Modelling of Equilibrium Between Mantle and Core: Refractory, Volatile, and Highly Siderophile Elements

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Righter, K.; Danielson, L.; Pando, K.; Shofner, G.; Lee, C. -T.

2013-01-01

Siderophile elements have been used to constrain conditions of core formation and differentiation for the Earth, Mars and other differentiated bodies [1]. Recent models for the Earth have concluded that the mantle and core did not fully equilibrate and the siderophile element contents of the mantle can only be explained under conditions where the oxygen fugacity changes from low to high during accretion and the mantle and core do not fully equilibrate [2,3]. However these conclusions go against several physical and chemical constraints. First, calculations suggest that even with the composition of accreting material changing from reduced to oxidized over time, the fO2 defined by metal-silicate equilibrium does not change substantially, only by approximately 1 logfO2 unit [4]. An increase of more than 2 logfO2 units in mantle oxidation are required in models of [2,3]. Secondly, calculations also show that metallic impacting material will become deformed and sheared during accretion to a large body, such that it becomes emulsified to a fine scale that allows equilibrium at nearly all conditions except for possibly the length scale for giant impacts [5] (contrary to conclusions of [6]). Using new data for D(Mo) metal/silicate at high pressures, together with updated partitioning expressions for many other elements, we will show that metal-silicate equilibrium across a long span of Earth s accretion history may explain the concentrations of many siderophile elements in Earth's mantle. The modeling includes refractory elements Ni, Co, Mo, and W, as well as highly siderophile elements Au, Pd and Pt, and volatile elements Cd, In, Bi, Sb, Ge and As.

[Mantle cell lymphoma: Towards a personalized therapeutic strategy?].

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Navarro Matilla, Belén; García-Marco, José A

2015-06-22

Mantle cell lymphoma (MCL) is a clinically heterogeneous non-Hodgkin lymphoma with an aggressive clinical behaviour and short survival in some cases and an indolent course in others. Advances in the biology and pathogenesis of MCL have unveiled several genes involved in deregulation of cell cycle checkpoints and the finding of subclonal populations with specific recurrent mutations (p53, ATM, NOTCH2) with an impact on disease progression and refractoriness to treatment. Prognostic stratification helps to distinguish between indolent and aggressive forms of MCL. Currently, younger fit patients benefit from more intensive front line chemotherapy regimens and consolidation with autologous transplantation, while older or frail patients are treated with less intensive regimens and rituximab maintenance. For relapsing disease, the introduction of bortezomib and lenalidomide containing regimens and B-cell receptor pathway inhibitors such as ibrutinib and idelalisib in combination with immunochemotherapy have emerged as therapeutic agents with promising clinical outcomes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Mantle Cell Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells.

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Ma, Jiao; Lu, Pin; Guo, Ailin; Cheng, Shuhua; Zong, Hongliang; Martin, Peter; Coleman, Morton; Wang, Y Lynn

2014-09-01

Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one-third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach. © 2014 John Wiley & Sons Ltd.

Use of acalabrutinib in patients with mantle cell lymphoma.

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Awan, Farrukh T; Jurczak, Wojciech

2018-06-01

Acalabrutinib, a selective Bruton tyrosine kinase (BTK) inhibitor, was granted accelerated approval by the FDA on 31 October 2017 for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Areas covered: This narrative review provides an overview of acalabrutinib, its use in clinical practice and potential future developments. Expert commentary: BTK inhibitors have demonstrated efficacy in patients with relapsed or refractory MCL. To prepare patients for therapy, all preexisting infections should be diagnosed and treated, and infection prophylaxis undertaken. Serious adverse reactions are rare with acalabrutinib; however, patients should be made aware of common adverse events such as headaches, which usually resolve within one month without medical treatment. Interaction with other drugs appears to be less of an issue with acalabrutinib than with ibrutinib; however, patients receiving acalabrutinib therapy must be advised not to take any additional medications without first consulting with their treating physician. A key unmet medical need is treatment options for patients in whom BTK inhibitors are discontinued, because of either intolerance or refractory disease. Patients not tolerating ibrutinib could be switched to acalabrutinib, which has improved selectivity and increased tolerability. First-line treatment with acalabrutinib is being investigated.

Ibrutinib Is Effective in the Treatment of Autoimmune Haemolytic Anaemia in Mantle Cell Lymphoma

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Aliénor Galinier

2017-01-01

Full Text Available Autoimmune haemolytic anaemia (AIHA in mantle cell lymphoma (MCL is a rare but life-threatening complication. To date, there are no relevant data for treatment of AIHA in MCL. Ibrutinib, which has been approved for relapse/refractory MCL, is an immunomodulatory drug inhibiting Th2 activation and consequently the production of autoantibodies. We report a case of MCL with AIHA in which this form of anaemia was not controlled with the usual chemotherapy. Ibrutinib was used when MCL with AIHA relapsed, and it allowed rapid remission of AIHA and rapid discontinuation of steroid therapy.

The mantle cells lymphoma: a proposed treatment

International Nuclear Information System (INIS)

Chavez Martinez, Marlene Elizabeth

2012-01-01

A literature review was performed on mantle cells lymphoma in the therapeutic schemes. The literature that has been used is published in journals of medicine specializing in hematology, oncology, radiation therapy, molecular biology and internal medicine. The literature review was performed to propose a scheme of treatment according to Costa Rica. Epigenetic alterations have been revealed in patients with mantle lymphoma on current researches. The mantle lymphoma pathology has been described in various forms of clinical and histological presentation, stressing the importance of detailing the different methods and diagnostic reports. Working groups have proposed and developed various chemotherapy regimens and concluded that CHOP alone is without effect in mantle cell lymphoma unlike R-hyper-CVAD, CHOP / DHAP, high-dose Ara-C. Researchers have tried to develop new treatments based vaccines, use of modified viruses, specific monoclonal antibodies. The classic treatment has been triple intrathecal therapy. The central nervous system has been one of the most momentous sites of mantle cell lymphoma infiltration because poorer patient prognosis [es

Lenalidomide-bendamustine-rituximab in untreated mantle cell lymphoma > 65 years with untreated mantle cell lymphoma

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Albertsson-Lindblad, Alexandra; Kolstad, Arne; Laurell, Anna

2016-01-01

For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years with untr......For elderly patients with mantle cell lymphoma (MCL), there is no defined standard therapy. In this multicenter open-label phase I/II trial we evaluated the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment to elderly MCL patients. Patients >65 years...

Mantle cell lymphoma of the larynx: Primary case report

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Naciri Sarah

2012-07-01

Full Text Available Abstract Introduction Primary laryngeal lymphomas are exceedingly rare. Only about a hundred cases have been reported. They consist mainly of non-Hodgkin lymphoma, especially of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue. We report the first case of a primary laryngeal mantle cell lymphoma. Case presentation We report a case of a primary mantle cell lymphoma of the larynx in a 70-year-old North African non-smoker male. We present a detailed report of his clinical and paraclinical data as well as treatment options. Conclusions Mantle cell lymphoma is a very aggressive lymphoma subset associated with poor prognosis. Laryngeal mantle cell lymphoma is exceedingly rare. To the best of our knowledge, this is the first case to ever be reported.

Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

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2017-10-10

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

CAR-T cells and allogeneic hematopoietic stem cell transplantation for relapsed/refractory B-cell acute lymphoblastic leukemia.

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Liu, Jun; Zhang, Xi; Zhong, Jiang F; Zhang, Cheng

2017-10-01

Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL. In this review, we first discuss the different types of CAR-T cells. We then discuss the treatment of relapsed/refractory ALL using only CAR-T cells. Finally, we discuss the use of CAR-T cells, followed by allo-HSCT, for the treatment of relapsed/refractory ALL.

Dynamical geochemistry of the mantle

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G. F. Davies

2011-09-01

Full Text Available The reconciliation of mantle chemistry with the structure of the mantle inferred from geophysics and dynamical modelling has been a long-standing problem. This paper reviews three main aspects. First, extensions and refinements of dynamical modelling and theory of mantle processing over the past decade. Second, a recent reconsideration of the implications of mantle heterogeneity for melting, melt migration, mantle differentiation and mantle segregation. Third, a recent proposed shift in the primitive chemical baseline of the mantle inferred from observations of non-chondritic ¹⁴²Nd in the Earth. It seems most issues can now be resolved, except the level of heating required to maintain the mantle's thermal evolution.

A reconciliation of refractory trace elements and their isotopes with the dynamical mantle, proposed and given preliminary quantification by Hofmann, White and Christensen, has been strengthened by work over the past decade. The apparent age of lead isotopes and the broad refractory-element differences among and between ocean island basalts (OIBs and mid-ocean ridge basalts (MORBs can now be quantitatively accounted for with some assurance.

The association of the least radiogenic helium with relatively depleted sources and their location in the mantle have been enigmatic. The least radiogenic helium samples have recently been recognised as matching the proposed non-chondritic primitive mantle. It has also been proposed recently that noble gases reside in a so-called hybrid pyroxenite assemblage that is the result of melt from fusible pods reacting with surrounding refractory peridotite and refreezing. Hybrid pyroxenite that is off-axis may not remelt and erupt at MORs, so its volatile constituents would recirculate within the mantle. Hybrid pyroxenite is likely to be denser than average mantle, and thus some would tend to settle in the D" zone at the base of the mantle, along with some old subducted

Oceanic mantle rocks reveal evidence for an ancient, 1.2-1.3 Ga global melting event

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Dijkstra, A. H.; Sergeev, D.; McTaminey, L.; Dale, C. W.; Meisel, T. C.

2011-12-01

It is now increasingly being recognized that many oceanic peridotites are refertilized harzburgites, and that the refertilization often masks an extremely refractory character of the original mantle rock 'protolith'. Oceanic peridotites are, when the effects of melt refertilization are undone, often too refractory to be simple mantle melting residues after the extraction of mid-ocean ridge basalts at a spreading center. Rhenium-osmium isotope analysis is a powerful method to look through the effects of refertilization and to obtain constraints on the age of the melting that produced the refractory mantle protolith. Rhenium-depletion model ages of such anomalously refractory oceanic mantle rocks - found as abyssal peridotites or as mantle xenoliths on ocean islands - are typically >1 Ga, i.e., much older than the ridge system at which they were emplaced. In my contribution I will show results from two case studies of refertilized anciently depleted mantle rocks (Macquarie Island 'abyssal' peridotites and Lanzarote mantle xenoliths). Interestingly, very refractory oceanic mantle rocks from sites all around the world show recurring evidence for a Mesoproterozoic (~1.2-1.3 Ga) melting event [1]. Therefore, oceanic mantle rocks seem to preserve evidence for ancient melting events of global significance. Alternatively, such mantle rocks may be samples of rafts of ancient continental lithospheric mantle. Laser-ablation osmium isotope 'dating' of large populations of individual osmium-bearing alloys from mantle rocks is the key to better constrain the nature and significance of these ancient depletion events. Osmium-bearing alloys form when mantle rocks are melted to high-degrees. We have now extracted over >250 detrital osmium alloys from placer gold occurrences in the river Rhine. These alloys are derived from outcrops of ophiolitic mantle rocks in the Alps, which include blocks of mantle rocks emplaced within the Tethys Ocean, and ultramafic lenses of unknown

MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

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2014-05-22

Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

Uranium in mantle processes

International Nuclear Information System (INIS)

Cortini, M.

1984-01-01

(1) Metasomatism is an effective process in the mantle. It controls the distribution of U, Th and Pb in the mantle before the onset of magma formation. (2) Radioactive disequilibria demonstrate that magma formation is an open-system very fast process in which Ra, U and Th are extracted in large amounts from a mantle source that is geochemically distinct from the mantle fraction from which the melt is formed. (3) Because the enrichment of U, Th and Ra in the magma is so fast, the concept of mineral-melt partition coefficient is not valid for these elements during magma formation. (4) Metasomatism seems to generally produce an increase in μ and a decrease in K of the metasomatized mantle region. (5) Magma formation at oceanic ridges and islands seems to generally produce a decrease in K, in its mantle source region. (6) The major source of U, Th, Ra and Pb in a magma probably is the metasomatic mantle component. Instead, the major source of Sr and Nd in a magma is the non-metasomatic, more 'refractory' mantle component. (7) This proposed model is testable. It predicts isotopic disequilibrium of Pb between coexisting minerals and whole rocks, and a correlation of Pb with Th isotopes. (author)

Origin of Fe-rich lherzolites and wehrlites from Tok, SE Siberia by reactive melt percolation in refractory mantle peridotites

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Ionov, Dmitri A.; Chanefo, Ingrid; Bodinier, Jean-Louis

2005-10-01

Lherzolite-wehrlite (LW) series xenoliths from the quaternary Tok volcanic field in the southeastern Siberian craton are distinguished from the more common lherzolite-harzburgite (LH) series by (a) low Mg numbers (0.84-0.89) at high modal olivine (66-84%) and (b) widespread replacement of orthopyroxene (0-12%) and spinel by clinopyroxene (7-22%). The LW series peridotites are typically enriched in Ca, Fe, Mn and Ti, and depleted in Si, Ni and Cr relative to refractory LH series rocks (Mg number ≥0.89), which are metasomatised partial melting residues. Numerical modelling of Fe-Mg solid/liquid exchange during melt percolation demonstrates that LW series rocks can form by reaction of host refractory peridotites with evolved (Mg numbers 0.6-0.7), silica-undersaturated silicate melts at high melt/rock ratios, which replace orthopyroxene with clinopyroxene and decrease Mg numbers. This process is most likely related to underplating and fractionation of basaltic magma in the shallow mantle, which also produced olivine-clinopyroxene cumulates found among the Tok xenoliths.

Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

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2018-03-13

Burkitt Lymphoma; CD20-Positive Neoplastic Cells Present; Diffuse Large B-Cell Lymphoma; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mature B-Cell Non-Hodgkin Lymphoma

Early-stage mantle cell lymphoma

DEFF Research Database (Denmark)

Dabaja, B S; Zelenetz, A D; Ng, A K

2017-01-01

Background: Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. Patients and methods: In this 13-institution study, we examined...

A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia

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Tucker DL

2015-06-01

Full Text Available David L Tucker, Simon A Rule Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK Abstract: Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL and chronic lymphocytic leukemia (CLL, small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. Keywords: ibrutinib, mantle cell lymphoma, chronic lymphocytic leukemia, Bruton’s tyrosine kinase, lymphoproliferative disorders

Gastric and colonic mantle cell lymphoma - incidental discovery.

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Pitigoi, Dan; Stoica, Victor; Stoia, Razvan; Dobrea, Camelia; Becheanu, Gabriel; Diculescu, Mircea

2009-03-01

A 65-year old patient, with no medical history, was admitted for lower gastrointestinal bleeding. On clinical examination the patient seemed to be in good health. However the examination was completed with a rectosigmoidoscopy revealing the presence of mucosal erosions, ulcerations, multiple papulae. The histopathological examination raised the suspicion of a colonic lymphoma. Gastric biopsies suggested a gastric MALT type lymphoma associated to the colonic lymphoma, but the immunohistochemical profile corresponded to a mantle cell lymphoma. In spite of the general poor prognosis of mantle cell lymphoma, our patient had a good clinical and endoscopic response to the standard cyclophosphamide, vincristine, prednisone (CVP) therapy. The cases of gastric and colonic mantle lymphoma are rare, the response to therapy is poor; fortunately, our patient had a complete resolution after completion of the six cycles of chemotherapy.

Radiation therapy is an effective modality in the treatment of mantle cell lymphoma, even in heavily pretreated patients.

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Haque, Waqar; Voong, K Ranh; Shihadeh, Ferial; Arzu, Isidora; Pinnix, Chelsea; Mazloom, Ali; Medeiros, L Jeffrey; Romaguera, Jorge; Rodriguez, Alma; Wang, Michael; Allen, Pamela; Dabaja, Bouthaina

2014-12-01

Mantle cell lymphoma has an aggressive clinical course and continuous relapse pattern with a median survival of 3 to 7 years. Multiple courses of chemotherapy are the basis of treatment. Radiotherapy is underutilized in this disease. We undertook this study to assess the role of radiation therapy. A total of 41 consecutive patients with mantle cell lymphoma diagnosed from December, 1999 to January, 2010 who received radiation therapy were reviewed retrospectively. The main endpoint was in-field lymphoma response at each irradiated disease site. There were 39 evaluable patients (68 symptomatic sites). Sites treated included: nodal stations (n = 31), soft tissue (n = 13), mucosal sites (n = 11), central nervous system (n = 10), gastrointestinal tract (n = 2), and bone (n = 1). Median maximum tumor size at presentation was 3.5 cm (range, 1.3 cm-9.6 cm). The median dose of radiation was 30.6 Gy (range 18-40 Gy). Median follow-up post radiation per site was 12.3 months (range, 0.6-80.9 months). Response to treatment was complete in 47 sites (69.1%), partial in 16 sites (23.5%), and 5 sites (7.4%) had stable disease. In 9 (13.2%) sites local relapse occurred (median 7 months; range 2-21). The mean size of lymphoma at time of RT correlated with relapse, with tumors with local relapse larger than those without a local relapse (P = .005). Our data add to accumulating evidence that mantle cell lymphoma is a radio-sensitive disease with excellent responses to relatively low radiation doses, even in patients with chemo-refractory disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Cutaneous lesions as presentation form of mantle cell lymphoma

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Nayra Merino de Paz

2011-12-01

Full Text Available Mantle cell lymphoma is a type of no-Hodgkin lymphoma that affects extranodal areas, especially, bone narrow, digestive tract and Waldeyer ring. Here we report a case of mantle cell lymphoma IV Ann Arbor stage with cutaneous lesions on nasal dorsum and gland as the first manifestations. Skin involvement is a very rare manifestation and less than 20 cases have been reported in the literature. The importance of stablishing multidisciplinary relationships for a global approach has been shown by this clinical case.

Synchronous Pulmonary Malignancies: Atypical Presentation of Mantle Cell Lymphoma Masking a Lung Malignancy.

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Masha, Luke; Zinchuk, Andrey; Boosalis, Valia

2015-09-07

We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of Sickle Cell Disease.

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Monabbati, Ahmad; Noori, Sadat; Safaei, Akbar; Ramzi, Mani; Eghbali, Seyedsajjad; Adib, Ali

2016-01-01

Sickle cell disease (SCD) is a well known hemoglobinopathy with usual manifestations including anemia, hyperbilirubinemia, and vasoocclusive complications. Despite presence of mild splenomegaly in early phase of the disease, lymphadenopathy is not an often finding of SCD. We introduce an undiagnosed case of SCD who presented in third decade of his life with multiple cervical lymphadenopathies and mild splenomegaly persistent for about five years. Histopathologic examination of the resected lymph nodes showed expansion of the mantle cell layers of secondary follicles as well as several monomorphic mantle cell nodules. To rule out possibility of a malignant process involving lymph nodes, an immunohistochemical panel was ordered which was in favor of benign mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal bands and confirmed benign nature of the process. Respecting mild abnormalities on Complete Blood Count, peripheral blood smear was reviewed revealing some typical sickle red blood cells as well as rare nucleated red blood cells. Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis confirmed diagnosis of homozygous HbS disease.

The Role of Cyclin D1 in the Chemoresistance of Mantle Cell Lymphoma

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2017-09-01

AWARD NUMBER: W81XWH-15-1-0297 TITLE: The Role of Cyclin D1 in the Chemoresistance of Mantle Cell Lymphoma PRINCIPAL INVESTIGATOR: Vu Ngo...AND SUBTITLE The Role of Cyclin D1 in the Chemoresistance of Mantle Cell Lymphoma 5a. CONTRACT NUMBER The Role of Cyclin D1 in the Chemoresistance of...Mantle Cell Lymphoma 5b. GRANT NUMBER GRANT1173 9905 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Vu Ngo 5e. TASK NUMBER E

Synchronous pulmonary malignancies: atypical presentation of mantle cell lymphoma masking a lung malignancy

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Luke Masha

2015-09-01

Full Text Available We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

MicroRNAs in mantle cell lymphoma

DEFF Research Database (Denmark)

Husby, Simon; Geisler, Christian; Grønbæk, Kirsten

2013-01-01

Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. New treatment modalities, including intensive induction regimens with immunochemotherapy and autologous stem cell transplant, have improved survival. However, many patients still relapse, and there is a need...... for novel therapeutic strategies. Recent progress has been made in the understanding of the role of microRNAs (miRNAs) in MCL. Comparisons of tumor samples from patients with MCL with their normal counterparts (naive B-cells) have identified differentially expressed miRNAs with roles in cellular growth...

Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

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2018-04-23

Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

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2018-05-21

Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

Management of mantle cell lymphoma in the elderly: current and potential strategies.

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Vignon, Marguerite; Venon, Marie-Dominique; Hermine, Olivier; Delarue, Richard

2013-12-01

Mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin lymphoma, accounting for 3-10 % of all non-Hodgkin lymphoma cases. The median age at diagnosis is nearly 70 years. The prognosis of patients is based on the Mantle Cell Lymphoma International Prognostic Index, which is calculated on the basis of four independent prognostic factors (age, performance status, serum lactate dehydrogenase and leukocyte count). Treatment of elderly patients with de novo untreated mantle cell lymphoma is based on rituximab combined with chemotherapy. The most commonly used regimen is the classical CHOP21 (cyclophosphamide, doxorubicin, vincristine and prednisone) regimen. Bendamustine is also an option, especially for patients with cardiac comorbidities. In elderly patients who are relatively young and fit, an approach based on treatment usually used for younger patients, with cytarabine-based induction followed by autologous stem cell transplantation, should be discussed. Treatment of relapsing patients is based on the use of newer effective drugs, including bortezomib, lenalidomide and thalidomide, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus. These drugs are often combined with rituximab and can be prescribed in combination with chemotherapy. Promising new drugs are Bruton tyrosine kinase inhibitors and other inhibitors of the phosphoinositide 3-kinase (PI3K)-mTOR-protein kinase B (AKT) pathway. Despite these new advances, mantle cell lymphoma remains an incurable disease, and further basic and clinical research is warranted.

Treatment of older patients with mantle-cell lymphoma

DEFF Research Database (Denmark)

Kluin-Nelemans, H C; Hoster, E; Hermine, O

2012-01-01

The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether...

A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma

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Scally John

2003-12-01

Full Text Available Abstract Background Mantle cell lymphoma (MCL is a rare variety of non-Hodgkin's lymphoma which originates from CD5+ B-cell population in the mantle zones of lymphoid follicles. Coexistence of such tumours in the axillary lymph nodes with invasive breast cancers without prior history of adjuvant chemotherapy or radiotherapy has not been previously reported in literature. Case report We report a rare case of breast cancer co-existing with stage I mantle cell lymphoma of the ipsilateral axillary lymph node detected fortuitously by population screening. Conclusion Though some studies have tried to prove breast carcinomas and lymphomas to share a common molecular or viral link, more research needs to be done to establish whether such a link truly exists.

Immunohistochemical detection of cdc2 is useful in predicting survival in patients with mantle cell lymphoma.

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Hui, David; Reiman, Tony; Hanson, John; Linford, Rick; Wong, Winson; Belch, Andrew; Lai, Raymond

2005-09-01

Recent cDNA microarray studies have reported the prognostic value of several genes in mantle cell lymphoma patients. We aimed to validate the prognostic significance of three of these genes: alpha-tubulin, cdc2, and CENP-F. The protein expression of alpha-tubulin, cdc2, and CENP-F was assessed using immunohistochemistry. Their immunoreactivity in 48 formalin-fixed/paraffin-embedded mantle cell lymphoma tumors was determined by estimating the percentage of positive cells. These results were correlated with the expression of proliferation marker Ki67 and survival. Of these 48 mantle cell lymphoma patients, 41 were men and seven were women. The median age at time of diagnosis was 64.5 years, and the overall median survival was 40 months. In benign lymph nodes, the expression of cdc2 and alpha-tubulin was restricted to the germinal centers; mantle zones were negative. Expression of CENP-F was more uniformly distributed. In mantle cell lymphoma, Ki67 significantly correlated with all three markers (P50%) and cdc2 (>25%) significantly correlated with shorter survival (Por=2 correlated with worse clinical outcome, and high clinical stage (ie 4 vs mantle cell lymphoma patients. Immunohistochemical detection of cdc2 and Ki67 may be a useful and simple method in evaluating the prognosis of mantle cell lymphoma patients.

Autologous stem cell transplantation in refractory Asherman′s syndrome: A novel cell based therapy

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Neeta Singh

2014-01-01

Full Text Available Background : There is substantial evidence that adult stem cell populations exist in human endometrium, and hence it is suggested that either endogenous endometrial stem/progenitor cells can be activated or bone marrow derived stem cells can be transplanted in the uterine cavity for endometrial regeneration in Asherman′s syndrome (AS. Aims and Objectives : The objective was to evaluate the role of sub-endometrial autologous stem cell implantation in women with refractory AS in attaining menstruation and fertility. Setting : Tertiary care referral center. DESIGN: Prospective case series. Materials and Methods : Six cases of refractory AS with failed standard treatment option of hysteroscopic adhesiolysis in the past were included. Mononuclear stem cells (MNCs were implanted in sub-endometrial zone followed by exogenous oral estrogen therapy. Endometrial thickness (ET was assessed at 3, 6, and 9 months. RESULTS: Descriptive statistics and statistical analysis of study variables was carried out using STATA version 9.0. The mean MNC count was 103.3 × 106 (±20.45 with mean CD34+ count being 203,642 (±269,274. Mean of ET (mm at 3 months (4.05 ± 1.40, 6 months (5.46 ± 1.36 and 9 months (5.48 ± 1.14 were significantly (P < 0.05 increased from pretreatment level (1.38 ± 0.39. Five out of six patients resumed menstruation. Conclusion : The autologous stem cell implantation leads to endometrial regeneration reflected by restoration of menstruation in five out of six cases. Autologous stem cell implantation is a promising novel cell based therapy for refractory AS.

Os-Hf-Sr-Nd isotope and PGE systematics of spinel peridotite xenoliths from Tok, SE Siberian craton: Effects of pervasive metasomatism in shallow refractory mantle

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Ionov, Dmitri A.; Shirey, Steven B.; Weis, Dominique; Brügmann, Gerhard

2006-01-01

Os-Hf-Sr-Nd isotopes and PGE were determined in peridotite xenoliths carried to the surface by Quaternary alkali basaltic magmas in the Tokinsky Stanovik Range on the Aldan shield. These data constrain the timing and nature of partial melting and metasomatism in the lithospheric mantle beneath SE Siberian craton. The xenoliths range from the rare fertile spinel lherzolites to the more abundant, strongly metasomatised olivine-rich (70-84%) rocks. Hf-Sr-Nd isotope compositions of the xenoliths are mainly within the fields of oceanic basalts. Most metasomatised xenoliths have lower 143Nd / 144Nd and 176Hf / 177Hf and higher 87Sr / 86Sr than the host basalts indicating that the metasomatism is older and has distinct sources. A few xenoliths have elevated 176Hf / 177Hf (up to 0.2838) and plot above the Hf-Nd mantle array defined by oceanic basalts. 187Os / 188Os in the poorly metasomatised, fertile to moderately refractory (Al2O3 ≥ 1.6%) Tok peridotites range from 0.1156 to 0.1282, with oldest rhenium depletion ages being about 2 Ga. The 187Os / 188Os in these rocks show good correlations with partial melting indices (e.g. Al2O3, modal cpx); the intercept of the Al-187Os / 188Os correlation with lowest Al2O3 estimates for melting residues (∼0.3-0.5%) has a 187Os / 188Os of ∼0.109 suggesting that these peridotites may have experienced melt extraction as early as 2.8 Gy ago. 187Os / 188Os in the strongly metasomatised, olivine-rich xenoliths (0.6-1.3% Al2O3) ranges from 0.1164 to 0.1275 and shows no apparent links to modal or chemical compositions. Convex-upward REE patterns and high abundances of heavy to middle REE in these refractory rocks indicate equilibration with evolved silicate melts at high melt / rock ratios, which may have also variably elevated their 187Os / 188Os. This inference is supported by enrichments in Pd and Pt on chondrite-normalised PGE abundance patterns in some of the rocks. The melt extraction ages for the Tok suite of 2.0 to 2.8 Ga are

Central nervous system involvement in mantle cell lymphoma : clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network

NARCIS (Netherlands)

Cheah, C. Y.; George, A.; Gine, E.; Chiappella, A.; Kluin-Nelemans, H. C.; Jurczak, W.; Krawczyk, K.; Mocikova, H.; Klener, P.; Salek, D.; Walewski, J.; Szymczyk, M.; Smolej, L.; Auer, R. L.; Ritchie, D. S.; Arcaini, L.; Williams, M. E.; Dreyling, M.; Seymour, J. F.

Central nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. We present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions.

Stochastic histories of refractory interstellar dust

International Nuclear Information System (INIS)

Liffman, K.; Chayton, D.D.

1988-01-01

The authors calculate histories for refractory dust particles in the interstellar medium. The double purposes are to learn something of the properties of interstellar dust as a system and to evaluate with specific assumptions the cosmic chemical memory interpretation of a specific class of isotopic anomalies. They assemble the profile of a particle population from a large number of stochastic, or Monte Carlo, histories of single particles, which are necessarily taken to be independent with this approach. They specify probabilities for each of the events that may befall a given particle and unfold its history by a sequence of random numbers. They assume that refractory particles are created only by thermal condensation within stellar material during its ejection from stars, and that these refractory particles can be destroyed only by being sputtered to a size too small for stability or by being incorporated into the formation of new stars. In order to record chemical detail, the authors take each new refractory particle to consist of a superrefractory core plus a more massive refractory mantle. They demonstrate that these superrefractory cores have effective lifetimes much longer than the turnover time of dust mass against sputtering. As examples of cosmic chemical memory they evaluate the 16 O-richness of interstellar aluminum and mechanisms for the 48 Ca/ 50 Ti correlation. Several related consequences of this approach are discussed

Conjunctival mass as an initial presentation of mantle cell lymphoma: a case report

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Khanlari Mahsa

2012-12-01

Full Text Available Abstract Background To describe a rare manifestation of mantle cell lymphoma (MCL in conjunctiva, with clinical, hisologic, immunohistologic and genetic findings together with review of the Literature. Case presentation Most ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT. A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as right conjunctival mass of at least three months duration in a 64-year-old man. Histopathologic examination showed a proliferation of monomorphous small-to-medium-sized lymphoid cells with cleaved nuclei in the subconjunctiva. By immunohistochemistry, the infiltrate was positive for CD20, CD5, BCL-2, cyclin D1, and the transcription factor SOX11. Fluorescent in situ hybridization demonstrated the presence of IGH-CCND1 fusion indicating t(11;14. Conclusion A rigorous approach to initial diagnosis and staging of small cell lymphomas of the ocular adnexa is needed. The recognition of ocular MCL requires appropriate immunohistochemical staining and/or genetic confirmation to differentiate this rare form of presentation of MCL from other more frequent small cell lymphomas.

Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network

DEFF Research Database (Denmark)

Hoster, Eva; Klapper, Wolfram; Hermine, Olivier

2014-01-01

PURPOSE: Mantle-cell lymphoma (MCL) is a distinct B-cell lymphoma associated with poor outcome. In 2008, the MCL International Prognostic Index (MIPI) was developed as the first prognostic stratification tool specifically directed to patients with MCL. External validation was planned.......9) and 2.6 (2.0 to 3.3), respectively. MIPI was similarly prognostic for TTF. All four clinical baseline characteristics constituting the MIPI, age, performance status, lactate dehydrogenase level, and WBC count, were confirmed as independent prognostic factors for OS and TTF. The validity of MIPI...

Stochastic evolution of refractory interstellar dust during the chemical evolution of a two-phase interstellar medium

International Nuclear Information System (INIS)

Liffman, K.; Clayton, D.D.

1989-01-01

The evolution course of refractory interstellar dust during the chemical evolution of a two-phase interstellar medium (ISM) is studied using a simple model of the chemical evolution of ISM. It is assumed that, in this medium, the stars are born in molecular clouds, but new nucleosynthesis products and stellar return are entered into a complementary diffuse medium; the well-mixed matter of each interstellar phase is repeatedly cycled stochastically through the complementary phase and back. The dust is studied on a particle-by-particle bases as it is sputtered by shock waves in the diffuse medium, accretes an amorphous mantle of gaseous refractory atoms while its local medium joins the molecular cloud medium, and encounters the possibility of astration within molecular clouds. Results are presented relevant to the size spectrum of accreted mantles, its age spectrum and the distinction among its several lifetimes, depletion factors of refractory atoms in the diffuse gas, and isotopic anomalies. 26 refs

Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

Science.gov (United States)

2018-05-09

Follicular T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides AJCC v7; Stage II Mycosis Fungoides AJCC v7; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides AJCC v7; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides AJCC v7

Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions – case report and review of literature

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Abo Stephen M

2009-07-01

Full Text Available Abstract Background Mantle cell lymphoma (MCL is an aggressive type of B-cell non-Hodgkin's lymphoma that originates from small to medium sized lymphocytes located in the mantle zone of the lymph node. Extra nodal involvement is present in the majority of cases, with a peculiar tendency to invade the gastro-intestinal tract in the form of multiple lymphomatous polyposis. MCL can be accurately diagnosed with the use of the highly specific marker Cyclin D1. Few cases of mantle cell lymphoma presenting with intussuception have been reported. Here we present a rare case of multiple intussusceptions caused by mantle cell lymphoma and review the literature of this disease. Case presentation A 68-year-old male presented with pain, tenderness in the right lower abdomen, associated with nausea and non-bilious vomiting. CT scan of abdomen revealed ileo-colic intussusception. Laparoscopy confirmed multiple intussusceptions involving ileo-colic and ileo-ileal segments of gastrointestinal tract. A laparoscopically assisted right hemicolectomy and extended ileal resection was performed. Postoperative recovery was uneventful. The histology and immuno-histochemistry of the excised small and large bowel revealed mantle cell lymphoma with multiple lymphomatous polyposis and positivity to Cyclin D1 marker. The patient was successfully treated with Rituximab-CHOP chemotherapy and remains in complete remission at one-year follow-up. Conclusion This is a rare case of intestinal lymphomatous polyposis due to mantle cell lymphoma presenting with multiple small bowel intussusceptions. Our case highlights laparoscopic-assisted bowel resection as a potential and feasible option in the multi-disciplinary treatment of mantle cell lymphoma.

Silica-enriched mantle sources of subalkaline picrite-boninite-andesite island arc magmas

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Bénard, A.; Arculus, R. J.; Nebel, O.; Ionov, D. A.; McAlpine, S. R. B.

2017-02-01

Primary arc melts may form through fluxed or adiabatic decompression melting in the mantle wedge, or via a combination of both processes. Major limitations to our understanding of the formation of primary arc melts stem from the fact that most arc lavas are aggregated blends of individual magma batches, further modified by differentiation processes in the sub-arc mantle lithosphere and overlying crust. Primary melt generation is thus masked by these types of second-stage processes. Magma-hosted peridotites sampled as xenoliths in subduction zone magmas are possible remnants of sub-arc mantle and magma generation processes, but are rarely sampled in active arcs. Published studies have emphasised the predominantly harzburgitic lithologies with particularly high modal orthopyroxene in these xenoliths; the former characteristic reflects the refractory nature of these materials consequent to extensive melt depletion of a lherzolitic protolith whereas the latter feature requires additional explanation. Here we present major and minor element data for pristine, mantle-derived, lava-hosted spinel-bearing harzburgite and dunite xenoliths and associated primitive melts from the active Kamchatka and Bismarck arcs. We show that these peridotite suites, and other mantle xenoliths sampled in circum-Pacific arcs, are a distinctive peridotite type not found in other tectonic settings, and are melting residues from hydrous melting of silica-enriched mantle sources. We explore the ability of experimental studies allied with mantle melting parameterisations (pMELTS, Petrolog3) to reproduce the compositions of these arc peridotites, and present a protolith ('hybrid mantle wedge') composition that satisfies the available constraints. The composition of peridotite xenoliths recovered from erupted arc magmas plausibly requires their formation initially via interaction of slab-derived components with refractory mantle prior to or during the formation of primary arc melts. The liquid

Rate of primary refractory disease in B and T-cell non-Hodgkin's lymphoma: correlation with long-term survival.

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Corrado Tarella

Full Text Available BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL. This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%, intensive therapy with autograft (16.9%, or other therapies (19.9%. Among B-cell NHL, 1,356 (47.8% received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2% patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001. Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001. Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001. CONCLUSION: Chemosensitivity to primary

Major element composition of the lithospheric mantle under the North Atlantic craton

DEFF Research Database (Denmark)

Bizzarro, Martin; Stevenson, R.K.

2003-01-01

nature of the Sarfartoq mantle showing comparable degrees of depletion to other cratonic roots. Modal analyses indicate that the Sarfartoq mantle is not typified by the orthopyroxene enrichment observed in the Kaapvaal root, but shows more affinity with the Canadian Arctic (Somerset Island), Tanzania...... is compositionally layered as follows: (1) an internally stratified upper layer (70 to 180 km) consisting of coarse, un-deformed, refractory garnet-bearing and garnet-free peridotites and, (2) a lower layer (180 to 225 km) characterized by fertile, CPX-bearing, porphyroclastic garnet lherzolites. The stratification...

Refractoriness in human atria

DEFF Research Database (Denmark)

Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

2016-01-01

BACKGROUND: Refractoriness of cardiac cells limits maximum frequency of electrical activity and protects the heart from tonic contractions. Short refractory periods support major arrhythmogenic substrates and augmentation of refractoriness is therefore seen as a main mechanism of antiarrhythmic...... drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...

Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Science.gov (United States)

2018-04-17

Aggressive Non-Hodgkin Lymphoma; CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

NARCIS (Netherlands)

Queirós, A.C. (Ana C.); R. Beekman (Renée); Vilarrasa-Blasi, R. (Roser); Duran-Ferrer, M. (Martí); Clot, G. (Guillem); Merkel, A. (Angelika); Raineri, E. (Emanuele); Russiñol, N. (Nuria); Castellano, G. (Giancarlo); S. Bea (Silvia); Navarro, A. (Alba); Kulis, M. (Marta); Verdaguer-Dot, N. (Núria); P. Jares (Pedro); A. Enjuanes (Anna); M.J. Calasanz (Maria); Bergmann, A. (Anke); Vater, I. (Inga); Salaverría, I. (Itziar); H.J.G. van de Werken (Harmen); W.H. Wilson (Wyndham); Datta, A. (Avik); P. Flicek (Paul); Royo, R. (Romina); J.H.A. Martens (Joost); Giné, E. (Eva); Lopez-Guillermo, A. (Armando); H. Stunnenberg (Henk); W. Klapper (Wolfram); C. Pott (Christiane); Heath, S. (Simon); I. Gut (Ivo); R. Siebert (Reiner); G. Campo (Gianluca); J.I. Martin-Subero (J.)

2016-01-01

textabstractWe analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and

Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma

Science.gov (United States)

2018-02-05

Chronic Lymphocytic Leukemia; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

The basal part of the Oman ophiolitic mantle: a fossil Mantle Wedge?

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Prigent, Cécile; Guillot, Stéphane; Agard, Philippe; Godard, Marguerite; Chauvet, Alain; Dubacq, Benoit; Monié, Patrick; Yamato, Philippe

2014-05-01

Although the Oman ophiolite is classically regarded as being the direct analog of oceanic lithosphere created at fast spreading ridges, the geodynamic context of its formation is still highly debated. The other alternative end-member model suggests that this ophiolite entirely formed in a supra-subduction zone setting. Fluids involved in the hydration of the oceanic lithosphere and in the presence of a secondary boninitic and andesitic volcanism may provide a way to discriminate between these two interpretations: are they descending near-axis hydrothermal fluxes (first model) or ascending from a subducting slab (second model)? We herein focus on the base of the ophiolitic mantle in order to characterize the origin of fluids and decipher hydration processes. Samples were taken along hecto- to kilometre-long sections across the basal banded unit directly overlying the amphibolitic/granulitic metamorphic sole. We carried out a petrological, structural and geochemical study on these rocks and their constitutive minerals. Our results show that, unlike the generally refractory character of Oman harzburgites, all the basal mantle rocks display secondary crystallization of clinopyroxene and amphibole through metasomatic processes. The microstructures and the chronology of these secondary mineralizations (clinopyroxene, pargasitic amphibole, antigorite and then lizardite/chrysotile) suggest that these basal rocks have been affected by cooling from mantle temperatures (serpentines (B, Sr, Rb, Ba, As), are consistent with amphibolite-derived fluids (Ishikawa et al., 2005) and cannot be easily explained by other sources. Based on these observations, we propose a geodynamic model in which intense and continuous metasomatism of the cooling base of the ophiolitic mantle is due to the release of fluids coming from the progressive dehydration of underlying amphibolitic rocks. This process is compatible with the progressive subduction of the Arabian margin during the Upper

Screening for adenoviruses in haematological neoplasia: High prevalence in mantle cell lymphoma.

Science.gov (United States)

Kosulin, Karin; Rauch, Margit; Ambros, Peter F; Pötschger, Ulrike; Chott, Andreas; Jäger, Ulrich; Drach, Johannes; Nader, Alexander; Lion, Thomas

2014-02-01

Human adenoviruses possess oncogenic capacity which is well documented in mammalian animal models, but their possible implication in human malignancy has remained enigmatic. Following primary infection, adenoviruses can persist in a latent state in lymphocytes where the virus is apparently able to evade immune surveillance. In the present study, we have employed a broad-spectrum adenovirus polymerase chain reaction (PCR) assay to systematically screen more than 200 diagnostic specimens of different lymphoid malignancies including acute lymphocytic leukaemia (n=50), chronic lymphocytic leukaemia (n=50), various types of malignant lymphoma (n=100) and multiple myeloma (n=11) for the presence of adenoviral sequences. While most entities analysed revealed negative findings in virtually all specimens tested, adenoviral DNA was detected in 15/36 (42%) mantle cell lymphomas investigated. The most prevalent adenoviral species detected was C, and less commonly B. Adenovirus-positive findings in patients with mantle cell lymphoma were made at different sites including bone marrow (n=7), intestine (n=5), lymph nodes (n=2) and tonsillar tissue (n=1). The presence of adenoviral sequences identified by PCR was confirmed in individual cells by fluorescence in-situ hybridisation (FISH). The frequent observation of adenoviruses in mantle cell lymphoma is intriguings, and raises questions about their possible involvement in the pathogenesis of this lymphoid malignancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Amrubicin therapy improves patients with refractory small-cell lung cancer: A single-arm confirmatory Chinese clinical study

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Mengli Zheng

2016-09-01

Full Text Available Our objective was to evaluate an open-label, multicenter, single-arm study to appraise whether amrubicin therapy improves patients with refractory small-cell lung cancer in Chinese clinical study. Patients (n=95 with refractory small-cell lung cancer received 3 consecutive days amrubicin therapy for 21 days. Overall response rate of response to amrubicin was 39%. Anemia, febrile neutropenia, thrombocytopenia, hyperglycemia, hyponatremia, infection, elevated serum transaminases levels were appeared, but the incidences of adverse events were very few. Our results suggest amrubicin therapy can improve patients with refractory small-cell lung cancer and may be an effective and safe treatment option.

Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

Science.gov (United States)

2017-11-15

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies

Science.gov (United States)

2017-11-29

Hematologic Malignancy; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia in Blast Crisis; Anemia, Refractory, With Excess of Blasts; Chronic Myeloproliferative Disease; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Marginal Zone B-cell Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle-Cell Lymphoma; Prolymphocytic Lymphoma; Large Cell Non-Hodgkin's Lymphoma; Lymphoblastic Lymphoma; Burkitt's Lymphoma; High Grade Non-Hodgkin's Lymphoma

HA-1 T TCR T Cell Immunotherapy for the Treating of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant

Science.gov (United States)

2018-04-30

HLA-A*0201 HA-1 Positive Cells Present; Minimal Residual Disease; Recurrent Acute Biphenotypic Leukemia; Recurrent Acute Undifferentiated Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

Mesenchymal stromal cell derived endothelial progenitor treatment in patients with refractory angina

DEFF Research Database (Denmark)

Friis, Tina; Haack-Sørensen, Mandana; Mathiasen, Anders B

2011-01-01

Abstract Aims. We evaluated the feasibility, safety and efficacy of intra-myocardial injection of autologous mesenchymal stromal cells derived endothelial progenitor cell (MSC) in patients with stable coronary artery disease (CAD) and refractory angina in this first in man trial. Methods and resu......Abstract Aims. We evaluated the feasibility, safety and efficacy of intra-myocardial injection of autologous mesenchymal stromal cells derived endothelial progenitor cell (MSC) in patients with stable coronary artery disease (CAD) and refractory angina in this first in man trial. Methods...... and results. A total of 31 patients with stable CAD, moderate to severe angina and no further revascularization options, were included. Bone marrow MSC were isolated and culture expanded for 6-8 weeks. It was feasible and safe to establish in-hospital culture expansion of autologous MSC and perform intra......-myocardial injection of MSC. After six months follow-up myocardial perfusion was unaltered, but the patients increased exercise capacity (p angina attacks (p Angina Questionnaire (SAQ) evaluations (p

Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma

DEFF Research Database (Denmark)

Andersen, Niels S; Pedersen, Lone B; Laurell, Anna

2009-01-01

PURPOSE: Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell...

A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura

Directory of Open Access Journals (Sweden)

Foroulis Christophoros N

2008-12-01

Full Text Available Abstract Background Coexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition. Case presentation A 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14. The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later. Conclusion This is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

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Bo Cai

2016-11-01

Full Text Available Abstract Background Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. Case presentation We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Conclusions Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Trial registration Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT02799550

Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

Science.gov (United States)

2018-05-15

Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

A review of refractory materials for vapor-anode AMTEC cells

Science.gov (United States)

King, Jeffrey C.; El-Genk, M. S.

2000-01-01

Recently, refractory alloys have been considered as structural materials for vapor-anode Alkali Metal Thermal-to-Electric Conversion (AMTEC) cells, for extended (7-15 years) space missions. This paper reviewed the existing database for refractory metals and alloys of potential use as structural materials for vapor-anode sodium AMTEC cells. In addition to requiring that the vapor pressure of the material be below 10-9 torr (133 nPa) at a typical hot side temperature of 1200 K, other screening considerations were: (a) low thermal conductivity, low thermal radiation emissivity, and low linear thermal expansion coefficient; (b) low ductile-to-brittle transition temperature, high yield and rupture strengths and high strength-to-density ratio; and (c) good compatibility with the sodium AMTEC operating environment, including high corrosion resistance to sodium in both the liquid and vapor phases. Nb-1Zr (niobium-1% zirconium) alloy is recommended for the hot end structures of the cell. The niobium alloy C-103, which contains the oxygen gettering elements zirconium and hafnium as well as titanium, is recommended for the colder cell structure. This alloy is stronger and less thermally conductive than Nb-1Zr, and its use in the cell wall reduces parasitic heat losses by conduction to the condenser. The molybdenum alloy Mo-44.5Re (molybdenum-44.5% rhenium) is also recommended as a possible alternative for both structures if known problems with oxygen pick up and embrittlement of the niobium alloys proves to be intractable. .

Randomized phase II study of a bendamustine monotherapy schedule for relapsed or refractory low-grade B-cell non-Hodgkin lymphoma or mantle cell lymphoma (RABBIT-14).

Science.gov (United States)

Itoh, Kuniaki; Igarashi, Tadahiko; Irisawa, Hiroyuki; Aotsuka, Nobuyuki; Masuda, Shinichi; Utsu, Yoshikazu; Tsujimura, Hideki; Tsukasaki, Kunihiro; Wakita, Hisashi

2017-10-30

The aim of this randomized phase II study was to improve the treatment delays and discontinuations associated with bendamustine use by comparing the effect of Benda-14 (intravenous bendamustine, 120 mg/m 2 on days 1 and 15, repeated every 4 weeks for a total of 6 cycles) with those of the standard treatment in relapsed indolent lymphoma and/or mantle cell lymphoma. Forty-six patients were randomly assigned to the treatments from September 2012 to February 2016. Treatment accomplishment rate and median relative dose intensity were similar in both arms: 38 and 63.4% in the Benda-14 arm and 41 and 66.3% in the standard treatment arm, respectively. The overall response rate and median progression-free survival, respectively, were 83% and 21.0 months for Benda-14, and 77% and 15.5 months for the standard treatment. Benda-14 induced favorable responses with less frequent hematological toxicities.

Leuconostoc sp. Meningitis in a Patient Treated with Rituximab for Mantle Cell Lymphoma

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Hrvoje Holik

2015-09-01

Full Text Available We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery.

Primary mantle cell lymphoma of tonsil: Case report

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Knežević Snežana B.

2017-01-01

Full Text Available Introduction: Mantle cell lymphoma is rare type of the mature B cell lymphoma. It includes 4% - 6% of all Non Hodgkin's Lymphomas. Compared to the other subtypes of lymphoma it develops more often in older men, and the median age of patients is 65 years. Primary tonsillar lymphoma accounts for less than 1% of head and neck malignancies. Method: Data obtained from medical records of the patient. Objective: Emphasize the importance of early and accurate diagnosis and early treatment of malignant diseases. Case report: Patient RP, 63 years old, presents with difficult swallowing, hoarseness, enlarged tonsils, snoring. Left tonsil almost sets into the right tonsillar vine, displaces the uvula and covers the isthmus. Respiratory sound is normal, with rhythmic action of the heart and soft abdomen. Good general condition. Echo: enlarged and actively altered lymph glands of the middle right jugular chain, the largest 148x77 mm, on the left side lymph nodes are enlarged, the largest is 143x72 mm. Echo of the abdomen inconspicuous. Lab: WBC 5.9, RBC 5.2, Hb 152, Hct 0.44, SE 10, CK 129, LDH 331, CRP 4.6, ALP 61, fibrinogen 2.4, Ca2+ 2.3, phosphate 0.8; BK, HCV, HBsAg, EB, HIV negative. X-ray of the chest inconspicuous. Admitted to the hematology department of the General Hospital. PH: Immunoproliferative disease. Immunohistochemistry, at the institute of Pathology: IHH CK AE1-AE3, PAX5 +, CD20 +, CD3, bcl2 +, bcl6-, CyklinD1 +, CD23-, CD43 +, MUM1 - / +, Ki67 + in about 20% of the tumor cells. Morphological and immunohistochemical findings: Mantle cell lymphoma. MSCD of the neck, chest and upper abdomen: Left tonsil diameter is 28x32 mm and length is 36mm, with lobular contour and heterogeneous structure, asymmetrically narrowing lumen of the airways to 7 mm. pathologically enlarged submandibular and par jugular lymph nodes (10-15 mm diameter on the left. There were no pathological findings in the lung parenchyma. Abdominal and retroperitoneal lymph nodes

Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

2017-01-01

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

Mixing and Progressive Melting of Deep and Shallow Mantle Sources in the NE Atlantic and Arctic

DEFF Research Database (Denmark)

Trønnes, Reidar; Debaille, Vincianne; Erambert, M.

2013-01-01

). The SCLM-component was mixed with the local asthenosphere during and shortly after the continental rifting and ocean basin opening. Using combined Sr-Nd-Pb- Os-He-isotope systematics, the Iceland plume can be modelled as a mixture of 70% refractory/primordial lower mantle (LM) and 30% recycled oceanic...

On the nature and origin of garnet in highly-refractory Archean lithosphere: implications for continent stabilisation

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Gibson, Sally

2014-05-01

The nature and timescales of garnet formation in the Earth's subcontinental lithospheric mantle (SCLM) are important to our understanding of how this rigid outer shell has evolved and stabilised since the Archean. Nevertheless, the widespread occurrence of pyrope garnet in the sub-cratonic mantle remains one of the 'holy grails' of mantle petrology. The paradox is that garnet often occurs in mantle lithologies (dunites and harzburgites) which represent residues of major melting events (up to 40 %) whereas experimental studies on fertile peridotite suggest this phase should be exhausted by years. The garnets display systematic trends from ultra-depleted to enriched compositions that have not been recognised in peridotite suites from elsewhere (Gibson et al., 2013). Certain harzburgite members of the xenolith suite contain the first reported occurrence of pyrope garnets with rare-earth element (REE) patterns similar to hypothetical garnets proposed by Stachel et al. (2004) to have formed in the Earth's SCLM during the Archean, prior to metasomatism. These rare ultra-depleted low-Cr garnets occur in low temperature (~1050 oC) xenoliths derived from depths of ~120 km and coexist in chemical and textural equilibrium with highly-refractory olivine (Fo95.4) and orthopyroxene (Mg#=96.4). These phases are all more magnesian than generally encountered in global samples of depleted mantle, i.e. harzburgites and diamond inclusion suites. The Tanzanian ultra-depleted garnets form interconnecting networks ('necklaces') around grains of orthopyroxene, which is of key importance to their origin. This close spatial relationship of garnet and orthopyroxene together with the major, trace and REE contents of the ultra-depleted garnets, are consistent with an origin by isochemical exsolution. The significance of ultra-depleted low-Cr garnets has not previously been recognised in global suites of mantle xenoliths or diamond inclusions: they appear to have been overlooked, primarily

REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

OpenAIRE

Emmanuel Gyan; François Dreyfus; Pierre Fenaux

2015-01-01

Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD) as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT), and refractory neutropenia (RN), characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medi...

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

Science.gov (United States)

2018-04-10

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Plate-Tectonic Circulation is Driven by Cooling From the Top and is Closed Within the Upper Mantle

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Hamilton, W. B.

2001-12-01

Subduction drives plate tectonics and is due to cooling from the top: circulation is self-organized, and likely is closed above the discontinuity near 660 km. The contrary consensus that plate tectonics is driven by bottom heating and involves the entire mantle combines misunderstood kinematics with flawed concepts of through-the-mantle plumes and subduction. Plume conjecture came from the Emperor-Hawaii progression, the 45 Ma inflection in which was assumed to mark a 60-degree change in direction of that part of the Pacific plate over a fixed plume. Smooth spreading patterns around the east and south margin of the Pacific plate, and paleomagnetic data, disprove such a change. Speculations that plumes move, jump, etc. do not revive falsified conjecture. Geochemical distinctions between enriched island and depleted ridge basalts (which overlap) are expected products of normal upper-mantle processes, not plumes. MORB traverses solidus-T asthenosphere, whereas OIB zone-refines through subsolidus lithosphere and crust, crystallizing refractories to retain T of diminishing melt while assimilating and retaining fusibles. Tomographic inference of deep-mantle subduction is presented misleadingly and may reflect methodological and sampling artifacts (downward smearing, and concentration of recorded body waves in bundles within broad anomalies otherwise poorly sampled). Planetological and other data require hot Earth accretion, and thorough early fractionation, from material much more refractory than primitive meteorites, and are incompatible with the little-fractionated lower mantle postulated to permit whole-mantle circulation. The profound seismic discontinuity near 660 km is a thermodynamic and physical barrier to easy mass transfer in either direction. Refractory lower mantle convects slowly, perhaps in layers, and loses primarily original heat, whereas upper mantle churns rapidly, and the 660 decoupling boundary must have evolved into a compositional barrier also

Nacre formation by epithelial cell cultures from mantle of the black-lip pearl oyster, Pinctada margaritifera.

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Jayasankar, Vidya; Vasudevan, Srinivasa Raghavan; Poulose, Suja C; Divipala, Indira

2018-06-12

Mantle tissue from the black-lip pearl oyster, Pinctada margaritifera, was cultured in vitro using sterilized seawater supplemented with 0.1% yeast extract as the culture medium. Granular and agranular epithelial cells, hyalinocytes, and fibroblast-like cells were observed in the initial stages of culture. Epithelial cells later formed pseudopodial cell networks containing clusters of granulated cells, which upon maturation released their colored granules. These granules induced formation of nacre crystal deposits on the bottom of the culture plate. Cultures comprised of only granulated epithelial cells were established through periodic sub-culturing of mantle cells and maintained for over 18 mo in a viable condition. Reverse transcriptase PCR of cultured cells demonstrated gene expression of the shell matrix protein, nacrein. To further evaluate the functional ability of cultured granulated epithelial cells, nuclear shell beads were incubated in culture medium containing these cells to induce nacre formation on the beads. Observation of the bead surface under a stereomicroscope at periodic intervals showed the gradual formation of blackish yellow colored nacre deposits. Examination of the bead surface by scanning electron microscopy and energy dispersive X-ray analysis at periodic intervals revealed a distinct brick and mortar formation characteristic of nacre, comprised of aragonite platelets and matrix proteins. Calcium, carbon, and oxygen were the major elements in all stages examined. Our study shows that mantle epithelial cells in culture retain the ability to secrete nacre and can therefore form the basis for future studies on the biomineralization process and its application in development of sustainable pearl culture.

Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies.

Science.gov (United States)

Rule, Simon; Dreyling, Martin; Goy, Andre; Hess, Georg; Auer, Rebecca; Kahl, Brad; Cavazos, Nora; Liu, Black; Yang, Shiyi; Clow, Fong; Goldberg, Jenna D; Beaupre, Darrin; Vermeulen, Jessica; Wildgust, Mark; Wang, Michael

2017-11-01

Ibrutinib is highly active in treating mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. We pooled data from three ibrutinib studies to explore the impact of baseline patient characteristics on treatment response. Patients with relapsed/refractory MCL (n = 370) treated with ibrutinib had an objective response rate (ORR) of 66% (20% complete response; 46% partial response); median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were 18·6, 12·8 and 25·0 months, respectively. Univariate analyses showed patients with one versus >one prior line of therapy had longer OS. Multivariate analyses identified that one prior line of therapy affected PFS; Eastern Cooperative Oncology Group (ECOG) performance status, simplified MCL international prognostic index (sMIPI) score, bulky disease, and blastoid histology affected OS and PFS. Patients with blastoid versus non-blastoid histology had similar time to best response, but lower ORR, DOR, PFS and OS. OS and PFS were longer in patients with better sMIPI, patients with ECOG performance status 0-1, non-bulky disease and non-blastoid histology. Additionally, the proportion of patients with poor prognostic factors increased with increasing lines of therapy. Together, results suggest that patient outcomes following treatment failure with ibrutinib are related to the natural biological evolution of the disease. © 2017 John Wiley & Sons Ltd.

Receptor units responding to movement in the octopus mantle.

Science.gov (United States)

Boyle, P R

1976-08-01

1. A preparation of the mantle of Octopus which is inverted over a solid support and which exposes the stellate ganglion and associated nerves is described. 2. Afferent activity can be recorded from stellar nerves following electrical stimulation of the pallial nerve. The latency and frequency of the phasic sensory response is correlated with the contraction of the mantle musculature. 3. It is proposed that receptors cells located in the muscle, and their activity following mantle contraction, form part of a sensory feedback system in the mantle. Large, multipolar nerve cells that were found between the two main layers of circular muscle in the mantle could be such receptors.

Extreme Hf and light Fe isotopes in Archean komatiites - a remnant of very early mantle depletion?

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Nebel, O.; Sossi, P.; Campbell, I. H.; Van Kranendonk, M. J.

2014-12-01

Hafnium isotope signatures in some Archean komatiites (ca. 3.5-3.0 billion years old) require a mantle source with a time-integrated Lu/Hf that exceeds average modern depleted mantle. Investigation of the timing and locus of parent-daughter fractionation in their mantle sources potentially constrains differentiation processes in the early Earth and their subsequent distribution and storage. In addition, they may help to constrain the Hf isotope evolution of the greater depleted mantle. In order to shed light on these processes, we discuss radiogenic Hf isotopes in conjunction with stable Fe isotope systematics in Archean komatiites from the Pilbara craton in Western Australia. Our findings indicate that, after careful evaluation of the effects of alteration, pristine samples are characterised by initial 176Hf/177Hf, which lie above the age-corrected depleted mantle, as a consequence of ancient melt extraction. Iron isotope systematics for these samples further point to a mantle source that is isotopically lighter than average modern depleted mantle, which is also consistent with melt-depletion. Taken together, these observations require a component of an old, super-depleted reservoir in the komatiite mantle source(s) that survived in the mantle for possibly hundreds of millions of years. The Lu/Hf of this refractory mantle appears to be complementary to, and therefore contemporaneous with, the first terrestrial crust, as preserved in Hadean (i.e., > 4 Ga) detrital zircon cores, which may indicate a causal relationship between them. We will discuss implications for very early mantle dynamics and the formation of very early mantle reservoirs.

Emerging treatment options for refractory angina pectoris: ranolazine, shock wave treatment, and cell-based therapies.

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Gennari, Marco; Gambini, Elisa; Bassetti, Beatrice; Capogrossi, Maurizio; Pompilio, Giulio

2014-01-01

A challenge of modern cardiovascular medicine is to find new, effective treatments for patients with refractory angina pectoris, a clinical condition characterized by severe angina despite optimal medical therapy. These patients are not candidates for surgical or percutaneous revascularization. Herein we review the most up-to-date information regarding the modern approach to the patient with refractory angina pectoris, from conventional medical management to new medications and shock wave therapy, focusing on the use of endothelial precursor cells (EPCs) in the treatment of this condition. Clinical limitations of the efficiency of conventional approaches justify the search for new therapeutic options. Regenerative medicine is considered the next step in the evolution of organ replacement therapy. It is driven largely by the same health needs as transplantation and replacement therapies, but it aims further than traditional approaches, such as cell-based therapy. Increasing knowledge of the role of circulating cells derived from bone marrow (EPCs) on cardiovascular homeostasis in physiologic and pathologic conditions has prompted the clinical use of these cells to relieve ischemia. The current state of therapeutic angiogenesis still leaves many questions unanswered. It is of paramount importance that the treatment is delivered safely. Direct intramyocardial and intracoronary administration has demonstrated acceptable safety profiles in early trials, and may represent a major advance over surgical thoracotomy. The combined efforts of bench and clinical researchers will ultimately answer the question of whether cell therapy is a suitable strategy for treatment of patients with refractory angina.

Plerixafor and Filgrastim For Mobilization of Donor Peripheral Blood Stem Cells Before A Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Science.gov (United States)

2017-06-26

Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia

Directory of Open Access Journals (Sweden)

K.S. Schwab

2016-06-01

Full Text Available Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.

CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia

Science.gov (United States)

2018-01-25

B Acute Lymphoblastic Leukemia; CD19 Positive; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly; Minimal Residual Disease; Philadelphia Chromosome Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

Plumes do not Exist: Plate Circulation is Confined to Upper Mantle

Science.gov (United States)

Hamilton, W. B.

2002-12-01

Plumes from deep mantle are widely conjectured to define an absolute reference frame, inaugurate rifting, drive plates, and profoundly modify oceans and continents. Mantle properties and composition are assumed to be whatever enables plumes. Nevertheless, purported critical evidence for plume speculation is false, and all data are better interpreted without plumes. Plume fantasies are made ever more complex and ad hoc to evade contradictory data, and have no predictive value because plumes do not exist. All plume conjecture derives from Hawaii and the guess that the Emperor-Hawaii inflection records a 60-degree change in Pacific plate direction at 45 Ma. Paleomagnetic latitudes and smooth Pacific spreading patterns disprove any such change. Rationales for other fixed plumes collapse when tested, and hypotheses of jumping, splitting, and gyrating plumes are specious. Thermal and physical properties of Hawaiian lithosphere falsify plume predictions. Purported tomographic support elsewhere represents artifacts and misleading presentations. Asthenosphere is everywhere near solidus temperature, so melt needs a tensional setting for egress but not local heat. Gradational and inconsistent contrasts between MORB and OIB are as required by depth-varying melt generation and behavior in contrasted settings and do not indicate systematically unlike sources. MORB melts rise, with minimal reaction, through hot asthenosphere, whereas OIB melts react with cool lithosphere, and lose mass, by crystallizing refractories and retaining and assimilating fusibles. The unfractionated lower mantle of plume conjecture is contrary to cosmologic and thermodynamic data, for mantle below 660 km is more refractory than that above. Subduction, due to density inversion by top-down cooling that forms oceanic lithosphere, drives plate tectonics and upper-mantle circulation. It organizes plate motions and lithosphere stress, which controls plate boundaries and volcanic chains. Hinge rollback is the

Human adipose cells in vitro are either refractory or responsive to insulin, reflecting host metabolic state.

Directory of Open Access Journals (Sweden)

Vladimir A Lizunov

Full Text Available While intercellular communication processes are frequently characterized by switch-like transitions, the endocrine system, including the adipose tissue response to insulin, has been characterized by graded responses. Yet here individual cells from adipose tissue biopsies are best described by a switch-like transition between the basal and insulin-stimulated states for the trafficking of the glucose transporter GLUT4. Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells. Furthermore, subjects exhibiting high systemic insulin sensitivity indices (SI have high fractions of responsive adipose cells in vitro, while subjects exhibiting decreasing SI have increasing fractions of refractory cells in vitro. Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI. Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.

How to manage mantle cell lymphoma.

Science.gov (United States)

Dreyling, M; Ferrero, S; Hermine, O

2014-11-01

Mantle cell lymphoma (MCL) is no longer a hopeless disease. Considered to carry a uniformly dismal prognosis so far, during the last years it has been rediscovered as a heterogeneous clinical and biological entity. Such a complexity has been highlighted by molecular genetics, unraveling different pathways of cell survival and progression. Concurrently, the application of new therapeutic paradigms including rituximab, high-dose cytarabine and stem cell transplantation dramatically improved treatment activity and the introduction of innovative targeted molecules has already led to new patient perspectives. In this completely new and continually evolving landscape, the clinical hemato-oncologist might feel disoriented on what are the best current strategies to handle such a critical disease and the gold standard therapeutic options for MCL. Here we address some burning questions on how to manage MCL patients, spacing from prognostic issues to the dilemma of personalized treatment in different scenarios of the disease: how to diagnose an MCL? Which are the fundamental staging procedures? What are the most reliable prognosticators? Is there a place for watch and wait? Which are the best treatment options for younger, elderly and frail patients? Which patients are addressable to high-dose therapy? What is the role of allogeneic transplantation? What is the most appropriate approach for relapsing disease in different categories of patients? What novelties are going to be introduced in the near future? The practical algorithms here discussed represent an evidence-based approach derived from results of multicenter and randomized trials.

A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study.

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Fenske, Timothy S; Shah, Namrata M; Kim, Kyung Mann; Saha, Sandeep; Zhang, Chong; Baim, Arielle E; Farnen, John P; Onitilo, Adedayo A; Blank, Jules H; Ahuja, Harish; Wassenaar, Tim; Qamar, Rubina; Mansky, Patrick; Traynor, Anne M; Mattison, Ryan J; Kahl, Brad S

2015-10-01

Proteasome inhibitors and mammalian target of rapamycin inhibitors each have activity in various B-cell malignancies and affect distinct cellular pathways. Their combination has demonstrated synergy in vitro and in mouse models. The authors conducted a single-arm, phase 2 trial of combined temsirolimus and bortezomib in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (NHL) using a dosing scheme that was previously tested in multiple myeloma. The patients received bortezomib and temsirolimus weekly on days 1, 8, 15, and 22 of a 35-day cycle. Of 39 patients who received treatment, 3 achieved a complete response (7.7%; 95% confidence interval [CI], 1.6%-21%), and 9 had a partial response (PR) (23%; 95% CI, 11%-39%). Thus, the overall response rate (12 of 39 patients) was 31% (95% CI, 17%-48%), and the median progression-free survival was 4.7 months (95% CI, 2.1-7.8 months; 2 months for patients with diffuse large B-cell lymphoma [n = 18], 7.5 months for those with mantle cell lymphoma [n = 7], and 16.5 months for those with follicular lymphoma [n = 9]). Two extensively treated patients with diffuse large B-cell lymphoma achieved a complete response. There were no unexpected toxicities from the combination. The current results demonstrate that the combination of a mammalian target of rapamycin inhibitor and a proteasome inhibitor is safe and has activity in patients with heavily pretreated B-cell NHL. Further studies with this combination are warranted in specific subtypes of NHL. © 2015 American Cancer Society.

Role of Radiation Therapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

Ng, Andrea K; Yahalom, Joachim; Goda, Jayant S

2018-01-01

Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with a...

Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma

Science.gov (United States)

2018-01-26

Adult Grade III Lymphomatoid Granulomatosis; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

[The mantle zone in lymphatic follicles and its stratification].

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Bednár, B

1993-04-01

Ten inguinal lymph nodes and spleens from autopsies were chosen according to age decades in order to get an idea about usual appearance of follicular structures. The group was complemented by 4 palatine tonsils from routine biopsies. Phenotype was ascertained by using about 30 standard markers and results were compared with a basic histocytological picture. The appearance of lymphatic tissue was quite different according to location and age categories, nevertheless, there were common immunophenotypic and structural features of follicular mantle in younger persons. It mostly comprised four cellular layers, more conspicuous at the upper pole of the follicle. An innermost layer was small-celled blastic, MB 2 and IgD positive, the next B monocytoid layer had medium sized cells of a similar phenotype but more alc, phosphatase positive. An inconstant plasmacytoid layer and a clarocellular layer used to be incomplete. It was cytostructurally characteristic but immunohistologically non-standard (faint CD 19 et CD 20 positivity). T 4 lymphocytes and perhaps some other elements leaving germinal centres were admixed into the inner mantle layer. Various small lymphoid cells, especially T 8 lymphocytes and sometimes litoral cells, were admixed into mantle periphery. Mutual exchange of lymphatic cells between the germinal and mantle zones was very scant. The mantle zone is presumed therefore to be independent from the structural and functional point of view as well.

Up-regulation of VEGF and its receptor in refractory leukemia cells

OpenAIRE

Wang, Lei; Zhang, Wenjun; Ding, Yi; Xiu, Bing; Li, Ping; Dong, Yan; Zhu, Qi; Liang, Aibin

2015-01-01

Objective: To analyze the causative mechanisms in refractory leukemia cells. Methods: Vascular endothelial growth factor (VEGF) blood plasma concentrations in 35 de novo, 6 relapse, 20 remission leukemia patients and 10 healthy kids were determined via ELISA analyses. Transcription levels of the VEGF receptors (VEGFR) Fms-like tyrosine kinase-1 (Flt-1) and kinase-domain insert containing receptor (KDR) were determined in participants’ leucocytes with RT-PCR. Apoptosis rates as well as Cyt-C a...

Linking lowermost mantle structure, core-mantle boundary heat flux and mantle plume formation

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Li, Mingming; Zhong, Shijie; Olson, Peter

2018-04-01

The dynamics of Earth's lowermost mantle exert significant control on the formation of mantle plumes and the core-mantle boundary (CMB) heat flux. However, it is not clear if and how the variation of CMB heat flux and mantle plume activity are related. Here, we perform geodynamic model experiments that show how temporal variations in CMB heat flux and pulses of mantle plumes are related to morphologic changes of the thermochemical piles of large-scale compositional heterogeneities in Earth's lowermost mantle, represented by the large low shear velocity provinces (LLSVPs). We find good correlation between the morphologic changes of the thermochemical piles and the time variation of CMB heat flux. The morphology of the thermochemical piles is significantly altered during the initiation and ascent of strong mantle plumes, and the changes in pile morphology cause variations in the local and the total CMB heat flux. Our modeling results indicate that plume-induced episodic variations of CMB heat flux link geomagnetic superchrons to pulses of surface volcanism, although the relative timing of these two phenomena remains problematic. We also find that the density distribution in thermochemical piles is heterogeneous, and that the piles are denser on average than the surrounding mantle when both thermal and chemical effects are included.

Birch's Mantle

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Anderson, D. L.

2002-12-01

Francis Birch's 1952 paper started the sciences of mineral physics and physics of the Earth's interior. Birch stressed the importance of pressure, compressive strain and volume in mantle physics. Although this may seem to be an obvious lesson many modern paradoxes in the internal constitution of the Earth and mantle dynamics can be traced to a lack of appreciation for the role of compression. The effect of pressure on thermal properties such as expansivity can gravitational stratify the Earth irreversibly during accretion and can keep it chemically stratified. The widespread use of the Boussinesq approximation in mantle geodynamics is the antithesis of Birchian physics. Birch pointed out that eclogite was likely to be an important component of the upper mantle. Plate tectonic recycling and the bouyancy of oceanic crust at midmantle depths gives credence to this suggestion. Although peridotite dominates the upper mantle, variations in eclogite-content may be responsible for melting- or fertility-spots. Birch called attention to the Repetti Discontinuity near 900 km depth as an important geodynamic boundary. This may be the chemical interface between the upper and lower mantles. Recent work in geodynamics and seismology has confirmed the importance of this region of the mantle as a possible barrier. Birch regarded the transition region (TR ; 400 to 1000 km ) as the key to many problems in Earth sciences. The TR contains two major discontinuities ( near 410 and 650 km ) and their depths are a good mantle thermometer which is now being exploited to suggest that much of plate tectonics is confined to the upper mantle ( in Birch's terminology, the mantle above 1000 km depth ). The lower mantle is homogeneous and different from the upper mantle. Density and seismic velocity are very insensitive to temperature there, consistent with tomography. A final key to the operation of the mantle is Birch's suggestion that radioactivities were stripped out of the deeper parts of

Primary Refractory and Relapsed Classical Hodgkin Lymphoma - Significance of Differential CD15 Expression in Hodgkin-Reed-Sternberg Cells

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Daniel Benharroch, Shai Pilosof, Jacob Gopas, Itai Levi

2012-01-01

Full Text Available We recognized a few possible complications of classical Hodgkin lymphoma therapy in a cohort of 209 patients: 8 developed a primary refractory disease (primary progression, 36 showed an early relapse and 21 showed a late relapse. Sialyl-CD15 expression in Hodgkin-Reed-Sternberg cells was significantly more positive in primary refractory Hodgkin lymphoma, which confirms our previously published findings. Bcl-2 showed a significantly lower level of expression in primary refractory disease than in the other follow-up groups. This is in contrast with a previous finding of Bcl-2, associated with a poor prognosis in primary refractory illness. Another category of variables, old age and advanced stages, was significantly different in the various complications but this finding is probably to be expected. We could not demonstrate a difference between the sequels and the control group with regard to several clinical and immunohistochemical markers. Sialyl-CD15 and Bcl-2 expression, in contrast, were confirmed as prognostic factors, mainly of tumor progression into primary refractory disease.

VEGF 165 Gene Therapy for Patients with Refractory Angina: Mobilization of Endothelial Progenitor Cells

International Nuclear Information System (INIS)

Rodrigues, Clarissa G.; Plentz, Rodrigo D.M.; Dipp, Thiago; Salles, Felipe B.; Giusti, Imarilde I.; Sant'Anna, Roberto T.; Eibel, Bruna; Nesralla, Ivo A.; Markoski, Melissa; Beyer, Nance N.; Kalil, Renato A. K.

2013-01-01

Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9 th and 27 th was comparable to that at baseline. We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on 9 th and 27 th days

Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma.

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Sangha, Randeep; Davies, Andrew; Dang, Nam H; Ogura, Michinori; MacDonald, David A; Ananthakrishnan, Revathi; Paccagnella, M Luisa; Vandendries, Erik; Boni, Joseph; Goh, Yeow Tee

2017-01-01

Objective : To evaluate safety, tolerability, and preliminary activity of inotuzumab ozogamicin (InO) plus rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). Methods : Patients received InO plus R-GDP (21-day cycle; six-cycle maximum) using up-and-down dose-escalation schema for gemcitabine and cisplatin to define the highest dosage regimen(s) with acceptable toxicity (Part 1; n  = 27). Part 2 ( n  = 10) confirmed safety and tolerability; Part 3 ( n  = 18) evaluated preliminary efficacy. Results: Among 55 patients enrolled, 42% were refractory at baseline (median 2 [range, 1-6] prior therapies); 38% had diffuse large B-cell lymphoma (DLBCL). The highest dosage regimen with acceptable toxicity was InO 0.8 mg/m 2 , rituximab 375 mg/m 2 , cisplatin 50 mg/m 2 , gemcitabine 500 mg/m 2 (day 1 only) and dexamethasone 40 mg (days 1-4); this was confirmed in Part 2, in which three patients had dose-limiting toxicities (grade 4 thrombocytopenia [ n  = 2], febrile neutropenia [ n  = 2]). Most frequent treatment-related adverse events were thrombocytopenia (any grade, 85%; grade ≥3, 75%) and neutropenia (69%; 62%). Overall (objective) response rate (ORR) was 53% (11 complete, 18 partial responses); ORR was 71%, 33%, and 62% in patients with follicular lymphoma ( n  = 14), DLBCL ( n  = 21), and mantle cell lymphoma ( n  = 13), respectively. Conclusions: InO 0.8 mg/m 2 plus R-GDP was associated with manageable toxicity, although gemcitabine and cisplatin doses were lower than in the standard R-GDP regimen due to hematologic toxicity. Evidence of antitumor activity was observed; however, these exploratory data should be interpreted with caution due to the small sample size and short follow-up duration (Clinicaltrials.gov number: NCT01055496).

Highly refractory Archaean peridotite cumulates: Petrology and geochemistry of the Seqi Ultramafic Complex, SW Greenland

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Kristoffer Szilas

2018-05-01

Full Text Available This paper investigates the petrogenesis of the Seqi Ultramafic Complex, which covers a total area of approximately 0.5 km2. The ultramafic rocks are hosted by tonalitic orthogneiss of the ca. 3000 Ma Akia terrane with crosscutting granitoid sheets providing an absolute minimum age of 2978 ± 8 Ma for the Seqi Ultramafic Complex. The Seqi rocks represent a broad range of olivine-dominated plutonic rocks with varying modal amounts of chromite, orthopyroxene and amphibole, i.e. various types of dunite (s.s., peridotite (s.l., as well as chromitite. The Seqi Ultramafic Complex is characterised primarily by refractory dunite, with highly forsteritic olivine with core compositions having Mg# ranging from about 91 to 93. The overall high modal contents, as well as the specific compositions, of chromite rule out that these rocks represent a fragment of Earth's mantle. The occurrence of stratiform chromitite bands in peridotite, thin chromite layers in dunite and poikilitic orthopyroxene in peridotite instead supports the interpretation that the Seqi Ultramafic Complex represents the remnant of a fragmented layered complex or a magma conduit, which was subsequently broken up and entrained during the formation of the regional continental crust.Integrating all of the characteristics of the Seqi Ultramafic Complex points to formation of these highly refractory peridotites from an extremely magnesian (Mg# ∼ 80, near-anhydrous magma, as olivine-dominated cumulates with high modal contents of chromite. It is noted that the Seqi cumulates were derived from a mantle source by extreme degrees of partial melting (>40%. This mantle source could potentially represent the precursor for the sub-continental lithospheric mantle (SCLM in this region, which has previously been shown to be ultra-depleted. The Seqi Ultramafic Complex, as well as similar peridotite bodies in the Fiskefjord region, may thus constitute the earliest cumulates that formed during the

REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

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Emmanuel Gyan

2015-02-01

Full Text Available Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT, and refractory neutropenia (RN, characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS. Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS, and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008 are quite rare.These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates.

17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.

Science.gov (United States)

Xiao, Y; Guan, J

2015-01-01

Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.

Carbonate stability in the reduced lower mantle

Science.gov (United States)

Dorfman, Susannah M.; Badro, James; Nabiei, Farhang; Prakapenka, Vitali B.; Cantoni, Marco; Gillet, Philippe

2018-05-01

Carbonate minerals are important hosts of carbon in the crust and mantle with a key role in the transport and storage of carbon in Earth's deep interior over the history of the planet. Whether subducted carbonates efficiently melt and break down due to interactions with reduced phases or are preserved to great depths and ultimately reach the core-mantle boundary remains controversial. In this study, experiments in the laser-heated diamond anvil cell (LHDAC) on layered samples of dolomite (Mg, Ca)CO3 and iron at pressure and temperature conditions reaching those of the deep lower mantle show that carbon-iron redox interactions destabilize the MgCO3 component, producing a mixture of diamond, Fe7C3, and (Mg, Fe)O. However, CaCO3 is preserved, supporting its relative stability in carbonate-rich lithologies under reducing lower mantle conditions. These results constrain the thermodynamic stability of redox-driven breakdown of carbonates and demonstrate progress towards multiphase mantle petrology in the LHDAC at conditions of the lowermost mantle.

Mesenchymal stromal cells for treatment of steroid-refractory GvHD: a review of the literature and two pediatric cases

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Wernicke Caroline M

2011-08-01

Full Text Available Abstract Severe acute graft versus host disease (GvHD is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children. Our meta-analysis demonstrates that the overall response-rate is high (73.8% and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively. These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients.

Remission induction using alemtuzumab can permit chemotherapy-refractory chronic lymphocytic leukemia (CLL) patients to undergo allogeneic stem cell transplantation.

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Knauf, Wolfgang; Rieger, Kathrin; Blau, Wolfgang; Hegenbart, Ute; Von Gruenhagen, Ulrich; Niederwieser, Dietger; Thiel, Eckhard

2004-12-01

The outcome of allogeneic stem cell transplantation depends upon the disease status before transplantation. Patients with refractory disease are at high risk for relapse. To improve the curative potential of the transplant procedure, we treated 3 chemotherapy-refractory CLL patients with alemtuzumab before allogeneic stem cell transplantation. Prior to therapy, all patients suffered from B-symptoms, and had massive adenopathy, splenomegaly, thrombocytopenia, and anemia; two patients had hepatomegaly. Alemtuzumab greatly reduced tumor mass in blood and bone marrow, B-symptoms resolved, and organomegaly improved. Two patients became blood product independent. All patients proceeded to transplantation after conditioning with TBI 2 Gy (n=1) or Treosulfan (n=2) in combination with Fludarabine either from an HLA-matched sibling (n=2) or from an HLA-matched unrelated donor (n=1). All patients engrafted, and are alive and well. Two patients reached complete remission (CR); one patient attained stable partial remission (PR). These heavily pre-treated refractory patients gained substantial clinical benefit from alemtuzumab, and received successful allografts.

VEGF 165 Gene Therapy for Patients with Refractory Angina: Mobilization of Endothelial Progenitor Cells

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Rodrigues, Clarissa G. [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Duke University Medical Center, Durham, North Carolina (United States); Plentz, Rodrigo D.M. [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Dipp, Thiago [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Salles, Felipe B. [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Giusti, Imarilde I.; Sant' Anna, Roberto T.; Eibel, Bruna; Nesralla, Ivo A.; Markoski, Melissa [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Beyer, Nance N. [Instituto de Cardiologia/Fundação Universitária de Cardiologia - Programa de Pós Graduação em Ciências da Saúde: Cardiologia, Porto Alegre, RS (Brazil); Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Kalil, Renato A. K., E-mail: kalil.pesquisa@gmail.com [Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

2013-08-15

Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9{sup th} and 27{sup th} was comparable to that at baseline. We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on 9{sup th} and 27{sup th}days.

[Cytostructure of the mantle zone in lymphatic tissue].

Science.gov (United States)

Bednár, B

1993-04-01

Four cellular layers of the follicular mantle zone in palatine tonsil lymphatic tissue were studied by electron microscopy after simultaneous immunophenotypical investigation. The first layer of the mantle zone consisting of small blastic cells was analogous to the small (centrocytoid) blastic layer of germinal centres. The second B monocytoid layer was lacking analogy in basic series of lymphocytes and seemed to be an independent morphological and probably functional unit. Plasmacytoid and clarocellular elements in outer layers of follicular mantle zone were in a way similar to T plasmacytoid and clarocellular components of Sézary syndrome infiltrates but considering transitional forms they had a local origin from incompletely transformed elements of B monocytoid layer. Inner follicular mantle zone was discussed as a source of incompletely transformed B lymphocytes for further mantle layers where their immunophenotypical modulation is taking place according to actual need. Outer mantle layers are aggressive against damaged epithelial and litoral structures and may be instrumental in a common reaction of B and T components.

Toll-like receptor 2 expression in refractory periapical lesions.

Science.gov (United States)

Desai, S V; Love, R M; Rich, A M; Seymour, G J

2011-10-01

To investigate the expression of TLR2 in refractory periapical lesions. Refractory periapical lesion biopsies were histopathologically and clinically categorized into asymptomatic periapical granuloma (n=10), symptomatic periapical granuloma (n=10) or periapical cyst (n=10) and prepared for immunohistochemical staining using antibodies to TLR2, CD3 and CD19 or staining with methyl green pyronin. Sections were viewed under light microscopy and the presence or absence of the target cells was correlated with the histopathological and clinical data. Additionally, TLR2 expression was quantified by counting TLR(+) cells. Various mononuclear inflammatory cells in the bacteria-induced periapical lesions were reactive to TLR2 antibody, with many showing morphological similarities to lymphocytes and plasma cells. Lymphocytes were the most numerous cells in the inflammatory infiltrate. In refractory periapical granuloma, CD3(+) T cells were more numerous, whereas in periapical cysts, CD19(+) B cells were more numerous. There was a statistically significant (Pperiapical granuloma than asymptomatic periapical granuloma or periapical cyst. The presence of TLR-expressing cells in periapical granulomas and cysts provides further evidence that periapical cysts are likely to be sustained by the immune system via reaction to bacterial antigens. © 2011 International Endodontic Journal.

DKK1 is a potential novel mediator of cisplatin-refractoriness in non-small cell lung cancer cell lines

International Nuclear Information System (INIS)

Salim, Hogir; Zong, Dali; Hååg, Petra; Novak, Metka; Mörk, Birgitta; Lewensohn, Rolf; Lundholm, Lovisa; Viktorsson, Kristina

2015-01-01

Platinum compounds are the mainstay of chemotherapy for lung cancer. Unfortunately treatment failure remains a critical issue since about 60 % of all non-small cell lung cancer (NSCLC) patients display intrinsic platinum resistance. We analyzed global gene expression profiles of NSCLC clones surviving a pulse treatment with cisplatin and mapped deregulated signaling networks in silico by Ingenuity Pathway Analysis (IPA). Further validation was done using siRNA. The pooled cisplatin-surviving NSCLC clones from each of the biological replicates demonstrated heterogeneous gene expression patterns both in terms of the number and the identity of the altered genes. Genes involved in Wnt signaling pathway (Dickkopf-1, DKK1), DNA repair machinery (XRCC2) and cell-cell/cell-matrix interaction (FMN1, LGALS9) were among the top deregulated genes by microarray in these replicates and were validated by q-RT-PCR. We focused on DKK1 which previously was reported to be overexpressed in NSCLC patients. IPA network analysis revealed coordinate up-regulation of several DKK1 transcriptional regulators (TCF4, EZH2, DNAJB6 and HDAC2) in cisplatin-surviving clones from that biological replicate. Knockdown of DKK1 by siRNA sensitized for cisplatin in two different NSCLC cell lines and in ovarian A2780 cells, but not in the A2780 cis subline made resistant to cisplatin by chronic exposure, suggesting a role of DKK1 in intrinsic but not acquired platinum refractoriness. We identified DKK1 as a possible marker of a cisplatin-refractory phenotype and as a potential novel therapeutic target to improve platinum response of NSCLC cells. The online version of this article (doi:10.1186/s12885-015-1635-9) contains supplementary material, which is available to authorized users

[Ibrutinib: A new drug of B-cell malignancies].

Science.gov (United States)

Thieblemont, Catherine

2015-06-01

Ibrutinib (Imbruvica®) is a first-in-class, orally administered once-daily, that inhibits B-cell antigen receptor signaling downstream of Bruton's tyrosine kinase (BTK). Ibrutinib has been approved in USA in February 2014 and in France in October 2014 for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL) or chronic lymphocytic leukaemia (CLL) and for the treatment of patients with CLL and a chromosome 17 deletion (del 17p) or TP53 mutation. In clinical studies, ibrutinib induced an impressive overall response rate (68%) in patients with relapsed/refractory MCL (phase II study). In CLL, ibrutinib has shown to significantly improve progression-free survival, response rate and overall survival in patients with relapsed/refractory CLL, including in those with del 17p. Ibrutinib had an acceptable tolerability profile. Less than 10% of patients discontinued their treatment because of adverse events. Results are pending in other B-cell lymphomas subtypes such as in diffuse large B-cell lymphoma and in follicular lymphoma. An approval extension has already been enregistered for Waldenström disease in USA in January 2015. Given its efficacy and tolerability, ibrutinib is an emerging treatment option for patients with B-cell malignancies. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy

DEFF Research Database (Denmark)

Eskelund, Christian W.; Dahl, Christina; Hansen, Jakob W.

2017-01-01

Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM...

Effects of iron on the lattice thermal conductivity of Earth's deep mantle and implications for mantle dynamics.

Science.gov (United States)

Hsieh, Wen-Pin; Deschamps, Frédéric; Okuchi, Takuo; Lin, Jung-Fu

2018-04-17

Iron may critically influence the physical properties and thermochemical structures of Earth's lower mantle. Its effects on thermal conductivity, with possible consequences on heat transfer and mantle dynamics, however, remain largely unknown. We measured the lattice thermal conductivity of lower-mantle ferropericlase to 120 GPa using the ultrafast optical pump-probe technique in a diamond anvil cell. The thermal conductivity of ferropericlase with 56% iron significantly drops by a factor of 1.8 across the spin transition around 53 GPa, while that with 8-10% iron increases monotonically with pressure, causing an enhanced iron substitution effect in the low-spin state. Combined with bridgmanite data, modeling of our results provides a self-consistent radial profile of lower-mantle thermal conductivity, which is dominated by pressure, temperature, and iron effects, and shows a twofold increase from top to bottom of the lower mantle. Such increase in thermal conductivity may delay the cooling of the core, while its decrease with iron content may enhance the dynamics of large low shear-wave velocity provinces. Our findings further show that, if hot and strongly enriched in iron, the seismic ultralow velocity zones have exceptionally low conductivity, thus delaying their cooling.

Mantle cell lymphoma pathogenesis: another turn of the screw to cyclin D1 overexpression

OpenAIRE

Albero Gallego, Robert

2017-01-01

[eng] Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm derived from mature B cells characterized by the presence of the t(11;14)(q13;q32) translocation that leads to the overexpression of Cyclin D1. Cyclin D1 plays a well-established role in G1/S progression, although other functions including transcription or DNA damage response (DDR) can be regulated by this cyclin. Therefore, the main goal of this thesis is the characterization of the cyclin D1 non-canonical function in MCL a...

Mantle cell lymphoma pathogenesis: another turn of the screw to cyclin D1 overexpression

OpenAIRE

Albero Gallego, Robert

2017-01-01

Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm derived from mature B cells characterized by the presence of the t(11;14)(q13;q32) translocation that leads to the overexpression of Cyclin D1. Cyclin D1 plays a well-established role in G1/S progression, although other functions including transcription or DNA damage response (DDR) can be regulated by this cyclin. Therefore, the main goal of this thesis is the characterization of the cyclin D1 non-canonical function in MCL and lymp...

Detailed Functional and Proteomic Characterization of Fludarabine Resistance in Mantle Cell Lymphoma Cells.

Directory of Open Access Journals (Sweden)

Lucie Lorkova

Full Text Available Mantle cell lymphoma (MCL is a chronically relapsing aggressive type of B-cell non-Hodgkin lymphoma considered incurable by currently used treatment approaches. Fludarabine is a purine analog clinically still widely used in the therapy of relapsed MCL. Molecular mechanisms of fludarabine resistance have not, however, been studied in the setting of MCL so far. We therefore derived fludarabine-resistant MCL cells (Mino/FR and performed their detailed functional and proteomic characterization compared to the original fludarabine sensitive cells (Mino. We demonstrated that Mino/FR were highly cross-resistant to other antinucleosides (cytarabine, cladribine, gemcitabine and to an inhibitor of Bruton tyrosine kinase (BTK ibrutinib. Sensitivity to other types of anti-lymphoma agents was altered only mildly (methotrexate, doxorubicin, bortezomib or remained unaffacted (cisplatin, bendamustine. The detailed proteomic analysis of Mino/FR compared to Mino cells unveiled over 300 differentially expressed proteins. Mino/FR were characterized by the marked downregulation of deoxycytidine kinase (dCK and BTK (thus explaining the observed crossresistance to antinucleosides and ibrutinib, but also by the upregulation of several enzymes of de novo nucleotide synthesis, as well as the up-regulation of the numerous proteins of DNA repair and replication. The significant upregulation of the key antiapoptotic protein Bcl-2 in Mino/FR cells was associated with the markedly increased sensitivity of the fludarabine-resistant MCL cells to Bcl-2-specific inhibitor ABT199 compared to fludarabine-sensitive cells. Our data thus demonstrate that a detailed molecular analysis of drug-resistant tumor cells can indeed open a way to personalized therapy of resistant malignancies.

Distribution of lithium in the Cordilleran Mantle wedge

Science.gov (United States)

Shervais, J. W.; Jean, M. M.; Seitz, H. M.

2015-12-01

Enriched fluid-mobile element (i.e., B, Li, Be) concentrations in peridotites from the Coast Range ophiolite are compelling evidence that this ophiolite originated in a subduction environment. A new method presented in Shervais and Jean (2012) for modeling the fluid enrichment process, represents the total addition of material to the mantle wedge source region and can be applied to any refractory mantle peridotite that has been modified by melt extraction and/or metasomatism. Although the end-result is attributed to an added flux of aqueous fluid or fluid-rich melt phase derived from the subducting slab, in the range of tens of parts per million - the nature and composition of this fluid could not be constrained. To address fluid(s) origins, we have analyzed Li isotopes in bulk rock peridotite and eclogite, and garnet separates, to identify possible sources, and fluid flow mechanisms and pathways. Bulk rock Li abundances of CRO peridotites (δ7Li = -14.3 to 5.5‰; 1.9-7.5 ppm) are indicative of Li addition and δ7Li-values are lighter than normal upper mantle values. However, Li abundances of clino- and orthopyroxene appear to record different processes operating during the CRO-mantle evolution. Low Li abundances in orthopyroxene (2 ppm) record subsequent interaction with Li-enriched fluids (or melts). The preferential partitioning of lithium in clinopyroxene could be indicative of a particular metasomatic agent, e.g., fluids from a dehydrating slab. Future in-situ peridotite isotope studies via laser ablation will further elucidate the fractionation of lithium between orthopyroxene, clinopyroxene, and serpentine. To obtain a more complete picture of the slab to arc transfer processes, we also measured eclogites and garnet separates to δ7Li= -18 to 3.5‰ (11.5-32.5 ppm) and δ7Li= 1.9 to 11.7‰ (0.7-3.9 ppm), respectively. In connection with previous studies focused on high-grade metamorphic assemblages within the Franciscan complex, an overall framework exists

Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes.

Science.gov (United States)

Cheah, C Y; Chihara, D; Romaguera, J E; Fowler, N H; Seymour, J F; Hagemeister, F B; Champlin, R E; Wang, M L

2015-06-01

Although ibrutinib is highly effective in patients with relapsed/refractory mantle cell lymphoma (MCL), a substantial proportion of patients have resistant disease. The subsequent outcomes of such patients are unknown. We carried out a retrospective review of all patients with MCL treated with ibrutinib at MD Anderson Cancer Center between January 2011 and January 2014 using pharmacy and clinical databases. Patients who had discontinued ibrutinib for any reason were included in the study. We identified 42 patients with MCL who discontinued therapy due to disease progression on treatment (n = 28), toxicity (n = 6), elective stem-cell transplant in remission (n = 4) or withdrawn consent (n = 4). The median age was 69 years, 35 (83%) were male; the median number of prior treatments was 2 (range 1-8) and the median time from initial diagnosis of MCL to commencing ibrutinib was 3.0 (range 0.5-15.5) years. Patients had received a median of 6.5 (range 1-43) cycles of ibrutinib. Among 31 patients who experienced disease progression following ibrutinib and underwent salvage therapy, the overall and complete response rates were 32% and 19%, respectively. After a median follow-up of 10.7 (range 2.4-38.9) months from discontinuation of ibrutinib, the median overall survival (OS) among patients with disease progression was 8.4 months. By univariate analysis, elevated serum lactate dehydrogenase at progression was associated with inferior OS. The outcome of patients with MCL who experience disease progression following ibrutinib therapy is poor, with both low response rates to salvage therapy and short duration of responses. Further studies to better understand and overcome ibrutinib resistance are urgently needed. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Investigation of aluminosilicate refractory for solid oxide fuel cell applications

Science.gov (United States)

Gentile, Paul Steven

Stationary solid oxide fuel cells (SOFCs) have been demonstrated to provide clean and reliable electricity through electro-chemical conversion of various fuel sources (CH4 and other light hydrocarbons). To become a competitive conversion technology the costs of SOFCs must be reduced to less than $400/kW. Aluminosilicate represents a potential low cost alternative to high purity alumina for SOFC refractory applications. The objectives of this investigation are to: (1) study changes of aluminosilicate chemistry and morphology under SOFC conditions, (2) identify volatile silicon species released by aluminosilicates, (3) identify the mechanisms of aluminosilicate vapor deposition on SOFC materials, and (4) determine the effects of aluminosilicate vapors on SOFC electrochemical performance. It is shown thermodynamically and empirically that low cost aluminosilicate refractory remains chemically and thermally unstable under SOFC operating conditions between 800°C and 1000°C. Energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) of the aluminosilicate bulk and surface identified increased concentrations of silicon at the surface after exposure to SOFC gases at 1000°C for 100 hours. The presence of water vapor accelerated surface diffusion of silicon, creating a more uniform distribution. Thermodynamic equilibrium modeling showed aluminosilicate remains stable in dry air, but the introduction of water vapor indicative of actual SOFC gas streams creates low temperature (active anode interface.

Mantle cell lymphoma relapsing at the lymphedematous arm.

Directory of Open Access Journals (Sweden)

Giuseppina Massini

2013-02-01

Full Text Available Lymphedema (LE is a chronic medical condition characterized by lymphatic fluid retention, resulting in tissue swelling. Cancer treatments involving lymph nodes can damage lymph drainage routes, causing accumulation of lymph fluid in the interstitial tissue of related limbs and body areas and secondary LE.  Basically, the LE has a negative impact on physical and mental quality of life. Moreover, 0.07-0.04% of long term survivors (most patients undergone mastectomy can develop the Stewart-Treves syndrome,  a rare and aggressive multifocal lymphangiosarcoma arising within the LE region. Here we describe a   45-year-old woman  with a massive LE of the left arm,  as a consequence of previous breast cancer,  who  was diagnosed after 4 years  of stage IV mantle cell lymphoma (MCL . The patient after obtaining complete remission with chemotherapy and ABMT  relapsed of MCL in lymphedema site.

Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease

Science.gov (United States)

Rosiñol, Laura; García-Sanz, Ramón; Lahuerta, Juan José; Hernández-García, Miguel; Granell, Miquel; de la Rubia, Javier; Oriol, Albert; Hernández-Ruiz, Belén; Rayón, Consuelo; Navarro, Isabel; García-Ruiz, Juan Carlos; Besalduch, Joan; Gardella, Santiago; Jiménez, Javier López; Díaz-Mediavilla, Joaquín; Alegre, Adrián; Miguel, Jesús San; Bladé, Joan

2012-01-01

Background Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. Design and Methods In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (≥25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. Results There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). Conclusions Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. (ClinicalTrials.gov:NCT00560053) PMID:22058223

High-dose chemotherapy and auto-SCT for relapsed and refractory Hodgkin's lymphoma patients refractory to first-line salvage chemotherapy but responsive to second-line salvage chemotherapy.

Science.gov (United States)

Rauf, Muhammad Shahzad; Maghfoor, Irfan; Elhassan, Tusneem Ahmed M; Akhtar, Saad

2015-01-01

Relapsed or primary refractory Hodgkin's lymphoma (HL) patients refractory to first-line salvage chemotherapy (first salvage) and unable to undergo high-dose chemotherapy (HDC) and autologous stem cell transplant (auto-SCT) have very poor outcome. Some patients are offered second-line salvage chemotherapy (second salvage), if they are responsive and may receive HDC auto-SCT. We identified 31 patients (18 males, 13 females) from 1996-2012 who received second salvage prior to auto-SCT. Median age at auto-SCT is 22 years. Patients were grouped as (1) relapsed-refractory (Rel:Ref): patients with prior complete response (CR) and on relapse found refractory to first salvage and received second salvage and (2) refractory-refractory (Ref:Ref): patients refractory to both primary treatment and first salvage and received second salvage. Median follow-up is 63 months (18-170). Disease status after second salvage prior to HDC was CR 16 %, partial response (PR) 71 % and stable disease 13 %. After HDC auto-SCT, CR:PR: progressive disease was observed in 18 (58 %): four (12 %): nine (29 %) patients, respectively. Five-year overall survival (OS) for whole group is 57 % (Rel:Ref vs. Ref:Ref, 73 % vs. 48 %, p = 0.48). Progression-free survival (PFS) for whole group is 52 % (Rel:Ref vs. Ref:Ref, 73 % vs. 40 % respectively, p = 0.11). Second-line salvage is a valid approach with no long-term side effects for those HL patients who do not respond to first-line salvage chemotherapy and they can be candidate of HDC and stem cell transplant with a high ORR, the PFS and OS in relapse-refractory and refractory-refractory group of patients.

Slagging gasifier refractories. A new pathway to longer refractory life

Energy Technology Data Exchange (ETDEWEB)

Schnake, Mark [Harbinson-Walker Refractories Company, Mexico, MO (United States)

2013-07-01

Solid fuel slagging gasification to convert coal or petroleum coke feedstocks into syngas has rapidly evolved over the last 25 years. The gasifier is a high temperature, high pressure reaction chamber. Operating temperatures are between 1250 and 1575 C. Pressures will be between 20.4 and 68 atm. Syngas has been typically used for chemical feedstocks, fuel for power plants, or for steam and hydrogen generation in other industrial applications. Ash which comes from the solid fuel during gasification has many impurities. It melts during the gasifier reactor operation forming a liquid that penetrates the refractory lining. Given time, the refractory will wear away from thermal spalling, structural spalling, or overheating of the refractory. In some cases, all three wear mechanisms are seen in the same gasifier lining. Industry users have identified refractory life as one major limiting factor in worldwide use of this technology. Users have stated if the refractory liner can increase on-line availability of the gasifier operation, more industry acceptance of this technology is possible. Harbison-Walker Refractories Company will review destructive factors affecting lining life and discuss new refractory materials that have dramatically increased gasifier lining life and reliability. New refractory materials will be presented and supported by field trial results and post mortem analysis.

High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

Science.gov (United States)

Pan, J; Yang, J F; Deng, B P; Zhao, X J; Zhang, X; Lin, Y H; Wu, Y N; Deng, Z L; Zhang, Y L; Liu, S H; Wu, T; Lu, P H; Lu, D P; Chang, A H; Tong, C R

2017-12-01

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD + ) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10 5 /kg and were eventually settled at 1 × 10 5 /kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD + patients achieved MRD - . All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD - with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10 5 /kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

Mineralogy of the Hydrous Lower Mantle

Science.gov (United States)

Shim, S. H.; Chen, H.; Leinenweber, K. D.; Kunz, M.; Prakapenka, V.; Bechtel, H.; Liu, Z.

2017-12-01

The hydrous ringwoodite inclusions found in diamonds suggest water storage in the mantle transition zone. However, water storage in the lower mantle remains unclear. Bridgmanite and magnesiowustite appear to have very little storage capacity for water. Here, we report experimental results indicating significant changes in the lower-mantle mineralogy under the presence of water. We have synthesized Mg2SiO4 ringwoodite with 2 wt% water in multi-anvil press at 20 GPa and 1573 K at ASU. The hydrous ringwoodite sample was then loaded to diamond anvil cells with Ar or Ne as a pressure medium. We heated the pure hydrous ringwoodite samples at lower-mantle pressure using a CO2 laser heating system at ASU. We measured X-ray diffraction patterns at the GSECARS sector of the Advanced Photon Source (APS) and 12.2.2 sector of the Advanced Light Source (ALS). For the separate Pt-mixed samples, we have conducted in situ heating at the beamlines using near IR laser heating systems. We measured the infrared spectra of the heated samples at high pressure and after pressure quench at 1.4.4 sector of ALS. In the in situ experiments with hydrous ringwoodite + Pt mixture as a starting material, we found formation of stishovite together with bridgmanite and periclase during heating with a near IR laser beams at 1300-2500 K and 35-66 GPa. However, some hydrous ringwoodite still remains even after a total of 45 min of heating. In contrast, the hydrous ringwoodite samples heated without Pt by CO2 laser beams are transformed completely to bridgmanite, periclase and stishovite at 31-55 GPa and 1600-1900 K. We have detected IR active OH mode of stishovite from the samples heated at lower-mantle pressures. The unit-cell volume of stishovite measured after pressure quench is greater than that of dry stishovite by 0.3-0.6%, supporting 0.5-1 wt% of H2O in stishovite in these samples. Stishovite is a thermodynamically forbidden phase in the dry lower mantle because of the existence of periclase and

High alumina refractories

International Nuclear Information System (INIS)

Simao, L.C.; Lopes, A.B.; Galvao Filho, N.B.; Souza, R.B. de

1989-01-01

High alumina refractories with 92 to 96.5% Al 2 O 3 were produced using brown and white fused as aggregate. Those refractories present only alumina-α and mullite as crystalline mineralogical phase. Other physical and chemical characteristics are similar to the ones found in refractories produced in Brazil, Japan and U.S.A. The most important physical and chemical tests used for the characterization of the raw materials and refractories, complemented by those realized at high temperatures, plus X-ray Difractometry and optical microscopy are presented, besides the refractory formulation and main parameters of production [pt

Iron-carbonate interaction at Earth's core-mantle boundary

Science.gov (United States)

Dorfman, S. M.; Badro, J.; Nabiei, F.; Prakapenka, V.; Gillet, P.

2015-12-01

Carbon storage and flux in the deep Earth are moderated by oxygen fugacity and interactions with iron-bearing phases. The amount of carbon stored in Earth's mantle versus the core depends on carbon-iron chemistry at the core-mantle boundary. Oxidized carbonates subducted from Earth's surface to the lowermost mantle may encounter reduced Fe0 metal from disproportionation of Fe2+ in lower mantle silicates or mixing with the core. To understand the fate of carbonates in the lowermost mantle, we have performed experiments on sandwiches of single-crystal (Ca0.6Mg0.4)CO3 dolomite and Fe foil in the laser-heated diamond anvil cell at lower mantle conditions of 49-110 GPa and 1800-2500 K. Syntheses were conducted with in situ synchrotron X-ray diffraction to identify phase assemblages. After quench to ambient conditions, samples were sectioned with a focused Ga+ ion beam for composition analysis with transmission electron microscopy. At the centers of the heated spots, iron melted and reacted completely with the carbonate to form magnesiowüstite, iron carbide, diamond, magnesium-rich carbonate and calcium carbonate. In samples heated at 49 and 64 GPa, the two carbonates exhibit a eutectoid texture. In the sample heated at 110 GPa, the carbonates form rounded ~150-nm-diameter grains with a higher modal proportion of interspersed diamonds. The presence of reduced iron in the deep lower mantle and core-mantle boundary region will promote the formation of diamonds in carbonate-bearing subducted slabs. The complete reaction of metallic iron to oxides and carbides in the presence of mantle carbonate supports the formation of these phases at the Earth's core-mantle boundary and in ultra-low velocity zones.

Identification of compounds that selectively target highly chemotherapy refractory neuroblastoma cancer stem cells.

Science.gov (United States)

Díaz-Carballo, David; Acikelli, Ali Haydar; Bardenheuer, Walter; Gustmann, Sebastian; Malak, Sascha; Stoll, Raphael; Kedziorski, Thorsten; Nazif, Mhd Ali; Jastrow, Holger; Wennemuth, Gunter; Dammann, Philip; Feigel, Martin; Strumberg, Dirk

2014-09-01

Relapse of cancer months or years after an apparently successful therapy is probably caused by cancer stem cells (CSCs) due to their intrinsic features like dormant periods, radiorefraction, and acquired multidrug resistance (MDR) phenotypes, among other mechanisms of cellular drug evasiveness. Thus, the lack of currently efficacious interventions remains a major problem in the treatment of malignancies, together with the inability of existing drugs to destroy specifically CSCs. Neuroblastomas per se are highly chemotherapy-refractory extracranial tumors in infants with very low survival rates. So far, no effective cytostatics against this kind of tumors are clinically available. Therefore, we have put much effort into the development of agents to efficiently combat this malignancy. For this purpose, we tested several compounds isolated from Cuban propolis on induced CSCs (iCSC) derived from LAN-1 neuroblastoma cells which expressed several characteristics of tumor-initiating cells both in in-vitro and in-vivo models. Some small molecules such as flavonoids and polycyclic polyprenylated acylphloroglucinols (PPAP) were isolated using successive RT-HPLC cycles and identified employing mass spectrometry and NMR spectroscopic techniques. Their cytotoxicity was first screened in sensitive cell systems by MTT proliferation assays and afterwards studied in less sensitive neuroblastoma iCSC models. We found several compounds with considerable anti-iCSC activity, most of them belonging to the PPAP class. The majority of the compounds act in a pleiotropic manner on the molecular biology of tumors although their specific targets remain unclear. Nevertheless, two substances, one of them a flavonoid, induced a strong disruption of tubulin polymerization. In addition, an unknown compound strongly inhibited replicative enzymes like toposimerases I/II and DNA polymerase. Here, we report for the first time cytotoxic activities of small molecules isolated from Caribbean propolis

Diagnosis and management of refractory celiac disease: a systematic review.

Science.gov (United States)

Labidi, Asma; Serghini, Meriem; Karoui, Sami; Boubaker, Jalel; Filali, Azza

2013-01-01

Refractory celiac disease is defined by persisting malabsorptive symptoms in spite of a strict gluten free diet for at least 6 to 12 months. Alternatives to gluten free diet seem to be still controversial. To describe the clinical and epidemiologic aspects of refractory celiac disease, and to identify therapeutic options in this condition. Systematic review and critical analysis of observational studies, clinical trials and case reports that focused on diagnosis and management of refractory celiac disease. Refractory celiac disease can be classified as type 1 or type 2 according to the phenotype of intraepithelial lymphocytes. Great complications such as enteropathy-associated T-cell lymphoma may occur in a subgroup of these patients mainly in refractory celiac disease type 2. Curative therapies are still lacking. Refractory celiac disease remains a diagnosis of exclusion. Its prognosis remains still dismal by the absence yet of curative therapies. However, some new treatments seem to hold promise during few cohort-studies.

Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma

Directory of Open Access Journals (Sweden)

Hung-Bo Wu

2013-01-01

Full Text Available Up to 40% of patients with advanced Hodgkin lymphoma (HL become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

International Nuclear Information System (INIS)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others

2005-01-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20∼70 mg) immediately prior to administration of therapeutic dose (51.4∼152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted

Radioimmunotherapy in refractory b-cell nonhodgkins lymphoma with I-131-labeled chimeric anti cd-20 c2b8 (I-131 rituximab): preliminary result

Energy Technology Data Exchange (ETDEWEB)

Kang, Hye Jin; Park, Yeon Hee; Kim, Sung Eun and others [Korea University Medical School, Seoul (Korea, Republic of)

2005-07-01

Recently, the native chimeric human-mouse anti CD-20 antibody IDEC-C2B8 (Rituximab) has been widely applied in NHL. This ongoing phase study was to evaluate whether radioimmunotherapy (RIT) with I-131 rituximab is effective in refractory B-cell NHL. Inclusion criteria were as follows: B-cell NHL with relapsed or refractory to primary standard therapy, measurable disease, adequate hematologic, renal, and hepatic function, informed consent. The rituximab (Mabthera, Roach) was radiolabeled with iodine-131(I-131) using a modified chloramine T method with high radiochemical purity (95%) and preservation of immuno-reactivity. All patients received loading doses of unlabeled rituximab (median, 40 mg: range, 20{approx}70 mg) immediately prior to administration of therapeutic dose (51.4{approx}152.2 MBq/kg), and then underwent gamma camera scan. 11 patients were enrolled (4 low-grade B-cell NHL, 7 DLBCL, median age 63 years). Patients had received a median of three prior chemotherapy regimens. The objective response rate was 36.4% (1 CR, 3 PRs). These all responses were observed in low-grade B-cell NHL, except one with DLBCL. Adverse events were primarily hematologic toxicities; the incidence of grade 3/4 neutropenia, thrombocytopenia, and anemia was 27.3%, 45.5%, and 18.2%, respectively. The treatment-related mortality was observed in one patient, who had been previously treated with high-dose chemotherapy plus TBI with autologous stem cell transplantation. RIT with I-131 rituximab seems to be effective tolerable in refractory low-grade B-cell NHL, although modest activity in refractory DLBCL. Further studies to define the efficacy of I-131 rituximab in DLBCL are warranted.

Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma

DEFF Research Database (Denmark)

Casneuf, Tineke; Xu, Xu Steven; Adams, Homer C

2017-01-01

Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and......, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy...

Forodesine in the treatment of relapsed/refractory peripheral T-cell lymphoma: an evidence-based review

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Makita S

2018-04-01

Full Text Available Shinichi Makita,1 Akiko Miyagi Maeshima,2 Dai Maruyama,1 Koji Izutsu,1 Kensei Tobinai1 1Department of Hematology, 2Department of Pathology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan Abstract: T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL generally have a poor prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor, brentuximab vedotin (antibody–drug conjugate targeting CD30, chidamide (histone deacetylase inhibitor, and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody, have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan. Forodesine is a novel, potent purine nucleoside phosphorylase inhibitor that is effective against T-cell malignancies. Although the clinical development of forodesine was discontinued in the US and Europe, a multicenter Phase I/II study of oral forodesine for relapsed PTCL was recently completed in Japan. The overall response rate was 24% (10 of 41 patients, which included four patients with complete response. In general, the toxicity of forodesine is manageable. As the study met the primary end point, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in March 2017, which was the first approval of forodesine in the world. As forodesine is an oral formulation, it is more convenient than other novel intravenous agents approved for PTCL

Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does affect IL-2/IFN-γ expression of T cells in vitro?

Science.gov (United States)

Zhou, Naibao; Fu, Zhijian; Li, Hao; Wang, Kaiguo

2017-01-01

Abstract Background: Ketamine has been used as an analgesic adjuvant with morphine in the treatment of refractory cancer pain recently. But both morphine and ketamine have been reported to produce a number of immunomodulatory effects. The current study was performed to assess whether the concentration of ketamine, as adjuvant analgesics for patient with refractory cancer pain, was related to its effect on T cells interleukin-2 (IL-2)/interferon-γ (IFN-γ) expression in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients with refractory cancer pain over a Ficoll-Hypaque density gradient. T cells were isolated from by positive selection using anti-CD3 beads. T cells were then treated with vehicle (C group), morphine (200 ng/mL, M group), morphine (200 ng/mL), and different dose of ketamine (100, 200, 1000 ng/mL; MK1, MK5, MK10 group) for 24 hours before stimulation with anti-CD3 and anti-CD28. Then supernatant IL-2 and IFN-γ protein analysis, quantitative reverse transcription polymerase chain reaction (RT-PCR) for IL-2 and IFN-γ were done. Results: There were no significant difference of supernatant IL-2 and IFN-γ among C group, M group, and MK1 group, but the mRNA of M group and MK1 group were decreased compared with C group (P ketamine dose-dependently suppressed IL-2 and IFN-γ of activated T lymphocyte of patients with refractory cancer pain in vitro, but the inhibitory action of low dose ketamine could be neglected. PMID:28422864

The Effects of Mg/Si on the Exoplanetary Refractory Oxygen Budget

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Unterborn, Cayman T.; Panero, Wendy R.

2017-08-01

Solar photospheric abundances of refractory elements mirror the Earth’s to within ˜10 mol% when normalized to the dominant terrestrial-planet-forming elements Mg, Si, and Fe. This allows for the adoption of solar composition as an order-of-magnitude proxy for Earth’s. It is not known, however, the degree to which this mirroring of stellar and terrestrial planet abundances holds true for other star-planet systems without determination of the composition of initial planetesimals via condensation sequence calculations and post condensation processes. We present the open-source Arbitrary Composition Condensation Sequence calculator (ArCCoS) to assess how the elemental composition of a parent star affects that of the planet-building material, including the extent of oxidation within the planetesimals. We demonstrate the utility of ArCCoS by showing how variations in the abundance of the stellar refractory elements Mg and Si affect the condensation of oxygen, a controlling factor in the relative proportions of planetary core and silicate mantle material. This thereby removes significant degeneracy in the interpretation of the structures of exoplanets, as well as provides observational tests for the validity of this model.

Long-term outcomes of high dose treatment and autologous stem cell transplantation in follicular and mantle cell lymphomas – a single centre experience

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Boltezar Lucka

2016-06-01

Full Text Available Advanced follicular lymphoma (FL and mantle cell lymphoma (MCL are incurable diseases with conventional treatment. The high dose treatment (HDT with autologous stem cell transplantation (ASCT, however, offers a certain proportion of these patients the prospect of a prolonged disease-free and overall survival. The aim of this study was to investigate the event free survival (EFS and overall survival (OS in patients with FL and MCL treated with ASCT.

Merits of using andalusite-based refractories compared to bauxite-based refractories

OpenAIRE

Nyoka, M.; Brazier, D.; Courtney, T.; Parry, R.A.

2013-01-01

Historically bauxite-based refractories have been used in applications where andalusite-based refractories could work. Bauxite-based refractories were chosen over andalusite-based refractories mainly because of the availability of low-cost Chinese bauxite and also because many furnaces were designed by international companies that cannot easily access high-quality products. Currently, the availability of low-cost bauxite is under threat as a result of high export duties and tariffs as well as...

Incipient boninitic arc crust built on denudated mantle: the Khantaishir ophiolite (western Mongolia)

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Gianola, Omar; Schmidt, Max W.; Jagoutz, Oliver; Sambuu, Oyungerel

2017-12-01

The 570 Ma old Khantaishir ophiolite is built by up to 4 km harzburgitic mantle with abundant pyroxenites and dunites followed by 2 km of hornblende-gabbros and gabbronorites and by a 2.5 km thick volcanic unit composed of a dyke + sill complex capped by pillow lavas and some volcanoclastics. The volcanics are mainly basaltic andesites and andesites (or boninites) with an average of 58.2 ± 1.0 wt% SiO2, X Mg = 0.61 ± 0.03 ( X Mg = molar MgO/(MgO + FeOtot), TiO2 = 0.4 ± 0.1 wt% and CaO = 7.5 ± 0.6 wt% (errors as 2 σ). Normalized trace element patterns show positive anomalies for Pb and Sr, a negative Nb-anomaly, large ion lithophile elements (LILE) concentrations between N- and E-MORB and distinctly depleted HREE. These characteristics indicate that the Khantaishir volcanics were derived from a refractory mantle source modified by a moderate slab-component, similar to boninites erupted along the Izu-Bonin-Mariana subduction system and to the Troodos and Betts Cove ophiolites. Most strikingly and despite almost complete outcrops over 260 km2, there is no remnant of any pre-existing MORB crust, suggesting that the magmatic suite of this ophiolite formed on completely denudated mantle, most likely upon subduction initiation. The architecture of this 4-5 km thick early arc crust resembles oceanic crust formed at mid ocean ridges, but lacks a sheeted dyke complex; volcanic edifices are not observed. Nevertheless, low melting pressures combined with moderate H2O-contents resulted in high-Si primitive melts, in abundant hornblende-gabbros and in a fast enrichment in bulk SiO2. Fractional crystallization modeling starting from the observed primitive melts (56.6 wt% SiO2) suggests that 25 wt% pyroxene + plagioclase fractionation is sufficient to form the average Khantaishir volcanic crust. Most of the fractionation happened in the mantle, the observed pyroxenite lenses and layers in and at the top of the harzburgites account for the required cumulate volumes. Finally

Papilledema secondary to a superior sagittal sinus thrombosis. Mantle cell lymphoma paraneoplastic syndrome.

Science.gov (United States)

Platas-Moreno, I; Antón-Benito, A; Pérez-Cid-Rebolleda, M T; Rosado Sierra, M B

2016-01-01

A 46 year old patient presented with visual loss in the left eye during the previous months. Ophthalmoscopic examination and magnetic resonance angiography found the presence of papilledema due to thrombosis in superior sagittal sinus. The examination findings revealed a mantle cell lymphoma. Cerebral venous thrombosis is an unusual cause of papilledema. This type of thrombosis may be secondary to hyper-viscosity within a context of a paraneoplastic syndrome. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

When myasthenia gravis is deemed refractory: clinical signposts and treatment strategies

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Mantegazza, Renato; Antozzi, Carlo

2018-01-01

The prognosis for patients with myasthenia gravis (MG) has improved significantly over the past half century, including substantial reductions in mortality and morbidity. However, approximately 10% of patients fails to respond adequately to current therapies and are considered treatment refractory, or treatment intolerant, and up to 80% have disease that fails to achieve complete stable remission. Although patients with autoantibodies to muscle-specific tyrosine kinase (anti-MuSK positive) are more likely to become treatment refractory than those with autoantibodies to the acetylcholine receptor (anti-AChR positive), each of these serotypes is substantially represented in the refractory MG population. Other risk factors for becoming treatment refractory include history of thymoma or thymectomy and female sex. A modified treatment algorithm for MG is proposed: patients who have disease that fails to respond to the stepwise approach to therapy, are treatment intolerant, or who require chronic rescue measures despite ongoing therapy, should be considered treatment refractory and emerging therapies should be considered. Three emerging monoclonal antibody-based therapies are discussed: the anti-B-cell agent rituximab; the terminal complement activation inhibitor eculizumab; and belimumab, which targets B-cell activating factor. Increased understanding of molecular pathophysiology and accurate antibody subtyping in MG should lead to the use of new therapeutic agents and successful management of treatment-refractory patients. PMID:29403543

Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells.

Science.gov (United States)

Cheng, Wan-Li; Huang, Chien-Yu; Tai, Cheng-Jeng; Chang, Yu-Jia; Hung, Chin-Sheng

2018-02-01

Androgen deprivation therapy remains the principal treatment for patients with advanced prostate cancer, though, most patients will eventually develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated maspin-induction has been identified in cancer patients. However, the role of maspin on the anticancer activity of curcumin derived from turmeric (Curcuma longa) in HRPC cells has not been elucidated. The anticancer action of curcumin in hormone-independent prostate cancer cells (DU145, and PC-3) was determined by measures of cell survival rate. The cause of maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was evaluated by measures of cell survival rate, cell-cycle distribution, and apoptosis signaling analysis. Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression). RNA interference-mediated maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with control cells. Maspin can enhance the sensitivity of HRPC cells to curcumin treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Vorinostat Combined with High-Dose Gemcitabine, Busulfan, and Melphalan with Autologous Stem Cell Transplantation in Patients with Refractory Lymphomas.

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Nieto, Yago; Valdez, Benigno C; Thall, Peter F; Ahmed, Sairah; Jones, Roy B; Hosing, Chitra; Popat, Uday; Shpall, Elizabeth J; Qazilbash, Muzaffar; Gulbis, Alison; Anderlini, Paolo; Alousi, Amin; Shah, Nina; Bashir, Qaiser; Liu, Yan; Oki, Yasuhiro; Hagemeister, Frederick; Fanale, Michelle; Dabaja, Bouthaina; Pinnix, Chelsea; Champlin, Richard; Andersson, Borje S

2015-11-01

More active high-dose regimens are needed for refractory/poor-risk relapsed lymphomas. We previously developed a regimen of infusional gemcitabine/busulfan/melphalan, exploiting the synergistic interaction. Its encouraging activity in refractory lymphomas led us to further enhance its use as a platform for epigenetic modulation. We previously observed increased cytotoxicity in refractory lymphoma cell lines when the histone deacetylase inhibitor vorinostat was added to gemcitabine/busulfan/melphalan, which prompted us to clinically study this four-drug combination. Patients ages 12 to 65 with refractory diffuse large B cell lymphoma (DLCL), Hodgkin (HL), or T lymphoma were eligible. Vorinostat was given at 200 mg/day to 1000 mg/day (days -8 to -3). Gemcitabine was infused continuously at 10 mg/m(2)/minute over 4.5 hours (days -8 and -3). Busulfan dosing targeted 4000 μM-minute/day (days -8 to -5). Melphalan was infused at 60 mg/m(2)/day (days -3 and -2). Patients with CD20(+) tumors received rituximab (375 mg/m(2), days +1 and +8). We enrolled 78 patients: 52 DLCL, 20 HL, and 6 T lymphoma; median age 44 years (range, 15 to 65); median 3 prior chemotherapy lines (range, 2 to 7); and 48% of patients had positron emission tomography-positive tumors at high-dose chemotherapy (29% unresponsive). The vorinostat dose was safely escalated up to 1000 mg/day, with no treatment-related deaths. Toxicities included mucositis and dermatitis. Neutrophils and platelets engrafted promptly. At median follow-up of 25 (range, 16 to 41) months, event-free and overall survival were 61.5% and 73%, respectively (DLCL) and 45% and 80%, respectively (HL). In conclusion, vorinostat/gemcitabine/busulfan/melphalan is safe and highly active in refractory/poor-risk relapsed lymphomas, warranting further evaluation. This trial was registered at ClinicalTrials.gov (NCI-2011-02891). Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights

Stem Cells in the Treatment of Refractory Chronic Migraines

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Alexander Mauskop

2017-06-01

Full Text Available Background: Autologous adipose-derived stromal vascular fraction (SVF, which is rich in mesenchymal stromal cells, has been reported to be effective for the treatment of trigeminal neuropathic pain and chronic migraine and tension-type headaches. It is possible that stem cell activity targets neurogenic inflammation, which is a well-documented aspect of migraine pathogenesis. Methods: Adult patients with severe migraine-related disability as measured by the Migraine Disability Assessment (MIDAS score who failed botulinum toxin injections and at least 3 prophylactic drugs were included in this study. The primary outcome measure was the change in MIDAS score 3 months after treatment. Standard liposuction was performed to obtain adipose tissue, from which SVF was isolated by centrifugation. A sample of each patient’s SVF was tested for the number of nucleated cells and their viability. Between 8 and 10 mL of SVF with 2.5–8.6 million viable cells were injected into the pericranial, neck, and trapezius muscles. Results: One man and 8 women were enrolled in the study. The mean age was 48 years, the mean duration of headaches was 16 years, the mean number of prophylactic drugs tried was 10, and the mean MIDAS score at baseline was 122. Three months after the procedure the mean MIDAS score was 88. Seven out of 9 patients had a decrease in their MIDAS score, but only 2 had meaningful improvement. Conclusion: The use of autologous adipose-derived SVF may be effective in the treatment of chronic refractory migraines. It is possible that the use of allogenic stem cells could offer a more practical and more effective approach.

Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

Science.gov (United States)

2017-11-29

; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage

Refractory Materials for Flame Deflector Protection System Corrosion Control: Refractory Ceramics Literature Survey

Science.gov (United States)

Calle, Luz Marina; Hintze, Paul E.; Parlier, Christopher R.; Curran, Jerome P.; Kolody, Mark; Perusich, Stephen; Whitten, Mary C.; Trejo, David; Zidek, Jason; Sampson, Jeffrey W.;

Refractory vasculitis

NARCIS (Netherlands)

Rutgers, Bram; Kallenberg, Cees G. M.

Refractory vasculitis occurs in 4-5% of patients with anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Differences between therapies used for refractory disease are mostly reflected in the percentages of complete and partial remissions, but also in the number of serious side

Density Anomalies in the Mantle and the Gravitational Core-Mantle Interaction

Science.gov (United States)

Kuang, Weijia; Liu, Lanbo

2003-01-01

Seismic studies suggest that the bulk of the mantle is heterogeneous, with density variations in depth as well as in horizontal directions (latitude and longitude). This density variation produces a three- dimensional gravity field throughout the Earth. On the other hand, the core density also varies in both time and space, due to convective core flow. Consequently, the fluid outer core and the solid mantle interact gravitationally due to the mass anomalies in both regions. This gravitational core-mantle interaction could play a significant role in exchange of angular momentum between the core and the mantle, and thus the change in Earth's rotation on time scales of decades and longer. Aiming at estimating the significance of the gravitational core-mantle interaction on Earth's rotation variation, we introduce in our MoSST core dynamics model a heterogeneous mantle, with a density distribution derived from seismic results. In this model, the core convection is driven by the buoyancy forces. And the density variation is determined dynamically with the convection. Numerical simulation is carried out with different parameter values, intending to extrapolate numerical results for geophysical implications.

Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma.

Science.gov (United States)

Moccia, Alden A; Hitz, Felicitas; Hoskins, Paul; Klasa, Richard; Power, Maryse M; Savage, Kerry J; Shenkier, Tamara; Shepherd, John D; Slack, Graham W; Song, Kevin W; Gascoyne, Randy D; Connors, Joseph M; Sehn, Laurie H

2017-02-01

The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83 HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

Safety and Efficacy of Pralatrexate in the Management of Relapsed or Refractory Peripheral T-cell Lymphoma

OpenAIRE

Tom C. Karagiannis; Katherine Ververis; Annabelle L. Rodd

2012-01-01

Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas, with generally poor prognosis. Historically, there has been a lack of consensus regarding appropriate therapeutic measures for the disease, with conventional frontline chemotherapies being utilized in most cases. Following promising results obtained in 2009, the methotrexate analogue, pralatrexate, became the first drug to gain US FDA approval for the treatment of refractory PTCL. This...

Upper mantle fluids evolution, diamond formation, and mantle metasomatism

Science.gov (United States)

Huang, F.; Sverjensky, D. A.

2017-12-01

During mantle metasomatism, fluid-rock interactions in the mantle modify wall-rock compositions. Previous studies usually either investigated mineral compositions in xenoliths and xenocrysts brought up by magmas, or examined fluid compositions preserved in fluid inclusions in diamonds. However, a key study of Panda diamonds analysed both mineral and fluid inclusions in the diamonds [1] which we used to develop a quantitative characterization of mantle metasomatic processes. In the present study, we used an extended Deep Earth Water model [2] to simulate fluid-rock interactions at upper mantle conditions, and examine the fluids and mineral assemblages together simultaneously. Three types of end-member fluids in the Panda diamond fluid inclusions include saline, rich in Na+K+Cl; silicic, rich in Si+Al; and carbonatitic, rich in Ca+Mg+Fe [1, 3]. We used the carbonatitic end-member to represent fluid from a subducting slab reacting with an excess of peridotite + some saline fluid in the host environment. During simultaneous fluid mixing and reaction with the host rock, the logfO2 increased by about 1.6 units, and the pH increased by 0.7 units. The final minerals were olivine, garnet and diamond. The Mg# of olivine decreased from 0.92 to 0.85. Garnet precipitated at an early stage, and its Mg# also decreased with reaction progress, in agreement with the solid inclusions in the Panda diamonds. Phlogopite precipitated as an intermediate mineral and then disappeared. The aqueous Ca, Mg, Fe, Si and Al concentrations all increased, while Na, K, and Cl concentrations decreased during the reaction, consistent with trends in the fluid inclusion compositions. Our study demonstrates that fluids coming from subducting slabs could trigger mantle metasomatism, influence the compositions of sub-lithospherc cratonic mantle, precipitate diamonds, and change the oxygen fugacity and pH of the upper mantle fluids. [1] Tomlinson et al. EPSL (2006); [2] Sverjensky, DA et al., GCA (2014

Pharmacotherapy for Refractory and Super-Refractory Status Epilepticus in Adults.

Science.gov (United States)

Holtkamp, Martin

2018-03-01

Patients with prolonged seizures that do not respond to intravenous benzodiazepines and a second-line anticonvulsant suffer from refractory status epilepticus and those with seizures that do not respond to continuous intravenous anesthetic anticonvulsants suffer from super-refractory status epilepticus. Both conditions are associated with significant morbidity and mortality. A strict pharmacological treatment regimen is urgently required, but the level of evidence for the available drugs is very low. Refractory complex focal status epilepticus generally does not require anesthetics, but all intravenous non-anesthetizing anticonvulsants may be used. Most descriptive data are available for levetiracetam, phenytoin and valproate. Refractory generalized convulsive status epilepticus is a life-threatening emergency, and long-term clinical consequences are eminent. Administration of intravenous anesthetics is mandatory, and drugs acting at the inhibitory gamma-aminobutyric acid (GABA) A receptor such as midazolam, propofol and thiopental/pentobarbital are recommended without preference for one of those. One in five patients with anesthetic treatment does not respond and has super-refractory status epilepticus. With sustained seizure activity, excitatory N-methyl-d-aspartate (NMDA) receptors are increasingly expressed post-synaptically. Ketamine is an antagonist at this receptor and may prove efficient in some patients at later stages. Neurosteroids such as allopregnanolone increase sensitivity at GABA A receptors; a Phase 1/2 trial demonstrated safety and tolerability, but randomized controlled data failed to demonstrate efficacy. Adjunct ketogenic diet may contribute to termination of difficult-to-treat status epilepticus. Randomized controlled trials are needed to increase evidence for treatment of refractory and super-refractory status epilepticus, but there are multiple obstacles for realization. Hitherto, prospective multicenter registries for pharmacological

Molybdenum isotope fractionation in the mantle

Science.gov (United States)

Liang, Yu-Hsuan; Halliday, Alex N.; Siebert, Chris; Fitton, J. Godfrey; Burton, Kevin W.; Wang, Kuo-Lung; Harvey, Jason

2017-02-01

concentrations of all the ultramafic xenoliths of 40-400 ppb, similar to or, significantly higher than, current estimates for the BSE (39 ppb). On this basis a revised best estimate of the Mo content in the BSE based on these concentrations would be in the range 113-180 ppb, significantly higher than previously assumed. These values are similar to the levels of depletion in the other refractory moderately siderophile elements W, Ni and Co. A simpler explanation may be that the subcontinental lithospheric mantle has been selectively enriched in Mo leading to the higher concentrations observed. Cryptic melt metasomatism would be difficult to reconcile with the high Mo/Ce of the most LREE depleted xenoliths. Ancient Mo-enriched subducted components would be expected to have heavy δ98/95Mo, which is not observed. The Mo isotope composition of the BSE, cannot be reliably resolved from that of chondrites at this time despite experimental evidence for metal-silicate fractionation. An identical isotopic composition might result from core-mantle differentiation under very high temperatures such as were associated with the Moon-forming Giant Impact, or from the BSE inventory reflecting addition of moderately siderophile elements from an oxidised Moon-forming impactor (O'Neill, 1991). However, the latter would be inconsistent with the non-chondritic radiogenic W isotopic composition of the BSE. Based on mantle fertility arguments, Mo in the BSE could even be lighter (lower 98/95Mo) than that in chondrites, which might be explained by loss of S rich liquids from the BSE during core formation (Wade et al., 2012). Such a late removal model is no longer required to explain the Mo concentration of the BSE if its abundance is in fact much higher, and similar to the values for ultramafic xenoliths.

Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China

Directory of Open Access Journals (Sweden)

Yuankai Shi

2017-03-01

Full Text Available Abstract The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL. This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256, the overall response rate (ORR and disease control rate (DCR were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127. For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS was 129 (95% CI 82 to 194 days for the monotherapy group and 152 (95% CI 93 to 201 days for the combined therapy group (P = 0.3266. Most adverse events (AEs were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2% and neutropenia (6.2%. For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%, neutropenia (12.6%, anemia (7.1%, and fatigue (5.5%. This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.

Dehydration of δ-AlOOH in the lower mantle

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Piet, H.; Shim, S. H.; Tappan, J.; Leinenweber, K. D.; Greenberg, E.; Prakapenka, V. B.

2017-12-01

Hydrous phase δ-AlOOH is an important candidate for water transport and storage in the Earth's deep mantle [1]. Knowing the conditions, under which it is stable and dehydrated, is therefore important for understanding the water transportation to the deep mantle or even to the core. A few experimental studies [1, 2] have shown that δ-AlOOH may be stable in cold descending slabs while it is dehydrated into a mixture of corundum and water under normal mantle conditions, up to 25 GPa. A subsequent study [3] reported the stability of δ-AlOOH in cold descending slabs to the core-mantle boundary conditions (2300 K at 135 GPa). However, the dehydration of δ-AlOOH has not bee directly observed in the experiments conducted at pressures above 25 GPa. We have synthesized δ-AlOOH from diaspore and Al(OH)3 in multi-anvil press at ASU. The sample was mixed with Au for coupling with near IR laser beams and loaded in diamond-anvil cells. We performed the laser-heated diamond anvil cell experiments at the 13IDD beamline of the Advanced Photon Source and ASU. At APS, we measured X-ray diffraction patterns at in situ high pressure and temperature. We observed the appearance of the corundum diffraction lines at 1700-2000 K and 55-90 GPa, indicating the dehydration of δ-AlOOH to Al2O3+ H2O. We found that the transition occurs over a broad range of temperature (500 K). We also observed that the dehydration of δ-AlOOH was accompanied by sudden change in laser coupling, most likely due to the release of fluids. The property change also helps us to determine the dehydration at ASU without in situ XRD. Our new experimental results indicate that δ-AlOOH would be stable in most subducting slabs in the deep mantle. However, because the dehydration occurs very close to the temperatures expected for the lower mantle, its stability is uncertain in the normal mantle. [1] Ohtani et al. 2001, Stability field of new hydrous phase, delta-AlOOH, Geophysical Research Letters 28, 3991-3993. [2

Two-component mantle melting-mixing model for the generation of mid-ocean ridge basalts: Implications for the volatile content of the Pacific upper mantle

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Shimizu, Kei; Saal, Alberto E.; Myers, Corinne E.; Nagle, Ashley N.; Hauri, Erik H.; Forsyth, Donald W.; Kamenetsky, Vadim S.; Niu, Yaoling

2016-03-01

We report major, trace, and volatile element (CO2, H2O, F, Cl, S) contents and Sr, Nd, and Pb isotopes of mid-ocean ridge basalt (MORB) glasses from the Northern East Pacific Rise (NEPR) off-axis seamounts, the Quebrada-Discovery-GoFar (QDG) transform fault system, and the Macquarie Island. The incompatible trace element (ITE) contents of the samples range from highly depleted (DMORB, Th/La ⩽ 0.035) to enriched (EMORB, Th/La ⩾ 0.07), and the isotopic composition spans the entire range observed in EPR MORB. Our data suggest that at the time of melt generation, the source that generated the EMORB was essentially peridotitic, and that the composition of NMORB might not represent melting of a single upper mantle source (DMM), but rather mixing of melts from a two-component mantle (depleted and enriched DMM or D-DMM and E-DMM, respectively). After filtering the volatile element data for secondary processes (degassing, sulfide saturation, assimilation of seawater-derived component, and fractional crystallization), we use the volatiles to ITE ratios of our samples and a two-component mantle melting-mixing model to estimate the volatile content of the D-DMM (CO2 = 22 ppm, H2O = 59 ppm, F = 8 ppm, Cl = 0.4 ppm, and S = 100 ppm) and the E-DMM (CO2 = 990 ppm, H2O = 660 ppm, F = 31 ppm, Cl = 22 ppm, and S = 165 ppm). Our two-component mantle melting-mixing model reproduces the kernel density estimates (KDE) of Th/La and 143Nd/144Nd ratios for our samples and for EPR axial MORB compiled from the literature. This model suggests that: (1) 78% of the Pacific upper mantle is highly depleted (D-DMM) while 22% is enriched (E-DMM) in volatile and refractory ITE, (2) the melts produced during variable degrees of melting of the E-DMM controls most of the MORB geochemical variation, and (3) a fraction (∼65% to 80%) of the low degree EMORB melts (produced by ∼1.3% melting) may escape melt aggregation by freezing at the base of the oceanic lithosphere, significantly enriching it in

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib.

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Lee, Chung-Shien; Rattu, Mohammad A; Kim, Sara S

2016-02-01

Ibrutinib, a Bruton's kinase inhibitor, was granted an accelerated approval by the US Food and Drug Administration in November, 2013, for the treatment of relapsed or refractory mantle cell lymphoma and subsequently for the treatment of relapsed refractory chronic lymphocytic leukemia in February, 2014. In the pivotal phase 2 study of 111 patients with relapsed or refractory mantle cell lymphoma, the overall response rate in patients who received ibrutinib 560 mg daily was 68%. The median progression-free survival was 13.9 months, and the overall survival was 58% at 18 months. In a recently published phase 3 trial (RESONATE) that compared ibrutinib and ofatumumab for the treatment of relapsed and refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, ibrutinib at the daily dosage of 420 mg demonstrated a significantly higher overall response rate (43% in ibrutinib vs. 4% in ofatumumab) and a significantly improved overall survival at 12 months (90% ibrutinib vs. 81% ofatumumab). Similar clinical benefits were shown regardless of del (17 p). Ibrutinib was well tolerated, and dose-limiting toxicity was not observed. Ibrutinib has shown durable remission, improved progression-free survival and overall survival, and favorable safety profile in indolent B-cell lymphoid malignancies. Ibrutinib, as a monotherapy, is an effective treatment modality as a salvage therapy for treatment of mantle cell lymphoma and chronic lymphocytic leukemia / small lymphocytic lymphoma, particularly in older patients (age ≥70 years) who are not a candidate for intensive chemotherapy and/or those with del (17 p). In patients with chronic lymphocytic leukemia and del (17 p), the current practice guideline recommends ibrutinib as an upfront treatment option. Current on-going trials will further define its role as upfront therapy and/or as a combination therapy in indolent B-cell lymphoid malignancies. © The Author(s) 2014.

Autoradiographic study of corrosion of refractories

International Nuclear Information System (INIS)

Lisenenkova, S.B.; Kucheryavyi, M.N.; Bursteva, T.A.

1988-01-01

A comparative study was made of the character of the interaction between a container-glass melt consisting of sodium calcium silicate and refractories in various furnace sections using an autoradiographic method. Static tests were conducted on specimens of the following refractories: chrome-aluminum-zircon, Bakor 41, corundum, a high alumina refractory, and a refractory based on tin dioxide. The specimens were activated by calcium 45. Autoradiography and photomicrography indicated that an intrinsic feature of all refractories was that calcium from the melt penetrated the refractories along the weak link; for fused-cast refractories, the glass phase; and for sintered refractories, through the binder and cracks

Thoracic radiation therapy (RT) before autologous bone marrow transplantation (ABMT) in relapsed or refractory Hodgkin's disease (HD)

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Tsang, Richard W.; Gospodarowicz, Mary K.; Sutcliffe, Simon B.; Crump, Michael; Keating, Armand

1997-01-01

Purpose: To assess the relationship between peri-ABMT RT and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and ABMT for recurrent/refractory HD. Materials and Methods: Between 12/1986 and 12/1992, 90 patients (pts) with HD were treated with HDCT (etoposide 60 mg/kg, melphalan 160 mg/m 2 ) +ABMT in Toronto. Fifty-nine of these had all or part of their treatment (RT and/or CT) at the PMH, and they form the basis of this report. HDCT + ABMT was performed for refractory (11 pts) or relapsed (48 pts) HD. The median age at ABMT was 29 (range 16-47), F:M ratio was 1:1.2. Salvage chemotherapy consisted of DHAP (36), mini-BEAM (7), both (8), other chemotherapy (5), and no chemotherapy (3). RT have been incorporated in the salvage treatment with the intent to achieve complete disease control of active disease at relapse or disease progression. RT was given pre-ABMT in 33 pts (3 mantle, 8 mantle with lung, 7 modified mantle excluding axillae, 4 involved field, 1 mantle with TBI, 1 TBI, and 9 non-thoracic), and post-ABMT in 4 pts (2 mantle, 2 modified mantle). Planned RT tumor dose was 35 Gy over 4 weeks (median 35 Gy, range 25-40 Gy), lower doses were used for lung RT (15-17.5 Gy). Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. Results: We observed 36 deaths, and 10 of these were treatment-related (TR) deaths. With an average follow-up of 4.9 years (range 1.2-7.4 years), the actuarial overall survival was 52% ± 13% at 3 years, and 41% ± 14% at 5 years. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, with 3 solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure as a major medical problem with complicating sepsis and pancytopenia. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 pts with

miR-18b overexpression identifies mantle cell lymphoma patients with poor outcome and improves the MIPI-B prognosticator

DEFF Research Database (Denmark)

Husby, Simon; Ralfkiær, Ulrik Methner; Garde, Christian

2015-01-01

Recent studies show that mantle cell lymphoma (MCL) express aberrant microRNA (miRNA) profiles; however, the clinical effect of miRNA expression has not previously been examined and validated in large prospective homogenously treated cohorts. We performed genome-wide miRNA microarray profiling...... by decelerating cell proliferation. We conclude that overexpression of miR-18b identifies patients with poor prognosis in 2 large prospective MCL cohorts and adds prognostic information to the MIPI-B. MiR-18b may reduce the proliferation rate of MCL cells as a mechanism of chemoresistance....

Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia

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Kuan-Hsiang Lin

2013-05-01

Full Text Available Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory erythromelalgia. The symptoms of erythromelalgia presented as refractory to any medical treatment. Due to the unresponsive nature of her condition, botulinum toxin type A (onabotulinumtoxin A was injected over both of her cheeks, periodically for six cycles. Her symptoms responded dramatically to subcutaneous and intradermal injection of botulinum toxin type A. Repetitive injection demonstrated consistent and reproducible responses, and the efficacy was maintained for approximately 1 month. No adverse effects or complications were noted. Botulinum toxin type A might be safe and effective as an alternative treatment for refractory erythromelalgia, but further large-scale studies are required.

Neuroblastoma Cell Lines Are Refractory to Genotoxic Drug-Mediated Induction of Ligands for NK Cell-Activating Receptors

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Irene Veneziani

2018-01-01

Full Text Available Neuroblastoma (NB, the most common extracranial solid tumor of childhood, causes death in almost 15% of children affected by cancer. Treatment of neuroblastoma is based on the combination of chemotherapy with other therapeutic interventions such as surgery, radiotherapy, use of differentiating agents, and immunotherapy. In particular, adoptive NK cell transfer is a new immune-therapeutic approach whose efficacy may be boosted by several anticancer agents able to induce the expression of ligands for NK cell-activating receptors, thus rendering cancer cells more susceptible to NK cell-mediated lysis. Here, we show that chemotherapeutic drugs commonly used for the treatment of NB such as cisplatin, topotecan, irinotecan, and etoposide are unable to induce the expression of activating ligands in a panel of NB cell lines. Consistently, cisplatin-treated NB cell lines were not more susceptible to NK cells than untreated cells. The refractoriness of NB cell lines to these drugs has been partially associated with the abnormal status of genes for ATM, ATR, Chk1, and Chk2, the major transducers of the DNA damage response (DDR, triggered by several anticancer agents and promoting different antitumor mechanisms including the expression of ligands for NK cell-activating receptors. Moreover, both the impaired production of reactive oxygen species (ROS in some NB cell lines and the transient p53 stabilization in response to our genotoxic drugs under our experimental conditions could contribute to inefficient induction of activating ligands. These data suggest that further investigations, exploiting molecular strategies aimed to potentiate the NK cell-mediated immunotherapy of NB, are warranted.

Neuroblastoma Cell Lines Are Refractory to Genotoxic Drug-Mediated Induction of Ligands for NK Cell-Activating Receptors

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Veneziani, Irene; Brandetti, Elisa; Ognibene, Marzia; Pezzolo, Annalisa; Pistoia, Vito

2018-01-01

Neuroblastoma (NB), the most common extracranial solid tumor of childhood, causes death in almost 15% of children affected by cancer. Treatment of neuroblastoma is based on the combination of chemotherapy with other therapeutic interventions such as surgery, radiotherapy, use of differentiating agents, and immunotherapy. In particular, adoptive NK cell transfer is a new immune-therapeutic approach whose efficacy may be boosted by several anticancer agents able to induce the expression of ligands for NK cell-activating receptors, thus rendering cancer cells more susceptible to NK cell-mediated lysis. Here, we show that chemotherapeutic drugs commonly used for the treatment of NB such as cisplatin, topotecan, irinotecan, and etoposide are unable to induce the expression of activating ligands in a panel of NB cell lines. Consistently, cisplatin-treated NB cell lines were not more susceptible to NK cells than untreated cells. The refractoriness of NB cell lines to these drugs has been partially associated with the abnormal status of genes for ATM, ATR, Chk1, and Chk2, the major transducers of the DNA damage response (DDR), triggered by several anticancer agents and promoting different antitumor mechanisms including the expression of ligands for NK cell-activating receptors. Moreover, both the impaired production of reactive oxygen species (ROS) in some NB cell lines and the transient p53 stabilization in response to our genotoxic drugs under our experimental conditions could contribute to inefficient induction of activating ligands. These data suggest that further investigations, exploiting molecular strategies aimed to potentiate the NK cell-mediated immunotherapy of NB, are warranted. PMID:29805983

Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

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Man-Hsin Hung

2013-04-01

Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

Selected CD133⁺ progenitor cells to promote angiogenesis in patients with refractory angina: final results of the PROGENITOR randomized trial.

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Jimenez-Quevedo, Pilar; Gonzalez-Ferrer, Juan Jose; Sabate, Manel; Garcia-Moll, Xavier; Delgado-Bolton, Roberto; Llorente, Leopoldo; Bernardo, Esther; Ortega-Pozzi, Aranzazu; Hernandez-Antolin, Rosana; Alfonso, Fernando; Gonzalo, Nieves; Escaned, Javier; Bañuelos, Camino; Regueiro, Ander; Marin, Pedro; Fernandez-Ortiz, Antonio; Neves, Barbara Das; Del Trigo, Maria; Fernandez, Cristina; Tejerina, Teresa; Redondo, Santiago; Garcia, Eulogio; Macaya, Carlos

2014-11-07

Refractory angina constitutes a clinical problem. The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133(+) cells to foster angiogenesis in patients with refractory angina. In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133(+) cells or no treatment. The primary end point was the safety of transendocardial injection of CD133(+) cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, -8.5 [95% confidence interval, -15.0 to -4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, -1.0 [95% confidence interval, -1.9 to -0.1]) but not in the control arm. Our findings support feasibility and safety of transendocardial injection of CD133(+) cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial. © 2014 American Heart Association, Inc.

THE REINCARNATION OF INTERSTELLAR DUST: THE IMPORTANCE OF ORGANIC REFRACTORY MATERIAL IN INFRARED SPECTRA OF COMETARY COMAE AND CIRCUMSTELLAR DISKS

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Kimura, Hiroshi, E-mail: hiroshi_kimura@cps-jp.org [Graduate School of Science, Kobe University, c/o CPS (Center for Planetary Science), Chuo-ku Minatojima Minamimachi 7-1-48, Kobe 650-0047 (Japan)

2013-09-20

We consider the reincarnation of interstellar dust to be reborn in protoplanetary disks as aggregates consisting of submicron-sized grains with a crystalline or amorphous silicate core and an organic-rich carbonaceous mantle. We find that infrared spectra of reincarnated interstellar dust reproduce emission peaks at correct wavelengths where the peaks were observed in cometary comae, debris disks, and protoplanetary disks if the volume fraction of organic refractory meets the constraints on elemental abundances. We discuss what we can learn from the infrared spectra of reincarnated interstellar dust in cometary comae and circumstellar disks.

The Reincarnation of Interstellar Dust: The Importance of Organic Refractory Material in Infrared Spectra of Cometary Comae and Circumstellar Disks

Science.gov (United States)

Kimura, Hiroshi

2013-09-01

We consider the reincarnation of interstellar dust to be reborn in protoplanetary disks as aggregates consisting of submicron-sized grains with a crystalline or amorphous silicate core and an organic-rich carbonaceous mantle. We find that infrared spectra of reincarnated interstellar dust reproduce emission peaks at correct wavelengths where the peaks were observed in cometary comae, debris disks, and protoplanetary disks if the volume fraction of organic refractory meets the constraints on elemental abundances. We discuss what we can learn from the infrared spectra of reincarnated interstellar dust in cometary comae and circumstellar disks.

THE REINCARNATION OF INTERSTELLAR DUST: THE IMPORTANCE OF ORGANIC REFRACTORY MATERIAL IN INFRARED SPECTRA OF COMETARY COMAE AND CIRCUMSTELLAR DISKS

International Nuclear Information System (INIS)

Kimura, Hiroshi

2013-01-01

We consider the reincarnation of interstellar dust to be reborn in protoplanetary disks as aggregates consisting of submicron-sized grains with a crystalline or amorphous silicate core and an organic-rich carbonaceous mantle. We find that infrared spectra of reincarnated interstellar dust reproduce emission peaks at correct wavelengths where the peaks were observed in cometary comae, debris disks, and protoplanetary disks if the volume fraction of organic refractory meets the constraints on elemental abundances. We discuss what we can learn from the infrared spectra of reincarnated interstellar dust in cometary comae and circumstellar disks

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia.

Science.gov (United States)

Davila, Marco L; Brentjens, Renier J

2016-10-01

Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable. CD19-targeted CAR T cells have induced complete remissions of disease in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), who have an expected complete response rate of 30% in response to chemotherapy. The high efficacy of CAR T cells in B-ALL suggests that regulatory approval of this therapy for this routinely fatal leukemia is on the horizon. We review the preclinical development of CAR T cells and their early clinical application for lymphoma. We also provide a comprehensive analysis of the use of CAR T cells in patients with B-ALL. In addition, we discuss the unique toxicities associated with this therapy and the management schemes that have been developed.

Mantle dynamics following supercontinent formation

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Heron, Philip J.

This thesis presents mantle convection numerical simulations of supercontinent formation. Approximately 300 million years ago, through the large-scale subduction of oceanic sea floor, continental material amalgamated to form the supercontinent Pangea. For 100 million years after its formation, Pangea remained relatively stationary, and subduction of oceanic material featured on its margins. The present-day location of the continents is due to the rifting apart of Pangea, with supercontinent dispersal being characterized by increased volcanic activity linked to the generation of deep mantle plumes. The work presented here investigates the thermal evolution of mantle dynamics (e.g., mantle temperatures and sub-continental plumes) following the formation of a supercontinent. Specifically, continental insulation and continental margin subduction are analyzed. Continental material, as compared to oceanic material, inhibits heat flow from the mantle. Previous numerical simulations have shown that the formation of a stationary supercontinent would elevate sub-continental mantle temperatures due to the effect of continental insulation, leading to the break-up of the continent. By modelling a vigorously convecting mantle that features thermally and mechanically distinct continental and oceanic plates, this study shows the effect of continental insulation on the mantle to be minimal. However, the formation of a supercontinent results in sub-continental plume formation due to the re-positioning of subduction zones to the margins of the continent. Accordingly, it is demonstrated that continental insulation is not a significant factor in producing sub-supercontinent plumes but that subduction patterns control the location and timing of upwelling formation. A theme throughout the thesis is an inquiry into why geodynamic studies would produce different results. Mantle viscosity, Rayleigh number, continental size, continental insulation, and oceanic plate boundary evolution are

Genomic Instability: The Driving Force behind Refractory/Relapsing Hodgkin’s Lymphoma

International Nuclear Information System (INIS)

Knecht, Hans; Righolt, Christiaan; Mai, Sabine

2013-01-01

In classical Hodgkin’s lymphoma (HL) the malignant mononuclear Hodgkin (H) and multinuclear, diagnostic Reed-Sternberg (RS) cells are rare and generally make up <3% of the total cellular mass of the affected lymph nodes. During recent years, the introduction of laser micro-dissection techniques at the single cell level has substantially improved our understanding of the molecular pathogenesis of HL. Gene expression profiling, comparative genomic hybridization analysis, micro-RNA expression profiling and viral oncogene sequencing have deepened our knowledge of numerous facets of H- and RS-cell gene expression deregulation. The question remains whether disturbed signaling pathways and deregulated transcription factors are at the origin of refractory/relapsing Hodgkin’s lymphoma or whether these hallmarks are at least partially related to another major factor. We recently showed that the 3D nuclear organization of telomeres and chromosomes marked the transition from H- to RS-cells in HL cell lines. This transition is associated with progression of telomere dysfunction, shelterin disruption and progression of complex chromosomal rearrangements. We reported analogous findings in refractory/relapsing HL and identified the shelterin proteins TRF1, TRF2 and POT1 as targets of the LMP1 oncogene in post-germinal center B-cells. Here we summarize our findings, including data not previously published, and propose a model in which progressive disruption of nuclear integrity, a form of genomic instability, is the key-player in refractory/relapsing HL. Therapeutic approaches should take these findings into account

Development Refractoriness of MLL-Rearranged Human B Cell Acute Leukemias to Reprogramming into Pluripotency

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Alvaro Muñoz-López

2016-10-01

Full Text Available Induced pluripotent stem cells (iPSCs are a powerful tool for disease modeling. They are routinely generated from healthy donors and patients from multiple cell types at different developmental stages. However, reprogramming leukemias is an extremely inefficient process. Few studies generated iPSCs from primary chronic myeloid leukemias, but iPSC generation from acute myeloid or lymphoid leukemias (ALL has not been achieved. We attempted to generate iPSCs from different subtypes of B-ALL to address the developmental impact of leukemic fusion genes. OKSM(L-expressing mono/polycistronic-, retroviral/lentiviral/episomal-, and Sendai virus vector-based reprogramming strategies failed to render iPSCs in vitro and in vivo. Addition of transcriptomic-epigenetic reprogramming “boosters” also failed to generate iPSCs from B cell blasts and B-ALL lines, and when iPSCs emerged they lacked leukemic fusion genes, demonstrating non-leukemic myeloid origin. Conversely, MLL-AF4-overexpressing hematopoietic stem cells/B progenitors were successfully reprogrammed, indicating that B cell origin and leukemic fusion gene were not reprogramming barriers. Global transcriptome/DNA methylome profiling suggested a developmental/differentiation refractoriness of MLL-rearranged B-ALL to reprogramming into pluripotency.

Mechanical Stimulation in Preventing Bone Density Loss in Patients Undergoing Donor Stem Cell Transplant

Science.gov (United States)

2012-07-05

Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Malignant Testicular Germ Cell Tumor; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Small Lymphocytic Lymphoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Breast Cancer; Stage IV Chronic Lymphocytic Leukemia

Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement

International Nuclear Information System (INIS)

Lee, Seung Sook; Cho, Kyung Ja; Lee, Sun Joo

1996-12-01

We reclassified a large series of non-Hogkin's lymphoma diagnosed at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification, and compared the efficacy of immunohistochemical study for cyclin D1 protein and PCR for bcl-1 gene rearrangement to diagnose mantle cell lymphoma (MCL). By REAL classification, 7 %, diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified (10%) and angiocentric lymphoma (7.5%). The most reliable histologic finding was mitosis to make a differential diagnosis. Mitoses of MCL were 17/10 HPF in average and all the cases showed more than 10/10 HPF. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclin D1 was the most important for diagnosis of MCL . Both immunohistochemistry for cyclin D1 and PCR for bcl-1 were specific for MCL and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL + MALT + LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclin D1 has a practical usefulness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management. (author). 27 refs., 6 tabs., 4 figs

Diagnosis of mantle cell lymphoma and detection of bcl-1 gene rearrangement

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Lee, Seung Sook; Cho, Kyung Ja; Lee, Sun Joo [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

1996-12-01

We reclassified a large series of non-Hogkin`s lymphoma diagnosed at Korea Cancer Center Hospital from 1991 to 1995, according to REAL classification, and compared the efficacy of immunohistochemical study for cyclin D1 protein and PCR for bcl-1 gene rearrangement to diagnose mantle cell lymphoma (MCL). By REAL classification, 7 %, diffuse large B-cell lymphoma was the most common type (51.8%) and was followed by peripheral T-cell lymphoma-unspecified (10%) and angiocentric lymphoma (7.5%). The most reliable histologic finding was mitosis to make a differential diagnosis. Mitoses of MCL were 17/10 HPF in average and all the cases showed more than 10/10 HPF. Immunophenotypic study alone cannot lead to a differential diagnosis between MCL and SLL, and the overexpression of cyclin D1 was the most important for diagnosis of MCL . Both immunohistochemistry for cyclin D1 and PCR for bcl-1 were specific for MCL and immunohistochemistry was more sensitive than PCR. Statistical analysis showed a different survival rate between MCL and the other low-grade B-cell lymphomas (SLL + MALT + LPL) and a difference between MCL and SLL. Immunohistochemical detection of cyclin D1 has a practical usefulness in making routine diagnosis of MCL. The initial accurate diagnosis of MCL will help clinicians make a proper management. (author). 27 refs., 6 tabs., 4 figs.

P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines

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Shirsath Nitesh P

2012-10-01

Full Text Available Abstract Background Mantle cell lymphoma (MCL is a well-defined aggressive lymphoid neoplasm characterized by proliferation of mature B-lymphocytes that have a remarkable tendency to disseminate. This tumor is considered as one of the most aggressive lymphoid neoplasms with poor responses to conventional chemotherapy and relatively short survival. Since cyclin D1 and cell cycle control appears as a natural target, small-molecule inhibitors of cyclin-dependent kinases (Cdks and cyclins may play important role in the therapy of this disorder. We explored P276-00, a novel selective potent Cdk4-D1, Cdk1-B and Cdk9-T1 inhibitor discovered by us against MCL and elucidated its potential mechanism of action. Methods The cytotoxic effect of P276-00 in three human MCL cell lines was evaluated in vitro. The effect of P276-00 on the regulation of cell cycle, apoptosis and transcription was assessed, which are implied in the pathogenesis of MCL. Flow cytometry, western blot, immunoflourescence and siRNA studies were performed. The in vivo efficacy and effect on survival of P276-00 was evaluated in a Jeko-1 xenograft model developed in SCID mice. PK/PD analysis of tumors were performed using LC-MS and western blot analysis. Results P276-00 showed a potent cytotoxic effect against MCL cell lines. Mechanistic studies confirmed down regulation of cell cycle regulatory proteins with apoptosis. P276-00 causes time and dose dependent increase in the sub G1 population as early as from 24 h. Reverse transcription PCR studies provide evidence that P276-00 treatment down regulated transcription of antiapoptotic protein Mcl-1 which is a potential pathogenic protein for MCL. Most importantly, in vivo studies have revealed significant efficacy as a single agent with increased survival period compared to vehicle treated. Further, preliminary combination studies of P276-00 with doxorubicin and bortezomib showed in vitro synergism. Conclusion Our studies thus provide

Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does affect IL-2/IFN-γ expression of T cells in vitro?: A prospective, randomized, double-blind study.

Science.gov (United States)

Zhou, Naibao; Fu, Zhijian; Li, Hao; Wang, Kaiguo

2017-04-01

Ketamine has been used as an analgesic adjuvant with morphine in the treatment of refractory cancer pain recently. But both morphine and ketamine have been reported to produce a number of immunomodulatory effects. The current study was performed to assess whether the concentration of ketamine, as adjuvant analgesics for patient with refractory cancer pain, was related to its effect on T cells interleukin-2 (IL-2)/interferon-γ (IFN-γ) expression in vitro. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood of patients with refractory cancer pain over a Ficoll-Hypaque density gradient. T cells were isolated from by positive selection using anti-CD3 beads. T cells were then treated with vehicle (C group), morphine (200 ng/mL, M group), morphine (200 ng/mL), and different dose of ketamine (100, 200, 1000 ng/mL; MK1, MK5, MK10 group) for 24 hours before stimulation with anti-CD3 and anti-CD28. Then supernatant IL-2 and IFN-γ protein analysis, quantitative reverse transcription polymerase chain reaction (RT-PCR) for IL-2 and IFN-γ were done. There were no significant difference of supernatant IL-2 and IFN-γ among C group, M group, and MK1 group, but the mRNA of M group and MK1 group were decreased compared with C group (P ketamine dose-dependently suppressed IL-2 and IFN-γ of activated T lymphocyte of patients with refractory cancer pain in vitro, but the inhibitory action of low dose ketamine could be neglected.

Heat transfer correlations in mantle tanks

DEFF Research Database (Denmark)

Furbo, Simon; Knudsen, Søren

2005-01-01

on calculations with a CFD-model, which has earlier been validated by means of experiments. The CFD-model is used to determine the heat transfer between the solar collector fluid in the mantle and the walls surrounding the mantle in all levels of the mantle as well as the heat transfer between the wall...... transfer correlations are suitable as input for a detailed simulation model for mantle tanks. The heat transfer correlations determined in this study are somewhat different from previous reported heat transfer correlations. The reason is that this study includes more mantle tank designs and operation......Small solar domestic hot water systems are best designed as low flow systems based on vertical mantle tanks. Theoretical investigations of the heat transfer in differently designed vertical mantle tanks during different operation conditions have been carried out. The investigations are based...

Detection of Active Epstein-Barr Virus Infection in Duodenal Mucosa of Patients With Refractory Celiac Disease.

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Perfetti, Vittorio; Baldanti, Fausto; Lenti, Marco Vincenzo; Vanoli, Alessandro; Biagi, Federico; Gatti, Marta; Riboni, Roberta; Dallera, Elena; Paulli, Marco; Pedrazzoli, Paolo; Corazza, Gino Roberto

2016-08-01

Refractory celiac disease is characterized by mucosal damage in patients with celiac disease despite a gluten-free diet. Little is known about the mechanisms that cause persistent intestinal inflammation in these patients. We performed a case-control study of 17 consecutive patients diagnosed with refractory celiac disease from 2001 through 2014 (median age, 51 y; 10 women) and 24 patients with uncomplicated celiac disease (controls) to determine whether refractory disease is associated with infection by lymphotropic oncogenic viruses. We performed real-time PCR analyses of duodenal biopsy samples from all patients to detect Epstein-Barr virus (EBV), human herpesvirus-8, and human T-cell lymphotropic virus-I, -II, or -III. We used in situ hybridization and immunohistochemical analyses to identify infected cells and viral proteins. We did not detect human herpesvirus-8 or human T-cell lymphotropic viruses in any of the biopsy specimens. However, 12 of 17 (70.5%) biopsy specimens from patients with refractory celiac disease were positive for EBV, compared with 4 of 24 (16.6%) biopsy specimens from controls (P disease and enteropathy-associated T-cell lymphoma. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

DHAP plus filgrastim as an effective peripheral stem cell mobilization regimen for autologous stem-cell transplantation in patients with relapsed/refractory lymphoma: A single center experience.

Science.gov (United States)

Berber, Ilhami; Erkurt, Mehmet Ali; Kuku, Irfan; Kaya, Emin; Bag, Harika Gozukara; Nizam, Ilknur; Koroglu, Mustafa; Ozgul, Mustafa

2016-02-01

This study aimed to evaluate the efficiency of DHAP regimen plus filgrastim for mobilization of stem cells in patients with recurrent and/or refractory lymphoma. Thirty-four patients who took DHAP as salvage therapy prior to autologous stem cell transplantation were included. After chemotherapies, 2 cycles of DHAP plus filgrastim were administered to the patients. Stem cells from 32 patients (94%) were collected on median 11th day (8-12), and the median collected CD34(+) cell dose was 9.7 × 10(6)/kg (range 3.8-41.6). DHAP plus filgrastim was found to be an effective chemotherapy regimen in mobilizing CD34(+) stem cells into the peripheral. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evolution of the earliest mantle caused by the magmatism-mantle upwelling feedback: Implications for the Moon and the Earth

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Ogawa, M.

2017-12-01

The two most important agents that cause mantle evolution are magmatism and mantle convection. My earlier 2D numerical models of a coupled magmatism-mantle convection system show that these two agents strongly couple each other, when the Rayleigh number Ra is sufficiently high: magmatism induced by a mantle upwelling flow boosts the upwelling flow itself. The mantle convection enhanced by this positive feedback (the magmatism-mantle upwelling, or MMU, feedback) causes vigorous magmatism and, at the same time, strongly stirs the mantle. I explored how the MMU feedback influences the evolution of the earliest mantle that contains the magma ocean, based on a numerical model where the mantle is hot and its topmost 1/3 is partially molten at the beginning of the calculation: The evolution drastically changes its style, as Ra exceeds the threshold for onset of the MMU feedback, around 107. At Ra 107, however, the mantle remains compositionally more homogeneous in spite of the widespread magmatism, and the deep mantle remains hotter than the shallow mantle, because of the strong convective stirring caused by the feedback. The threshold value suggests that the mantle of a planet larger than Mars evolves in a way substantially different from that in the Moon does. Indeed, in my earlier models, magmatism makes the early mantle compositionally stratified in the Moon, but the effects of strong convective stirring overwhelms that of magmatism to keep the mantle compositionally rather homogeneous in Venus and the Earth. The MMU feedback is likely to be a key to understanding why vestiges of the magma ocean are so scarce in the Earth.

Spin Transition in the Lower Mantle: Deep Learning and Pattern Recognition of Superplumes from the Mid-mantle and Mid-mantle Slab Stagnation

Science.gov (United States)

Yuen, D. A.; Shahnas, M. H.; De Hoop, M. V.; Pysklywec, R.

2016-12-01

The broad, slow seismic anomalies under Africa and Pacific cannot be explained without ambiguity. There is no well-established theory to explain the fast structures prevalent globally in seismic tomographic images that are commonly accepted to be the remnants of fossil slabs at different depths in the mantle. The spin transition from high spin to low spin in iron in ferropericlase and perovskite, two major constituents of the lower mantle can significantly impact their physical properties. We employ high resolution 2D-axisymmetric and 3D-spherical control volume models to reconcile the influence of the spin transition-induced anomalies in density, thermal expansivity, and bulk modulus in ferropericlase and perovskite on mantle dynamics. The model results reveal that the spin transition effects increase the mixing in the lower regions of mantle. Depending on the changes of bulk modulus associated with the spin transition, these effects may also cause both stagnation of slabs and rising plumes at mid-mantle depths ( 1600 km). The stagnation may be followed by downward or upward penetration of cold or hot mantle material, respectively, through an avalanche process. The size of these mid-mantle plumes reaches 1500 km across with a radial velocity reaching 20 cm/yr near the seismic transition zone and plume heads exceeding 2500 km across. We will employ a deep-learning algorithm to formulate this challenge as a classification problem where modelling/computation aids in the learning stage for detecting the particular patterns.The parameters based on which the convection models are developed are poorly constrained. There are uncertainties in initial conditions, heterogeneities and boundary conditions in the simulations, which are nonlinear. Thus it is difficult to reconstruct the past configuration over long time scales. In order to extract information and better understand the parameters in mantle convection, we employ deep learning algorithm to search for different

The Earth's mantle and geoneutrinos

International Nuclear Information System (INIS)

Fiorentini, Giovanni; Fogli, Gian Luigi; Lisi, Eligio; Mantovani, Fabio; Rotunno, Anna Maria; Xhixha, Gerti

2013-01-01

The KamLAND and Borexino experiments have observed, each at ∼4σ level, signals of electron antineutrinos produced in the decay chains of thorium and uranium in the Earth's crust and mantle (Th and U geoneutrinos). Various pieces of geochemical and geophysical information allow an estimation of the crustal geoneutrino flux components with relatively small uncertainties. The mantle component may then be inferred by subtracting the estimated crustal flux from the measured total flux. We find that crust-subtracted signals show hints of a residual mantle component, emerging at ∼2.4σ level by combining the KamLAND and Borexino data. The inferred mantle flux, slightly favoring scenarios with relatively high Th and U abundances, within ∼1σ uncertainties is comparable to the predictions from recent mantle models

Mantle wedge serpentinization effects on slab dips

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Eh Tan

2017-01-01

Full Text Available The mechanical coupling between a subducting slab and the overlying mantle wedge is an important factor in controlling the subduction dip angle and the flow in mantel wedge. This paper investigates the role of the amount of mantle serpentinization on the subduction zone evolution. With numerical thermos-mechanical models with elasto-visco-plastic rheology, we vary the thickness and depth extent of mantle serpentinization in the mantle wedge to control the degree of coupling between the slab and mantle wedge. A thin serpentinized mantle layer is required for stable subduction. For models with stable subduction, we find that the slab dip is affected by the down-dip extent and the mantle serpentinization thickness. A critical down-dip extent exists in mantle serpentinization, determined by the thickness of the overriding lithosphere. If the down-dip extent does not exceed the critical depth, the slab is partially coupled to the overriding lithosphere and has a constant dip angle regardless of the mantle serpentinization thickness. However, if the down-dip extent exceeds the critical depth, the slab and the base of the overriding lithosphere would be separated and decoupled by a thick layer of serpentinized peridotite. This allows further slab bending and results in steeper slab dip. Increasing mantle serpentinization thickness will also result in larger slab dip. We also find that with weak mantle wedge, there is no material flowing from the asthenosphere into the serpentinized mantle wedge. All of these results indicate that serpentinization is an important ingredient when studying the subduction dynamics in the mantle wedge.

Plasma spraying of refractory metals and refractory hard materials. State of the art

International Nuclear Information System (INIS)

Eschnauer, H.; Lugscheider, E.; Jaeger, D.

1989-01-01

Suitable spraying processes for manufacturing refractory metals, refractory hard materials as well as spray materials with refractory components are the VPS- and IPS-spraying techniques. The advantages of these special spraying process variations are described. The reactive spraying materials are systematically organized. The characteristical properties used in purpose of improving the substrate surfaces are explained. Finally some examples of the latest results of research concerning plasma spraying of reactive materials are shown. 16 refs., 10 figs. (Author)

Safety and efficacy of pralatrexate in the management of relapsed or refractory peripheral T-cell lymphoma.

Science.gov (United States)

Rodd, Annabelle L; Ververis, Katherine; Karagiannis, Tom C

2012-01-01

Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas, with generally poor prognosis. Historically, there has been a lack of consensus regarding appropriate therapeutic measures for the disease, with conventional frontline chemotherapies being utilized in most cases. Following promising results obtained in 2009, the methotrexate analogue, pralatrexate, became the first drug to gain US FDA approval for the treatment of refractory PTCL. This antimetabolite was designed to have a higher affinity for reduced folate carrier (RFC) and folylpolyglutamate synthetase (FPGS). RFC is the principal transporter for cell entrance of folates and antifolates. Once inside the cell, pralatrexate is efficiently polyglutamated by FPGS. Pralatrexate has demonstrated varying degrees of efficacy in peripheral T-cell lymphoma, with response rates differing between the multiple subtypes of the disease. While phase III studies are still to be completed, early clinical trials indicate that pralatrexate is promising new therapeutic for PTCL.

Chemical provinces and dynamic melting of the NE Atlantic mantle

Science.gov (United States)

Tronnes, R. G.

2009-12-01

Low-degree melting of fertile parts of the NE Atlantic mantle yields primitive alkaline basalts in the Icelandic off-rift zones and at Jan Mayen. Olivine tholeiites in the Icelandic rift zones and oceanic spreading ridges are formed by protracted decompressional melting. The V-shaped ridges SW and NE of Iceland indicate that rising, hot material is supplied by a pulsating plume and deflected laterally for distances of about 1000 km from Iceland (Jones et al. GGG 2002; Breivik et al. JGR 2006). Plume material deflected along the rift zones and spreading ridges undergoes mixing with the ambient asthenosphere and extensive melting at shallow level, whereas material deflected in other directions may flow laterally at deeper levels and remain largely unmelted and fertile. A recent investigation of a suite of primitive off-rift basalts from Iceland and Jan Mayen (Debaille et al., 2009, GCA) demonstrated an important source contribution from subcontinental lithospheric mantle (SCLM). Available data on the primitive off-rift basalts and tholeiitic basalts from Iceland and the NE Atlantic ridges indicates the existence of three main composite mantle components, characterized by the following relative isotope ratios (H: high, I: intermediate and L: low ratio) for 87/86Sr, 143/144Nd, 206/204Pb, 187/188Os and 3/4He, respectively: 1. Iceland plume with depleted lower mantle mixed with recycled oceanic crust: I, I, H, H, H 2. Strongly depleted and later re-enriched SCLM: H, L, I, L, L 3. Depleted asthenosphere: L, H, L, I, L The two first composite components contain enriched and depleted subcomponents with distinct isotope signatures. The isotope ratio variations between the fertile components are larger than between the refractory components. The 3/4He ratio, however, is much higher in the depleted plume component than in the depleted SCLM and asthenospheric components. The old SCLM material could in principle be recycled and embedded in the lower mantle and supplied to the

Eutectic melting temperature of the lowermost Earth's mantle

Science.gov (United States)

Andrault, D.; Lo Nigro, G.; Bolfan-Casanova, N.; Bouhifd, M.; Garbarino, G.; Mezouar, M.

2009-12-01

Partial melting of the Earth's deep mantle probably occurred at different stages of its formation as a consequence of meteoritic impacts and seismology suggests that it even continues today at the core-mantle boundary. Melts are important because they dominate the chemical evolution of the different Earth's reservoirs and more generally the dynamics of the whole planet. Unfortunately, the most critical parameter, that is the temperature profile inside the deep Earth, remains poorly constrained accross the planet history. Experimental investigations of the melting properties of materials representative of the deep Earth at relevant P-T conditions can provide anchor points to refine past and present temperature profiles and consequently determine the degree of melting at the different geological periods. Previous works report melting relations in the uppermost lower mantle region, using the multi-anvil press [1,2]. On the other hand, the pyrolite solidus was determined up to 65 GPa using optical observations in the laser-heated diamond anvil cell (LH-DAC) [3]. Finally, the melting temperature of (Mg,Fe)2SiO4 olivine is documented at core-mantle boundary (CMB) conditions by shock wave experiments [4]. Solely based on these reports, experimental data remain too sparse to draw a definite melting curve for the lower mantle in the relevant 25-135 GPa pressure range. We reinvestigated melting properties of lower mantle materials by means of in-situ angle dispersive X-ray diffraction measurements in the LH-DAC at the ESRF [5]. Experiments were performed in an extended P-T range for two starting materials: forsterite and a glass with chondrite composition. In both cases, the aim was to determine the onset of melting, and thus the eutectic melting temperatures as a function of pressure. Melting was evidenced from drastic changes of diffraction peak shape on the image plate, major changes in diffraction intensities in the integrated pattern, disappearance of diffraction rings

Mantle Convection on Modern Supercomputers

Science.gov (United States)

Weismüller, J.; Gmeiner, B.; Huber, M.; John, L.; Mohr, M.; Rüde, U.; Wohlmuth, B.; Bunge, H. P.

2015-12-01

Mantle convection is the cause for plate tectonics, the formation of mountains and oceans, and the main driving mechanism behind earthquakes. The convection process is modeled by a system of partial differential equations describing the conservation of mass, momentum and energy. Characteristic to mantle flow is the vast disparity of length scales from global to microscopic, turning mantle convection simulations into a challenging application for high-performance computing. As system size and technical complexity of the simulations continue to increase, design and implementation of simulation models for next generation large-scale architectures is handled successfully only in an interdisciplinary context. A new priority program - named SPPEXA - by the German Research Foundation (DFG) addresses this issue, and brings together computer scientists, mathematicians and application scientists around grand challenges in HPC. Here we report from the TERRA-NEO project, which is part of the high visibility SPPEXA program, and a joint effort of four research groups. TERRA-NEO develops algorithms for future HPC infrastructures, focusing on high computational efficiency and resilience in next generation mantle convection models. We present software that can resolve the Earth's mantle with up to 1012 grid points and scales efficiently to massively parallel hardware with more than 50,000 processors. We use our simulations to explore the dynamic regime of mantle convection and assess the impact of small scale processes on global mantle flow.

Bone marrow mesenchymal stem cells accelerate the hyperglycemic refractory wound healing by inhibiting an excessive inflammatory response.

Science.gov (United States)

Nan, Wenbin; Xu, Zhihao; Chen, Zhibin; Yuan, Xin; Lin, Juntang; Feng, Huigen; Lian, Jie; Chen, Hongli

2017-05-01

The aim of the present study was to evaluate the healing effect of bone marrow-derived mesenchymal stem cells administered to hyperglycemia model mice with skin wounds, and to explore the underlying mechanism contributing to their effects in promoting refractory wound healing. A full‑thickness skin wound mouse model was established, and refers to a wound of the skin and subcutaneous tissue. The mice were randomly divided into three groups: Blank control group, hyperglycemic group and a hyperglycemic group treated with stem cells. Wound healing was monitored and the wound‑healing rate was determined at 3, 6, 9, and 12 days following trauma. The structure of the organization of new skin tissue was observed by hematoxylin and eosin staining, and expression levels of the inflammatory cytokines interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α were determined from 1 to 6 days following trauma. The wound healing of the hyperglycemic group was slower than that of the blank group, and the hyperglycemic mice treated with stem cells presented faster healing than the hyperglycemia group. The horny layer and granular layer of the skin were thinner and incomplete in the new skin tissue of the hyperglycemic group, whereas the new skin wound tissue basal layer was flat and demonstrated better fusion with the wound edge in the other two groups. The expression of inflammatory cytokines (IL‑6 and TNF‑α) was significantly increased in all three groups, with continuously higher expression in the hyperglycemic group and decreased expression in the other two groups over time. Hyperglycemia refractory wounds are likely related to the excessive expression of inflammatory cytokines surrounding the wound area. Stem cells may be able to alleviate the excessive inflammatory reaction in the wound tissue of hyperglycemic mice, so as to promote wound healing.

Discovery and characterization of a novel CCND1/MRCK gene fusion in mantle cell lymphoma

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Chioniso Patience Masamha

2016-03-01

Full Text Available Abstract The t(11;14 translocation resulting in constitutive cyclin D1 expression is an early event in mantle cell lymphoma (MCL transformation. Patients with a highly proliferative phenotype produce cyclin D1 transcripts with truncated 3′UTRs that evade miRNA regulation. Here, we report the recurrence of a novel gene fusion in MCL cell lines and MCL patient isolates that consists of the full protein coding region of cyclin D1 (CCND1 and a 3′UTR consisting of sequences from both the CCND1 3′UTR and myotonic dystrophy kinase-related Cdc42-binding kinase's (MRCK intron one. The resulting CCND1/MRCK mRNA is resistant to CCND1-targeted miRNA regulation, and targeting the MRCK region of the chimeric 3′UTR with siRNA results in decreased CCND1 levels.

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.

Science.gov (United States)

Weber, Jeffrey S; Kudchadkar, Ragini Reiney; Yu, Bin; Gallenstein, Donna; Horak, Christine E; Inzunza, H David; Zhao, Xiuhua; Martinez, Alberto J; Wang, Wenshi; Gibney, Geoffrey; Kroeger, Jodi; Eysmans, Cabell; Sarnaik, Amod A; Chen, Y Ann

2013-12-01

Nivolumab, a human immunoglobulin G4-blocking antibody against the T-cell programmed death-1 checkpoint protein, has activity against metastatic melanoma. Its safety, clinical efficacy, and correlative biomarkers were assessed with or without a peptide vaccine in ipilimumab-refractory and -naive melanoma. In this phase I study, 90 patients with unresectable stage III or IV melanoma who were ipilimumab naive and had experienced progression after at least one prior therapy (cohorts 1 to 3, 34 patients) or experienced progression after prior ipilimumab (cohorts 4 to 6, 56 patients) received nivolumab at 1, 3, or 10 mg/kg every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. Nivolumab with vaccine was well tolerated and safe at all doses. The RECIST 1.1 response rate for both ipilimumab-refractory and -naive patients was 25%. Median duration of response was not reached at a median of 8.1 months of follow-up. High pretreatment NY-ESO-1 and MART-1-specific CD8(+) T cells were associated with progression of disease. At week 12, increased peripheral-blood T regulatory cells and decreased antigen-specific T cells were associated with progression. PD-L1 tumor staining was associated with responses to nivolumab, but negative staining did not rule out a response. Patients who experienced progression after nivolumab could respond to ipilimumab. In patients with ipilimumab-refractory or -naive melanoma, nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks. Responses to nivolumab in ipilimumab-refractory patients or to ipilimumab in nivolumab-refractory patients support combination or sequencing of nivolumab and ipilimumab.

Bendamustine/Mitoxantrone/Rituximab (BMR): a very effective, well tolerated outpatient chemoimmunotherapy for relapsed and refractory CD20-positive indolent malignancies. Final results of a pilot study.

Science.gov (United States)

Weide, Rudolf; Pandorf, Annette; Heymanns, Jochen; Köppler, Hubert

2004-12-01

We have developed a new chemoimmunotherapy for patients with relapsed or refractory CD20-positive indolent lymphomas and CLL by combining the chemotherapeutic agents Bendamustine (B) and Mitoxantrone (M) with the monoclonal antibody Rituximab. Treatment consisted of (B): 90 mg/m2 (80 mg/m2 in CLL) day 1 + 2, (M): 10 mg/m2 day 1 and (R): 375 mg/m2 day 8,15,22 and 29. BM was repeated 3 times starting on day 36, thereafter every 4 weeks. The maximal therapy consisted of 1 x BMR followed by 5 x BM. We have treated 54 patients with BMR. Median age was 68 years (36-82). Disease distribution was as follows: 21 B-CLL, 1 B-PLL, 8 lymphoplasmacytic, 14 follicular, 2 mantle cell, 2 marginal zone, 6 secondary high grade. Median number of previous treatments was 2 (1-7). ORR was 96% with 41% CR and 55% PR. Median time to progression is 17 months in CLL and has not been reached in indolent lymphomas with a median observation time of 27 months (3-60+). The time to next antilymphoma treatment is prolonged significantly by BMR. No therapy associated death or hospitalization occurred within the study period. BMR is a well tolerated very effective outpatient treatment for relapsed and refractory CD20-positive indolent lymphomas and CLL.

Theoretical and practical aspects about corrosion of refractories used in steel metallurgy: part 3: characterization of commercial refractories

International Nuclear Information System (INIS)

Braganca, S.R.

2012-01-01

In this study, it was reviewed the main aspects found in the literature about refractories corrosion, evaluating the feasibility of certain tests and relating them with experimental results. The physical properties and microstructure of commercial refractories were analyzed, considering the differences between them and the quality implications and probable life of the refractory. Thus, it was studied the various types of refractories used as lining on steel ladle. Magnesia-carbon and doloma-carbon refractories were analyzed, highlighting the differences between them. The examined refractory showed characteristics favoring high resistance to corrosion process, presenting a series of properties to be selected in accordance with industry practice. (author)

Discordant lymphoma consisting of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood: a case report

Directory of Open Access Journals (Sweden)

Caracciolo Francesco

2011-09-01

Full Text Available Abstract Introduction Discordant lymphomas are rare entities characterized by the simultaneous presence of two distinct types of lymphomas in different anatomic sites. We describe a very rare case of simultaneous occurrence of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood. Case presentation We report the case of a 60-year-old asymptomatic Caucasian woman in whom discordant lymphomas were discovered when a slight lymphocytosis and a conspicuous splenomegaly were observed. The different morphological, immunophenotypical and immunohistochemical features found in the different pathologic samples obtained from peripheral blood, bone marrow and spleen sections made it possible to differentiate two types of non-Hodgkin B-cell lymphomas: a mantle cell lymphoma infiltrating the spleen and a marginal zone lymphoma involving both the bone marrow and peripheral blood. Since a similar IgH gene rearrangement was found both in the bone marrow and in the spleen, the hypothesis of a common origin, followed by a different clonal selection of the neoplastic lymphocytes may be taken into consideration. Conclusion Our case emphasizes the usefulness of investigating simultaneous specimens from different anatomic sites from the same patient and the relevant diagnostic role of splenectomy.

Metastatic Mantle Cell Lymphoma to the Pituitary Gland: Case Report and Literature Review

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Arthur Wang

2016-01-01

Full Text Available We present an unusual case of a metastatic mantle cell lymphoma (MCL to the pituitary gland. The patient had a known history of MCL for which she previously received chemotherapy. She presented with new-onset diplopia and confusion, and reported a history of progressive vision blurriness associated with headache, nausea, and vomiting. MRI of the brain showed an enhancing lesion within the sella turcica involving the cavernous sinuses bilaterally, extending into Meckel's cave on the left, and abutting the optic nerves bilaterally. Following surgical excision, histopathology revealed the tumor to be a MCL. Metastatic pituitary tumors are rare and have been estimated to make up 1% of tumors discovered in the sellar region. The two most common secondary metastatic lesions to the sella are breast and lung carcinoma followed by prostate, renal cell, and gastrointestinal carcinoma. Metastatic lymphoma to the pituitary gland is especially rare and is estimated to constitute 0.5% of all metastatic tumors to the sella turcica. To our knowledge, this is the first reported case of MCL metastasizing to the pituitary gland.

Large-scale global convection in the mantle beneath Australia from 55 Ma to now

International Nuclear Information System (INIS)

Zhang, M.

1999-01-01

Full text: The global-scale mantle convection cells in the asthenosphere are not geochemically homogeneous. The heterogeneity is most prominently reflected in the isotopic compositions (Pb-Sr-Nd) of the mid-ocean ridge basalts (MORB) that are direct partial melts from the underlying asthenosphere. Of particular relevance to Australia's geodynamic evolution from about 100 million years, are the distinctive geochemical signatures of the asthenosphere beneath the Pacific Ocean (Pacific MORB) and Indian Ocean (Indian MORB). Therefore, delineation of the boundary between the two distinct mantle reservoirs and any change in that boundary with time provide information about the patterns of global-scale asthenospheric mantle convection. This information has also allowed us to track large-scale mantle chemical reservoirs such as the distinctive Gondwana lithospheric mantle, and hence better understand the geodynamic evolution of the Australian continent from the time of Gondwana dispersal. Pb-Sr-Nd isotope data for Cenozoic basalts in eastern Australia (Zhang et al, 1999) indicate that Pacific-MORB type isotopic signatures characterise the lava-field basalts (55-14 Ma) in southeastern Australia, whereas Indian-MORB type isotopic signatures characterise younger basalts (6-0 Ma) from northeastern Australia. This discovery helps to constrain the changing locus of the major asthenospheric mantle convection cells represented by the Pacific and Indian MORB sources during and following the breakup of the eastern part of Gondwana, and locates, for the first time, the boundary of these convection cells beneath the Australian continent. This extends previous work in the SW Pacific back-arc basins (eg Hickey-Vargas et al., 1995) and the Southern Ocean (Lanyon et al., 1995) that indicates that the 1- and P-MORB mantle convection cells have been moving in opposite directions since the early Tertiary. These new data also indicate that the Indian-MORB source is a long-term asthenospheric

Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

Directory of Open Access Journals (Sweden)

Kahl Brad S

2008-05-01

Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

Phase I study of obinutuzumab (GA101) in Japanese patients with relapsed or refractory B-cell non-Hodgkin lymphoma.

Science.gov (United States)

Ogura, Michinori; Tobinai, Kensei; Hatake, Kiyohiko; Uchida, Toshiki; Suzuki, Tatsuya; Kobayashi, Yukio; Mori, Masakazu; Terui, Yasuhito; Yokoyama, Masahiro; Hotta, Tomomitsu

2013-01-01

As CD20 has become an established target for treating B-cell malignancies, there is interest in developing anti-CD20 antibodies with different functional activity from rituximab that might translate into improved efficacy. Obinutuzumab (GA101) is a glycoengineered, humanized type II anti-CD20 monoclonal antibody that has demonstrated superior activity to type I antibodies in preclinical studies and is currently being investigated in phase III trials. In this phase I dose-escalating study in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the primary endpoint was to characterize the safety of GA101; secondary endpoints were efficacy, pharmacokinetics and pharmacodynamics. Patients received up to nine doses of GA101 with up to 52 weeks' follow up. Most adverse events were grade 1 or 2 infusion-related reactions, and 10 grade 3/4 adverse events occurred. No dose-limiting toxicities were observed and the maximum tolerated dose was not identified. Out of 12 patients, 7 responded (end-of-treatment response rate 58%), with 2 complete responses and 5 partial responses. Responses were observed from low to high doses, and no dose-efficacy relationship was observed. B-cell depletion occurred in all patients after the first infusion and was maintained for the duration of treatment. Serum levels of GA101 increased in a dose-dependent fashion, although there was inter-patient variability. This phase I study demonstrated that GA101 has an acceptable safety profile and offers encouraging activity to Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. © 2012 Japanese Cancer Association.

Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma.

Science.gov (United States)

Peponi, Evangelia; Drakos, Elias; Reyes, Guadalupe; Leventaki, Vasiliki; Rassidakis, George Z; Medeiros, L Jeffrey

2006-12-01

Mantle cell lymphoma (MCL) is characterized by the t(11;14) and cyclin D1 overexpression. However, additional molecular events are most likely required for oncogenesis, possibly through cell cycle and apoptosis deregulation. We hypothesized that mammalian target of rapamycin (mTOR) is activated in MCL and contributes to tumor proliferation and survival. In MCL cell lines, pharmacological inhibition of the phosphoinositide 3-kinase/AKT pathway was associated with decreased phosphorylation (activation) of mTOR and its downstream targets phosphorylated (p)-4E-BP1, p-p70S6 kinase, and p-ribosomal protein S6, resulting in apoptosis and cell cycle arrest. These changes were associated with down-regulation of cyclin D1 and the anti-apoptotic proteins cFLIP, BCL-XL, and MCL-1. Furthermore, silencing of mTOR expression using mTOR-specific short interfering RNA decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis. Silencing of eukaryotic initiation factor (eIF4E), a downstream effector of mTOR, recapitulated these results. We also assessed mTOR signaling in MCL tumors using immunohistochemical methods and a tissue microarray: 10 of 30 (33%) expressed Ser473p-AKT, 13 of 21 (62%) Ser2448p-mTOR, 22 of 22 (100%) p-p70S6K, and 5 of 20 (25%) p-ribosomal protein S6. Total eIF4E binding protein 1 and eukaryotic initiation factor 4E were expressed in 13 of 14 (93%) and 16 of 29 (55%) MCL tumors, respectively. These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL.

Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group

OpenAIRE

Kollmannsberger, C; Rick, O; Klaproth, H; Kubin, T; Sayer, H G; Hentrich, M; Welslau, M; Mayer, F; Kuczyk, M; Spott, C; Kanz, L; Bokemeyer, C

2002-01-01

Despite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell...

Uterine CD56dim and CD16+ Cells in Refractory Antiphospholipid Antibody-Related Pregnancy Loss and Chromosomally Intact Abortuses: A Case–Control Study

Directory of Open Access Journals (Sweden)

Mostafa F Gomaa

2017-01-01

Full Text Available Aim: To evaluate the role of uterine natural killer (uNK CD56dim and CD16+ cells in patients with refractory antiphospholipid, antibody-mediated, recurrent, pregnancy loss. Settings and Design: A case–control study was conducted between 2012 and 2015 at a university hospital. Patients and Methods: A group of 118 women with a history of antiphospholipid antibody syndrome experiencing fetal loss in spite of low dose aspirin (LDA and low molecular weight heparin (LMWH treatment in the current pregnancy were included in this study. A group of 32 patients undergoing an elective termination of viable pregnancies before 20 weeks were taken as controls. Suction evacuation was performed to collect abortus specimens, and uterine wall curettage was performed to collect decidua specimens, which were then stained using monoclonal antibodies specific to CD56 and CD16. Statistics: Statistical analyses were performed using the Statistical Package for the Social Sciences version 18 software. Chi-square and Fisher exact tests were used for making comparison between the groups. Results: Abnormal fetal karyotype was found in nine (9/97 cases of the study group, which means that abnormal karyotype accounts for only 9.3% of the causes of failure of treatment. Abnormal karyotype was found in four cases of the control group. Only cases with normal karyotyping were subjected to decidual uNK cells analysis. We found that CD56dim and CD16+ were found in the decidua of 79 cases (79/97, which means that aberrant natural killer cells expression might account for 81.4% of the cases of refractory antiphospholipid antibody (APA-mediated recurrent pregnancy loss. Conclusion: CD56dim and CD16+uNK cells might be correlated with refractory APA-mediated recurrent pregnancy loss.

Seismic Imaging of Mantle Plumes

Science.gov (United States)

Nataf, Henri-Claude

The mantle plume hypothesis was proposed thirty years ago by Jason Morgan to explain hotspot volcanoes such as Hawaii. A thermal diapir (or plume) rises from the thermal boundary layer at the base of the mantle and produces a chain of volcanoes as a plate moves on top of it. The idea is very attractive, but direct evidence for actual plumes is weak, and many questions remain unanswered. With the great improvement of seismic imagery in the past ten years, new prospects have arisen. Mantle plumes are expected to be rather narrow, and their detection by seismic techniques requires specific developments as well as dedicated field experiments. Regional travel-time tomography has provided good evidence for plumes in the upper mantle beneath a few hotspots (Yellowstone, Massif Central, Iceland). Beneath Hawaii and Iceland, the plume can be detected in the transition zone because it deflects the seismic discontinuities at 410 and 660 km depths. In the lower mantle, plumes are very difficult to detect, so specific methods have been worked out for this purpose. There are hints of a plume beneath the weak Bowie hotspot, as well as intriguing observations for Hawaii. Beneath Iceland, high-resolution tomography has just revealed a wide and meandering plume-like structure extending from the core-mantle boundary up to the surface. Among the many phenomena that seem to take place in the lowermost mantle (or D''), there are also signs there of the presence of plumes. In this article I review the main results obtained so far from these studies and discuss their implications for plume dynamics. Seismic imaging of mantle plumes is still in its infancy but should soon become a turbulent teenager.

Direct intramyocardial mesenchymal stromal cell injections in patients with severe refractory angina - one year follow-up

DEFF Research Database (Denmark)

Haack-Sørensen, Mandana; Friis, Tina; Mathiasen, Anders B

2013-01-01

Aims: In patients with stable coronary artery disease (CAD) and refractory angina we performed direct intra-myocardial injections of autologous mesenchymal stromal cells (MSCs) and followed the safety and efficacy of the treatment for 12 months. Methods and Results: A total of 31 patients...... with stable CAD, moderate to severe angina, normal left ventricular ejection fraction and no further revascularization options, were included. Bone marrow MSCs were isolated and culture expanded for 6 - 8 weeks and then stimulated with vascular endothelial growth factor (VEGF) for one week.The 12 months...... follow-up demonstrated, that it was safe to culture expand MSCs and use the cells for clinical treatment. The patients maximal metabolic equivalent (MET) during exercise increased from 4.23 MET at baseline to 4.72 MET at 12 months follow-up (p...

Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group.

Science.gov (United States)

Buckstein, Rena; Kuruvilla, John; Chua, Neil; Lee, Christina; Macdonald, David A; Al-Tourah, Abdulwahab J; Foo, Alison H; Walsh, Wendy; Ivy, S Percy; Crump, Michael; Eisenhauer, Elizabeth A

2011-05-01

There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3-4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity.

Large-scale compositional heterogeneity in the Earth's mantle

Science.gov (United States)

Ballmer, M.

2017-12-01

Seismic imaging of subducted Farallon and Tethys lithosphere in the lower mantle has been taken as evidence for whole-mantle convection, and efficient mantle mixing. However, cosmochemical constraints point to a lower-mantle composition that has a lower Mg/Si compared to upper-mantle pyrolite. Moreover, geochemical signatures of magmatic rocks indicate the long-term persistence of primordial reservoirs somewhere in the mantle. In this presentation, I establish geodynamic mechanisms for sustaining large-scale (primordial) heterogeneity in the Earth's mantle using numerical models. Mantle flow is controlled by rock density and viscosity. Variations in intrinsic rock density, such as due to heterogeneity in basalt or iron content, can induce layering or partial layering in the mantle. Layering can be sustained in the presence of persistent whole mantle convection due to active "unmixing" of heterogeneity in low-viscosity domains, e.g. in the transition zone or near the core-mantle boundary [1]. On the other hand, lateral variations in intrinsic rock viscosity, such as due to heterogeneity in Mg/Si, can strongly affect the mixing timescales of the mantle. In the extreme case, intrinsically strong rocks may remain unmixed through the age of the Earth, and persist as large-scale domains in the mid-mantle due to focusing of deformation along weak conveyor belts [2]. That large-scale lateral heterogeneity and/or layering can persist in the presence of whole-mantle convection can explain the stagnation of some slabs, as well as the deflection of some plumes, in the mid-mantle. These findings indeed motivate new seismic studies for rigorous testing of model predictions. [1] Ballmer, M. D., N. C. Schmerr, T. Nakagawa, and J. Ritsema (2015), Science Advances, doi:10.1126/sciadv.1500815. [2] Ballmer, M. D., C. Houser, J. W. Hernlund, R. Wentzcovitch, and K. Hirose (2017), Nature Geoscience, doi:10.1038/ngeo2898.

A >100 Ma Mantle Geochemical Record: Retiring Mantle Plumes may be Premature

Science.gov (United States)

Konter, J. G.; Hanan, B. B.; Blichert-Toft, J.; Koppers, A. A.; Plank, T.; Staudigel, H.

2006-12-01

Hotspot volcanism has long been attributed to mantle plumes, but in recent years suggestions have been made that plate tectonic processes, such as extension, can account for all hotspot tracks. This explanation involves a profoundly less dynamic lower mantle, which justifies a critical evaluation before the plume model is dismissed. Such an evaluation has to involve a wide range of geochemical, geological, and geophysical techniques, broadly investigating the products of volcanism as well as the underlying lithosphere and mantle. We argue here that the combined geological record and geochemistry of intraplate volcanoes holds some important clues that help us decide between models of plume-like upwelling versus passive upwelling with lithospheric extension. The best of these integrated datasets can be obtained from the long seamount chains in the Pacific Ocean. A new combined dataset of trace element and isotopic compositions, along with modern 40Ar/39Ar ages from seamounts in the Gilbert Ridge, Tokelau chain, and West Pacific Seamount Province (WPSP) provides a record of current to Cretaceous volcanism in the South Pacific. We have reconstructed the eruptive locations of the seamounts using a range of absolute plate motion models, including some models with hotspot motion and others that use the Indo-Atlantic hotspot reference frame. Our results show that the backtracked locations consistently form clusters (300km radius) around the active ends of the Macdonald, Rurutu and Rarotonga hotspot chains, while closely matching their distinct C-HIMU and C-EM1 signatures. The oldest WPSP seamounts (older than 100 Ma) form the only exception and backtrack, with larger uncertainty, to north of Rarotonga. Therefore, the mantle currently underlying the Cook-Austral islands has produced volcanoes in three geochemically distinct areas for at least 100 m.y. Furthermore, we find the shortest mantle residence time, 0.6 Ga, for a source of mixed recycled DMM and an EM1-like

Evaluation of the reusing of MGO-C refractory brick in refractory mixes

International Nuclear Information System (INIS)

Silva, R.D.S. da; Braganca, S.R.

2012-01-01

The residue from the use of MgO-C refractories in electric arc furnace presents, mostly, magnesium oxide in its composition and some slag contamination and impurities from the process of electrofusion scrap iron/steel. In this study, it was studied the characteristics of this residue and reused through its introduction into a commercial refractory mix, employed as material of coating and repair. This refractory mix was tested by thermogravimetric analysis, compressive strength, evaluation of plasticity and porosity as well as aspects of its installation, such as adhesion in situ. Results showed that there potential for reuse with the introduction of the waste in commercial mix was 30%, with little loss of compressive strength and plasticity. (author)

[Mantle cell lymphoma, response to treatment and prognosis in 45 patients].

Science.gov (United States)

Sorigue, Marc; Sancho, Juan-Manuel; García, Olga; Vila, Jordi; Moreno, Miriam; Ribera, Josep-Maria

2016-07-01

Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients. Retrospective study of MCL patients diagnosed in a single institution between 1996 and 2013. The cohort was divided according to the treatment received. Forty-five patients were included (32 male) with a median age of 66 years old. Twenty-one received intensive chemotherapy or chemoimmunotherapy (based on high-dose cytarabine), 13 semi-intensive (without high-dose cytarabine), 8 not intensive and 3 did not require treatment. Overall response rate was 85% in the intensive and 77% in the semi-intensive treatment groups. In multivariate analysis, intensive treatment was correlated with a longer progression-free survival (hazard ratio 9.8 [95% CI 2.7-35.5], P=.001) and overall survival (4.5 [1.2-17.8], P=.03). In this retrospective series of MCL patients, intensive treatment was correlated with better outcomes than the other treatment modalities. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

IgV H mutations in blastoid mantle cell lymphoma characterize a subgroup with a tendency to more favourable clinical outcome.

Science.gov (United States)

Cogliatti, Sergio B; Bertoni, Francesco; Zimmermann, Dieter R; Henz, Samuel; Diss, Tim C; Ghielmini, Michele; Schmid, Ulrico

2005-07-01

Mantle cell lymphoma (MCL) is associated with a very unfavourable clinical course. This is particularly true for mantle cell lymphoma of the blastoid subtype (MCL-b). In order to define prognostic factors, we analysed the impact of immunoglobulin heavy chain variable (IgV H) gene somatic hypermutations on clinical outcome in a series of 21 cases of morphologically, phenotypically, and genotypically well-characterized MCL-b. Testing and estimation were performed using log-rank statistics and displayed on Kaplan-Meier graphs. Thirteen of 21 cases of MCL-b revealed a homology rate of > or = 99% compared to IgV H germ-line sequences in the databases and were scored as non-mutated. Eight of 21 cases (38%) of MCL-b were mutated. In MCL-b the mutation frequency was usually low and the mutation pattern was only rarely antigen-selected, in contrast to a control group of 11 cases with morphologically almost identical, but phenotypically and genotypically clearly distinguishable, diffuse large B cell lymphoma, derived, most likely, from germinal centre B cells. In our series of 21 MCL-b, positive IgV H mutational status, irrespective of varying homology thresholds, had no statistically significant prognostic impact on event-free or overall survival. However, mutated MCL-b tended to present more frequently at an earlier stage and without bone marrow involvement and to show lower rates of relapse and death, resulting in a more favourable clinical outcome. Copyright 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Asymmetric three-dimensional topography over mantle plumes.

Science.gov (United States)

Burov, Evgueni; Gerya, Taras

2014-09-04

The role of mantle-lithosphere interactions in shaping surface topography has long been debated. In general, it is supposed that mantle plumes and vertical mantle flows result in axisymmetric, long-wavelength topography, which strongly differs from the generally asymmetric short-wavelength topography created by intraplate tectonic forces. However, identification of mantle-induced topography is difficult, especially in the continents. It can be argued therefore that complex brittle-ductile rheology and stratification of the continental lithosphere result in short-wavelength modulation and localization of deformation induced by mantle flow. This deformation should also be affected by far-field stresses and, hence, interplay with the 'tectonic' topography (for example, in the 'active/passive' rifting scenario). Testing these ideas requires fully coupled three-dimensional numerical modelling of mantle-lithosphere interactions, which so far has not been possible owing to the conceptual and technical limitations of earlier approaches. Here we present new, ultra-high-resolution, three-dimensional numerical experiments on topography over mantle plumes, incorporating a weakly pre-stressed (ultra-slow spreading), rheologically realistic lithosphere. The results show complex surface evolution, which is very different from the smooth, radially symmetric patterns usually assumed as the canonical surface signature of mantle upwellings. In particular, the topography exhibits strongly asymmetric, small-scale, three-dimensional features, which include narrow and wide rifts, flexural flank uplifts and fault structures. This suggests a dominant role for continental rheological structure and intra-plate stresses in controlling dynamic topography, mantle-lithosphere interactions, and continental break-up processes above mantle plumes.

Water in Earth's mantle: Hydrogen analysis of mantle olivine, pyroxenes and garnet using the SIMS

Science.gov (United States)

Kurosawa, Masanori; Yurimoto, Hisayoshi; Sueno, Shigeho

1993-01-01

Hydrogen (or water) in the Earth's interior plays a key role in the evolution and dynamics of the planet. However, the abundance and the existence form of the hydrogen have scarcely been clear in practice. Hydrogen in the mantle was incorporated in the interior during the formation of the Earth. The incorporated hydrogen was hardly possible to concentrate locally inside the Earth considering its high mobility and high reactivity. The hydrogen, preferably, could be distributed homogeneously over the mantle and the core by the subsequent physical and chemical processes. Therefore, hydrogen in the mantle could be present in the form of trace hydrogen in nominally anhydrous mantle minerals. The hydrogen and the other trace elements in mantle olivines, orthopyroxenes, clinopyroxenes, and garnets were determined using secondary ion mass spectrometry (SIMS) for elucidating (1) the exact hydrogen contents, (2) the correlation between the hydrogen and the other trace elements, (3) the dependence of the hydrogen contents on the depth, and (4) the dependence of the whole rock water contents on the depth.

131I-MIBG followed by consolidation with busulfan, melphalan and autologous stem cell transplantation for refractory neuroblastoma.

Science.gov (United States)

French, Sarah; DuBois, Steven G; Horn, Biljana; Granger, Meaghan; Hawkins, Randall; Pass, Amy; Plummer, Ellen; Matthay, Katherine

2013-05-01

(131) I-metaiodobenzylguanidine (MIBG) produces a 37% response rate in relapsed/refractory neuroblastoma, and could be used to improve remission status prior to myeloablative chemotherapy with autologous stem cell transplant (ASCT). The purpose of our report was to evaluate safety and response with MIBG therapy followed by myeloablative busulfan and melphalan (BuMel) with ASCT in patients with refractory neuroblastoma. Retrospective chart review was done on patients treated with MIBG (18 mCi/kg) on Day 1 and ASCT on day 14. Six to eight weeks after MIBG, patients without progressive disease received IV busulfan on days -6 to -2 (target Css 700-900), melphalan (140 mg/m2 IV) on day -1, and ASCT on Day 0. Response and toxicity were evaluated after MIBG and again after myeloablative therapy. Eight patients completed MIBG/ASCT followed by BuMel/ASCT. MIBG was well tolerated, with grade 3 or 4 non-hematologic toxicity limited to one patient with sepsis. Grade 3 mucositis occurred in six patients after BuMel/ASCT. One patient developed sinusoidal obstructive syndrome (SOS) and died 50 days post-ASCT following myeloablative conditioning. All patients engrafted neutrophils (median 16.5 days) and platelets (median 32 days) after BuMel, excluding the patient with SOS. After all therapy, there were three complete, two partial, and one minor response in seven evaluable patients. MIBG at doses up to 18 mCi/kg can be safely administered 6 weeks prior to a BuMel consolidative regimen for refractory neuroblastoma. Preceding MIBG did not impair engraftment following BuMel. This regimen is being further evaluated in a Children's Oncology Group (COG) trial. Copyright © 2012 Wiley Periodicals, Inc.

Thermal Stratification in Vertical Mantle Tanks

DEFF Research Database (Denmark)

Knudsen, Søren; Furbo, Simon

2001-01-01

It is well known that it is important to have a high degree of thermal stratification in the hot water storage tank to achieve a high thermal performance of SDHW systems. This study is concentrated on thermal stratification in vertical mantle tanks. Experiments based on typical operation conditions...... are carried out to investigate how the thermal stratification is affected by different placements of the mantle inlet. The heat transfer between the solar collector fluid in the mantle and the domestic water in the inner tank is analysed by CFD-simulations. Furthermore, the flow pattern in the vertical mantle...

Compatibility of refractory materials with boiling sodium

International Nuclear Information System (INIS)

Meacham, S.A.

1976-01-01

The program employed to determine the compatibility of commercially available refractories with boiling sodium is described. The effects of impurities contained within the refractory material, and their relations with the refractory's physical stability are discussed. Also, since consideration of refractories for use as an insulating material within Liquid Metal Fast Breeder Reactor Plants (LMFBR's) is currently under investigation; recommendations, based upon this program, are presented

Gondwana subduction-modified mantle domain prevents magmatic seafloor generation in the Central Indian Ridge

Science.gov (United States)

Morishita, T.; Nakamura, K.; Senda, R.; Suzuki, K.; Kumagai, H.; Sato, H.; Sato, T.; Shibuya, T.; Minoguchi, K.; Okino, K.

2013-12-01

The creation of oceanic crust at mid-ocean ridges is essential to understanding the genesis of oceanic plate and the evolution of the Earth. Detailed bathymetric measurements coupled with dense sample recovery at mid-ocean ridge revealed a wide range of variations in the ridge and seafloor morphologies, which cannot be simply explained by a spreading rate, but also by ridge geometry, mantle compositions and thermal structure (Dick et al., 2003 Nature; Cannat et al. 2006 Geology). It is now widely accepted that very limited magmatic activity with tectonic stretching generates oceanic core complex and/or smooth seafloor surface in the slow to ultraslow-spreading ridges, where serpentinized peridotite and gabbros are expected to be exposed associated with detachment faults (Cann et al., 1997 Nature; Cannat et al., 2006), although magmatism might be an essential role for the formation of oceanic core complexes (Buck et al., 2005 Nature; Tucholke et al 2008 JGR). A rising question is why magmatic activity is sometimes prevented during the oceanic plate formation. Ancient melting domain, that are too refractory to melt even in adiabatically upwelling to the shallow upper mantle, might cause the amagmatic spreading ridges (Harvey et al., 2006 EPSL, Liu et al.,2008 Nature). Its origin and effect on seafloor generations are, however, not well understood yet. We report an oceanic hill as an example of an ancient subduction-modified mantle domain, probably formed at continental margin of the Gondwanaland~Pangea supercontinent, existing beneath the Central Indian Ridge. This domain is the most likely to have prevented magmatic seafloor generation, resulting in creation of very deep oceanic valley and serpentine diaper (now the studied oceanic hill) at the present Central Indian ridge.

Refractory bin for burning

Energy Technology Data Exchange (ETDEWEB)

McPherson, D.L.; McPherson, T.L.

1989-12-26

This patent describes a refractory bin. It has a generally rectangular horizontal cross sectional configuration. It has wall structures each comprising an upper and a lower pair of elongated horizontal vertically spaced generally parallel support beams each having a vertical flange defining a support edge along its upper surface, a first generally rectangular refractory panel arranged with its lower edge at the bottom of the bin and with its outer surface in flat face contacting relation with the vertical flanges of the lower pair of support beams, a plurality of brackets each having a horizontal part and a vertical part and being secured to the outer surface of the first refractory panel.

Archean crust-mantle geochemical differentiation

Science.gov (United States)

Tilton, G. R.

Isotope measurements on carbonatite complexes and komatiites can provide information on the geochemical character and geochemical evolution of the mantle, including the sub-continental mantle. Measurements on young samples establish the validity of the method. These are based on Sr, Nd and Pb data from the Tertiary-Mesozoic Gorgona komatiite and Sr and Pb data from the Cretaceous Oka carbonatite complex. In both cases the data describe a LIL element-depleted source similar to that observed presently in MORB. Carbonatite data have been used to study the mantle beneath the Superior Province of the Canadian Shield one billion years (1 AE) ago. The framework for this investigation was established by Bell et al., who showed that large areas of the province appear to be underlain by LIL element-depleted mantle (Sr-85/Sr-86=0.7028) at 1 AE ago. Additionally Bell et al. found four complexes to have higher initial Sr ratios (Sr-87/Sr-86=0.7038), which they correlated with less depleted (bulk earth?) mantle sources, or possibly crustal contamination. Pb isotope relationships in four of the complexes have been studied by Bell et al.

Archean crust-mantle geochemical differentiation

Science.gov (United States)

Tilton, G. R.

1983-01-01

Isotope measurements on carbonatite complexes and komatiites can provide information on the geochemical character and geochemical evolution of the mantle, including the sub-continental mantle. Measurements on young samples establish the validity of the method. These are based on Sr, Nd and Pb data from the Tertiary-Mesozoic Gorgona komatiite and Sr and Pb data from the Cretaceous Oka carbonatite complex. In both cases the data describe a LIL element-depleted source similar to that observed presently in MORB. Carbonatite data have been used to study the mantle beneath the Superior Province of the Canadian Shield one billion years (1 AE) ago. The framework for this investigation was established by Bell et al., who showed that large areas of the province appear to be underlain by LIL element-depleted mantle (Sr-85/Sr-86=0.7028) at 1 AE ago. Additionally Bell et al. found four complexes to have higher initial Sr ratios (Sr-87/Sr-86=0.7038), which they correlated with less depleted (bulk earth?) mantle sources, or possibly crustal contamination. Pb isotope relationships in four of the complexes have been studied by Bell et al.

Molecular Determinants of Hormone Refractory Prostate Cancer

Science.gov (United States)

2017-07-01

receptor is no longer essential for survival, collectively termed androgen pathway independent prostate cancer (APIPC) (Nelson, 2012). A subset of these...Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer . Cancer Cell. 2011 May 17;19(5):575-86. Chen J, Li...2005a). The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer . Part 1: Modifications to the androgen receptor

Improving outcomes of refractory celiac disease – current and emerging treatment strategies

Directory of Open Access Journals (Sweden)

Woodward J

2016-08-01

Full Text Available Jeremy Woodward Department of Gastroenterology and Clinical Nutrition, Addenbrooke’s Hospital, Cambridge, UK Abstract: Intestinal inflammation and symptoms of celiac disease (CD usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness. Keywords: celiac disease, gluten, small intestine, lymphoma, lymphocytes

The role of plumes in mantle helium fluxes

International Nuclear Information System (INIS)

Kellogg, L.H.; Wasserburg, G.J.

1990-01-01

We present a simple model of 3 He and 4 He transport in the mantle using the appropriate rates of mass and species transfer and 4 He production. Previous workers have shown the presence of excess 3 He in hotspots such as Hawaii and Iceland and inferred that these hotspots tap a source with a higher 3 He/ 4 He ratio than the source region of mid-ocean ridge basalts (MORB). Hotspot ocean islands probably originate over upwelling plumes which carry material from the lower mantle to the upper mantle. Melting at hotspots and at mid-ocean ridges degasses the mantle of volatiles such as helium. The upper mantle is outgassed largely of helium due to melting at mid-ocean ridges and hotspots. We postulate that the excess 3 He seen in MORB originates in material that was carried from the lower mantle in plumes but not completely outgassed at hotspots. This helium is incoporated into the depleted upper mantle. Assuming that the upper mantle is in a quasi-steady-state with respect to helium, a simple model balancing 3 He and 4 He fluxes in the upper mantle indicates that the hotspots significantly outgas the lower mantle of 3 He. The concentration of 4 He in the plume source reservoir is 2-3 orders of magnitude lower than the concentration in carbonaceous chondrites. The residence time of helium in the upper mantle depends on the outgassing efficiency at hotspots, since the hotspots may outgas some upper mantle material which has been entrained in the plumes. The residence time of He in the upper mantle is about 1.4x10 9 yr. We conclude that the efficiency of outgassing of He from plumes is high and that the plumes dominate the present 3 He loss to the atmosphere. The 4 He in the less depleted layer of the mantle is not trapped ''primordial'' but is predominantly from in situ decay of U and Th in the depleted layer over ≅ 1.4x10 9 yr. The 4 He in the lower mantle is dominantly from in situ decay of U and Th over 4.4x10 9 yr. (orig./WL)

Nd-isotopes in selected mantle-derived rocks and minerals and their implications for mantle evolution

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Basu, A.R.; Tatsumoto, M.

1980-01-01

The Sm-Nd systematics in a variety of mantle-derived samples including kimberlites, alnoite, carbonatite, pyroxene and amphibole inclusions in alkali basalts and xenolithic eclogites, granulites and a pyroxene megacryst in kimberlites are reported. The additional data on kimberlites strengthen our earlier conclusion that kimberlites are derived from a relatively undifferentiated chondritic mantle source. This conclusion is based on the observation that the e{open}Nd values of most of the kimberlites are near zero. In contrast with the kimberlites, their garnet lherzolite inclusions show both time-averaged Nd enrichment and depletion with respect to Sm. Separated clinopyroxenes in eclogite xenoliths from the Roberts Victor kimberlite pipe show both positive and negative e{open}Nd values suggesting different genetic history. A whole rock lower crustal scapolite granulite xenolith from the Matsoku kimberlite pipe shows a negative e{open}Nd value of -4.2, possibly representative of the base of the crust in Lesotho. It appears that all inclusions, mafic and ultramafic, in kimberlites are unrelated to their kimberlite host. The above data and additional Sm-Nd data on xenoliths in alkali basalts, alpine peridotite and alnoite-carbonatites are used to construct a model for the upper 200 km of the earth's mantle - both oceanic and continental. The essential feature of this model is the increasing degree of fertility of the mantle with depth. The kimberlite's source at depths below 200 km in the subcontinental mantle is the most primitive in this model, and this primitive layer is also extended to the suboceanic mantle. However, it is clear from the Nd-isotopic data in the xenoliths of the continental kimberlites that above 200 km the continental mantle is distinctly different from their suboceanic counterpart. ?? 1980 Springer-Verlag.

Archean greenstone-tonalite duality: Thermochemical mantle convection models or plate tectonics in the early Earth global dynamics?

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Kerrich, Robert; Polat, Ali

2006-03-01

Mantle convection and plate tectonics are one system, because oceanic plates are cold upper thermal boundary layers of the convection cells. As a corollary, Phanerozoic-style of plate tectonics or more likely a different version of it (i.e. a larger number of slowly moving plates, or similar number of faster plates) is expected to have operated in the hotter, vigorously convecting early Earth. Despite the recent advances in understanding the origin of Archean greenstone-granitoid terranes, the question regarding the operation of plate tectonics in the early Earth remains still controversial. Numerical model outputs for the Archean Earth range from predominantly shallow to flat subduction between 4.0 and 2.5 Ga and well-established steep subduction since 2.5 Ga [Abbott, D., Drury, R., Smith, W.H.F., 1994. Flat to steep transition in subduction style. Geology 22, 937-940], to no plate tectonics but rather foundering of 1000 km sectors of basaltic crust, then "resurfaced" by upper asthenospheric mantle basaltic melts that generate the observed duality of basalts and tonalities [van Thienen, P., van den Berg, A.P., Vlaar, N.J., 2004a. Production and recycling of oceanic crust in the early earth. Tectonophysics 386, 41-65; van Thienen, P., Van den Berg, A.P., Vlaar, N.J., 2004b. On the formation of continental silicic melts in thermochemical mantle convection models: implications for early Earth. Tectonophysics 394, 111-124]. These model outputs can be tested against the geological record. Greenstone belt volcanics are composites of komatiite-basalt plateau sequences erupted from deep mantle plumes and bimodal basalt-dacite sequences having the geochemical signatures of convergent margins; i.e. horizontally imbricated plateau and island arc crust. Greenstone belts from 3.8 to 2.5 Ga include volcanic types reported from Cenozoic convergent margins including: boninites; arc picrites; and the association of adakites-Mg andesites- and Nb-enriched basalts. Archean cratons

Numerical simulations of the mantle lithosphere delamination

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Morency, C.; Doin, M.-P.

2004-03-01

Sudden uplift, extension, and increased igneous activity are often explained by rapid mechanical thinning of the lithospheric mantle. Two main thinning mechanisms have been proposed, convective removal of a thickened lithospheric root and delamination of the mantle lithosphere along the Moho. In the latter case, the whole mantle lithosphere peels away from the crust by the propagation of a localized shear zone and sinks into the mantle. To study this mechanism, we perform two-dimensional (2-D) numerical simulations of convection using a viscoplastic rheology with an effective viscosity depending strongly on temperature, depth, composition (crust/mantle), and stress. The simulations develop in four steps. (1) We first obtain "classical" sublithospheric convection for a long time period (˜300 Myr), yielding a slightly heterogeneous lithospheric temperature structure. (2) At some time, in some simulations, a strong thinning of the mantle occurs progressively in a small area (˜100 km wide). This process puts the asthenosphere in direct contact with the lower crust. (3) Large pieces of mantle lithosphere then quickly sink into the mantle by the horizontal propagation of a detachment level away from the "asthenospheric conduit" or by progressive erosion on the flanks of the delaminated area. (4) Delamination pauses or stops when the lithospheric mantle part detaches or when small-scale convection on the flanks of the delaminated area is counterbalanced by heat diffusion. We determine the parameters (crustal thicknesses, activation energies, and friction coefficients) leading to delamination initiation (step 2). We find that delamination initiates where the Moho temperature is the highest, as soon as the crust and mantle viscosities are sufficiently low. Delamination should occur on Earth when the Moho temperature exceeds ˜800°C. This condition can be reached by thermal relaxation in a thickened crust in orogenic setting or by corner flow lithospheric erosion in the

Clinicopathological Features of Ocular Adnexal Mantle-Cell Lymphoma in an International Multicenter Cohort

DEFF Research Database (Denmark)

Knudsen, Marina K H; Rasmussen, Peter K; Coupland, Sarah E

2017-01-01

Importance: To our knowledge, the clinical features of ocular adnexal mantle-cell lymphoma (OA-MCL) have not previously been evaluated in a large multicenter cohort. Objective: To characterize the clinical features of OA-MCL. Design, Setting, and Participants: This retrospective multicenter study...... included patient data collected from January 1, 1980, through December 31, 2015, at 6 eye cancer centers in 4 countries. Medical records of 55 patients with OA-MCL were reviewed; the median length of follow-up was 33 months. Main Outcomes and Measures: Overall survival, disease-specific survival....... Overall survival rates for the entire cohort were 65% at 3 years (95% CI, 52%-78%) and 34% at 5 years (95% CI, 21%-47%). Disease-specific survival after 5 years was 38% for the entire cohort (95% CI, 25%-51%); the disease-specific survival adjusted by eye cancer center was better in patients who had...

Gemcitabine and treatment of diffuse large B-cell lymphoma in relapsed or refractory elderly patients: A prospective randomized trial in Algeria

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Aribi Mourad

2010-01-01

Full Text Available Context: Support for non-Hodgkin′s lymphoma (NHL with large cells that is refractory or relapsed after first-line chemotherapy poses a greater therapeutic problem with bone marrow transplant therapy or when old age is a contra-indication for high-dose chemotherapy, especially among developing countries such as Algeria. Aim: To show that the regimen, including gemcitabine, could be more effective in treating elderly patients with diffuse large B-cell lymphoma (DLBCL in relapse / refractory, without complete remission, when compared with the ESHAP (etoposide, cisplatine, solumedrol, aracytine regimen. Materials and Methods: Ninety-six patients in the age group of 60-70 years were volunteers for a prospective randomized single-blind study, carried out for three years. Patients were divided into two groups by the drawing of lots. The first group (GA, n = 48, relapse; n = 27 [56.3%], refractory; n = 21 [43.7%] received treatment with ESHAP protocol and the second one (GB, n = 48, relapse; n = 28 [58%], refractory; n = 20 [42%] with GPD (gemcitabine, dexamethasone, cisplatine protocol. Results: The overall response rates and mean survival at three years were significantly higher among patients subjected to GPD treatment compared with those subjected to ESHAP treatment (63% vs. 55%, P = 0.01 and 20.5% [95% CI 16.5-24.5] vs. 11.8% [8.9-14.6], respectively. Additionally, three-year progression-free and event-free survival rates were 20.5% (16.3-24 and 19.7% (15.9-23.5, respectively, for the GPD regimen and 10.9% (8.2-13.7 and 11.1% (95% CI 8.5-13.7, respectively, for the ESHAP regimen. Moreover, the GPD regimen was associated with improving overall survival (RR=2.02, 95% CI 1.59-2.56; P = 0.000, event-free survival (2.03, 1.64-2.52; P < 0.001 and progression-free survival (1.86, 1.46-2.37; P < 0.001. Conclusion: In cases of contra-indication for high-dose chemotherapy for elderly patients with DLBCL, without complete remission, the Gemcitabine

Emergency Surgery for Refractory Status Epilepticus.

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Botre, Abhijeet; Udani, Vrajesh; Desai, Neelu; Jagadish, Spoorthy; Sankhe, Milind

2017-08-15

Management of refractory status epilepticus in children is extremely challenging. Two children with medically refractory status epilepticus, both of whom had lesional pathology on MRI and concordant data on EEG and PET scan. Emergency hemispherotomy performed in both patients. A complete, sustained seizure freedom obtained postoperatively. Emergency surgery is a treatment option in selected cases of drug refractory status epilepticus with lesional pathology and concordant data.

Traveltime dispersion in an isotropic elastic mantle: strong lower-mantle signal in differential-frequency residuals

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Schuberth, Bernhard S. A.; Zaroli, Christophe; Nolet, Guust

2015-12-01

We study wavefield effects of direct P- and S-waves in elastic and isotropic 3-D seismic structures derived from the temperature field of a high-resolution mantle circulation model. More specifically, we quantify the dispersion of traveltime residuals caused by diffraction in structures with dynamically constrained length scales and magnitudes of the lateral variations in seismic velocities and density. 3-D global wave propagation is simulated using a spectral element method. Intrinsic attenuation (i.e. dissipation of seismic energy) is deliberately neglected, so that any variation of traveltimes with frequency can be attributed to structural effects. Traveltime residuals are measured at 15, 22.5, 34 and 51 s dominant periods by cross-correlation of 3-D and 1-D synthetic waveforms. Additional simulations are performed for a model in which 3-D structure is removed in the upper 800 km to isolate the dispersion signal of the lower mantle. We find that the structural length scales inherent to a vigorously convecting mantle give rise to significant diffraction-induced body-wave traveltime dispersion. For both P- and S-waves, the difference between long-period and short-period residuals for a given source-receiver pair can reach up to several seconds for the period bands considered here. In general, these `differential-frequency' residuals tend to increase in magnitude with increasing short-period delay. Furthermore, the long-period signal typically is smaller in magnitude than the short-period one; that is, wave-front healing is efficient independent of the sign of the residuals. Unlike the single-frequency residuals, the differential-frequency residuals are surprisingly similar between the `lower-mantle' and the `whole-mantle' model for corresponding source-receiver pairs. The similarity is more pronounced in case of S-waves and varies between different combinations of period bands. The traveltime delay acquired in the upper mantle seems to cancel in these differential

Mantle flow influence on subduction evolution

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Chertova, Maria V.; Spakman, Wim; Steinberger, Bernhard

2018-05-01

The impact of remotely forced mantle flow on regional subduction evolution is largely unexplored. Here we investigate this by means of 3D thermo-mechanical numerical modeling using a regional modeling domain. We start with simplified models consisting of a 600 km (or 1400 km) wide subducting plate surrounded by other plates. Mantle inflow of ∼3 cm/yr is prescribed during 25 Myr of slab evolution on a subset of the domain boundaries while the other side boundaries are open. Our experiments show that the influence of imposed mantle flow on subduction evolution is the least for trench-perpendicular mantle inflow from either the back or front of the slab leading to 10-50 km changes in slab morphology and trench position while no strong slab dip changes were observed, as compared to a reference model with no imposed mantle inflow. In experiments with trench-oblique mantle inflow we notice larger effects of slab bending and slab translation of the order of 100-200 km. Lastly, we investigate how subduction in the western Mediterranean region is influenced by remotely excited mantle flow that is computed by back-advection of a temperature and density model scaled from a global seismic tomography model. After 35 Myr of subduction evolution we find 10-50 km changes in slab position and slab morphology and a slight change in overall slab tilt. Our study shows that remotely forced mantle flow leads to secondary effects on slab evolution as compared to slab buoyancy and plate motion. Still these secondary effects occur on scales, 10-50 km, typical for the large-scale deformation of the overlying crust and thus may still be of large importance for understanding geological evolution.

Survival of the primitive mantle reservoir?

Science.gov (United States)

Huang, S.; Jacobsen, S. B.; Mukhopadhyay, S.

2010-12-01

The high-3He lavas are thought to originate from a deep primitive mantle source that has not been much modified since the formation of Earth’s core. Comparison of 4He/3He in MORBs and plume lavas indicate that the plume sources must be a lower mantle feature, in agreement with most geophysical inferences. However, the lithophile element isotope systems of plume lavas are not primitive. The idea that the high-3He source is significantly less processed and more primitive than MORB source is clearly supported by mixing trends in plots of 4He/3He versus Sr, Nd and Pb isotope ratios, which have been extrapolated to an inferred 4He/3He of ~17,000 (~43x the atmospheric ratio), a mantle reservoir named PHEM (Primitive HElium Mantle). Slightly lower 4He/3He, ~15,000, were reported for Baffin Island picrites. Recently, Jackson et al. (2010) claimed that some Baffin Island and Greenland picrites with single-stage Pb model ages of ~4.5 Ga have low 4He/3He, and argued that “their source is the most ancient accessible reservoir in the Earth’s mantle, and it may be parental to all mantle reservoirs”. However, the available data are insufficient to make such a claim, and we suggest an alternative interpretation. Specially: 1. Four out of ten Baffin Island and Greenland picrites used by Jackson et al. (2010) have 4He/3He higher than average MORB value and all are far removed from the lowest measured value of 15,000. 2. Five Greenland picrites which cluster around the 4.50 Gyr geochron (Jackson et al., 2010) form a curved 207Pb*/206Pb*-4He/3He trend. This trend is best explained as a mixing line, implying that the single-stage Pb ages of these lavas are meaningless. 3. In a 207Pb*/206Pb*-4He/3He plot, Koolau lavas from Hawaii overlap with Baffin Island and Greenland picrites. If Baffin Island and Greenland picrites represent melts from the primitive mantle based on their Pb and He isotopes (Jackson et al., 2010), a similar argument can be applied to Koolau lavas. However, it

Refractory Lactic Acidosis in Small Cell Carcinoma of the Lung

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Daniel J. Oh

2017-01-01

Full Text Available Background. Elevated lactate levels in critically ill patients are most often thought to be indicative of relative tissue hypoxia or type A lactic acidosis. Shock, severe anemia, and thromboembolic events can all cause elevated lactate due to tissue hypoperfusion, as well as the mitochondrial dysfunction thought to occur in sepsis and other critically ill states. Malignancy can also lead to elevation in lactate, a phenomenon described as type B lactic acidosis, which is much less commonly encountered in the critically ill. Case Presentation. We present the case of a 73-year-old Caucasian woman with type 2 diabetes and hypertension who presented with abdominal pain, nausea, vomiting, nonbloody diarrhea, and weight loss over five weeks and was found to have unexplained refractory lactic acidosis despite fluids and antibiotics. She was later diagnosed with small cell carcinoma of the lung. Conclusions. In this case report, we describe a critically ill patient whose elevated lactate was incorrectly attributed to her acute illness, when in truth it was an indicator of an underlying, as yet undiagnosed, malignancy. We believe this case is instructive to the critical care clinician as a reminder of the importance of considering malignancy on the differential diagnosis of a patient presenting with elevated lactate out of proportion to their critical illness.

Stagnant lids and mantle overturns: Implications for Archaean tectonics, magmagenesis, crustal growth, mantle evolution, and the start of plate tectonics

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Jean H. Bédard

2018-01-01

Full Text Available The lower plate is the dominant agent in modern convergent margins characterized by active subduction, as negatively buoyant oceanic lithosphere sinks into the asthenosphere under its own weight. This is a strong plate-driving force because the slab-pull force is transmitted through the stiff sub-oceanic lithospheric mantle. As geological and geochemical data seem inconsistent with the existence of modern-style ridges and arcs in the Archaean, a periodically-destabilized stagnant-lid crust system is proposed instead. Stagnant-lid intervals may correspond to periods of layered mantle convection where efficient cooling was restricted to the upper mantle, perturbing Earth's heat generation/loss balance, eventually triggering mantle overturns. Archaean basalts were derived from fertile mantle in overturn upwelling zones (OUZOs, which were larger and longer-lived than post-Archaean plumes. Early cratons/continents probably formed above OUZOs as large volumes of basalt and komatiite were delivered for protracted periods, allowing basal crustal cannibalism, garnetiferous crustal restite delamination, and coupled development of continental crust and sub-continental lithospheric mantle. Periodic mixing and rehomogenization during overturns retarded development of isotopically depleted MORB (mid-ocean ridge basalt mantle. Only after the start of true subduction did sequestration of subducted slabs at the core-mantle boundary lead to the development of the depleted MORB mantle source. During Archaean mantle overturns, pre-existing continents located above OUZOs would be strongly reworked; whereas OUZO-distal continents would drift in response to mantle currents. The leading edge of drifting Archaean continents would be convergent margins characterized by terrane accretion, imbrication, subcretion and anatexis of unsubductable oceanic lithosphere. As Earth cooled and the background oceanic lithosphere became denser and stiffer, there would be an increasing

Mantle strength of the San Andreas fault system and the role of mantle-crust feedbacks

NARCIS (Netherlands)

Chatzaras, V.; Tikoff, B.; Newman, J.; Withers, A.C.; Drury, M.R.

2015-01-01

In lithospheric-scale strike-slip fault zones, upper crustal strength is well constrained from borehole observations and fault rock deformation experiments, but mantle strength is less well known. Using peridotite xenoliths, we show that the upper mantle below the San Andreas fault system

Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib- based chemotherapy

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Zhao J

2015-06-01

Full Text Available Junmei Zhao,* Chao Wang,* Yongping Song, Yuzhang Liu, Baijun FangHenan Key Lab of Experimental Haematology, Henan Institute of Haematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China  *These authors contributed equally to this work Abstract: Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT. Eight (88.9% patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results. Keywords: acute lymphoblastic leukemia, refractory, relapsed, bortezomib

The mantle-plume model, its feasibility and consequences

NARCIS (Netherlands)

Calsteren, van P.W.C.

1981-01-01

High beat-flow foci on the Earth have been named ‘hot-spots’ and are commonly correlated with ‘mantle-plumes’ in the deep. A mantle plume may be described as a portion of mantle material with a higher heat content than its surroundings. The intrusion of a mantle-plume is inferred to be similar to

Contrasting geochemical trends in the fertile and refractory parts of the NE Atlantic mantle source

Science.gov (United States)

Tronnes, R. G.; Debaille, V.; Brandon, A. D.; Waight, T. E.; Graham, D. W.; Williams, A.; Lee, C. A.

2008-12-01

Primitive alkaline basalts from the Icelandic off-rift volcanic zones and Jan Mayen represent low-degree melts from the fertile parts of the NE Atlantic mantle. Olivine tholeiites and picrites from the Icelandic rift zones and nearby oceanic spreading ridges are formed by protracted decompressional melting. The V-shaped ridges along the Reykjanes, Kolbeinsey and Aegir ridges indicate that ascending source material is supplied by a pulsating plume and deflected laterally for distances of about 1000 km from Iceland (Jones et al. GGG 2002; Breivik et al. JGR 2006). Plume material deflected in the direction of the rift zones and spreading ridges undergoes extensive melting at shallow level, whereas material deflected in other directions flows laterally at deeper levels and remains largely unmelted and more fertile. The comparison of a sample suite of primitive off-rift basalts from Iceland and Jan Mayen (Debaille et al., in prep.) with olivine tholeiites and picrites from the Icelandic rift zones (mainly Brandon et al. GCA 2007) demonstrate opposing geochemical trends. The degree of source enrichment, expressed by the La/Sm-ratio, is positively and negatively correlated with 87/86Sr and 143/144Nd throughout the entire range of depleted rift zone tholeiites and enriched off-rift basalts. In the rift zone tholeiites the La/Sm-ratio has negative correlations with Mg# and Mg-content and positive correlations with 187/188Os and 3/4He. These four trends have opposite equivalents for the off-rift basalts. The most enriched and alkaline basalts from Jan Mayen and Snæfellsnes have the lowest 3/4He of 6-9*Ra and 187/188Os of 0.12-0.13. The trends seem to require a source component with ancient melt depletion and subsequent enrichment. A subcontinental lithospheric mantle keel (SCLM) is the most likely origin for the enriched component with high LILE, La/Sm and 87/86Sr and low 143/144Nd, 3/4He and 187/188Os. The most enriched alkaline basalts have notably higher Mg# and Mg and

Updates in Refractory Status Epilepticus

Science.gov (United States)

Mahulikar, Advait; Suchdev, Kushak; Shah, Aashit

2018-01-01

Refractory status epilepticus is defined as persistent seizures despite appropriate use of two intravenous medications, one of which is a benzodiazepine. It can be seen in up to 40% of cases of status epilepticus with an acute symptomatic etiology as the most likely cause. New-onset refractory status epilepticus (NORSE) is a recently coined term for refractory status epilepticus where no apparent cause is found after initial testing. A large proportion of NORSE cases are eventually found to have an autoimmune etiology needing immunomodulatory treatment. Management of refractory status epilepticus involves treatment of an underlying etiology in addition to intravenous anesthetics and antiepileptic drugs. Alternative treatment options including diet therapies, electroconvulsive therapy, and surgical resection in case of a focal lesion should be considered. Short-term and long-term outcomes tend to be poor with significant morbidity and mortality with only one-third of patients reaching baseline neurological status. PMID:29854452

Mantle geofluid and uranium ore-formation model

International Nuclear Information System (INIS)

Wu Jianhua; Liu Shuai; Yu Dagan; Zhang Bangtong

2005-01-01

Results of the recent research show that volcanic-type and granite-type uranium deposits have both early and late phases of uranium mineralization, and the early phase uranium mineralization is characterized by metallogenetic features of mantle fluids. This paper discusses the geofluids and related metallogenesis, as well as characteristics of early phase uranium mineralisation, and emphasizes, that the ΣCO 2 , U and H 2 O, that comprise the bulk of the ore-forming hot fluids, are originated from different sources, namely CO 2 comes from mantle fluids, U comes from country rocks the mantle fluids have passed during their ascending way, and H 2 O comes from mantle fluids and country rocks the mantle fluids have passed during their ascending way. (authors)

Identification of methylated genes associated with aggressive clinicopathological features in mantle cell lymphoma.

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Anna Enjuanes

Full Text Available BACKGROUND: Mantle cell lymphoma (MCL is genetically characterized by the t(11;14(q13;q32 translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. METHODOLOGY/PRINCIPAL FINDINGS: To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n = 38. After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n = 25 in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9, HOXA9, AHR, NR2F2, and ROBO1 frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. CONCLUSIONS: We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP that may influence the behaviour of the tumours.

Sub-Moho Reflectors, Mantle Faults and Lithospheric Rheology

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Brown, L. D.

2013-12-01

One of the most unexpected and dramatic observations from the early years of deep reflection profiling of the continents using multichannel CMP techniques was the existing of prominent reflections from the upper mantle. The first of these, the Flannan thrust/fault/feature, was traced by marine profiling of the continental margin offshore Britain by the BIRPS program, which soon found them to be but one of several clear sub-crustal discontinuities in that area. Subsequently, similar mantle reflectors have been observed in many areas around the world, most commonly beneath Precambrian cratonic areas. Many, but not all, of these mantle reflections appear to arise from near the overlying Moho or within the lower crust before dipping well into the mantle. Others occur as subhorizontal events at various depths with the mantle, with one suite seeming to cluster at a depth of about 75 km. The dipping events have been variously interpreted as mantle roots of crustal normal faults or the deep extension of crustal thrust faults. The most common interpretation, however, is that these dipping events are the relicts of ancient subduction zones, the stumps of now detached Benioff zones long since reclaimed by the deeper mantle. In addition to the BIRPS reflectors, the best known examples include those beneath Fennoscandia in northern Europe, the Abitibi-Grenville of eastern Canada, and the Slave Province of northwestern Canada (e.g. on the SNORCLE profile). The most recently reported example is from beneath the Sichuan Basin of central China. The preservation of these coherent, and relatively delicate appearing, features beneath older continental crust and presumably within equally old (of not older) mantle lithosphere, has profound implications for the history and rheology of the lithosphere in these areas. If they represent, as widely believe, some form of faulting with the lithosphere, they provide corollary constraints on the nature of faulting in both the lower crust and

Trace element distribution in peridotite xenoliths from Tok, SE Siberian craton: A record of pervasive, multi-stage metasomatism in shallow refractory mantle

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Ionov, Dmitri A.; Chazot, Gilles; Chauvel, Catherine; Merlet, Claude; Bodinier, Jean-Louis

2006-03-01

Spinel peridotite xenoliths in alkali basalts at Tok, SE Siberian craton range from fertile lherzolites to harzburgites and wehrlites; olivine-rich (70-84%) rocks are dominant. REE patterns in the lherzolites range from nearly flat for fertile rocks (14-17% cpx) to LREE-enriched; the enrichments are positively correlated with modal olivine, consistent with high-permeability of olivine-rich rocks during melt percolation. Clinopyroxene in olivine-rich Tok peridotites typically has convex-upward trace element patterns (La/Nd PM 1); the LREE-enrichments are positively correlated with phosphorus abundances and are mainly hosted by accessory phosphates and P-rich cryptocrystalline materials. In addition to apatite, some Tok xenoliths contain whitlockite (an anhydrous, halogen-poor and Na-Mg-rich phosphate), which is common in meteorites and lunar rocks, but has not been reported from any terrestrial mantle samples. Some olivine-rich peridotites have generations of clinopyroxene with distinct abundances of Na, LREE, Sr and Zr. The mineralogical and trace element data indicate that the lithospheric mantle section represented by the xenoliths experienced a large-scale metasomatic event produced by upward migration of mafic silicate melts followed by percolation of low- T, alkali-rich melts and fluids. Chromatographic fractionation and fractional crystallisation of the melts close to the percolation front produced strong LREE-enrichments, which are most common in the uppermost mantle and are related to carbonate- and P 2O 5-rich derivatives of the initial melt. Reversal and gradual retreat of the percolation front during thermal relaxation to ambient geotherm ("retrograde" metasomatism) caused local migration and entrapment of small-volume residual fluids and precipitation of volatile-rich accessory minerals. A distinct metasomatic episode, which mainly produced "anhydrous" late-stage interstitial materials was concomitant with the alkali basaltic magmatism, which brought

Thermoconvective waves in the earth's mantle

Science.gov (United States)

Birger, B. I.

1980-06-01

The thermoconvective instability of the Earth's mantle is analysed. The mantle is modelled as an infinite horizontal layer with a free upper surface, heated from below. The creep in the mantle is supposed to be transient when strains are small. This transient creep is described by Lomnitz's law modified by Jeffreys (1958a). It is shown that disturbances, in the form of thermoconvective waves with a period of 10 8 - 10 9y and wavelength of the order 10 3 km, can propagate through the mantle without attenuation. These waves induce oscillations of the Earth's surface. The pattern of flows differs greatly from that suggested by plate tectonics. An attempt is made to give a new explanation for the linear magnetic anomalies over oceanic ridges.

Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM).

Science.gov (United States)

Bader, Peter; Kuçi, Zyrafete; Bakhtiar, Shahrzad; Basu, Oliver; Bug, Gesine; Dennis, Michael; Greil, Johann; Barta, Aniko; Kállay, Krisztián M; Lang, Peter; Lucchini, Giovanna; Pol, Raj; Schulz, Ansgar; Sykora, Karl-Walter; von Luettichau, Irene; Herter-Sprie, Grit; Uddin, Mohammad Ashab; Jenkin, Phil; Alsultan, Abdulrahman; Buechner, Jochen; Stein, Jerry; Kelemen, Agnes; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Hutter, Martin; Schäfer, Richard; Seifried, Erhard; Klingebiel, Thomas; Bonig, Halvard; Kuçi, Selim

2018-01-29

The inability to generate mesenchymal stromal cells (MSCs) of consistent potency likely is responsible for inconsistent clinical outcomes of patients with aGvHD receiving MSC products. We developed a novel MSC manufacturing protocol characterized by high in vitro potency and near-identity of individual doses, referred to as "MSC-Frankfurt am Main (MSC-FFM)". Herein, we report outcomes of the 69 patients who have received MSC-FFM. These were 51 children and 18 adults with refractory aGvHD grade II (4%), III (36%) or IV (59%). Patients were refractory either to frontline therapy (steroids) (29%) or to steroids and 1-5 additional lines of immunosuppressants (71%) were given infusions in four weekly intervals. The day 28 overall response rate was 83%; at the last follow-up, 61% and 25% of patients were in complete or partial remission. The median follow-up was 8.1 months. Six-month estimate for cumulative incidence of non-relapse mortality was 27% (range, 16-38); leukemia relapse mortality was 2% (range, 0-5). This was associated with a superior six-month overall survival (OS) probability rate of 71% (range, 61-83), compared to the outcome of patients not treated with MSC-FFM. This novel product was effective in children and adults, suggesting that MSC-FFM represents a promising therapy for steroid refractory aGvHD.

Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

Science.gov (United States)

Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

2017-02-01

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

Does cement mantle thickness really matter?

OpenAIRE

Caruana, J.

2008-01-01

The thickness of the cement mantle around the femoral component of total hip replacements is a contributing factor to aseptic loosening and revision. Nevertheless, various designs of stems and surgical tooling lead to cement mantles of differing thicknesses. This thesis is concerned with variability in cement thickness around the Stanmore Hip, due to surgical approach, broach size and stem orientation, and its effects on stress and cracking in the cement. The extent to which cement mantle thi...

Refractory status epilepticus

Directory of Open Access Journals (Sweden)

Sanjay P Singh

2014-01-01

Full Text Available Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED, i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits.

Refractory status epilepticus

Science.gov (United States)

Singh, Sanjay P; Agarwal, Shubhi; Faulkner, M

2014-01-01

Refractory status epilepticus is a potentially life-threatening medical emergency. It requires early diagnosis and treatment. There is a lack of consensus upon its semantic definition of whether it is status epilepticus that continues despite treatment with benzodiazepine and one antiepileptic medication (AED), i.e., Lorazepam + phenytoin. Others regard refractory status epilepticus as failure of benzodiazepine and 2 antiepileptic medications, i.e., Lorazepam + phenytoin + phenobarb. Up to 30% patients in SE fail to respond to two antiepileptic drugs (AEDs) and 15% continue to have seizure activity despite use of three drugs. Mechanisms that have made the treatment even more challenging are GABA-R that is internalized during status epilepticus and upregulation of multidrug transporter proteins. All patients of refractory status epilepticus require continuous EEG monitoring. There are three main agents used in the treatment of RSE. These include pentobarbital or thiopental, midazolam and propofol. RSE was shown to result in mortality in 35% cases, 39.13% of patients were left with severe neurological deficits, while another 13% had mild neurological deficits. PMID:24791086

Formation and modification of chromitites in the mantle

Science.gov (United States)

Arai, Shoji; Miura, Makoto

2016-11-01

Podiform chromitites have long supplied us with unrivaled information on various mantle processes, including the peridotite-magma reaction, deep-seated magmatic evolution, and mantle dynamics. The recent discovery of ultrahigh-pressure (UHP) chromitites not only sheds light on a different aspect of podiform chromitites, but also changes our understanding of the whole picture of podiform chromitite genesis. In addition, new evidence was recently presented for hydrothermal modification/formation chromite/chromitite in the mantle, which is a classical but innovative issue. In this context, we present here an urgently needed comprehensive review of podiform chromitites in the upper mantle. Wall-rock control on podiform chromitite genesis demonstrates that the peridotite-magma reaction at the upper mantle condition is an indispensable process. We may need a large system in the mantle, far larger than the size of outcrops or mining areas, to fulfill the Cr budget requirement for podiform chromitite genesis. The peridotite-magma reaction over a large area may form a melt enriched with Na and other incompatible elements, which mixes with a less evolved magma supplied from the depth to create chromite-oversaturated magma. The incompatible-element-rich magma trapped by the chromite mainly precipitates pargasite and aspidolite (Na analogue of phlogopite), which are stable under upper mantle conditions. Moderately depleted harzburgites, which contain chromite with a moderate Cr# (0.4-0.6) and a small amount of clinopyroxene, are the best reactants for the chromitite-forming reaction, and are the best hosts for podiform chromitites. Arc-type chromitites are dominant in ophiolites, but some are of the mid-ocean ridge type; chromitites may be common beneath the ocean floor, although it has not yet been explored for chromitite. The low-pressure (upper mantle) igneous chromitites were conveyed through mantle convection or subduction down to the mantle transition zone to form

Development of refractory concrete for extreme conditions

International Nuclear Information System (INIS)

Pundiene, I; Antonovich, V; Stonys, R; Demidova-Buiziniene, I

2011-01-01

Comparative analysis is provided for the properties of medium-cement refractory concrete with microsilica based on mullite filler in relation to different type of deflocculant. The effect of different deflocculants on refractory concrete structure formation, hydration, rheology, strength and heat resistance is discussed. Corrosion resistance test, determined that samples with hybrid deflocculant showed better resistance for slag penetration than samples with only the sodium tripolyphosphate or polycarboxylate ether deflocculant. Moreover, a composition of hybrid deflocculant let to control the rate of the hydration process and to get features of refractory refractory concrete.

A retrospective study on the management of patients with rituximab refractory follicular lymphoma.

Science.gov (United States)

Solal-Céligny, Philippe; Leconte, Pierre; Bardet, Aurélie; Hernandez, Juana; Troussard, Xavier

2018-01-01

Given that there are currently no clear recommendations regarding therapeutic options for rituximab refractory/relapsed follicular lymphoma patients, this study aimed to describe the real-life management of patients with refractory follicular lymphoma after systemic rituximab-containing regimens (rFL), and rFL patient characteristics. In this retrospective, national, multicentre study, descriptive analyses were mainly performed according to rituximab-containing regimen at rFL diagnosis [rituximab monotherapy (R-MONO), rituximab + chemotherapy (R-COMBO), and ongoing rituximab maintenance (R-MAINTAIN)]. The 459 analysed patients experienced rituximab-refractoriness between October 2013 and September 2015: R-MONO: 58 (13%), R-COMBO: 197 (43%), R-MAINTAIN: 204 (44%). Post-refractoriness strategies were heterogeneous: idelalisib ± rituximab (22%), without anti-lymphoma treatment (21%), rituximab-chemotherapy (21%) and stem cell transplantation (18%). Rituximab was continued in combination in 41% of cases. Chosen strategies varied according to patient age (without anti-lymphoma treatment: 28% of patients if ≥65 years vs. 12% if management and for the design of clinical trials in these patients. © 2017 John Wiley & Sons Ltd.

High-Density Infrared Surface Treatments of Refractories

Energy Technology Data Exchange (ETDEWEB)

Tiegs, T.N.

2005-03-31

Refractory materials play a crucial role in all energy-intensive industries and are truly a crosscutting technology for the Industries of the Future (IOF). One of the major mechanisms for the degradation of refractories and a general decrease in their performance has been the penetration and corrosion by molten metals or glass. Methods and materials that would reduce the penetration, wetting, and corrosive chemistry would significantly improve refractory performance and also maintain the quality of the processed liquid, be it metal or glass. This report presents the results of an R&D project aimed at investigating the use of high-density infrared (HDI) heating to surface treat refractories to improve their performance. The project was a joint effort between Oak Ridge National Laboratory (ORNL) and the University of Missouri-Rolla (UMR). HDI is capable of heating the near-surface region of materials to very high temperatures where sintering, diffusion, and melting can occur. The intended benefits of HDI processing of refractories were to (1) reduce surface porosity (by essentially sealing the surface to prevent liquid penetration), (2) allow surface chemistry changes to be performed by bonding an adherent coating onto the underlying refractory (in order to inhibit wetting and/or improve corrosion resistance), and (3) produce noncontact refractories with high-emissivity surface coatings.

Sublithospheric flows in the mantle

Science.gov (United States)

Trifonov, V. G.; Sokolov, S. Yu.

2017-11-01

The estimated rates of upper mantle sublithospheric flows in the Hawaii-Emperor Range and Ethiopia-Arabia-Caucasus systems are reported. In the Hawaii-Emperor Range system, calculation is based on motion of the asthenospheric flow and the plate moved by it over the branch of the Central Pacific plume. The travel rate has been determined based on the position of variably aged volcanoes (up to 76 Ma) with respect to the active Kilauea Volcano. As for the Ethiopia-Arabia-Caucasus system, the age of volcanic eruptions (55-2.8 Ma) has been used to estimate the asthenospheric flow from the Ethiopian-Afar superplume in the northern bearing lines. Both systems are characterized by variations in a rate of the upper mantle flows in different epochs from 4 to 12 cm/yr, about 8 cm/yr on average. Analysis of the global seismic tomographic data has made it possible to reveal rock volumes with higher seismic wave velocities under ancient cratons; rocks reach a depth of more than 2000 km and are interpreted as detached fragments of the thickened continental lithosphere. Such volumes on both sides of the Atlantic Ocean were submerged at an average velocity of 0.9-1.0 cm/yr along with its opening. The estimated rates of the mantle flows clarify the deformation properties of the mantle and regulate the numerical models of mantle convection.

Ixabepilone: a new chemotherapeutic option for refractory metastatic breast cancer

Directory of Open Access Journals (Sweden)

Shannon Puhalla

2008-09-01

Full Text Available Shannon Puhalla, Adam BrufskyUPMC Magee-Womens Cancer Program, University of Pittsburgh, Pittsburgh, Pennsylvania, USAAbstract: Taxane therapy is commonly used in the treatment of metastatic breast cancer. However, most patients will eventually become refractory to these agents. Ixabepilone is a newly approved chemotherapeutic agent for the treatment of metastatic breast cancer. Although it targets microtubules similarly to docetaxel and paclitaxel, ixabepilone has activity in patients that are refractory to taxanes. This review summarizes the pharmacology of ixapebilone and clinical trials with the drug both as a single agent and in combination. Data were obtained using searches of PubMed and abstracts of the annual meetings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium from 1995 to 2008. Ixapebilone is a semi-synthetic analog of epothilone B that acts to induce apoptosis of cancer cells via the stabilization of microtubules. Phase I clinical trials have employed various dosing schedules ranging from daily to weekly to 3-weekly. Dose-limiting toxicites included neuropathy and neutropenia. Responses were seen in a variety of tumor types. Phase II studies verified activity in taxane-refractory metastatic breast cancer. The FDA has approved ixabepilone for use as monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer. Ixabepilone is an efficacious option for patients with refractory metastatic breast cancer. The safety profile is similar to that of taxanes, with neuropathy and neutropenia being dose-limiting. Studies are ongoing with the use of both iv and oral formulations and in combination with other chemotherapeutic and biologic agents.Keywords: ixabepilone, epothilone, metastatic breast cancer, taxane-refractory

Genetics Home Reference: iron-refractory iron deficiency anemia

Science.gov (United States)

... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

Characteristics of Vertical Mantle Heat Exchangers for Solar Water Heaters

DEFF Research Database (Denmark)

Shah, Louise Jivan; Morrison, G.L.; Behnia, M.

1999-01-01

- The flow structure in vertical mantle heat exchangers was investigated using a full-scale tank designed to facilitate flow visualisation. The flow structure and velocities in the mantle were measured using a particle Image Velocimetry (PIV) system. A CFD simulation model of vertical mantle heat...... exchangers was also developed for detailed evaluation of the heat flux distribution over the mantle surface. Both the experimental and simulation results indicate that distribution of the flow around the mantle gap is governed by buoyancy driven recirculation in the mantle. The operation of the mantle...

MODELLING MANTLE TANKS FOR SDHW SYSTEMS USING PIV AND CFD

DEFF Research Database (Denmark)

Shah, Louise Jivan; Morrison, G.L.; Behnia, Masud

1999-01-01

Characteristics of vertical mantle heat exchanger tanks for SDHW systems have been investigated experimentally and theoretically using particle image velocimetry (PIV) and CFD modelling. A glass model of a mantle heat exchanger tank was constructed so that the flow distribution in the mantle could...... be studied using the PIV test facility. Two transient three-dimensional CFD-models of the glass model mantle tank were developed using the CFD-programmes CFX and FLUENT.The experimental results illustrate that the mantle flow structure in the mantle is complicated and the distribution of flow in the mantle...

Refractory hypertension: definition, prevalence, and patient characteristics.

Science.gov (United States)

Acelajado, Maria Czarina; Pisoni, Roberto; Dudenbostel, Tanja; Dell'Italia, Louis J; Cartmill, Falynn; Zhang, Bin; Cofield, Stacey S; Oparil, Suzanne; Calhoun, David A

2012-01-01

Among patients with resistant hypertension (RHTN), there are those whose blood pressure (BP) remains uncontrolled in spite of maximal medical therapy. This retrospective analysis aims to characterize these patients with refractory hypertension. Refractory hypertension was defined as BP that remained uncontrolled after ≥3 visits to a hypertension clinic within a minimum 6-month follow-up period. Of the 304 patients referred for RHTN, 29 (9.5%) remained refractory to treatment. Patients with refractory hypertension and those with controlled RHTN had similar aldosterone levels and plasma renin activity (PRA). Patients with refractory hypertension had higher baseline BP (175±23/97±15 mm Hg vs 158±25/89±15 mm Hg; P=.001/.005) and heart rate, and higher rates of prior stroke and congestive heart failure. During follow-up, the BP of patients with refractory hypertension remained uncontrolled (168.4±14.8/93.8±17.7 mm Hg) in spite of use of an average of 6 antihypertensive medications, while those of patients with controlled RHTN decreased to 129.3±11.2/77.6±10.8 mm Hg. Spironolactone reduced the BP by 12.9±17.8/6.6±13.7 mm Hg in patients with refractory hypertension and by 24.1±16.7/9.2±12.0 mm Hg in patients with controlled RHTN. In patients with RHTN, approximately 10% remain refractory to treatment. Similar aldosterone and PRA levels and a diminished response to spironolactone suggest that aldosterone excess does not explain the treatment failure. © 2011 Wiley Periodicals, Inc.

Salvage chemotherapy of gemcitabine, dexamethasone, and cisplatin (GDP) for patients with relapsed or refractory peripheral T-cell lymphomas: a consortium for improving survival of lymphoma (CISL) trial.

Science.gov (United States)

Park, Byeong-Bae; Kim, Won Seog; Suh, Cheolwon; Shin, Dong-Yeop; Kim, Jeong-A; Kim, Hoon-Gu; Lee, Won Sik

2015-11-01

There is no standard salvage chemotherapy for relapsed or refractory peripheral T-cell lymphomas (PTCLs). Gemcitabine combined with cisplatin has been known as an effective regimen for lymphoma treatment in the salvage setting. We investigated the efficacy and toxicity of gemcitabine, dexamethasone, and cisplatin (GDP) for relapsed or refractory PTCLs in search of a more effective and less toxic therapy. Patients with relapsed or refractory PTCLs with more than one previous regimen were eligible. Treatment consisted of gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4, and cisplatin 70 mg/m(2) i.v. on day 1, and then every 21 days. Patients could proceed to autologous stem cell transplantation (ASCT) after four cycles of GDP or receive up to six treatment cycles. Twenty-five eligible patients were evaluated for toxicity and response. The diagnoses of participants included 14 cases of PTCL-not otherwise specified (NOS) (56 %) and four cases of angioimmunoblastic T-cell lymphoma (16 %) among others. The median age of the patients was 59 years (range 20-75 years). After treatments with GDP, which delivered a median of four GDP cycles, there were 12 patients with complete responses (CR; 48 %) and six with partial responses (PR; 24 %). The overall response rate (RR) was 72 %. Four patients preceded to ASCT, and three patients finally achieved CR. The median progression free survival was 9.3 months (95 % confidence interval (CI); 4.1-14.6) with a median follow-up duration of 27.1 months. In a total of 86 cycles of GDP, grade 3 or 4 neutropenia and thrombocytopenia occurred in 16.3 and 12.8 % of cycles, respectively. Three patients (3.3 %) experienced febrile neutropenia. GDP is a highly effective and optimal salvage regimen for relapsed or refractory PTCLs and can be administered with acceptable toxicity.

Clinical Options in Relapsed or Refractory Hodgkin Lymphoma: An Updated Review

Directory of Open Access Journals (Sweden)

Roberta Fedele

2015-01-01

Full Text Available Hodgkin lymphoma (HL is a potentially curable lymphoma, and modern therapy is expected to successfully cure more than 80% of the patients. Second-line salvage high-dose chemotherapy and autologous stem cell transplantation (auto-SCT have an established role in the management of refractory and relapsed HL, leading to long-lasting responses in approximately 50% of relapsed patients and a minority of refractory patients. Patients progressing after intensive treatments, such as auto-SCT, have a very poor outcome. Allogeneic SCT represents the only strategy with a curative potential for these patients; however, its role is controversial. Based on recent knowledge of HL pathology, biology, and immunology, antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints are currently explored. This review will discuss the clinical results regarding auto-SCT and allo-SCT as well as the current role of emerging new treatment strategies.

The ruthenium isotopic composition of the oceanic mantle

Science.gov (United States)

Bermingham, K. R.; Walker, R. J.

2017-09-01

The approximately chondritic relative, and comparatively high absolute mantle abundances of the highly siderophile elements (HSE), suggest that their concentrations in the bulk silicate Earth were primarily established during a final ∼0.5 to 1% of ;late accretion; to the mantle, following the cessation of core segregation. Consequently, the isotopic composition of the HSE Ru in the mantle reflects an amalgamation of the isotopic compositions of late accretionary contributions to the silicate portion of the Earth. Among cosmochemical materials, Ru is characterized by considerable mass-independent isotopic variability, making it a powerful genetic tracer of Earth's late accretionary building blocks. To define the Ru isotopic composition of the oceanic mantle, the largest portion of the accessible mantle, we report Ru isotopic data for materials from one Archean and seven Phanerozoic oceanic mantle domains. A sample from a continental lithospheric mantle domain is also examined. All samples have identical Ru isotopic compositions, within analytical uncertainties, indicating that Ru isotopes are well mixed in the oceanic mantle, defining a μ100Ru value of 1.2 ± 7.2 (2SD). The only known meteorites with the same Ru isotopic composition are enstatite chondrites and, when corrected for the effects of cosmic ray exposure, members of the Main Group and sLL subgroup of the IAB iron meteorite complex which have a collective CRE corrected μ100Ru value of 0.9 ± 3.0. This suggests that materials from the region(s) of the solar nebula sampled by these meteorites likely contributed the dominant portion of late accreted materials to Earth's mantle.

Mantle Circulation Models with variational data assimilation: Inferring past mantle flow and structure from plate motion histories and seismic tomography

Science.gov (United States)

Bunge, H.; Hagelberg, C.; Travis, B.

2002-12-01

EarthScope will deliver data on structure and dynamics of continental North America and the underlying mantle on an unprecedented scale. Indeed, the scope of EarthScope makes its mission comparable to the large remote sensing efforts that are transforming the oceanographic and atmospheric sciences today. Arguably the main impact of new solid Earth observing systems is to transform our use of geodynamic models increasingly from conditions that are data poor to an environment that is data rich. Oceanographers and meteorologists already have made substantial progress in adapting to this environment, by developing new approaches of interpreting oceanographic and atmospheric data objectively through data assimilation methods in their models. However, a similarly rigorous theoretical framework for merging EarthScope derived solid Earth data with geodynamic models has yet to be devised. Here we explore the feasibility of data assimilation in mantle convection studies in an attempt to fit global geodynamic model calculations explicitly to tomographic and tectonic constraints. This is an inverse problem not quite unlike the inverse problem of finding optimal seismic velocity structures faced by seismologists. We derive the generalized inverse of mantle convection from a variational approach and present the adjoint equations of mantle flow. The substantial computational burden associated with solutions to the generalized inverse problem of mantle convection is made feasible using a highly efficient finite element approach based on the 3-D spherical fully parallelized mantle dynamics code TERRA, implemented on a cost-effective topical PC-cluster (geowulf) dedicated specifically to large-scale geophysical simulations. This dedicated geophysical modeling computer allows us to investigate global inverse convection problems having a spatial discretization of less than 50 km throughout the mantle. We present a synthetic high-resolution modeling experiment to demonstrate that mid

Refractories for Industrial Processing. Opportunities for Improved Energy Efficiency

Energy Technology Data Exchange (ETDEWEB)

Hemrick, James G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hayden, H. Wayne [Metals Manufacture Process and Controls Technology, Inc., Oak Ridge, TN (United States); Angelini, Peter [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Moore, Robert E. [R.E. Moore Associates, Maricopa, AZ (United States); Headrick, William L. [R.E. Moore Associates, Maricopa, AZ (United States)

2005-01-01

Refractories are a class of materials of critical importance to manufacturing industries with high-temperature unit processes. This study describes industrial refractory applications and identifies refractory performance barriers to energy efficiency for processing. The report provides recommendations for R&D pathways leading to improved refractories for energy-efficient manufacturing and processing.

Atlas of the underworld: Slab remnants in the mantle, their sinking history, and a new outlook on lower mantle viscosity

Science.gov (United States)

van der Meer, Douwe G.; van Hinsbergen, Douwe J. J.; Spakman, Wim

2018-01-01

Across the entire mantle we interpret 94 positive seismic wave-speed anomalies as subducted lithosphere and associate these slabs with their geological record. We document this as the Atlas of the Underworld, also accessible online at www.atlas-of-the-underworld.org, a compilation comprising subduction systems active in the past 300 Myr. Deeper slabs are correlated to older geological records, assuming no relative horizontal motions between adjacent slabs following break-off, using knowledge of global plate circuits, but without assuming a mantle reference frame. The longest actively subducting slabs identified reach the depth of 2500 km and some slabs have impinged on Large Low Shear Velocity Provinces in the deepest mantle. Anomously fast sinking of some slabs occurs in regions affected by long-term plume rising. We conclude that slab remnants eventually sink from the upper mantle to the core-mantle boundary. The range in subduction-age versus - depth in the lower mantle is largely inherited from the upper mantle history of subduction. We find a significant depth variation in average sinking speed of slabs. At the top of the lower mantle average slab sinking speeds are between 10 and 40 mm/yr, followed by a deceleration to 10-15 mm/yr down to depths around 1600-1700 km. In this interval, in situ time-stationary sinking rates suggest deceleration from 20 to 30 mm/yr to 4-8 mm/yr, increasing to 12-15 mm/yr below 2000 km. This corroborates the existence of a slab deceleration zone but we do not observe long-term (> 60 My) slab stagnation, excluding long-term stagnation due to compositional effects. Conversion of slab sinking profiles to viscosity profiles shows the general trend that mantle viscosity increases in the slab deceleration zone below which viscosity slowly decreases in the deep mantle. This is at variance with most published viscosity profiles that are derived from different observations, but agrees qualitatively with recent viscosity profiles suggested

Temperature Profile of the Upper Mantle

International Nuclear Information System (INIS)

Anderson, O.L.

1980-01-01

Following the procedure outlined by Magnitsky [1971], thermal profiles of the upper mantle are computed by deriving the thermal gradient from the seismic data given as dv/sub s//drho used along with the values of (dv/sub s//dT9/sub p/ and (dv/sub s//dP)/sub T/ of selected minerals, measured at high temperature. The resulting values of dT/dZ are integrated from 380 km upward toward the surface, where the integrating constant is taken from Akagi and Akimoto's work, T=1400 0 C at 380 km. The resulting geotherms for minerals are used to derive geotherms for an eclogite mantle and a lherzolite mantle, with and without partial melting in the low-velocity zone. The geotherms are all subadiabatic, and some are virtually isothermal in the upper mantle. Some are characterized by a large thermal hump at the lithosphere boundary

Primary pulmonary lymphoma mimicking a refractory lung abscess: A case report.

Science.gov (United States)

Matsumoto, Takeshi; Otsuka, Kojiro; Funayama, Yuki; Imai, Yukihiro; Tomii, Keisuke

2015-04-01

The current study presents a case of primary pulmonary lymphoma (PPL) mimicking refractory lung abscess that was diagnosed at autopsy. An 80-year-old male with clinically inapparent aspiration presented with a large cavitated mass and pleural effusion. A lung abscess and empyema was diagnosed, therefore, antibiotics were administered and the pleural effusion was drained. Various examinations, including a biopsy, yielded no specific diagnosis. The lesion was considered inoperable due to the poor general condition of the patient. Subsequently, the mass that had been diagnosed as a refractory lung abscess became enlarged and a repeat biopsy resulted in a diagnosis of diffuse large B-cell lymphoma. The patient succumbed to sudden respiratory failure, and the final diagnosis of PPL was confirmed at autopsy. PPL is a rare disease that accounts for 0.45% of all pulmonary malignant tumors and is difficult to diagnose in inoperable cases. Therefore, patients with PPL who do not undergo surgery can be misdiagnosed and consequently treated inappropriately. PPL should therefore be considered in the differential diagnosis of a refractory lung abscess.

Oral cyclosporine therapy for refractory severe vernal keratoconjunctivitis

Directory of Open Access Journals (Sweden)

Nikhil S Gokhale

2012-01-01

Full Text Available We report the success of oral cyclosporine therapy in a patient with severe vision-threatening vernal keratoconjunctivitis. A child presented with severe allergy which was not controlled with topical steroids, cyclosporine and mast cell stabilizers. Oral steroids were required repeatedly to suppress inflammation. Child showed a dramatic improvement and stabilization with oral cyclosporine therapy. Oral cyclosporine therapy can be tried in severe vision-threatening allergy refractory to conventional therapy.

Tomography of core-mantle boundary and lowermost mantle coupled by geodynamics: joint models of shear and compressional velocity

Directory of Open Access Journals (Sweden)

Gaia Soldati

2015-03-01

Full Text Available We conduct joint tomographic inversions of P and S travel time observations to obtain models of delta v_P  and delta v_S in the entire mantle. We adopt a recently published method which takes into account the geodynamic coupling between mantle heterogeneity and core-mantle boundary (CMB topography by viscous flow, where sensitivity of the seismic travel times to the CMB is accounted for implicitly in the inversion (i.e. the CMB topography is not explicitly inverted for. The seismic maps of the Earth's mantle and CMB topography that we derive can explain the inverted seismic data while being physically consistent with each other. The approach involved scaling P-wave velocity (more sensitive to the CMB to density anomalies, in the assumption that mantle heterogeneity has a purely thermal origin, so that velocity and density heterogeneity are proportional to one another. On the other hand, it has sometimes been suggested that S-wave velocity might be more directly sensitive to temperature, while P heterogeneity is more strongly influenced by chemical composition. In the present study, we use only S-, and not P-velocity, to estimate density heterogeneity through linear scaling, and hence the sensitivity of core-reflected P phases to mantle structure. Regardless of whether density is more closely related to P- or S-velocity, we think it is worthwhile to explore both scaling approaches in our efforts to explain seismic data. The similarity of the results presented in this study to those obtained by scaling P-velocity to density suggests that compositional anomaly has a limited impact on viscous flow in the deep mantle.

OPTIMISATION OF MANTLE TANKS FOR LOW FLOW SOLAR HEATING SYSTEMS

DEFF Research Database (Denmark)

Shah, Louise Jivan; Furbo, Simon

1996-01-01

A model, describing the heat transfer coefficients in the mantle of a mantle tank has been developed. The model is validated by means of measurements with varying operational conditions for different designed mantle tanks. The model has been implemented in an existing detailed mathematical...... with the programme and by means of tests of three SDHW systems with different designed mantle tanks. Based on the investigations design rules for mantle tanks are proposed. The model, describing the heat transfer coefficients in the mantle is approximate. In addition, the measurements have revealed...... that a temperature stratification in the hot water tank, above the mantle is built up. This phenomenon may be important, but it is not taken into calculation in the programme. Therefore, theoretical and practical work is continuing in order to make a more precise model for the whole mantle tank....

Mantle structure and tectonic history of SE Asia

Science.gov (United States)

Hall, Robert; Spakman, Wim

2015-09-01

Seismic travel-time tomography of the mantle under SE Asia reveals patterns of subduction-related seismic P-wave velocity anomalies that are of great value in helping to understand the region's tectonic development. We discuss tomography and tectonic interpretations of an area centred on Indonesia and including Malaysia, parts of the Philippines, New Guinea and northern Australia. We begin with an explanation of seismic tomography and causes of velocity anomalies in the mantle, and discuss assessment of model quality for tomographic models created from P-wave travel times. We then introduce the global P-wave velocity anomaly model UU-P07 and the tectonic model used in this paper and give an overview of previous interpretations of mantle structure. The slab-related velocity anomalies we identify in the upper and lower mantle based on the UU-P07 model are interpreted in terms of the tectonic model and illustrated with figures and movies. Finally, we discuss where tomographic and tectonic models for SE Asia converge or diverge, and identify the most important conclusions concerning the history of the region. The tomographic images of the mantle record subduction beneath the SE Asian region to depths of approximately 1600 km. In the upper mantle anomalies mainly record subduction during the last 10 to 25 Ma, depending on the region considered. We interpret a vertical slab tear crossing the entire upper mantle north of west Sumatra where there is a strong lateral kink in slab morphology, slab holes between c.200-400 km below East Java and Sumbawa, and offer a new three-slab explanation for subduction in the North Sulawesi region. There is a different structure in the lower mantle compared to the upper mantle and the deep structure changes from west to east. What was imaged in earlier models as a broad and deep anomaly below SE Asia has a clear internal structure and we argue that many features can be identified as older subduction zones. We identify remnants of slabs

Role of mantle flow in Nubia-Somalia plate divergence

Science.gov (United States)

Stamps, D. S.; Iaffaldano, G.; Calais, E.

2015-01-01

Present-day continental extension along the East African Rift System (EARS) has often been attributed to diverging sublithospheric mantle flow associated with the African Superplume. This implies a degree of viscous coupling between mantle and lithosphere that remains poorly constrained. Recent advances in estimating present-day opening rates along the EARS from geodesy offer an opportunity to address this issue with geodynamic modeling of the mantle-lithosphere system. Here we use numerical models of the global mantle-plates coupled system to test the role of present-day mantle flow in Nubia-Somalia plate divergence across the EARS. The scenario yielding the best fit to geodetic observations is one where torques associated with gradients of gravitational potential energy stored in the African highlands are resisted by weak continental faults and mantle basal drag. These results suggest that shear tractions from diverging mantle flow play a minor role in present-day Nubia-Somalia divergence.

Hf isotope evidence for a hidden mantle reservoir

DEFF Research Database (Denmark)

Bizzarro, Martin; Simonetti, A.; Stevenson, R.K.

2002-01-01

High-precision Hf isotopic analyses and U-Pb ages of carbonatites and kimberlites from Greenland and eastern North America, including Earth's oldest known carbonatite (3 Ga), indicate derivation from an enriched mantle source. This previously unidentified mantle reservoir-marked by an unradiogenic...... Hf isotopic composition and preserved in the deep mantle for at least 3 b.y.-may account for the mass imbalance in Earth's Hf-Nd budget. The Hf isotopic data presented here support a common mantle source region and genetic link between carbonatite and some oceanic-island basalt volcanoes....

Egress of CD19+CD5+ cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients

Science.gov (United States)

Francesco, Michelle; De Rooij, Martin F. M.; Magadala, Padmaja; Steggerda, Susanne M.; Huang, Min Mei; Kuil, Annemieke; Herman, Sarah E. M.; Chang, Stella; Pals, Steven T.; Wilson, Wyndham; Wiestner, Adrian; Spaargaren, Marcel; Buggy, Joseph J.; Elias, Laurence

2013-01-01

Ibrutinib (PCI-32765) is a highly potent oral Bruton tyrosine kinase (BTK) inhibitor in clinical development for treating B-cell lymphoproliferative diseases. Patients with chronic lymphocytic leukemia (CLL) often show marked, transient increases of circulating CLL cells following ibrutinib treatments, as seen with other inhibitors of the B-cell receptor (BCR) pathway. In a phase 1 study of ibrutinib, we noted similar effects in patients with mantle cell lymphoma (MCL). Here, we characterize the patterns and phenotypes of cells mobilized among patients with MCL and further investigate the mechanism of this effect. Peripheral blood CD19+CD5+ cells from MCL patients were found to have significant reduction in the expression of CXCR4, CD38, and Ki67 after 7 days of treatment. In addition, plasma chemokines such as CCL22, CCL4, and CXCL13 were reduced 40% to 60% after treatment. Mechanistically, ibrutinib inhibited BCR- and chemokine-mediated adhesion and chemotaxis of MCL cell lines and dose-dependently inhibited BCR, stromal cell, and CXCL12/CXCL13 stimulations of pBTK, pPLCγ2, pERK, or pAKT. Importantly, ibrutinib inhibited migration of MCL cells beneath stromal cells in coculture. We propose that BTK is essential for the homing of MCL cells into lymphoid tissues, and its inhibition results in an egress of malignant cells into peripheral blood. This trial was registered at www.clinicaltrials.gov as #NCT00114738. PMID:23940282

Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients.

Science.gov (United States)

Chang, Betty Y; Francesco, Michelle; De Rooij, Martin F M; Magadala, Padmaja; Steggerda, Susanne M; Huang, Min Mei; Kuil, Annemieke; Herman, Sarah E M; Chang, Stella; Pals, Steven T; Wilson, Wyndham; Wiestner, Adrian; Spaargaren, Marcel; Buggy, Joseph J; Elias, Laurence

2013-10-03

Ibrutinib (PCI-32765) is a highly potent oral Bruton tyrosine kinase (BTK) inhibitor in clinical development for treating B-cell lymphoproliferative diseases. Patients with chronic lymphocytic leukemia (CLL) often show marked, transient increases of circulating CLL cells following ibrutinib treatments, as seen with other inhibitors of the B-cell receptor (BCR) pathway. In a phase 1 study of ibrutinib, we noted similar effects in patients with mantle cell lymphoma (MCL). Here, we characterize the patterns and phenotypes of cells mobilized among patients with MCL and further investigate the mechanism of this effect. Peripheral blood CD19(+)CD5(+) cells from MCL patients were found to have significant reduction in the expression of CXCR4, CD38, and Ki67 after 7 days of treatment. In addition, plasma chemokines such as CCL22, CCL4, and CXCL13 were reduced 40% to 60% after treatment. Mechanistically, ibrutinib inhibited BCR- and chemokine-mediated adhesion and chemotaxis of MCL cell lines and dose-dependently inhibited BCR, stromal cell, and CXCL12/CXCL13 stimulations of pBTK, pPLCγ2, pERK, or pAKT. Importantly, ibrutinib inhibited migration of MCL cells beneath stromal cells in coculture. We propose that BTK is essential for the homing of MCL cells into lymphoid tissues, and its inhibition results in an egress of malignant cells into peripheral blood. This trial was registered at www.clinicaltrials.gov as #NCT00114738.

The Earth's heterogeneous mantle a geophysical, geodynamical, and geochemical perspective

CERN Document Server

Khan, Amir

2015-01-01

This book highlights and discusses recent developments that have contributed to an improved understanding of observed mantle heterogeneities and their relation to the thermo-chemical state of Earth's mantle, which ultimately holds the key to unlocking the secrets of the evolution of our planet. This series of topical reviews and original contributions address 4 themes. Theme 1 covers topics in geophysics, including global and regional seismic tomography, electrical conductivity and seismic imaging of mantle discontinuities and heterogeneities in the upper mantle, transition zone and lower mantle. Theme 2 addresses geochemical views of the mantle including lithospheric evolution from analysis of mantle xenoliths, composition of the deep Earth and the effect of water on subduction-zone processes. Theme 3 discusses geodynamical perspectives on the global thermo-chemical structure of the deep mantle. Theme 4 covers application of mineral physics data and phase equilibrium computations to infer the regional-scale ...

SEM investigation of incandescent lamp mantle structure on durability

International Nuclear Information System (INIS)

Gerneke, D.; Lang, C.

2002-01-01

Full text: The incandescent mantle as used on pressure and non-pressure liquid fuel lamps has been in use for over 100 years. What remains unexplained is the way in which the resistance to mechanical shock and the decline in tensile strength with usage is experienced. It has been suggested that to improve durability it is necessary to continuously burn a new mantle for the first two to three hours. The known factors in mantle durability and mechanical strength are chemical composition and fabric weave. This study was undertaken to investigate the effects of burning time and temperature on thorium oxide mantles. The operating temperature of mantles on a range of kerosene pressure lamps was measured and found to be between 800 and 1100 deg C. Heat treatments of thorium based Coleman mantles were carried out in a laboratory furnace within these ranges of temperatures for periods ranging from 2 minutes to 2 hours. The mantles were then viewed in a LEO S440 analytical SEM. Results at 800 deg C show a distinct change in surface morphology with increasing exposure time. At the shorter times (2-5 minutes) the surface was relatively smooth. With increased time periods (15 - 120 minutes) the surface was observed to have a large lumpy structure. At 1100 deg C the difference in surface morphology was not apparent between the shortest and longest times. The surface appears much smoother and no lumpy structure was observed. This suggests that when a mantle is operated at the higher temperature of 1100 deg C the structure of the Thorium oxide is quickly transformed into the known stronger amorphous form. This is taken as the observed smooth structure seen in the SEM images of the 1100 deg C samples. Thus the mantle is expected to be more resistant to mechanical shock and have increased durability. Practical field test results confirm these observations. The mantle on a lamp that is operating efficiently, burns brightly, will far outlast a mantle on an inefficient lamp which bums

Tungsten and refractory metals 3, proceedings

International Nuclear Information System (INIS)

Bose, A.; Dowding, R.J.

1996-01-01

The Third International Conference on Tungsten and Refractory Metals was held in Greater Washington DC at the McLean Hilton, McLean Virginia, on November 15--16, 1995. This meeting was the third in a series of conferences held in the Washington DC area. The first meeting was in 1992 and was entitled ''International Conference on Tungsten and Tungsten Alloys.'' In 1994, the scope of the meeting was expanded to include other refractory metals such as molybdenum, iridium, rhenium, tantalum and niobium. The tremendous success of that meeting was the primary motivation for this Conference. The broader scope (the inclusion of other refractory metals and alloys) of the Conference was kept intact for this meeting. In fact, it was felt that the developments in the technology of these materials required a common forum for the interchange of current research information. The papers presented in this meeting examined the rapid advancements in the technology of refractory metals, with special emphasis on the processing, structure, and properties. Among the properties there was emphasis on both quasi-static and dynamic rates. Another topic that received considerable interest was the area of refractory carbides and tungsten-copper composites. One day of concurrent session was necessary to accommodate all of the presentations

Pembrolizumab Alone or With Idelalisib or Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Other Low-Grade B-Cell Non-Hodgkin Lymphomas

Science.gov (United States)

2017-06-30

Recurrent Chronic Lymphocytic Leukemia; Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Splenic Marginal Zone Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Nodal Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma; Refractory Splenic Marginal Zone Lymphoma; Richter Syndrome; Waldenstrom Macroglobulinemia

Rapid Treatment of Leukostasis in Leukemic Mantle Cell Lymphoma Using Therapeutic Leukapheresis: A Case Report

Directory of Open Access Journals (Sweden)

Xuan Duc Nguyen

2011-01-01

Full Text Available We describe a case of severe leukocytosis caused by leukemic mantle cell lymphoma (MCL, complicated by leukostasis with myocardial infarction in which leukapheresis was used in the initial management. A 73-year-old male presented to the emergency department because of fatigue and thoracic pain. Blood count revealed 630 × 109/L WBC (white blood cells. The electrocardiogram showed ST-elevation with an increase of troponin and creatinine kinase. The diagnosis was ST-elevation myocardial infarction (STEMI induced and complicated by leukostasis. Immunophenotyping, morphology, cytogenetic and fluorescence-in-situ-hybridization analysis revealed the diagnosis of a blastoid variant of MCL. To remove leukocytes rapidly, leukapheresis was performed in the intensive care unit. Based on the differential blood count with 95% blasts, which were assigned to the lymphocyte population by the automatic hematology analyzer, leukapheresis procedures were then performed with the mononuclear cell standard program on the Spectra cell separator. The patient was treated with daily leukapheresis for 3 days. The WBC count decreased to 174 × 109/L after the third leukapheresis, with a 72% reduction. After the second apheresis, treatment with vincristine, cyclophosphamide, and prednisolone was started. The patient fully recovered in the further course of the treatment. To the best of our knowledge, this is the first report on blastoid MCL with leukostasis associated with a STEMI that was successfully treated by leukapheresis. Effective harvest of circulating lymphoma cells by leukapheresis requires adaptation of instrument settings based on the results of the differential blood count prior to apheresis.

Radiation doses from radioactivity in incandescent mantles

International Nuclear Information System (INIS)

1985-01-01

Thorium nitrate is used in the production of incandescent mantles for gas lanterns. In this report dose estimates are given for internal and external exposure that result from the use of the incandescent mantles for gas lanterns. The collective, effective dose equivalent for all users of gas mantles is estimated to be about 100 Sv per annum in the Netherlands. For the population involved (ca. 700,000 persons) this is roughly equivalent to 5% to 10% of the collective dose equivalent associated with exposure to radiation from natural sources. The major contribution to dose estimates comes from inhalation of radium during burning of the mantles. A pessimistic approach results in individual dose estimates for inhalation of up to 0.2 mSv. Consideration of dose consequences in case of a fire in a storage department learns that it is necessary for emergency personnel to wear respirators. It is concluded that the uncontrolled removal of used gas mantles to the environment (soil) does not result in a significant contribution to environmental radiation exposure. (Auth.)

Potential refractory alloy requirements for space nuclear power applications

International Nuclear Information System (INIS)

Cooper, R.H. Jr.

1984-01-01

In reviewing design requirements for refractory alloys for space nuclear applications, several key points are identified. First, the successful utilization of refractory alloys is considered an enabling requirement for the successful deployment of high efficiency, lightweight, and small space nuclear systems. Second, the recapture of refractory alloy nuclear technology developed in the 1960s and early 1970s appears to be a pacing activity in the successful utilization of refractory alloys. Third, the successful application of refractory alloys for space nuclear applications will present a significant challenge to both the materials and the systems design communities

European Lithospheric Mantle; geochemical, petrological and geophysical processes

Science.gov (United States)

Ntaflos, Th.; Puziewicz, J.; Downes, H.; Matusiak-Małek, M.

2017-04-01

The second European Mantle Workshop occurred at the end of August 2015, in Wroclaw, Poland, attended by leading scientists in the study the lithospheric mantle from around the world. It built upon the results of the first European Mantle Workshop (held in 2007, in Ferrara, Italy) published in the Geological Society of London Special Publication 293 (Coltorti & Gregoire, 2008).

A mantle plume model for the Equatorial Highlands of Venus

Science.gov (United States)

Kiefer, Walter S.; Hager, Bradford H.

1991-01-01

The possibility that the Equatorial Highlands are the surface expressions of hot upwelling mantle plumes is considered via a series of mantle plume models developed using a cylindrical axisymmetric finite element code and depth-dependent Newtonian rheology. The results are scaled by assuming whole mantle convection and that Venus and the earth have similar mantle heat flows. The best model fits are for Beta and Atla. The common feature of the allowed viscosity models is that they lack a pronounced low-viscosity zone in the upper mantle. The shape of Venus's long-wavelength admittance spectrum and the slope of its geoid spectrum are also consistent with the lack of a low-viscosity zone. It is argued that the lack of an asthenosphere on Venus is due to the mantle of Venus being drier than the earth's mantle. Mantle plumes may also have contributed to the formation of some smaller highland swells, such as the Bell and Eistla regions and the Hathor/Innini/Ushas region.

Refractories for steel-works

International Nuclear Information System (INIS)

Villanova, R.A.; Galant, C.L.; Haas, C.; Rosenbaum, V.

The routine procedures utilized for quality control of refractory materials used by PIRATINI's steel-works, are presented ' under an objetive and practical maner. The attention of the paper is concentrated upon the following' refractory types with higher consume: silicon-aluminous; aluminous; basic magnesia; basic chrom-magnesia. All steps of utilization are described, including specification, supplies programation, storage; sampling; physical tests, and also aplication procedures. Results from routine analysis during a six month period, by ' means of X-Ray Quantometry, using the fusion pearls procedure, are presented compared with Atomic Absorption [pt

Medical versus surgical treatment for refractory or recurrent peptic ulcer.

Science.gov (United States)

Gurusamy, Kurinchi Selvan; Pallari, Elena

2016-03-29

authors do not state whether these were recurrent or refractory ulcers. It appears that the participants did not have previous complications such as bleeding or perforation. Of the 77 included participants, 37 participants continued to have medical therapy while 40 participants received surgical therapy (antrectomy with or without vagotomy; subtotal gastrectomy with or without vagotomy; vagotomy; pyloroplasty and suture of the ulcer; suture or closure of ulcer without vagotomy or excision of the ulcer; proximal gastric or parietal cell vagotomy alone; suture or closure of the ulcer with proximal gastric or parietal cell vagotomy). Whether to use medical or surgical treatment was determined by participant's or treating physician's preference.The study authors reported that two participants in the medical treatment group (2 out of 37; 5.4%) had gastric cancer, which was identified by repeated biopsy. They did not report the proportion of participants who had gastric cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of gastric cancer in the medical treatment group. They did not report any other outcomes of interest for this review (that is health-related quality of life (using any validated scale), adverse events and serious adverse events, peptic ulcer bleeding, peptic ulcer perforation, abdominal pain, and long-term mortality). We found no studies that provide the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies that evaluate the natural history of recurrent and refractory peptic ulcers are urgently required to determine whether randomised controlled trials comparing medical versus surgical management in patients with recurrent or refractory peptic ulcers or both are necessary. Such studies will also provide information for the design of such randomised controlled trials. A minimum follow-up of two to three years will allow the calculation of the

Salvaged allogeneic hematopoietic stem cell transplantation for pediatric chemotherapy refractory acute leukemia.

Science.gov (United States)

Wang, Jingbo; Yuan, Lei; Cheng, Haoyu; Fei, Xinhong; Yin, Yumin; Gu, Jiangying; Xue, Song; He, Junbao; Yang, Fan; Wang, Xiaocan; Yang, Yixin; Zhang, Weijie

2018-01-09

There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis. A total of 44 patients, of whom 28 had acute myeloid leukemia (AML), 13 had acute lymphocytic leukemia (ALL), and 3 had mixed phenotype leukemia (MPL), were enrolled in this study. With a median follow-up of 19 months, the estimated 2-year overall survival (OS) and progression free survival (PFS) were 34.3% (95% CI, 17.9-51.4%) and 33.6% (95% CI, 18.0-50.1%), respectively. The estimated 2-year incidence rates of relapse and non-relapse mortality (NRM) were 43.8% (95% CI 26.4-60.0%) and 19.6% (95% CI 9.1-32.9%), respectively. The estimated 100-day cumulative incidence of acute graft versus host disease (aGvHD) was 43.6% (95% CI 28.7-57.5%), and the 1-year cumulative incidence of chronic GvHD (cGvHD) was 45.5% (95% CI 30.5-59.3%). Compared with the previous studies, the multivariate analysis in this study additionally identified that female donors and cGvHD were associated with lower relapse and better PFS and OS. Male recipients, age younger than 10 years, a diagnosis of ALL, and the intermediate-adverse cytogenetic risk group were associated with increased relapse. On the contrary, extramedullary disease (EMD) and aGvHD were only linked to worse PFS. These data suggested that although only one-third of the patients would obtain PFS over 2 years, salvaged allo-HSCT is still the most reliable and best therapeutic strategy for refractory pediatric acute leukemia. If probable, choosing a female donor, better

Development of AZS refractories for the glass industry

International Nuclear Information System (INIS)

Guzman, A.M.; Rodriguez, P.

2004-01-01

Refractory materials can support high temperatures, thermal strength and the contact with aggressive environments, for this reason they are widely used in the cement, glass and steel industry. Commercial AZS (alumina-zirconia-silica) refractories are a good alternative in refractory materials for the glass industry' because they can support the aggressive conditions during liquid processing of glass. However, another problem encountered in glass industry is contamination by refractory' material that fall into the molten glass, which can produce a series of defects in the final product. This research was conducted to develop new formulations of AZS refractories with different amounts of ZrO 2 with the purpose of improving the characteristics, properties and the work conditions in the glass melting furnaces and, at the same time, lower the costs this type of refractories. The results obtained indicate that the composition with low content of ZrO 2 can provide better properties than the commercial product, with some modifications in the particle size distribution. Copyright (2004) AD-TECH - International Foundation for the Advancement of Technology Ltd

Pillars of the Mantle

KAUST Repository

Pugmire, David

2017-07-05

In this work, we investigate global seismic tomographic models obtained by spectral-element simulations of seismic wave propagation and adjoint methods. Global crustal and mantle models are obtained based on an iterative conjugate-gradient type of optimization scheme. Forward and adjoint seismic wave propagation simulations, which result in synthetic seismic data to make measurements and data sensitivity kernels to compute gradient for model updates, respectively, are performed by the SPECFEM3D-GLOBE package [1] [2] at the Oak Ridge Leadership Computing Facility (OLCF) to study the structure of the Earth at unprecedented levels. Using advances in solver techniques that run on the GPUs on Titan at the OLCF, scientists are able to perform large-scale seismic inverse modeling and imaging. Using seismic data from global and regional networks from global CMT earthquakes, scientists are using SPECFEM3D-GLOBE to understand the structure of the mantle layer of the Earth. Visualization of the generated data sets provide an effective way to understand the computed wave perturbations which define the structure of mantle in the Earth.

Can Lower Mantle Slab-like Seismic Anomalies be Explained by Thermal Coupling Between the Upper and Lower Mantles?

NARCIS (Netherlands)

Cízková, H. (Hana); Cadek, O.; Berg, A.P. van den; Vlaar, N.J.

1999-01-01

Below subduction zones, high resolution seismic tomographic models resolve fast anomalies that often extend into the deep lower mantle. These anomalies are generally interpreted as slabs penetrating through the 660-km seismic discontinuity, evidence in support of whole-mantle convection. However,

Mantle superplumes induce geomagnetic superchrons

Directory of Open Access Journals (Sweden)

Peter eOlson

2015-07-01

Full Text Available We use polarity reversal systematics from numerical dynamos to quantify the hypothesis that the modulation of geomagnetic reversal frequency, including geomagnetic superchrons, results from changes in core heat flux related to growth and collapse of lower mantle superplumes. We parameterize the reversal frequency sensitivity from numerical dynamos in terms of average core heat flux normalized by the difference between the present-day core heat flux and the core heat flux at geomagnetic superchron onset. A low-order polynomial fit to the 0-300 Ma Geomagnetic Polarity Time Scale (GPTS reveals that a decrease in core heat flux relative to present-day of approximately 30% can account for the Cretaceous Normal Polarity and Kiaman Reverse Polarity Superchrons, whereas the hyper-reversing periods in the Jurassic require a core heat flux equal to or higher than present-day. Possible links between GPTS transitions, large igneous provinces (LIPs, and the two lower mantle superplumes are explored. Lower mantle superplume growth and collapse induce GPTS transitions by increasing and decreasing core heat flux, respectively. Age clusters of major LIPs postdate transitions from hyper-reversing to superchron geodynamo states by 30-60 Myr, suggesting that superchron onset may be contemporaneous with LIP-forming instabilities produced during collapses of lower mantle superplumes.

The origin of volatiles in the Earth's mantle

Science.gov (United States)

Hier-Majumder, Saswata; Hirschmann, Marc M.

2017-08-01

The Earth's deep interior contains significant reservoirs of volatiles such as H, C, and N. Due to the incompatible nature of these volatile species, it has been difficult to reconcile their storage in the residual mantle immediately following crystallization of the terrestrial magma ocean (MO). As the magma ocean freezes, it is commonly assumed that very small amounts of melt are retained in the residual mantle, limiting the trapped volatile concentration in the primordial mantle. In this article, we show that inefficient melt drainage out of the freezing front can retain large amounts of volatiles hosted in the trapped melt in the residual mantle while creating a thick early atmosphere. Using a two-phase flow model, we demonstrate that compaction within the moving freezing front is inefficient over time scales characteristic of magma ocean solidification. We employ a scaling relation between the trapped melt fraction, the rate of compaction, and the rate of freezing in our magma ocean evolution model. For cosmochemically plausible fractions of volatiles delivered during the later stages of accretion, our calculations suggest that up to 77% of total H2O and 12% of CO2 could have been trapped in the mantle during magma ocean crystallization. The assumption of a constant trapped melt fraction underestimates the mass of volatiles in the residual mantle by more than an order of magnitude.Plain Language SummaryThe Earth's deep interior contains substantial amounts of volatile elements like C, H, and N. How these elements got sequestered in the Earth's interior has long been a topic of debate. It is generally assumed that most of these elements escaped the interior of the Earth during the first few hundred thousand years to create a primitive atmosphere, leaving the mantle reservoir nearly empty. In this work, we show that the key to this paradox involves the very early stages of crystallization of the mantle from a global magma ocean. Using numerical models, we show

Refractory migraine in a headache clinic population

Directory of Open Access Journals (Sweden)

Fernandez-Torron Roberto

2011-08-01

Full Text Available Abstract Background Many migraineurs who seek care in headache clinics are refractory to treatment, despite advances in headache therapies. Epidemiology is poorly characterized, because diagnostic criteria for refractory migraine were not available until recently. We aimed to determine the frequency of refractory migraine in patients attended in the Headache Unit in a tertiary care center, according to recently proposed criteria. Methods The study population consisted of a consecutive sample of 370 patients (60.8% females with a mean age of 43 years (range 14-86 evaluated for the first time in our headache unit over a one-year period (between October 2008 and October 2009. We recorded information on clinical features, previous treatments, Migraine Disability Assessment Score (MIDAS, and final diagnosis. Results Overall migraine and tension-type headache were found in 46.4% and 20.5% of patients, respectively. Refractory migraine was found in 5.1% of patients. In refractory migraineurs, the mean MIDAS score was 96, and 36.8% were medication-overusers. Conclusions Refractory migraine is a relatively common and very disabling condition between the patients attended in a headache unit. The proposed operational criteria may be useful in identifying those patients who require care in headache units, the selection of candidates for combinations of prophylactic drugs or invasive treatments such as neurostimulation, but also to facilitate clinical studies in this patient group.

NOvel Refractory Materials for High Alkali, High Temperature Environments

Energy Technology Data Exchange (ETDEWEB)

Hemrick, J.G.; Griffin, R. (MINTEQ International, Inc.)

2011-08-30

Refractory materials can be limited in their application by many factors including chemical reactions between the service environment and the refractory material, mechanical degradation of the refractory material by the service environment, temperature limitations on the use of a particular refractory material, and the inability to install or repair the refractory material in a cost effective manner or while the vessel was in service. The objective of this project was to address the need for new innovative refractory compositions by developing a family of novel MgO-Al2O3 spinel or other similar magnesia/alumina containing unshaped refractory composition (castables, gunnables, shotcretes, etc) utilizing new aggregate materials, bond systems, protective coatings, and phase formation techniques (in-situ phase formation, altered conversion temperatures, accelerated reactions, etc). This family of refractory compositions would then be tailored for use in high-temperature, highalkaline industrial environments like those found in the aluminum, chemical, forest products, glass, and steel industries. A research team was formed to carry out the proposed work led by Oak Ridge National Laboratory (ORNL) and was comprised of the academic institution Missouri University of Science and Technology (MS&T), and the industrial company MINTEQ International, Inc. (MINTEQ), along with representatives from the aluminum, chemical, glass, and forest products industries. The two goals of this project were to produce novel refractory compositions which will allow for improved energy efficiency and to develop new refractory application techniques which would improve the speed of installation. Also methods of hot installation were sought which would allow for hot repairs and on-line maintenance leading to reduced process downtimes and eliminating the need to cool and reheat process vessels.

SINTERED REFRACTORY TUNGSTEN ALLOYS. Gesinterte hochschmelzende wolframlegierungen

Energy Technology Data Exchange (ETDEWEB)

Kieffer, R.; Sedlatschek, K.; Braun, H.

1971-12-15

Dependence of the melting point of the refractory metals on their positions in the periodic system - alloys of tungsten with other refractory metals - sintering of the alloys - processing of the alloys - technological properties.

Traveltime Dispersion in an Isotropic Elastic Mantle: Dominance of the Lower Mantle Signal in Differential-frequency Time Residuals

Science.gov (United States)

Schuberth, B. S. A.; Zaroli, C.; Nolet, G.

2014-12-01

We study wavefield effects in elastic isotropic 3-D seismic structures derived from the temperature field of a high resolution mantle circulation model. More specifically, we quantify the structural dispersion of traveltime residuals of direct P- and S-waves in a model with realistic length-scales and magnitudes of the variations in seismic velocities and density. 3-D global wave propagation is simulated using a spectral element method, and traveltime residuals are measured in four different frequency bands by cross-correlation of 3-D and 1-D synthetic waveforms. Intrinsic (dissipative) attenuation is deliberately neglected, so that any variation of traveltimes with frequency can be attributed to structural effects. Additional simulations are performed for a model in which 3-D structure is removed in the upper 800 km to isolate the dispersion signal of the lower mantle. One question that we address is whether the structural length-scales inherent to a vigorously convecting mantle give rise to significant body-wave dispersion. In our synthetic dataset, the difference between long-period and short-period traveltime residuals generally increases with increasing short-period residual. However, we do not find an exact linear dependence, and in case of P-waves even non-monotonic behaviour. At largest short-period residuals, average dispersion is on the order of 2 s for both P- and S-waves and even larger when structure is confined to the lower mantle. Dispersion also appears to be asymmetric; that is, larger for negative than for positive residuals. The standard deviations of both P- and S-wave residuals also increase with increasing period and we discuss possible explanations for this behaviour. Overall, wavefield effects in both models are generally stronger for P-waves than for S-waves at the same frequencies. We also find that for certain combinations of periods, the difference between the respective residuals is very similar between the "whole mantle" and the "lower

Deep mantle seismic heterogeneities in Western Pacific subduction zones

Science.gov (United States)

Bentham, H. L. M.; Rost, S.

2012-04-01

In recent years array seismology has been used extensively to image the small scale (~10 km) structure of the Earth. In the mantle, small scale structure likely represents chemical heterogeneity and is essential in our understanding of mantle convection and especially mantle mixing. As subduction is the main source of introducing crustal material into the Earth's mantle, it is of particular interest to track the transport of subducted crust through the mantle to resolve details of composition and deformation of the crust during the subduction process. Improved knowledge of subduction can help provide constraints on the mechanical mixing process of crustal material into the ambient mantle, as well as constraining mantle composition and convection. This study uses seismic array techniques to map seismic heterogeneities associated with Western Pacific subduction zones, where a variety of slab geometries have been previously observed. We use seismic energy arriving prior to PP, a P-wave underside reflection off the Earth's surface halfway between source and receiver, to probe the mantle for small-scale heterogeneities. PP precursors were analysed at Eielson Array (ILAR), Alaska using the recently developed Toolkit for Out-of-Plane Coherent Arrival Tracking (TOPCAT) algorithm. The approach combines the calculated optimal beampower and an independent semblance (coherency) measure, to improve the signal-to-noise ratio of coherent arrivals. 94 earthquakes with sufficient coherent precursory energy were selected and directivity information of the arrivals (i.e. slowness and backazimuth) was extracted from the data. The scattering locations for 311 out-of-plane precursors were determined by ray-tracing and minimising the slowness, backazimuth and differential travel time misfit. Initial analyses show that deep scattering (>1000 km) occurs beneath the Izu-Bonin subduction zone, suggesting that subducted crust does continue into the lower mantle in this location. Other

Dynamics of upper mantle rocks decompression melting above hot spots under continental plates

Science.gov (United States)

Perepechko, Yury; Sorokin, Konstantin; Sharapov, Victor

2014-05-01

Numeric 2D simulation of the decompression melting above the hot spots (HS) was accomplished under the following conditions: initial temperature within crust mantle section was postulated; thickness of the metasomatized lithospheric mantle is determined by the mantle rheology and position of upper asthenosphere boundary; upper and lower boundaries were postulated to be not permeable and the condition for adhesion and the distribution of temperature (1400-2050°C); lateral boundaries imitated infinity of layer. Sizes and distribution of lateral points, their symmetry, and maximum temperature varied between the thermodynamic condition for existences of perovskite - majorite transition and its excess above transition temperature. Problem was solved numerically a cell-vertex finite volume method for thermo hydrodynamic problems. For increasing convergence of iterative process the method of lower relaxation with different value of relaxation parameter for each equation was used. The method of through calculation was used for the increase in the computing rate for the two-layered upper mantle - lithosphere system. Calculated region was selected as 700 x (2100-4900) km. The time step for the study of the asthenosphere dynamics composed 0.15-0.65 Ma. The following factors controlling the sizes and melting degree of the convective upper mantle, are shown: a) the initial temperature distribution along the section of upper mantleb) sizes and the symmetry of HS, c) temperature excess within the HS above the temperature on the upper and lower mantle border TB=1500-2000oC with 5-15% deviation but not exceed 2350oC. It is found, that appearance of decompression melting with HS presence initiate primitive mantle melting at TB > of 1600oC. Initial upper mantle heating influence on asthenolens dimensions with a constant HS size is controlled mainly by decompression melting degree. Thus, with lateral sizes of HS = 400 km the decompression melting appears at TB > 1600oC and HS

Immunotoxin – a new treatment option in patients with relapsed and refractory Hodgkin lymphoma

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Novakovic Barbara Jezersek

2015-12-01

Full Text Available Background. Even though Hodgkin lymphoma is a highly curable disease, some of the patients have either a refractory disease or experience a relapse following a successful primary therapy. Durable responses and remissions in patients with relapsed or refractory disease may be achieved in approximately one-half with salvage chemotherapy followed by high dose chemotherapy (HDT and autologous hematopoietic cell rescue (SCT. On the other hand, patients who relapse after HDT and autologous SCT or those who have failed at least two prior multi-agent chemotherapy regimens and are not candidates for HDT have limited treatment options.

Response properties of the refractory auditory nerve fiber.

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Miller, C A; Abbas, P J; Robinson, B K

2001-09-01

The refractory characteristics of auditory nerve fibers limit their ability to accurately encode temporal information. Therefore, they are relevant to the design of cochlear prostheses. It is also possible that the refractory property could be exploited by prosthetic devices to improve information transfer, as refractoriness may enhance the nerve's stochastic properties. Furthermore, refractory data are needed for the development of accurate computational models of auditory nerve fibers. We applied a two-pulse forward-masking paradigm to a feline model of the human auditory nerve to assess refractory properties of single fibers. Each fiber was driven to refractoriness by a single (masker) current pulse delivered intracochlearly. Properties of firing efficiency, latency, jitter, spike amplitude, and relative spread (a measure of dynamic range and stochasticity) were examined by exciting fibers with a second (probe) pulse and systematically varying the masker-probe interval (MPI). Responses to monophasic cathodic current pulses were analyzed. We estimated the mean absolute refractory period to be about 330 micros and the mean recovery time constant to be about 410 micros. A significant proportion of fibers (13 of 34) responded to the probe pulse with MPIs as short as 500 micros. Spike amplitude decreased with decreasing MPI, a finding relevant to the development of computational nerve-fiber models, interpretation of gross evoked potentials, and models of more central neural processing. A small mean decrement in spike jitter was noted at small MPI values. Some trends (such as spike latency-vs-MPI) varied across fibers, suggesting that sites of excitation varied across fibers. Relative spread was found to increase with decreasing MPI values, providing direct evidence that stochastic properties of fibers are altered under conditions of refractoriness.

Refractory alloy technology for space nuclear power applications

International Nuclear Information System (INIS)

Cooper, R.H. Jr.; Hoffman, E.E.

1984-01-01

Purpose of this symposium is twofold: (1) to review and document the status of refractory alloy technology for structural and fuel-cladding applications in space nuclear power systems, and (2) to identify and document the refractory alloy research and development needs for the SP-100 Program in both the short and the long term. In this symposium, an effort was made to recapture the space reactor refractory alloy technology that was cut off in midstream around 1973 when the national space nuclear reactor program began in the early 1960s, was terminated. The six technical areas covered in the program are compatibility, processing and production, welding and component fabrication, mechanical and physical properties, effects of irradiation, and machinability. The refractory alloys considered are niobium, molybdenum, tantalum, and tungsten. Thirteen of the 14 pages have been abstracted separately. The remaining paper summarizes key needs for further R and D on refractory alloys

Mantle contamination and the Izu-Bonin-Mariana (IBM) 'high-tide mark': evidence for mantle extrusion caused by Tethyan closure

Science.gov (United States)

Flower, M. F. J.; Russo, R. M.; Tamaki, K.; Hoang, N.

2001-04-01

Western Pacific basins are characterized by three remarkable attributes: (1) complex kinematic histories linked to global-scale plate interactions; (2) DUPAL-like contaminated mantle; and (3) rapid post-Mesozoic rollback of the confining arc-trench systems. The coincidence of slab steepening, extreme arc curvature, and vigorous basin opening associated with the Mariana convergent margin suggests that rollback continues in response to an east-directed mantle 'wind'. Against a backdrop of conflicting kinematic and genetic interpretations we explore the notion that eastward asthenospheric flow driven by diachronous Tethyan closure caused stretching of eastern Eurasia and concomitant opening of western Pacific basins. Marking the eastern boundary of the latter, the Izu-Bonin-Mariana forearc may be regarded as a litho-tectonic 'high-tide mark' comprising igneous and metamorphic products from successive episodes (since ca. 45 Ma.) of arc sundering and backarc basin opening. The forearc also forms an isotopic boundary separating contaminated western Pacific mantle from the N-MORB Pacific Ocean reservoir. While the isotopic composition of western Pacific mantle resembles that feeding Indian Ocean hotspot and spreading systems, its spatial-temporal variation and the presence of subduction barriers to the south appear to preclude northward flow of Indian Ocean mantle and require an endogenous origin for sub-Eurasian contaminated mantle. It is concluded that the extrusion of Tethyan asthenosphere, contaminated by sub-Asian cratonic lithosphere, was a major cause of western Pacific arc rollback and basin opening. The model is consistent with paleomagnetic and geologic evidence supporting independent kinematic histories for constituent parts of the Philippine Sea and Sunda plates although interpretation of these is speculative. Compounded by effects of the Australia-Indonesia collision, late-Tethyan mantle extrusion appears to have produced the largest DUPAL domain in the

An investigation into mineral processing of north Semnan refractory earth

International Nuclear Information System (INIS)

Aslani, S.; Samin-Bani-Hashemi, H.R.; Taghi-Zadeh, O.

2002-01-01

This paper is dealing with refractory earth of North Semnan. Having an area of 2000 square kilometers, Semnan province is mainly formed by sedimentary rocks with a verity of refractory earth, red earth and kaolin containing heavy minerals. The refractory earth of this area contains a considerable rate of aluminum oxide in shape of dia spore minerals, behemoth and gybsite along with heavy minerals of iron and titanium. To improve the quality of refractory earth, in order to be used in related industries, these minerals have to be separated. To assess the quality of refractory earth of North Semnan as the raw materials of refractory industries, their genesis and mineralogy properties have been precisely studied. Based on the rate of aluminium oxide of the refractory earth of North Semnan mines, a suitable mineral deposit has been selected for more investigation. Using XRD and X RF methods along with electronic and photo microscopes, the refractory earth and heavy minerals of them have been assessed. The elementary laboratory experiments of fragmentation and magnetic separation have been performed. It has been proved that the iron minerals can be separated and, therefore, the quality of the refractory earth can be improved. The separation of titanium minerals has to be investigated with other methods

Preface: Deep Slab and Mantle Dynamics

Science.gov (United States)

Suetsugu, Daisuke; Bina, Craig R.; Inoue, Toru; Wiens, Douglas A.

2010-11-01

We are pleased to publish this special issue of the journal Physics of the Earth and Planetary Interiors entitled "Deep Slab and Mantle Dynamics". This issue is an outgrowth of the international symposium "Deep Slab and Mantle Dynamics", which was held on February 25-27, 2009, in Kyoto, Japan. This symposium was organized by the "Stagnant Slab Project" (SSP) research group to present the results of the 5-year project and to facilitate intensive discussion with well-known international researchers in related fields. The SSP and the symposium were supported by a Grant-in-Aid for Scientific Research (16075101) from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese Government. In the symposium, key issues discussed by participants included: transportation of water into the deep mantle and its role in slab-related dynamics; observational and experimental constraints on deep slab properties and the slab environment; modeling of slab stagnation to constrain its mechanisms in comparison with observational and experimental data; observational, experimental and modeling constraints on the fate of stagnant slabs; eventual accumulation of stagnant slabs on the core-mantle boundary and its geodynamic implications. This special issue is a collection of papers presented in the symposium and other papers related to the subject of the symposium. The collected papers provide an overview of the wide range of multidisciplinary studies of mantle dynamics, particularly in the context of subduction, stagnation, and the fate of deep slabs.

A new conceptual model for whole mantle convection and the origin of hotspot plumes

Science.gov (United States)

Yoshida, Masaki

2014-08-01

A new conceptual model of mantle convection is constructed for consideration of the origin of hotspot plumes, using recent evidence from seismology, high-pressure experiments, geodynamic modeling, geoid inversion studies, and post-glacial rebound analyses. This conceptual model delivers several key points. Firstly, some of the small-scale mantle upwellings observed as hotspots on the Earth's surface originate at the base of the mantle transition zone (MTZ), in which the Archean granitic continental material crust (TTG; tonalite-trondhjemite-granodiorite) with abundant radiogenic elements is accumulated. Secondly, the TTG crust and the subducted oceanic crust that have accumulated at the base of MTZ could act as thermal or mechanical insulators, leading to the formation of a hot and less viscous layer just beneath the MTZ; which may enhance the instability of plume generation at the base of the MTZ. Thirdly, the origin of some hotspot plumes is isolated from the large low shear-wave velocity provinces (LLSVPs) under Africa and the South Pacific. I consider that the conceptual model explains why almost all the hotspots around Africa are located above the margins of the African LLSVP. Because a planetary-scale trench system surrounding a “Pangean cell” has been spatially stable throughout the Phanerozoic, a large amount of the oceanic crustal layer is likely to be trapped in the MTZ under the Pangean cell. Therefore, under Africa, almost all of the hotspot plumes originate from the base of the MTZ, where a large amount of TTG and/or oceanic crusts has accumulated. This conceptual model may explain the fact that almost all the hotspots around Africa are located on margins above the African LLSVP. It is also considered that some of the hotspot plumes under the South Pacific thread through the TTG/oceanic crusts accumulated around the bottom of the MTZ, and some have their roots in the South Pacific LLSVP while others originate from the MTZ. The numerical simulations

Effects of 5-azacytidine on natural killer cell activating receptor expression in patients with refractory anemia with excess of blasts

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Régis T. Costello

2015-01-01

Full Text Available Epigenetic drugs modify DNA methylation and are used in refractory anemia with excess of blasts (RAEB. These drugs may reactivate anti-oncogene expression and restore a normal phenotype instead of inducing antitumor toxicity, although they also have immunosuppressive effects on T-lymphocytes [1] In RAEB and acute myeloid leukemia, a defect in natural killer (NK cell cytotoxicity has been shown, which relies on abnormal expression of activating receptors. Previous study has shown that 5-azacytidine impaired mRNA synthesis and induced apoptosis in NK cells [2]. In this study we investigated the effect of the demethylating drug 5-azacytidine (Vidaza® on NK receptors with the hypothesis that demethylation of the promoters of activating NK receptor genes induces gene reactivation and thus may increase their expression.

A Chinese patient with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin

Institute of Scientific and Technical Information of China (English)

Zhi-Gang Cao; Hong-Wei Zhou; Chao-Jin Peng; Mo Liu; Yu Du; Qing-Ming Yang

2013-01-01

At present, approximately 20% of Hodgkin lymphomas (HL) are relapsed and refractory, and therapeutic methods including chemotherapy, radiotherapy, and even stem cell transplantation are unsatisfactory. Brentuximab vedotin, composed of CD30 antibody and a chemotherapeutic agent, is a new targeted drug that eradicates tumor cel s by binding to the CD30 antigen on their surface. In clinical trials, the response rate and complete remission rate of this drug were 73% and 40%, respectively, for relapsed and refractory HL. Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab. Before the treatment with brentuximab, the patient underwent chemotherapy, radiotherapy, and autologous stem cell transplantation. However, the disease continued to progress, affecting multiple organs and prompting symptoms such as persistent fever. After the treatment with brentuximab, the patient′s condition improved. Body temperature returned to normal after 4 days. Lung nodules were reduced in size and number after a single course of treatment, and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment, respectively. The entire treatment process progressed smoothly, though the patient experienced some symptoms due to chemotherapy, including peripheral neuritis of the limbs, irritating dry cough, and mild increase in aminotransferase. No serious adverse effects were observed. The current general condition of the patient is good;the continuous complete remission has amounted to 6 months.

Refractory alloy technology for space nuclear power applications

Energy Technology Data Exchange (ETDEWEB)

Cooper, R.H. Jr.; Hoffman, E.E. (eds.)

1984-01-01

Purpose of this symposium is twofold: (1) to review and document the status of refractory alloy technology for structural and fuel-cladding applications in space nuclear power systems, and (2) to identify and document the refractory alloy research and development needs for the SP-100 Program in both the short and the long term. In this symposium, an effort was made to recapture the space reactor refractory alloy technology that was cut off in midstream around 1973 when the national space nuclear reactor program began in the early 1960s, was terminated. The six technical areas covered in the program are compatibility, processing and production, welding and component fabrication, mechanical and physical properties, effects of irradiation, and machinability. The refractory alloys considered are niobium, molybdenum, tantalum, and tungsten. Thirteen of the 14 pages have been abstracted separately. The remaining paper summarizes key needs for further R and D on refractory alloys. (DLC)

Whole-mantle P-wave velocity structure and azimuthal anisotropy

Science.gov (United States)

Yamamoto, Y.; Zhao, D.

2009-12-01

There are some hotspot volcanoes on Earth, such as Hawaii and Iceland. The mantle plume hypothesis was proposed forty years ago to explain hotspot volcanoes (e.g., Wilson, 1963; Morgan, 1971). Seismic tomography is a powerful technique to detect mantle plumes and determine their detailed structures. We determined a new whole-mantle 3-D P-wave velocity model (Tohoku model) using a global tomography method (Zhao, 2004, 2009). A flexible-grid approach with a grid interval of ~200 km is adopted to conduct the tomographic inversion. Our model shows that low-velocity (low-V) anomalies with diameters of several hundreds of kilometers are visible from the core-mantle boundary (CMB) to the surface under the major hotspot regions. Under South Pacific where several hotspots including Tahiti exist, there is a huge low-V anomaly from the CMB to the surface. This feature is consistent with the previous models. We conducted extensive resolution tests in order to understand whether this low-V anomaly shows a single superplume or a plume cluster. Unfortunately this problem is still not resolved because the ray path coverage in the mantle under South Pacific is not good enough. A network of ocean bottom seismometers is necessary to solve this problem. To better understand the whole-mantle structure and dynamics, we also conducted P-wave tomographic inversions for the 3-D velocity structure and azimuthal anisotropy. At each grid node there are three unknown parameters: one represents the isotropic velocity, the other two represent the azimuthal anisotropy. Our results show that in the shallow part of the mantle (Japan trench axis. In the Tonga subduction zone, the FVD is also perpendicular to the trench axis. Under the Tibetan region the FVD is NE-SW, which is parallel to the direction of the India-Asia collision. In the deeper part of the upper mantle and in the lower mantle, the amplitude of anisotropy is reduced. One interesting feature is that the FVD aligns in a radiated fashion

Circulation of carbon dioxide in the mantle: multiscale modeling

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Morra, G.; Yuen, D. A.; Lee, S.

2012-12-01

Much speculation has been put forward on the quantity and nature of carbon reservoirs in the deep Earth, because of its involvement in the evolution of life at the surface and inside planetary interiors. Carbon penetrates into the Earth's mantle mostly during subduction of oceanic crust, which contains carbonate deposits [1], however the form that it assumes at lower mantle depths is scarcely understood [2], hampering our ability to estimate the amount of carbon in the entire mantle by orders of magnitude. We present simulations of spontaneous degassing of supercritical CO2 using in-house developed novel implementations of the Fast-Multipole Boundary Element Method suitable for modeling two-phase flow (here mantle mineral and free CO2 fluid) through disordered materials such as porous rocks. Because the mutual interaction of droplets immersed either in a fluid or a solid matrix and their weakening effect to the host rock alters the strength of the mantle rocks, at the large scale the fluid phases in the mantle may control the creeping of mantle rocks [3]. In particular our study focuses on the percolation of supercritical CO2, estimated through the solution of the Laplace equation in a porous system, stochastically generated through a series of random Karhunen-Loeve decomposition. The model outcome is employed to extract the transmissivity of supercritical fluids in the mantle from the lowest scale up to the mantle scale and in combination with the creeping flow of the convecting mantle. The emerging scenarios on the global carbon cycle are finally discussed. [1] Boulard, E., et al., New host for carbon in the deep Earth. Proceedings of the National Academy of Sciences, 2011. 108(13): p. 5184-5187. [2] Walter, M.J., et al., Deep Mantle Cycling of Oceanic Crust: Evidence from Diamonds and Their Mineral Inclusions. Science, 2011. 334(6052): p. 54-57. [3] Morra, G., et al., Ascent of Bubbles in Magma Conduits Using Boundary Elements and Particles. Procedia Computer

Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

Science.gov (United States)

2018-02-07

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Temperature and Thermal Stress Analysis of Refractory Products

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Shaoyang Shi

2013-05-01

Full Text Available Firstly current status of temperature and thermal stress research of refractory product at home and aboard are analyzed. Finite element model of two classical refractory products is building by using APDL language. Distribution law of temperature and thermal stress of two typical refractory products-ladles and tundish are analyzed and their structures are optimized. Stress of optimal structure is dropped obviously, and operation life is increased effectively.

Chemotherapy refractory testicular germ cell tumor is associated with a variant in Armadillo Repeat gene deleted in Velco-Cardio-Facial syndrome (ARVCF

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Chunkit eFung

2012-12-01

Full Text Available Introduction: There is evidence that inherited genetic variation affects both testicular germ cell tumor (TGCT treatment outcome and risks of late-complications arising from cisplatin-based chemotherapy. Using a candidate gene approach, we examined associations of three genes involved in the cisplatin metabolism pathway, GSTP1, COMT, and TPMT, with TGCT outcome and cisplatin-induced neurotoxicity. Material and Methods: Our study population includes a subset of patients (n=137 from a genome-wide association study at the University of Pennsylvania that evaluates inherited genetic susceptibility to TGCT. All patients in our study had at least one course of cisplatin-based chemotherapy with at least one year of follow up. A total of 90 markers in GSTP1, COMT and TPMT and their adjacent genomic regions (± 20 kb were analyzed for associations with refractory TGCT after first course of chemotherapy, progression-free survival (PFS, overall survival (OS, peripheral neuropathy, and ototoxicity. Results: After adjustment for multiple comparisons, one SNP, rs2073743, in the flanking region (± 20 kb of COMT was associated with refractory TGCT after initial chemotherapy. This SNP lies within the intron region of the Armadillo Repeat gene deleted in Velco-Cardio-Facial syndrome (ARVCF. The G allele of rs2073743 predisposed patients to refractory disease with a relative risk of 2.6 (95% CI 1.1, 6.3; P=0.03. Assuming recessive inheritance, patients with the GG genotype had 22.7 times higher risk (95% CI 3.3, 155.8; P=0.04 of developing refractory disease when compared to those with the GC or CC genotypes. We found no association of our candidate genes with peripheral neuropathy, ototoxicity, PFS and OS. Discussion: This is the first study to suggest that germline genetic variants of ARVCF may affect TGCT outcome. The result of this study is hypothesis generating and should be validated in future studies.

Water Distribution in the Continental and Oceanic Upper Mantle

Science.gov (United States)

Peslier, Anne H.

2015-01-01

Nominally anhydrous minerals such as olivine, pyroxene and garnet can accommodate tens to hundreds of ppm H2O in the form of hydrogen bonded to structural oxygen in lattice defects. Although in seemingly small amounts, this water can significantly alter chemical and physical properties of the minerals and rocks. Water in particular can modify their rheological properties and its distribution in the mantle derives from melting and metasomatic processes and lithology repartition (pyroxenite vs peridotite). These effects will be examined here using Fourier transform infrared spectrometry (FTIR) water analyses on minerals from mantle xenoliths from cratons, plume-influenced cratons and oceanic settings. In particular, our results on xenoliths from three different cratons will be compared. Each craton has a different water distribution and only the mantle root of Kaapvaal has evidence for dry olivine at its base. This challenges the link between olivine water content and survival of Archean cratonic mantle, and questions whether xenoliths are representative of the whole cratonic mantle. We will also present our latest data on Hawaii and Tanzanian craton xenoliths which both suggest the intriguing result that mantle lithosphere is not enriched in water when it interacts with melts from deep mantle upwellings (plumes).

Mantle mixing and thermal evolution during Pangaea assembly and breakup

Science.gov (United States)

Rudolph, M. L.; Li, M.; Zhong, S.; Manga, M.

2016-12-01

Continents insulate the underlying mantle, and it has been suggested that the arrangement of the continents can have a significant effect on sub-continental mantle temperatures. Additionally, the dispersal or agglomeration of continents may affect the efficacy of continental insulation, with some studies suggesting warming of 100K beneath supercontinents. During the most recent supercontinent cycle, Pangaea was encircled by subduction, potentially creating a `curtain' of subducted material that may have prevented mixing of the sub-Pangaea mantle with the sub-Panthalassa mantle. Using 3D spherical shell geometry mantle convection simulations, we quantify the effect of insulation by continents and supercontinents. We explore the differences in model predictions for purely thermal vs. thermochemical convection, and we use tracers to quantify the exchange of material between the sub-oceanic to the sub-continental mantle.

Reconstructing mantle heterogeneity with data assimilation based on the back-and-forth nudging method: Implications for mantle-dynamic fitting of past plate motions

Science.gov (United States)

Glišović, Petar; Forte, Alessandro

2016-04-01

The paleo-distribution of density variations throughout the mantle is unknown. To address this question, we reconstruct 3-D mantle structure over the Cenozoic era using a data assimilation method that implements a new back-and-forth nudging algorithm. For this purpose, we employ convection models for a compressible and self-gravitating mantle that employ 3-D mantle structure derived from joint seismic-geodynamic tomography as a starting condition. These convection models are then integrated backwards in time and are required to match geologic estimates of past plate motions derived from marine magnetic data. Our implementation of the nudging algorithm limits the difference between a reconstruction (backward-in-time solution) and a prediction (forward-in-time solution) on over a sequence of 5-million-year time windows that span the Cenozoic. We find that forward integration of reconstructed mantle heterogeneity that is constrained to match past plate motions delivers relatively poor fits to the seismic-tomographic inference of present-day mantle heterogeneity in the upper mantle. We suggest that uncertainties in the past plate motions, related for example to plate reorganization episodes, could partly contribute to the poor match between predicted and observed present-day heterogeneity. We propose that convection models that allow tectonic plates to evolve freely in accord with the buoyancy forces and rheological structure in the mantle could provide additional constraints on geologic estimates of paleo-configurations of the major tectonic plates.

Is there an increased rate of additional malignancies in patients with mantle cell lymphoma?

Science.gov (United States)

Barista, I; Cabanillas, F; Romaguera, J E; Khouri, I F; Yang, Y; Smith, T L; Strom, S S; Medeiros, L J; Hagemeister, F B

2002-02-01

To examine the frequency of additional neoplasms preceding and following the diagnosis of mantle cell lymphoma (MCL). A total of 156 patients with MCL treated on the hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternated with methotrexate and cytosine arabinoside (Hyper-CVAD/M-A) program with or without rituximab from 1994 to 2000 were the subjects of this report. These patients were followed for a median time of 26 months, and a total of 32 (21%) additional neoplasms were diagnosed, 21 preceding the diagnosis of MCL and 11 following MCL. After excluding certain types of non-invasive neoplasms, including basal cell carcinoma, meningioma and cervical intraepithelial neoplasia, we observed seven second malignancies after the diagnosis of MCL, and the 5-year cumulative incidence rate of second malignancy was 11%. The observed-to-expected (O/E) ratio was 7/0.07 = 100 [95% confidence interval (CI) 49.3 to 186.6; P <0.0001]. Of the 21 malignancies diagnosed prior to MCL, 16 were invasive and five non-invasive. There were a total of 10 urologic malignancies occurring before or after the diagnosis of MCL was established. Our findings suggest that there is an increased incidence of second malignancies in patients with MCL. In addition, the high number of cases with urinary tract cancer in our series may substantiate prior reports describing a possible association between lymphoma and urologic malignancies.

Tracing Mantle Plumes: Quantifying their Morphology and Behavior from Seismic Tomography

Science.gov (United States)

O'Farrell, K. A.; Eakin, C. M.; Jones, T. D.; Garcia, E.; Robson, A.; Mittal, T.; Lithgow-Bertelloni, C. R.; Jackson, M. G.; Lekic, V.; Rudolph, M. L.

2016-12-01

Hotspot volcanism provides a direct link between the deep mantle and the surface, but the location, depth and source of the mantle plumes that feed hotspots are highly controversial. In order to address this issue it is important to understand the journey along which plumes have travelled through the mantle. The general behavior of plumes in the mantle also has the potential to tell us about the vigor of mantle convection, net rotation of the mantle, the role of thermal versus chemical anomalies, and important bulk physical properties of the mantle such as the viscosity profile. To address these questions we developed an algorithm to trace plume-like features in shear-wave (Vs) seismic tomographic models based on picking local minima in velocity and searching for continuous features with depth. We apply this method to several of the latest tomographic models and can recover 30 or more continuous plume conduits that are >750 km long. Around half of these can be associated with a known hotspot at the surface. We study the morphology of these plume chains and find that the largest lateral deflections occur near the base of the lower mantle and in the upper mantle. We analyze the preferred orientation of the plume deflections and their gradient to infer large scale mantle flow patterns and the depth of viscosity contrasts in the mantle respectively. We also retrieve Vs profiles for our traced plumes and compare with velocity profiles predicted for different mantle adiabat temperatures. We use this to constrain the thermal anomaly associated with these plumes. This thermal anomaly is then converted to a density anomaly and an upwelling velocity is derived. We compare this to buoyancy fluxes calculated at the surface and use this in conjunction with our measured plume tilts/deflections to estimate the strength of the "mantle wind".

Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Science.gov (United States)

2017-12-11

Acute Biphenotypic Leukemia; Acute Erythroid Leukemia in Remission; Acute Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2) or t(3;3) (q21.3;q26.2); GATA2, MECOM; Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2); GATA2, MECOM; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia With t(6;9) (p23;q34.1); DEK-NUP214; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Myelodysplastic Syndrome; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Acute Myeloid Leukemia; T Lymphoblastic Lymphoma

Imaging the Mediterranean upper mantle by p- wave travel time tomography

Directory of Open Access Journals (Sweden)

A. Morelli

1997-06-01

Full Text Available Travel times of P-waves in the Euro-Mediterranean region show strong and consistent lateral variations, which can be associated to structural heterogeneity in the underlying crust and mantle. We analyze regional and tele- seismic data from the International Seismological Centre data base to construct a three-dimensional velocity model of the upper mantle. We parameterize the model by a 3D grid of nodes -with approximately 50 km spacing -with a linear interpolation law, which constitutes a three-dimensional continuous representation of P-wave velocity. We construct summary travel time residuals between pairs of cells of the Earth's surface, both inside our study area and -with a broader spacing -on the whole globe. We account for lower mantle heterogeneity outside the modeled region by using empirical corrections to teleseismic travel times. The tomo- graphic images show generai agreement with other seismological studies of this area, with apparently higher detail attained in some locations. The signature of past and present lithospheric subduction, connected to Euro- African convergence, is a prominent feature. Active subduction under the Tyrrhenian and Hellenic arcs is clearly imaged as high-velocity bodies spanning the whole upper mantle. A clear variation of the lithospheric structure beneath the Northem and Southern Apennines is observed, with the boundary running in correspon- dence of the Ortona-Roccamonfina tectonic lineament. The western section of the Alps appears to have better developed roots than the eastern, possibly reflecting à difference in past subduction of the Tethyan lithosphere and subsequent continental collision.

Geodynamo Modeling of Core-Mantle Interactions

Science.gov (United States)

Kuang, Wei-Jia; Chao, Benjamin F.; Smith, David E. (Technical Monitor)

2001-01-01

Angular momentum exchange between the Earth's mantle and core influences the Earth's rotation on time scales of decades and longer, in particular in the length of day (LOD) which have been measured with progressively increasing accuracy for the last two centuries. There are four possible coupling mechanisms for transferring the axial angular momentum across the core-mantle boundary (CMB): viscous, magnetic, topography, and gravitational torques. Here we use our scalable, modularized, fully dynamic geodynamo model for the core to assess the importance of these torques. This numerical model, as an extension of the Kuang-Bloxham model that has successfully simulated the generation of the Earth's magnetic field, is used to obtain numerical results in various physical conditions in terms of specific parameterization consistent with the dynamical processes in the fluid outer core. The results show that depending on the electrical conductivity of the lower mantle and the amplitude of the boundary topography at CMB, both magnetic and topographic couplings can contribute significantly to the angular momentum exchange. This implies that the core-mantle interactions are far more complex than has been assumed and that there is unlikely a single dominant coupling mechanism for the observed decadal LOD variation.

Moho vs crust-mantle boundary: Evolution of an idea

Science.gov (United States)

O'Reilly, Suzanne Y.; Griffin, W. L.

2013-12-01

The concept that the Mohorovicic Discontinuity (Moho) does not necessarily coincide with the base of the continental crust as defined by rock-type compositions was introduced in the early 1980s. This had an important impact on understanding the nature of the crust-mantle boundary using information from seismology and from deep-seated samples brought to the surface as xenoliths in magmas, or as tectonic terranes. The use of empirically-constrained P-T estimates to plot the locus of temperature vs depth for xenoliths defined a variety of geotherms depending on tectonic environment. The xenolith geotherms provided a framework for constructing lithological sections through the deep lithosphere, and revealed that the crust-mantle boundary in off-craton regions commonly is transitional over a depth range of about 5-20 km. Early seismic-reflection data showed common layering near the Moho, correlating with the petrological observation of multiple episodes of basaltic intrusion around the crust-mantle boundary. Developments in seismology, petrophysics and experimental petrology have refined interpretation of lithospheric domains. The expansion of in situ geochronology (especially zircon U-Pb ages and Hf-isotopes; Os isotopes of mantle sulfides) has defined tectonic events that affected whole crust-mantle sections, and revealed that the crust-mantle boundary can change in depth through time. However, the nature of the crust-mantle boundary in cratonic regions remains enigmatic, mainly due to lack of key xenoliths or exposed sections. The observation that the Moho may lie significantly deeper than the crust-mantle boundary has important implications for modeling the volume of the crust. Mapping the crust using seismic techniques alone, without consideration of the petrological problems, may lead to an overestimation of crustal thickness by 15-30%. This will propagate to large uncertainties in the calculation of elemental mass balances relevant to crust-formation processes

Comparative evaluation of the locally manufactured low-alumina fireclay refractories

International Nuclear Information System (INIS)

Mohammad, D.; Ahmed, W.; Khan, M.I.

2007-01-01

Properties of domestically produced low-alumina refractories commonly known as medium duty fireclay refractories were studied and a comparative evaluation was performed. Refractory properties such as density, porosity, cold strength, reheat change and deformation at high-temperature were determined. Significant differences were discovered between these products sold as medium duty fireclay refractories. One brand marketed as medium duty refractory was found to be too inferior to be designated as medium duty firebrick. Absence of any standards and lack of awareness on the part of users of the various test methods appear to be the cause of this situation. (author)

Clustering of arc volcanoes caused by temperature perturbations in the back-arc mantle.

Science.gov (United States)

Lee, Changyeol; Wada, Ikuko

2017-06-29

Clustering of arc volcanoes in subduction zones indicates along-arc variation in the physical condition of the underlying mantle where majority of arc magmas are generated. The sub-arc mantle is brought in from the back-arc largely by slab-driven mantle wedge flow. Dynamic processes in the back-arc, such as small-scale mantle convection, are likely to cause lateral variations in the back-arc mantle temperature. Here we use a simple three-dimensional numerical model to quantify the effects of back-arc temperature perturbations on the mantle wedge flow pattern and sub-arc mantle temperature. Our model calculations show that relatively small temperature perturbations in the back-arc result in vigorous inflow of hotter mantle and subdued inflow of colder mantle beneath the arc due to the temperature dependence of the mantle viscosity. This causes a three-dimensional mantle flow pattern that amplifies the along-arc variations in the sub-arc mantle temperature, providing a simple mechanism for volcano clustering.

Directed light fabrication of refractory metals and alloys

International Nuclear Information System (INIS)

Fonseca, J.C.; Lewis, G.K.; Dickerson, P.G.; Nemec, R.B.

1999-01-01

This report covers deposition of refractory pure metals and alloys using the Directed Light Fabrication (DLF) process and represents progress in depositing these materials through September 1998. In extending the DLF process technology to refractory metals for producing fully dense, structurally sound deposits, several problems have become evident. (1) Control of porosity in DLF-deposited refractory metal is difficult because of gases, apparently present in commercially purchased refractory metal powder starting materials. (2) The radiant heat from the molten pool during deposition melts the DLF powder feed nozzle. (3) The high reflectivity of molten refractory metals, at the Nd-YAG laser wavelength (1.06microm), produces damaging back reflections to the optical train and fiber optic delivery system that can terminate DLF processing. (4) The current limits on the maximum available laser power to prevent back reflection damage limit the parameter range available for densification of refractory metals. The work to date concentrated on niobium, W-25Re, and spherodized tungsten. Niobium samples, made from hydride-dehydride powder, had minimal gas porosity and the deposition parameters were optimized; however, test plates were not made at this time. W-25Re samples, containing sodium and potassium from a precipitation process, were made and porosity was a problem for all samples although minimized with some process parameters. Deposits made from potassium reduced tungsten that was plasma spherodized were made with minimized porosity. Results of this work indicate that further gas analysis of starting powders and de-gassing of starting powders and/or gas removal during deposition of refractory metals is required

Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study.

Science.gov (United States)

Santamaria, Xavier; Cabanillas, Sergio; Cervelló, Irene; Arbona, Cristina; Raga, Francisco; Ferro, Jaime; Palmero, Julio; Remohí, Jose; Pellicer, Antonio; Simón, Carlos

2016-05-01

Could cell therapy using autologous peripheral blood CD133+ bone marrow-derived stem cells (BMDSCs) offer a safe and efficient therapeutic approach for patients with refractory Asherman's syndrome (AS) and/or endometrial atrophy (EA) and a wish to conceive? In the first 3 months, autologous cell therapy, using CD133+ BMDSCs in conjunction with hormonal replacement therapy, increased the volume and duration of menses as well as the thickness and angiogenesis processes of the endometrium while decreasing intrauterine adhesion scores. AS is characterized by the presence of intrauterine adhesions and EA prevents the endometrium from growing thicker than 5 mm, resulting in menstruation disorders and infertility. Many therapies have been attempted for these conditions, but none have proved effective. This was a prospective, experimental, non-controlled study. There were 18 patients aged 30-45 years with refractory AS or EA were recruited, and 16 of these completed the study. Medical history, physical examination, endometrial thickness, intrauterine adhesion score and neoangiogenesis were assessed before and 3 and 6 months after cell therapy. After the initial hysteroscopic diagnosis, BMDSC mobilization was performed by granulocyte-CSF injection, then CD133+ cells were isolated through peripheral blood aphaeresis to obtain a mean of 124.39 million cells (range 42-236), which were immediately delivered into the spiral arterioles by catheterization. Subsequently, endometrial treatment after stem cell therapy was assessed in terms of restoration of menses, endometrial thickness (by vaginal ultrasound), adhesion score (by hysteroscopy), neoangiogenesis and ongoing pregnancy rate. The study was conducted at Hospital Clínico Universitario of Valencia and IVI Valencia (Spain). All 11 AS patients exhibited an improved uterine cavity 2 months after stem cell therapy. Endometrial thickness increased from an average of 4.3 mm (range 2.7-5) to 6.7 mm (range 3.1-12) ( ITALIC! P = 0

Rb-Sr mantle isochrons from oceanic regions

Energy Technology Data Exchange (ETDEWEB)

Brooks, C; Hart, S R; Hofmann, A; James, D E [Carnegie Institution of Washington, D.C. (USA). Dept. of Terrestrial Magnetism

1976-09-01

Existing data for /sup 87/Sr//sup 86/Sr and Rb/Sr ratios of basalts from oceanic islands and mid-ocean spreading ridges show significant positive correlations on a Rb-Sr isochron diagram (when data are averaged by island group). Furthermore, tholeiites and alkali basalts occupy distinct non-overlapping fields on this plot. The tholeiite correlation is interpreted as a mantle isochron, and the agreement of this age (1.6+-0.2 b.y.) with that reported for Pb-Pb isochrons from oceanic basalts lends strong support to the use of such isochrons for tracing mantle evolution. Oceanic basalts are apparently sampling a mantle in which chemical heterogeneities have persisted for at least 1.5-2.0 b.y. The data support a kinematic model for the mantle in which a relatively uniform and non-radiogenic asthenosphere is penetrated by, and mixed with, blobs or plumes derived from an isolated (1.5-2 b.y.) and chemically heterogeneous mesosphere.

Mantle helium in the Red Sea brines

International Nuclear Information System (INIS)

Lupton, J.E.; Weiss, R.F.; Craig, H.

1977-01-01

It is stated that He isotope studies of terrestrial samples have shown the existence of two He components that are clearly distinct from atmospheric He. These are termed 'crustal' He and 'mantle' He; the latter was discovered as 'excess 3 He' in deep ocean water and attributed to a flux of primordial He from the mantle. Studies of the 3 He/ 4 He ratio in deep Pacific water and in He trapped in submarine basalt glasses showed that this 'mantle' component is characterised by ratios about ten times the atmospheric ratio and 100 times the ratio in 'crustal' He. Basalt glasses from other deep sea waters also showed similar ratios, and it is indicated that 'mantle' He in areas in which new lithosphere is being formed has a unique and uniform isotopic signature. Measurements of He and Ne are here reported that reveal additional information on the origin of Red Sea brines and their relationship to the Red Sea rifts. (U.K.)

Continental smokers couple mantle degassing and distinctive microbiology within continents

Science.gov (United States)

Crossey, Laura J.; Karlstrom, Karl E.; Schmandt, Brandon; Crow, Ryan R.; Colman, Daniel R.; Cron, Brandi; Takacs-Vesbach, Cristina D.; Dahm, Clifford N.; Northup, Diana E.; Hilton, David R.; Ricketts, Jason W.; Lowry, Anthony R.

2016-02-01

The discovery of oceanic black (and white) smokers revolutionized our understanding of mid-ocean ridges and led to the recognition of new organisms and ecosystems. Continental smokers, defined here to include a broad range of carbonic springs, hot springs, and fumaroles that vent mantle-derived fluids in continental settings, exhibit many of the same processes of heat and mass transfer and ecosystem niche differentiation. Helium isotope (3He/4He) analyses indicate that widespread mantle degassing is taking place in the western U.S.A., and that variations in mantle helium values correlate best with low seismic-velocity domains in the mantle and lateral contrasts in mantle velocity rather than crustal parameters such as GPS, proximity to volcanoes, crustal velocity, or composition. Microbial community analyses indicate that these springs can host novel microorganisms. A targeted analysis of four springs in New Mexico yield the first published occurrence of chemolithoautotrophic Zetaproteobacteria in a continental setting. These observations lead to two linked hypotheses: that mantle-derived volatiles transit through conduits in extending continental lithosphere preferentially above and at the edges of mantle low velocity domains. High CO2 and other constituents ultimately derived from mantle volatiles drive water-rock interactions and heterogeneous fluid mixing that help structure diverse and distinctive microbial communities.

Tectonic predictions with mantle convection models

Science.gov (United States)

Coltice, Nicolas; Shephard, Grace E.

2018-04-01

Over the past 15 yr, numerical models of convection in Earth's mantle have made a leap forward: they can now produce self-consistent plate-like behaviour at the surface together with deep mantle circulation. These digital tools provide a new window into the intimate connections between plate tectonics and mantle dynamics, and can therefore be used for tectonic predictions, in principle. This contribution explores this assumption. First, initial conditions at 30, 20, 10 and 0 Ma are generated by driving a convective flow with imposed plate velocities at the surface. We then compute instantaneous mantle flows in response to the guessed temperature fields without imposing any boundary conditions. Plate boundaries self-consistently emerge at correct locations with respect to reconstructions, except for small plates close to subduction zones. As already observed for other types of instantaneous flow calculations, the structure of the top boundary layer and upper-mantle slab is the dominant character that leads to accurate predictions of surface velocities. Perturbations of the rheological parameters have little impact on the resulting surface velocities. We then compute fully dynamic model evolution from 30 and 10 to 0 Ma, without imposing plate boundaries or plate velocities. Contrary to instantaneous calculations, errors in kinematic predictions are substantial, although the plate layout and kinematics in several areas remain consistent with the expectations for the Earth. For these calculations, varying the rheological parameters makes a difference for plate boundary evolution. Also, identified errors in initial conditions contribute to first-order kinematic errors. This experiment shows that the tectonic predictions of dynamic models over 10 My are highly sensitive to uncertainties of rheological parameters and initial temperature field in comparison to instantaneous flow calculations. Indeed, the initial conditions and the rheological parameters can be good enough

Pb evolution in the Martian mantle

Science.gov (United States)

Bellucci, J. J.; Nemchin, A. A.; Whitehouse, M. J.; Snape, J. F.; Bland, P.; Benedix, G. K.; Roszjar, J.

2018-03-01

The initial Pb compositions of one enriched shergottite, one intermediate shergottite, two depleted shergottites, and Nakhla have been measured by Secondary Ion Mass Spectrometry (SIMS). These values, in addition to data from previous studies using an identical analytical method performed on three enriched shergottites, ALH 84001, and Chassigny, are used to construct a unified and internally consistent model for the differentiation history of the Martian mantle and crystallization ages for Martian meteorites. The differentiation history of the shergottites and Nakhla/Chassigny are fundamentally different, which is in agreement with short-lived radiogenic isotope systematics. The initial Pb compositions of Nakhla/Chassigny are best explained by the late addition of a Pb-enriched component with a primitive, non-radiogenic composition. In contrast, the Pb isotopic compositions of the shergottite group indicate a relatively simple evolutionary history of the Martian mantle that can be modeled based on recent results from the Sm-Nd system. The shergottites have been linked to a single mantle differentiation event at 4504 Ma. Thus, the shergottite Pb isotopic model here reflects a two-stage history 1) pre-silicate differentiation (4504 Ma) and 2) post-silicate differentiation to the age of eruption (as determined by concordant radiogenic isochron ages). The μ-values (238U/204Pb) obtained for these two different stages of Pb growth are μ1 of 1.8 and a range of μ2 from 1.4-4.7, respectively. The μ1-value of 1.8 is in broad agreement with enstatite and ordinary chondrites and that proposed for proto Earth, suggesting this is the initial μ-value for inner Solar System bodies. When plotted against other source radiogenic isotopic variables (Sri, γ187Os, ε143Nd, and ε176Hf), the second stage mantle evolution range in observed mantle μ-values display excellent linear correlations (r2 > 0.85) and represent a spectrum of Martian mantle mixing-end members (depleted

T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia

DEFF Research Database (Denmark)

Vries, A.C. de; Langerak, A.W.; Verhaaf, B.

2008-01-01

(Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which...... the hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to separate from (v)SAA. Recently, studies provided a molecular signature of autoimmunity in adult (v)SAA, by showing oligoclonality based on the length of the TCR Vbeta CDR3 region. We investigated retrospectively the frequency...... and the discriminative value of TCR Vbeta CDR3 oligoclonality in pediatric (v)SAA and MDS patients. Peripheral blood (PB) and/or BM mononuclear cell samples of pediatric patients with (v)SAA (n=38), refractory cytopenia (MDS-RC) (n=28) and 18 controls were analysed via TCR Vbeta heteroduplex PCR analysis of extracted...

Thermally-Driven Mantle Plumes Reconcile Hot-spot Observations

Science.gov (United States)

Davies, D.; Davies, J.

2008-12-01

Hot-spots are anomalous regions of magmatism that cannot be directly associated with plate tectonic processes (e.g. Morgan, 1972). They are widely regarded as the surface expression of upwelling mantle plumes. Hot-spots exhibit variable life-spans, magmatic productivity and fixity (e.g. Ito and van Keken, 2007). This suggests that a wide-range of upwelling structures coexist within Earth's mantle, a view supported by geochemical and seismic evidence, but, thus far, not reproduced by numerical models. Here, results from a new, global, 3-D spherical, mantle convection model are presented, which better reconcile hot-spot observations, the key modification from previous models being increased convective vigor. Model upwellings show broad-ranging dynamics; some drift slowly, while others are more mobile, displaying variable life-spans, intensities and migration velocities. Such behavior is consistent with hot-spot observations, indicating that the mantle must be simulated at the correct vigor and in the appropriate geometry to reproduce Earth-like dynamics. Thermally-driven mantle plumes can explain the principal features of hot-spot volcanism on Earth.

Dose-escalated total body irradiation and autologous stem cell transplantation for refractory hematologic malignancy

International Nuclear Information System (INIS)

McAfee, Steven L.; Powell, Simon N.; Colby, Christine; Spitzer, Thomas R.

2002-01-01

Purpose: To evaluate the feasibility of dose escalation of total body irradiation (TBI) above the previously reported maximally tolerated dose, we have undertaken a Phase I-II trial of dose-escalated TBI with autologous peripheral blood stem cell transplantation (PBSCT) for chemotherapy-refractory lymphoma. Methods and Materials: Nine lymphoma patients with primary refractory disease (PRD) or in resistant relapse (RR) received dose-escalated TBI and PBSCT. The three dose levels of fractionated TBI (200 cGy twice daily) were 1,600 cGy, 1,800 cGy, and 2,000 cGy. Lung blocks were used to reduce the TBI transmission dose by 50%, and the chest wall dose was supplemented to the prescribed dose using electrons. Shielding of the kidneys was performed to keep the maximal renal dose at 1,600 cGy. Three patients, two with non-Hodgkin's lymphoma (NHL) in RR and one with PRD Hodgkin's disease, received 1,600 cGy + PBSCT, three patients (two NHL in RR, one PRD) received 1,800 cGy + PBSCT, and three patients with NHL (two in RR, one PRD) received 2,000 cGy + PBSCT. Results: Toxicities associated with this high-dose TBI regimen included reversible hepatic veno-occlusive disease in 1 patient, Grade 2 mucositis requiring narcotic analgesics in 8 patients, and neurologic toxicities consisting of a symmetrical sensory neuropathy (n=4) and Lhermitte's syndrome (n=1). Interstitial pneumonitis developed in 1 patient who received 1,800 cGy after receiving recombinant α-interferon (with exacerbation after rechallenge with interferon). Six (66%) patients achieved a response. Four (44%) patients achieved complete responses, three of which were of a duration greater than 1 year, and 2 (22%) patients achieved a partial response. One patient remains disease-free more than 5 years posttransplant. Corticosteroid-induced gastritis and postoperative infection resulted in the death of 1 patient in complete response, 429 days posttransplant. Conclusion: TBI in a dose range 1,600-2,000 cGy as

A phase I/II trial to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor Temsirolimus added to standard therapy of Rituximab and DHAP for the treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma – the STORM trial

International Nuclear Information System (INIS)

Witzens-Harig, Mathias; Memmer, Marie Luise; Dreyling, Martin; Hess, Georg

2013-01-01

The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches. The STORM study is a prospective, multicentre phase I/II study to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to the standard therapy rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. The primary objective of the phase I of the trial is to establish the maximum tolerated dose (MTD) of temsirolimus in combination with rituximab and DHAP. The secondary objective is to demonstrate that stem cells can be mobilized during this regimen in patients scheduled to proceed to high dose therapy. In phase II, the previously established maximum tolerated dose of temsirolimus will be used. The primary objective is to evaluate the overall response rate (ORR) in patients with relapsed DLBCL. The secondary objective is to evaluate progression free survival (PFS), overall survival (OS) and toxicity. The study will be accompanied by an analysis of lymphoma subtypes determined by gene expression analysis (GEP). The STORM trial evaluates the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to standard therapy of rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. It also might identify predictive markers for this treatment modality. ClinicalTrials.gov http

Machining refractory alloys: an overview

International Nuclear Information System (INIS)

Christopher, J.D.

1984-01-01

Nontraditional machining is a generic term for those material removal processes that differ drastically from the historic operations such as turning, milling, drilling, tapping, and grinding. The use of primary energy modes other than mechanical, such as thermal, electrical, and chemical, sets these operations apart and reinforces their nontraditional label. Several of these newer processes have been very successful in machining close tolerance parts from refractory materials. This paper provides a general overview of both traditional and nontraditional aspects of machining refractory materials. 11 figures, 7 tables

Lithology and temperature: How key mantle variables control rift volcanism

Science.gov (United States)

Shorttle, O.; Hoggard, M.; Matthews, S.; Maclennan, J.

2015-12-01

Continental rifting is often associated with extensive magmatic activity, emplacing millions of cubic kilometres of basalt and triggering environmental change. The lasting geological record of this volcanic catastrophism are the large igneous provinces found at the margins of many continents and abrupt extinctions in the fossil record, most strikingly that found at the Permo-Triassic boundary. Rather than being considered purely a passive plate tectonic phenomenon, these episodes are frequently explained by the involvement of mantle plumes, upwellings of mantle rock made buoyant by their high temperatures. However, there has been debate over the relative role of the mantle's temperature and composition in generating the large volumes of magma involved in rift and intra-plate volcanism, and even when the mantle is inferred to be hot, this has been variously attributed to mantle plumes or continental insulation effects. To help resolve these uncertainties we have combined geochemical, geophysical and modelling results in a two stage approach: Firstly, we have investigated how mantle composition and temperature contribute to melting beneath Iceland, the present day manifestation of the mantle plume implicated in the 54Ma break up of the North Atlantic. By considering both the igneous crustal production on Iceland and the chemistry of its basalts we have been able to place stringent constraints on the viable temperature and lithology of the Icelandic mantle. Although a >100°C excess temperature is required to generate Iceland's thick igneous crust, geochemistry also indicates that pyroxenite comprises 10% of its source. Therefore, the dynamics of rifting on Iceland are modulated both by thermal and compositional mantle anomalies. Secondly, we have performed a global assessment of the mantle's post break-up thermal history to determine the amplitude and longevity of continental insulation in driving excess volcanism. Using seismically constrained igneous crustal

Dynamical links between small- and large-scale mantle heterogeneity: Seismological evidence

Science.gov (United States)

Frost, Daniel A.; Garnero, Edward J.; Rost, Sebastian

2018-01-01

We identify PKP • PKP scattered waves (also known as P‧ •P‧) from earthquakes recorded at small-aperture seismic arrays at distances less than 65°. P‧ •P‧ energy travels as a PKP wave through the core, up into the mantle, then scatters back down through the core to the receiver as a second PKP. P‧ •P‧ waves are unique in that they allow scattering heterogeneities throughout the mantle to be imaged. We use array-processing methods to amplify low amplitude, coherent scattered energy signals and resolve their incoming direction. We deterministically map scattering heterogeneity locations from the core-mantle boundary to the surface. We use an extensive dataset with sensitivity to a large volume of the mantle and a location method allowing us to resolve and map more heterogeneities than have previously been possible, representing a significant increase in our understanding of small-scale structure within the mantle. Our results demonstrate that the distribution of scattering heterogeneities varies both radially and laterally. Scattering is most abundant in the uppermost and lowermost mantle, and a minimum in the mid-mantle, resembling the radial distribution of tomographically derived whole-mantle velocity heterogeneity. We investigate the spatial correlation of scattering heterogeneities with large-scale tomographic velocities, lateral velocity gradients, the locations of deep-seated hotspots and subducted slabs. In the lowermost 1500 km of the mantle, small-scale heterogeneities correlate with regions of low seismic velocity, high lateral seismic gradient, and proximity to hotspots. In the upper 1000 km of the mantle there is no significant correlation between scattering heterogeneity location and subducted slabs. Between 600 and 900 km depth, scattering heterogeneities are more common in the regions most remote from slabs, and close to hotspots. Scattering heterogeneities show an affinity for regions close to slabs within the upper 200 km of the

Flow in the Deep Mantle from Seisimc Anisotropy: Progress and Prospects

Science.gov (United States)

Long, M. D.

2017-12-01

Observations of seismic anisotropy, or the directional dependence of seismic wavespeeds, provide one some of the most direct constraints on the pattern of flow in the Earth's mantle. In particular, as our understanding of crystallographic preferred orientation (CPO) of olivine aggregates under a range of deformation conditions has improved, our ability to exploit observations of upper mantle anisotropy has led to fundamental discoveries about the patterns of flow in the upper mantle and the drivers of that flow. It has been a challenge, however, to develop a similar framework for understanding flow in the deep mantle (transition zone, uppermost lower mantle, and lowermost mantle), even though there is convincing observational evidence for seismic anisotropy at these depths. Recent progress on the observational front has allowed for an increasingly detailed view of mid-mantle anisotropy (transition zone and uppermost lower mantle), particularly in subduction systems, which may eventually lead to a better understanding of mid-mantle deformation and the dynamics of slab interaction with the surrounding mid-mantle. New approaches to the observation and modeling of lowermost mantle anisotropy, in combination with constraints from mineral physics, are progressing towards interpretive frameworks that allow for the discrimination of different mantle flow geometries in different regions of D". In particular, observational strategies that involve the use of multiple types of body wave phases sampled over a range of propagation azimuths enable detailed forward modeling approaches that can discriminate between different mechanisms for D" anisotropy (e.g., CPO of post-perovskite, bridgmanite, or ferropericlase, or shape preferred orientation of partial melt) and identify plausible anisotropic orientations. We have recently begun to move towards a full waveform modeling approach in this work, which allows for a more accurate simulation for seismic wave propagation. Ongoing

Production of lightweight refractory material by hydrothermal process

International Nuclear Information System (INIS)

Sulejmani, Ramiz B.

2002-01-01

Many different processes of production of lightweight refractories are well known over the World. Traditional production of lightweight refractories is by addition of combustibles or by a special frothing process. This work is concerned with hydrothermal of lightweight refractories from rice husk ash. The rice husk ash, used in present investigations were from Kocani region, R. Macedonia. The chemical analysis of the rice husk ash shows that it contains 91,8 - 93,7% SiO 2 and some alkaline and alkaline earth oxides. Microscopic and X - ray diffraction examinations of the rice husk ash have shown that it is composed of cristobalite, tridimite and amorphous silica. The composition of the mixture for lightweight refractory brick production is 93,4% rice husk ash and 6,6% Ca(OH) 2 . The mixtures were well mixed, moistened and pressed at 5 - 10 MPa. The hydrothermal reactions between calcium hydroxide and rice husk ash over the temperature range 80 - 160 o C were investigated. The period of autoclave treatment was from 2 to 72 h. After the hydrothermal treatment of the samples, the mineralogical composition, bulk density, density, cold crushing strength, porosity, refractoriness and thermal expansion were examined. Analysing the properties of the obtained samples it can be concluded that from rice husk ash and calcium hydroxide under hydrothermal condition it is possible to obtain lightweight acid refractory material with high quality.(Author)

Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

Directory of Open Access Journals (Sweden)

Francine Foss

2016-03-01

Full Text Available Abstract Background Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD. Histone deacetylase inhibitors are a novel class of drugs with activity in T cell malignancies. Romidepsin was approved by the US Food and Drug Administration for the treatment of relapsed/refractory PTCL based on a pivotal trial demonstrating an objective response rate of 25 % (33/130, including 15 % with confirmed/unconfirmed complete response and a median duration of response of 28 months. Our objective was to further study the clinical benefits of romidepsin in patients that had the best response of SD. Methods Patients with PTCL relapsed/refractory to ≥1 prior therapy were treated with the approved dose of 14 mg/m2 romidepsin on days 1, 8, and 15 of six 28-day cycles; patients with SD or response after cycle 6 were allowed to continue on study until progression. By protocol amendment, patients treated for ≥12 cycles could receive maintenance dosing twice per cycle; after cycle 24, dosing could be further reduced to once per cycle in those who had received maintenance dosing for ≥6 months. Results Of the 32 patients (25 % with the best response of SD, 22 had SD for ≥90 days (SD90; cycle 4 response assessment. The longest SD was >3 years in a patient who received maintenance dosing of 14 mg/m2 on days 1 and 15 beginning in cycle 13. Patients with the best response of SD90 or partial response achieved similar overall and progression-free survival. Prolonged dosing of romidepsin was well tolerated. Conclusions We concluded that patients who achieve SD may consider continuing treatment because the clinical benefits of romidepsin may extend beyond objective responses. Trial registration NCT00426764

CD19 CAR-T cell therapy for relapsed/refractory acute lymphoblastic leukemia: factors affecting toxicities and long-term efficacies.

Science.gov (United States)

Zhang, Li-Na; Song, Yongping; Liu, Delong

2018-03-15

The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy. CD-19 CAR-T cells have been recently approved for high-risk R/R ALL and lymphoma. The data from long-term follow-up of a single-center phase I study of 19-28z CAR-T cell therapy for adult R/R ALL were just published. At the same time, a multicenter phase II study of 19-41BB CAR-T cell therapy for children and young adults with R/R B cell ALL was also published. The two studies provided fresh information with long-term follow-up. This research highlight analyzed the data and proposed future perspectives for further investigation in this rapidly evolving field.

Quantifying mantle structure and dynamics using plume tracing in seismic tomography

Science.gov (United States)

O'Farrell, K. A.; Eakin, C. M.; Jackson, M. G.; Jones, T. D.; Lekic, V.; Lithgow-Bertelloni, C. R.

2017-12-01

Directly linking deep mantle processes with surface features and dynamics is a complex problem. Hotspot volcanism gives us surface observables of mantle signatures, but the depth and source of the mantle plumes feeding these hotspots are highly debated. To address these issues, it is necessary to consider the entire journey of a plume through the mantle. By analyzing the behavior of mantle plumes we can constrain the vigor of mantle convection, the net rotation of the mantle and the role of thermal versus chemical anomalies as well as the bulk physical properties such as the viscosity profile. To do this, we developed a new algorithm to trace plume-like features in shear-wave (Vs) seismic tomography models based on picking local minima in the velocity and searching for continuous features with depth. We applied this method to recent tomographic models and find 60+ continuous plume conduits that are > 750 km long. Approximately a third of these can be associated with known hotspots at the surface. We analyze the morphology of these continuous conduits and infer large scale mantle flow patterns and properties. We find the largest lateral deflections in the conduits occur near the base of the lower mantle and in the upper mantle (near the thermal boundary layers). The preferred orientation of the plume deflections show large variability at all depths and indicate no net mantle rotation. Plate by plate analysis shows little agreement in deflection below particular plates, indicating these deflected features might be long lived and not caused by plate shearing. Changes in the gradient of plume deflection are inferred to correspond with viscosity contrasts in the mantle and found below the transition zone as well as at 1000 km depth. From this inferred viscosity structure, we explore the dynamics of a plume through these viscosity jumps. We also retrieve the Vs profiles for the conduits and compare with the velocity profiles predicted for different mantle adiabat

Directed light fabrication of refractory metals and alloys

International Nuclear Information System (INIS)

Fonseca, J.C.; Lewis, G.K.; Dickerson, P.G.; Nemec, R.B.

1999-01-01

This report covers work performed under Order No. FA0000020 AN Contract DE-AC12-76SN00052 for deposition of refractory pure metals and alloys using the Directed Light Fabrication (DLF) process and represents the progress in depositing these materials through September 1998. In extending the DLF process technology to refractory metals for producing fully dense, structurally sound deposits, several problems have become evident. 1. Control of porosity in DLF-deposited refractory metal is difficult because of gases, apparently present in commercially purchased refractory metal powder starting materials. 2. The radiant heat from the molten pool during deposition melts the DLF powder feed nozzle. 3. The high reflectivity of molten refractory metals, at the Nd-YAG laser wavelength (1.06microm), produces damaging back reflections to the optical train and fiber optic delivery system that can terminate DLF processing. 4. The current limits on the maximum available laser power to prevent back reflection damage limit the parameter range available for densification of refractory metals. The work to date concentrated on niobium, W-25Re, and spherodized tungsten. Niobium samples, made from hydride-dehydride powder, had minimal gas porosity and the deposition parameters were optimized; however, test plates were not made at this time. W-25Re samples, containing sodium and potassium from a precipitation process, were made and porosity was a problem for all samples although minimized with some process parameters. Deposits made from potassium reduced tungsten that was plasma spherodized were made with minimized porosity. Results of this work indicate that further gas analysis of starting powders and de-gassing of starting powders and/or gas removal during deposition of refractory metals is required

Radiological safety assessment of gas mantle industries in India

International Nuclear Information System (INIS)

Sadagopan, G.; Venkataraman, G.

1994-01-01

Thorium, a radioactive element of actinide family was discovered by Berzelius in 1828 and named by him in honor of the Scandinavian God open-quote Thor close-quote. Following its discovery the earliest known use of thorium was in the making of gas mantles. The other use as an X-ray contrast medium open-quote Thorotrast close-quote has since long been discontinued, where as even today its use in gas mantles is continued. Gas lights have been used as a source of light since 1800's. In India, although electric bulbs have replaced most of the gas lights, even today in villages and in urban areas where there is no continuous power supply and in outdoor lightings gas lamps are used. The mantle which is used in these lamps is called the Welsbach mantle and is a netted hose that is impregnated with thorium nitrate and other metals. The function of a gas mantle is to produce a bright light during operation of the lighting device (gas or kerosene lamp) in which the mantle is placed. When placed in a lighting device and heated to 1300-1800 degree Celcius thorium in the mantle incandesces and gives off bright light. In India presently there are about 70 manufacturing units handling 150 metric tons of thorium nitrate annually. There are about four hundred persons involved in manufacturing 200 million mantles per year. Thorium is chosen because of its property of incadescence, however since it is radioactive, radiation safety of the workplace, handling personnel and safe environmental condition for members of public have to be maintained

Spinning of refractory metals

International Nuclear Information System (INIS)

Chang Wenkua; Zheng Han

1989-01-01

The effects of spinning process parameters including max. pass percentage reduction, spinning temperature, feed rate, lubricant and annealing technology on the quality of shaped components are summarized and discussed in the present paper. The above mentioned parameters are adopted in the process of spinning of barrel-shaped and specially shaped components of refractory metals and their alloys W, Mo, Nb, Zr, TZM molybdenum alloy, C-103, C-752 niobium alloy etc. The cause of leading to usual defects of spun products of refractory metals such as lamellar as 'scaling', crack, swelling, wrinkle, etc. have been analysed and the ways to eliminate the defects have been put forward. 8 figs., 5 tabs. (Author)

Executive Summary: “Mantle Frontier” Workshop

Directory of Open Access Journals (Sweden)

Workshop Report Writing Group

2011-03-01

Full Text Available The workshop on “Reaching the Mantle Frontier: Moho and Beyond” was held at the Broad Branch Road Campus of the Carnegie Institution of Washington on 9–11 September 2010. The workshop attracted seventy-four scientists and engineers from academia and industry in North America, Asia, and Europe.Reaching and sampling the mantle through penetration of the entire oceanic crust and the Mohorovičić discontinuity (Moho has been a longstanding goal of the Earth science community. The Moho is a seismic transition, often sharp, from a region with compressional wave velocities (Vp less than 7.5 km s-1 to velocities ~8 km s-1. It is interpreted in many tectonic settings, and particularly in tectonic exposures of oceanic lower crust, as the transition from igneous crust to mantle rocks that are the residues of melt extraction. Revealing the in situ geological meaning of the Moho is the heart of the Mohole project. Documenting ocean-crust exchanges and the nature and extent of the subseafloor biosphere have also become integral components of the endeavor. The purpose of the “Mantle Frontier” workshop was to identify key scientific objectives associated with innovative technology solutions along with associated timelines and costs for developments and implementation of this grandchallenge.

Migration of TRU-containing slag into candidate refractories for waste management

International Nuclear Information System (INIS)

Seymour, W.C.

1978-11-01

Results of initial tests on transuranic migration into commercial refractories are reported. Five castable refractories and a plastic-bonded refractory were tested using the cup test method. Initial results indicate that castable materials will not survive conditions expected in the slagging pyrolysis unit; plastic refractories appear to have better performance. The major mechanism of migration into the tested refractories is pore penetration. Al 2 O 3 and Al 2 O 3 -Cr 2 O 3 phases appear resistant to chemical diffusion of transuranics. 2 figures, 16 tables

Reconciling laboratory and observational models of mantle rheology in geodynamic modelling

Science.gov (United States)

King, Scott D.

2016-10-01

Experimental and geophysical observations constraining mantle rheology are reviewed with an emphasis on their impact on mantle geodynamic modelling. For olivine, the most studied and best-constrained mantle mineral, the tradeoffs associated with the uncertainties in the activation energy, activation volume, grain-size and water content allow the construction of upper mantle rheology models ranging from nearly uniform with depth to linearly increasing from the base of the lithosphere to the top of the transition zone. Radial rheology models derived from geophysical observations allow for either a weak upper mantle or a weak transition zone. Experimental constraints show that wadsleyite and ringwoodite are stronger than olivine at the top of the transition zone; however the uncertainty in the concentration of water in the transition zone precludes ruling out a weak transition zone. Both observational and experimental constraints allow for strong or weak slabs and the most promising constraints on slab rheology may come from comparing inferred slab geometry from seismic tomography with systematic studies of slab morphology from dynamic models. Experimental constraints on perovskite and ferropericlase strength are consistent with general feature of rheology models derived from geophysical observations and suggest that the increase in viscosity through the top of the upper mantle could be due to the increase in the strength of ferropericlase from 20-65 GPa. The decrease in viscosity in the bottom half of the lower mantle could be the result of approaching the melting temperature of perovskite. Both lines of research are consistent with a high-viscosity lithosphere, a low viscosity either in the upper mantle or transition zone, and high viscosity in the lower mantle, increasing through the upper half of the lower mantle and decreasing in the bottom half of the lower mantle, with a low viscosity above the core. Significant regions of the mantle, including high

Lithospheric mantle evolution in the Afro-Arabian domain: Insights from Bir Ali mantle xenoliths (Yemen)

Science.gov (United States)

Sgualdo, P.; Aviado, K.; Beccaluva, L.; Bianchini, G.; Blichert-Toft, J.; Bryce, J. G.; Graham, D. W.; Natali, C.; Siena, F.

2015-05-01

Detailed petrological and geochemical investigations of an extensive sampling of mantle xenoliths from the Neogene-Quaternary Bir Ali diatreme (southern Yemen) indicate that the underlying lithospheric mantle consists predominantly of medium- to fine-grained (often foliated) spinel-peridotites (85-90%) and spinel-pyroxenites (10-15%) showing thermobarometric estimates in the P-T range of 0.9-2.0 GPa and 900-1150 °C. Peridotites, including lherzolites, harzburgites and dunites delineate continuous chemical, modal and mineralogical variations compatible with large extractions of basic melts occurring since the late Proterozoic (~ 2 Ga, according to Lu-Hf model ages). Pyroxenites may represent intrusions of subalkaline basic melts interacting and equilibrated with the host peridotite. Subsequent metasomatism has led to modal changes, with evidence of reaction patches and clinopyroxene and spinel destabilization, as well as formation of new phases (glass, amphibole and feldspar). These changes are accompanied by enrichment of the most incompatible elements and isotopic compositions. 143Nd/144Nd ranges from 0.51419 to 0.51209 (εNd from + 30.3 to - 10.5), 176Hf/177Hf from 0.28459 to 0.28239 (εHf from + 64.4 to - 13.6), and 208Pb/204Pb from 36.85 to 41.56, thus extending from the depleted mantle (DM) towards the enriched OIB mantle (EM and HIMU) components. 3He/4He (R/RA) ratios vary from 7.2 to 7.9 with He concentrations co-varying with the most incompatible element enrichment, in parallel with metasomatic effects. These metasomatic events, particularly effective in harzburgites and dunites, are attributable to the variable interaction with alkaline basic melts related to the general extensional and rifting regime affecting the East Africa-Arabian domain during the Cenozoic. In this respect, Bir Ali mantle xenoliths resemble those occurring along the Arabian margins and the East Africa Rift system, similarly affected by alkaline metasomatism, whereas they are

Synergistic suppression of the PI3K inhibitor CAL-101 with bortezomib on mantle cell lymphoma growth

International Nuclear Information System (INIS)

Qu, Fu-Lian; Xia, Bing; Li, Su-Xia; Tian, Chen; Yang, Hong-Liang; Li, Qian; Wang, Ya-Fei; Yu, Yong; Zhang, Yi-Zhuo

2015-01-01

To investigate the effects of CAL-101, particularly when combined with bortezomib (BTZ) on mantle cell lymphoma (MCL) cells, and to explore its relative mechanisms. MTT assay was applied to detect the inhibitory effects of different concentrations of CAL-101. MCL cells were divided into four groups: control group, CAL-101 group, BTZ group, and CAL-101/BTZ group. The expression of PI3K-p110σ, AKT, ERK, p-AKT and p-ERK were detected by Western blot. The apoptosis rates of CAL-101 group, BTZ group, and combination group were detected by flow cytometry. The location changes of nuclear factor kappa-B (NF-κB) of 4 groups was investigated by NF-κB Kit exploring. Western blot was applied to detect the levels of caspase-3 and the phosphorylation of AKT in different groups. CAL-101 dose- and time-dependently induced reduction in MCL cell viability. CAL-101 combined with BTZ enhanced the reduction in cell viability and apoptosis. Western blot analysis showed that CAL-101 significantly blocked the PI3K/AKT and ERK signaling pathway in MCL cells. The combination therapy contributed to the inactivation of NF-κB and AKT in MCL cell lines. However, cleaved caspase-3 was up-regulated after combined treatment. Our study showed that PI3K/p110σ is a novel therapeutic target in MCL, and the underlying mechanism could be the blocking of the PI3K/AKT and ERK signaling pathways. These findings provided a basis for clinical evaluation of CAL-101 and a rationale for its application in combination therapy, particularly with BTZ

Beyond low-level activity: On a 'non-radioactive' gas mantle

International Nuclear Information System (INIS)

Poljanc, Karin; Steinhauser, Georg; Sterba, Johannes H.; Buchtela, Karl; Bichler, Max

2007-01-01

Gas mantles for camping gas lanterns sometimes contain thorium compounds. During the last years, the use of thorium-free gas mantles has become more and more popular due to the avoidance of a radioactive heavy metal. We investigated a gas mantle type that is declared to be 'non-radioactive' and that can be bought in Austria at the moment. Methods used were Instrumental Neutron Activation Analysis (INAA), γ-spectroscopy, and Liquid Scintillation Counting (LSC). We found massive thorium contents of up to 259 mg per gas mantle. Leaching experiments showed that only 0.4% of the Th but approximately 90% of the decay products of 232 Th can be leached under conditions simulating sucking and chewing with human saliva. In this paper, the investigation of these gas mantles including the consideration of the environmental hazard caused by disposed mantles and the health hazard for unsuspecting consumers is presented and legal consequences are discussed for this fraud

Refractory of Furnaces to Reduce Environmental Impact

International Nuclear Information System (INIS)

Hanzawa, Shigeru

2011-01-01

The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO 2 produced from this high energy load. To improve this situation, R and D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO 2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

Refractory of Furnaces to Reduce Environmental Impact

Science.gov (United States)

Hanzawa, Shigeru

2011-10-01

The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO2 produced from this high energy load. To improve this situation, R&D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

Development of alumino-silicate refractories in Ghana

International Nuclear Information System (INIS)

Kisiedu, A. K.; Tetteh, D.M.B.; Obiri, H. A.; Brenya, E. F.; Ayensu, A.

2008-01-01

Alumino-silicate (bauxite), andalusite, kaolin and clay were investigated for suitability in production of alumina, mullite and fireclay brick refractories. The raw materials were characterized by X-ray diffraction, differential thermal and silicate analyses. The x-ray diffraction analysis of alumina and mullite refractories fired at 1450 0 C, and fireclay bricks fired at 1350 0 C, indicated presence of corundum and alpha-alumina crystals. The values of thermal (fired) shrinkage, crushing, strength, porosity, water absorption and bulk density determined were 31.1%, 2.3 x 10 3 kg/m 3 , 4.86 x 10 6 N/m 2 and 13.2 % for mullite; 30.2%, 2.4 x 10 3 kg/m 3 , 3.20 x 10 6 N/m 2 and W = 12.8 % for alumina; and 25.2 %, 2.1 x 10 3 kg/m 3 , 2.61 x 10 6 N/m 2 and W = 11.8% for fireclay, respectively. Bauxite, andalusite and special kaolin were identified as potential raw materials for developing alumina and mullite refractories for construction of high temperature kilns and furnaces operating at 1350 0 C. The clay and kaolin minerals could be used to produce fireclay refractories for construction of incinerators operating at maximum temperatures of about 1000 0 C. The performance of the refractories was demonstrated by producing bricks to construct kilns and incinerators for the ceramic industry and hospitals. (au)

An operational definition of primary refractory acute myeloid leukemia allowing early identification of patients who may benefit from allogeneic stem cell transplantation

DEFF Research Database (Denmark)

Ferguson, Paul; Hills, Robert K; Grech, Angela

2016-01-01

Up to 30% of adults with acute myeloid leukemia fail to achieve a complete remission after induction chemotherapy - termed primary refractory acute myeloid leukemia. There is no universally agreed definition of primary refractory disease, nor have the optimal treatment modalities been defined. We...... studied 8907 patients with newly diagnosed acute myeloid leukemia, and examined outcomes in patients with refractory disease defined using differing criteria which have previously been proposed. These included failure to achieve complete remission after one cycle of induction chemotherapy (RES), less than...... a 50% reduction in blast numbers with >15% residual blasts after one cycle of induction chemotherapy (REF1) and failure to achieve complete remission after two courses of induction chemotherapy (REF2). 5-year overall survival was decreased in patients fulfilling any criteria for refractory disease...

Intraplate mantle oxidation by volatile-rich silicic magmas

Energy Technology Data Exchange (ETDEWEB)

Martin, Audrey M.; Médard, Etienne; Righter, Kevin; Lanzirotti, Antonio

2017-11-01

The upper subcontinental lithospheric mantle below the French Massif Central is more oxidized than the average continental lithosphere, although the origin of this anomaly remains unknown. Using iron oxidation analysis in clinopyroxene, oxybarometry, and melt inclusions in mantle xenoliths, we show that widespread infiltration of volatile (HCSO)-rich silicic melts played a major role in this oxidation. We propose the first comprehensive model of magmatism and mantle oxidation at an intraplate setting. Two oxidizing events occurred: (1) a 365–286 Ma old magmatic episode that produced alkaline vaugnerites, potassic lamprophyres, and K-rich calc-alkaline granitoids, related to the N–S Rhenohercynian subduction, and (2) < 30 Ma old magmatism related to W–E extension, producing carbonatites and hydrous potassic trachytes. These melts were capable of locally increasing the subcontinental lithospheric mantle fO2 to FMQ + 2.4. Both events originate from the melting of a metasomatized lithosphere containing carbonate + phlogopite ± amphibole. The persistence of this volatile-rich lithospheric source implies the potential for new episodes of volatile-rich magmatism. Similarities with worldwide magmatism also show that the importance of volatiles and the oxidation of the mantle in intraplate regions is underestimated.

De Novo CD5 Negative Blastic Mantle Cell Lymphoma Presented with Massive Bone Marrow Necrosis without Adenopathy or Organomegaly

Directory of Open Access Journals (Sweden)

Ghaleb Elyamany

2015-01-01

Full Text Available The recent World Health Organization (WHO classification defines mantle cell lymphoma (MCL as a distinct entity characterized by a unique immunophenotype and a molecular hallmark of chromosomal translocation t(11;14(q13;q32. We report an unusual case of an advanced stage of CD5 negative MCL with a blastoid variant with a massive bone marrow (BM necrosis as an initial presenting feature, with no adenopathy or hepatosplenomegaly. The pathologic features showed blastoid variant of MCL and flow cytometry showed that the tumor cells were CD5−, CD19+, CD20+, FMC-7+, CD23−, and lambda light chain restricted. Chromosomal analysis, using karyotype and fluorescent in situ hybridization (FISH, demonstrated karyotypic abnormalities in addition to the t(11;14. Our case study may be reported as a unique case of CD5− blastic MCL with unusual presentation and findings which made the diagnosis of MCL difficult.

Refractory disease in antineutrophil cytoplasmic antibodies associated vasculitis

NARCIS (Netherlands)

Rutgers, Abraham; Kallenberg, Cornelis

Purpose of review Induction treatment of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) is not always successful and nonresponding patients are considered refractory. Recent findings Refractory disease should be subdefined to the treatment that was received.

Water in geodynamical models of mantle convection and plate tectonics

Science.gov (United States)

Rodríguez-González, J.; Van Hunen, J.; Chotalia, K.; Lithgow-Bertelloni, C. R.; Rozel, A.; Tackley, P. J.; Nakagawa, T.

2017-12-01

The presence of water in the the mantle has a significant effect in the dynamical and thermal evolution of Earth, which partially explains the differences with other planets and is a key factor for the presence of life on Earth. First, a small amount of water can decrease the mantle viscosity by a several orders of magnitude, thereby changing the convection regime and affecting the thermal evolution. Second, the presence of water significantly changes the solidus curve, with crucial implications for melting. Third, water in the mantle can change the Clapeyron slope of mantle materials, which changes the depth at which phase transitions take place. The thermal and dynamical evolution of Earth under the presence of water in the mantle has been the focus of recent studies, but many questions remain unanswered. In this project we intend to investigate how the maximum water capacity of different mantle regions affects water transport and Earth's convective regime. We will study the effect phase transitions under the presence of water, which can change the buoyancy of slabs in the transition zone. We present preliminary results numerical models of global mantle convection for the whole history of earth using the numerical geodynamics software tool StagYY. We will use a new parametrisation of dehydration processes, obtained from high-resolution numerical simulations, to implement a more accurate description of the water released from the slab as it travels through the mantle. We have integrated recent experimental results of the water capacity of deep mantle minerals to study the water circulation and the total water budget. We use data from the most recent experiments and ab-inito calculations to implement a realistic rheology.

Solar combi system based on a mantle tank

DEFF Research Database (Denmark)

Yazdanshenas, Eshagh; Furbo, Simon

2007-01-01

A solar combisystem based on a mantle tank is investigated numerically and experimentally. Three different houses with four different radiator systems are considered for the simulations. The needed temperature for the auxiliary heater is determined for different houses and radiator systems....... The thermal performance of the solar combisystem is compared to the thermal performance of a solar domestic hot water system based on a mantle tank. In the experimental study, tank temperatures and the heat transfer coefficient for the top mantle for a discharge test is determined. The investigations showed...

Mantle temperature under drifting deformable continents during the supercontinent cycle

Science.gov (United States)

Yoshida, Masaki

2013-04-01

The thermal heterogeneity of the Earth's mantle under the drifting continents during a supercontinent cycle is a controversial issue in earth science. Here, a series of numerical simulations of mantle convection are performed in 3D spherical-shell geometry, incorporating drifting deformable continents and self-consistent plate tectonics, to evaluate the subcontinental mantle temperature during a supercontinent cycle. Results show that the laterally averaged temperature anomaly of the subcontinental mantle remains within several tens of degrees (±50 °C) throughout the simulation time. Even after the formation of the supercontinent and the development of subcontinental plumes due to the subduction of the oceanic plates, the laterally averaged temperature anomaly of the deep mantle under the continent is within +10 °C. This implies that there is no substantial temperature difference between the subcontinental and suboceanic mantles during a supercontinent cycle. The temperature anomaly immediately beneath the supercontinent is generally positive owing to the thermal insulation effect and the active upwelling plumes from the core-mantle boundary. In the present simulation, the formation of a supercontinent causes the laterally averaged subcontinental temperature to increase by a maximum of 50 °C, which would produce sufficient tensional force to break up the supercontinent. The periodic assembly and dispersal of continental fragments, referred to as the supercontinent cycle, bear close relation to the evolution of mantle convection and plate tectonics. Supercontinent formation involves complex processes of introversion, extroversion or a combination of these in uniting dispersed continental fragments, as against the simple opening and closing of individual oceans envisaged in Wilson cycle. In the present study, I evaluate supercontinent processes in a realistic mantle convection regime. Results show that the assembly of supercontinents is accompanied by a

Modern materials based on refractory compounds

International Nuclear Information System (INIS)

Kosolapova, T.Ya.

1979-01-01

Discussed are the existing methods for synthesizing powders of binary refractory compounds and high-productivity techniques which hold promise as regards the manufacture of highly disperse and pure powders. Plasmochemical synthesis is shown to be an effective method for obtaining practically all carbides, nitrides and borides. A description is given of three main methods for obtaining single crystals of refractory compounds (TiN, TiC, ZrC, ZrB 2 , NbC) fairly perfect in structure and composition. These processes include deposition from vapour-gas phase, melting in arc plasma and crystallization from solutions in metallic melts. The advantages have been shown of the self-propagating high-temperature synthesis of refractory compounds, ensuring the manufacture of products, close in composition to stoichiometric ones simultaneously with forming of items. Mechanical, thermal, abrasive, and resistive characteristics of the above materials are presented

The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma.

Science.gov (United States)

Ruella, Marco; Kenderian, Saad S; Shestova, Olga; Fraietta, Joseph A; Qayyum, Sohail; Zhang, Qian; Maus, Marcela V; Liu, Xiaobin; Nunez-Cruz, Selene; Klichinsky, Michael; Kawalekar, Omkar U; Milone, Michael; Lacey, Simon F; Mato, Anthony; Schuster, Stephen J; Kalos, Michael; June, Carl H; Gill, Saar; Wasik, Mariusz A

2016-06-01

Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner. MCL cell lines and primary MCL samples were combined with autologous or normal donor-derived anti-CD19 CAR T cells along with ibrutinib. The effect of the combination was studied in vitro and in mouse xenograft models. MCL cells strongly activated multiple CTL019 effector functions, and MCL killing by CTL019 was further enhanced in the presence of ibrutinib. In a xenograft MCL model, we showed superior disease control in the CTL019- as compared with ibrutinib-treated mice (median survival not reached vs. 95 days, P ibrutinib to CTL019 and showed that 80% to 100% of mice in the CTL019 + ibrutinib arm and 0% to 20% of mice in the CTL019 arm, respectively, remained in long-term remission (P ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma. Clin Cancer Res; 22(11); 2684-96. ©2016 AACR. ©2016 American Association for Cancer Research.

Coldspots and hotspots - Global tectonics and mantle dynamics of Venus

Science.gov (United States)

Bindschadler, Duane L.; Schubert, Gerald; Kaula, William M.

1992-01-01

Based on geologic observations provided by Magellan's first cycle of data collection and recent models of mantle convection in spherical shells and crustal deformation, the major topographic and geologic features of Venus are incorporated into a model of global mantle dynamics. Consideration is given to volcanic rises, such as Beta Regio and Atla Regio, plateau-shaped highlands dominated by complex ridged terrain (e.g., Ovda Regio and Alpha Regio), and circular lowland regions, such as Atalanta Planitia. Each of these features is related to either mantle plumes (hotspots) or mantle downwellings (coldspots).

Osmium Isotopic Evolution of the Mantle Sources of Precambrian Ultramafic Rocks

Science.gov (United States)

Gangopadhyay, A.; Walker, R. J.

2006-12-01

The Os isotopic composition of the modern mantle, as recorded collectively by ocean island basalts, mid- oceanic ridge basalts (MORB) and abyssal peridotites, is evidently highly heterogeneous (γ Os(I) ranging from +25). One important question, therefore, is how and when the Earth's mantle developed such large-scale Os isotopic heterogeneities. Previous Os isotopic studies of ancient ultramafic systems, including komatiites and picrites, have shown that the Os isotopic heterogeneity of the terrestrial mantle can be traced as far back as the late-Archean (~ 2.7-2.8 Ga). This observation is based on the initial Os isotopic ratios obtained for the mantle sources of some of the ancient ultramafic rocks determined through analyses of numerous Os-rich whole-rock and/or mineral samples. In some cases, the closed-system behavior of these ancient ultramafic rocks was demonstrated via the generation of isochrons of precise ages, consistent with those obtained from other radiogenic isotopic systems. Thus, a compilation of the published initial ^{187}Os/^{188}Os ratios reported for the mantle sources of komatiitic and picritic rocks is now possible that covers a large range of geologic time spanning from the Mesozoic (ca. 89 Ma Gorgona komatiites) to the Mid-Archean (e.g., ca. 3.3 Ga Commondale komatiites), which provides a comprehensive picture of the Os isotopic evolution of their mantle sources through geologic time. Several Precambrian komatiite/picrite systems are characterized by suprachondritic initial ^{187}Os/^{188}Os ratios (e.g., Belingwe, Kostomuksha, Pechenga). Such long-term enrichments in ^{187}Os of the mantle sources for these rocks may be explained via recycling of old mafic oceanic crust or incorporation of putative suprachondritic outer core materials entrained into their mantle sources. The relative importance of the two processes for some modern mantle-derived systems (e.g., Hawaiian picrites) is an issue of substantial debate. Importantly, however, the

Structure, preparation and properties of refractory compounds and systems

International Nuclear Information System (INIS)

Holleck, H.; Thuemmler, F.

1977-01-01

At the beginning of this report the possibilities of hardness optimization of refractory carbides are generally discussed. Three papers deal with TaC-basis refractories and hard metals. In particular, carbides with very low nonmetal/metal ratios and composites with hard phases formed by decomposition of tantalum carbonitrides are discussed. Another contribution reports investigations concerning the influence of the microstructure on the hardness of polycristaline mixed carbides. In a series of four papers, results are presented on the work of optimization conventional WC hard metals by introduction of a Fe,Co,Ni-binder: The influence of composition, carbon content and sintering conditions, as well as the wetting behaviour between carbides and binder metals are discussed. Phase relations in the refractory nitride and refractory nitride-binder metal systems as well as phase stabilities of ordered transition metal phases are reported in three papers, fundamental in character. Finally, the work concerning chemical analysis of refractory systems is described. (orig.) [de

Magnitude corrections for attenuation in the upper mantle

International Nuclear Information System (INIS)

Anon.

1978-01-01

Since 1969, a consistent discrepancy in seismic magnitudes of nuclear detonations at NTS compared with magnitudes of detonations elsewhere in the world has been observed. This discrepancy can be explained in terms of a relatively high seismic attenuation for compressional waves in the upper mantle beneath the NTS and in certain other locations. A correction has been developed for this attenuation based on a relationship between the velocity of compressional waves at the top of the earth's mantle (just beneath the Mohorovicic discontinuity) and the seismic attenuation further down in the upper mantle. Our new definition of body-wave magnitude includes corrections for attenuation in the upper mantle at both ends of the teleseismic body-wave path. These corrections bring the NTS oservations into line with measurements of foreign events, and enable one to make more reliable estimates of yields of underground nuclear explosions, wherever the explosion occurs

Assessment of local and regional isotopic equilibrium in the mantle

Energy Technology Data Exchange (ETDEWEB)

Hofmann, A W; Hart, S R [Carnegie Institution of Washington, D.C. (USA). Dept. of Terrestrial Magnetism

1978-02-01

The assumption of local equilibrium during partial melting is fundamental to the interpretation of isotope and trace element data for mantle-derived rocks. If disequilibrium melting is significant, the scale of the chemical and isotopic heterogeneity in the mantle indicated by the data could be as small as the grain size of the mantle rock, and the isotope data themselves are then of doubtful value to the understanding of mantle processes. To assess the scale of isotopic heterogeneity in a partially molten asthenosphere the authors review the Sr isotopic data of volcanic rocks from oceanic regions and the available experimental data on diffusion kinetics in minerals and melts similar to those existing in the mantle. Although diffusion data are scarce and afflicted with uncertainties, most of the diffusion coefficients for cations in mantle minerals at temperatures of 1000 to 1200/sup 0/C appear to be greater than 10/sup -13/ cm/sup 2/ s/sup -1/. Struntium diffusion in liquid basalt is more rapid, with diffusion coefficients of D = 10/sup -7/ to 10/sup -6/ cm/sup 2/ s/sup -1/ near 1300/sup 0/C. Simple model calculations show that, with these D values, a fluid-free mantle can maintain a state of disequilibrium on a centimeter scale for periods of 10/sup 8/ to 10/sup 9/ years. The state of disequilibrium found in many mantle-derived xenoliths is thus easily explained. A partially molten mantle, on the other hand, will tend to equilibrate locally in less than 10/sup 5/ to 10/sup 6/ years. The analytical data on natural rocks likewise indicate that the inhomogeneities are both old (> 1.5 b.y.) and regional in character and that the consistent isotopic differences between ocean island and ocean floor volcanics cannot be explained by small-scall hetorogeneity of the source rock.

Seismic Evidence for Lower Mantle Plume Under the Yellowstone Hotspot

Science.gov (United States)

Nelson, P.; Grand, S.

2017-12-01

The mantle plume hypothesis for the origin of intraplate volcanism has been controversial since its inception in the 1970s. The hypothesis proposes hot narrow upwelling of rock rooted at the core mantle boundary (CMB) rise through the mantle and interact with the base of the lithosphere forming linear volcanic systems such as Hawaii and Yellowstone. Recently, broad lower mantle (>500 km in diameter) slow velocity conduits, most likely thermochemical in origin, have been associated with some intraplate volcanic provinces (French and Romanowicz, 2015). However, the direct detection of a classical thin thermal plume in the lower mantle using travel time tomography has remained elusive (Anderson and Natland, 2014). Here we present a new shear wave tomography model for the mantle beneath the western United States that is optimized to find short wavelength, sub-vertical structures in the lower mantle. Our approach uses carefully measured SKS and SKKS travel times recorded by dense North American seismic networks in conjunction with finite frequency kernels to build on existing tomography models. We find the presence of a narrow ( 300 km diameter) well isolated cylindrically shaped slow anomaly in the lower most mantle which we associate with the Yellowstone Hotspot. The conduit has a 2% reduction in shear velocity and is rooted at the CMB near the California/Arizona/Nevada border. A cross sectional view through the anomaly shows that it is slightly tilted toward the north until about 1300 km depth where it appears to weaken and deflect toward the surficial positon of the hotspot. Given the anomaly's strength, proximity to the Yellowstone Hotspot, and morphology we argue that a thermal plume interpretation is the most reasonable. Our results provide strong support for a lower mantle plume origin of the Yellowstone hotspot and more importantly the existence of deep thermal plumes.

Steady state toroidal magnetic field at earth's core-mantle boundary

Science.gov (United States)

Levy, Eugene H.; Pearce, Steven J.

1991-01-01

Measurements of the dc electrical potential near the top of earth's mantle have been extrapolated into the deep mantle in order to estimate the strength of the toroidal magnetic field component at the core-mantle interface. Recent measurements have been interpreted as indicating that at the core-mantle interface, the magnetic toroidal and poloidal field components are approximately equal in magnitude. A motivation for such measurements is to obtain an estimate of the strength of the toroidal magnetic field in the core, a quantity important to our understanding of the geomagnetic field's dynamo generation. Through the use of several simple and idealized calculation, this paper discusses the theoretical relationship between the amplitude of the toroidal magnetic field at the core-mantle boundary and the actual amplitude within the core. Even with a very low inferred value of the toroidal field amplitude at the core-mantle boundary, (a few gauss), the toroidal field amplitude within the core could be consistent with a magnetohydrodynamic dynamo dominated by nonuniform rotation and having a strong toroidal magnetic field.

Development of realtime monitoring technology for laser photoreaction product - Development of glow discharge-mass spectrometry (GD-MS) hybrid techniques for trace analysis of refractory elements

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Chun [Kyungnam University, Masan (Korea); Kim, Ha Suck [Seoul National University, Seoul (Korea); Kim, Hyo Jin [Dongduk Women' s University, Seoul (Korea)

2000-04-01

This research is focusing on development of hybrid techniques of glow discharge-mass spectrometry for the trace analysis of refractory elements. At first, we developed a glow discharge(GD) ionization cell and its characteristics was investigated. The new GD cell was designed based on direct current hollow cathode glow discharge and it is used for quadrupole mass analyzer and time-of-flight mass analyzer. Currently, GD-quadrupole mass spectrometry is working for the analysis of refractory elements. The experimental results show relatively good for trace analysis. In addition, ion mobile spectrometry using plasma and liquid discharge technique were investigated for the analysis of refractory elements and both techniques need more investigation to deduce the their usefulness. 30 refs., 67 figs., 4 tabs. (Author)

Refractory versus resistant hypertension: Novel distinctive phenotypes

Science.gov (United States)

Dudenbostel, Tanja; Siddiqui, Mohammed; Gharpure, Nitin; Calhoun, David A.

2017-01-01

Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed. PMID:29034321

Nickel and helium evidence for melt above the core-mantle boundary.

Science.gov (United States)

Herzberg, Claude; Asimow, Paul D; Ionov, Dmitri A; Vidito, Chris; Jackson, Matthew G; Geist, Dennis

2013-01-17

High (3)He/(4)He ratios in some basalts have generally been interpreted as originating in an incompletely degassed lower-mantle source. This helium source may have been isolated at the core-mantle boundary region since Earth's accretion. Alternatively, it may have taken part in whole-mantle convection and crust production over the age of the Earth; if so, it is now either a primitive refugium at the core-mantle boundary or is distributed throughout the lower mantle. Here we constrain the problem using lavas from Baffin Island, West Greenland, the Ontong Java Plateau, Isla Gorgona and Fernandina (Galapagos). Olivine phenocryst compositions show that these lavas originated from a peridotite source that was about 20 per cent higher in nickel content than in the modern mid-ocean-ridge basalt source. Where data are available, these lavas also have high (3)He/(4)He. We propose that a less-degassed nickel-rich source formed by core-mantle interaction during the crystallization of a melt-rich layer or basal magma ocean, and that this source continues to be sampled by mantle plumes. The spatial distribution of this source may be constrained by nickel partitioning experiments at the pressures of the core-mantle boundary.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

Science.gov (United States)

Beköz, H; Karadurmus, N; Paydas, S; Türker, A; Toptas, T; Firatli Tuglular, T; Sönmez, M; Gülbas, Z; Tekgündüz, E; Kaya, A H; Özbalak, M; Tastemir, N; Kaynar, L; Yildirim, R; Karadogan, I; Arat, M; Pepedil Tanrikulu, F; Özkocaman, V; Abali, H; Turgut, M; Kurt Yüksel, M; Özcan, M; Dogu, M H; Kabukçu Hacioglu, S; Barista, I; Demirkaya, M; Köseoglu, F D; Toprak, S K; Yilmaz, M; Demirkürek, H C; Demirkol, O; Ferhanoglu, B

2017-10-01

Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with

Forming Refractory Insulation On Copper Wire

Science.gov (United States)

Setlock, J.; Roberts, G.

1995-01-01

Alternative insulating process forms flexible coat of uncured refractory insulating material on copper wire. Coated wire formed into coil or other complex shape. Wire-coating apparatus forms "green" coat on copper wire. After wire coiled, heating converts "green" coat to refractory electrical insulator. When cured to final brittle form, insulating material withstands temperatures above melting temperature of wire. Process used to make coils for motors, solenoids, and other electrical devices to be operated at high temperatures.

Short wavelength lateral variability of lithospheric mantle beneath the Middle Atlas (Morocco) as recorded by mantle xenoliths

Science.gov (United States)

El Messbahi, Hicham; Bodinier, Jean-Louis; Vauchez, Alain; Dautria, Jean-Marie; Ouali, Houssa; Garrido, Carlos J.

2015-05-01

The Middle Atlas is a region where xenolith-bearing volcanism roughly coincides with the maximum of lithospheric thinning beneath continental Morocco. It is therefore a key area to study the mechanisms of lithospheric thinning and constrain the component of mantle buoyancy that is required to explain the Moroccan topography. Samples from the two main xenolith localities, the Bou Ibalghatene and Tafraoute maars, have been investigated for their mineralogy, microstructures, crystallographic preferred orientation, and whole-rock and mineral compositions. While Bou Ibalghatene belongs to the main Middle Atlas volcanic field, in the 'tabular' Middle Atlas, Tafraoute is situated about 45 km away, on the North Middle Atlas Fault that separates the 'folded' Middle Atlas, to the South-East, from the 'tabular' Middle Atlas, to the North-West. Both xenolith suites record infiltration of sub-lithospheric melts that are akin to the Middle Atlas volcanism but were differentiated to variable degrees as a result of interactions with lithospheric mantle. However, while the Bou Ibalghatene mantle was densely traversed by high melt fractions, mostly focused in melt conduits, the Tafraoute suite records heterogeneous infiltration of smaller melt fractions that migrated diffusively, by intergranular porous flow. As a consequence the lithospheric mantle beneath Bou Ibalghaten was strongly modified by melt-rock interactions in the Cenozoic whereas the Tafraoute mantle preserves the record of extensional lithospheric thinning, most likely related to Mesozoic rifting. The two xenolith suites illustrate distinct mechanisms of lithospheric thinning: extensional thinning in Tafraoute, where hydrous incongruent melting triggered by decompression probably played a key role in favouring strain localisation, vs. thermal erosion in Bou Ibalghatene, favoured and guided by a dense network of melt conduits. Our results lend support to the suggestion that lithospheric thinning beneath the Atlas

Gravitational Core-Mantle Coupling and the Acceleration of the Earth

Science.gov (United States)

Rubincam, David Parry; Smith, David E. (Technical Monitor)

2001-01-01

Gravitational core-mantle coupling may be the cause of the observed variable acceleration of the Earth's rotation on the 1000 year timescale. The idea is that density inhomogeneities which randomly come and go in the liquid outer core gravitationally attract density inhomogeneities in the mantle and crust, torquing the mantle and changing its rotation state. The corresponding torque by the mantle on the core may also explain the westward drift of the magnetic field of 0.2 deg per year. Gravitational core-mantle coupling would stochastically affect the rate of change of the Earth's obliquity by just a few per cent. Its contribution to polar wander would only be about 0.5% the presently observed rate. Tidal friction is slowing down the rotation of the Earth, overwhelming a smaller positive acceleration from postglacial rebound. Coupling between the liquid outer core of the Earth and the mantle has long been a suspected reason for changes in the length-of-day. The present investigation focuses on the gravitational coupling between the density anomalies in the convecting liquid outer core and those in the mantle and crust as a possible cause for the observed nonsecular acceleration on the millenial timescale. The basic idea is as follows. There are density inhomogeneities caused by blobs circulating in the outer core like the blobs in a lava lamp; thus the outer core's gravitational field is not featureless. Moreover, these blobs will form and dissipate somewhat randomly. Thus there will be a time variability to the fields. These density inhomogeneities will gravitationally attract the density anomalies in the mantle.

Execution of mantle field with multileaf collimator: A simple approach

Directory of Open Access Journals (Sweden)

Prabhakar Ramachandran

2008-01-01

Full Text Available Background: Until very recently mantle field radiotherapy remained the gold standard for the treatment of favorable early-stage Hodgkin′s lymphoma. The classic mantle includes all the major lymph nodes above the diaphragm and extends from the inferior portion of the mandible to the level of the insertion of the diaphragm. Aims: To describe a simple technique that has been devised to treat the mantle field with the help of multileaf collimator and using computed tomography (CT-based treatment planning. Materials and Methods: CT scan was performed with the patient in the supine position and the datasets were transferred to the Eclipse™ treatment planning system. Elekta Precise™ linear accelerator equipped with 40 pairs of multileaf collimator (MLC was used for the execution of the mantle field. The MLC′s shapes were designed to take the shape of the conventional customized blocks used for treatment of mantle field. The anterior mantle field was divided into three separate MLC segments with the collimator kept at 0°. The first MLC segment was shaped to cover the neck, clavicular regions, and mediastinum. The second and the third MLC segments covered the right and left axilla, respectively. The posterior fields were opposed to the anterior subfields in a similar fashion. The dose was prescribed at the midplane, using reference points. Results and Conclusion: The technique described in this study is very simple, easy to implement, and avoids unnecessary delay in the execution of the mantle field. The mantle field can be easily shaped with the multileaf collimators, without any collimator rotation.

Compositional and isotopic heterogeneities in the Neo-Tethyan upper mantle recorded by coexisting Al-rich and Cr-rich chromitites in the Purang peridotite massif, SW Tibet (China)

Science.gov (United States)

Xiong, Fahui; Yang, Jingsui; Xu, Xiangzhen; Kapsiotis, Argyrios; Hao, Xiaolin; Liu, Zhao

2018-06-01

The Purang harzburgite massif in SW Tibet (China) hosts abundant chrome ore deposits. Ores consist of 20 to >95% modal chromian spinel (Cr-spinel) with mylonitic fabric in imbricate shaped pods. The composition of Cr-spinel in these ores ranges from Al-rich [Cr#Sp or Cr/(Cr + Al) × 100 = 47.60-57.56] to Cr-rich (Cr#Sp: 62.55-79.57). Bulk platinum-group element (PGE) contents of chromitites are also highly variable ranging from 17.5 ppb to ∼2.5 ppm. Both metallurgical and refractory chromitites show a general enrichment in the IPGE (Os, Ir and Ru) with respect to the PPGE (Rh, Pt and Pd), resulting mostly in right-sloping primitive mantle (PM)-normalized PGE profiles. The platinum-group mineral (PGM) assemblages of both chromitite types are dominated by heterogeneously distributed, euhedral Os-bearing laurite inclusions in Cr-spinel. The Purang chromitites have quite inhomogeneous 187Os/188Os ratios (0.12289-0.13194) that are within the range of those reported for mantle-hosted chromitites from other peridotite massifs. Geochemical calculations demonstrate that the parental melts of high-Cr chromitites were boninitic, whereas those of high-Al chromitites had an arc-type tholeiitic affinity. Chromite crystallization was most likely stimulated by changes in magma compositions due to melt-peridotite interaction, leading to the establishment of a heterogeneous physicochemical environment during the early crystallization of the PGM. The highly variable PGE contents, inhomogeneous Os-isotopic compositions and varying Cr#Sp ratios of these chromitites imply a polygenetic origin for them from spatially distinct melt inputs. The generally low γOs values (different sections of a heterogeneously depleted mantle source region. These melts were most likely produced in the mantle wedge above a downgoing lithospheric slab.

The composition of interstellar grain mantles

International Nuclear Information System (INIS)

Tielens, A.G.G.M.

1984-01-01

The molecular composition of interstellar grain mantles employing gas phase as well as grain surface reactions has been calculated. The calculated mixtures consist mainly of the molecules H 2 O H 2 CO, N 2 , CO, O 2 , CO 2 , H 2 O 2 , NH 3 , and their deuterated counterparts in varying ratios. The exact compositions depend strongly on the physical conditions in the gas phase. The calculated mixtures are compared to the observations by using laboratory spectra of grain mantle analogs. (author)

Refractory myasthenia gravis - clinical profile, comorbidities and response to rituximab.

Science.gov (United States)

Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar

2016-01-01

Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.

RESULTS OF OUTPATIENT PROGRAM ON EFFECTIVE THERAPY OF REFRACTORY ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

M. M. Batyushin

2015-12-01

Full Text Available Aim. To increase in efficacy of antihypertensive therapy in patients with refractory arterial hypertension (HT.Material and methods. Patients with refractory HT were revealed during first month of program. The causes of refractory HT were analyzed. Combined antihypertensive therapy was prescribed to reach target level of blood pressure (BP. This therapy lasted 24 weeks and included angiotensin converting enzyme (ACE inhibitor, thiazid diuretic (indapamide and dihydropyridine calcium antagonist (nifedipine XL.Results. 200 patients with refractory HT were revealed. True refractory HT took place in 59,9% of patients and pseudo refractory HT – in 40,1% of patients. Lack of diuretics or combined antihypertensive therapy were the main reason of insufficient BP control. Proposed 3-drugs therapy resulted in reduction of systolic BP from 190 to 132 Hg mm and diastolic BP from 104 to 81 Hg mm. Target level of BP was reached in 94% patients. There were no side effects which demanded to stop therapy.Conclusion. High incidence of pseudorefractory HT (40,1% is revealed. Significant prevalence of renal disturbances especially chronic interstitial inflammatory could be responsible for refractory HT development. Use of 3-drugs therapy (ACE inhibitor, indapamide and nifedipine XL provides effective control of BP in refractory and pseudorefractory HT.

RESULTS OF OUTPATIENT PROGRAM ON EFFECTIVE THERAPY OF REFRACTORY ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

M. M. Batyushin

2007-01-01

Full Text Available Aim. To increase in efficacy of antihypertensive therapy in patients with refractory arterial hypertension (HT.Material and methods. Patients with refractory HT were revealed during first month of program. The causes of refractory HT were analyzed. Combined antihypertensive therapy was prescribed to reach target level of blood pressure (BP. This therapy lasted 24 weeks and included angiotensin converting enzyme (ACE inhibitor, thiazid diuretic (indapamide and dihydropyridine calcium antagonist (nifedipine XL.Results. 200 patients with refractory HT were revealed. True refractory HT took place in 59,9% of patients and pseudo refractory HT – in 40,1% of patients. Lack of diuretics or combined antihypertensive therapy were the main reason of insufficient BP control. Proposed 3-drugs therapy resulted in reduction of systolic BP from 190 to 132 Hg mm and diastolic BP from 104 to 81 Hg mm. Target level of BP was reached in 94% patients. There were no side effects which demanded to stop therapy.Conclusion. High incidence of pseudorefractory HT (40,1% is revealed. Significant prevalence of renal disturbances especially chronic interstitial inflammatory could be responsible for refractory HT development. Use of 3-drugs therapy (ACE inhibitor, indapamide and nifedipine XL provides effective control of BP in refractory and pseudorefractory HT.

Profile of blinatumomab and its potential in the treatment of relapsed/refractory acute lymphoblastic leukemia

Directory of Open Access Journals (Sweden)

Ribera JM

2015-06-01

Full Text Available Josep-Maria Ribera, Albert Ferrer, Jordi Ribera, Eulàlia GenescàClinical Hematology Department, ICO-Hospital Germans Trias i Pujol, Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, SpainAbstract: The CD19 marker is expressed on the surface of normal and malignant immature or mature B-cells. On the other hand, immunotherapy involving T-cells is a promising modality of treatment for many neoplastic diseases including leukemias and lymphomas. The CD19/CD3-bispecific T-cell-engaging (BiTE® monoclonal antibody blinatumomab can transiently engage cytotoxic T-cells to CD19+ target B-cells inducing serial perforin-mediated lysis. In the first clinical trial, blinatumomab showed efficacy in non-Hodgkin’s lymphomas, but the most important trials have been conducted in relapsed/refractory (R/R acute lymphoblastic leukemia (ALL and in ALL with minimal residual disease. Encouraging reports on the activity of blinatumomab in R/R Philadelphia chromosome-negative B-cell precursor ALL led to its approval by the US Food and Drug Administration on December 3, 2014 after an accelerated review process. This review focuses on the profile of blinatumomab and its activity in R/R ALL.Keywords: acute lymphoblastic leukemia, relapsed/refractory, BiTE® monoclonal antibodies, blinatumomab

Ruxolitinib in steroid refractory graft-vs.-host disease: a case report

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Enrico Maffini

2016-08-01

Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT is potentially curative in a variety of hematological malignancies. Graft-vs.-host disease (GvHD remains a life-threatening complication. Standard treatment is high-dose (HD corticosteroids. Steroid-refractory (SR GvHD is associated with poor prognosis. At present, second-line treatment is ill-defined and includes a number of agents. Novel insights into the pathophysiology of acute GvHD (aGvHD highlight the relevant role of the host inflammatory response governed by several kinase families, including Janus kinases (JAK1/2. Ruxolitinib, a JAK1/2 inhibitor approved for intermediate-2/high-risk myelofibrosis, was recently employed in SR-GvHD with encouraging overall response rates. Clinical experience however remains limited. Case presentation A 51-year-old male with refractory anemia with excess blast type-2 underwent a myeloablative allogeneic HSCT from a 9/10 HLA-matched unrelated donor after conditioning with busulfan and cyclophosphamide. GvHD prophylaxis consisted of cyclosporine, methotrexate, and thymoglobulin. CD34+ cells/kg infused were 8.69 × 106 kg. On day 29, the patient developed overall grade IV aGvHD with biopsy proven stage IV gastrointestinal (GI GvHD refractory to HD corticosteroids. Patient conditions rapidly deteriorated and became critical despite the addition of mycophenolate mofetil and budesonide. On day 33, Ruxolitinib was started, and on day 39 the patient clinical conditions gradually improved. Complete resolution of aGvHD was also confirmed by histology on day 54. Conclusions At 5 months from HSCT, the patient is well and in continuous hematological complete remission without flare of GvHD. Ruxolitinib was discontinued on day 156. Ruxolitinib is feasible and effective in SR-aGvHD though large prospective clinical trials are warranted.

Modification of an ancient subcontinental lithospheric mantle by continental subduction: Insight from the Maowu garnet peridotites in the Dabie UHP belt, eastern China

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Chen, Yi; Su, Bin; Chu, Zhuyin

2017-05-01

Orogenic mantle-derived peridotites commonly originate from the subcontinental lithospheric mantle (SCLM) and thus provide a key target to investigate the modification of the SCLM by a subducting slab. The Maowu ultramafic rocks from the Dabie ultrahigh-pressure (UHP) metamorphic belt have formerly been debated as representing cumulates or mantle-derived peridotites. Detailed petrological and geochemical data presented in this study provide new constraints on the origin and formation of the peridotites involving melt depletion in the ancient SCLM and deep crustal metasomatism. The Maowu garnet dunites have refractory bulk compositions characterized by high Mg# (91.9-92.0) and Ni (2537-2892 ppm) values and low Al2O3 (0.26-0.76 wt.%), CaO (0.05-0.32 wt.%), TiO2 (China craton. Many garnet orthopyroxenite veins crosscutting the Maowu dunites preserve abundant metasomatic textures and show variable enrichment in incompatible elements. Mineral and whole-rock chemistry indicate that these veins represent metasomatic products between the wall dunites and silica-rich hydrous melts under UHP conditions. The veins show large variations in platinum-group element (PGE) signatures and Re-Os isotopes. The garnet-poor orthopyroxenite veins are characterized by low Al2O3 ( 6 wt.%) and S (99-306 ppm) contents and show melt-like PGE patterns and high 187Os/188Os ratios (up to 0.36910). These features, combined with the occurrence of interstitial sulfides in the garnet-rich orthopyroxenite veins, suggest that crust-derived sulfur-saturated silicate melts may have significantly modified the PGE signature and destroyed the Re-Os systematics of the SCLM. However, when the crust-derived silicate melts became sulfur-depleted, such melts would not significantly modify the PGE patterns, radiogenic Os-isotope compositions or the Re-depletion model ages of the SCLM. Consequently, deep crust-mantle interactions in continental subduction zones could induce high degrees of Os isotopic

Severe nivolumab-induced pneumonitis preceding durable clinical remission in a patient with refractory, metastatic lung squamous cell cancer: a case report

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Hong Li

2017-02-01

Full Text Available Abstract Background Programmed cell death 1 (PD-1 and its ligand 1 (PD-L1 inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab. Case presentation A patient with chemotherapy-refractory, metastatic lung SCC developed symptomatic pneumonitis by week 4 after nivolumab treatment, concurrently with onset of a potent antitumor response. Despite discontinuation of nivolumab after three doses and the use of high dose oral corticosteroids for grade 3 pneumonitis, continued tumor response to a complete remission by 3 months was evident by radiographic assessment. At the time of this submission, the patient has remained in clinical remission for 14 months. High PD-L1 expression by immunohistochemistry staining was seen in intra-alveolar macrophages and viable tumor cells in the pneumonitis and recurrent tumor specimens, respectively. Tumor genomic profiling by FoundationOne targeted exome sequencing revealed a very high tumor mutation burden (TMB corresponding to 95–96 percentile in lung SCC, i.e., 87.4–91.0 and 82.9 mut/Mb, respectively, in pre- and post-nivolumab tumor specimens. Except for one, the 13 functional genomic alterations remained the same in the diagnostic, recurrent, and post-treatment, relapsed tumor specimens, suggesting that nivolumab reset the patient’s immune system against one or more preexisting tumor-associated antigens (TAAs. One potential TAA candidate is telomerase reverse transcriptase (TERT in which an oncogenic promoter -146C>T mutation was detected. Human leukocyte antigen (HLA typing revealed HLA-A*0201 homozygosity, which is the prevalent HLA class I

Late-orogenic mantle garnet pyroxenites evidence mantle refertilization during exhumation of orogenic belt

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Chazot, G.; France, L.; Kornprobst, J.; Dallai, L.; Vannucci, R.

2008-12-01

The petrological and geochemical study of garnet bearing pyroxenites from four localities (FMC, Morocco, Jordan, Cameroon) demonstrates that these rocks are cumulates crystallised in the lithospheric mantle domain. Metamorphic reactions, exsolutions and trace elements WR analysis demonstrate that their crystallisation pressure ranges between 1 and 2GPa (30 to 60km). The elaboration of the PTt paths for the studied samples attests of important movements in the respective lithospheres. Replaced in the geodynamical contexts, the samples are interpreted to represent the crystallisation of melts formed during exhumation of orogenic domains. Radiogenic isotopes (Sr-Nd) show that in a very same region, the samples are isotopicaly heterogeneous but are similar to the respective regional lithosphere. Initial isotopic ratios lead to propose that the FMC samples have crystallised at the end of the Hercynian orogen and that the samples from the other localities (Morocco, Jordan and Cameroon) have crystallised at the end of the Pan-African orogen. After recalculation at the crystallisation time, the isotopic compositions are in good agreement with the respective regional lithosphere ones and so samples of this study could represent the product of the melting of these lithospheres. The analyses of oxygen stable isotopes allow to precise the model; they show that twelve of the samples come from the melting of a lherzolitic mantle and that the four others come from the melting of a heterogeneous mantle formed of lherzolites and eclogites. The presence of some hydrous minerals such as amphiboles and micas and the trace elements WR analyses show that some of the samples were affected by a late metasomatic event. Results of our study show that thermal relaxation following orogenic events lead to the crystallisation of pyroxenites in the lithosphere. The presence of lage amounts of mantle pyroxenites in old orogenic regions confers physical and chemical particularities to these

The role of upper mantle mineral phase transitions on the current structure of large-scale Earth's mantle convection.

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Thoraval, C.

2017-12-01

Describing the large-scale structures of mantle convection and quantifying the mass transfer between upper and lower mantle request to account for the role played by mineral phase transitions in the transition zone. We build a density distribution within the Earth mantle from velocity anomalies described by global seismic tomographic models. The density distribution includes thermal anomalies and topographies of the phase transitions at depths of 410 and 660 km. We compute the flow driven by this density distribution using a 3D spherical circulation model, which account for depth-dependent viscosity. The dynamic topographies at the surface and at the CMB and the geoid are calculated as well. Within the range of viscosity profiles allowing for a satisfying restitution of the long wavelength geoid, we perform a parametric study to decipher the role of the characteristics of phase diagrams - mainly the Clapeyron's slopes - and of the kinetics of phase transitions, which may modify phase transition topographies. Indeed, when a phase transition is delayed, the boundary between two mineral phases is both dragged by the flow and interfere with it. The results are compared to recent estimations of surface dynamic topography and to the phase transition topographies as revealed by seismic studies. The consequences are then discussed in terms of structure of mantle flow. Comparisons between various tomographic models allow us to enlighten the most robust features. At last, the role played by the phase transitions on the lateral variations of mass transfer between upper and lower mantle are quantified by comparison to cases with no phase transitions and confronted to regional tomographic models, which reflect the variability of the behaviors of the descending slabs in the transition zone.

Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood

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A.M. Aalbers (Anna Maartje); M.M. van den Heuvel-Eibrink (Marry); I. Baumann (Irith); M.N. Dworzak (Michael); H. Hasle (Henrik); F. Locatelli (Franco); B. de Moerloose (Barbara); M. Schmugge; E. Mejstříková (Ester); M. Nováková (Michaela); M. Zecca (Marco); C.M. Zwaan (Christian Michel); J.G. te Marvelde (Jeroen); A.W. Langerak (Anton); J.J.M. van Dongen (Jacques); R. Pieters (Rob); C.M. Niemeyer (Charlotte); V.H.J. van der Velden (Vincent)

2015-01-01

textabstractRefractory cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory cytopenia from the immune-mediated bone marrow

Phase I-II study of lenalidomide and alemtuzumab in refractory chronic lymphocytic leukemia (CLL): effects on T cells and immune checkpoints.

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Winqvist, Maria; Mozaffari, Fariba; Palma, Marzia; Eketorp Sylvan, Sandra; Hansson, Lotta; Mellstedt, Håkan; Österborg, Anders; Lundin, Jeanette

2017-01-01

This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2.5 mg/day was not efficient, and maximum tolerated dose was 5 mg/day. Grade 3-4 neutropenia and thrombocytopenia occurred in 84 and 55%, 30% had febrile neutropenia, and CMV-reactivation requiring valganciclovir occurred in 30% of patients. The frequency of proliferating (Ki67 + ) CD8 + T cells was increased at week 4, with further increase in both the CD4 + and CD8 + subsets (p cells increased at week 4 as the frequency of effector memory cells increased in the CD8 + subset (p cells decreased in both the CD8 + and CD4 + subsets (p regulatory T cells was reduced (p T cells decreased, and effector memory T cells increased (p T cells increased at 30-week follow-up (p T cells, including increased proliferative activity and cytotoxic potential.

Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells.

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Circu, Magdalena; Cardelli, James; Barr, Martin; O'Byrne, Kenneth; Mills, Glenn; El-Osta, Hazem

2017-01-01

was less pronounced in A549Pt cells. Blocking autophagy by ATG5 depletion using siRNA markedly enhances susceptibility to cisplatin in A549cisR cells. Taken together, our results underscore the utility of targeting lysosomal function in overcoming acquired cisplatin refractoriness in lung cancer.

Modulating lysosomal function through lysosome membrane permeabilization or autophagy suppression restores sensitivity to cisplatin in refractory non-small-cell lung cancer cells.

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Magdalena Circu

. Interestingly, this effect was less pronounced in A549Pt cells. Blocking autophagy by ATG5 depletion using siRNA markedly enhances susceptibility to cisplatin in A549cisR cells. Taken together, our results underscore the utility of targeting lysosomal function in overcoming acquired cisplatin refractoriness in lung cancer.

Early episodes of high-pressure core formation preserved in plume mantle

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Jackson, Colin R. M.; Bennett, Neil R.; Du, Zhixue; Cottrell, Elizabeth; Fei, Yingwei

2018-01-01

The decay of short-lived iodine (I) and plutonium (Pu) results in xenon (Xe) isotopic anomalies in the mantle that record Earth’s earliest stages of formation. Xe isotopic anomalies have been linked to degassing during accretion, but degassing alone cannot account for the co-occurrence of Xe and tungsten (W) isotopic heterogeneity in plume-derived basalts and their long-term preservation in the mantle. Here we describe measurements of I partitioning between liquid Fe alloys and liquid silicates at high pressure and temperature and propose that Xe isotopic anomalies found in modern plume rocks (that is, rocks with elevated 3He/4He ratios) result from I/Pu fractionations during early, high-pressure episodes of core formation. Our measurements demonstrate that I becomes progressively more siderophile as pressure increases, so that portions of mantle that experienced high-pressure core formation will have large I/Pu depletions not related to volatility. These portions of mantle could be the source of Xe and W anomalies observed in modern plume-derived basalts. Portions of mantle involved in early high-pressure core formation would also be rich in FeO, and hence denser than ambient mantle. This would aid the long-term preservation of these mantle portions, and potentially points to their modern manifestation within seismically slow, deep mantle reservoirs with high 3He/4He ratios.

Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.

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Advani, Ranjana H; Buggy, Joseph J; Sharman, Jeff P; Smith, Sonali M; Boyd, Thomas E; Grant, Barbara; Kolibaba, Kathryn S; Furman, Richard R; Rodriguez, Sara; Chang, Betty Y; Sukbuntherng, Juthamas; Izumi, Raquel; Hamdy, Ahmed; Hedrick, Eric; Fowler, Nathan H

2013-01-01

Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.

Modelling the possible interaction between edge-driven convection and the Canary Islands mantle plume

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Negredo, A. M.; Rodríguez-González, J.; Fullea, J.; Van Hunen, J.

2017-12-01

The close location between many hotspots and the edges of cratonic lithosphere has led to the hypothesis that these hotspots could be explained by small-scale mantle convection at the edge of cratons (Edge Driven Convection, EDC). The Canary Volcanic Province hotspot represents a paradigmatic example of this situation due to its close location to the NW edge of the African Craton. Geochemical evidence, prominent low seismic velocity anomalies in the upper and lower mantle, and the rough NE-SW age-progression of volcanic centers consistently point out to a deep-seated mantle plume as the origin of the Canary Volcanic Province. It has been hypothesized that the plume material could be affected by upper mantle convection caused by the thermal contrast between thin oceanic lithosphere and thick (cold) African craton. Deflection of upwelling blobs due to convection currents would be responsible for the broader and more irregular pattern of volcanism in the Canary Province compared to the Madeira Province. In this study we design a model setup inspired on this scenario to investigate the consequences of possible interaction between ascending mantle plumes and EDC. The Finite Element code ASPECT is used to solve convection in a 2D box. The compositional field and melt fraction distribution are also computed. Free slip along all boundaries and constant temperature at top and bottom boundaries are assumed. The initial temperature distribution assumes a small long-wavelength perturbation. The viscosity structure is based on a thick cratonic lithosphere progressively varying to a thin, or initially inexistent, oceanic lithosphere. The effects of assuming different rheologies, as well as steep or gradual changes in lithospheric thickness are tested. Modelling results show that a very thin oceanic lithosphere (models assuming temperature-dependent viscosity and large viscosity variations evolve to large-scale (upper mantle) convection cells, with upwelling of hot material being

Ibrutinib Treatment of Mantle Cell Lymphoma Relapsing at Central Nervous System: A Case Report and Literature Review

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Donato Mannina

2017-01-01

Full Text Available Mantle cell lymphoma (MCL accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement. Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK, has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD. In all of them, ibrutinib, at the dosage between 420 and 560 mg/day, showed an impressive effectiveness. Here we describe a case of MCL with CNS relapse showing an excellent response to ibrutinib administered at the unusual dose of 280 mg/day because of concomitant treatment of cardiological disease.

Geochemical Constraints on Core-Mantle Interaction from Fe/Mn Ratios

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Humayun, M.; Qin, L.

2003-12-01

The greater density of liquid iron alloy, and its immiscibility with silicate, maintains the physical separation of the core from the mantle. There are no a priori reasons, however, why the Earth's mantle should be chemically isolated from the core. Osmium isotopic variations in mantle plumes have been interpreted in terms of interaction between outer core and the source regions of deep mantle plumes. If chemical transport occurs across the core-mantle boundary its mechanism remains to be established. The Os isotope evidence has also been interpreted as the signatures of subducted Mn-sediments, which are known to have relatively high Pt/Os. In the mantle, Fe occurs mainly as the divalent ferrous ion, and Mn occurs solely as a divalent ion, and both behave in a geochemically coherent manner because of similarity in ionic charge and radius. Thus, the Fe/Mn ratio is a planetary constant insensitive to processes of mantle differentiation by partial melting. Two processes may perturb the ambient mantle Fe/Mn of 60: a) the subduction of Mn-sediments should decrease the Fe/Mn ratio in plume sources, while b) chemical transport from the outer core may increase the Fe/Mn ratio. The differentiation of the liquid outer core to form the solid inner core may increase abundances of the light element constituents (FeS, FeO, etc.) to the point of exsolution from the core at the CMB. The exact rate of this process is determined by the rate of inner core growth. Two end-member models include 1) inner core formation mainly prior to 3.5 Ga with heat release dominated by radioactive sources, or 2) inner core formation occurring mainly in the last 1.5 Ga with heat release dominated by latent heat. This latter model would imply large fluxes of Fe into the sources of modern mantle plumes. Existing Fe/Mn data for Gorgona and Hawaiian samples place limits on both these processes. We describe a new procedure for the precise determination of the Fe/Mn ratio in magmatic rocks by ICP-MS. This

Lower-mantle plume beneath the Yellowstone hotspot revealed by core waves

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Nelson, Peter L.; Grand, Stephen P.

2018-04-01

The Yellowstone hotspot, located in North America, is an intraplate source of magmatism the cause of which is hotly debated. Some argue that a deep mantle plume sourced at the base of the mantle supplies the heat beneath Yellowstone, whereas others claim shallower subduction or lithospheric-related processes can explain the anomalous magmatism. Here we present a shear wave tomography model for the deep mantle beneath the western United States that was made using the travel times of core waves recorded by the dense USArray seismic network. The model reveals a single narrow, cylindrically shaped slow anomaly, approximately 350 km in diameter that we interpret as a whole-mantle plume. The anomaly is tilted to the northeast and extends from the core-mantle boundary to the surficial position of the Yellowstone hotspot. The structure gradually decreases in strength from the deepest mantle towards the surface and if it is purely a thermal anomaly this implies an initial excess temperature of 650 to 850 °C. Our results strongly support a deep origin for the Yellowstone hotspot, and also provide evidence for the existence of thin thermal mantle plumes that are currently beyond the resolution of global tomography models.

An inverted continental Moho and serpentinization of the forearc mantle.

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Bostock, M G; Hyndman, R D; Rondenay, S; Peacock, S M

2002-05-30

Volatiles that are transported by subducting lithospheric plates to depths greater than 100 km are thought to induce partial melting in the overlying mantle wedge, resulting in arc magmatism and the addition of significant quantities of material to the overlying lithosphere. Asthenospheric flow and upwelling within the wedge produce increased lithospheric temperatures in this back-arc region, but the forearc mantle (in the corner of the wedge) is thought to be significantly cooler. Here we explore the structure of the mantle wedge in the southern Cascadia subduction zone using scattered teleseismic waves recorded on a dense portable array of broadband seismometers. We find very low shear-wave velocities in the cold forearc mantle indicated by the exceptional occurrence of an 'inverted' continental Moho, which reverts to normal polarity seaward of the Cascade arc. This observation provides compelling evidence for a highly hydrated and serpentinized forearc region, consistent with thermal and petrological models of the forearc mantle wedge. This serpentinized material is thought to have low strength and may therefore control the down-dip rupture limit of great thrust earthquakes, as well as the nature of large-scale flow in the mantle wedge.

Reworking of Archean mantle in the NE Siberian craton by carbonatite and silicate melt metasomatism: Evidence from a carbonate-bearing, dunite-to-websterite xenolith suite from the Obnazhennaya kimberlite

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Ionov, Dmitri A.; Doucet, Luc S.; Xu, Yigang; Golovin, Alexander V.; Oleinikov, Oleg B.

2018-03-01

reworked garnet-bearing peridotites are absent. The modal, chemical and Os-isotope compositions of the Obnazhennaya xenoliths produced by reaction of refractory peridotites with melts are very particular (high Ca/Al, no Mg#-Al correlations, highly variable Cr, low 187Os/188Os, continuous modal range from olivine-rich to low-olivine peridotites, wehrlites and websterites) and distinct from those of fertile lherzolites in off-craton xenoliths and peridotite massifs. These features argue against the concept of 'refertilization' of cratonic and other refractory peridotites by mantle-derived melts as a major mechanism to form fertile to moderately depleted lherzolites in continental lithosphere. The Obnazhennaya xenoliths represent a natural rock series produced by 'refertilization', but include no rocks equivalent in modal, major and trace element to the fertile lherzolites. This study shows that 'refertilization' yields broad, continuous ranges of modal and chemical compositions with common wehrlites and websterites that are rare among off-craton xenoliths.

Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn.

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Kandulski, A; Jechorek, D; Caro, C; Weigt, J; Wex, T; Mönkemüller, K; Malfertheiner, P

2013-09-01

Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain. To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH. Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated. Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001). These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH. © 2013 John Wiley & Sons Ltd.

The viscosity of Earth's lower mantle inferred from sinking speed of subducted lithosphere

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Čížková, H.; van den Berg, A.P.; Spakman, W.; Matyska, C.

2012-01-01

The viscosity of the mantle is indispensable for predicting Earth's mechanical behavior at scales ranging from deep mantle material flow to local stress accumulation in earthquakes zones. But, mantle viscosity is not well determined. For the lower mantle, particularly, only few constraints result

Aberrant Expression of CD19 and CD43 in a Patient With Therapy-Related Acute Myeloid Leukemia and a History of Mantle Cell Lymphoma

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Yen-Chuan Hsieh

2009-07-01

Full Text Available Mantle cell lymphoma (MCL is an aggressive B cell lymphoma with frequent involvement of the gastrointestinal tract and peripheral blood (PB. In addition to the B cell markers, the neoplastic cells express CD5 and CD43. In patients with a prior history of MCL with PB involvement, the appearance of leukemic cells after chemotherapy usually heralds a relapse, particularly if the leukemic cells express B cell markers and CD43. We report a patient with MCL who presented with multiple lymphomatous polyposis of the intestine. The staging procedures revealed the involvement of lymph nodes, bone marrow and PB. Three years after chemotherapy, thrombocytopenia with the appearance of rare leukemic cells in the PB was noted. Leukemic cells obtained from bone marrow aspirate expressed CD19 and CD43, suggesting a relapse. Detailed cytomorphological and immunophenotypic studies unveiled the myeloid nature of these leukemic cells, and a diagnosis of therapy-related acute myeloid leukemia was made. This case illustrates the importance of morphologic examination and performing a complete antibody panel in the diagnosis of a suspected relapse in patients with a prior history of lymphoma.

Microcystic adnexal carcinoma (MAC)-like squamous cell carcinoma as a differential diagnosis to Bell´s palsy: review of guidelines for refractory facial nerve palsy.

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Mueller, S K; Iro, H; Lell, M; Seifert, F; Bohr, C; Scherl, C; Agaimy, A; Traxdorf, M

2017-01-05

Bell´s palsy is the most common cause of facial paralysis worldwide and the most common disorder of the cranial nerves. It is a diagnosis of exclusion, accounting for 60-75% of all acquired peripheral facial nerve palsies. Our case shows the first case of a microcystic adnexal carcinoma-like squamous cell carcinoma as a cause of facial nerve palsy. The patient, a 70-year-old Caucasian male, experienced subsequent functional impairment of the trigeminal and the glossopharyngeal nerve about 1½ years after refractory facial nerve palsy. An extensive clinical work-up and tissue biopsy of the surrounding parotid gland tissue was not able to determine the cause of the paralysis. Primary infiltration of the facial nerve with subsequent spreading to the trigeminal and glossopharyngeal nerve via neuroanastomoses was suspected. After discussing options with the patient, the main stem of the facial nerve was resected to ascertain the diagnosis of MAC-like squamous cell carcinoma, and radiochemotherapy was subsequently started. This case report shows that even rare neoplastic etiologies should be considered as a cause of refractory facial nerve palsy and that it is necessary to perform an extended diagnostic work-up to ascertain the diagnosis. This includes high-resolution MRI imaging and, as perilesional parotid biopsies might be inadequate for rare cases like ours, consideration of a direct nerve biopsy to establish the right diagnosis.

Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

Science.gov (United States)

2015-05-06

Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia