribose) glycohydrolase (PARG) inhibitor ethacridine lactate synergized with ibrutinib in TEX and OCI-AML2 leukemia cell lines. The combination of ibrutinib and ethacridine induced a synergistic increase in reactive oxygen species that was functionally important to explain the observed cell death. Interestingly, synergistic cytotoxicity of ibrutinib and ethacridine was independent of the inhibitory effect of ibrutinib against BTK, as knockdown of BTK did not sensitize TEX and OCI-AML2 cells to ethacridine treatment. Thus, our findings indicate that ibrutinib may have a BTK-independent role in AML and that PARG inhibitors may have utility as part of a combination therapy for this disease.

  4. Blast Mitigation Using Water - A Status Report

    National Research Council Canada - National Science Library

    Kailasanath, K


    ..., and aggressive research and development', this report reviews the current knowledge base on blast mitigation using water and identifies the key issues that need to be resolved in order to develop...

  5. International blast furnace hearth and raceway symposium

    Energy Technology Data Exchange (ETDEWEB)


    Papers presented discussed some of the physical and chemical processes occuring in the raceway and hearths of blast furnaces. The injection of coal or fuel slurries to replace some of the coke was also covered. Fourteen papers are abstracted separately.

  6. A Software Framework for Blast Event Simulation

    National Research Council Canada - National Science Library

    Swensen, D. A; Denison, M. K; Guilkey, James; Harman, Todd; Goetz, Richard


    .... The BCF will provide a virtual test-bed where disparate computational models can seamlessly interact with one another to provide a unified modeling solution for blast-vehicle-occupant scenarios...

  7. Bomb blast imaging: bringing order to chaos. (United States)

    Dick, E A; Ballard, M; Alwan-Walker, H; Kashef, E; Batrick, N; Hettiaratchy, S; Moran, C G


    Blast injuries are complex, severe, and outside of our everyday clinical practice, but every radiologist needs to understand them. By their nature, bomb blasts are unpredictable and affect multiple victims, yet require an immediate, coordinated, and whole-hearted response from all members of the clinical team, including all radiology staff. This article will help you gain the requisite expertise in blast imaging including recognising primary, secondary, and tertiary blast injuries. It will also help you understand the fundamental role that imaging plays during mass casualty attacks and how to avoid radiology becoming a bottleneck to the forward flow of severely injured patients as they are triaged and treated. Copyright © 2018. Published by Elsevier Ltd.

  8. On firework blasts and qualitative parameter dependency. (United States)

    Zohdi, T I


    In this paper, a mathematical model is developed to qualitatively simulate the progressive time-evolution of a blast from a simple firework. Estimates are made for the blast radius that one can expect for a given amount of detonation energy and pyrotechnic display material. The model balances the released energy from the initial blast pulse with the subsequent kinetic energy and then computes the trajectory of the material under the influence of the drag from the surrounding air, gravity and possible buoyancy. Under certain simplifying assumptions, the model can be solved for analytically. The solution serves as a guide to identifying key parameters that control the evolving blast envelope. Three-dimensional examples are given.

  9. Blast effects physical properties of shock waves

    CERN Document Server


    This book compiles a variety of experimental data on blast waves. The book begins with an introductory chapter and proceeds to the topic of blast wave phenomenology, with a discussion Rankine-Hugoniot equations and the Friedlander equation, used to describe the pressure-time history of a blast wave. Additional topics include arrival time measurement, the initiation of detonation by exploding wires, a discussion of TNT equivalency, and small scale experiments. Gaseous and high explosive detonations are covered as well. The topics and experiments covered were chosen based on the comparison of used scale sizes, from small to large. Each characteristic parameter of blast waves is analyzed and expressed versus scaled distance in terms of energy and mass. Finally, the appendix compiles a number of polynomial laws that will prove indispensable for engineers and researchers.

  10. The rarity of ALDH(+) cells is the key to separation of normal versus leukemia stem cells by ALDH activity in AML patients. (United States)

    Hoang, Van T; Buss, Eike C; Wang, Wenwen; Hoffmann, Isabel; Raffel, Simon; Zepeda-Moreno, Abraham; Baran, Natalia; Wuchter, Patrick; Eckstein, Volker; Trumpp, Andreas; Jauch, Anna; Ho, Anthony D; Lutz, Christoph


    To understand the precise disease driving mechanisms in acute myeloid leukemia (AML), comparison of patient matched hematopoietic stem cells (HSC) and leukemia stem cells (LSC) is essential. In this analysis, we have examined the value of aldehyde dehydrogenase (ALDH) activity in combination with CD34 expression for the separation of HSC from LSC in 104 patients with de novo AML. The majority of AML patients (80 out of 104) had low percentages of cells with high ALDH activity (ALDH(+) cells; cells (≥1.9%; ALDH-numerous AML). In patients with ALDH-rare AML, normal HSC could be separated by their CD34(+) ALDH(+) phenotype, whereas LSC were exclusively detected among CD34(+) ALDH(-) cells. For patients with ALDH-numerous AML, the CD34(+) ALDH(+) subset consisted mainly of LSC and separation from HSC was not feasible. Functional analyses further showed that ALDH(+) cells from ALDH-numerous AML were quiescent, refractory to ARA-C treatment and capable of leukemic engraftment in a xenogenic mouse transplantation model. Clinically, resistance to chemotherapy and poor long-term outcome were also characteristic for patients with ALDH-numerous AML providing an additional risk-stratification tool. The difference in spectrum and relevance of ALDH activity in the putative LSC populations demonstrates, in addition to phenotypic and genetic, also functional heterogeneity of leukemic cells and suggests divergent roles for ALDH activity in normal HSC versus LSC. By acknowledging these differences our study provides a new and useful tool for prospective identification of AML cases in which separation of HSC from LSC is possible. © 2014 UICC.

  11. Blasting at a Superfund chemical waste site

    International Nuclear Information System (INIS)

    Burns, D.R.


    During the summer of 1989, Maine Drilling and Blasting of Gardiner, Maine was contracted by Cayer Corporation of Harvard, Massachusetts to drill and blast an interceptor trench at the Nyanza Chemical Superfund Site in Ashland, Massachusetts. The interceptor trench was to be 1,365 feet long and to be blasted out of granite. The trench was to be 12 feet wide at the bottom with 1/1 slopes, the deepest cut being 30 feet deep. A French drain 12 feet wide by 15 to 35 feet deep was blasted below the main trench on a 2% slope from its center to each end. A French drain is an excavation where the rock is blasted but not dug. The trench would be used as a perimeter road with any ground water flow going through the French drain flowing to both ends of the trench. Being a Superfund project turned a simple blasting project into a regulatory nightmare. The US Environmental Protection Agency performed all the chemical related functions on site. The US Army Corps of Engineers was overseeing all related excavation and construction on site, as was the Massachusetts Department of Environmental Quality Engineering, the local Hazardous Wastes Council, and the local Fire Department. All parties had some input with the blasting and all issues had to be addressed. The paper outlines the project, how it was designed and completed. Also included is an outline of the blast plan to be submitted for approval, an outline of the Safety/Hazardous Waste training and a description of all the problems which arose during the project by various regulatory agencies

  12. Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells* (United States)

    Pei, Shanshan; Minhajuddin, Mohammad; Callahan, Kevin P.; Balys, Marlene; Ashton, John M.; Neering, Sarah J.; Lagadinou, Eleni D.; Corbett, Cheryl; Ye, Haobin; Liesveld, Jane L.; O'Dwyer, Kristen M.; Li, Zheng; Shi, Lei; Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril; Hagen, Fred K.; Munger, Joshua; Crooks, Peter A.; Becker, Michael W.; Jordan, Craig T.


    The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34+) leukemic versus normal specimens. Our data indicate that CD34+ AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34+ AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34+ cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34+ AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34+ cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. PMID:24089526

  13. Blasting in hot zone - a case study

    Energy Technology Data Exchange (ETDEWEB)

    Nabiullah, B.M.P.; Pingua, J.; Dhar, B.B. [Central Mining Research Institute, Dhanbad (India)


    A significant quantity of coking coal reserves in the country are under fire particularly in Jharia coalfield. To control the fire and prevent loss of coal, an opencast mining method is adopted. The main problem with these opencast mines is drilling in hot strata and selection of suitable explosives and blasting in the fire zone. Trial blasts were conducted at two open cast mines. The problem was tackled by quenching the hot blast holes with water. Temperature of blast holes were recorded soon after drilling, after quenching with water and just before charging with explosives. The rise in temperature of charged explosives with time was also recorded until blasting. The thermal behaviour of commercially available explosives (including slurry, emulsion, ANFO and detonating cord) was investigated in laboratory and field simulated conditions. Emulsion, slurry compositions and detonating cord were found safe to use in hot holes up to 120{degree}C for duration of two hours. This paper describes the blasting practices adopted in the fire zones. 4 refs., 6 figs., 8 tabs.

  14. Ultra Safe And Secure Blasting System

    Energy Technology Data Exchange (ETDEWEB)

    Hart, M M


    The Ultra is a blasting system that is designed for special applications where the risk and consequences of unauthorized demolition or blasting are so great that the use of an extraordinarily safe and secure blasting system is justified. Such a blasting system would be connected and logically welded together through digital code-linking as part of the blasting system set-up and initialization process. The Ultra's security is so robust that it will defeat the people who designed and built the components in any attempt at unauthorized detonation. Anyone attempting to gain unauthorized control of the system by substituting components or tapping into communications lines will be thwarted in their inability to provide encrypted authentication. Authentication occurs through the use of codes that are generated by the system during initialization code-linking and the codes remain unknown to anyone, including the authorized operator. Once code-linked, a closed system has been created. The system requires all components connected as they were during initialization as well as a unique code entered by the operator for function and blasting.

  15. The second generation of electronic blasting systems

    Energy Technology Data Exchange (ETDEWEB)

    Hammelmann, F.; Petzold, J. [Dynamit Nobel GmbH (Germany)


    8 years after the market introduction of the first commercial electronic detonator - DYNATRONIC - the paper describes a new area of electronic blasting systems Made in Germany: i-kon. The results of a joint development between Dynamit Nobel and Orica is a unique universal electronic detonator, which is as simple to use as a standard non-electric detonator. The delay time or delay interval is not factory preprogrammed and the system is not based on a numbered system like conventional detonators. The miner or Blaster decides on site which delay timing he likes to use and is programming the whole blast on site. The new i-kon system allows delay times between 0 and 8000 ms by increments of 1 ms. With the control equipment it is possible to blast up to 1600 detonators in a single blast. The paper describes the construction and functionality of this new electronic blasting system - manufactured and developed by Precision Blasting Systems, a joint venture between Orica and Dynamic Nobel. (orig.)

  16. Effect of blasting on output increase of bucket wheel excavators

    Energy Technology Data Exchange (ETDEWEB)

    Musil, P.


    In brown coal surface mines, consolidated sediments become a problem as mining operations advance into greater depth below the original terrain. Owing to higher digging resistance, the output of bucket wheel excavators drops. This problem may be solved by blasting technology and using drilling machines with higher digging force. This paper describes the blasting operations at the Nastup Mines in Tusmice, Czechoslovakia. About 60% of blasting explosives used is a simple mixture of ammonium nitrate and fuel (ANFO), the rest falls on classic blasting gelatines and blasting explosives plasticized by slurry. It is found that blasting improves output by 30% while electric energy consumption is reduced.

  17. Proceedings of the twenty-seventh annual conference on explosives and blasting techniques

    Energy Technology Data Exchange (ETDEWEB)



    Various aspects of explosives and blasting techniques are covered. Those of particular interest to the coal industry buffer blasting versus cast blasting, post-blast cast profile shape prediction, fragmentation model to estimate ROM size distribution of soft rocks, blasting accidents, blast vibrations, ANFO explosives and carbon monoxide poisoning.


    Directory of Open Access Journals (Sweden)

    Y. A. Pranata


    Full Text Available A blast resistant single door was designed to withstand a 0.91 bar blast pressure and 44 ms blast duration. The analysis was done using Dynamic Time History Analysis using Blast Load modeled as Impact Load for given duration. The material properties used have been modified to accommodate dynamic effects. The analysis was done using dynamic finite element method (fem for time of the blast duration, and the maximum/minimum internal forces and displacement were taken from the time history output, in order to know the behavior under blast load and estimate the safety margin of the door. Results obtained from this research indicated that the maximum z-displacement is 1.709 mm, while in the term of serviceability, the permitted is 25 mm. The maximum reaction force is 73,960 N, while the maximum anchor capacity is 82,069 N. On blast condition, the maximum frame stress is 71.71 MPa, the maximum hinge shear stress is 45.28 MPa. While on rebound condition, the maximum frame stress is 172.11 MPa, the maximum hinge shear stress is 29.46 MPa. The maximum door edge rotation is 0.44 degree, which is not exceed the permitted boundary (1.2 degree. Keywords: Dynamic time history, blast resistant door, single door, finite element method.

  19. Raydet non-electric blast initiation system for efficient and environment-friendly surface blasts

    Energy Technology Data Exchange (ETDEWEB)

    Sarathy, M.O. [IDL Chemicals Ltd., Hyderabad (India). Technical Services Cell


    This paper discusses the advantages of using the Raydet shock tube based blast initiation system and reviews research work carried out on release of explosive energy in the drillhole, effect of stemming retention (stemming effectiveness) and advantages of `true bottom hole initiation` of drillholes in surface blasting. Some case studies are presented. 6 refs., 5 figs., 1 tab.

  20. A Novel Closed-head Model of Mild Traumatic Brain Injury Caused by Primary Overpressure Blast to the Cranium Produces Sustained Emotional Deficits in Mice

    Directory of Open Access Journals (Sweden)

    Scott A Heldt


    Full Text Available Emotional disorders are a common outcome from mild traumatic brain injury (TBI in humans, but their pathophysiological basis is poorly understood. We have developed a mouse model of closed-head blast injury using an air pressure wave delivered to a small area on one side of the cranium, which we have used to create mild TBI. We found that 20-psi blasts in 3-month old C57BL/6 male mice yielded no obvious behavioral or histological evidence of brain injury, while 25-40 psi blasts produced transient anxiety in an open field arena but little histological evidence of brain damage. By contrast, 50-60 psi blasts resulted in anxiety-like behavior in an open field arena that became more evident with time after blast. In additional behavioral tests conducted 2-8 weeks after blast, 50-60 psi mice also demonstrated increased acoustic startle, perseverance of learned fear, and enhanced contextual fear, as well as depression-like behavior and diminished prepulse inhibition. We found no evident cerebral pathology, however, and only scattered axonal degeneration in brain sections from 50-60 psi mice 3-8 weeks after blast. Thus, the TBI caused by single 50-60 psi blasts in mice exhibits the minimal neuronal loss coupled to diffuse axonal injury characteristic of human mild TBI. A reduction in the abundance of a subpopulation of excitatory projection neurons in basolateral amygdala enriched in Thy1 was, however, observed. The reported link of this neuronal population to fear suppression suggests their damage by mild TBI may contribute to the heightened anxiety and fearfulness observed after blast in our mice. Our overpressure air blast model of concussion in mice will enable further studies of the mechanisms underlying the diverse emotional deficits seen after mild TBI.

  1. Comparison of Some Blast Vibration Predictors for Blasting in Underground Drifts and Some Observations (United States)

    Bhagwat, Vaibhab Pramod; Dey, Kaushik


    Drilling and blasting are the most economical excavation techniques in underground drifts driven through hard rock formation. Burn cut is the most popular drill pattern, used in this case, to achieve longer advance per blast round. The ground vibration generated due to the propagation of blast waves on the detonation of explosive during blasting is the principal cause for structural and rock damage. Thus, ground vibration is a point of concern for the blasting engineers. The ground vibration from a blast is measured using a seismograph placed at the blast monitoring station. The measured vibrations, in terms of peak particle velocity, are related to the maximum charge detonated at one instant and the distance of seismograph from the blast point. The ground vibrations from a number of blast rounds of varying charge/delay and distances are monitored. A number of scaling factors of these dependencies (viz. Distance and maximum charge/delay) have been proposed by different researchers, namely, square root, cube root, CMRI, Langefors and Kihlstrom, Ghosh-Daemon, Indian standard etc. Scaling factors of desired type are computed for all the measured blast rounds. Regression analysis is carried out between the scaling factors and peak particle velocities to establish the coefficients of the vibration predictor equation. Then, the developed predictor equation is used for designing the blast henceforth. Director General of Mine Safety, India, specified that ground vibrations from eight to ten blast rounds of varying charge/delay and distances should be monitored to develop a predictor equation; however, there is no guideline about the type of scaling factor to be used. Further to this, from the statistical point of view, a regression analysis on a small sample population cannot be accepted without the testing of hypothesis. To show the importance of the above, in this paper, seven scaling factors are considered for blast data set of a hard-rock underground drift using burn

  2. BLAST-EXPLORER helps you building datasets for phylogenetic analysis

    Directory of Open Access Journals (Sweden)

    Claverie Jean-Michel


    Full Text Available Abstract Background The right sampling of homologous sequences for phylogenetic or molecular evolution analyses is a crucial step, the quality of which can have a significant impact on the final interpretation of the study. There is no single way for constructing datasets suitable for phylogenetic analysis, because this task intimately depends on the scientific question we want to address, Moreover, database mining softwares such as BLAST which are routinely used for searching homologous sequences are not specifically optimized for this task. Results To fill this gap, we designed BLAST-Explorer, an original and friendly web-based application that combines a BLAST search with a suite of tools that allows interactive, phylogenetic-oriented exploration of the BLAST results and flexible selection of homologous sequences among the BLAST hits. Once the selection of the BLAST hits is done using BLAST-Explorer, the corresponding sequence can be imported locally for external analysis or passed to the phylogenetic tree reconstruction pipelines available on the platform. Conclusions BLAST-Explorer provides a simple, intuitive and interactive graphical representation of the BLAST results and allows selection and retrieving of the BLAST hit sequences based a wide range of criterions. Although BLAST-Explorer primarily aims at helping the construction of sequence datasets for further phylogenetic study, it can also be used as a standard BLAST server with enriched output. BLAST-Explorer is available at

  3. Granulocytic Sarcoma by AML M4eo (inv16 after Allogeneic Stem Cell Transplantation without Bone Marrow Involvement

    Directory of Open Access Journals (Sweden)

    Stephan Zaenker


    Full Text Available Granulocytic sarcoma (GS represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML. We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT. The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.

  4. Incidence of extramedullary relapse after haploidentical SCT for advanced AML/myelodysplastic syndrome. (United States)

    Yoshihara, S; Ikegame, K; Kaida, K; Taniguchi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Soma, T; Ogawa, H


    Extramedullary (EM) relapse of leukemia after allo-SCT in patients with AML/myelodysplastic syndrome has been increasingly reported. The reduced effectiveness of the GVL effect in EM sites, as compared with BM, has been suggested to underlie this problem. We retrospectively analyzed the pattern of relapse after haploidentical SCT (haplo-SCT), performed as the first or second SCT. Among 38 patients who received haplo-SCT as their first SCT, the cumulative incidences of BM and EM relapse at 3 years were 40.5 and 10.9%, respectively. Among 19 patients who received haplo-SCT as their second SCT, the cumulative incidences of BM and EM relapse were 30.9 and 31.9%, respectively. Moreover, most of the patients who underwent repeat haplo-SCT for the treatment of EM relapse had further EM relapse at other sites. Post-relapse survival did not differ significantly with different patterns of relapse. The frequent occurrence of EM relapse after haplo-SCT, particularly when performed as a second SCT, suggests that the potent GVL effect elicited by an HLA disparity also occurs preferentially in BM. Our findings emphasize the need for a treatment strategy for EM relapse that recognizes the reduced susceptibility of EM relapse to the GVL effect.

  5. Chemical Space of FLT3 Inhibitors as Potential Anti-AML Drugs. (United States)

    Lan, Qing-Yuan; Zhi, Yan-Le; Heng, Hao; Tian, Jie-Yi; Guo, Xiao-Xing; Liu, Hai-Chun; Chen, Ya-Dong; Lu, Tao; Lu, Shuai


    FLT3 is a member of receptor tyrosine kinase III family, mainly expressed in hematopoietic cells. The aberrant expression and function of FLT3 are strongly related to leukemia, especially acute myeloid leukemia. Its varieties of amino-acid residues mutations, such as FLT3-ITDs and -TKDs, can induce constant proliferation of hematological tumor cells with poor prognosis. Hence FLT3 serves as a promising target in AML chemotherapy. This review focused on the progress of FLT3 inhibitors study including those that have entered clinical trials or were reported in numerous patents all over the world. Thus, we provided a useful reference for the development of new anti-leukemia drugs. Through a comprehensive retrospective study, FLT3 inhibitors in several patent applications were identified and classified into five categories, including quinolone-related, indole-related, ureas, pyrimidines and other compounds. For each category of compounds, the structural feature, SAR, biological activity and current research status were thoroughly reviewed and analyzed. Although some of those compounds expressed potent bioactivities and have reached the advanced clinical trials for the treatment of leukemia, there are still several problems need to be faced before they enter the market eventually, especially the drug resistance issue. The improvement of therapeutic potency for FLT3 inhibitors might depend on the useful combination therapy and further refinement of the intrinsic properties of FLT3 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at

  6. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. (United States)

    Luskin, Marlise R; Lee, Ju-Whei; Fernandez, Hugo F; Abdel-Wahab, Omar; Bennett, John M; Ketterling, Rhett P; Lazarus, Hillard M; Levine, Ross L; Litzow, Mark R; Paietta, Elisabeth M; Patel, Jay P; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Sun, Zhuoxin; Luger, Selina M


    The initial report of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group trial E1900 (#NCT00049517) showed that induction therapy with high-dose (HD) daunorubicin (90 mg/m(2)) improved overall survival in adults cytogenetics or aFLT3-ITD mutation. Here, we update the results of E1900 after longer follow-up (median, 80.1 months among survivors), focusing on the benefit of HD daunorubicin on common genetic subgroups. Compared with standard-dose daunorubicin (45 mg/m(2)), HD daunorubicin is associated with a hazard ratio (HR) for death of 0.74 (P= .001). Younger patients (cytogenetics (HR, 0.51;P= .03 and HR, 0.68;P= .01, respectively). Patients with unfavorable cytogenetics were shown to benefit from HD daunorubicin on multivariable analysis (adjusted HR, 0.66;P= .04). Patients with FLT3-ITD (24%),DNMT3A(24%), and NPM1(26%) mutant AML all benefited from HD daunorubicin (HR, 0.61,P= .009; HR, 0.62,P= .02; and HR, 0.50,P= .002; respectively). HD benefit was seen in the subgroup of older patients (50-60 years) with the FLT3-ITD or NPM1 mutation. Additionally, the presence of an NPM1 mutation confers a favorable prognosis only for patients receiving anthracycline dose intensification during induction. © 2016 by The American Society of Hematology.

  7. Compliance with the AM+L4776L/CFT International Standard; Lessons from a Cross-Country Analysis


    Concha Verdugo Yepes


    This paper assesses countries' compliance with the Anti-Money Laundering and Combating the Financing of Terrorism (AML/CFT) international standard during the period 2004 to 2011. We find that overall compliance is low; there is an adverse impact on financial transparency created by the cumulative effects of poor implementation of standards on customer identification; and the current measurements of compliance do not take into account an analysis of ML/FT risk, thereby undermining their credib...

  8. Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan


    Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in iden......-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients....

  9. Keep your mind off negative things: coping with long-term effects of acute myeloid leukemia (AML). (United States)

    Ghodraty-Jabloo, Vida; Alibhai, Shabbir M H; Breunis, Henriette; Puts, Martine T E


    Acute myeloid leukemia (AML) is characterized by sudden onset, intensive treatment, a poor prognosis, and significant relapse risk. Quality of life (QOL) and well-being among AML survivors have been extensively studied during the 6 months of active treatment. However, it is not clear what survivors experience after active treatment. The purpose of our study was to explore how AML survivors describe their longer-term physical and psychosocial well-being and how they cope with these challenges. We conducted a prospective qualitative study and interviewed 19 adult participants (11 had completed treatment, 8 were receiving maintenance chemotherapy). Data were collected using semi-structured interviews that were audio-recorded and transcribed verbatim. The grounded theory approach was used for data analysis. A marked improvement in physical health was reported; however, psychosocial well-being was compromised by enduring emotional distress. A range of emotion- and problem-focused coping strategies were reported. Keeping one's mind off negative things through engaging in formal work or informal activities and seeking control were the two most commonly used coping strategies. Seeking social support for reassurance was also common. Problem-focused strategies were frequently described by the ongoing treatment group to manage treatment side effects. Although physical symptoms improved after completion of treatment, psychosocial distress persisted over longer period of time. In addition, essential needs of AML survivors shifted across survivorship as psychological burden gradually displaced physical concerns. The integral role of coping mechanisms in the adaptation process suggests a need for effective and ongoing psychological interventions.

  10. Nuclear accumulation of SHIP1 mutants derived from AML patients leads to increased proliferation of leukemic cells. (United States)

    Nalaskowski, Marcus M; Ehm, Patrick; Rehbach, Christoph; Nelson, Nina; Täger, Maike; Modest, Kathrin; Jücker, Manfred


    The inositol 5-phosphatase SHIP1 acts as negative regulator of intracellular signaling in myeloid cells and is a tumor suppressor in myeloid leukemogenesis. After relocalization from the cytoplasm to the plasma membrane SHIP1 terminates PI3-kinase mediated signaling processes. Furthermore, SHIP1 is also found in distinct puncta in the cell nucleus and nuclear SHIP1 has a pro-proliferative function. Here we report the identification of five nuclear export signals (NESs) which regulate together with the two known nuclear localization signals (NLSs) the nucleocytoplasmic shuttling of SHIP1. Mutation of NLSs reduced the nuclear import and mutation of NESs decreased the nuclear export of SHIP1 in the acute myeloid leukemia (AML) cell line UKE-1. Interestingly, four SHIP1 mutants (K210R, N508D, V684E, Q1153L) derived from AML patients showed a nuclear accumulation after expression in UKE-1 cells. In addition, overexpression of the AML patient-derived mutation N508D caused an increased proliferation rate of UKE-1 cells in comparison to wild type SHIP1. Furthermore, we identified serine and tyrosine phosphorylation as a molecular mechanism for the regulation of nucleocytoplasmic shuttling of SHIP1 where tyrosine phosphorylation of distinct residues i.e. Y864, Y914, Y1021 reduces nuclear localization, whereas serine phosphorylation at S933 enhances nuclear localization of SHIP1. In summary, our data further implicate nuclear SHIP1 in cellular signaling and suggest that enhanced accumulation of SHIP1 mutants in the nucleus may be a contributory factor of abnormally high proliferation of AML cells. Copyright © 2017. Published by Elsevier Inc.

  11. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation

    DEFF Research Database (Denmark)

    Rishi, Loveena; Hannon, Maura; Salomè, Mara


    α (C/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop......The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein...... for E2F1, C/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPα-p42, and in normal granulocyte/macrophage progenitor cells, we detect C/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle...

  12. Induced Mitogenic Activity in AML-12 Mouse Hepatocytes Exposed to Low-dose Ultra-Wideband Electromagnetic Radiation

    Directory of Open Access Journals (Sweden)

    P. B. Tchounwou


    Full Text Available Ultra–wideband (UWB technology has increased with the use of various civilian and military applications. In the present study, we hypothesized that low-dose UWB electromagnetic radiation (UWBR could elicit a mitogenic effect in AML-12 mouse hepatocytes, in vitro. To test this hypothesis, we exposed AML-12 mouse hepatocytes, to UWBR in a specially constructed gigahertz transverse electromagnetic mode (GTEM cell. Cells were exposed to UWBR for 2 h at a temperature of 23°C, a pulse width of 10 ns, a repetition rate of 1 kHz, and field strength of 5-20 kV/m. UWB pulses were triggered by an external pulse generator for UWBR exposure but were not triggered for the sham exposure. We performed an MTT Assay to assess cell viability for UWBR-treated and sham-exposed hepatocytes. Data from viability studies indicated a time-related increase in hepatocytes at time intervals from 8-24 h post exposure. UWBR exerted a statistically significant (p < 0.05 dose-dependent response in cell viability in both serum-treated and serum free medium (SFM -treated hepatocytes. Western blot analysis of hepatocyte lysates demonstrated that cyclin A protein was induced in hepatocytes, suggesting that increased MTT activity after UWBR exposure was due to cell proliferation. This study indicates that UWBR has a mitogenic effect on AML-12 mouse hepatocytes and implicates a possible role for UWBR in hepatocarcinoma.

  13. Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain. (United States)

    Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi


    AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

  14. Exchange Transfusion and Leukapheresis in Pediatric Patients with AML With High Risk of Early Death by Bleeding and Leukostasis. (United States)

    Creutzig, Ursula; Rössig, Claudia; Dworzak, Michael; Stary, Jan; von Stackelberg, Arend; Wössmann, Wilhelm; Zimmermann, Martin; Reinhardt, Dirk


    The risk of early death (ED) by bleeding/leukostasis is high in patients with AML with hyperleukocytosis (>100,000/μl). Within the pediatric AML-BFM (Berlin-Frankfurt-Münster) 98/04 studies, emergency strategies for these children included exchange transfusion (ET) or leukapheresis (LPh). Risk factors for ED and interventions performed were analyzed. Two hundred thirty-eight of 1,251 (19%) patients with AML presented with hyperleukocytosis; 23 of 1,251 (1.8%) patients died of bleeding/leukostasis. ED due to bleeding/leukostasis was highest at white blood cell (WBC) count >200,000/μl (14.3%). ED rates were even higher (20%) in patients with FAB (French-American-British) M4/M5 and hyperleukocytosis >200,000/μl. Patients with WBC >200,000/μl did slightly better with ET/LPh compared to those without ET/LPh (ED rate 7.5% vs. 21.2%, P = 0.055). Multivariate WBC >200,000/μl was of strongest prognostic significance for ED (P(χ(2) ) rate due to bleeding/leukostasis and is recommended at WBC >200,000/μl, and in FAB M4/M5 even at lower WBC. © 2015 Wiley Periodicals, Inc.

  15. Research on Effects of Blast Casting Vibration and Vibration Absorption of Presplitting Blasting in Open Cast Mine

    Directory of Open Access Journals (Sweden)

    Li Ma


    Full Text Available The impact energy produced by blast casting is able to break and cast rocks, yet the strong vibration effects caused at the same time would threaten the safety of mines. Based on the theory of Janbu’s Limit Equilibrium Method (LEM, pseudo-static method has been incorporated to analyze the influence of dynamic loads of blasting on slope stability. The horizontal loads produced by blast vibrations cause an increase in sliding forces, and this leads to a lower slope stability coefficient. When the tensile stresses of the two adjacent blast holes are greater than the tensile strength of rock mass, the radical oriented cracks are formed, which is the precondition for the formation of presplit face. Thus, the formula for calculating the blast hole spacing of presplit blasting can be obtained. Based on the analysis of the principles of vibration tester and vibration pick-up in detecting blast vibrations, a detection scheme of blast vibration is worked out by taking the blast area with precrack rear and non-precrack side of the detection object. The detection and research results of blast vibration show that presplit blasting can reduce the attenuation coefficient of stress wave by half, and the vibration absorption ratio could reach 50.2%; the impact of dynamic loads on the end-wall slope stability coefficient is 1.98%, which proves that presplit blasting plays an important role in shock absorption of blast casting.

  16. Blast densification trials for oilsands tailings

    Energy Technology Data Exchange (ETDEWEB)

    Port, A. [Klohn Crippen Berger Ltd., Vancouver, BC (Canada); Martens, S. [Klohn Crippen Berger Ltd., Calgary, AB (Canada); Eaton, T. [Shell Canada Ltd., Calgary, AB (Canada)


    The Shell Canada Muskeg River Mine External Tailings Facility (ETF) is an upstream constructed tailings facility located near Fort McMurray, Alberta. Raises have incrementally stepped out over the beach since construction of the starter dam and deposition within standing water has left some parts of the beach in a loose state. In order to assess the effectiveness of blast densification, a blast densification trial program that was conducted in 2006 at the ETF. The primary purpose of the test program was to determine the effectiveness of blast densification in tailings containing layers and zones of bitumen. The paper described the site characterization and explosive compaction trial program, with particular reference to test layout; drilling methodology; and blasting and timing sequence. The paper also described the instrumentation, including the seismographs; high pressure electric piezometers; low pressure electric piezometers; vibrating wire piezometers; inclinometers; settlement gauges; and surveys. Trial observations and post-trial observations were also presented. It was concluded that controlled blasting techniques could be used to safely induce liquefaction in localized areas within the tailings deposit, with a resulting increase in the tailings density. 5 refs., 1 tab., 14 figs.

  17. Spalling of concrete walls under blast load

    International Nuclear Information System (INIS)

    Kot, C.A.


    A common effect of the detonation of explosives in close proximity of concrete shield walls is the spalling (scabbing) of the back face of the wall. Spalling is caused by the free surface reflection of the shock wave induced in the wall by high pressure air blast and occurs whenever the dynamic tensile rupture strength is exceeded. While a complex process, reasonable analytical spall estimates can be obtained for brittle materials with low tensile strengths, such as concrete, by assuming elastic material behavior and instantaneous spall formation. Specifically, the spall thicknesses and velocities for both normal and oblique incidence of the shock wave on the back face of the wall are calculated. The complex exponential decay wave forms of the air blast are locally approximated by simple power law expressions. Variations of blast wave strength with distance to the wall, charge weight and angle of incidence are taken into consideration. The shock wave decay in the wall is also accounted for by assuming elastic wave propagation. For explosions close-in to the wall, where the reflected blast wave pressures are sufficiently high, multiple spall layers are formed. Successive spall layers are of increasing thickness, at the same time the spall velocities decrease. The spall predictions based on elastic theory are in overall agreement with experimntal results and provide a rapid means of estimating spalling trends of concrete walls subjected to air blast. (Auth.)

  18. Treatment for Relapsed/Refractory AML Based on a High Throughput Drug Sensitivity Assay (United States)


    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  19. 30 CFR 75.1316 - Preparation before blasting. (United States)


    ... two working faces are approaching each other, cutting, drilling and blasting shall be done at only one... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Preparation before blasting. 75.1316 Section 75... HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Explosives and Blasting § 75.1316 Preparation...

  20. Divide and Conquer (DC BLAST: fast and easy BLAST execution within HPC environments

    Directory of Open Access Journals (Sweden)

    Won Cheol Yim


    Full Text Available Bioinformatics is currently faced with very large-scale data sets that lead to computational jobs, especially sequence similarity searches, that can take absurdly long times to run. For example, the National Center for Biotechnology Information (NCBI Basic Local Alignment Search Tool (BLAST and BLAST+ suite, which is by far the most widely used tool for rapid similarity searching among nucleic acid or amino acid sequences, is highly central processing unit (CPU intensive. While the BLAST suite of programs perform searches very rapidly, they have the potential to be accelerated. In recent years, distributed computing environments have become more widely accessible and used due to the increasing availability of high-performance computing (HPC systems. Therefore, simple solutions for data parallelization are needed to expedite BLAST and other sequence analysis tools. However, existing software for parallel sequence similarity searches often requires extensive computational experience and skill on the part of the user. In order to accelerate BLAST and other sequence analysis tools, Divide and Conquer BLAST (DCBLAST was developed to perform NCBI BLAST searches within a cluster, grid, or HPC environment by using a query sequence distribution approach. Scaling from one (1 to 256 CPU cores resulted in significant improvements in processing speed. Thus, DCBLAST dramatically accelerates the execution of BLAST searches using a simple, accessible, robust, and parallel approach. DCBLAST works across multiple nodes automatically and it overcomes the speed limitation of single-node BLAST programs. DCBLAST can be used on any HPC system, can take advantage of hundreds of nodes, and has no output limitations. This freely available tool simplifies distributed computation pipelines to facilitate the rapid discovery of sequence similarities between very large data sets.

  1. Blast-induced traumatic brain injury: a new trend of blast injury research. (United States)

    Zhao, Yan; Wang, Zheng-Guo


    Blast injury has become the major life- and function-threatening injuries in recent warfares. There is increased research interest in the mental disorders caused by blast-induced traumatic brain injury (bTBI), which has been proved as one of the "signature wounds" in modern battlefield. We reviewed the recent progresses in bTBI-related researches and concluded that the new era of blast injury research has shifted from the traditional physical impairments to cognitive dysfunctional/mental disorders that are proved to be more related to the outcome of combat casualty care.

  2. New techniques for improved performance in surface blasting operation and optimisation of blast design parameters

    Energy Technology Data Exchange (ETDEWEB)

    Roy, P.P. [Central Mining Research Institute, Dhanbad (India). Blasting Dept.


    Experimental blasts were conducted for optimisation of blasting parameters using separate technologies involving non-electric initiation systems, air decking accessories in conjunction with different explosive products like emulsion (cartridge and site-mixed), slurries (cartridge and site-mixed) and ANFO. The cost associated with each such technology was then compared with the conventional methods of drilling and blasting operations. The results of cost analyses are given. Theoretical and practical aspects of such technologies and their best possible usage in order to establish the desired fragmentation, muck profile, wall control and ultimately the accepted level of costs are mentioned in subsequent sections. 16 refs., 17 figs., 8 plates, 11 tabs.

  3. FastBLAST: homology relationships for millions of proteins.

    Directory of Open Access Journals (Sweden)

    Morgan N Price

    Full Text Available BACKGROUND: All-versus-all BLAST, which searches for homologous pairs of sequences in a database of proteins, is used to identify potential orthologs, to find new protein families, and to provide rapid access to these homology relationships. As DNA sequencing accelerates and data sets grow, all-versus-all BLAST has become computationally demanding. METHODOLOGY/PRINCIPAL FINDINGS: We present FastBLAST, a heuristic replacement for all-versus-all BLAST that relies on alignments of proteins to known families, obtained from tools such as PSI-BLAST and HMMer. FastBLAST avoids most of the work of all-versus-all BLAST by taking advantage of these alignments and by clustering similar sequences. FastBLAST runs in two stages: the first stage identifies additional families and aligns them, and the second stage quickly identifies the homologs of a query sequence, based on the alignments of the families, before generating pairwise alignments. On 6.53 million proteins from the non-redundant Genbank database ("NR", FastBLAST identifies new families 25 times faster than all-versus-all BLAST. Once the first stage is completed, FastBLAST identifies homologs for the average query in less than 5 seconds (8.6 times faster than BLAST and gives nearly identical results. For hits above 70 bits, FastBLAST identifies 98% of the top 3,250 hits per query. CONCLUSIONS/SIGNIFICANCE: FastBLAST enables research groups that do not have supercomputers to analyze large protein sequence data sets. FastBLAST is open source software and is available at

  4. Drilling-and-blasting method of demolition

    Directory of Open Access Journals (Sweden)

    Sinitsyn Denis


    Full Text Available This article analyzes the experience and gives the examples of dismantling and demolition of the construction structures of the buildings and facilities using the drilling-and-blasting method. The drilling-and-blasting method is widely used in construction and reconstruction. The demolition means may be classified according to impact on a material of structures to be demolished and to forces application, where, by virtue of an impact energy type, we choose the blasting method. This method is used during the complete demolition or fragmentation of concrete, reinforced concrete, masonry structures, of old buildings and facilities demolition to their base or in the intended direction. Blasting method may be used as well during the steel and reinforced concrete structures demolition to the smaller easy-to-move parts. Reviewed are the organizational-process activities, which are performed during the various structures dismantling. Given are the areas of application for the various methods of structures demolition. Given is the example of demolition of “Sevemaya” boiler house brick chimney at the territory of Murmansk DSK using the blast in confined spaces of the operating company. Subject of research: methods of construction structures demolition in alarm situations and acts of God. Objects: determination of the most efficient demolition methods in the present conditions of construction operations development. Materials and methods: the developed activities on the construction structures dismantling are given. Results: the most efficient methods and ways of construction structures demolition are defined. Conclusions: it is required for improvement of methods and ways of the structures drilling-and-blasting demolition.

  5. Spalling of concrete subjected to blast loading

    Directory of Open Access Journals (Sweden)

    Foglar M.


    Full Text Available This paper presents outcomes of the blast field tests of FRC and reinforced concrete specimens, which were performed in cooperation with the Czech Army corps and Police of the Czech Republic in the military training area Boletice. The numerical evaluation of the experiments focused on the spalling of concrete subjected to blast loading started after the first set of the tests, took almost 3 years and required further small-scale experiments performed in the labs of the Czech Technical University.

  6. Implementations of BLAST for parallel computers. (United States)

    Jülich, A


    The BLAST sequence comparison programs have been ported to a variety of parallel computers-the shared memory machine Cray Y-MP 8/864 and the distributed memory architectures Intel iPSC/860 and nCUBE. Additionally, the programs were ported to run on workstation clusters. We explain the parallelization techniques and consider the pros and cons of these methods. The BLAST programs are very well suited for parallelization for a moderate number of processors. We illustrate our results using the program blastp as an example. As input data for blastp, a 799 residue protein query sequence and the protein database PIR were used.

  7. Dry blasting decontaminating method for radioactive waste

    International Nuclear Information System (INIS)

    Nishiwaki, Hitoshi.


    In the present invention, when abrasives are dry blasted on the surface of radioactive wastes and the recovered abrasives are classified for re-use, abrasives having a microvicker's hardness (HMV) of greater than 600 and a grain size of greater than 1mm are used in a case where the radioactive wastes to be abraded are stainless steels. This enables dry blasting decontamination for stainless steels which has been considered to be impossible. In addition since the amount of secondary wastes are reduced, it is extremely effective. (T.M.)

  8. Predictive control of thermal state of blast furnace (United States)

    Barbasova, T. A.; Filimonova, A. A.


    The work describes the structure of the model for predictive control of the thermal state of a blast furnace. The proposed model contains the following input parameters: coke rate; theoretical combustion temperature, comprising: natural gas consumption, blasting temperature, humidity, oxygen, blast furnace cooling water; blast furnace gas utilization rate. The output parameter is the cast iron temperature. The results for determining the cast iron temperature were obtained following the identification using the Hammerstein-Wiener model. The result of solving the cast iron temperature stabilization problem was provided for the calculated values of process parameters of the target area of the respective blast furnace operation mode.

  9. Modeling and simulation of blast-induced, early-time intracranial wave physics leading to traumatic brain injury.

    Energy Technology Data Exchange (ETDEWEB)

    Ford, Corey C. (University of New Mexico, Albuquerque, NM); Taylor, Paul Allen


    The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm{sup 3} voxels), 5 material model of the human head was created by segmentation of color cryosections from the Visible Human Female dataset. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior and lateral directions. Three dimensional plots of maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric (shear) stress within the first 2 milliseconds of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 msec time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.

  10. Low-cost blast wave generator for studies of hearing loss and brain injury: blast wave effects in closed spaces. (United States)

    Newman, Andrew J; Hayes, Sarah H; Rao, Abhiram S; Allman, Brian L; Manohar, Senthilvelan; Ding, Dalian; Stolzberg, Daniel; Lobarinas, Edward; Mollendorf, Joseph C; Salvi, Richard


    Military personnel and civilians living in areas of armed conflict have increased risk of exposure to blast overpressures that can cause significant hearing loss and/or brain injury. The equipment used to simulate comparable blast overpressures in animal models within laboratory settings is typically very large and prohibitively expensive. To overcome the fiscal and space limitations introduced by previously reported blast wave generators, we developed a compact, low-cost blast wave generator to investigate the effects of blast exposures on the auditory system and brain. The blast wave generator was constructed largely from off the shelf components, and reliably produced blasts with peak sound pressures of up to 198dB SPL (159.3kPa) that were qualitatively similar to those produced from muzzle blasts or explosions. Exposure of adult rats to 3 blasts of 188dB peak SPL (50.4kPa) resulted in significant loss of cochlear hair cells, reduced outer hair cell function and a decrease in neurogenesis in the hippocampus. Existing blast wave generators are typically large, expensive, and are not commercially available. The blast wave generator reported here provides a low-cost method of generating blast waves in a typical laboratory setting. This compact blast wave generator provides scientists with a low cost device for investigating the biological mechanisms involved in blast wave injury to the rodent cochlea and brain that may model many of the damaging effects sustained by military personnel and civilians exposed to intense blasts. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Nineteen-Foot Diameter Explosively Driven Blast Simulator; TOPICAL

    International Nuclear Information System (INIS)



    This report describes the 19-foot diameter blast tunnel at Sandia National Laboratories. The blast tunnel configuration consists of a 6 foot diameter by 200 foot long shock tube, a 6 foot diameter to 19 foot diameter conical expansion section that is 40 feet long, and a 19 foot diameter test section that is 65 feet long. Therefore, the total blast tunnel length is 305 feet. The development of this 19-foot diameter blast tunnel is presented. The small scale research test results using 4 inch by 8 inch diameter and 2 foot by 6 foot diameter shock tube facilities are included. Analytically predicted parameters are compared to experimentally measured blast tunnel parameters in this report. The blast tunnel parameters include distance, time, static, overpressure, stagnation pressure, dynamic pressure, reflected pressure, shock Mach number, flow Mach number, shock velocity, flow velocity, impulse, flow duration, etc. Shadowgraphs of the shock wave are included for the three different size blast tunnels

  12. CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia


    Wang, Jinghua; Chen, Siyu; Xiao, Wei; Li, Wende; Wang, Liang; Yang, Shuo; Wang, Weida; Xu, Liping; Liao, Shuangye; Liu, Wenjian; Wang, Yang; Liu, Nawei; Zhang, Jianeng; Xia, Xiaojun; Kang, Tiebang


    Background Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreov...

  13. Consideration on local blast vibration control by delay blasting; Danpatsu happa ni yoru kyokuchiteki shindo seigyo ni kansuru ichikosatsu

    Energy Technology Data Exchange (ETDEWEB)

    Mogi, Gento; Adachi, Tsuyoshi; Yamatomi, Jiro [The University of Tokyo School of Engineering Department of Geosystem Engineering, Tokyo (Japan); Hoshino, Tatsuya [Mitsui Mining and Smelting Corp., Tokyo (Japan)


    In this research, local blast vibration control based on the theory of superposition of waves was investigated. Firstly, the influence of delay time errors of conventional electric detonators upon the level of local blast vibration was examined. Secondly, for a further effective local blast vibration control, a new delay blasting design concept 'combined delay blasting' that postulates the use of electronic detonators, which virtually have no delay time errors, is proposed. For a delay blasting with uniform detonation time intervals, an optimum time interval to minimize the local PPV (Peak Particle Velocity) is obtained based on the relationship between the PPV and the time interval, which is derived by superposing identical vibration time histories of each single hole shot. However, due to the scattering of the actual delay time caused by errors, PPV of a production blast seldom coincides with the estimated one. Since the expected value and the variance of PPV mainly depend on sensitivity of PPV around the nominal delay time, it is proposed that not only the optimum but also several sub-optimum candidates of delay time should be examined taking error into consideration. Concerning the 'combined delay blasting', its concept and some simulation results are presented. The estimated reduction effect of blast vibration of a delay blast based on this concept was quite favorable, indicating a possibility for further effective local blast vibration control. (author)

  14. Hoxa9 and Hoxa10 induce CML myeloid blast crisis development through activation of Myb expression. (United States)

    Negi, Vijay; Vishwakarma, Bandana A; Chu, Su; Oakley, Kevin; Han, Yufen; Bhatia, Ravi; Du, Yang


    Mechanisms underlying the progression of Chronic Myeloid Leukemia (CML) from chronic phase to myeloid blast crisis are poorly understood. Our previous studies have suggested that overexpression of SETBP1 can drive this progression by conferring unlimited self-renewal capability to granulocyte macrophage progenitors (GMPs). Here we show that overexpression of Hoxa9 or Hoxa10 , both transcriptional targets of Setbp1 , is also sufficient to induce self-renewal of primary myeloid progenitors, causing their immortalization in culture. More importantly, both are able to cooperate with BCR/ABL to consistently induce transformation of mouse GMPs and development of aggressive leukemias resembling CML myeloid blast crisis, suggesting that either gene can drive CML progression by promoting the self-renewal of GMPs. We further identify Myb as a common critical target for Hoxa9 and Hoxa10 in inducing self-renewal of myeloid progenitors as Myb knockdown significantly reduced colony-forming potential of myeloid progenitors immortalized by the expression of either gene. Interestingly, Myb is also capable of immortalizing primary myeloid progenitors in culture and cooperating with BCR/ABL to induce leukemic transformation of mouse GMPs. Significantly increased levels of MYB transcript also were detected in all human CML blast crisis samples examined over chronic phase samples, further suggesting the possibility that MYB overexpression may play a prevalent role in driving human CML myeloid blast crisis development. In summary, our results identify overexpression of HOXA9 , HOXA10 , and MYB as critical drivers of CML progression, and suggest MYB as a key therapeutic target for inhibiting the self-renewal of leukemia-initiating cells in CML myeloid blast crisis patients.

  15. Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group. (United States)

    Manara, E; Basso, G; Zampini, M; Buldini, B; Tregnago, C; Rondelli, R; Masetti, R; Bisio, V; Frison, M; Polato, K; Cazzaniga, G; Menna, G; Fagioli, F; Merli, P; Biondi, A; Pession, A; Locatelli, F; Pigazzi, M


    Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, <0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P<0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P<0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.

  16. 8 Museve NBI BombBlast.indd

    African Journals Online (AJOL)

    Professionals, executives, managers, semi professionals and skilled workers comprised 89.5% of the victims when ... dependants. Being inside a building and within 100 metres from the blast carried the largest risk of injury. A ... Kenya had never experienced a suicidal terrorist bombing ..... Rapid assessment of Injuries.

  17. Ice blasting device for washing pump

    International Nuclear Information System (INIS)

    Hirose, Yasuo.


    In a nuclear power plant, when the inside of a pump casing such as a recycling pump is scrubbed, since operator's safety should be ensured, it requires a large-scaled operation. Then, a cover is attached to a flange of the pump casing, in which a driving portion is disposed passing through the cover vertically movably and rotatably, an arm is disposed bendably to the top end of the arm, and a blast nozzle is disposed to the top end of the arm for jetting ice particles, with a camera being disposed to the blast nozzle. The inside of the casing can be scrubbed safely and rapidly by an ice blast method by remote operation while monitoring the state of scrubbing for the inside of the casing by a camera. Further, since the flange of the pump casing for installing the ice blast device is covered by the cover, mists are not scattered to the outside. In addition, mists may be sucked and removed by an exhaustion duct. (N.H.)

  18. Modeling of Near-Field Blast Performance (United States)


    The freeze-out temperature is chosen by comparison of calorimetry experiments (2, 3) and thermoequilibrium calculations using CHEETAH (4). The near...P.; Vitello, P. CHEETAH Users Manual; Lawrence Livermore National Laboratory: Livermore, CA, 2012. 5. Walter, P. Introduction to Air Blast

  19. Blast Injuries: What Clinicians Need to Know

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. Richard C. Hunt, Director of the CDC’s Division of Injury Response, National Center for Injury Prevention and Control provides a brief overview for health care providers on how to respond and care for persons injured by an explosion or blast event.

  20. Tumor SHB gene expression affects disease characteristics in human acute myeloid leukemia. (United States)

    Jamalpour, Maria; Li, Xiujuan; Cavelier, Lucia; Gustafsson, Karin; Mostoslavsky, Gustavo; Höglund, Martin; Welsh, Michael


    The mouse Shb gene coding for the Src Homology 2-domain containing adapter protein B has recently been placed in context of BCRABL1-induced myeloid leukemia in mice and the current study was performed in order to relate SHB to human acute myeloid leukemia (AML). Publicly available AML databases were mined for SHB gene expression and patient survival. SHB gene expression was determined in the Uppsala cohort of AML patients by qPCR. Cell proliferation was determined after SHB gene knockdown in leukemic cell lines. Despite a low frequency of SHB gene mutations, many tumors overexpressed SHB mRNA compared with normal myeloid blood cells. AML patients with tumors expressing low SHB mRNA displayed longer survival times. A subgroup of AML exhibiting a favorable prognosis, acute promyelocytic leukemia (APL) with a PMLRARA translocation, expressed less SHB mRNA than AML tumors in general. When examining genes co-expressed with SHB in AML tumors, four other genes ( PAX5, HDAC7, BCORL1, TET1) related to leukemia were identified. A network consisting of these genes plus SHB was identified that relates to certain phenotypic characteristics, such as immune cell, vascular and apoptotic features. SHB knockdown in the APL PMLRARA cell line NB4 and the monocyte/macrophage cell line MM6 adversely affected proliferation, linking SHB gene expression to tumor cell expansion and consequently to patient survival. It is concluded that tumor SHB gene expression relates to AML survival and its subgroup APL. Moreover, this gene is included in a network of genes that plays a role for an AML phenotype exhibiting certain immune cell, vascular and apoptotic characteristics.

  1. Distinguishing Realistic Military Blasts from Firecrackers in Mitigation Studies of Blast Induced Traumatic Brain Injury

    Energy Technology Data Exchange (ETDEWEB)

    Moss, W C; King, M J; Blackman, E G


    In their Contributed Article, Nyein et al. (1,2) present numerical simulations of blast waves interacting with a helmeted head and conclude that a face shield may significantly mitigate blast induced traumatic brain injury (TBI). A face shield may indeed be important for future military helmets, but the authors derive their conclusions from a much smaller explosion than typically experienced on the battlefield. The blast from the 3.16 gm TNT charge of (1) has the following approximate peak overpressures, positive phase durations, and incident impulses (3): 10 atm, 0.25 ms, and 3.9 psi-ms at the front of the head (14 cm from charge), and 1.4 atm, 0.32 ms, and 1.7 psi-ms at the back of a typical 20 cm head (34 cm from charge). The peak pressure of the wave decreases by a factor of 7 as it traverses the head. The blast conditions are at the threshold for injury at the front of the head, but well below threshold at the back of the head (4). The blast traverses the head in 0.3 ms, roughly equal to the positive phase duration of the blast. Therefore, when the blast reaches the back of the head, near ambient conditions exist at the front. Because the headform is so close to the charge, it experiences a wave with significant curvature. By contrast, a realistic blast from a 2.2 kg TNT charge ({approx} an uncased 105 mm artillery round) is fatal at an overpressure of 10 atm (4). For an injury level (4) similar to (1), a 2.2 kg charge has the following approximate peak overpressures, positive phase durations, and incident impulses (3): 2.1 atm, 2.3 ms, and 18 psi-ms at the front of the head (250 cm from charge), and 1.8 atm, 2.5 ms, and 16.8 psi-ms at the back of the head (270 cm from charge). The peak pressure decreases by only a factor of 1.2 as it traverses the head. Because the 0.36 ms traversal time is much smaller than the positive phase duration, pressures on the head become relatively uniform when the blast reaches the back of the head. The larger standoff implies

  2. 29 CFR 1926.906 - Initiation of explosive charges-electric blasting. (United States)


    ...) After firing an electric blast from a blasting machine, the leading wires shall be immediately... 29 Labor 8 2010-07-01 2010-07-01 false Initiation of explosive charges-electric blasting. 1926.906... Use of Explosives § 1926.906 Initiation of explosive charges—electric blasting. (a) Electric blasting...

  3. Siglec-7 tetramers characterize B-cell subpopulations and leukemic blasts. (United States)

    Gieseke, Friederike; Mang, Philippa; Viebahn, Susanne; Sonntag, Inga; Kruchen, Anne; Erbacher, Annika; Pfeiffer, Matthias; Handgretinger, Rupert; Müller, Ingo


    Cell surface glycosylation has important regulatory functions in the maturation, activation, and homeostasis of lymphocytes. The family of human sialic acid-binding immunoglobulin-like lectins (siglecs) comprises inhibitory as well as activating receptors intimately involved in the regulation of immune responses. Analyses of the interaction between siglecs and glycans are hampered by the low affinity of this interaction. Therefore, we expressed siglec-7 in eukaryotic cells, allowing for glycosylation, and oligomerized the protein in analogy to MHC tetramers. Using this tool, flow cytometric analysis of lymphocytes became possible. Sialic acid-dependent binding of siglec-7 tetramers was confirmed by glycan array analysis and loss of siglec tetramer binding after neuraminidase treatment of lymphocytes. In contrast to most lymphocyte subpopulations, which showed high siglec-7 ligand expression, B-cell subpopulations could be further subdivided according to different siglec-7 ligand expression levels. We also analyzed blasts from acute lymphoblastic leukemias of the B-cell lineage as well as the T-cell lineage, since malignant transformation is often associated with aberrant cell surface glycosylation. While pediatric T-ALL blasts highly expressed siglec-7 ligands, siglec-7 ligands were barely detectable on cALL blasts. Taken together, oligomerization of recombinant soluble siglec-7 enabled flow cytometric identification of physiologic lymphocyte subpopulations and malignant blasts. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Damage Curves of a Nuclear Reactor Structure exposed to Air Blast Loading

    International Nuclear Information System (INIS)

    Brandys, I.; Ornai, D.; Ronen, Y.


    Nuclear Power Plant (NPP) radiological hazards due to accidental failure or deliberated attacks are of most concern due to their destructive and global consequences: large area contaminations, injuries, exposure to ionizing radiation (which can cause death or illness, depends on the levels of exposure), loss of lives of both humans and animals, and severe damage to the environment. Prevention of such consequences is of a global importance and it has led to the definition of safety & design guidelines, and regulations by various authorities such as IAEA, U.S. NRC, etc. The guidelines define general requirements for the integrity of a NPP’s physical barriers (such as protective walls) when challenged by external events, for example human induced explosion. A more specific relation to the design of a NPP is that its structures and equipment (reactor building, fuel building, safeguards building, diesel-generator building, pumping station, nuclear auxiliaries building, and effluent treatment building) must function properly: shutdown the reactor, removal of decayed heat, storage of spent fuel, and treatment and containment of radioactive effluents) under external explosion. It requires that the NPP’s structures and equipment resistance to external explosion should be analyzed and verified. The air blast loading created by external explosion, as well as its effects & consequences on different kinds of structures are described in the literature. Structural elements response to the air blast can be analyzed in general by a Single Degree of Freedom (SDOF) system that converts a distributed mass, loads, and resistance to concentrated mass, force, and stiffness located at a representative point of the structure's element where the displacements are the highest one. Proper shielding should be designed if the explosion blast effects are greater than the resistance capacity.External explosion effects should be considered within the Screening Distance Value (SDV) of the NPP

  5. Oil injection into the blast furnace

    Energy Technology Data Exchange (ETDEWEB)

    Dongsheng Liao; Mannila, P.; Haerkki, J.


    Fuel injection techniques have been extensively used in the commercial blast furnaces, a number of publications concerning the fuels injection have been reported. This present report only summarizes the study achievements of oil injection due to the research need the of authors, it includes the following parts: First, the background and the reasons reducing coke rate of oil injection are analyzed. Reducing coke rate and decreasing the ironmaking costs are the main deriving forces, the contents of C, H and ash are direct reasons reducing coke rate. It was also found that oil injection had great effects on the state of blast furnace, it made operation stable, center gas flow develop fully, pressure drop increase, descent speed of burden materials decrease and generation of thermal stagnation phenomena, the quality of iron was improved. Based on these effects, as an ideal mean, oil injection was often used to adjust the state of blast furnace. Secondly, combustion behavior of oil in the raceway and tuyere are discussed. The distribution of gas content was greatly changed, the location of CO, H{sub 2} generation was near the tuyere; the temperature peak shifts from near the raceway boundary to the tuyere. Oxygen concentration and blast velocity were two important factors, it was found that increasing excess oxygen ratio 0.9 to 1.3, the combustion time of oil decreases 0.5 msec, an increase of the blast velocity results in increasing the flame length. In addition, the nozzle position and oil rate had large effects on the combustion of oil. Based on these results, the limit of oil injection is also discussed, soot formation is the main reason limiting to further increase oil injection rate, it was viewed that there were three types of soot which were generated under blast furnace operating conditions. The reason generating soot is the incomplete conversion of the fuel. Finally, three methods improving combustion of oil in the raceway are given: Improvement of oil

  6. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy☆ (United States)

    Alibhai, Shabbir M.H.; O’Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M.; Timilshina, Narhari; Tomlinson, George A.; Klepin, Heidi D.; Culos-Reed, S. Nicole


    Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. PMID:22726923

  7. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy. (United States)

    Alibhai, Shabbir M H; O'Neill, Sara; Fisher-Schlombs, Karla; Breunis, Henriette; Brandwein, Joseph M; Timilshina, Narhari; Tomlinson, George A; Klepin, Heidi D; Culos-Reed, S Nicole


    Patients with acute myeloid leukemia (AML) receiving induction chemotherapy (IC) were enrolled in a supervised exercise intervention to determine safety, feasibility, and efficacy. Physical fitness measures, quality of life (QOL) and fatigue were assessed using standardized measures at baseline, post-induction, and post first consolidation. Retention was excellent, the intervention was safe, and efficacy estimates suggested benefits in physical fitness and QOL outcomes. Exercise is a safe, promising intervention for improving fitness and QOL in this patient population. These results provide a foundation for a randomized trial to better understand the impact of exercise during IC on clinically important outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction

    DEFF Research Database (Denmark)

    Burnett, A. K.; Russell, N. H.; Hills, R. K.


    Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m(2) has shown benefit for some patient subgroups when compared with a dose of 45 mg/m(2), and has been...... = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at as #ISRCTN55675535....

  9. Azacitidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the Study Alliance Leukemia. (United States)

    Müller-Tidow, C; Tschanter, P; Röllig, C; Thiede, C; Koschmieder, A; Stelljes, M; Koschmieder, S; Dugas, M; Gerss, J; Butterfaß-Bahloul, T; Wagner, R; Eveslage, M; Thiem, U; Krause, S W; Kaiser, U; Kunzmann, V; Steffen, B; Noppeney, R; Herr, W; Baldus, C D; Schmitz, N; Götze, K; Reichle, A; Kaufmann, M; Neubauer, A; Schäfer-Eckart, K; Hänel, M; Peceny, R; Frickhofen, N; Kiehl, M; Giagounidis, A; Görner, M; Repp, R; Link, H; Kiani, A; Naumann, R; Brümmendorf, T H; Serve, H; Ehninger, G; Berdel, W E; Krug, U


    DNA methylation changes are a constant feature of acute myeloid leukemia. Hypomethylating drugs such as azacitidine are active in acute myeloid leukemia (AML) as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, controlled trial compared the efficacy of azacitidine applied before each cycle of intensive chemotherapy with chemotherapy alone in older patients with untreated AML. Event-free survival (EFS) was the primary end point. In total, 214 patients with a median age of 70 years were randomized to azacitidine/chemotherapy (arm-A) or chemotherapy (arm-B). More arm-A patients (39/105; 37%) than arm-B (25/109; 23%) showed adverse cytogenetics (P=0.057). Adverse events were more frequent in arm-A (15.44) versus 13.52 in arm-B, (P=0.26), but early death rates did not differ significantly (30-day mortality: 6% versus 5%, P=0.76). Median EFS was 6 months in both arms (P=0.96). Median overall survival was 15 months for patients in arm-A compared with 21 months in arm-B (P=0.35). Azacitidine added to standard chemotherapy increases toxicity in older patients with AML, but provides no additional benefit for unselected patients.

  10. Infectious Complications in Children With Acute Myeloid Leukemia and Down Syndrome: Analysis of the Prospective Multicenter Trial AML-BFM 2004. (United States)

    Hassler, Angela; Bochennek, Konrad; Gilfert, Julia; Perner, Corinna; Schöning, Stefan; Creutzig, Ursula; Reinhardt, Dirk; Lehrnbecher, Thomas


    Children with acute myeloid leukemia (AML) and Down syndrome have high survival rates with intensity-reduced chemotherapeutic regimens, although the optimal balance between dose intensity and treatment toxicity has not been determined. We, therefore, characterized infectious complications in children with AML and Down syndrome treated according to AML-BFM 2004 study ( NCT00111345; amended 2006 for Down syndrome with reduced intensity). Data on infectious complications were gathered from the medical records in the hospital where the patient was treated. Infectious complications were categorized as fever without identifiable source (FUO), or as microbiologically or clinically documented infections. A total of 157 infections occurred in 61 patients (60.5% FUO, 9.6% and 29.9% clinically and microbiologically documented infections, respectively). Almost 90% of the pathogens isolated from the bloodstream were Gram-positive bacteria, and approximately half of them were viridans group streptococci. All seven microbiologically documented episodes of pneumonia were caused by viruses. Infection-related mortality was 4.9%, and all three patients died due to viral infection. Our data demonstrate that a reduced-intensity chemotherapeutic regimen in children with AML and Down syndrome is still associated with high morbidity. Although no patient died due to bacteria or fungi, viruses were responsible for all lethal events. Future studies, therefore, have to focus on the impact of viruses on morbidity and mortality of patients with AML and Down syndrome. © 2016 Wiley Periodicals, Inc.

  11. Blast injury prevalence in skeletal remains: Are there differences between Bosnian war samples and documented combat-related deaths? (United States)

    Dussault, Marie Christine; Hanson, Ian; Smith, Martin J


    Court cases at the International Criminal Tribunal for the Former Yugoslavia (ICTY) have seen questions raised about the recognition and causes of blast-related trauma and the relationship to human rights abuses or combat. During trials, defence teams argued that trauma was combat related and prosecutors argued that trauma was related to executions. We compared a sample of 81 cases (males between 18 and 75) from a Bosnian mass grave investigation linked to the Kravica warehouse killings to published combat-related blast injury data from World War One, Vietnam, Northern Ireland, the first Gulf War, Operation Iraqi Freedom and Afghanistan. We also compared blast fracture injuries from Bosnia to blast fracture injuries sustained in bombings of buildings in two non-combat 'civilian' examples; the Oklahoma City and Birmingham pub bombings. A Chi-squared statistic with a Holm-Bonferroni correction assessed differences between prevalence of blast-related fractures in various body regions, where data were comparable. We found statistically significant differences between the Bosnian and combat contexts. We noted differences in the prevalence of head, torso, vertebral area, and limbs trauma, with a general trend for higher levels of more widespread trauma in the Bosnian sample. We noted that the pattern of trauma in the Bosnian cases resembled the pattern from the bombing in buildings civilian contexts. Variation in trauma patterns can be attributed to the influence of protective armour; the context of the environment; and the type of munition and its injuring mechanism. Blast fracture injuries sustained in the Bosnian sample showed patterns consistent with a lack of body armour, blast effects on people standing in enclosed buildings and the use of explosive munitions. Copyright © 2017 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.

  12. Blasting as a method for abandoned mine land reclamation

    International Nuclear Information System (INIS)

    Workman, J.L.; Fletcher, L.R.


    Blasting methods have been proposed for reclaiming abandoned underground coal mine sites having unstable conditions. The objective of blasting is twofold: the permanent stabilization of an area by the collapse of underground workings to prevent any future subsidence, and the use of blasting to close existing sinkholes. This paper presents the results of two research projects funded by the Bureau of Mines Abandoned Mine Land Research Program to investigate the feasibility of blasting to assist in the reclamation of shallow abandoned coal mine sites. Blasting tests were conducted at Beulah, North Dakota and at Scobey, Montana, involving different configurations. The first test was a 10-acre site where blasting was used to collapse regular room and pillar panels for which good mine layout information was available. The second test involved a one acre site containing very irregular workings for which there was little available information. Finally, blasting techniques were used to close 13 individual vertical openings. The depths to the coal seams were 60 feet or less at all sites. When blasting for Abandoned Mine Land Reclamation, material must be cast downward into the abandoned developments or laterally into the sinkhole. Designs based on cratering concepts and spherical charges worked well. The blasting techniques successfully collapsed and stabilized the test areas. Cost of reclamation for the two test sites are presented. Data from blast vibration monitoring are presented because control of vibrations is of concern when mitigation efforts are conducted near homes

  13. Acute myeloblastic leukemia with minimal myeloid differentiation (FAB AML-M0): a study of eleven cases. (United States)

    Sempere, A; Jarque, I; Guinot, M; Palau, J; García, R; Sanz, G F; Gomis, F; Pérez-Sirvent, M L; Senent, L; Sanz, M A


    The main clinical, morphological, cytochemical, immunological features and therapy results of eleven patients diagnosed as acute myeloblastic leukemia M0 (AML-M0) are reported here. There were no clinical characteristics, abnormalities on physical examination or initial laboratory parameters that distinguished these eleven patients. Bone marrow aspirates were hypocellular in four patients. The leukemic cells were undifferentiated by light microscopy and myeloperoxidase (MPO) and/or Sudan Black B (SBB) stains were negative in all cases. Myeloid differentiation antigens were present on the leukemic cells of all eleven patients, whereas B and T cell markers were clearly negative except for CD4 and CD7 antigens. Whatever the treatment employed survival was very short. Eight of the eleven patients were treated and two achieved complete remission (CR) but only one of them is alive in continuous CR. Our results like those previously reported, suggest that AML-M0 patients have a very poor prognosis with standard induction therapies and should perhaps be considered for experimental therapeutic approaches.

  14. Treatment strategies in patients with AML or high-risk myelodysplastic syndrome relapsed after Allo-SCT. (United States)

    Sauer, T; Silling, G; Groth, C; Rosenow, F; Krug, U; Görlich, D; Evers, G; Albring, J; Besoke, R; Mesters, R M; Müller-Tidow, C; Kessler, T; Büchner, T; Berdel, W E; Stelljes, M


    Non-relapse mortality after Allo-SCT has significantly decreased over the last years. Nevertheless, relapse remains a major cause for post SCT mortality in patients with AML and high-risk myelodysplastic syndrome (MDS). In this retrospective single-center analysis, we have analyzed the treatment outcomes of 108 patients with AML or MDS, who relapsed after Allo-SCT. Seventy of these patients (65%) were treated with salvage therapies containing chemotherapy alone, allogeneic cell-based treatment or the combination of both. Thirty-eight patients (35%) received palliative treatment. Median OS after diagnosis of relapse was 130 days. Compared with patients who received chemotherapy alone, response to salvage therapy was significantly improved in patients treated with a combination of chemo- and allogeneic cell-based therapy (CR rate 57% vs 13%, P=0.002). Among risk factors concerning pretreatment characteristics, disease status before first Allo-SCT, and details of transplantation, only the time interval from Allo-SCT to relapse was an independent predictor of response to salvage therapy and OS. These data confirmed that time to relapse after transplantation is an important prognostic factor. Up to now, only patients eligible for treatment regimens containing allogeneic cell-based interventions achieved relevant response rates.

  15. Geotourism and Sustainability: The Kızılcahamam – Çamlıdere Geopark Case

    Directory of Open Access Journals (Sweden)

    M. Sercan Gürsay


    Full Text Available Today, geotourism is one of the popular types of special interest tourism. On the other hand, poorly managed tourism can have some negative economic, environmental and socio-cultural impacts on destinations. Therefore, all types of tourism should be managed with a sustainable approach. The concept of sustainability, which had been first introduced in 1987, in the Report entitled “Our Common Future” as a fundamental of development, and has three dimensions of social, economic and environmental aspects. The purpose of this study is to evaluate sustainable tourism practices in Kızılcahamam - Çamlıdere Geopark. In this context, local stakeholders’ opinion on the importance of sustainable tourism in the management of the geopark area is determined. The qualitative method was used in this study. Data were collected through review of the related literature, observation and in-depth interviews. As a result of the study, physical and legal deficiencies in the protection and the management of the geopark area were identified. The lack of trained and qualified work force, sustainable financial resources, local participation, and education are the other major issues in terms of sustaining geotourismin Kızılcahamam - Çamlıdere Geopark. These deficiencies can be corrected under the UNESCO GGN (Global Geopark Network criteria.

  16. Development of a Continuous Drill and Blast Tunneling Concept, Phase II (United States)


    A spiral drilling pattern is described which offers high efficiency drill and blast tunnelling via frequent small blasts rather than occasional large blasts. Design work is presented for a machine which would stay at the face to provide essentially c...

  17. 77 FR 31878 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Blasting... (United States)


    ... requirements designed to protect covered employees working with and around blasting operations. Inventories of... for OMB Review; Comment Request; Blasting Operations and Use of Explosives Standard ACTION: Notice... (OSHA) sponsored information collection request (ICR) titled, ``Blasting Operations and Use of...

  18. Concepts and strategies for clinical management of blast-induced traumatic brain injury and posttraumatic stress disorder. (United States)

    Chen, Yun; Huang, Wei; Constantini, Shlomi


    After exposure of the human body to blast, kinetic energy of the blast shock waves might be transferred into hydraulic energy in the cardiovascular system to cause a rapid physical movement or displacement of blood (a volumetric blood surge). The volumetric blood surge moves through blood vessels from the high-pressure body cavity to the low-pressure cranial cavity, causing damage to tiny cerebral blood vessels and the blood-brain barrier (BBB). Large-scale cerebrovascular insults and BBB damage that occur globally throughout the brain may be the main causes of non-impact, blast-induced brain injuries, including the spectrum of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). The volumetric blood surge may be a major contributor not only to blast-induced brain injuries resulting from physical trauma, but may also be the trigger to psychiatric disorders resulting from emotional and psychological trauma. Clinical imaging technologies, which are able to detect tiny cerebrovascular insults, changes in blood flow, and cerebral edema, may help diagnose both TBI and PTSD in the victims exposed to blasts. Potentially, prompt medical treatment aiming at prevention of secondary neuronal damage may slow down or even block the cascade of events that lead to progressive neuronal damage and subsequent long-term neurological and psychiatric impairment.

  19. Application of Carbon Composite Bricks for Blast Furnace Hearth (United States)

    Zuo, Haibin; Wang, Cong; Zhang, Jianliang; Zhao, Yongan; Jiao, Kexin

    Traditional refractory materials for blast furnace hearth lining are mainly composed of carbon bricks and the ceramic cup. However, these materials can't meet the demands for long service life design of blast furnaces. In this paper, a new refractory called carbon composite brick (CCB) was introduced, which combined the advantages of carbon bricks and the ceramic cup. In this case, the resistance of the CCB against corrosion was equal to the ceramic cup and the thermal conductivity of the CCB was equal to carbon bricks. From the results of more than 20 blast furnaces, the CCB could be well used in small blast furnaces and large blast furnaces. In the bad condition of low grade burden and high smelting intensity, the CCB gave full play to the role of cooling system, and effectively resisted the erosion of hot metal to improve the service life of blast furnaces.

  20. Safety management system during rock blasting at FRFCF construction site

    International Nuclear Information System (INIS)

    Vijayakumaran, C.; Kandasamy, S.; Satpathy, K.K.


    Blasting is an important activity during rock excavation to reach required depth for obtaining stability of the civil structure. For the construction of various Plant Buildings of Fast Reactor Fuel Cycle Facility (FRFCF), IGCAR at Kalpakkam, based on the geological survey it is required to reach a depth of 21.4 meters from existing ground level. This paper details about the procedures and precaution adopted during the rock blasting activities at FRFCF site. The volume of rock removed by blasting was 3 lakh cubic meters. The total number of blasting carried out was 304 using 105.73 tons of blasting material. The entire blasting work could be completed within 174 days without any incident. (author)

  1. Hematopoietic growth factors and human acute leukemia. (United States)

    Löwenberg, B; Touw, I


    The study of myelopoietic maturation arrest in acute myeloblastic leukemia (AML) has been eased by availability of the human recombinant hemopoietic growth factors, macrophage colony stimulating factor (M-CSF), granulocyte-(G-CSF), granulocyte-macrophage-(GM-CSF) and multilineage stimulating factor (IL-3). Nonphysiological expansion of the leukemic population is not due to escape from control by these factors. Proliferation in vitro of AML cells is dependent on the presence of one or several factors in most cases. The pattern of factor-dependency does not correlate with morphological criteria in individual cases, and may thus offer a new tool for classification of AML. Overproduction of undifferentiated cells is not due to abnormal expression of receptors for the stimulating factors acting at an immature level. Rather, autocrine secretion of early acting lymphokines maintains proliferation of the leukemic clone. When looking at causes of leukemic dysregulation, yet undefined inhibitors of differentiation probably are of equal importance as dysequilibrated stimulation by lymphokines.

  2. Proceedings of the seventeenth annual conference on explosives and blasting technique. Volume 1

    International Nuclear Information System (INIS)



    Papers from this conference dealt with the following topics: surface and underground mine blasting, control of blast effects in sensitive areas, blasthole deviation, regulatory impact when blasting at Superfund sites, computer-aided blast design and monitoring, tunneling techniques, shaft excavations, video camera analysis of blasting operations, soil densification, cost optimization, mine blasting accidents, non-electric initiation systems, and delay detonators. Papers have been indexed separately for inclusion on the data base

  3. Pathological Fingerprints, Systems Biology and Biomarkers of Blast Brain Injury (United States)


    changes after blast injury. J. Trauma 56, 393–403. Murthy, J.M., Chopra, J.S., and Gulati, D.R. (1979). Subdural hematoma in an adult following a blast...neuronal damage), diffuse brain injury, and subdural hemorrhage. It is still controversial whether primary blast forces directly damage the brain, and if...emboli, leading to infarction (Guy et al., 2000a; Guy et al., 2000b). The most common types of TBI are diffuse axonal injury, contusion, and subdural

  4. Resveratrol Downregulates Interleukin-6-Stimulated Sonic Hedgehog Signaling in Human Acute Myeloid Leukemia (United States)

    Su, Yu-Chieh; Li, Szu-Chin; Wu, Yin-Chi; Wang, Li-Min; Chao, K. S. Clifford; Liao, Hui-Fen


    IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the growth of cancer stem cells (CSCs). Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1β in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted. PMID:23533494

  5. A Phased Array Approach to Rock Blasting

    Energy Technology Data Exchange (ETDEWEB)

    Leslie Gertsch; Jason Baird


    A series of laboratory-scale simultaneous two-hole shots was performed in a rock simulant (mortar) to record the shock wave interference patterns produced in the material. The purpose of the project as a whole was to evaluate the usefulness of phased array techniques of blast design, using new high-precision delay technology. Despite high-speed photography, however, we were unable to detect the passage of the shock waves through the samples to determine how well they matched the expected interaction geometry. The follow-up mine-scale tests were therefore not conducted. Nevertheless, pattern analysis of the vectors that would be formed by positive interference of the shockwaves from multiple charges in an ideal continuous, homogeneous, isotropic medium indicate the potential for powerful control of blast design, given precise characterization of the target rock mass.

  6. Proceedings of the eighteenth annual conference on explosives and blasting technique

    International Nuclear Information System (INIS)



    This edition of the Proceedings of the Annual Conference on Explosives and Blasting Techniques is the eighteenth in a series published by the International Society of Explosives Engineers. The papers cover a wide variety of explosives and blasting techniques, including: rock mechanics, rock drilling, perimeter control handling and documenting blasting complaints, blast vibration frequencies, blasting techniques for surface and underground coal mines, explosives for permafrost blasting, lightning detection, use of slow motion video to analyze blasts, tunneling, and close-in blasting control. Papers have been processed individually for inclusion on the data base

  7. Experimental Study and Engineering Practice of Pressured Water Coupling Blasting

    Directory of Open Access Journals (Sweden)

    J. X. Yang


    Full Text Available Overburden strata movement in large space stope is the major reason that induces the appearance of strong mining pressure. Presplitting blasting for hard coal rocks is crucial for the prevention and control of strong pressure in stope. In this study, pressured water coupling blasting technique was proposed. The process and effect of blasting were analyzed by orthogonal test and field practice. Results showed that the presence of pressure-bearing water and explosive cartridges in the drill are the main influence factors of the blasting effect of cement test block. The high load-transmitting performance of pore water and energy accumulation in explosive cartridges were analyzed. Noxious substances produced during the blasting process were properly controlled because of the moistening, cooling, and diluting effect of pore water. Not only the goal of safe and static rock fragmentation by high-explosive detonation but also a combination of superdynamic blast loading and static loading effect of the pressured water was achieved. Then the practice of blasting control of hard coal rocks in Datong coal mine was analyzed to determine reasonable parameters of pressured water coupling blasting. A good presplitting blasting control effect was achieved for the hard coal rocks.

  8. Assessment of Blasting Operations Effects During Highway Tunnel Construction

    Directory of Open Access Journals (Sweden)

    Valašková Veronika


    Full Text Available Blasting operations are one of the fundamental parts of daily civil engineering. Drilling and blasting still remain the only possible ways of tunnelling in very adverse geological conditions. However, this method is a source of various disadvantages, the main one being tremors propagating through the geological environment which not only affect buildings, but also disturb the comfort of living in the vicinity of the source. Designing this procedure is mostly done using standardized empirical relations. This article shows the possibility of using a FEM technique in predicting blast effects. This approach is demonstrated in a simple case study on the impact of blasting operations on steel pipes.

  9. Collapse of rocks by blasting. Razrusheniye gornykh porod Vzryvom

    Energy Technology Data Exchange (ETDEWEB)

    Sukhanov, A F; Kutuzov, B N


    Information is provided about drilling boreholes and wells, explosives and the means for initiating them, storage, transporting and calculation of the explosive materials. Physical essence of the destructive, scientific and air effect of the blast are presented, principles of arrangement and calculation of the charges, reasons for malfunctions and methods of eliminating them, measures for protecting the surrounding objects from harmful effect of the industrial blast. Questions are examined of planning, organization and safety of the blasting operations. The second edition (first edition 1967) has been revised with regard for changes that occurred in the field of blasting operations.

  10. Water-Depth-Based Prediction Formula for the Blasting Vibration Velocity of Lighthouse Caused by Underwater Drilling Blasting

    Directory of Open Access Journals (Sweden)

    Wenbin Gu


    Full Text Available Lighthouses are the most important hydraulic structures that should be protected during underwater drilling blasting. Thus, the effect of blasting vibration on lighthouse should be studied. On the basis of the dimensional analysis, we deduced a revised formula for water depth based on Sodev’s empirical formula and established the linear fitting model. During the underwater reef project in the main channel of Shipu Harbor in the Ningbo–Zhoushan Port, the blasting vibration data of the lighthouse near the underwater blasting area were monitored. The undetermined coefficient, resolvable coefficient, and F value of the two formulas were then obtained. The comparison of the data obtained from the two formulas showed that they can effectively predict the blasting vibration on the lighthouse. The correction formula that considers water depth can obviously reduce prediction errors and accurately predict blasting vibration.

  11. Blast Injuries: What Clinicians Need to Know

    Centers for Disease Control (CDC) Podcasts


    In this podcast, Dr. Richard C. Hunt, Director of the CDC’s Division of Injury Response, National Center for Injury Prevention and Control provides a brief overview for health care providers on how to respond and care for persons injured by an explosion or blast event.  Created: 11/5/2008 by National Center for Injury Prevention and Control (NCIPC), Division of Injury Response (DIR).   Date Released: 11/6/2008.

  12. Prevention of Blast-Related Injuries (United States)


    in a canvas harness. The harness was further supported by a steel frame which was suspended from a metal beam (3.7 m off the ground) mounted on...direction of the wave propagation (Figure 5). After proper alignment of the head with respect to the center of the C4 charge, the steel frame was...further tied to four hooks cemented to the concrete ground with straps to prevent excessive motion during the blast exposure. The intensity of the two

  13. Blast vibration monitoring, July to December, 1983

    Energy Technology Data Exchange (ETDEWEB)


    The complexity of the vibration waveforms produced appears at this stage to preclude simple comparison of different blasts. A modelling approach is indicated from the preliminary experiments. The required elemental charge length and the steady state column length of ANFO in 381 mm holes must be determined for further development of a model. This information may be acquired by firing a number of charges of varying lengths with all other variables held constant.

  14. Centrifugal shot blasting. Innovative technology summary report

    International Nuclear Information System (INIS)


    At the US Department of Energy (DOE) Fernald Environmental Management Project (FEMP), the Facilities Closure and Demolition Projects Integrated Remedial Design/Remedial Action (RD/RA) work plan calls for the removal of one inch (1 in) depth of concrete surface in areas where contamination with technetium-99 has been identified. This report describes a comparative demonstration between two concrete removal technologies: an innovative system using Centrifugal Shot Blasting (CSB) and a modified baseline technology called a rotary drum planer

  15. Blast furnace hearth lining: post mortem analysis

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Bruno Vidal de; Vernilli Junior, Fernando, E-mail: [Universidade de Sao Paulo (USP), Lorena, SP (Brazil). Escola de Engenharia; Neves; Elton Silva; Silva, Sidiney Nascimento [Companhia Siderugica Nacional (CSN), Rio de Janeiro, RJ (Brazil)


    The main refractory lining of blast furnace hearth is composed by carbon blocks that operates in continuous contact with hot gases, liquid slag and hot metal, in temperatures above 1550 deg C for 24 hours a day. To fully understand the wear mechanism that acts in this refractory layer system it was performed a Post Mortem study during the last partial repair of this furnace. The samples were collected from different parts of the hearth lining and characterized using the following techniques: Bulk Density and Apparent Porosity, X-Ray Fluorescence, X-ray Diffraction, Scanning Electron Microscopy with Energy-dispersive X-Ray Spectroscopy. The results showed that the carbon blocks located at the opposite side of the blast furnace tap hole kept its main physicochemical characteristics preserved even after the production of 20x10{sup 6} ton of hot metal. However, the carbon blocks around the Tap Hole showed infiltration by hot metal and slag and it presents a severe deposition of zinc and sulfur over its carbon flakes. The presence of these elements is undesired because it reduces the physic-chemical stability of this refractory system. This deposition found in the carbon refractory is associated with impurities present in the both coke and the sinter feed used in this blast furnace in the last few years. (author)

  16. Blast furnace hearth lining: post mortem analysis

    International Nuclear Information System (INIS)

    Almeida, Bruno Vidal de; Vernilli Junior, Fernando


    The main refractory lining of blast furnace hearth is composed by carbon blocks that operates in continuous contact with hot gases, liquid slag and hot metal, in temperatures above 1550 deg C for 24 hours a day. To fully understand the wear mechanism that acts in this refractory layer system it was performed a Post Mortem study during the last partial repair of this furnace. The samples were collected from different parts of the hearth lining and characterized using the following techniques: Bulk Density and Apparent Porosity, X-Ray Fluorescence, X-ray Diffraction, Scanning Electron Microscopy with Energy-dispersive X-Ray Spectroscopy. The results showed that the carbon blocks located at the opposite side of the blast furnace tap hole kept its main physicochemical characteristics preserved even after the production of 20x10"6 ton of hot metal. However, the carbon blocks around the Tap Hole showed infiltration by hot metal and slag and it presents a severe deposition of zinc and sulfur over its carbon flakes. The presence of these elements is undesired because it reduces the physic-chemical stability of this refractory system. This deposition found in the carbon refractory is associated with impurities present in the both coke and the sinter feed used in this blast furnace in the last few years. (author)

  17. The Blast Fungus Decoded: Genomes in Flux

    Directory of Open Access Journals (Sweden)

    Thorsten Langner


    Full Text Available Plant disease outbreaks caused by fungi are a chronic threat to global food security. A prime case is blast disease, which is caused by the ascomycete fungus Magnaporthe oryzae (syn. Pyricularia oryzae, which is infamous as the most destructive disease of the staple crop rice. However, despite its Linnaean binomial name, M. oryzae is a multihost pathogen that infects more than 50 species of grasses. A timely study by P. Gladieux and colleagues (mBio 9:e01219-17, 2018, reports the most extensive population genomic analysis of the blast fungus thus far. M. oryzae consists of an assemblage of differentiated lineages that tend to be associated with particular host genera. Nonetheless, there is clear evidence of gene flow between lineages consistent with maintaining M. oryzae as a single species. Here, we discuss these findings with an emphasis on the ecologic and genetic mechanisms underpinning gene flow. This work also bears practical implications for diagnostics, surveillance, and management of blast diseases.

  18. D-BLAST OFDM with Channel Estimation

    Directory of Open Access Journals (Sweden)

    Du Jianxuan


    Full Text Available Multiple-input and multiple-output (MIMO systems formed by multiple transmit and receive antennas can improve performance and increase capacity of wireless communication systems. Diagonal Bell Laboratories Layered Space-Time (D-BLAST structure offers a low-complexity solution for realizing the attractive capacity of MIMO systems. However, for broadband wireless communications, channel is frequency-selective and orthogonal frequency division multiplexing (OFDM has to be used with MIMO techniques to reduce system complexity. In this paper, we investigate D-BLAST for MIMO-OFDM systems. We develop a layerwise channel estimation algorithm which is robust to channel variation by exploiting the characteristic of the D-BLAST structure. Further improvement is made by subspace tracking to considerably reduce the error floor. Simulation results show that the layerwise estimators require 1 dB less signal-to-noise ratio (SNR than the traditional blockwise estimator for a word error rate (WER of when Doppler frequency is 40 Hz. Among the layerwise estimators, the subspace-tracking estimator provides a 0.8 dB gain for WER with 200 Hz Doppler frequency compared with the DFT-based estimator.

  19. The Blast Fungus Decoded: Genomes in Flux. (United States)

    Langner, Thorsten; Białas, Aleksandra; Kamoun, Sophien


    Plant disease outbreaks caused by fungi are a chronic threat to global food security. A prime case is blast disease, which is caused by the ascomycete fungus Magnaporthe oryzae (syn. Pyricularia oryzae ), which is infamous as the most destructive disease of the staple crop rice. However, despite its Linnaean binomial name, M. oryzae is a multihost pathogen that infects more than 50 species of grasses. A timely study by P. Gladieux and colleagues (mBio 9:e01219-17, 2018, reports the most extensive population genomic analysis of the blast fungus thus far. M. oryzae consists of an assemblage of differentiated lineages that tend to be associated with particular host genera. Nonetheless, there is clear evidence of gene flow between lineages consistent with maintaining M. oryzae as a single species. Here, we discuss these findings with an emphasis on the ecologic and genetic mechanisms underpinning gene flow. This work also bears practical implications for diagnostics, surveillance, and management of blast diseases. Copyright © 2018 Langner et al.

  20. Verification of wet blasting decontamination technology

    International Nuclear Information System (INIS)

    Matsubara, Sachito; Murayama, Kazunari; Yoshida, Hirohisa; Igei, Shigemitsu; Izumida, Tatsuo


    Macoho Co., Ltd. participated in the projects of 'Decontamination Verification Test FY 2011 by the Ministry of the Environment' and 'Decontamination Verification Test FY 2011 by the Cabinet Office.' And we tested verification to use a wet blasting technology for decontamination of rubble and roads contaminated by the accident of Fukushima Daiichi Nuclear Power Plant of the Tokyo Electric Power Company. As a results of the verification test, the wet blasting decontamination technology showed that a decontamination rate became 60-80% for concrete paving, interlocking, dense-grated asphalt pavement when applied to the decontamination of the road. When it was applied to rubble decontamination, a decontamination rate was 50-60% for gravel and approximately 90% for concrete and wood. It was thought that Cs-134 and Cs-137 attached to the fine sludge scraped off from a decontamination object and the sludge was found to be separated from abrasives by wet cyclene classification: the activity concentration of the abrasives is 1/30 or less than the sludge. The result shows that the abrasives can be reused without problems when the wet blasting decontamination technology is used. (author)

  1. Water-Depth-Based Prediction Formula for the Blasting Vibration Velocity of Lighthouse Caused by Underwater Drilling Blasting


    Gu, Wenbin; Wang, Zhenxiong; Liu, Jianqing; Xu, Jinglin; Liu, Xin; Cao, Tao


    Lighthouses are the most important hydraulic structures that should be protected during underwater drilling blasting. Thus, the effect of blasting vibration on lighthouse should be studied. On the basis of the dimensional analysis, we deduced a revised formula for water depth based on Sodev’s empirical formula and established the linear fitting model. During the underwater reef project in the main channel of Shipu Harbor in the Ningbo–Zhoushan Port, the blasting vibration data of the lighthou...

  2. Numerical Investigation of Structural Response of Corrugated Blast Wall Depending on Blast Load Pulse Shapes

    Directory of Open Access Journals (Sweden)

    Jung Min Sohn

    Full Text Available Abstract Hydrocarbon explosions are one of most hazardous events for workers on offshore platforms. To protect structures against explosion loads, corrugated blast walls are typically installed. However, the profiles of real explosion loads are quite different depending on the congestion and confinement of Topside structures. As the level of congestion and confinement increases, the explosion load increases by up to 8 bar, and the rising time of the load decreases. This study primarily aims to investigate the structural behavior characteristics of corrugated blast walls under different types of explosion loadings. Four loading shapes were applied in the structural response analysis, which utilized a dynamic nonlinear finite element method.

  3. Evaluation of Blast Resistance of Fiber Reinforced Composite Specimens under Contact Blast Load (United States)

    Janota, O.; Foglar, M.


    This paper presents results of experimental programme which took place in 2014, 2015 and 2016. Experiments were focused on the resistance of full scale concrete panels subjected to contact blast loading. Specimens were loaded by contact blast by plastic explosive. All specimens were reinforced concrete slabs made of fiber concrete. Basalt mesh and textile sheets were added to some of the experiments for creating more heterogeneous material to achieve better resistance of the specimens. Evaluation of experiments was mainly focused on the damaged area on the contact side and soffit of the specimens. Dependency of the final damage of concrete panels on the weight of explosive and concrete strength was assessed.

  4. Modeling and simulation of explosion effectiveness as a function of blast and crowd characteristics (United States)

    Usmani, Zeeshan-Ul-Hassan

    Suicide bombing has become one of the most lethal and favorite modus operandi of terrorist organizations around the world. On average, there is a suicide bombing attack every six days somewhere in the world. While various attempts have been made to assess the impact of explosions on structures and military personnel, little has been done on modeling the impact of a blast wave on a crowd in civilian settings. The assessment of an explosion's effect on a crowd can lead to better management of disasters, triage of patients, locating blast victims under the debris, development of protective gear, and safe distance recommendations to reduce the casualties. The overall goal of this work is to predict the magnitude of injuries and lethality on humans from a blast-wave with various explosive and crowd characteristics, and to compare, contrast, and analyze the performance of explosive and injury models against the real-life data of suicide bombing incidents. This thesis introduces BlastSim---a physics based stationary multi-agent simulation platform to model and simulate a suicide bombing event. The agents are constrained by the physical characteristics and mechanics of the blast wave. The BlastSim is programmed to test, analyze, and validate the results of different model combinations under various conditions with different sets of parameters, such as the crowd and explosive characteristics, blockage and human shields, fragmentation and the bomber's position, in 2-dimensional and 3-dimensional environments. The suicide bombing event can be re-created for forensic analysis. The proposed model combinations show a significant performance---the Harold Brode explosive model with Catherine Lee injury model using the blockage stands out consistently to be the best with an overall cumulative accuracy of 87.6%. When comparing against actual data, overall, prediction accuracy can be increased by 71% using this model combination. The J. Clutter with Reflection explosive model using

  5. Blast-induced electromagnetic fields in the brain from bone piezoelectricity. (United States)

    Lee, Ka Yan Karen; Nyein, Michelle K; Moore, David F; Joannopoulos, J D; Socrate, Simona; Imholt, Timothy; Radovitzky, Raul; Johnson, Steven G


    In this paper, we show that bone piezoelectricity-a phenomenon in which bone polarizes electrically in response to an applied mechanical stress and produces a short-range electric field-may be a source of intense blast-induced electric fields in the brain, with magnitudes and timescales comparable to fields with known neurological effects. We compute the induced charge density in the skull from stress data on the skull from a finite-element full-head model simulation of a typical IED-scale blast wave incident on an unhelmeted human head as well as a human head protected by a kevlar helmet, and estimate the resulting electric fields in the brain in both cases to be on the order of 10 V/m in millisecond pulses. These fields are more than 10 times stronger than the IEEE safety guidelines for controlled environments (IEEE Standards Coordinating Committee 28, 2002) and comparable in strength and timescale to fields from repetitive Transcranial Magnetic Stimulation (rTMS) that are designed to induce neurological effects (Wagner et al., 2006a). They can be easily measured by RF antennas, and may provide the means to design a diagnostic tool that records a quantitative measure of the head's exposure to blast insult. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Clonal evolution of AML on novel FMS-like tyrosine kinase-3 (FLT3 inhibitor therapy with evolving actionable targets

    Directory of Open Access Journals (Sweden)

    Pashtoon M. Kasi


    Full Text Available For acute myeloid leukemia (AML, identification of activating mutations in the FMS-like tyrosine kinase-3 (FLT3 has led to the development of several FLT3-inhibitors. Here we present clinical and next generation sequencing data at the time of progression of a patient on a novel FLT3-inhibitor clinical trial (ASP2215 to show that employing therapeutic interventions with these novel targeted therapies can lead to consequences secondary to selective pressure and clonal evolution of cancer. We describe novel findings alongside data on treatment directed towards actionable aberrations acquired during the process. (Clinical Trial: NCT02014558; registered at: 〈〉

  7. A case of AML with preceding hypoplastic stage after oophoro-hysterectomy and 60Co-irradiation

    International Nuclear Information System (INIS)

    Yoshida, Takashi; Nakamura, Shinobu; Hattori, Kenichi; Tanimoto, Kazuo.


    A case of AML (preceded by a hypoplastic stage) which developed after oophoro-hysterectomy and 60 Co-irradiation is presented, and related literature concerning irradiation-induced leukemia and the early diagnosis of leukemia and/or preleukemia are discussed. The patient, a 47 year old female had had surgery and irradiation with a subsequent normachromic anemia necessitating transfusions 11 years prior to her presenting herself at our hospital because of anemia. Her pancytopenic peripheral blood picture combined with a relatively hypererythroid marron led to a diagnosis of atypical hypoplastic anemia. Two years after this she suddenly developed a high fever, general fatigue and a severe anemia. Hematological studies revealed acute myeloblastic leukemia. A combination therapy consisting of DM, 6MP, prednisolon and blood transfusions was given with no effect and 3 months after the onset, the patient died of asphyxia resulting from gross hemoptysis. Autopsy revealed pulmonary hemorrhage secondary to the leukemia. (J. Evans)

  8. Detection of TET2, KRAS and CBL variants by Next Generation Sequencing and analysis of their correlation with JAK2 and FLT3 in childhood AML

    Directory of Open Access Journals (Sweden)

    Dilara Fatma Akin


    Conclusion: We found novel mutations for TET2, KRAS, and CBL. The detected variants in this article seem to be the first screening results of genes studied by NGS in childhood AML patients. Our results also showed some degree of association between FLT3-ITD and TET2, KRAS, CBL mutations.

  9. The impact of center experience on results of reduced intensity:allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

    DEFF Research Database (Denmark)

    Giebel, S; Labopin, M; Mohty, M


    Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related...

  10. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more : results of a multicenter phase 3 study

    NARCIS (Netherlands)

    Lowenberg, Bob; Beck, Joachim; Graux, Carlos; van Putten, Wim; Schouten, Harry C.; Verdonck, Leo F.; Ferrant, Augustin; Sonneveld, Pieter; Jongen-Lavrencic, Mojca; von Lilienfeld-Toal, Marie; Biemond, Bart J.; Vellenga, Edo; Breems, Dimitri; de Muijnck, Hilde; Schaafsma, Ron; Verhoef, Gregor; Doehner, Hartmut; Gratwohl, Alois; Pabst, Thomas; Ossenkoppele, Gert J.; Maertens, Johan


    In older patients with acute myeloid leukemia (AML), the prevention of relapse has remained one of the major therapeutic challenges, with more than 75% relapses after complete remission. The anti-CD33 immunotoxin conjugate gemtuzumab ozogamicin (GO) has shown antileukemic remission induction

  11. Acute myeloid leukemia associated with t(10;17)(p13-15;q12-21) and phagocytic activity by leukemic blasts: a clinical study and review of the literature. (United States)

    Oh, Seung Hwan; Park, Tae Sung; Cho, Sun Young; Kim, Min Jin; Huh, Jungwon; Kim, Bomi; Song, Sae Am; Lee, Ja Young; Jun, Kyung Ran; Shin, Jeong Hwan; Kim, Hye Ran; Lee, Jeong Nyeo


    Translocation (10;17)(p13-15;q12-21) in acute leukemia is rarely reported in the literature. Here, we present both a novel t(10;17) case study and a review of relevant literature on t(10;17) in acute leukemia (10 cases). In summary, we came to the following preliminary conclusions: t(10;17) is associated with poorly differentiated acute leukemia subtype [90%; eight cases of acute myeloid leukemia (AML M0, M1) and one case of acute undifferentiated leukemia], phagocytic activity by blasts occurs (30%), and the survival time was short in three of the seven t(10;17) cases for whom follow-up data were available (median, 8 months). More clinical studies concerning the prognosis, treatment response, and survival of patients with t(10;17) are necessary. 2010 Elsevier Inc. All rights reserved.

  12. 30 CFR 57.6605 - Isolation of blasting circuits. (United States)


    ... NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Explosives Extraneous Electricity-Surface and Underground § 57.6605 Isolation of blasting circuits. Lead wires and blasting lines shall be isolated and insulated from power conductors, pipelines, and railroad tracks, and...

  13. Blasting Standards for the Ghanaian Mining Industry | Amegbey ...

    African Journals Online (AJOL)

    Ghana is a well known mining nation and hard rock mining has been going on since the 10th century. Mining companies in Ghana are well aware of the regulatory requirements to carry out blasting activities such that neighbouring communities are protected from excessive impact as a result of blast vibrations amongst other ...

  14. Liquid flow in the hearth of the blast furnace

    International Nuclear Information System (INIS)

    Gauje, P.; Nicolle, R.; Steiler, J.M.; Venturini, M.J.; Libralesso, J.M.


    The hearth of a blast furnace is poorly known. Our approach to characterize the hearth involves classical methods of chemical engineering, assessing the flow conditions by means of radioactive tracer techniques. The most important feature of this study is to combine measurements on industrial blast furnaces, experiments on a small scale model and flow model. calculations. 8 refs., 16 figs

  15. Implementation of a user defined mine blast model in LSDYNA

    NARCIS (Netherlands)

    Tyler-Street, M.; Leerdam, P.J.C.


    A user defined mine blast model has been developed and implemented into the explicit finite element code LS-DYNA to provide a numerically efficient method for simulating an antivehicular mine blast. The objective is to provide a simple and robust numerical method which is able to represent both the

  16. Inheritance of blast resistance and identification of SSR marker ...

    Indian Academy of Sciences (India)


    Aug 2, 2013 ... arm of chromosome 6 and in close proximity of blast resis- ... resistance to a M. oryzae race in a gene-for-gene manner. DNA markers have been ... order to identify the new sources of resistance against blast, there is need for ...

  17. 30 CFR 75.1310 - Explosives and blasting equipment. (United States)


    ... for use so long as the present approval is maintained. (e) Electric detonators shall be compatible... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Explosives and blasting equipment. 75.1310... SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Explosives and Blasting § 75.1310...

  18. Equipment Specific Optimum Blast-Design Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Rahul Upadhyay


    Full Text Available Design of blasting parameters plays an important role in the optimization of mining cost as well as cost of subsequent processing of ore. Drilling and handling costs are the major mining cost. This work presents an indirect optimization model for mining cost through optimization of blasting parameters for a particular set of drilling and loading equipment.

  19. Storage stability of flour-blasted brown rice (United States)

    Brown rice was blasted with rice flour rather than sand in a sand blaster to make microscopic nicks and cuts so that water can easily penetrate into the brown rice endosperm and cook the rice in a shorter time. The flour-blasted American Basmati brown rice, long grain brown rice, and parboiled long...

  20. Reducing Drill and Blast Cost through Blast Optimisation – A Case ...

    African Journals Online (AJOL)

    Michael O. Mensah


    Dec 2, 2015 ... Case Study* ... using the proposed blast parameters increased by 14.3 to 50.0% for ore zones and 12.5 ... of gold, compels technologists in the industry to .... 127. Bench Height (H), m. 4. 4. 4.5. 4.5. 4.5. 4.5. Sub-drill (U), m. 0.5.

  1. Evaluating the Effectiveness of Various Blast Loading Descriptors as Occupant Injury Predictors for Underbody Blast Events (United States)


    expressed herein do not necessarily state or reflect those of the United States Government or the DoD, and shall not be used for advertising or...Trembelay, J., “Validation of a Loading Model for Simulating Blast Mine Effects on Armoured Vehicles,” 7th International LS-DYNA Users Conference

  2. Blasting and Blast Effects in Cold Regions. Part 3. Explosions in Ground Materials (United States)


    121- York, Ontario: Technical Marketing Services- 123. Explosives, Canadian Industries, 6th edition. Gaffney, E.S. (1984b) Hugoniot of water ice. In...Mines, blasting. U.S. Bureau of Nlines , Report of Insesti- Report of lnsestigations RI 7751. gations 8507. Piekutoiski. A.J. (1974) I.aborator,, scale

  3. ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1-RUNX1T1 and associated with a better prognosis. (United States)

    Yamato, Genki; Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Hara, Yusuke; Ohki, Kentaro; Okubo, Jun; Okuno, Haruna; Chiba, Kenichi; Tanaka, Hiroko; Kinoshita, Akitoshi; Moritake, Hiroshi; Kiyokawa, Nobutaka; Tomizawa, Daisuke; Park, Myoung-Ja; Sotomatsu, Manabu; Taga, Takashi; Adachi, Souichi; Tawa, Akio; Horibe, Keizo; Arakawa, Hirokazu; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide


    ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event-free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild-type (5-year OS, 75% vs. 100% vs. 91% and 5-year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously. © 2017 Wiley Periodicals, Inc.

  4. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells. (United States)

    Saenz, D T; Fiskus, W; Qian, Y; Manshouri, T; Rajapakshe, K; Raina, K; Coleman, K G; Crew, A P; Shen, A; Mill, C P; Sun, B; Qiu, P; Kadia, T M; Pemmaraju, N; DiNardo, C; Kim, M-S; Nowak, A J; Coarfa, C; Crews, C M; Verstovsek, S; Bhalla, K N


    The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.

  5. [Dexamethasone and vorinostat cooperatively promote differentiation and apoptosis in Kasumi-1 leukemia cells through ubiquitination and degradation of AML1-ETO]. (United States)

    Chen, Li-ping; Zhang, Jian-wei; Xu, Fa-mei; Xing, Hai-yan; Tian, Zheng; Wang, Min; Wang, Jian-xiang


    To probe the effects of dexamethasone (DEX) combined with histone deacetylase (HDAC) inhibitor vorinostat on inhibiting proliferation and inducing differentiation and apoptosis in Kasumi-1 leukemia cells, and its possible mechanisms in order to provide a theoretical basis for the treatment of AML1-ETO positive AML. The cell survival, differentiation and apoptosis rates were tested by MTT or flow cytometry analysis after Kasumi-1 cells were treated by DMSO, DEX (20 nmol/L), vorinostat (1 μmol/L) or DEX (20 nmol/L) in combination with vorinostat (1 μmol/L). WB and IP-WB were performed to detect AML1-ETO and its ubiquitination. Treatment with the combination of DEX and vorinostat for 48 h led to statistically significant differences of inhibited proliferation [(42.06±8.20)%], increased differentiation [(52.83±8.97)%] and apoptosis [(52.92±2.53)%] of Kasumi-1 cells when compared with vorinostat [(33.82±9.41)%, (43.93±9.04)% and (42.98±3.01)%, respectively], DEX [(17.30±3.49)%, (22.53±4.51)% and (19.57±2.17)%, respectively] or control [(6.96±0.39)%, (21.73±2.03)% and (6.96±0.39)%, respectively]. Also significant ubiquitination and decreased AML1-ETO protein in Kasumi-1 cells after the combination treatment over single agent or control were observed. The results indicated that DEX and vorinostat could synergistically inhibit the Kasumi-1 cells proliferation, induce Kasumi-1 cells differentiation and apoptosis through ubiquitination and degradation of AML1-ETO.

  6. DHX15 is associated with poor prognosis in acute myeloid leukemia (AML) and regulates cell apoptosis via the NF-kB signaling pathway. (United States)

    Pan, Lili; Li, Yang; Zhang, Hai-Ying; Zheng, Yi; Liu, Xiao-Li; Hu, Zheng; Wang, Yi; Wang, Jing; Cai, Yuan-Hua; Liu, Qiao; Chen, Wan-Ling; Guo, Ying; Huang, Yuan-Mao; Qian, Feng; Jin, Li; Wang, Jiucun; Wang, Shao-Yuan


    The role of DHX15 , a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in DHX15 (NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally, DHX15 was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of DHX15 . DHX15 was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells. DHX15 was down-regulated when AML patients achieved disease remission or when leukemia cell lines were induced to differentiate. DHX15 silencing greatly inhibited leukemia cell proliferation and induced cell apoptosis and G1-phase arrest. In contrast, the restoration of DHX15 expression rescued cell viability and reduced cell apoptosis. In addition, we found that DHX15 was down-regulated when cell apoptosis was induced by ATO (arsenic trioxide); overexpression of DHX15 caused dramatic resistance to ATO-induced cell apoptosis, suggesting an important role for DHX15 in cell apoptosis. We further explored the mechanism of DHX15 in apoptosis and found that overexpression of DHX15 activated NF-kB transcription. Knockdown of DHX15 inhibited the nuclear translocation and activation of the NF-kB subunit P65 in leukemia cells. Several downstream targets of the NF-kB pathway were also down-regulated, and apoptosis-associated genes CASP3 and PARP were activated. In conclusion, this study represents the first demonstration that DHX15 plays an important role in leukemogenesis via the NF-kB signaling pathway and may serve as an independent prognostic marker for AML.

  7. Effect of Surface Blasting on Subway Tunnels- A Parametric Study

    Directory of Open Access Journals (Sweden)

    Hossein Entezari Zarch


    Full Text Available During wars and crises, the underground tunnels are used as a safe space. Therefore, the stability and safety of them under a blast is of particular importance. In this paper, the Finite Difference Method has been used to study the influence of the change in geotechnical parameters and depth on surface blasting on subway tunnels. Results showed that increasing the internal friction angle, modulus of elasticity and cohesion of the soil reduced the effects of blast loads on the vertical displacement and bending moment in the center of tunnel crown. Furthermore, the results showed that increasing the depth of the tunnel reduced the effects of blast loading. Comparing all parameters collectively showed that the increase in the modulus of elasticity of the soil and depth of the tunnel is the most effective in reducing the influence of the blast loads on the vertical displacement and bending moment of the tunnel crown, respectively.

  8. Confirmation of the decontamination ability using the dry blasting device

    International Nuclear Information System (INIS)

    Izuka, Hirotaka; Tsuhara, Yuuki; Ito, Hajime; Fukuda, Kazuhiro; Sugahara, Yasuhiro; Kanamori, Yoji


    The decontamination method of metallic waste was considered to reduce the radioactive waste in decommissioning a nuclear power plant. Stainless steel occupies most for the material of the system equipment of PWR. The contamination by radioactive materials is stuck in the surface in the equipment as the metal oxide (e.g. chromium oxide, iron oxide). The method of efficient abrasion by the dry blasting device was considered to remove metal oxide from stainless steel. The kind of blasting abrasives material and the abrasive operation condition (the blasting angle, rate) were considered to investigate the abrasion ability to stainless steel. The abrasive condition which was appropriate abrasive ability was investigated and appropriate blasting abrasives was selected to stainless steel. The decontamination test by selected blasting abrasives and abrasive operation condition was performed using samples and the relation between abrasive rate and activity concentration was confirmed. The metallic radioactive waste was confirmed to be able to decontaminate to the clearance level. (author)

  9. The CNGRC-GG-D(KLAKLAK)2 peptide induces a caspase-independent, Ca2+-dependent death in human leukemic myeloid cells by targeting surface aminopeptidase N/CD13


    Bouchet, Sandrine; Tang, Ruoping; Fava, Fanny; Legrand, Ollivier; Bauvois, Brigitte


    The CD13 antigen's binding site for the Asn-Gly-Arg (NGR) motif enables NGR-containing chemotherapeutic drugs to be delivered to CD13-positive tumours. Human CD13-positive acute myeloid leukemia (AML) cells proliferate abnormally and escape death. Here, we show that the CNGRC-GG-D(KLAKLAK)2 peptide induces death in AML cell lines (U937, THP-1, NB4, HL-60) and primary blood cells from AML patients. Cell death was characterized as a caspase-independent mechanism, without DNA fragmentation, but ...

  10. Attenuation of blast pressure behind ballistic protective vests. (United States)

    Wood, Garrett W; Panzer, Matthew B; Shridharani, Jay K; Matthews, Kyle A; Capehart, Bruce P; Myers, Barry S; Bass, Cameron R


    Clinical studies increasingly report brain injury and not pulmonary injury following blast exposures, despite the increased frequency of exposure to explosive devices. The goal of this study was to determine the effect of personal body armour use on the potential for primary blast injury and to determine the risk of brain and pulmonary injury following a blast and its impact on the clinical care of patients with a history of blast exposure. A shock tube was used to generate blast overpressures on soft ballistic protective vests (NIJ Level-2) and hard protective vests (NIJ Level-4) while overpressure was recorded behind the vest. Both types of vest were found to significantly decrease pulmonary injury risk following a blast for a wide range of conditions. At the highest tested blast overpressure, the soft vest decreased the behind armour overpressure by a factor of 14.2, and the hard vest decreased behind armour overpressure by a factor of 56.8. Addition of body armour increased the 50th percentile pulmonary death tolerance of both vests to higher levels than the 50th percentile for brain injury. These results suggest that ballistic protective body armour vests, especially hard body armour plates, provide substantial chest protection in primary blasts and explain the increased frequency of head injuries, without the presence of pulmonary injuries, in protected subjects reporting a history of blast exposure. These results suggest increased clinical suspicion for mild to severe brain injury is warranted in persons wearing body armour exposed to a blast with or without pulmonary injury.

  11. Survey of rice blast race identity for blast resistance gene identification in the USA and Puerto Rico (United States)

    Rice blast disease is a significant threat to stable rice production in the USA and worldwide. The major resistance gene (Pi-ta) located within a cluster of resistance genes on rice chromosome 12 has been demonstrated to confer resistance to the rice blast disease. Katy, a rice cultivar released in ...

  12. Experimental investigation of blast mitigation and particle-blast interaction during the explosive dispersal of particles and liquids (United States)

    Pontalier, Q.; Loiseau, J.; Goroshin, S.; Frost, D. L.


    The attenuation of a blast wave from a high-explosive charge surrounded by a layer of inert material is investigated experimentally in a spherical geometry for a wide range of materials. The blast wave pressure is inferred from extracting the blast wave velocity with high-speed video as well as direct measurements with pressure transducers. The mitigant consists of either a packed bed of particles, a particle bed saturated with water, or a homogeneous liquid. The reduction in peak blast wave overpressure is primarily dependent on the mitigant to explosive mass ratio, M/ C, with the mitigant material properties playing a secondary role. Relative peak pressure mitigation reduces with distance and for low values of M/ C (compaction, deformation, and fracture of the powders plays an important role. The difference in scaled arrival time of the blast and material fronts increases with M/ C and scaled distance, with solid particles giving the largest separation between the blast wave and cloud of particles. Surrounding a high-explosive charge with a layer of particles reduces the positive-phase blast impulse, whereas a liquid layer has no influence on the impulse in the far field. Taking the total impulse due to the blast wave and material impact into account implies that the damage to a nearby structure may actually be augmented for a range of distances. These results should be taken into consideration in the design of explosive mitigant systems.

  13. Proceedings of the seventeenth annual conference on explosives and blasting technique. Volume 2

    International Nuclear Information System (INIS)



    Papers from this conference dealt with the following topics: surface and underground mine blasting, ground vibrations and blast effects, design for explosive fracturing of rock, sequential timing for blasting control, design for production optimization, use of blasting for abandoned mine reclamation, chemical explosives, lightning warning systems, magazine security, fire safety, and drilling equipment. Papers have been indexed separately for inclusion on the data base

  14. 22 CFR 121.11 - Military demolition blocks and blasting caps. (United States)


    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Military demolition blocks and blasting caps... blasting caps. Military demolition blocks and blasting caps referred to in Category IV(a) do not include the following articles: (a) Electric squibs. (b) No. 6 and No. 8 blasting caps, including electric...

  15. Rock breaking methods to replace blasting (United States)

    Zhou, Huisheng; Xie, Xinghua; Feng, Yuqing


    The method of breaking rock by blasting has a high efficiency and the cost is relatively low, but the associated vibration, flyrock, production of toxic gases since the 1970’s, the Western developed countries began to study the safety of breaking rock. This paper introduces different methods and their progress to safely break rock. Ideally, safe rock breaking would have little vibration, no fly stone, and no toxic gases, which can be widely used in municipal engineering, road excavation, high-risk mining, quarrying and complex environment.

  16. Explosive and accessories in rock blasting

    Energy Technology Data Exchange (ETDEWEB)

    Pingua, B.M.P.; Nabiullah, M.; Jagdish, S.; Mishra, G.D.; Singh, T.N. [Central Mining Research Institute, Dhanbad (India)


    Chemical explosives are commonly used in the mining industry. Those used in India include nitroglycerine (NG) base, ammonium nitrate fuel oil mixture (ANFO), slurry emulsion and liquid oxygen (LOX). Examples of each type and their general properties are lighted. The electric and non-electric detonating systems used are described. Two Indian companies are producing non-electric in-hole delay system. Raydet (IDL-make) and Excel (ICI-make). Their firing characteristics are listed. Tables are given for burden for different density of rock and explosive strength. Causes of bad blast are itemised. 7 refs., 4 figs., 7 tabs.

  17. Reliability of engineered basements as blast shelters

    International Nuclear Information System (INIS)

    Longinow, A.; Mohammadi, J.; Robinson, R.R.


    A method for predicting the probability of failure of structures by considering multiple failure modes was formulated. It was applied to the analysis of a reinforced concrete slab when subjected to a uniformly distributed blast load over its surface. Currently available criteria for failure due to flexure and shear were used in predicting the probability of failure. This method is capable of considering all major components of a structure, the respective failure modes of each component, and of predicting the probability of failure of the structure as a whole

  18. Design of blast simulators for nuclear testing

    International Nuclear Information System (INIS)

    Mark, A.; Opalka, K.O.; Kitchens, C.W. Jr.


    A quasi-one-dimensional computational technique is used to model the flow of a large, complicated shock tube. The shock tube, or Large Blast Simulator, is used to simulate conventional or nuclear explosions by shaping the pressure history. Results from computations show favorable agreement when compared with data taken in the facility at Gramat, France. Such future shock tubes will include a thermal irradiation capability to better simulate a nuclear event. The computations point to the need for venting of the combustion products since the pressure history will be considerably altered as the shock propagates through these hot gases

  19. Prevention of Blast-Related Injuries (United States)


    influence of cerebrospinal fluid (CSF) on the shock wave response 3. Development of the geometric model for the head of a 23 55-kg Yucatan pig 4...of Tissue-Tek® optimum cutting compound and 20% sucrose (w/v) and frozen in a stream of liquid nitrogen (Saljo et al, 2008). The frozen blocks of current models of the pig head under air blast loading 2. Development of a 2-D pig head FE model to study the influence of cerebrospinal fluid

  20. Impact of Drill and Blast Excavation on Repository Performance Confirmation

    International Nuclear Information System (INIS)

    Keller, R.; Francis, N.; Houseworth, J.; Kramer, N.


    There has been considerable work accomplished internationally examining the effects of drill and blast excavation on rock masses surrounding emplacement openings of proposed nuclear waste repositories. However, there has been limited discussion tying the previous work to performance confirmation models such as those proposed for Yucca Mountain, Nevada. This paper addresses a possible approach to joining the available information on drill and blast excavation and performance confirmation. The method for coupling rock damage data from drill and blast models to performance assessment models for fracture flow requires a correlation representing the functional relationship between the peak particle velocity (PPV) vibration levels and the potential properties that govern water flow rates in the host rock. Fracture aperture and frequency are the rock properties which may be most influenced by drill and blast induced vibration. If it can be shown (using an appropriate blasting model simulation) that the effect of blasting is far removed from the waste package in an emplacement drift, then disturbance to the host rock induced in the process of drill and blast excavation may be reasonably ignored in performance assessment calculations. This paper proposes that the CANMET (Canada Center for Mineral and Energy Technology) Criterion, based on properties that determine rock strength, may be used to define a minimum PPV. This PPV can be used to delineate the extent of blast induced damage. Initial applications have demonstrated that blasting models can successfully be coupled with this criterion to predict blast damage surrounding underground openings. The Exploratory Studies Facility at Yucca Mountain has used a blasting model to generate meaningful estimates of near-field vibration levels and damage envelopes correlating to data collected from pre-existing studies conducted. Further work is underway to expand this application over a statistical distribution of geologic

  1. Blast-Resistant Improvement of Sandwich Armor Structure with Aluminum Foam Composite


    Yang, Shu; Qi, Chang


    Sandwich armor structures with aluminum foam can be utilized to protect a military vehicle from harmful blast load such as a landmine explosion. In this paper, a system-level dynamic finite element model is developed to simulate the blast event and to evaluate the blast-resistant performance of the sandwich armor structure. It is found that a sandwich armor structure with only aluminum foam is capable of mitigating crew injuries under a moderate blast load. However, a severe blast load causes...

  2. Control of City Shallow Buried Tunnel Blasting Hazard to Surface Buildings

    Directory of Open Access Journals (Sweden)

    Yang Deqiang


    Full Text Available Combining with the blasting test of an under-construction tunnel, this paper optimizes the overall blasting construction scheme. The optimized blasting scheme is used in the site construction test and the peak particle vibration velocity is strictly controlled under working conditions through blasting vibration monitoring to ensure the safety of surrounding buildings and structures in the construction process. The corresponding control measures are proposed to reduce the blasting vibration which brings certain guiding significance to the following construction project.

  3. A simple grid implementation with Berkeley Open Infrastructure for Network Computing using BLAST as a model

    Directory of Open Access Journals (Sweden)

    Watthanai Pinthong


    Full Text Available Development of high-throughput technologies, such as Next-generation sequencing, allows thousands of experiments to be performed simultaneously while reducing resource requirement. Consequently, a massive amount of experiment data is now rapidly generated. Nevertheless, the data are not readily usable or meaningful until they are further analysed and interpreted. Due to the size of the data, a high performance computer (HPC is required for the analysis and interpretation. However, the HPC is expensive and difficult to access. Other means were developed to allow researchers to acquire the power of HPC without a need to purchase and maintain one such as cloud computing services and grid computing system. In this study, we implemented grid computing in a computer training center environment using Berkeley Open Infrastructure for Network Computing (BOINC as a job distributor and data manager combining all desktop computers to virtualize the HPC. Fifty desktop computers were used for setting up a grid system during the off-hours. In order to test the performance of the grid system, we adapted the Basic Local Alignment Search Tools (BLAST to the BOINC system. Sequencing results from Illumina platform were aligned to the human genome database by BLAST on the grid system. The result and processing time were compared to those from a single desktop computer and HPC. The estimated durations of BLAST analysis for 4 million sequence reads on a desktop PC, HPC and the grid system were 568, 24 and 5 days, respectively. Thus, the grid implementation of BLAST by BOINC is an efficient alternative to the HPC for sequence alignment. The grid implementation by BOINC also helped tap unused computing resources during the off-hours and could be easily modified for other available bioinformatics software.

  4. Determination of Destress Blasting Effectiveness Using Seismic Source Parameters (United States)

    Wojtecki, Łukasz; Mendecki, Maciej J.; Zuberek, Wacaław M.


    Underground mining of coal seams in the Upper Silesian Coal Basin is currently performed under difficult geological and mining conditions. The mining depth, dislocations (faults and folds) and mining remnants are responsible for rockburst hazard in the highest degree. This hazard can be minimized by using active rockburst prevention, where destress blastings play an important role. Destress blastings in coal seams aim to destress the local stress concentrations. These blastings are usually performed from the longwall face to decrease the stress level ahead of the longwall. An accurate estimation of active rockburst prevention effectiveness is important during mining under disadvantageous geological and mining conditions, which affect the risk of rockburst. Seismic source parameters characterize the focus of tremor, which may be useful in estimating the destress blasting effects. Investigated destress blastings were performed in coal seam no. 507 during its longwall mining in one of the coal mines in the Upper Silesian Coal Basin under difficult geological and mining conditions. The seismic source parameters of the provoked tremors were calculated. The presented preliminary investigations enable a rapid estimation of the destress blasting effectiveness using seismic source parameters, but further analysis in other geological and mining conditions with other blasting parameters is required.

  5. Evaluation of blast-induced vibration effects on structures 1

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Rim; Jeon, Gyu Shick; Lee, Dae Soo; Joo, Kwang Ho; Lee, Woong Keon [Korea Electrotechnology Research Inst., Changwon (Korea, Republic of); Ryu, Chang Ha; Chung, So Keul; Lee, Kyung Won; Shin, Hee Soon; Chun, Sun Woo; Park, Yeon Jun; Synn, Joong Ho; Choi, Byung Hee [Korea Inst. of Geology Mining and Materials, Taejon (Korea, Republic of)


    Due to the difficulties of obtaining construction site for new plants, following ones are inevitably being built in the site adjacent to existing power plants. Therefore considerable thought has been recently given to the dynamic loading generated by blasting works near the plants to maintain the safety of structures and facilities in power plants. Our own standard for safety level of blast vibration is not prepared yet, and foreign standards have been generally employed without theoretical and experimental verification. Safety-related structures of power plants and facilities have to be protected against the effects of possible hazards due to blast vibration. Earthquakes have been considered a major dynamic design loading as a requirement of plant design, but the effects of blast-induced vibration are not. In order to ensure the safety, rational safe criterion should be established and blast design should be satisfy it, which requires the development of a model for prediction of vibration level through more systematic measurement and analysis. The main objectives of the study are : to provide background data for establishing the rational safe vibration limits, to develop models for prediction of blast vibration level, to establish safe blast design criterion, and to accumulate techniques for field measurements, data acquisition and analysis (author). 80 refs., 347 figs.

  6. Spectrum of abdominal organ injury in a primary blast type

    Directory of Open Access Journals (Sweden)

    Amin Abid


    Full Text Available Abstract Introduction Abdominal organ injury in a primary blast type is always challenging for diagnosis. Air containing abdominal viscera is most vulnerable to effects of primary blast injury. In any patient exposed to a primary blast wave who presents with an acute abdomen, an abdominal organ injury is to be kept in a clinical suspicion. Aim Study various abdominal organ injuries occurring in a primary type of blast injury. Material and methods: All those who had exploratory laparotomy for abdominal organ injuries after a primary blast injury for a period of 10 years from January 1998 - January 2008 were included in this retrospective study. Results Total 154 patients had laparotomy for abdominal organ injuries with a primary blast type of injury. Small intestine was damaged in 48 patients (31.1% followed by spleen in 22.7% cases. 54 patients (35.06% had more than one organ injured. Liver laceration was present in 30 patients (19.48%. Multiple small gut perforations were present in 37 patients (77.08%. Negative laparotomy was found in 5 patients (3.24% whereas 3 (1.94% had re-exploration. Mortality was present in 6 patients (3.89%. Conclusions Primary blast injury causes varied abdominal organ injuries. Single or multiple organ damage can be there. Small intestine is commonest viscera injured. Laparotomy gives final diagnosis.

  7. [Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT]. (United States)

    Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian


    To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

  8. RIP Input Tables From WAPDEG for LA Design Selection: Repository Horizon Elevation - 2-Level AML 50% and Near Maximum

    International Nuclear Information System (INIS)

    B.E. Bullard


    The purpose of this calculation is to document the WAPDEG version 3.09 (CRWMS M and O 1998b). Software Routine Report for WAPDEG (Version 3.09) simulations used to analyze waste package degradation and failure under the repository exposure conditions characterized by a two-tier thermal loading repository design. Also documented is the post-processing of these results into tables of waste-package-degradation-time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) computer program. Specifically, the WAPDEG simulations discussed in this calculation correspond to waste package emplacement conditions (repository environment and design) as defined in the Total System Performance Assessment-Viability Assessment (CRWMS M and O 1998a). Total System Performance Assessment-Viability Assessment (TSPA-VA) Analyses Technical Basis Document--Chapter 5, Waste Package Degradation Modeling And Abstraction, pp. 5-27 to 5-29, with the exception that a two-tier thermal loading design feature as specified in the License Application Design Selection (LADS) study was analyzed. The particular design feature evaluated in this report is a modification of the repository horizon elevation and layout within the Topopah Springs Member of Yucca Mountain. Specifically, the modification consists of adding a second level, 50-m above the base case repository layout. Two options were considered, representing two variations in thermal loading. In Design Feature 25e (designated DF25e), each level has an Areal Mass Loading (AML) of 42.5 MTU/acre (i.e., half the VA base case). In Design Feature 25f (designated DF25), each level has an AML of 64MTU/acre. As a result of the change in waste package placement relative to the TSPA-VA base-case design, different temperature and relative humidity time histories at the waste package surface are calculated (input to the WAPDEG simulations), and consequently

  9. Faruk Nafiz Çamlıbel’in Suda Halkalar Adlı Eserinde Su İmajları ve Benzetmeler Water Images and Metaphors in Suda Halkalar Which Faruk Nafiz Çamlıbel’s Work

    Directory of Open Access Journals (Sweden)



    Full Text Available Suda Halkalar (Circles in Water which the poetry book of Faruk Nafiz Çamlıbel, has not been translated into the Latin alphabet to the present day. The images of the water and metaphors which used in this work brought new connotations and approaches to the Turkish poetry. The images of the water in the poetry book are used instead of the poet's soul and dreams sometimes. These images are thought with poet’s darling and sometimes are used as a background. The poetformed the images of the water in his poem sadly. There are the poetand his darling in these tables. The images of the water and thedreams of the poet form the background of the poem. The backgroundsin this poem are repeated as a leitmotiv. Visuality and individualitybecomes important feature in these tables created by the poet. Themetaphors in the work created differently from classical Turkish poetry.These metaphors brought a new meaning to the poem. The poem basedon the intellectual grounds via metaphors. This can be considered asone of the significant achievements of Turkish poetry. We can see thatthe past remembered and desired both in poetry and metaphors bypessimistic feeling. In this respect the past affects the poet's dreamscombining with a sense of mourning, water images and metaphors inpoetry. The metaphors can be grouped as imaginary, visual andstrongly poetic ground. The feelings of pessimism and sadness arepredominant in these metaphors. The images and metaphors used bythe poet can be considered as an improvement for Turkish poetry. It isthe first research done on Suda Halkalar (Circles in Water will help tobetter understand and identify Çamlıbel’s aspect of poetry and literaryline. Faruk Nafiz Çamlıbel’in Suda Halkalar adlı şiir kitabı günümüze kadar Latin harflerine aktarılmamıştır. Bu eserde kullanılan su imajları ve benzetmeler Türk şiirine yeni yaklaşımlar ve çağrışımlar getirmiştir. Eserdeki su imajları bazen şairin ruhu ve hayalleri

  10. High-speed measurement of firearm primer blast waves


    Courtney, Michael; Daviscourt, Joshua; Eng, Jonathan; Courtney, Amy


    This article describes a method and results for direct high-speed measurements of firearm primer blast waves employing a high-speed pressure transducer located at the muzzle to record the blast pressure wave produced by primer ignition. Key findings are: 1) Most of the lead styphnate based primer models tested show 5.2-11.3% standard deviation in the magnitudes of their peak pressure. 2) In contrast, lead-free diazodinitrophenol (DDNP) based primers had standard deviations of the peak blast p...

  11. The tank's dynamic response under nuclear explosion blast wave

    International Nuclear Information System (INIS)

    Xu Mei; Wang Lianghou; Li Xiaotian; Yu Suyuan; Zhang Zhengming; Wan Li


    To weapons and equipment, blast wave is the primary destructive factor. In this paper, taken the real model-59 tank as an example, we try to transform the damage estimation problem into computing a fluid structure interaction problem with finite element method. The response of tank under nuclear explosion blast wave is computed with the general-coupling algorithm. Also, the dynamical interaction of blast wave and tank is reflected in real time. The deformation of each part of the tank is worked out and the result corresponds to the real-measured data. (authors)

  12. Lateral blasts at Mount St. Helens and hazard zonation (United States)

    Crandell, D.R.; Hoblitt, R.P.


    Lateral blasts at andesitic and dacitic volcanoes can produce a variety of direct hazards, including ballistic projectiles which can be thrown to distances of at least 10 km and pyroclastic density flows which can travel at high speed to distances of more than 30 km. Indirect effect that may accompany such explosions include wind-borne ash, pyroclastic flows formed by the remobilization of rock debris thrown onto sloping ground, and lahars. Two lateral blasts occurred at a lava dome on the north flank of Mount St. Helens about 1200 years ago; the more energetic of these threw rock debris northeastward across a sector of about 30?? to a distance of at least 10 km. The ballistic debris fell onto an area estimated to be 50 km2, and wind-transported ash and lapilli derived from the lateral-blast cloud fell on an additional lobate area of at least 200 km2. In contrast, the vastly larger lateral blast of May 18, 1980, created a devastating pyroclastic density flow that covered a sector of as much as 180??, reached a maximum distance of 28 km, and within a few minutes directly affected an area of about 550 km2. The May 18 lateral blast resulted from the sudden, landslide-induced depressurization of a dacite cryptodome and the hydrothermal system that surrounded it within the volcano. We propose that lateral-blast hazard assessments for lava domes include an adjoining hazard zone with a radius of at least 10 km. Although a lateral blast can occur on any side of a dome, the sector directly affected by any one blast probably will be less than 180??. Nevertheless, a circular hazard zone centered on the dome is suggested because of the difficulty of predicting the direction of a lateral blast. For the purpose of long-term land-use planning, a hazard assessment for lateral blasts caused by explosions of magma bodies or pressurized hydrothermal systems within a symmetrical volcano could designate a circular potential hazard area with a radius of 35 km centered on the volcano

  13. Protecting the lower extremity against a/p blast mines

    CSIR Research Space (South Africa)

    van Dyk, T


    Full Text Available the Lower Extremity against a/p Blast Mines J T van Dyk DEFENCE, PEACE, SAFETY AND SECURITY LANDWARDS SCIENCES COMPETENCY AREA Slide 2 © CSIR 2006 Contents • R&D overview • Effect of a/p blast mines • Basic... explosive principles – Shock effect (brisance) – Blast effect • Test methods • Protection concepts • Test results Slide 3 © CSIR 2006 Goals: Compare LEAP study results with field injuries Investigate energy...

  14. Scale testing of a partially confined blast chamber

    CSIR Research Space (South Africa)

    Grundling, W


    Full Text Available in pressure readings. A scale model of the blast chamber, Emily, was constructed with the addition of a pendulum plate hanging concentrically covering 65% of the open area. PURPOSE OF SCALED BLAST CHAMBER The purpose of this particular test is to evaluate... PHASE Illustrated in Figure 3 and 4 are the results obtained during testing of the scaled blast chamber. In both cases the pressure dissipates over time, showing pulsating behaviour as the shockwaves reflect off the chamber walls. By looking...

  15. Massive injection of coal and superoxygenated blast into the blast furnace

    Energy Technology Data Exchange (ETDEWEB)

    Toxopeus, H.L.; Danloy, G.; Franssen, R.; Havelange, O. [Corus, IJmuiden (Netherlands)


    The aim of the present project was to demonstrate the industrial feasibility of a massive injection of coal, {+-}270 kg/tHM, combined with a high O{sub 2} enrichment of the blast. The coke rate would thus be reduced to well below 250 kg/tHM. A reference level of 200-220 kg coal/tHM was successfully accomplished. However, the technical condition of the blast furnace hearths overruled all ambitions, the anticipated trial scheme had to be abandoned and no further trials were performed. A very short trial was aborted shortly after reaching an injection level of around 265 coal/tHM, due to excessive generation of very fine sludge originating from incomplete combustion. This forced the operators to investigate the merits of combustion more in depth. At the aimed low coke-rate detailed information about the gas distribution is of utmost importance. Therefore, in conjunction with the industrial tests, CRM designed a gas tracing method. Measurement of the transfer time between the injection point (a tuyere) and the sampling points (on an above-burden probe) would allow deduction of the radial gas distribution. CRM made the design and the start-up of an installation built by Hoogovens on blast furnace 7 of IJmuiden. Since then, repeated measurements have shown that the gas transfer time profiles are consistent with the data measured at the blast furnace top and at the wall. The modifications of the moveable armour position are reflected better and faster on the gas distribution as measured by helium tracing than on the skin flow temperatures.

  16. Experimental investigation of blast mitigation and particle-blast interaction during the explosive dispersal of particles and liquids (United States)

    Pontalier, Q.; Loiseau, J.; Goroshin, S.; Frost, D. L.


    The attenuation of a blast wave from a high-explosive charge surrounded by a layer of inert material is investigated experimentally in a spherical geometry for a wide range of materials. The blast wave pressure is inferred from extracting the blast wave velocity with high-speed video as well as direct measurements with pressure transducers. The mitigant consists of either a packed bed of particles, a particle bed saturated with water, or a homogeneous liquid. The reduction in peak blast wave overpressure is primarily dependent on the mitigant to explosive mass ratio, M/C, with the mitigant material properties playing a secondary role. Relative peak pressure mitigation reduces with distance and for low values of M/C (pressure levels in the mid-to-far field. Solid particles are more effective at mitigating the blast overpressure than liquids, particularly in the near field and at low values of M/C, suggesting that the energy dissipation during compaction, deformation, and fracture of the powders plays an important role. The difference in scaled arrival time of the blast and material fronts increases with M/C and scaled distance, with solid particles giving the largest separation between the blast wave and cloud of particles. Surrounding a high-explosive charge with a layer of particles reduces the positive-phase blast impulse, whereas a liquid layer has no influence on the impulse in the far field. Taking the total impulse due to the blast wave and material impact into account implies that the damage to a nearby structure may actually be augmented for a range of distances. These results should be taken into consideration in the design of explosive mitigant systems.

  17. Brief Report: Human Acute Myeloid Leukemia Reprogramming to Pluripotency Is a Rare Event and Selects for Patient Hematopoietic Cells Devoid of Leukemic Mutations. (United States)

    Lee, Jong-Hee; Salci, Kyle R; Reid, Jennifer C; Orlando, Luca; Tanasijevic, Borko; Shapovalova, Zoya; Bhatia, Mickie


    Induced pluripotent stem cell reprogramming has provided critical insights into disease processes by modeling the genetics and related clinical pathophysiology. Human cancer represents highly diverse genetics, as well as inter- and intra-patient heterogeneity, where cellular model systems capable of capturing this disease complexity would be invaluable. Acute myeloid leukemia (AML) represents one of most heterogeneous cancers and has been divided into genetic subtypes correlated with unique risk stratification over the decades. Here, we report our efforts to induce pluripotency from the heterogeneous population of human patients that represents this disease in the clinic. Using robust optimized reprogramming methods, we demonstrate that reprogramming of AML cells harboring leukemic genomic aberrations is a rare event with the exception of those with de novo mixed-lineage leukemia (MLL) mutations that can be reprogrammed and model drug responses in vitro. Our findings indicate that unlike hematopoietic cells devoid of genomic aberrations, AML cells harboring driver mutations are refractory to reprogramming. Expression of MLL fusion proteins in AML cells did not contribute to induced reprogramming success, which continued to select for patient derived cells devoid of AML patient-specific aberrations. Our study reveals that unanticipated blockades to achieving pluripotency reside within the majority of transformed AML patient cells. Stem Cells 2017;35:2095-2102. © 2017 AlphaMed Press.

  18. Çamlıbel - Ulubey (Uşak) Beyaz Mermerinin Jeolojik ve Fiziko-Mekanik Özelliklerinin Araştırılması


    ÇELİK, Mustafa Yavuz; KIRILIVEREN, Sabri


    Menderes Masifinde yer alan Uşak bölgesi önemli bir mermer potansiyeline sahiptir. Bölgede Karahallı, Sivaslı ve Ulubey ilçeleri civarında mermer blok üretimi yapılmaktadır. Bu makalede, Çamlıbel-Ulubey (Uşak) beyaz mermerinin, mermer olarak kullanılabilirliği irdelenmiş ve yöre mermerleriyle karşılaştırılmaları yapılmıştır. Çamlıbel-Ulubey (Uşak) beyaz mermerinin özelliklerini belirlemek amacıyla yapılan deneylerde özgül kütle 2,73 g/cm3, kütlece su emme oranı % 0,06, doluluk oranı % 99,3, b...

  19. Environmental problems associated with blasting in mines: public apprehensions of damage due to blast vibrations - case studies

    Energy Technology Data Exchange (ETDEWEB)

    Padhi, S.N. [DGMS, Bhubaneswar (India)


    Blast vibrations may be felt in intensities as small as 1/100 of that required to cause any damage to structures. Therefore, the public response and thus complaints regarding damages are often imaginary. The paper deals with three case studies, involving alleged damage from blasting in surface and underground coal mines where public litigations and agitations resulted due to such apprehensions. The paper is written in simple technical language as the situations warranted that the blast vibration studies should be understood by the general public. 7 tabs.

  20. Linking blast physics to biological outcomes in mild traumatic brain injury: Narrative review and preliminary report of an open-field blast model. (United States)

    Song, Hailong; Cui, Jiankun; Simonyi, Agnes; Johnson, Catherine E; Hubler, Graham K; DePalma, Ralph G; Gu, Zezong


    Blast exposures are associated with traumatic brain injury (TBI) and blast-induced TBIs are common injuries affecting military personnel. Department of Defense and Veterans Administration (DoD/VA) reports for TBI indicated that the vast majority (82.3%) has been mild TBI (mTBI)/concussion. mTBI and associated posttraumatic stress disorders (PTSD) have been called "the invisible injury" of the current conflicts in Iraq and Afghanistan. These injuries induce varying degrees of neuropathological alterations and, in some cases, chronic cognitive, behavioral and neurological disorders. Appropriate animal models of blast-induced TBI will not only assist the understanding of physical characteristics of the blast, but also help to address the potential mechanisms. This report provides a brief overview of physical principles of blast, injury mechanisms related to blast exposure, current blast animal models, and the neurological behavioral and neuropathological findings related to blast injury in experimental settings. We describe relationships between blast peak pressures and the observed injuries. We also report preliminary use of a highly reproducible and intensity-graded blast murine model carried out in open-field with explosives, and describe physical and pathological findings in this experimental model. Our results indicate close relationships between blast intensities and neuropathology and behavioral deficits, particularly at low level blast intensities relevant to mTBI. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine. (United States)

    Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette


    Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Seismic stations with GSM telemetry for registration of quarry blasts

    Czech Academy of Sciences Publication Activity Database

    Brož, Milan; Číž, Radim; Málek, Jiří; Žanda, Libor


    Roč. 2000, 16 (118) (2000), s. 25-32 ISSN 1211-1910 Institutional research plan: CEZ:AV0Z3046908 Keywords : blasting * seismic station * GSM mobile modem Subject RIV: DC - Siesmology, Volcanology, Earth Structure

  3. Analysing Blast and Fragment Penetration Effects on Composite Helicopter Structures

    National Research Council Canada - National Science Library

    van't Hof, C; Herlaar, K; Luyten, J. M; van der Jagt, M. J


    .... The last decades the threat of helicopters has increased in military circumstances. Consequently the helicopters will be exposed to weapon effects like high blast loads and fragment impact more frequently...

  4. Gene interactions and genetics of blast resistance and yield ...

    Indian Academy of Sciences (India)


    Aug 11, 2014 ... of chemical measures for the control and management of blast, which are not .... tion of genetic components of variation, epistasis model and gene effects in two .... and environmental variance is estimated from mean variance.

  5. Seismic safety in conducting large-scale blasts (United States)

    Mashukov, I. V.; Chaplygin, V. V.; Domanov, V. P.; Semin, A. A.; Klimkin, M. A.


    In mining enterprises to prepare hard rocks for excavation a drilling and blasting method is used. With the approach of mining operations to settlements the negative effect of large-scale blasts increases. To assess the level of seismic impact of large-scale blasts the scientific staff of Siberian State Industrial University carried out expertise for coal mines and iron ore enterprises. Determination of the magnitude of surface seismic vibrations caused by mass explosions was performed using seismic receivers, an analog-digital converter with recording on a laptop. The registration results of surface seismic vibrations during production of more than 280 large-scale blasts at 17 mining enterprises in 22 settlements are presented. The maximum velocity values of the Earth’s surface vibrations are determined. The safety evaluation of seismic effect was carried out according to the permissible value of vibration velocity. For cases with exceedance of permissible values recommendations were developed to reduce the level of seismic impact.

  6. Measurement and Modelling of Blast Movement to Reduce Ore ...

    African Journals Online (AJOL)


    geologists at Newmont Ahafo Mine have realised the impact of blast movement on ore losses and dilution and have ... Movement to Reduce Ore Losses and Dilution at Ahafo Gold Mine in Ghana”, Ghana Mining Journal, pp. .... classification.

  7. Evaluation of Grade 120 Granulated Ground blast Furnace Slag. (United States)


    This study evaluates Grade 120 Granulated Ground Blast Furnace Slag (GGBFS) and its effect on the properties of hydraulic cement concretes used in structural and pavement construction. Several mix designs, structural and pavement, were used for this ...

  8. Assessment of Environmental Effects of Post-Blasted Explosive on ...

    African Journals Online (AJOL)


    Assessment of Environmental Effects of Post-Blasted Explosive on the Ecosystem of Old ... intensity and temperature of explosive dissolution in the mine environment shows that TNT ... based on their physical/chemical properties as: gelatin.

  9. An Operational Model for the Prediction of Jet Blast (United States)


    This paper presents an operational model for the prediction of jet blast. The model was : developed based upon three modules including a jet exhaust model, jet centerline decay : model and aircraft motion model. The final analysis was compared with d...

  10. Blast Impact Prediction Studies at Ghana Manganese Company ...

    African Journals Online (AJOL)



    Jun 1, 2015 ... Keywords: Blast impact, Environment, Prediction, Regulatory threshold. 1 Introduction ... Noise is an environmental nuisance. .... explosion energy released into the ground generates vibration waves within the rock. Several.

  11. Damage to underground coal mines caused by surface blasting

    International Nuclear Information System (INIS)

    Fourie, A.B.; Green, R.W.


    An investigation of the potential damage to underground coal workings as a result of surface blasting at an opencast coal mine is described. Seismometers were installed in a worked out area of an underground mine, in the eastern Transvaal region of South Africa, and the vibration caused by nearby surface blasting recorded. These measurements were used to derive peak particle velocities. These velocities were correlated with observed damage underground in order to establish the allowable combination of the two blasting parameters of charge mass per relay, and blast-to-gage point distance. An upper limit of 110mm/sec peak particle velocity was found to be sufficient to ensure that the damage to the particular workings under consideration was minimal. It was further found that a cube-root scaling law provided a better fit to the field data than the common square-root law. 11 refs., 6 figs., 5 tabs

  12. Blast overpressure after tire explosion: a fatal case. (United States)

    Pomara, Cristoforo; D'Errico, Stefano; Riezzo, Irene; Perilli, Gabriela; Volpe, Umberto; Fineschi, Vittorio


    Fatal blast injuries are generally reported in literature as a consequence of the detonation of explosives in war settings. The pattern of lesion depends on the position of the victim in relation to the explosion, on whether the blast tracks through air or water, and whether it happens in the open air or within an enclosed space and the distance from the explosion. Tire explosion-related injuries are rarely reported in literature. This study presents a fatal case of blast overpressure due to the accidental explosion of a truck tire occurring in a tire repair shop. A multidisciplinary approach to the fatality involving forensic pathologists and engineers revealed that the accidental explosion, which caused a series of primary and tertiary blast wave injuries, was due to tire deterioration.

  13. Blast Load Response of Steel Sandwich Panels with Liquid Encasement

    Energy Technology Data Exchange (ETDEWEB)

    Dale Karr; Marc Perlin; Benjamin Langhorst; Henry Chu


    We describe an experimental investigation of the response of hybrid blast panels for protection from explosive and impact forces. The fundamental notion is to dissipate, absorb, and redirect energy through plastic collapse, viscous dissipation, and inter-particle forces of liquid placed in sub-structural compartments. The panels are designed to absorb energy from an impact or air blast by elastic-plastic collapse of the panel substructure that includes fluid-filled cavities. The fluid contributes to blast effects mitigation by providing increased initial mass and resistance, by dissipation of energy through viscosity and fluid flow, and by redirecting the momentum that is imparted to the system from the impact and blast impulse pressures. Failure and deformation mechanisms of the panels are described.

  14. Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study. (United States)

    Locatelli, F; Masetti, R; Rondelli, R; Zecca, M; Fagioli, F; Rovelli, A; Messina, C; Lanino, E; Bertaina, A; Favre, C; Giorgiani, G; Ripaldi, M; Ziino, O; Palumbo, G; Pillon, M; Pession, A; Rutella, S; Prete, A


    We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.

  15. Blast response of corroded steel plates

    Energy Technology Data Exchange (ETDEWEB)

    Eslamimajd, Alireza; RahbarRanji, Ahmad [AmirKabir University of Technology, Tehran (Korea, Republic of)


    Numerical results for one- and both-sided corroded steel plates subjected to blast loading are presented. Finite element analysis, with ABAQUS software, is employed to determine the deformation and stress distributions. The results for the case of triangular pulse pressure on un-corroded plates are validated against literature-based data and then, detailed parametric studies are carried-out. The effects of influential parameters including, plate aspect ratio, degree of pit and different ratio of pit depth at each sides of the plate are investigated. The results show that position of pitted surface in respect to applied pressure is the most influential parameter on reduction of dynamic load carrying capacity of pitted plates. By increasing degree of pitting, reduction of dynamic load carrying capacity decrease more.

  16. Power Tillers for Demining: Blast Test

    Directory of Open Access Journals (Sweden)

    Emanuela Elisa Cepolina


    Full Text Available Power tillers are very simple and versatile machines with large scale diffusion in developing countries, where they are commonly used both for agriculture and for transportation purposes. A new integrated participatory approach that makes use of and improves local end-users knowledge has been used to design a new robotic system for humanitarian demining applications in Sri Lanka, using power tiller as core module. A demining machine composed by a tractor unit, a ground processing tool and a vegetation cutting tool is here presented together with results obtained from the first blast test on the preliminary version of tractor unit armouring. Different breakable connections between wheels and axle have been designed to cause physical detachment and interrupt the transmission of the shock wave released by the explosion of a mine under one wheel. Effects of explosions on different types of wheels and on the chassis have been recorded and commented.

  17. Power Tillers for Demining: Blast Test

    Directory of Open Access Journals (Sweden)

    Emanuela Elisa Cepolina


    Full Text Available Power tillers are very simple and versatile machines with large scale diffusion in developing countries, where they are commonly used both for agriculture and for transportation purposes. A new integrated participatory approach that makes use of and improves local end-users knowledge has been used to design a new robotic system for humanitarian demining applications in Sri Lanka, using power tiller as core module. A demining machine composed by a tractor unit, a ground processing tool and a vegetation cutting tool is here presented together with results obtained from the first blast test on the preliminary version of tractor unit armouring. Different breakable connections between wheels and axle have been designed to cause physical detachment and interrupt the transmission of the shock wave released by the explosion of a mine under one wheel. Effects of explosions on different types of wheels and on the chassis have been recorded and commented.

  18. Blasting detonators incorporating semiconductor bridge technology

    Energy Technology Data Exchange (ETDEWEB)

    Bickes, R.W. Jr.


    The enormity of the coal mine and extraction industries in Russia and the obvious need in both Russia and the US for cost savings and enhanced safety in those industries suggests that joint studies and research would be of mutual benefit. The author suggests that mine sites and well platforms in Russia offer an excellent opportunity for the testing of Sandia`s precise time-delay semiconductor bridge detonators, with the potential for commercialization of the detonators for Russian and other world markets by both US and Russian companies. Sandia`s semiconductor bridge is generating interest among the blasting, mining and perforation industries. The semiconductor bridge is approximately 100 microns long, 380 microns wide and 2 microns thick. The input energy required for semiconductor bridge ignition is one-tenth the energy required for conventional bridgewire devices. Because semiconductor bridge processing is compatible with other microcircuit processing, timing and logic circuits can be incorporated onto the chip with the bridge. These circuits can provide for the precise timing demanded for cast effecting blasting. Indeed tests by Martin Marietta and computer studies by Sandia have shown that such precise timing provides for more uniform rock fragmentation, less fly rock, reduce4d ground shock, fewer ground contaminants and less dust. Cost studies have revealed that the use of precisely timed semiconductor bridges can provide a savings of $200,000 per site per year. In addition to Russia`s vast mineral resources, the Russian Mining Institute outside Moscow has had significant programs in rock fragmentation for many years. He anticipated that collaborative studies by the Institute and Sandia`s modellers would be a valuable resource for field studies.

  19. Remote operated vehicle with carbon dioxide blasting (ROVCO2)

    International Nuclear Information System (INIS)

    Resnick, A.M.


    The Remote Operated Vehicle with Carbon Dioxide Blasting (ROVCO 2 ), as shown in a front view, is a six-wheeled remote land vehicle used to decontaminate concrete floors. The remote vehicle has a high pressure Cryogenesis blasting subsystem, Oceaneering Technologies (OTECH) developed a CO 2 xY Orthogonal Translational End Effector (COYOTEE) subsystem, and a vacuum/filtration and containment subsystem. Figure 2 shows a block diagram with the various subsystems labeled



    Branko Božić; Karlo Braun


    The optimalization of exploitation in »Lakovići« limestone quarry is described. Based on determined discontinuities in the rock mass and their densities, the best possible working site have been located in order to obtain the best possible sizes of blasted rocks and work slope stability. Optimal lowest resistance line size for the quarry has been counted and proved experimentally. New blasting parameters have resulted in considerable saving of drilling and explosive (the paper is published in...

  1. The Pre-Blast Concept for use on Armour Materials (United States)


    distribution is displayed. The (1 1 1) pole figure for TWIP steel (FCC crystal structure) is shown representatively, while (1 0 0) is chosen for Dual...avoid the blasted plates impacting the ceiling of the blast chamber. A type ‘k’ thermocouple was then welded to a corner on the top side of the plates...angle distribution is displayed. The (1 1 1) pole figure for TWIP steel (FCC crystal structure) is shown representatively, while (1 0 0) is chosen

  2. Study of wet blasting of components in nuclear power stations

    International Nuclear Information System (INIS)

    Hall, J.


    This report looks at the method of wet blasting radioactive components in nuclear power stations. The wet blaster uses pearl shaped glass beads with the dimensions of 150-250 μm mixed with water as blasting media. The improved design, providing outer operator's positions with proper radiation protection and more efficient blasting equipment has resulted in a lesser dose taken by the operators. The main reason to decontaminate components in nuclear power plants is to enable service on these components. On components like valves, pump shafts, pipes etc. oxides form and bind radiation. These components are normally situated at some distance from the reactor core and will mainly suffer from radiation from so called activation products. When a component is to be decontaminated it can be decontaminated to a radioactive level where it will be declassified. This report has found levels ranging from 150-1000 Bq/kg allowing declassification of radioactive materials. This difference is found between different countries and different organisations. The report also looks at the levels of waste generated using wet blasting. This is done by tracking the contamination to determine where it collects. It is either collected in the water treatment plant or collected in the blasting media. At Barsebaeck the waste levels, from de-contaminating nearly 800 components in one year, results in a waste volume of about 0,250 m 3 . This waste consists of low and medium level waste and will cost about 3 600 EURO to store. The conclusions of the report are that wet blasting is an indispensable way to treat contaminated components in modern nuclear power plants. The wet blasting equipment can be improved by using a robot enabling the operators to remotely treat components from the outer operator's positions. There they will benefit from better radiation protection thus further reduce their taken dose. The wet blasting equipment could also be used to better control the levels of radioactivity on

  3. PaperBLAST: Text Mining Papers for Information about Homologs. (United States)

    Price, Morgan N; Arkin, Adam P


    Large-scale genome sequencing has identified millions of protein-coding genes whose function is unknown. Many of these proteins are similar to characterized proteins from other organisms, but much of this information is missing from annotation databases and is hidden in the scientific literature. To make this information accessible, PaperBLAST uses EuropePMC to search the full text of scientific articles for references to genes. PaperBLAST also takes advantage of curated resources (Swiss-Prot, GeneRIF, and EcoCyc) that link protein sequences to scientific articles. PaperBLAST's database includes over 700,000 scientific articles that mention over 400,000 different proteins. Given a protein of interest, PaperBLAST quickly finds similar proteins that are discussed in the literature and presents snippets of text from relevant articles or from the curators. PaperBLAST is available at IMPORTANCE With the recent explosion of genome sequencing data, there are now millions of uncharacterized proteins. If a scientist becomes interested in one of these proteins, it can be very difficult to find information as to its likely function. Often a protein whose sequence is similar, and which is likely to have a similar function, has been studied already, but this information is not available in any database. To help find articles about similar proteins, PaperBLAST searches the full text of scientific articles for protein identifiers or gene identifiers, and it links these articles to protein sequences. Then, given a protein of interest, it can quickly find similar proteins in its database by using standard software (BLAST), and it can show snippets of text from relevant papers. We hope that PaperBLAST will make it easier for biologists to predict proteins' functions.

  4. Application of Grid Planning Method in Drilling-Blasting Operations


    Dambov, Risto; Spasovski, Orce


    The problem occurs almost every day in operation and causes troubles to mining engineers. The right performance of drilling-blasting work is important for the successful operation of the entire excavation. The aim of the paper is to point out the importance of planning and how it can contribute to the right organization and make drilling-blasting and other mining activities in mine operations easier. Defining the activities and practical example that has been given are carried out by the u...

  5. Droplet Breakup Mechanisms in Air-blast Atomizers (United States)

    Aliabadi, Amir Abbas; Taghavi, Seyed Mohammad; Lim, Kelly


    Atomization processes are encountered in many natural and man-made phenomena. Examples are pollen release by plants, human cough or sneeze, engine fuel injectors, spray paint and many more. The physics governing the atomization of liquids is important in understanding and utilizing atomization processes in both natural and industrial processes. We have observed the governing physics of droplet breakup in an air-blast water atomizer using a high magnification, high speed, and high resolution LASER imaging technique. The droplet breakup mechanisms are investigated in three major categories. First, the liquid drops are flattened to form an oblate ellipsoid (lenticular deformation). Subsequent deformation depends on the magnitude of the internal forces relative to external forces. The ellipsoid is converted into a torus that becomes stretched and disintegrates into smaller drops. Second, the drops become elongated to form a long cylindrical thread or ligament that break up into smaller drops (Cigar-shaped deformation). Third, local deformation on the drop surface creates bulges and protuberances that eventually detach themselves from the parent drop to form smaller drops.

  6. Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Münster AML-study group (United States)

    Coenen, Eva A.; Zwaan, C. Michel; Reinhardt, Dirk; Harrison, Christine J.; Haas, Oskar A.; de Haas, Valerie; Mihál, Vladimir; De Moerloose, Barbara; Jeison, Marta; Rubnitz, Jeffrey E.; Tomizawa, Daisuke; Johnston, Donna; Alonzo, Todd A.; Hasle, Henrik; Auvrignon, Anne; Dworzak, Michael; Pession, Andrea; van der Velden, Vincent H. J.; Swansbury, John; Wong, Kit-fai; Terui, Kiminori; Savasan, Sureyya; Winstanley, Mark; Vaitkeviciene, Goda; Zimmermann, Martin; Pieters, Rob; van den Heuvel-Eibrink, Marry M.


    In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases. PMID:23974201

  7. Comprehensive Numerical Modeling of the Blast Furnace Ironmaking Process (United States)

    Zhou, Chenn; Tang, Guangwu; Wang, Jichao; Fu, Dong; Okosun, Tyamo; Silaen, Armin; Wu, Bin


    Blast furnaces are counter-current chemical reactors, widely utilized in the ironmaking industry. Hot reduction gases injected from lower regions of the furnace ascend, reacting with the descending burden. Through this reaction process, iron ore is reduced into liquid iron that is tapped from the furnace hearth. Due to the extremely harsh environment inside the blast furnace, it is difficult to measure or observe internal phenomena during operation. Through the collaboration between steel companies and the Center for Innovation through Visualization and Simulation, multiple computational fluid dynamics (CFD) models have been developed to simulate the complex multiphase reacting flow in the three regions of the furnace, the shaft, the raceway, and the hearth. The models have been used effectively to troubleshoot and optimize blast furnace operations. In addition, the CFD models have been integrated with virtual reality. An interactive virtual blast furnace has been developed for training purpose. This paper summarizes the developments and applications of blast furnace CFD models and the virtual blast furnace.

  8. Characterization of viscoelastic materials for low-magnitude blast mitigation (United States)

    Bartyczak, S.; Mock, W.


    Recent research indicates that exposure to low amplitude blast waves, such as IED detonation or multiple firings of a weapon, causes damage to brain tissue resulting in Traumatic Brain Injury (TBI) and Post Traumatic Stress Disorder (PTSD). Current combat helmets are not sufficiently protecting warfighters from this danger and the effects are debilitating, costly, and long-lasting. The objective of the present work is to evaluate the blast mitigating behavior of current helmet materials and new materials designed for blast mitigation using a test fixture recently developed at the Naval Surface Warfare Center Dahlgren Division for use with an existing gas gun. The 40-mm-bore gas gun was used as a shock tube to generate blast waves (ranging from 0.5 to 2 bar) in the test fixture mounted on the gun muzzle. A fast opening valve was used to release helium gas from the breech which formed into a blast wave and impacted instrumented targets in the test fixture. Blast attenuation of selected materials was determined through the measurement of stress data in front of and behind the target. Materials evaluated in this research include polyurethane foam from currently fielded US Army and Marine Corps helmets, polyurea 1000, and three hardnesses of Sorbothane (48, 58, and 70 durometer, Shore 00). Polyurea 1000 and 6061-T6 aluminum were used to calibrate the stress gauges.

  9. prfectBLAST: a platform-independent portable front end for the command terminal BLAST+ stand-alone suite. (United States)

    Santiago-Sotelo, Perfecto; Ramirez-Prado, Jorge Humberto


    prfectBLAST is a multiplatform graphical user interface (GUI) for the stand-alone BLAST+ suite of applications. It allows researchers to do nucleotide or amino acid sequence similarity searches against public (or user-customized) databases that are locally stored. It does not require any dependencies or installation and can be used from a portable flash drive. prfectBLAST is implemented in Java version 6 (SUN) and runs on all platforms that support Java and for which National Center for Biotechnology Information has made available stand-alone BLAST executables, including MS Windows, Mac OS X, and Linux. It is free and open source software, made available under the GNU General Public License version 3 (GPLv3) and can be downloaded at or

  10. Numerical analysis of blast flow-field of baffle type muzzle brake

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D.H. [Graduate School, Chungnam National University, Taejon (Korea); Ko, S. [Chungnam National University, Taejon (Korea)


    A three-dimensional unsteady, inviscid blast flow-field of a baffle type muzzle brake has been simulated by solving the Euler equation. The blast flow-field includes the effect of the free air blast, precursor blast flow and the propellant blast gas flow. Chimera grid scheme was used to generate 9 multi-block volume grids for the complex geometry. The evolution of the blast flow-field is presented by showing the contours of pressure, density and Mach number for certain time step. The comparison of the calculated and measured peak pressures on the surfaces of the muzzle brake is also presented. (author). 4 refs., 5 figs., 1 tab.

  11. Wound Ballistics Modeling for Blast Loading Blunt Force Impact and Projectile Penetration

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Paul A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Cooper, Candice Frances [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Burnett, Damon J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    Light body armor development for the warfighter is based on trial-and-error testing of prototype designs against ballistic projectiles. Torso armor testing against blast is virtually nonexistent but necessary to ensure adequate protection against injury to the heart and lungs. In this report, we discuss the development of a high-fidelity human torso model, it's merging with the existing Sandia Human Head-Neck Model, and development of the modeling & simulation (M&S) capabilities necessary to simulate wound injury scenarios. Using the new Sandia Human Torso Model, we demonstrate the advantage of virtual simulation in the investigation of wound injury as it relates to the warfighter experience. We present the results of virtual simulations of blast loading and ballistic projectile impact to the tors o with and without notional protective armor. In this manner, we demonstrate the ad vantages of applying a modeling and simulation approach to the investigation of wound injury and relative merit assessments of protective body armor without the need for trial-and-error testing.

  12. Full-scale testing of leakage of blast waves inside a partially vented room exposed to external air blast loading (United States)

    Codina, R.; Ambrosini, D.


    For the last few decades, the effects of blast loading on structures have been studied by many researchers around the world. Explosions can be caused by events such as industrial accidents, military conflicts or terrorist attacks. Urban centers have been prone to various threats including car bombs, suicide attacks, and improvised explosive devices. Partially vented constructions subjected to external blast loading represent an important topic in protective engineering. The assessment of blast survivability inside structures and the development of design provisions with respect to internal elements require the study of the propagation and leakage of blast waves inside buildings. In this paper, full-scale tests are performed to study the effects of the leakage of blast waves inside a partially vented room that is subjected to different external blast loadings. The results obtained may be useful for proving the validity of different methods of calculation, both empirical and numerical. Moreover, the experimental results are compared with those computed using the empirical curves of the US Defense report/manual UFC 3-340. Finally, results of the dynamic response of the front masonry wall are presented in terms of accelerations and an iso-damage diagram.

  13. Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Hanumantha Rao Madala


    Full Text Available Isocitrate dehydrogenases 1 and 2 (IDH1,2, the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs and gain an unusual new activity of reducing the α-ketoglutarate (α-KG to D-2 hydroxyglutarate (D-2HG in a NADPH-consuming reaction. The oncometabolite D-2HG, which accumulates >35 mM, is widely accepted to drive a progressive oncogenesis besides exacerbating the already increased oxidative stress in these cancers. More importantly, D-2HG competes with α-KG and inhibits a large number of α-KG-dependent dioxygenases such as TET (Ten-eleven translocation, JmjC domain-containing KDMs (histone lysine demethylases, and the ALKBH DNA repair proteins that ultimately lead to hypermethylation of the CpG islands in the genome. The resulting CpG Island Methylator Phenotype (CIMP accounts for major gene expression changes including the silencing of the MGMT (O6-methylguanine DNA methyltransferase repair protein in gliomas. Glioma patients with IDH1 mutations also show better therapeutic responses and longer survival, the reasons for which are yet unclear. There has been a great surge in drug discovery for curtailing the mutant IDH activities, and arresting tumor proliferation; however, given the unique and chronic metabolic effects of D-2HG, the promise of these compounds for glioma treatment is uncertain. This comprehensive review discusses the biology, current drug design and opportunities for improved therapies through exploitable synthetic lethality pathways, and an intriguing oncometabolite-inspired strategy for primary glioblastoma.

  14. BLAST: Building energy simulation in Hong Kong (United States)

    Fong, Sai-Keung


    The characteristics of energy use in buildings under local weather conditions were studied and evaluated using the energy simulation program BLAST-3.0. The parameters used in the energy simulation for the study and evaluation include the architectural features, different internal building heat load settings and weather data. In this study, mathematical equations and the associated coefficients useful to the industry were established. A technology for estimating energy use in buildings under local weather conditions was developed by using the results of this study. A weather data file of Typical Meteorological Years (TMY) has been compiled for building energy studies by analyzing and evaluating the weather of Hong Kong from the year 1979 to 1988. The weather data file TMY and the example weather years 1980 and 1988 were used by BLAST-3.0 to evaluate and study the energy use in different buildings. BLAST-3.0 was compared with other building energy simulation and approximation methods: Bin method and Degree Days method. Energy use in rectangular compartments of different volumes varying from 4,000 m3 to 40,000 m3 with different aspect ratios were analyzed. The use of energy in buildings with concrete roofs was compared with those with glass roofs at indoor temperature 21°C, 23°C and 25°C. Correlation relationships among building energy, space volume, monthly mean temperature and solar radiation were derived and investigated. The effects of space volume, monthly mean temperature and solar radiation on building energy were evaluated. The coefficients of the mathematical relationships between space volume and energy use in a building were computed and found satisfactory. The calculated coefficients can be used for quick estimation of energy use in buildings under similar situations. To study energy use in buildings, the cooling load per floor area against room volume was investigated. The case of an air-conditioned single compartment with 5 m ceiling height was

  15. 30 CFR 56.6404 - Separation of blasting circuits from power source. (United States)


    ... LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL... when closed to fire the blast. (b) Lead wires shall not be connected to the blasting switch until the...

  16. Quality of computerized blast load simulation for non-linear dynamic ...

    African Journals Online (AJOL)

    Quality of computerized blast load simulation for non-linear dynamic response ... commercial software system and a special-purpose, blast-specific software product to ... depend both on the analysis model of choice and the stand-off distances.

  17. Proceedings of the seventh annual symposium on explosives and blasting research

    International Nuclear Information System (INIS)



    Papers from this symposium dealt with the following topics: advanced primer designs, seismic effects of blasting, systems for velocity of detonation measurement and pressure measurement, toxic fumes from explosions, blast performance, blasting for rock fragmentation, computer-aided blast design, characteristics of liquid oxygen explosives, and correlations of performance of explosives with ground vibration, partitioning of energy, and firing time scatter effects. Papers have been indexed separately for inclusion on the data base

  18. Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells. (United States)

    Rushworth, Stuart A; Pillinger, Genevra; Abdul-Aziz, Amina; Piddock, Rachel; Shafat, Manar S; Murray, Megan Y; Zaitseva, Lyubov; Lawes, Matthew J; MacEwan, David J; Bowles, Kristian M


    Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro. We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment. We obtained acute myeloid leukaemia blast cells from unselected patients attending our UK hospital between Feb 19, 2010, and Jan 20, 2014. We isolated primary acute myeloid leukaemia blast cells from heparinised blood and human peripheral blood mononuclear cells to establish the activity of BTK in response to CD117 activation. Furthermore, we investigated the effects of ibrutinib on CD117-induced BTK activation, downstream signalling, adhesion to primary bone-marrow mesenchymal stromal cells, and proliferation of primary acute myeloid leukaemia blast cells. We used the Mann-Whitney U test to compare results between groups. We obtained acute myeloid leukaemia blast cells from 29 patients. Ibrutinib significantly inhibited CD117-mediated proliferation of primary acute myeloid leukaemia blast cells (p=0·028). CD117 activation increased BTK activity by inducing phosphorylated BTK in patients with CD117-positive acute myeloid leukaemia. Furthermore, ibrutinib inhibited CD117-induced activity of BTK and downstream kinases at a concentration of 100 nM or more. CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0·028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond. Our findings show that BTK has specific pro-tumoural biological actions downstream of surface CD117 activation, which are inhibited by ibrutinib

  19. Human parvovirus B19 in childhood acute lymphoblastic leukaemia in Basrah. (United States)

    Ibrahem, Wijdan Nazar; Hasony, Hassan Jaber; Hassan, Jenan Ghulam


    To investigate the association of human parvovirus B19 infection with the onset of acute lymphoblastic leukaemia and its effect on TEL-AML-1 fusion gene and the presence of mutant P53. The case-control study was conducted at Basrah Hospital for Paediatrics and Gynaecology, Basrah, Iraq, from May 2009 to April 2010. A total of 100 blood samples were collected from 40 newly diagnosed cases and 60 healthy children to serve as control matched by age and gender. Human parvovirus B19-IgG and anti-P53 antibody were detected by enzyme-linked immunosorbent assay and TEL-AML-1 fusion gene was detected by reverse transcriptase-polymerase chain reaction on extracted ribonucleic acid from fresh blood samples using specified primers. SPSS 15 was used for statistical analysis. A higher proportion of human parvovirus B19-positive cases was found in leukaemic patients (n=19; 47.5%) compared to 12 (20%) in the control group (pparvovirus-B19 infection as 10 (71.4%) of TEL-AML-1 translocation-positive cases had human parvovirus-B19 IgG. On the other hand, there was no association between such infections and P53 gene mutation in the patients. Human parvovirus-B19 infection is common in the population, with higher prevalence among leukaemic patients with significant association between human parvovirus-B19 and TEL-AML-1 fusion gene in patients of acute lymphoblastic leukaemia.

  20. Primary blast-induced traumatic brain injury: lessons from lithotripsy (United States)

    Nakagawa, A.; Ohtani, K.; Armonda, R.; Tomita, H.; Sakuma, A.; Mugikura, S.; Takayama, K.; Kushimoto, S.; Tominaga, T.


    Traumatic injury caused by explosive or blast events is traditionally divided into four mechanisms: primary, secondary, tertiary, and quaternary blast injury. The mechanisms of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury mechanism is associated with the response of brain tissue to the initial blast wave. Among the four mechanisms of bTBI, there is a remarkable lack of information regarding the mechanism of primary bTBI. On the other hand, 30 years of research on the medical application of shock waves (SWs) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by shock-accelerated flow. The resultant tissue injury includes several features observed in primary bTBI, such as hemorrhage, edema, pseudo-aneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation are all important factors in determining the extent of SW-induced tissue and cellular injury. In addition, neuropsychiatric aspects of blast events need to be taken into account, as evidenced by reports of comorbidity and of some similar symptoms between physical injury resulting in bTBI and the psychiatric sequelae of post-traumatic stress. Research into blast injury biophysics is important to elucidate specific pathophysiologic mechanisms of blast injury, which enable accurate differential diagnosis, as well as development of effective treatments. Herein we describe the requirements for an adequate experimental setup when investigating blast-induced tissue and cellular injury; review SW physics

  1. Oridonin effectively reverses the drug resistance of cisplatin involving induction of cell apoptosis and inhibition of MMP expression in human acute myeloid leukemia cells

    Directory of Open Access Journals (Sweden)

    Yuan Zhang


    Full Text Available Cisplatin is the first generation platinum-based chemotherapy agent. However, the extensive application of cisplatin inevitably causes drug resistance, which is a major obstacle to cancer chemotherapy. Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia (AML cells. The effect of oridonin on human AML cell proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells. Furthermore, cell apoptosis was examined by flow cytometry. The inhibitive effect of oridonin in vivo was determined using xenografted nude mice. In addition, the expressions of MMP2 and MMP9 were detected by Western blot. There was a synergistic antitumor effect between cisplatin and oridonin on cisplatin-resistant human AML cells in vitro and in vivo. In addition, the combination of cisplatin and oridonin synergistically induced cell apoptosis. Furthermore, the combination treatment not only inhibited AML cell migration and invasion, but more significantly, decreased the expressions of MMP2 and MMP9 proteins. Our results suggest that the synergistic effect between both agents is likely to be driven by the inhibition of MMP expression and the resulting increased apoptosis.

  2. Blast wave interaction with a rigid surface

    International Nuclear Information System (INIS)

    Josey, T.; Whitehouse, D.R.; Ripley, R.C.; Dionne, J.P.


    A simple model used to investigate blast wave interactions with a rigid surface is presented. The model uses a constant volume energy source analogue to predict pressure histories at gauges located directly above the charge. A series of two-dimensional axi-symmetric CFD calculations were performed, varying the height of the charge relative to the ground. Pressure histories, along with isopycnic plots are presented to evaluate the effects of placing a charge in close proximity to a rigid surface. When a charge is placed near a solid surface the pressure histories experienced at gauges above the charge indicate the presence of two distinct pressure peaks. The first peak is caused by the primary shock and the second peak is a result of the wave reflections from the rigid surface. As the distance from the charge to the wall is increased the magnitude of the second pressure peak is reduced, provided that the distance between the charge and the gauge is maintained constant. The simple model presented is able to capture significant, predictable flow features. (author)

  3. Report of a Phase II Study of Clofarabine and Cytarabine in De Novo and Relapsed and Refractory AML Patients and in Selected Elderly Patients at High Risk for Anthracycline Toxicity (United States)

    Cooper, Barry; Holmes, Houston; Vance, Estil; Berryman, Robert Brian; Maisel, Christopher; Li, Sandy; Saracino, Giovanna; Tadic-Ovcina, Mirjana; Fay, Joseph


    Purpose. To determine the efficacy and safety of clofarabine and cytarabine (Ara-C) in adult patients with relapsed or refractory acute myeloid leukemia (AML) and in elderly patients with untreated AML and heart disease. Patients and Methods. Patients with relapsed/refractory AML and older patients for whom there was a concern over toxicity from additional anthracyclines received 5 days of clofarabine, 40 mg/m2 per day i.v. over 1 hour, followed 4 hours later by Ara-C, 1,000 mg/m2 per day i.v. over 2 hours. Results. Thirty patients were enrolled. The median age was 67 years (range, 38–82 years) and 18 (60%) had received at least one prior therapy. Eleven (37%) patients had a history of cardiovascular disease and were considered to be at high risk for anthracycline toxicity. High-risk cytogenetic abnormalities were present in 14 (47%) patients. The overall response rate (complete remission [CR] plus partial remission) was 53%, including a CR in 14 patients (47%). Responses were observed in all cytogenetic risk groups and in patients who had received up to five prior therapies. The median disease-free survival interval was 9.5 months. The 30-day mortality rate was 20% (de novo AML, 8%; relapsed/refractory AML, 28%). Of the 14 patients achieving a CR, half were able to proceed to curative hematopoietic stem cell transplantation. Conclusions. Clofarabine in combination with Ara-C is effective in both untreated and previously treated patients with AML. In addition, it represents a useful remission induction strategy to serve as a bridge to transplantation in older patients with AML. PMID:21273514

  4. Controlled Blasting for Deconstruction of a Railway Bridge Near Sahibganj (United States)

    Mandal, S. K.; Ghosh, A. K.; Oraon, S.


    Some of the Indian Railway bridges require reconstruction for electrification and expansion of railway tracks. Dismantling of bridge within time schedule in densely populated area requires controlled and pre-planned blasting methodology for safe pulling down of the structure and quick removal of blasted debris for fast restoration of tracks and smooth plying of trains. The three arched railway bridge (Bridge No. 61) located between Sahibganj and Karamtola cases one such example where the bridge was dismantled and the track was restored within 4 h of blasting, though the stipulated block period for demolition and restoration of tracks was 6 h. The 25.48 m long three-arched bridge was drilled and blasted with 225 number of blastholes (32 mm diameter) and 100 kg explosive (25 mm diameter). Length of blastholes varied between 0.5 and 1.8 m with blast geometry of 0.3-0.35 m burden and 0.33 m spacing. This paper deals with the conceptual and theoretical model developed for identification of the key locations for drilling and implementation of the same. It also discusses about the precautionary measures and the drilling pattern adopted for quick demolition and speedy restoration of tracks.

  5. Blast tests of expedient shelters in the DICE THROW event

    International Nuclear Information System (INIS)

    Kearny, C.H.; Chester, C.V.


    To determine the worst blast environments that eight types of expedient shelters can withstand, we subjected a total of 18 shelters to the 1-kiloton blast effects of Defense Nuclear Agency's DICE THROW main event. These expedient shelters included two Russian and two Chinese types. The best shelter tested was a Small-Pole Shelter that had a box-like room of Russian design with ORNL-designed expedient blast entries and blast doors added. It was undamaged at the 53-psi peak overpressure range; the pressure rise inside was only 1.5 psi. An unmodified Russian Pole-Covered Trench Shelter was badly damaged at 6.8 psi. A Chinese ''Man'' Shelter, which skillfully uses very small poles to attain protective earth arching, survived 20 psi, undamaged. Two types of expedient shelters built of materials found in and around most American homes gave good protection at overpressures up to about 6 psi. Rug-Covered Trench Shelters were proved unsatisfactory. Water storage pits lined with ordinary plastic trash bags were proven practical at up to 53 psi, as were triangular expedient blast doors made of poles

  6. Modelling of turbulent combustion in the blast furnace raceway

    Energy Technology Data Exchange (ETDEWEB)

    Karvinen, R; Maekiranta, R [Tampere Univ. (Finland). Energy and Process Engineering


    The phenomena concerning coke-gas -suspension and simultaneous combustion of solid coke particles and residual fuel oil in a blast furnace raceway are modelled. The flow field of suspension is predicted by using the two fluid model, which is based on the Eulerian method, in the Phoenics code. The standard k-e -model of turbulence is used. Pyrolysis of oil droplets is calculated with the own coded subroutine, which is based on the Lagrangian approach. Gas phase reaction rate is assumed to be controlled by chemical kinetics. Radiative heat transfer is calculated by using the six-flux method. Heterogenous surface reactions are used for the coke particles. Calculations without coke combustion show that due to a poor mixing in the hot blast, pyrolysis gases of residual fuel oil have not time enough to react with oxygen. It is obvious that if combustion of coke particles is taken into account, the oxygen content in the blast decreases to such a level, that unburnt pyrolysis gases can flow out of the raceway causing problems. The distribution of coke void fraction has been succeeded to predict in the raceway domain. Coke particles fall from the upper part of the raceway to the hot blast forming locally high concentrations, which affect very strongly the oxygen distribution of the hot blast. (orig.) SULA 2 Research Programme; 10 refs.

  7. Modelling of turbulent combustion in the blast furnace raceway

    Energy Technology Data Exchange (ETDEWEB)

    Karvinen, R.; Maekiranta, R. [Tampere Univ. (Finland). Energy and Process Engineering


    The phenomena concerning coke-gas -suspension and simultaneous combustion of solid coke particles and residual fuel oil in a blast furnace raceway are modelled. The flow field of suspension is predicted by using the two fluid model, which is based on the Eulerian method, in the Phoenics code. The standard k-e -model of turbulence is used. Pyrolysis of oil droplets is calculated with the own coded subroutine, which is based on the Lagrangian approach. Gas phase reaction rate is assumed to be controlled by chemical kinetics. Radiative heat transfer is calculated by using the six-flux method. Heterogenous surface reactions are used for the coke particles. Calculations without coke combustion show that due to a poor mixing in the hot blast, pyrolysis gases of residual fuel oil have not time enough to react with oxygen. It is obvious that if combustion of coke particles is taken into account, the oxygen content in the blast decreases to such a level, that unburnt pyrolysis gases can flow out of the raceway causing problems. The distribution of coke void fraction has been succeeded to predict in the raceway domain. Coke particles fall from the upper part of the raceway to the hot blast forming locally high concentrations, which affect very strongly the oxygen distribution of the hot blast. (orig.) SULA 2 Research Programme; 10 refs.

  8. Effects of air blast on power plant structures and components

    International Nuclear Information System (INIS)

    Kot, C.A.; Valentin, R.A.; McLennan, D.A.; Turula, P.


    The effects of air blast from high explosives detonation on selected power plant structures and components are investigated analytically. Relying on a synthesis of state of the art methods estimates of structural response are obtained. Similarly blast loadings are determined from compilations of experimental data reported in the literature. Plastic-yield line analysis is employed to determine the response of both concrete and steel flat walls (plates) under impulsive loading. Linear elastic theory is used to investigate the spalling of concrete walls and mode analysis methods predict the deflection of piping. The specific problems considered are: the gross deformation of reinforced concrete shield and containment structures due to blast impulse, the spalling of concrete walls, the interaction or impact of concrete debris with steel containments and liners, and the response of exposed piping to blast impulse. It is found that for sufficiently close-in detonations and/or large explosive charge weights severe damage or destruction will result. This is particularly true for structures or components directly exposed to blast impulse

  9. Atmospheric particulate emissions from dry abrasive blasting using coal slag

    Energy Technology Data Exchange (ETDEWEB)

    Bhaskar Kura; Kalpalatha Kambham; Sivaramakrishnan Sangameswaran; Sandhya Potana [University of New Orleans, New Orleans, LA (United States). Department of Civil and Environmental Engineering


    Coal slag is one of the widely used abrasives in dry abrasive blasting. Atmospheric emissions from this process include particulate matter (PM) and heavy metals, such as chromium, lead, manganese, nickel. Quantities and characteristics of PM emissions depend on abrasive characteristics and process parameters. Emission factors are key inputs to estimate emissions. Experiments were conducted to study the effect of blast pressure, abrasive feed rate, and initial surface contamination on total PM (TPM) emission factors for coal slag. Rusted and painted mild steel surfaces were used as base plates. Blasting was carried out in an enclosed chamber, and PM was collected from an exhaust duct using U.S. Environment Protection Agency source sampling methods for stationary sources. Results showed that there is significant effect of blast pressure, feed rate, and surface contamination on TPM emissions. Mathematical equations were developed to estimate emission factors in terms of mass of emissions per unit mass of abrasive used, as well as mass of emissions per unit of surface area cleaned. These equations will help industries in estimating PM emissions based on blast pressure and abrasive feed rate. In addition, emissions can be reduced by choosing optimum operating conditions. 40 refs., 5 figs., 2 tabs.

  10. Blasting vibrations control: The shortcomings of traditional methods

    Energy Technology Data Exchange (ETDEWEB)

    Vuillaume, P.M.; Kiszlo, M. [Institut National de l`Environnement Industriel et des Risques, Verneuil en Halatte (France); Bernard, T. [Compagnie Nouvelle de Scientifiques, Nice (France)


    In the context of its studies for the French ministry of the environment and for the French national coal board, INERIS (the French institute for the industrial environment and hazards, formerly CERCHAR) has made a complete critical survey of the methods generally used to reduce the levels of blasting vibrations. It is generally acknowledged that the main parameter to control vibrations is the so-called instantaneous charge, or charge per delay. This should be reduced as much as possible in order to diminish vibration levels. On account of this, the use of a new generation of blasting devices, such as non-electric detonators or electronic sequential timers has been developed since the seventies. INERIS has collected data from about 900 blasts in 2 quarries and 3 open pit mines. These data include input parameters such as borehole diameter, burden, spacing, charge per hole, charge per delay, total fired charge, etc ... They also include output measurements, such as vibration peak particle velocities, and main frequencies. These data have been analyzed with the help of multi variable statistical tools. Blasting tests were undertaken to evaluate new methods of vibrations control, such as the superposition of vibration signals. These methods appear to be accurate in many critical cases, but certainly would be highly improved with a better accuracy of firing delays. The development of electronic detonators seems to be the way of the future for a better blasting control.

  11. Controlled Blasting for Deconstruction of a Railway Bridge Near Sahibganj (United States)

    Mandal, S. K.; Ghosh, A. K.; Oraon, S.


    Some of the Indian Railway bridges require reconstruction for electrification and expansion of railway tracks. Dismantling of bridge within time schedule in densely populated area requires controlled and pre-planned blasting methodology for safe pulling down of the structure and quick removal of blasted debris for fast restoration of tracks and smooth plying of trains. The three arched railway bridge (Bridge No. 61) located between Sahibganj and Karamtola cases one such example where the bridge was dismantled and the track was restored within 4 h of blasting, though the stipulated block period for demolition and restoration of tracks was 6 h. The 25.48 m long three-arched bridge was drilled and blasted with 225 number of blastholes (32 mm diameter) and 100 kg explosive (25 mm diameter). Length of blastholes varied between 0.5 and 1.8 m with blast geometry of 0.3-0.35 m burden and 0.33 m spacing. This paper deals with the conceptual and theoretical model developed for identification of the key locations for drilling and implementation of the same. It also discusses about the precautionary measures and the drilling pattern adopted for quick demolition and speedy restoration of tracks.

  12. Analysis of MINIE2013 Explosion Air-Blast Data

    Energy Technology Data Exchange (ETDEWEB)

    Schnurr, Julie M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of Hawaii, Manoa, HI (United States); Rodgers, Arthur J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Kim, Keehoon [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ford, Sean R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Ramirez, Abelardo L. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    We report analysis of air-blast overpressure measurements from the MINIE2013 explosive experiments. The MINIE2013 experiment involved a series of nearly 70 near-surface (height-ofburst, HOB, ranging from -1 to +4 m) low-yield (W=2-20 kg TNT equivalent) chemical highexplosives tests that were recorded at local distances (230 m – 28.5 km). Many of the W and HOB combinations were repeated, allowing for quantification of the variability in air-blast features and corresponding yield estimates. We measured canonical signal features (peak overpressure, impulse per unit area, and positive pulse duration) from the air-blast data and compared these to existing air-blast models. Peak overpressure measurements showed good agreement with the models at close ranges but tended to attenuate more rapidly at longer range (~ 1 km), which is likely caused by upward refraction of acoustic waves due to a negative vertical gradient of sound speed. We estimated yields of the MINIE2013 explosions using the Integrated Yield Determination Tool (IYDT). Errors of the estimated yields were on average within 30% of the reported yields, and there were no significant differences in the accuracy of the IYDT predictions grouped by yield. IYDT estimates tend to be lower than ground truth yields, possibly because of reduced overpressure amplitudes by upward refraction. Finally, we report preliminary results on a development of a new parameterized air-blast waveform.

  13. A review of three cases of mobile blast: The new culprit of hand injury

    Directory of Open Access Journals (Sweden)

    Nikunj B Mody


    Full Text Available Although blast injuries are common with war; cooking gas; firecracker, mobile phone blast cases are increasing in number in last couple of years. We present 3 cases of mobile blast in 3 children causing injury to dominant hand in them.


    Directory of Open Access Journals (Sweden)

    Hongxian Fu


    Full Text Available In this study, criteria and blasting technologies are introduced in order to control the stability of surrounding rock of tunnel built using drill-and-blast safety. The paper is composed of three parts, namely, a blast vibration propagation law in roof surrounding rock in close proximity to tunnel face, two formulae to calculate particle critical vibration velocity of shotcrete and key structural element at the roof of tunnel, and innovative technologies of tunnel blasting. The blast vibration propagation law is the base to control the stability of surrounding rock during tunnel blasting. Based on Morhr-Coulomb criterion and the dynamic analysis, two formulae to calculate the critical particle vibration velocity are proposed. Based on a series of trial blasts using electronic detonators, two innovative blasting technologies are derived. One is the blast holes detonated one by one by using electronic detonator, and another is the blast holes detonated by combining initiation system of electronic detonators and nonel detonators. The use of electronic detonators in tunnel blasting not only leads to a smaller blast vibration but also to a smaller extent of the EDZ (excavation damaged zone.

  15. Controlled blasting and its implications for the NNWSI project exploratory shaft

    International Nuclear Information System (INIS)

    Van Eeckhout, E.M.


    This report reviews controlled blasting techniques for shaft sinking. Presplitting and smooth blasting are the techniques of principal interest. Smooth blasting is preferred for the Nevada Nuclear Waste Storage Investigations exploratory shaft. Shaft damage can be monitored visually or by peak velocity measurements and refractive techniques. Damage into the rock should be limited to 3 ft. 40 refs., 22 figs., 7 tabs

  16. 29 CFR 1926.904 - Storage of explosives and blasting agents. (United States)


    ..., electric blasting caps, detonating primers, and primed cartridges shall not be stored in the same magazine... feet of explosives and detonator storage magazine. (d) No explosives or blasting agents shall be... 29 Labor 8 2010-07-01 2010-07-01 false Storage of explosives and blasting agents. 1926.904 Section...

  17. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation (United States)

    Messias, Carolina V.; Santana-Van-Vliet, Eliane; Lemos, Julia P.; Moreira, Otacilio C.; Cotta-de-Almeida, Vinicius; Savino, Wilson; Mendes-da-Cruz, Daniella Arêas


    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5). S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL) did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM) did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000–10000 nM) through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts. PMID:26824863

  18. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation.

    Directory of Open Access Journals (Sweden)

    Carolina V Messias

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5. S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000-10000 nM through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts.

  19. NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML. (United States)

    Chretien, Anne-Sophie; Devillier, Raynier; Fauriat, Cyril; Orlanducci, Florence; Harbi, Samia; Le Roy, Aude; Rey, Jérôme; Bouvier Borg, Gaelle; Gautherot, Emmanuel; Hamel, Jean-François; Ifrah, Norbert; Lacombe, Catherine; Cornillet-Lefebvre, Pascale; Delaunay, Jacques; Toubert, Antoine; Arnoulet, Christine; Vey, Norbert; Blaise, Didier; Olive, Daniel


    NKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT). NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46 high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46 low phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46 high phenotype ( p = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression ( p = 0.303). In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness.

  20. Thermal valorisation of automobile shredder residue: injection in blast furnace. (United States)

    Mirabile, Daphne; Pistelli, Maria Ilaria; Marchesini, Marina; Falciani, Roberta; Chiappelli, Lisa


    Wastes with residual heating value, according to the trend of the world legislation, could be thermally reused. The present study is conducted to verify the possibility of thermal valorisation of a waste, denominated fluff, by injection in blast furnace. The fluff, arising from the automobile shredder operations, is a waste characterised by a high organic matrix and is potentially dangerous due to the heavy metals, oils filter and halogenated plastics content. The first step of the work is the chemical, physical and toxicological characterisation of this material. Then the fluff injection in a blast furnace tuyere is theoretically analysed with a mathematical model. Finally, experimental trials are conducted in a pilot plant, simulating the most important part of the blast furnace: the raceway, in order to analyse process and industrial aspects. In view of an industrial application a first economical evaluation is carried out on the basis of model and experimental results.

  1. Radiometric report for a blast furnace tracing with radioactive isotopes

    International Nuclear Information System (INIS)

    Tanase, G.; Tanase, M.


    One of the methods to monitor refractory wall of blast furnace is its tracing with radioactive isotopes. The tracer isotope can be detected by two ways: the external dosimetric measurement at the armour of the blast furnace and/or the radiometric measurement of the iron sample charge by charge. Any change in radiometric situation of tracer radioisotope is recorded in a radiometric report. This paper presents an original concept of radiometric report based upon PARADOX and CORELDRAW soft kits. Their advantage are: quick and easy changes, easy recording of current radioactivity of tracer isotope, short history of changes, visual mapping of the tracer isotope and others. In this way we monitored 6 blast furnaces and more than 180 radioactive sources

  2. Production of blast furnace coke from soft brown coal

    Energy Technology Data Exchange (ETDEWEB)

    Scholz, G.; Wundes, H.; Schkommodau, F.; Zinke, H.-G. (VEB Gaskombinat Schwarze Pumpe (German Democratic Republic))


    Reviews experimental production and utilization of high quality brown coal coke in the GDR during 1985 and 1986. The technology of briquetting and coking brown coal dust is described; the superior parameters of produced coke quality are listed in comparison to those of regular industrial coke made from brown and black coal. Dust emission from high quality brown coal coke was suppressed by coke surface treatment with dispersion foam. About 4,200 t of this coke were employed in black coal coke substitution tests in a blast furnace. Substitution rate was 11%, blast furnace operation was positive, a substitution factor of 0.7 t black coal coke per 1 t of brown coal coke was calculated. Technology development of high quality brown coal coke production is regarded as complete; blast furnace coke utilization, however, requires further study. 8 refs.

  3. Effect of surface conditions on blast wave propagation

    International Nuclear Information System (INIS)

    Song, Seung Ho; Li, Yi Bao; Lee, Chang Hoon; Choi, Jung Il


    We performed numerical simulations of blast wave propagations on surfaces by solving axisymmetric two-dimensional Euler equations. Assuming the initial stage of fireball at the breakaway point after an explosion, we investigated the effect of surface conditions considering surface convex or concave elements and thermal conditions on blast wave propagations near the ground surface. Parametric studies were performed by varying the geometrical factors of the surface element as well as thermal layer characteristics. We found that the peak overpressure near the ground zero was increased due to the surface elements, while modulations of the blast wave propagations were limited within a region for the surface elements. Because of the thermal layer, the precursor was formed in the propagations, which led to the attenuation of the peak overpressure on the ground surface

  4. Superficial characterization of titanium league when submitted to abrasive blasting

    International Nuclear Information System (INIS)

    Suzuki, L.Y.; Leite, I.V.; Szesz, E.M.; Siqueira, C.J.M.


    Commercially pure titanium and some of its alloys exhibit a good biocompatibility. These characteristics are frequently used in the manufacture of orthopedic and dental implants. It is possible to modify its surface making it the bioactive using various methods, such as deposition of hydroxyapatite by plasma spray and increasing the roughness of the surface by abrasive blasting. This work is to modify the surface of titanium alloy Ti6Al4V ELI (ASTM F136: 02a) for abrasive blasting and study the morphology, crystallographic phases and the mechanical characteristics of the surface obtained. For such purpose, SEM images, diffraction of X-rays and tests of risk produced by nanoindenter. The sandblasting was done using alumina powder and blasting time of 6s. The morphology of the surfaces of Ti6Al4V ELI changed after sandblasting with increased roughness. It is possible to conclude that after sandblasting the titanium surface do not have a ductile behavior. (author)

  5. Blast venting through blanket material in the HYLIFE ICF reactor

    International Nuclear Information System (INIS)

    Liu, J.C.; Peterson, P.F.; Schrock, V.E.


    This work presents a numerical study of blast venting through various blanket configurations in the HYLIFE ICF reactor design. The study uses TSUNAMI -- a multi-dimensional, high-resolution, shock capturing code -- to predict the momentum exchange and gas dynamics for blast venting in complex geometries. In addition, the study presents conservative predictions of wall loading by gas shock and impulse delivered to the protective liquid blanket. Configurations used in the study include both 2700 MJ and 350 MJ fusion yields per pulse for 5 meter and 3 meter radius reactor chambers. For the former, an annular jet array is used for the blanket geometry, while in the latter, both annular jet array as well as slab geometries are used. Results of the study indicate that blast venting and wall loading may be manageable in the HYLIFE-II design by a judicious choice of blanket configuration

  6. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). (United States)

    Goodyear, Oliver C; Dennis, Mike; Jilani, Nadira Y; Loke, Justin; Siddique, Shamyla; Ryan, Gordon; Nunnick, Jane; Khanum, Rahela; Raghavan, Manoj; Cook, Mark; Snowden, John A; Griffiths, Mike; Russell, Nigel; Yin, John; Crawley, Charles; Cook, Gordon; Vyas, Paresh; Moss, Paul; Malladi, Ram; Craddock, Charles F


    Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8(+) T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8(+) T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD.

  7. Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study

    Directory of Open Access Journals (Sweden)

    Ezz-Eldin Azza M


    Full Text Available Abstract Objectives We have analyzed t(12;21(p13:q22 in an attempt to evaluate the frequency and prognostic significance of TEL-AML1 fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH. Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD. Methods All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH for t(12;21 in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD. We determined the prognostic significance of TEL-AML1 fusion represented by disease course and survival. Results TEL-AML1 fusion gene was positive in (37.5% in newly diagnosed patients. There was a significant correlation between TEL-AML1 fusion gene both at diagnosis (r = 0.5, P = 0.003 and as a MRD (r = 0.4, P = 0.01 with favorable course. Kaplan-Meier curve for the presence of TEL-AML1 fusion at the diagnosis was associated with a better probability of overall survival (OS; mean survival time was 47 ± 1 month, in contrast to 28 ± 5 month in its absence (P = 0.006. Also, the persistence at TEL-AML1 fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 ± 2 months in the presence of MRD and it was 40 ± 1 months in its absence. So, persistence of TEL-AML1 fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS. Conclusion For most patients, the presence of TEL-AML1 fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of TEL-AML1 fusion as MRD has no additive prognostic value.

  8. A review of blasting activity in the former Soviet Union

    Energy Technology Data Exchange (ETDEWEB)

    Leith, W. [Geological Survey, Reston, VA (United States); Bruk, L. [BRUK Hydrogeologcal Consulting, Inc., Rockville, MD (United States)


    Monitoring a comprehensive nuclear test ban by seismic means will require identification of seismic sources at lower magnitudes, where industrial explosions (primarily mining blasts) may comprise a significant fraction of the total number of events recorded and may, for some countries, dominate the seismicity. The USGS has recently obtained preliminary data on blasting activities in the former Soviet Union (FSU), one of the few countries in which the use of explosives exceeded that of the United States. A review of the Soviet data suggests that there are both similarities and differences in blasting practices between the U.S. and the FSU. These data are important because they provide some insight into variations form U.S. practice and because they can be used directly to estimate the assets needed to effectively monitor that country. Key findings include: (1) in 1988, approximately 2.6 million metric tons of high explosives were detonated in the FSu; this compares with 2.1 million metric tons in the U.S. in the same year; (2) about 80% of the explosives were used in mining, 10% in construction and 10% for other uses; (3) 84% of the explosives were consumed by only six Ministries of the FSU, and 66% were consumed in the three main mining industries: MinCherMet, MinTsvetMet and MinUgleProm; (4) in 1988 alone, the FSU conducted over 100 explosions in excess of 1 kt total charge (compare with one blast over 1 kt in the U.S. in 1987), and none of these were in the coal mining industry; (5) most very large blasts occurred on the surface, and in only a small number of mines; most underground blasts were less than 100 tons.

  9. PaperBLAST: Text Mining Papers for Information about Homologs

    International Nuclear Information System (INIS)

    Price, Morgan N.; Arkin, Adam P.


    Large-scale genome sequencing has identified millions of protein-coding genes whose function is unknown. Many of these proteins are similar to characterized proteins from other organisms, but much of this information is missing from annotation databases and is hidden in the scientific literature. To make this information accessible, PaperBLAST uses EuropePMC to search the full text of scientific articles for references to genes. PaperBLAST also takes advantage of curated resources (Swiss-Prot, GeneRIF, and EcoCyc) that link protein sequences to scientific articles. PaperBLAST’s database includes over 700,000 scientific articles that mention over 400,000 different proteins. Given a protein of interest, PaperBLAST quickly finds similar proteins that are discussed in the literature and presents snippets of text from relevant articles or from the curators. With the recent explosion of genome sequencing data, there are now millions of uncharacterized proteins. If a scientist becomes interested in one of these proteins, it can be very difficult to find information as to its likely function. Often a protein whose sequence is similar, and which is likely to have a similar function, has been studied already, but this information is not available in any database. To help find articles about similar proteins, PaperBLAST searches the full text of scientific articles for protein identifiers or gene identifiers, and it links these articles to protein sequences. Then, given a protein of interest, it can quickly find similar proteins in its database by using standard software (BLAST), and it can show snippets of text from relevant papers. We hope that PaperBLAST will make it easier for biologists to predict proteins’ functions.

  10. 77 FR 49277 - Takes of Marine Mammals During Specified Activities; Confined Blasting Operations by the U.S... (United States)


    ... effects that confined blasting can have on marine animals near the blast (Keevin et al., 1999). The visual... Atmospheric Administration Takes of Marine Mammals During Specified Activities; Confined Blasting Operations... Marine Mammals During Specified Activities; Confined Blasting Operations by the U.S. Army Corps of...

  11. Air Blasts from Cased and Uncased Explosives

    Energy Technology Data Exchange (ETDEWEB)

    Glenn, L. A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)


    The problem of a spherical blast in air is solved using the STUN code. For bare charges, the calculations are shown to be in excellent agreement with previous published results. It is demonstrated that, for an unconfined (uncased) chemical explosive, both range and time to effect scale inversely as the cube root of the yield and directly as the cube root of the ambient air density. It is shown that the peak overpressure decays to roughly 1/10 of ambient pressure in a scaled range of roughly 10 m/kg1/3 at sea level. At a height of 30 km, where the ambient density is a factor of 64 less, the range to the same decay increases to 40 m/kg1/3 . As a direct result of the scaling a single calculation suffices for all charge sizes and altitudes. Although the close-in results are sensitive to the nature of the explosive source and the equation of state of the air, this sensitivity is shown to virtually disappear at scaled ranges > 0.5 m/kg1/3 . For cased explosives the case thickness introduces an additional scale factor. Moreover, when the blast wave arrives at the inner case radius the case begins to expand. Fracture occurs when a critical value of the resulting hoop strain is reached, causing the case to shatter into fragments. A model is proposed to describe the size distribution of the fragments and their subsequent motion via drag interaction with the explosion products and ambient air. It is shown that a significant fraction of the charge energy is initially transmitted to the case fragments in the form of kinetic energy; for example, a 1 kg spherical charge with a 5 mm thick steel case has almost 29% of the total charge energy as initial kinetic energy of case fragments. This percentage increases with increasing case thickness and decreases with increasing charge size. The peak overpressure at a given range is 70-85% for cased explosives as compared with uncased and the peak impulse per unit area is 90-95%. The peak overpressure and

  12. Nodal wear model: corrosion in carbon blast furnace hearths

    International Nuclear Information System (INIS)

    Verdeja, L. F.; Gonzalez, R.; Alfonso, A.; Barbes, M. F.


    Criteria developed for the Nodal Wear Model (NWM) were applied to estimate the shape of the corrosion profiles that a blast furnace hearth may acquire during its campaign. Taking into account design of the hearth, the boundary conditions, the characteristics of the refractory materials used and the operation conditions of the blast furnace, simulation of wear profiles with central well, mushroom and elephant foot shape were accomplished. The foundations of the NWM are constructed considering that the corrosion of the refractory is a function of the temperature present at each point (node) of the liquid metal-refractory interface and the corresponding physical and chemical characteristics of the corrosive fluid. (Author) 31 refs

  13. Study of wet blasting of components in nuclear power stations

    Energy Technology Data Exchange (ETDEWEB)

    Hall, J


    This report looks at the method of wet blasting radioactive components in nuclear power stations. The wet blaster uses pearl shaped glass beads with the dimensions of 150-250 {mu}m mixed with water as blasting media. The improved design, providing outer operator's positions with proper radiation protection and more efficient blasting equipment has resulted in a lesser dose taken by the operators. The main reason to decontaminate components in nuclear power plants is to enable service on these components. On components like valves, pump shafts, pipes etc. oxides form and bind radiation. These components are normally situated at some distance from the reactor core and will mainly suffer from radiation from so called activation products. When a component is to be decontaminated it can be decontaminated to a radioactive level where it will be declassified. This report has found levels ranging from 150-1000 Bq/kg allowing declassification of radioactive materials.This difference is found between different countries and different organisations. The report also looks at the levels of waste generated using wet blasting. This is done by tracking the contamination to determine where it collects. It is either collected in the water treatment plant or collected in the blasting media. At Barsebaeck the waste levels, from de-contaminating nearly 800 components in one year, results in a waste volume of about 0,250 m{sup 3}. This waste consists of low and medium level waste and will cost about 3 600 EURO to store. The conclusions of the report are that wet blasting is an indispensable way to treat contaminated components in modern nuclear power plants. The wet blasting equipment can be improved by using a robot enabling the operators to remotely treat components from the outer operator's positions. There they will benefit from better radiation protection thus further reduce their taken dose. The wet blasting equipment could also be used to better control the levels of


    Directory of Open Access Journals (Sweden)

    Branko Božić


    Full Text Available The optimalization of exploitation in »Lakovići« limestone quarry is described. Based on determined discontinuities in the rock mass and their densities, the best possible working site have been located in order to obtain the best possible sizes of blasted rocks and work slope stability. Optimal lowest resistance line size for the quarry has been counted and proved experimentally. New blasting parameters have resulted in considerable saving of drilling and explosive (the paper is published in Croatian.

  15. Optimizing cast blasting efficiency using ANFO with liners

    Energy Technology Data Exchange (ETDEWEB)

    Madsen, A.


    As part of a five research project funded by the National Science Foundation, Peabody Energy studied three experimental cast blasts conducted at the North Antelope Rochelle mine site on July 24,28 and 31 2005. The initial purpose of this research project was to determine the influence that blast initiation sequence have on: NOx production; Face Displacement; Highwall damage; Explosive performance; Vibration emissions; Displacement; Surface swell; and Cast benefit. Two new discoveries on velocity of detonation (VoD) and pressure of detonation (PoD) were made as a result of this research project. Furthermore, a relationship between surface swell velocity and face velocity was also noted. 7 figs., 3 tabs.

  16. Use of coal-water mixtures in blast furnaces

    Energy Technology Data Exchange (ETDEWEB)

    Malgarini, G; Giuli, M; Davide, A; Carlesi, C [Centro Sviluppo Materiali, Rome (Italy); Italsider, Genoa [Italy; Deltasider, Piombino [Italy


    At the present time, an ironworks blast furnace employing a pulverized coal injection (PCI) system is in operation at the Piombino Works (Italy). A wide development, within this industry, of PCI techniques is expected in the near future to limit, as much as possible, the rebuilding of coke ovens. Research activities and industrial trials aimed at maximizing the use of coal injection into blast furnaces are in course of development. This paper uses flowsheets to illustrate such a system and provides graphs to indicate the economic convenience of PCI systems as compared with systems using naphtha as an injected fuel.

  17. Windows .NET Network Distributed Basic Local Alignment Search Toolkit (W.ND-BLAST

    Directory of Open Access Journals (Sweden)

    Oliver Melvin J


    Full Text Available Abstract Background BLAST is one of the most common and useful tools for Genetic Research. This paper describes a software application we have termed Windows .NET Distributed Basic Local Alignment Search Toolkit (W.ND-BLAST, which enhances the BLAST utility by improving usability, fault recovery, and scalability in a Windows desktop environment. Our goal was to develop an easy to use, fault tolerant, high-throughput BLAST solution that incorporates a comprehensive BLAST result viewer with curation and annotation functionality. Results W.ND-BLAST is a comprehensive Windows-based software toolkit that targets researchers, including those with minimal computer skills, and provides the ability increase the performance of BLAST by distributing BLAST queries to any number of Windows based machines across local area networks (LAN. W.ND-BLAST provides intuitive Graphic User Interfaces (GUI for BLAST database creation, BLAST execution, BLAST output evaluation and BLAST result exportation. This software also provides several layers of fault tolerance and fault recovery to prevent loss of data if nodes or master machines fail. This paper lays out the functionality of W.ND-BLAST. W.ND-BLAST displays close to 100% performance efficiency when distributing tasks to 12 remote computers of the same performance class. A high throughput BLAST job which took 662.68 minutes (11 hours on one average machine was completed in 44.97 minutes when distributed to 17 nodes, which included lower performance class machines. Finally, there is a comprehensive high-throughput BLAST Output Viewer (BOV and Annotation Engine components, which provides comprehensive exportation of BLAST hits to text files, annotated fasta files, tables, or association files. Conclusion W.ND-BLAST provides an interactive tool that allows scientists to easily utilizing their available computing resources for high throughput and comprehensive sequence analyses. The install package for W.ND-BLAST is


    Directory of Open Access Journals (Sweden)

    Zvonimir Deković


    Full Text Available The paper describes organisational-technological characteristics of blasting works during the excavation of the Grič Tunnel. The significance of blasting works during the excavation of the tunnel is shown through adjustment of blasting parameters taking into consideration the dynamics of the works, cost-effectiveness and influence of geological circumstances. Successfulness of blasting directly influences the subsequent tunnel excavation cycle both in terms of duration as well as eventually in terms of influence on the entire tunnel investment. Comparison of changes of basic blasting parameters during tunnel excavation ensured optimal excavation progress with minimal price per meter of tunnel progress.

  19. The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia : results of the international study Relapsed AML 2001/01

    NARCIS (Netherlands)

    Creutzig, Ursula; Zimmermann, Martin; Dworzak, Michael N.; Gibson, Brenda; Tamminga, Rienk; Abrahamsson, Jonas; Ha, Shau-Yin; Hasle, Henrik; Maschan, Alexey; Bertrand, Yves; Leverger, Guy; von Neuhoff, Christine; Razzouk, Bassem; Rizzari, Carmelo; Smisek, Petr; Smith, Owen P.; Stark, Batia; Reinhardt, Dirk; Kaspers, Gertjan L.


    The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by

  20. Controlled blasting experiments in a small drift at the CANMET experimental mine

    Energy Technology Data Exchange (ETDEWEB)

    Lizotte, Y.C.


    Experiments on controlled blasting conducted at the CANMET Experimental Mine to develop suitable controlled blasting techniques for small development headings are described. The methods selected for study must maintain the drill-blast-muck cycle achieved each work shift. The experiments also examine blast damage mechanisms to formulate criteria for dilution minimization with blast designs in stopes. The drift faces are 2.4 m square, with 34 to 43 holes drilled 2.4 m deep. Cartridged water gels, emulsions, and semi-gelatin dynamite were used in the cuts and as primers, ANFO as the main explosive, and semi- gelatin dynamite in 19 mm diameter cartridges was used in perimeter holes. The results of the first set of experiments show the efficiency of controlled blasting techniques to reduce blast damage. 60 refs., 71 figs., 9 tabs.

  1. [Monoclonal antibodies ICO-02 to blast cell antigens in patients with chronic myeloleukemia in blast crisis]. (United States)

    Baryshnikov, A Iu


    Mice were immunized with blood cells of a patient with chronic granulocytic leukemia, and their cells were subsequently used for the preparation of hybridoma ICO-02. This hybridoma is continuously producing monoclonal antibodies which reacted with cells in 4 out of 13 patients with blastic crisis of chronic granulocytic leukemia and in 6 out of 38 patients with acute lymphoblastic leukemia. Antibodies reacted with blast cells in 2 out of 3 patients with undifferentiated blastic crisis of chronic myelocytic leukemia and in 2 out of 5 patients with lymphoid variant of blastic crisis of chronic granulocytic leukemia. Cells of 6 patients with acute lymphoblastic leukemia which reacted with the monoclonal antibodies had immunological markers of T lymphocytes bone-marrow precursors. Monoclonal antibodies did not react with cells of blood and bone marrow from healthy people and from patients with chronic lymphocytic leukemia, acute myeloblastic leukemia, acute myelomonocytic leukemia, acute monoblastic leukemia and lymphosarcoma.

  2. Analysis of ways to control the supply of the blast, and their impact on gas-dynamic processes in the blast furnace

    Directory of Open Access Journals (Sweden)

    Віктор Петрович Кравченко


    Full Text Available The article presents the analysis of two methods of control over hot blast supply into a blast furnace with constant pressure and constant amount (consumption. The analysis of these two methods was performed with the aim of determining their influence upon changes in gas pressure in the blast furnace top. The blast furnace was considered as a unity of vessels (furnace hearth, the top and gas-dynamic resistance (a column of charge materials. A differential equation was obtained, with regard to the dynamic balance of gas flow at the inlet and outlet of the top; the equation relates the pressure and gas consumption at the top to the pressure and hot blast consumption at the inlet and outlet of the furnace and to the resistance of the column of charge materials. The column of charge materials is considered as n-th number of channels through which gas flow inside the furnace moves and which resist to the flow. By the analysis of this equation at steady state (automatic stabilization of gas pressure in the top, the conditions were obtained to be satisfied with the specified value of gas pressure in the top. This value is equal to a half of the sum of the value of hot blast pressure at the inlet into the furnace and the value of pressure inside the collector of blast furnace gas. This conclusion is verified by the operation practice of blast furnaces in Ukraine. While analyzing the second method of controlling the supply of blast supply-stabilization of consumption (amount of hot blast supplied into the furnace it has been shown that the method could be realized in condition of stabilization of the amount of blast furnace gas, going out of the furnace. As the resistance of the column of charge materials constantly changes it is necessary to change the hot blast pressure in order to ensure the constant amount of blast, supplied into the furnace. It is often connected with possible substantial pressure fluctuations of hot blast at the inlet of the

  3. Testing and modeling the dynamic response of foam materials for blast protection (United States)

    Fitek, John H.

    The pressure wave released from an explosion can cause injury to the lungs. A personal armor system concept for blast lung injury protection consists of a polymer foam layer behind a rigid armor plate to be worn over the chest. This research develops a method for testing and modeling the dynamic response of foam materials to be used for down-selection of materials for this application. Constitutive equations for foam materials are incorporated into a lumped parameter model of the combined armor plate and foam system. Impact testing and shock tube testing are used to measure the foam model parameters and validate the model response to a pressure wave load. The plate and foam armor model is then coupled to a model of the human thorax. With a blast pressure wave input, the armor model is evaluated based on how it affects the injury-causing mechanism of chest wall motion. Results show that to reduce chest wall motion, the foam must compress at a relatively constant stress level, which requires a sufficient foam thickness.

  4. Importance of No. 21 chromosome in translocation t(8:21) in acute myelocytic leukemia (AML) to the genesis of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, T; Minamihisamatsu, M


    The results are reported of the chromosome analysis of 17 cases of acute myelocytic leukemia (AML), mostly belonging to M2 of the FAB classification, especially on the translocation t(8:21) and its variant translocations. The presence of two cases with simple variant translocation not involving No. 8 chromosome seems to suggest that No. 21 chromosome is more important to the genesis of AML than the No. 8 chromosome. This assumption appears to be supported by findings on cases with complex translocation: In two cases with complex translocation, the portion translocated from No. 21 chromosome onto No. 8 was firmly maintained in the specific site (q21) on No. 8 whereas the portion translocated from No. 8 chromosome onto No. 21 was involved in further translocation with another chromosome, onto which it was re-translocated. The results of the present cytogenetic study indicate that the analysis of variant translocations in various specific chromosome translocations in leukemia and other malignant disorders is very useful to elucidate the problem as to whether the genesis of such disorders lies in either one or both of the pair of chromosomes involved in the specific translocations of the respective diseases.

  5. In patients older than 55 years with AML in first CR, should we search for a matched unrelated donor when an old sibling donor is available?

    DEFF Research Database (Denmark)

    Peffault de Latour, R; Labopin, M; Cornelissen, J


    Allogeneic hematopoietic transplantation is increasingly used in patients aged 55 years or more with AML. The question of whether outcomes can be improved with an allele-level 8/8 HLA-matched unrelated donor (MUD) rather than an older HLA-matched sibling (MSD, more than 55 years) is still...... unanswered. We thus analyzed outcomes in 714 patients aged 55 years and older with AML in first CR (CR1) who received PBSCs after a reduced-intensity conditioning hematopoietic cell transplant from a MUD (n=310) or a MSD (n=404) in a recent period (2005-2010). The 3-year cumulative incidences (CIs) of non......-relapse mortality were 17% and 23% with MSD and MUD, respectively (P=0.17). The 3-year CIs of relapse were 37% and 30%, respectively (P=0.12), resulting in a 3-year CI of leukemia-free survival of 46% and 47%, respectively (P=0.51). The 3-year overall survival was 49% with both MSD and MUD. In conclusion, HLA...

  6. Normal karyotype mosaicism in adult AML patients with adverse-risk and undefined karyotype: preliminary report of treatment outcomes after hematopoietic stem cell transplantation. (United States)

    Yoon, Jae-Ho; Kim, Hee-Je; Shin, Seung-Hwan; Yahng, Seung-Ah; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won


    Karyotype analysis in acute myeloid leukemia (AML) is one of the powerful prognostic factors for complete remission (CR), relapse, and overall survival (OS). Cytogenetic mosaicism is considered to be one of the important characteristics in expression of phenotypic manifestations. However, it has not come into focus due to emerging molecular biological approaches and the results of a number of mutation studies. Clinical correlates and prognostic relevance of mosaicism were evaluated in 163 AML patients [adverse-risk karyotypes (n = 72) and undefined karyotypes (n = 91)]. All patients were treated by induction and consolidation chemotherapies and finally went on hematopoietic stem cell transplantations (HSCT). Patients were divided into two subgroups, either with or without normal karyotype (NK) mosaicism. Seventy patients exhibited NK mosaicism and 93 did not. There were no significant differences in age, gender, chemotherapy cycles to achieve CR, HSCT donor type, source or intensity properties between the two subgroups. We found that NK mosaicism remaining in adverse-risk and undefined karyotype at diagnosis significantly correlates with better OS (p = 0.001) and lower CIR (p = 0.021) rate after HSCT. Our data show that the poor prognostic properties of unfavorable risk karyotype can be overcome to a great extent by allogeneic HSCT and chronic GVHD, especially in the subgroup with NK mosaicism. Cytogenetic mosaicism at initial diagnosis can be an influential factor for survival outcomes, even after HSCT.

  7. Differences between the CD34+ and CD34- blast compartments in apoptosis resistance in acute myeloid leukemia.

    NARCIS (Netherlands)

    Stijn, van A.; Pol, van der M.A.; Kok, A.; Bontje, PM; Roemen, GM; Beelen, R.H.J.; Ossenkoppele, G.J.; Schuurhuis, G.J.


    BACKGROUND AND OBJECTIVES: Altered expression of members of the Bcl-2 family might account for the observed apoptosis resistance to chemotherapy in acute myeloid leukemia (AML). Given the poor prognosis associated with CD34+ expression in AML, we studied the role of spontaneous apoptosis and

  8. Blasted copper slag as fine aggregate in Portland cement concrete. (United States)

    Dos Anjos, M A G; Sales, A T C; Andrade, N


    The present work focuses on assessing the viability of applying blasted copper slag, produced during abrasive blasting, as fine aggregate for Portland cement concrete manufacturing, resulting in an alternative and safe disposal method. Leaching assays showed no toxicity for this material. Concrete mixtures were produced, with high aggregate replacement ratios, varying from 0% to 100%. Axial compressive strength, diametrical compressive strength, elastic modulus, physical indexes and durability were evaluated. Assays showed a significant improvement in workability, with the increase in substitution of fine aggregate. With 80% of replacement, the concrete presented lower levels of water absorption capacity. Axial compressive strength and diametrical compressive strength decreased, with the increase of residue replacement content. The greatest reductions of compressive strength were found when the replacement was over 40%. For tensile strength by diametrical compression, the greatest reduction occurred for the concrete with 80% of replacement. After the accelerated aging, results of mechanic properties showed a small reduction of the concrete with blasted copper slag performance, when compared with the reference mixture. Results indicated that the blasted copper slag is a technically viable material for application as fine aggregate for concrete mixtures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Effect of blasting on the strength of a rock mass

    Energy Technology Data Exchange (ETDEWEB)

    Muller, L


    Although the fact that blasting concussions tend to loosen a rock mass has always been known, the enormous reduction in strength associated with such loosening is not generally recognized. Recent investigations of the effect of blasting on a rock mass have shown that even slight loosening may markedly reduce the strength. This factor introduces a new slant on modern blasting methods, some of which will have to be considered more critically. The sensitivity of the mass to impacts depends on stress concentrations at the end of joints (Kerbspannungen) and on tensile stresses developed in the immediate vicinity of a joint, even in regions where the field stresses are not tensile. Thus, the sensitivity depends on the shape and orientation of the joints and particularly on the degree of separation of the individual joint families. The orientation of the joint families to the strains produced by blasting is just as important as the reduction in overall strength arising from the drop in friction due to the effects of the ''knocking out'' process (Foppl) on the joint body complex. Concussions may critically increase the degree of separation of the joint network thus reducing the tensile and shear strengths of the rock mass. (19 refs.)

  10. Injection of heavy fuel oil into the blast furnace

    Energy Technology Data Exchange (ETDEWEB)

    Paloposki, T. [Helsinki Univ. of Technology, Otaniemi (Finland); Hakala, J.; Mannila, P.; Laukkanen, J. [Oulu Univ. (Finland)


    This study deals with the injection and combustion of heavy fuel oil in blast furnaces. The injection of the oil was studied experimentally in a small-scale test rig. The combustion of the oil was analysed with a commercial computer program for flow and combustion simulations. Results from computer simulations show that the combustion of the oil can be improved by decreasing the size of the oil drops and by enhancing the mixing between the oil drops and the hot blast. The devolatilization rate of the oil mainly depends on the size of the oil drops. The combustion rate of the volatiles mainly depends on the effectiveness of turbulent mixing with combustion air. Methods to decrease the size of the oil drops were sought in the experimental part of the study. Experimental results show that the size of the oil drops increases with increasing mass flow rate of the oil and decreases with increasing velocity of the hot blast. Methods to improve the mixing between the oil drops and the hot blast are suggested but have not yet been experimentally tested. (author) (4 refs.)

  11. blastjs: a BLAST+ wrapper for Node.js. (United States)

    Page, Martin; MacLean, Dan; Schudoma, Christian


    To cope with the ever-increasing amount of sequence data generated in the field of genomics, the demand for efficient and fast database searches that drive functional and structural annotation in both large- and small-scale genome projects is on the rise. The tools of the BLAST+ suite are the most widely employed bioinformatic method for these database searches. Recent trends in bioinformatics application development show an increasing number of JavaScript apps that are based on modern frameworks such as Node.js. Until now, there is no way of using database searches with the BLAST+ suite from a Node.js codebase. We developed blastjs, a Node.js library that wraps the search tools of the BLAST+ suite and thus allows to easily add significant functionality to any Node.js-based application. blastjs is a library that allows the incorporation of BLAST+ functionality into bioinformatics applications based on JavaScript and Node.js. The library was designed to be as user-friendly as possible and therefore requires only a minimal amount of code in the client application. The library is freely available under the MIT license at

  12. Spreading of sediment due to underwater blasting and dredging

    DEFF Research Database (Denmark)

    Nielsen, Morten Holtegaard; Bach, Lis; Bollwerk, Sandra


    out in connection with the construction of a new quay at the existing harbour of Sisimiut, Greenland. Subsequent to the largest of a series of underwater blasts, the distribution of suspended sediment in the water column at and around the construction site was observed using a CTD (Conductivity...

  13. Grit blasting nozzle fabricated from mild tool steel proves satisfactory (United States)

    Mc Farland, J. E.; Turbitt, B.


    Dry blasting with glass beads through a nozzle assembly descales both the outside and inside surfaces of tubes of Inconel 718 used for the distribution of gaseous oxygen. The inside of the nozzle is coated with polyurethane and the deflector with a commercially available liquid urethane rubber.

  14. Enhancements and Analysis of CTH Software for Underbody Blast (United States)


    authors expressed herein do not necessarily state or reflect those of the United States Government or the DoD, and shall not be used for advertising or...Trembelay, J., “Validation of a Loading Model for Simulating Blast Mine Effects on Armoured Vehicles,” 7th International LS-DYNA Users Conference

  15. A numerical technique to design blast noise mitigation measures

    NARCIS (Netherlands)

    Berg, F. van den; Eerden, F.J.M. van der


    Large weapons, such as armor, artillery or demolitions, create a high-energy blast wave. It has a low frequency content, typically between 15 and 125 Hz, and can propagate over large distances. As a result it is a relative important cause for annoyance. Mitigation measures need to be close to the

  16. Test methods for protective footwear against AP mine blast

    NARCIS (Netherlands)

    Cronin, D.S.; Williams, K.; Bass, C.R.; Magnan, P.; Dosquet, F.; Bergeron, D.M.; Bree, J.L.M.J. van


    The testing and development of protective footwear for anti-personnel landmine blast threats is of great importance to civilian and military deminers, and peacekeepers. This study will review the wide range of test methods that have been developed by NATO countries to test footwear against the

  17. Predicting fragmentation sizing profiles for different blasting patterns

    International Nuclear Information System (INIS)

    Sheikh, A.M.; Chung, S.H.


    This paper evaluates the efficiency of blasting in a large scale underground heap leaching operation. The prediction model is based on the dynamic tensile breaking strength of rock formation, the detonation characteristics of the explosives and the drill hole pattern. The modelling includes crack pattern development and fragmentation computation fitted by the Rosin-Rammler distribution equation

  18. Experimental studies on intake headloss of a blasted lake tap

    International Nuclear Information System (INIS)

    Yang, James; Billstein, Mats; Engström, Fredrik; Strand, Rikard


    In existing reservoirs, construction of an intake is sometimes achieved by so-called lake tapping, a submerged tunnel piercing by blasting out the rock plug at the intake. The blasting process involves phases of rock, water, air and gas released from the explosive charge; the resulting entrance profile often differs from design assumptions. The intake headloss is a factor of concern for power generation. For a vertical intake formed by lake tapping, experiments have been carried out in a 1:30 physical model to examine the effect of entrance shapes on intake headlosses. The purpose is that, if there is potential to reduce the headlosses, the originally blasted intake shape would be modified. In the model, five alternative shapes are evaluated. The test results show that to enlarge the vertical shaft area is the most effective way to reduce the intake headloss; to further blast out a narrow channel upstream does not give much effect. Bearing in mind the risk of free-surface vortex at the intake, the influence of the intake modifications on vortex is also checked

  19. Brain Vulnerability to Repeated Blast Overpressure and Polytrauma (United States)


    Gould , 1994; Yu et al ., 2004; Montaron et al ., 2006); with males showing...ety, and depression (Gentilini et al ., 1985; Schoenhuber and Gentilini, 1988 ; Ponsford et al ., 1995). Blast induced traumatic brain injury (bTBI...into neuronal circuits (Kempermann, 2002a; Kozorovitskiy and Gould , 2003; Abrous et al ., 2005; Hagg, 2005; Ming and Song, 2005; Zhao et al .,

  20. [A new cause of ocular trauma due to "blast" injury]. (United States)

    Chiriac, I


    Are presented five observations of ocular trauma caused by blast of plastic siphon-bottles during their loading. Two of them result in eyeball evisceration, in the three others the visual function was kept. We deem necessary the respecting of single use instruction for these plastic containers and possibly--the ban of theirs using like siphon.