Ibrutinib plus Venetoclax for the Treatment of Mantle-Cell Lymphoma.

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Tam, Constantine S; Anderson, Mary Ann; Pott, Christiane; Agarwal, Rishu; Handunnetti, Sasanka; Hicks, Rodney J; Burbury, Kate; Turner, Gillian; Di Iulio, Juliana; Bressel, Mathias; Westerman, David; Lade, Stephen; Dreyling, Martin; Dawson, Sarah-Jane; Dawson, Mark A; Seymour, John F; Roberts, Andrew W

2018-03-29

Both the BTK inhibitor ibrutinib and the BCL2 inhibitor venetoclax are active as monotherapy in the treatment of mantle-cell lymphoma. Complete response rates of 21% have been observed for each agent when administered as long-term continuous therapy. Preclinical models predict synergy in combination. We conducted a single-group, phase 2 study of daily oral ibrutinib and venetoclax in patients, as compared with historical controls. Patients commenced ibrutinib monotherapy at a dose of 560 mg per day. After 4 weeks, venetoclax was added in stepwise, weekly increasing doses to 400 mg per day. Both drugs were continued until progression or an unacceptable level of adverse events. The primary end point was the rate of complete response at week 16. Minimal residual disease (MRD) was assessed by flow cytometry in bone marrow and by allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR) in blood. The study included 24 patients with relapsed or refractory mantle-cell lymphoma (23 patients) or previously untreated mantle-cell lymphoma (1 patient). Patients were 47 to 81 years of age, and the number of previous treatments ranged from none to six. Half the patients had aberrations of TP53, and 75% had a high-risk prognostic score. The complete response rate according to computed tomography at week 16 was 42%, which was higher than the historical result of 9% at this time point with ibrutinib monotherapy (Pibrutinib and venetoclax was consistent with improved outcomes in patients with mantle-cell lymphoma who had been predicted to have poor outcomes with current therapy. (Funded by Janssen and others; AIM ClinicalTrials.gov number, NCT02471391 .).

Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

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2018-06-13

CCND1 Positive; CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Treatment of older patients with mantle-cell lymphoma

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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.

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.

Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

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2017-04-17

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle 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 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; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

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

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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...

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.

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

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

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

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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.

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

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

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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

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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

Mantle cell lymphoma-current literature overview.

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Pejcic, Ivica; Petkovic, Ivan; Vrbic, Svetislav; Filipovic, Sladjana; Balic, Mirjana; Cvetanovic, Ana

2014-01-01

Mantle cell lymphoma (MCL) is a distinct subtype of lymphoma identified as a particular entity in the early 1990s. The prognosis of MCL is generally poor, and is considered one of the worst among all B-cell lymphomas. In general, conventional chemotherapy is only palliative and the median duration of remissions is only 1-2 years. With the exception of allogeneic hematopoietic stem cell transplantation (allo-SCT), current treatment approaches are not curative and the corresponding survival curve is characterized by a relatively steep and continuous decline, with a median survival of about 4 years and watch and wait strategy. Optimal first-line therapy in MCL is not established yet. Very intensive regimens, including autologous (auto-SCT) and allo-SCT, seem to be required to improve the outcome. Allogeneic stem cell transplantation is the only therapy that can achieve a plateau in the survival curve, but, however, it is not applicable in most of the cases due to the patients' older age when the disease mostly occurs. Molecular knowledge of MCL has progressed and therefore a large number of molecular targeted therapies have been introduced in relapsed and refractory disease.

Evaluation of CD307a expression patterns during normal B-cell maturation and in B-cell malignancies by flow cytometry.

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Auat, Mariangeles; Cardoso, Chandra Chiappin; Santos-Pirath, Iris Mattos; Rudolf-Oliveira, Renata Cristina Messores; Matiollo, Camila; Lange, Bárbara Gil; da Silva, Jessica Pires; Dametto, Gisele Cristina; Pirolli, Mayara Marin; Colombo, Maria Daniela Holthausen Perico; Santos-Silva, Maria Claudia

2018-02-24

Flow cytometric immunophenotyping is deemed a fundamental tool for the diagnosis of B-cell neoplasms. Currently, the investigation of novel immunophenotypic markers has gained importance, as they can assist in the precise subclassification of B-cell malignancies by flow cytometry. Therefore, the purpose of the present study was to evaluate the expression of CD307a during normal B-cell maturation and in B-cell malignancies as well as to investigate its potential role in the differential diagnosis of these entities. CD307a expression was assessed by flow cytometry in normal precursor and mature B cells and in 115 samples collected from patients diagnosed with precursor and mature B-cell neoplasms. CD307a expression was compared between neoplastic and normal B cells. B-acute lymphoblastic leukemia cases exhibited minimal expression of CD307a, displaying a similar expression pattern to that of normal B-cell precursors. Mantle cell lymphoma (MCL) cases showed the lowest levels of CD307a among mature B-cell neoplasms. CD307a expression was statistically lower in MCL cases than in chronic B lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL) cases. No statistical differences were observed between CD307a expression in neoplastic and normal plasma cells. These results indicate that the assessment of CD307a expression by flow cytometry could be helpful to distinguish CLL from MCL, and the latter from MZL. Although these results are not entirely conclusive, they provide a basis for further studies in a larger cohort of patients. © 2018 International Clinical Cytometry Society. © 2018 International Clinical Cytometry Society.

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.

Mantle superplumes induce geomagnetic superchrons

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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.

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.

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.

Receptor units responding to movement in the octopus mantle.

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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.

[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.

Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

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Dreyling, Martin; Jurczak, Wojciech; Jerkeman, Mats; Silva, Rodrigo Santucci; Rusconi, Chiara; Trneny, Marek; Offner, Fritz; Caballero, Dolores; Joao, Cristina; Witzens-Harig, Mathias; Hess, Georg; Bence-Bruckler, Isabelle; Cho, Seok-Goo; Bothos, John; Goldberg, Jenna D; Enny, Christopher; Traina, Shana; Balasubramanian, Sriram; Bandyopadhyay, Nibedita; Sun, Steven; Vermeulen, Jessica; Rizo, Aleksandra; Rule, Simon

2016-02-20

Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma. This randomised, open-label, multicentre, phase 3 clinical trial enrolled patients with relapsed or refractory mantle-cell lymphoma confirmed by central pathology in 21 countries who had received one or more rituximab-containing treatments. Patients were stratified by previous therapy and simplified mantle-cell lymphoma international prognostic index score, and were randomly assigned with a computer-generated randomisation schedule to receive daily oral ibrutinib 560 mg or intravenous temsirolimus (175 mg on days 1, 8, and 15 of cycle 1; 75 mg on days 1, 8, and 15 of subsequent 21-day cycles). Randomisation was balanced by using randomly permuted blocks. The primary efficacy endpoint was progression-free survival assessed by a masked independent review committee with the primary hypothesis that ibrutinib compared with temsirolimus significantly improves progression-free survival. The analysis followed the intention-to-treat principle. The trial is ongoing and is registered with ClinicalTrials.gov (number NCT01646021) and with the EU Clinical Trials Register, EudraCT (number 2012-000601-74). Between Dec 10, 2012, and Nov 26, 2013, 280 patients were randomised to ibrutinib (n=139) or temsirolimus (n=141). Primary efficacy analysis showed significant improvement in progression-free survival (pibrutinib versus temsirolimus (hazard ratio 0·43 [95% CI 0·32-0·58]; median progression-free survival 14·6 months [95% CI 10·4-not estimable] vs 6·2 months [4·2-7·9], respectively). Ibrutinib was better tolerated than temsirolimus, with grade 3 or higher treatment-emergent adverse events reported for 94 (68%) versus 121 (87

Cryptococcal meningoencephalitis in patients with mantle cell lymphoma on ibrutinib.

Science.gov (United States)

Sun, Kai; Kasparian, Saro; Iyer, Swaminathan; Pingali, Sai Ravi

2018-01-01

Ibrutinib, a Bruton's tyrosine kinase inhibitor, has been increasingly widely used in relapsed and refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia [1, 2]. With its use becoming more common, there have been emerging case reports of opportunistic infections like cryptococcal infections [3-8]. These infections in patients receiving ibrutinib were mostly reported in patients with chronic lymphocytic leukaemia, who have poor immune reconstitution. Here, we report two cases of cryptococcal meningoencephalitis in patients with MCL on ibrutinib.

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Are cancer cells really softer than normal cells?

Science.gov (United States)

Alibert, Charlotte; Goud, Bruno; Manneville, Jean-Baptiste

2017-05-01

Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Birch's Mantle

Science.gov (United States)

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

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

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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.

[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.

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...

Ibrutinib for the treatment of mantle cell lymphoma.

Science.gov (United States)

Herrera, Alex F; Jacobsen, Eric D

2014-11-01

Ibrutinib (PCI-32765)--a potent, covalent inhibitor of Bruton tyrosine kinase (BTK), an important kinase in the B-cell receptor signaling pathway--was recently approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The drug was granted accelerated approval based on the findings of an international, multicenter, single-arm phase II study that enrolled patients with relapsed or refractory MCL. In the study, ibrutinib (560 mg daily) was well tolerated as a single agent and resulted in an overall response rate of 68% and an estimated median response duration of 17.5 months. Ibrutinib's response rate and duration of response compare favorably with those for other novel agents approved for the treatment of relapsed or refractory MCL, while being less toxic than most chemotherapy or chemoimmunotherapy regimens. Ibrutinib is currently being studied in combination with chemoimmunotherapy, monoclonal antibody therapy, and novel agents in both the initial and the relapsed/refractory treatment settings. We review the mechanism of action, preclinical and clinical development, and the role of ibrutinib in the context of other available treatments. ©2014 American Association for Cancer Research.

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.

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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.

An inverted continental Moho and serpentinization of the forearc mantle.

Science.gov (United States)

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.

Sub-Moho Reflectors, Mantle Faults and Lithospheric Rheology

Science.gov (United States)

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

Mantle cell lymphoma relapsing at the lymphedematous arm.

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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.

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

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.

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.

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

Directory of Open Access Journals (Sweden)

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.

Interaction between mantle and crustal detachments: A nonlinear system controlling lithospheric extension

Science.gov (United States)

Rosenbaum, Gideon; Regenauer-Lieb, Klaus; Weinberg, Roberto F.

2010-11-01

We use numerical modeling to investigate the development of crustal and mantle detachments during lithospheric extension. Our models simulate a wide range of extensional systems with varying values of crustal thickness and heat flow, showing how strain localization in the mantle interacts with localization in the upper crust and controls the evolution of extensional systems. Model results reveal a richness of structures and deformation styles as a response to a self-organized mechanism that minimizes the internal stored energy of the system by localizing deformation. Crustal detachments, here referred as low-angle normal decoupling horizons, are well developed during extension of overthickened (60 km) continental crust, even when the initial heat flow is relatively low (50 mW m-2). In contrast, localized mantle deformation is most pronounced when the extended lithosphere has a normal crustal thickness (30-40 km) and an intermediate heat flow (60-70 mW m-2). Results show a nonlinear response to subtle changes in crustal thickness or heat flow, characterized by abrupt and sometimes unexpected switches in extension modes (e.g., from diffuse extensional deformation to effective lithospheric-scale rupturing) or from mantle- to crust-dominated strain localization. We interpret this nonlinearity to result from the interference of doming wavelengths in the presence of multiple necking instabilities. Disharmonic crust and mantle doming wavelengths results in efficient communication between shear zones at different lithospheric levels, leading to rupturing of the whole lithosphere. In contrast, harmonic crust and mantle doming inhibits interaction of shear zones across the lithosphere and results in a prolonged history of extension prior to continental breakup.

A possible mechanism for earthquakes found in the mantle wedge of the Nazca subduction zone

Science.gov (United States)

Warren, L. M.; Chang, Y.; Prieto, G. A.

2017-12-01

Beneath Colombia, the Cauca cluster of intermediate-depth earthquakes extends for 200 km along the trench (3.5°N-5.5°N, 77.0°W-75.3°W) and, with 58 earthquakes per year with local magnitude ML >= 2.5, has a higher rate of seismicity than the subduction zone immediately to the north or south. By precisely locating 433 cluster earthquakes from 1/2010-3/2014 with data from the Colombian National Seismic Network, we found that the earthquakes are located both in a continuous Nazca plate subducting at an angle of 33°-43° and in the overlying mantle wedge. The mantle wedge earthquakes (12% of the earthquakes) form two isolated 40-km-tall columns extending perpendicular to the subducting slab. Using waveform inversion, we computed focal mechanisms for 69 of the larger earthquakes. The focal mechanisms are variable, but the intraslab earthquakes are generally consistent with an in-slab extensional stress axis oriented 25° counterclockwise from the down-dip direction. We suggest that the observed mantle wedge earthquakes are the result of hydrofracture in a relatively cool mantle wedge. This segment of the Nazca Plate is currently subducting at a normal angle, but Wagner et al. (2017) suggested that a flat slab slowly developed in the region between 9-5.9 Ma and persisted until 4 Ma. During flat slab subduction, the overlying mantle wedge typically cools because it is cut off from mantle corner flow. After hydrous minerals in the slab dehydrate, the dehydrated fluid is expelled from the slab and migrates through the mantle wedge. If a cool mantle wedge remains today, fluid dehydrated from the slab may generate earthquakes by hydrofracture, with the mantle wedge earthquakes representing fluid migration pathways. Dahm's (2000) model of water-filled fracture propagation in the mantle wedge shows hydrofractures propagating normal to the subducting slab and extending tens of km into the mantle wedge, as we observe.

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.

Ibrutinib (Imbruvica). Relapsed chronic lymphocytic leukaemia and mantle cell lymphoma: uncertain impact on survival.

Science.gov (United States)

January

2016-04-01

codynamic interactions are also likely in view of its adverse effect profile. There is no consensus on the treatment of patients with refractory or relapsed mantle cell lymphoma, or for patients with relapsed or possibly refractory chronic lymphocytic leukaemia. Ibrutinib inhibits an enzyme involved in regulating B lymphocyte activity. It has been authorised in the European Union for these conditions. Clinical evaluation of ibrutinib in mantle cell lymphoma is based on a single non-comparative trial in 111 patients, in which the median overall survival time was 22.5 months. Clinical evaluation of ibrutinib in chronic lymphocytic leukaemia is based on two randomised trials. One unblinded trial compared ibrutinib versus ofatumumab and involved 391 patients, most of whom were sufficiently fit to receive anticancer combination therapy. Ibrutinib was more effective than ofatumumab, but the choice of this comparator might not have been appropriate for most of the patients who received it. The other double-blind, placebo-controlled trial involved 578 patients with relapsed or refractory chronic lymphocytic leukaemia. Ibrutinib was added to the bendamustine + rituximab combination. No significant difference in mortality was observed between the two groups. The main adverse effects of ibrutinib were: gastrointestinal disorders such as diarrhoea; life-threatening infections and bleeding disorders; and cardiac disorders, including atrial fibrillation. Ibrutinib carries a risk of multiple pharmacokinetic interactions. Pharmacodynamic interactions are also likely in view of its adverse effect profile.

DNA amplification is rare in normal human cells

International Nuclear Information System (INIS)

Wright, J.A.; Watt, F.M.; Hudson, D.L.; Stark, G.R.; Smith, H.S.; Hancock, M.C.

1990-01-01

Three types of normal human cells were selected in tissue culture with three drugs without observing a single amplification event from a total of 5 x 10 8 cells. No drug-resistant colonies were observed when normal foreskin keratinocytes were selected with N-(phosphonacetyl)-L-aspartate or with hydroxyurea or when normal mammary epithelial cells were selected with methotrexate. Some slightly resistant colonies with limited potential for growth were obtained when normal diploid fibroblast cells derived from fetal lung were selected with methotrexate or hydroxyurea but careful copy-number analysis of the dihydrofolate reductase and ribonucleotide reductase genes revealed no evidence of amplification. The rarity of DNA amplification in normal human cells contrasts strongly with the situation in tumors and in established cell lines, where amplification of onogenes and of genes mediating drug resistance is frequent. The results suggest that tumors and cell lines have acquired the abnormal ability to amplify DNA with high frequency

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

Science.gov (United States)

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.

Mantle hydration along outer-rise faults inferred from serpentinite permeability.

Science.gov (United States)

Hatakeyama, Kohei; Katayama, Ikuo; Hirauchi, Ken-Ichi; Michibayashi, Katsuyoshi

2017-10-24

Recent geophysical surveys indicate that hydration (serpentinization) of oceanic mantle is related to outer-rise faulting prior to subduction. The serpentinization of oceanic mantle influences the generation of intermediate-depth earthquakes and subduction water flux, thereby promoting arc volcanism. Since the chemical reactions that produce serpentinite are geologically rapid at low temperatures, the flux of water delivery to the reaction front appears to control the lateral extent of serpentinization. In this study, we measured the permeability of low-temperature serpentinites composed of lizardite and chrysotile, and calculated the lateral extent of serpentinization along an outer-rise fault based on Darcy's law. The experimental results indicate that serpentinization extends to a region several hundred meters wide in the direction normal to the outer-rise fault in the uppermost oceanic mantle. We calculated the global water flux carried by serpentinized oceanic mantle ranging from 1.7 × 10 11 to 2.4 × 10 12  kg/year, which is comparable or even higher than the water flux of hydrated oceanic crust.

Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

Directory of Open Access Journals (Sweden)

Tozeren Aydin

2006-11-01

Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

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.

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)

Inverse models of plate coupling and mantle rheology: Towards a direct link between large-scale mantle flow and mega thrust earthquakes

Science.gov (United States)

Gurnis, M.; Ratnaswamy, V.; Stadler, G.; Rudi, J.; Liu, X.; Ghattas, O.

2017-12-01

We are developing high-resolution inverse models for plate motions and mantle flow to recover the degree of mechanical coupling between plates and the non-linear and plastic parameters governing viscous flow within the lithosphere and mantle. We have developed adjoint versions of the Stokes equations with fully non-linear viscosity with a cost function that measures the fit with plate motions and with regional constrains on effective upper mantle viscosity (from post-glacial rebound and post seismic relaxation). In our earlier work, we demonstrate that when the temperature field is known, the strength of plate boundaries, the yield stress and strain rate exponent in the upper mantle are recoverable. As the plate boundary coupling drops below a threshold, the uncertainty of the inferred parameters increases due to insensitivity of plate motion to plate coupling. Comparing the trade-offs between inferred rheological parameters found from a Gaussian approximation of the parameter distribution and from MCMC sampling, we found that the Gaussian approximation—which is significantly cheaper to compute—is often a good approximation. We have extended our earlier method such that we can recover normal and shear stresses within the zones determining the interface between subducting and over-riding plates determined through seismic constraints (using the Slab1.0 model). We find that those subduction zones with low seismic coupling correspond with low inferred values of mechanical coupling. By fitting plate motion data in the optimization scheme, we find that Tonga and the Marianas have the lowest values of mechanical coupling while Chile and Sumatra the highest, among the subduction zones we have studies. Moreover, because of the nature of the high-resolution adjoint models, the subduction zones with the lowest coupling have back-arc extension. Globally we find that the non-linear stress-strain exponent, n, is about 3.0 +/- 0.25 (in the upper mantle and lithosphere) and a

Influence of the interplanetary magnetic field on the occurrence and thickness of the plasma mantle

Science.gov (United States)

Sckopke, N.; Paschmann, G.; Rosenbauer, H.; Fairfield, D. H.

1976-01-01

The response of the plasma mantle to the orientation of the interplanetary magnetic field (IMF) has been studied by correlating Heos 2 plasma and Imp 6 magnetic field data. The mantle is nearly always present when the IMF has a southward component and often also when the field has a weak northward component. In addition, the mantle appears increasingly thicker with greater southward components. On the other hand, the mantle is thin or missing (from the region where it is normally found) when the average IMF has a strong northward component. This result supports the idea that polar cap convection plays a dominant role in the formation of the plasma mantle: mantle plasma originates in the magnetosheath, enters the magnetosphere through the day side polar cusps, and is transported across the cusp to the night side by means of a convection electric field whose magnitude is controlled by the orientation of the IMF.

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

Electromagnetic exploration of the oceanic mantle.

Science.gov (United States)

Utada, Hisashi

2015-01-01

Electromagnetic exploration is a geophysical method for examining the Earth's interior through observations of natural or artificial electromagnetic field fluctuations. The method has been in practice for more than 70 years, and 40 years ago it was first applied to ocean areas. During the past few decades, there has been noticeable progress in the methods of instrumentation, data acquisition (observation), data processing and inversion. Due to this progress, applications of this method to oceanic regions have revealed electrical features of the oceanic upper mantle down to depths of several hundred kilometers for different geologic and tectonic environments such as areas around mid-oceanic ridges, areas around hot-spot volcanoes, subduction zones, and normal ocean areas between mid-oceanic ridges and subduction zones. All these results estimate the distribution of the electrical conductivity in the oceanic mantle, which is key for understanding the dynamics and evolution of the Earth together with different physical properties obtained through other geophysical methods such as seismological techniques.

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....

Early mantle differentiation: constraint from 146Sm-142Nd systematics

International Nuclear Information System (INIS)

Caro, G.

2005-07-01

We present new ultra-high precision 142 Nd/ 144 Nd measurements of early Archaean rocks using the new generation thermal ionization mass spectrometer TRITON. Repeated measurements of the Ames Nd standard demonstrate that the 142 Nd/ 144 Nd ratio can be determined with external precision of 2 ppm (2s), allowing confident resolution of anomalies as small as 5 ppm. A major analytical improvement lies in the elimination of the double normalization procedure required to correct our former measurements from a secondary mass fractionation effect. Our new results indicate that metasediments, meta-basalts and orthogneisses from the 3.6 - 3.8 Ga West Greenland craton display positive 142 Nd anomalies ranging from 8 to 15 ppm. Using a simple two-stage model with initial e 143 Nd value of 1.9 ± 0.6 e-units, coupled 147 Sm- 143 Nd and 146 Sm- 142 Nd chronometry constrains mantle differentiation to 50 to 200 Ma after formation of the solar system. This chronological constraint is consistent with differentiation of the Earth's mantle during the late stage of crystallization of a magma ocean. We have developed a two-box model describing 142 Nd and 143 Nd isotopic evolution of depleted mantle during the subsequent evolution of the crust-mantle system. Our results indicate that early terrestrial proto-crust had a lifetime of ca. 500 Ma in order to produce the observed Nd isotope signature of Archaean rocks. In the context of this two box mantle-crust system, we model the evolution of isotopic and chemical heterogeneity of depleted mantle as a function of the mantle stirring time. Using the dispersion of 142 Nd/ 144 Nd and 143 Nd/ 144 Nd ratios observed in early Archaean rocks, we constrain the stirring time of early Earth's mantle to 100 - 150 Ma, a factor of 5 to 10 shorter than stirring time inferred from modern oceanic basalts. (author)

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.

Stable radioresistance in ataxia-telangiectasia cells containing DNA from normal human cells

International Nuclear Information System (INIS)

Kapp, L.N.; Painter, R.B.

1989-01-01

SV40-transformed ataxia-telangiectasia (AT) cells were transfected with a cosmid containing a normal human DNA library and selectable marker, the neo gene, which endows successfully transformed mammalian cells with resistance to the antibiotic G418. Cells from this line were irradiated with 50 Gy of X-rays and fused with non-transfected AT cells. Among the G418-resistant colonies recovered was one stably resistant to radiation. Resistance to ionizing radiation of both primary transfectant line and its fusion derivative was intermediate between that of AT cells and normal cells, as assayed by colony-forming ability and measurement of radiation-induced G 2 chromatic aberrations; both cell lines retained AT-like radioresistant DNA synthesis. Results suggest that, because radioresistance in transfected cells was not as great as in normal human cells, two hallmarks of AT, radiosensitivity and radioresistant DNA synthesis, may still be the result of a single defective AT gene. (author)

Dynamical geochemistry of the mantle

Directory of Open Access Journals (Sweden)

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

Abnormal lithium isotope composition from the ancient lithospheric mantle beneath the North China Craton.

Science.gov (United States)

Tang, Yan-Jie; Zhang, Hong-Fu; Deloule, Etienne; Su, Ben-Xun; Ying, Ji-Feng; Santosh, M; Xiao, Yan

2014-03-04

Lithium elemental and isotopic compositions of olivines in peridotite xenoliths from Hebi in the North China Craton provide direct evidence for the highly variable δ(7)Li in Archean lithospheric mantle. The δ(7)Li in the cores of olivines from the Hebi high-Mg# peridotites (Fo > 91) show extreme variation from -27 to +21, in marked deviation from the δ(7)Li range of fresh MORB (+1.6 to +5.6) although the Li abundances of the olivines are within the range of normal mantle (1-2 ppm). The Li abundances and δ(7)Li characteristics of the Hebi olivines could not have been produced by recent diffusive-driven isotopic fractionation of Li and therefore the δ(7)Li in the cores of these olivines record the isotopic signature of the subcontinental lithospheric mantle. Our data demonstrate that abnormal δ(7)Li may be preserved in the ancient lithospheric mantle as observed in our study from the central North China Craton, which suggest that the subcontinental lithospheric mantle has experienced modification of fluid/melt derived from recycled oceanic crust.

Fungal invasion of normally non-phagocytic host cells.

Directory of Open Access Journals (Sweden)

Scott G Filler

2006-12-01

Full Text Available Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.

Mantle dynamics following supercontinent formation

Science.gov (United States)

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

DNA-repair, cell killing and normal tissue damage

International Nuclear Information System (INIS)

Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

1998-01-01

Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial.

Science.gov (United States)

Wang, Michael L; Lee, Hun; Chuang, Hubert; Wagner-Bartak, Nicolaus; Hagemeister, Frederick; Westin, Jason; Fayad, Luis; Samaniego, Felipe; Turturro, Francesco; Oki, Yasuhiro; Chen, Wendy; Badillo, Maria; Nomie, Krystle; DeLa Rosa, Maria; Zhao, Donglu; Lam, Laura; Addison, Alicia; Zhang, Hui; Young, Ken H; Li, Shaoying; Santos, David; Medeiros, L Jeffrey; Champlin, Richard; Romaguera, Jorge; Zhang, Leo

2016-01-01

Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progressive disease or unacceptable toxic effects. Rituximab 375 mg/m(2) was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing patients. Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45-86), and the median number of previous regimens was three (range 1-9). At a median follow-up of 16·5 months (IQR 12·09-19·28), 44 (88%, 95% CI 75·7-95·5) patients achieved an objective response, with 22 (44%, 30·0-58·7) patients achieving a complete response, and 22 (44%, 30·0-58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one

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

Energy Technology Data Exchange (ETDEWEB)

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.

Mast cell distribution in normal adult skin

NARCIS (Netherlands)

A.S. Janssens (Artiena Soe); R. Heide (Rogier); J.C. den Hollander (Jan); P.G.M. Mulder (P. G M); B. Tank (Bhupendra); A.P. Oranje (Arnold)

2005-01-01

markdownabstract__AIMS:__ To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. __METHODS:__ Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults.

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

We report double-spike molybdenum (Mo) isotope data for forty-two mafic and fifteen ultramafic rocks from diverse locations and compare these with results for five chondrites. The δ98/95Mo values (normalized to NIST SRM 3134) range from -0.59 ± 0.04 to +0.10 ± 0.08‰. The compositions of one carbonaceous (CI) and four ordinary chondrites are relatively uniform (-0.14 ± 0.01‰, 95% ci (confidence interval)) in excellent agreement with previous data. These values are just resolvable from the mean of 10 mid-ocean ridge basalts (MORBs) (0.00 ± 0.02‰, 95% ci). The compositions of 13 mantle-derived ultramafic xenoliths from Kilbourne Hole, Tariat and Vitim are more diverse (-0.39 to -0.07‰) with a mean of -0.22 ± 0.06‰ (95% ci). On this basis, the isotopic composition of the bulk silicate Earth (BSE or Primitive Mantle) is within error identical to chondrites. The mean Mo concentration of the ultramafic xenoliths (0.19 ± 0.07 ppm, 95% ci) is similar in magnitude to that of MORB (0.48 ± 0.13 ppm, 95% ci), providing evidence, either for a more compatible behaviour than previously thought or for selective Mo enrichment of the subcontinental lithospheric mantle. Intraplate and ocean island basalts (OIBs) display significant isotopic variability within a single locality from MORB-like to strongly negative (-0.59 ± 0.04‰). The most extreme values measured are for nephelinites from the Cameroon Line and Trinidade, which also have anomalously high Ce/Pb and low Mo/Ce relative to normal oceanic basalts. δ98/95Mo correlates negatively with Ce/Pb and U/Pb, and positively with Mo/Ce, explicable if a phase such as an oxide or a sulphide liquid selectively retains isotopically heavy Mo in the mantle and fractionates its isotopic composition in low degree partial melts. If residual phases retain Mo during partial melting, it is possible that the [Mo] for the BSE may be misrepresented by values estimated from basalts. This would be consistent with the high Mo

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

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...

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

Science.gov (United States)

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.

Deep Mantle Origin for the DUPAL Anomaly?

Science.gov (United States)

Ingle, S.; Weis, D.

2002-12-01

Twenty years after the discovery of the Dupal Anomaly, its origin remains a geochemical and geophysical enigma. This anomaly is associated with the Southern Hemisphere oceanic mantle and is recognized by basalts with geochemical characteristics such as low 206Pb/204Pb and high 87Sr/86Sr. Both mid-ocean ridge basalts (MORB) and ocean island basalts (OIB) are affected, despite originating from melting at different depths and of different mantle sources. We compile geochemical data for both MORB and OIB from the three major oceans to help constrain the physical distribution and chemical composition of the Dupal Anomaly. There is a clear decrease in 206Pb/204Pb and an increase in 87Sr/86Sr with more southerly latitude for Indian MORB and OIB; these correlations are less obvious in the Atlantic and non-existent in the Pacific. The average* 143Nd/144Nd for Pacific and Atlantic OIB is 0.5129, but is lower for Indian OIB (0.5128). Interestingly, Pacific, Atlantic and Indian OIB all have 176Hf/177Hf averages of 0.2830. Indian MORB also record this phenomenon of low Nd with normal Hf isotopic compositions (Chauvel and Blichert-Toft, EPSL, 2001). Hf isotopes appear, therefore, to be a valid isotopic proxy for measuring the presence and magnitude of the Dupal Anomaly at specific locations. Wen (EPSL, 2001) reported a low-velocity layer at the D'' boundary beneath the Indian Ocean from which the Dupal Anomaly may originate. This hypothesis may be consistent with our compilations demonstrating that the long-lived Dupal Anomaly does not appear to be either mixing efficiently into the upper mantle or spreading to other ocean basins through time. We suggest that the Dupal source could be continually tapped by upwelling Indian Ocean mantle plumes. Plumes would then emplace pockets of Dupal material into the upper mantle and other ascending plumes might further disperse this material into the shallow asthenosphere. This could explain both the presence of the Dupal signature in MORB

Mitogen-stimulated phospholipid synthesis in normal and immune-deficient human B cells

International Nuclear Information System (INIS)

Chien, M.M.; Yokoyama, W.M.; Ashman, R.F.

1986-01-01

Eight patients with common variable panhypogammaglobulinemia were shown in the in vitro Ig biosynthesis assay to have defective B cell responses to pokeweed mitogen (PWM). Phospholipid synthesis was assessed in the B cell plus monocyte fraction (MB) and irradiated T cells (T*) of patients and paired normal controls. Cell populations were studied separately and in the four possible combinations (1:1), with and without PWM, to reveal the effect of cell interactions. At 16 to 20 hr the mean stimulation index (SI) +/- standard error for MB cells alone was 1.01 +/- 0.02 for eight patients and 0.99 +/- 0.02 for the paired normals; the T* cell SI was 1.25 +/- 0.04 for patients and 1.28 +/- 0.05 for normals. Combinations of normal MB cells with normal T* cells showed significantly higher SI when compared with the combinations of normal MB cells with patient T* cells (p less than 0.005). However, the combination of patient MB cells with patient T* cells and the combination of patient MB cells with normal T* cells were not significantly different in SI (0.05 less than p less than 0.1). Isolation of patient and normal B cells, T* cells, and monocytes after the choline pulse showed that patient B cells gave a higher SI with normal T* help than with patient T* help. Of greatest interest is the finding that patient B cells that were defective in PWM-stimulated Ig production nevertheless showed a phospholipid synthesis response to PWM in the normal range, suggesting that the maturation defect in these B cells occurs later than the phospholipid synthesis acceleration step, or on a different pathway

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.

Respiratory function tests after mantle irradiation in patients with Hodgkin's disease

Energy Technology Data Exchange (ETDEWEB)

Cionini, L; Pacini, P; De Paola, E; Corrado, A; De Luca Cardillo, C; Mungai, V; Biti, G P; Ponticelli, P

1984-01-01

Pulmonary function tests were performed in 43 patients with Hodgkin's disease before mantle irradiation and at 3, 6, 9, 12 and 15 or more months thereafter. Treatment was given with a telecobalt unit to a total dose of 36 to 42 Gy, the higher dose being reserved for cases with considerable mediastinal involvement. The functional parameters explored included static and dynamic lung volumes, gas exchanges, ventilatory efficiency, and airway resistance. Measured parameters were expressed as a percentage of the pre-treatment value (PTV) in the individual patient. In the whole group, only small variations in the functional indices were observed at 3 to 6 months after mantle irradiation. In patients with normal PTVs a greater variation in static and dynamic volumes was observed at 3 to 6 months after mantle irradiation, with complete recovery thereafter. The gas exchange parameters also showed a similar variation at 3 to 6 months but no recovery was demonstrated in the subsequent examinations. No changes in ventilatory efficiency and airway resistance were observed. In patients with abnormal PTVs, usually presenting large mediastinal adenopathy, all parameters improved after mantle irradiation, and the favourable effect of tumour regression was probably more important than the radiation damage on the pulmonary parenchyma.

Cell survival of human tumor cells compared with normal fibroblasts following 60Co gamma irradiation

International Nuclear Information System (INIS)

Lloyd, E.L.; Henning, C.B.; Reynolds, S.D.; Holmblad, G.L.; Trier, J.E.

1982-01-01

Three tumor cell lines, two of which were shown to be HeLa cells, were irradiated with 60 Co gamma irradiation, together with two cell cultures of normal human diploid fibroblasts. Cell survival was studied in three different experiments over a dose range of 2 to 14 gray. All the tumor cell lines showed a very wide shoulder in the dose response curves in contrast to the extremely narrow shoulder of the normal fibroblasts. In addition, the D/sub o/ values for the tumor cell lines were somewhat greater. These two characteristics of the dose response curves resulted in up to 2 orders of magnitude less sensitivity for cell inactivation of HeLa cells when compared with normal cells at high doses (10 gray). Because of these large differences, the extrapolation of results from the irradiation of HeLa cells concerning the mechanisms of normal cell killing should be interpreted with great caution

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.

Study on 3-D velocity structure of crust and upper mantle in Sichuan-yunnan region, China

Science.gov (United States)

Wang, C.; Mooney, W.D.; Wang, X.; Wu, J.; Lou, H.; Wang, F.

2002-01-01

Based on the first arrival P and S data of 4 625 regional earthquakes recorded at 174 stations dispersed in the Yunnan and Sichuan Provinces, the 3-D velocity structure of crust and upper mantle in the region is determined, incorporating with previous deep geophysical data. In the upper crust, a positive anomaly velocity zone exists in the Sichuan basin, whereas a negative anomaly velocity zone exists in the western Sichuan plateau. The boundary between the positive and negative anomaly zones is the Longmenshan fault zone. The images of lower crust and upper mantle in the Longmenshan fault, Xianshuihe fault, Honghe fault and others appear the characteristic of tectonic boundary, indicating that the faults litely penetrate the Moho discontinuity. The negative velocity anomalies at the depth of 50 km in the Tengchong volcanic area and the Panxi tectonic zone appear to be associated with the temperature and composition variations in the upper mantle. The overall features of the crustal and the upper mantle structures in the Sichuan-Yunnan region are the lower average velocity in both crust and uppermost mantle, the large crustal thickness variations, and the existence of high conductivity layer in the crust or/and upper mantle, and higher geothermal value. All these features are closely related to the collision between the Indian and the Asian plates. The crustal velocity in the Sichuan-Yunnan rhombic block generally shows normal.value or positive anomaly, while the negative anomaly exists in the area along the large strike-slip faults as the block boundary. It is conducive to the crustal block side-pressing out along the faults. In the major seismic zones, the seismicity is relative to the negative anomaly velocity. Most strong earthquakes occurred in the upper-mid crust with positive anomaly or normal velocity, where the negative anomaly zone generally exists below.

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

Directory of Open Access Journals (Sweden)

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.

Glycosaminoglycan-sac formation in vitro. Interactions between normal and malignant cells

OpenAIRE

Logothetou-Rella, H.

1994-01-01

The interaction of monolayer normal human or normal rat cells with suspension Walker rat tumor cells was demonstrated cytologically, during a cocultivation period of thirty days. At ten days, Walker rat tumor cells were interiorized in the cytoplasm of the normal monolayer host cells. At twenty days, degeneration of the interiorized tumor cells followed by mucification led to glycosaminoglycan-sac formation. At thirty days, tumor nodules and protease (a,- c...

Mantle updrafts and mechanisms of oceanic volcanism

Science.gov (United States)

Anderson, Don L.; Natland, James H.

2014-10-01

Convection in an isolated planet is characterized by narrow downwellings and broad updrafts-consequences of Archimedes' principle, the cooling required by the second law of thermodynamics, and the effect of compression on material properties. A mature cooling planet with a conductive low-viscosity core develops a thick insulating surface boundary layer with a thermal maximum, a subadiabatic interior, and a cooling highly conductive but thin boundary layer above the core. Parts of the surface layer sink into the interior, displacing older, colder material, which is entrained by spreading ridges. Magma characteristics of intraplate volcanoes are derived from within the upper boundary layer. Upper mantle features revealed by seismic tomography and that are apparently related to surface volcanoes are intrinsically broad and are not due to unresolved narrow jets. Their morphology, aspect ratio, inferred ascent rate, and temperature show that they are passively responding to downward fluxes, as appropriate for a cooling planet that is losing more heat through its surface than is being provided from its core or from radioactive heating. Response to doward flux is the inverse of the heat-pipe/mantle-plume mode of planetary cooling. Shear-driven melt extraction from the surface boundary layer explains volcanic provinces such as Yellowstone, Hawaii, and Samoa. Passive upwellings from deeper in the upper mantle feed ridges and near-ridge hotspots, and others interact with the sheared and metasomatized surface layer. Normal plate tectonic processes are responsible both for plate boundary and intraplate swells and volcanism.

Use of acalabrutinib in patients with mantle cell lymphoma.

Science.gov (United States)

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.

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.

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.

Widespread melt/rock interaction and seismic properties of the lithosphere above mantle plumes: Evidence from mantle xenoliths from French Polynesia

Science.gov (United States)

Tommasi, A.; Godard, M.; Coromina, G.; Dautria, J. M.; Barczus, H.

2003-04-01

In addition to thermal erosion, plume/lithosphere interaction may induce significant changes in the lithosphere chemical composition. To constrain the extent of this process in an oceanic environment and its consequences on the lithosphere seismic properties, we studied the relationship between petrological processes and microstructure in mantle xenoliths from the Austral-Cook, Society and Marquesas islands. Olivine forsterite contents in our sp-peridotites vary continuously from Fo91 to Fo83, the lowest Fo being observed in dunites and wehrlites. Yet, their high Ni content (up to 2500 ppm) precludes a cumulate origin. These rocks are rather interpreted as resulting from melt/rock reactions involving olivine precipitation and pyroxene dissolution, the dunites indicating high melt-rock ratios. Moreover, wehrlites display poikiloblastic diopside enclosing corroded olivines. Late crystallization of clinopyroxene, also observed in lherzolites, may result from a near-solidus melt-freezing reaction occurring at the boundary of a partial melting domain developed at the expenses of lithospheric mantle. These data suggest that the lithosphere above a mantle plume undergoes a complex sequence of magmatic processes that significantly change its composition. Yet, crystal preferred orientations and thus seismic anisotropy are little affected by these processes. Lherzolites and harzburgites, independent from composition, show high-temperature porphyroclastic microstructures and strong olivine CPO. Although dunites and wehrlites display annealing microstructures to which is associated a progressive dispersion of the olivine CPO, very weak CPO are limited to a few dunites and wehrlites, suggesting that CPO destruction is restricted to domains of intense magma-rock interaction due to localized flow or accumulation of magmas. Conversely, the compositional changes result in lower seismic velocities for P- and S-waves. Relative to normal mantle, seismic anomalies may attain -2.5 (2

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON)

DEFF Research Database (Denmark)

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin

2018-01-01

BACKGROUND: Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data...... performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56...... days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m2) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle...

Cell Survival and DNA Damage in Normal Prostate Cells Irradiated Out-of-Field.

LENUS (Irish Health Repository)

Shields, L

2014-10-31

Interest in out-of-field radiation dose has been increasing with the introduction of new techniques, such as volumetric modulated arc therapy (VMAT). These new techniques offer superior conformity of high-dose regions to the target compared to conventional techniques, however more normal tissue is exposed to low-dose radiation with VMAT. There is a potential increase in radiobiological effectiveness associated with lower energy photons delivered during VMAT as normal cells are exposed to a temporal change in incident photon energy spectrum. During VMAT deliveries, normal cells can be exposed to the primary radiation beam, as well as to transmission and scatter radiation. The impact of low-dose radiation, radiation-induced bystander effect and change in energy spectrum on normal cells are not well understood. The current study examined cell survival and DNA damage in normal prostate cells after exposure to out-of-field radiation both with and without the transfer of bystander factors. The effect of a change in energy spectrum out-of-field compared to in-field was also investigated. Prostate cancer (LNCaP) and normal prostate (PNT1A) cells were placed in-field and out-of-field, respectively, with the PNT1A cells being located 1 cm from the field edge when in-field cells were being irradiated with 2 Gy. Clonogenic and γ-H2AX assays were performed postirradiation to examine cell survival and DNA damage. The assays were repeated when bystander factors from the LNCaP cells were transferred to the PNT1A cells and also when the PNT1A cells were irradiated in-field to a different energy spectrum. An average out-of-field dose of 10.8 ± 4.2 cGy produced a significant reduction in colony volume and increase in the number of γ-H2AX foci\\/cell in the PNT1A cells compared to the sham-irradiated control cells. An adaptive response was observed in the PNT1A cells having first received a low out-of-field dose and then the bystander factors. The PNT1A cells showed a significant

Seismic Imaging of Mantle Plumes

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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.

Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy.

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Johnsen, Hans Erik; Bergkvist, Kim Steve; Schmitz, Alexander; Kjeldsen, Malene Krag; Hansen, Steen Møller; Gaihede, Michael; Nørgaard, Martin Agge; Bæch, John; Grønholdt, Marie-Louise; Jensen, Frank Svendsen; Johansen, Preben; Bødker, Julie Støve; Bøgsted, Martin; Dybkær, Karen

2014-06-01

Recent findings have suggested biological classification of B-cell malignancies as exemplified by the "activated B-cell-like" (ABC), the "germinal-center B-cell-like" (GCB) and primary mediastinal B-cell lymphoma (PMBL) subtypes of diffuse large B-cell lymphoma and "recurrent translocation and cyclin D" (TC) classification of multiple myeloma. Biological classification of B-cell derived cancers may be refined by a direct and systematic strategy where identification and characterization of normal B-cell differentiation subsets are used to define the cancer cell of origin phenotype. Here we propose a strategy combining multiparametric flow cytometry, global gene expression profiling and biostatistical modeling to generate B-cell subset specific gene signatures from sorted normal human immature, naive, germinal centrocytes and centroblasts, post-germinal memory B-cells, plasmablasts and plasma cells from available lymphoid tissues including lymph nodes, tonsils, thymus, peripheral blood and bone marrow. This strategy will provide an accurate image of the stage of differentiation, which prospectively can be used to classify any B-cell malignancy and eventually purify tumor cells. This report briefly describes the current models of the normal B-cell subset differentiation in multiple tissues and the pathogenesis of malignancies originating from the normal germinal B-cell hierarchy.

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial.

Science.gov (United States)

Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin; Räty, Riikka; Wader, Karin Fahl; Laurell, Anna; Toldbod, Helle; Pedersen, Lone Bredo; Niemann, Carsten Utoft; Dahl, Christina; Kuitunen, Hanne; Geisler, Christian H; Grønbæk, Kirsten; Kolstad, Arne

2018-03-01

Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m 2 ) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-to-treat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17·8 months (IQR 14·7-20·9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a

Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

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Magnusson Magnus K

2010-07-01

Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

Interaction between mantle and crustal detachments: a non-linear system controlling lithospheric extension

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Rosenbaum, G.; Regenauer-Lieb, K.; Weinberg, R. F.

2009-12-01

We use numerical modelling to investigate the development of crustal and mantle detachment faults during lithospheric extension. Our models simulate a wide range of rift systems with varying values of crustal thickness and heat flow, showing how strain localization in the mantle interacts with localization in the upper crust and controls the evolution of extensional systems. Model results reveal a richness of structures and deformation styles, which grow in response to a self-organized mechanism that minimizes the internal stored energy of the system by localizing deformation at different levels of the lithosphere. Crustal detachment faults are well developed during extension of overthickened (60 km) continental crust, even when the initial heat flow is relatively low (50 mW/m2). In contrast, localized mantle deformation is most pronounced when the extended lithosphere has a normal crustal thickness (30-40 km) and an intermediate (60-70 mW/m2) heat flow. Results show a non-linear response to subtle changes in crustal thickness or heat flow, characterized by abrupt and sometime unexpected switches in extension modes (e.g. from diffuse rifting to effective lithospheric-scale rupturing) or from mantle- to crust-dominated strain localization. We interpret this non-linearity to result from the interference of doming wavelengths. Disharmony of crust and mantle doming wavelengths results in efficient communication between shear zones at different lithospheric levels, leading to rupturing of the whole lithosphere. In contrast, harmonious crust and mantle doming inhibits interaction of shear zones across the lithosphere and results in a prolonged rifting history prior to continental breakup.

Partial delamination of continental mantle lithosphere, uplift-related crust mantle decoupling, volcanism and basin formation: a new model for the Pliocene Quaternary evolution of the southern East-Carpathians, Romania

Science.gov (United States)

Chalot-Prat, F.; Girbacea, R.

2000-11-01

extension are consequences of uplift, induced by asthenospheric upwelling triggered by intra-mantle delamination. This model enables to conceive that delamination-induced decoupling began to be efficient 9.4 My ago at the northern end of the East-Carpathians, when the mantle slab dipped westwards. Since then, intra-mantle delamination migrated laterally, normal to the slab strike, and follows the arcuate shape (NW→SE→SW) of the Carpathians. Nowadays, whereas the mantle slab is still actively foundering below the Vrancea seismic zone to the SE of the most recent volcanic area (South Harghita-Persani), a significant southwestward shift of the delamination process can be discerned.

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

OpenAIRE

Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of...

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.

Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004

Directory of Open Access Journals (Sweden)

Michael Wang

2017-11-01

Full Text Available Abstract Background The observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance. Methods The primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria. Results Of 58 enrolled patients (median age, 71 years; range, 50–89, 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment. Most patients (88% had received ≥ 3 prior therapies (median 4; range, 1–13. Median time from last dose of ibrutinib to the start of lenalidomide was 1.3 weeks (range, 0.1–21.7; 45% of patients had partial responses or better to prior ibrutinib. Primary reasons for ibrutinib discontinuation were lack of efficacy (88% and ibrutinib toxicity (9%. After a median of two cycles (range, 0–11 of lenalidomide-based treatment, 17 patients responded (8 complete responses, 9 partial responses, for a 29% overall response rate (95% confidence interval, 18–43% and a median duration of response of 20 weeks (95% confidence interval, 2.9 to not available. Overall response rate to lenalidomide-based therapy was similar for patients with relapsed/progressive disease after previous response to ibrutinib (i.e., ≥PR versus ibrutinib-refractory (i.e., ≤SD patients (30 versus 32%, respectively. The most common all-grade treatment-emergent adverse events after lenalidomide-containing therapy (n = 58 were fatigue (38% and cough, dizziness, dyspnea, nausea, and peripheral edema (19% each. At data cutoff, 28 patients have died, primarily due to mantle cell lymphoma. Conclusion Lenalidomide-based treatment showed clinical activity, with no unexpected toxicities, in patients with relapsed/refractory mantle cell lymphoma who previously failed ibrutinib therapy. Trial registration Clinicaltrials.gov identifier NCT02341781 . Date of

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

[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.

Water Content in the SW USA Mantle Lithosphere: FTIR Analysis of Dish Hill and Kilbourne Hole Pyroxenites

Science.gov (United States)

Gibler, Robert; Peslier, Anne H.; Schaffer, Lillian Aurora; Brandon, Alan D.

2014-01-01

Kilbourne Hole (NM, USA) and Dish Hill (CA, USA) mantle xenoliths sample continental mantle in two different tectonic settings. Kilbourne Hole (KH) is located in the Rio Grande rift. Dish Hill (DH) is located in the southern Mojave province, an area potentially affected by subduction of the Farallon plate beneath North America. FTIR analyses were obtained on well characterized pyroxenite, dunite and wehrlite xenoliths, thought to represent crystallized melts at mantle depths. PUM normalized REE patterns of the KH bulk-rocks are slightly LREE enriched and consistent with those of liquids generated by 6% melting of a spinel peridotite source. Pyroxenite pyroxenes have no detectable water but one DH wehrlite, which bulk-rock is LREE enriched, has 4 ppm H2O in orthopyroxene and 2 Ga. The Farallon subduction appears to have enriched in water the southwestern United States lithospheric mantle further east than DH, beneath the Colorado plateau.

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.

Radial and Azimuthal Anisotropy Tomography of the NE Japan Subduction Zone: Implications for the Pacific Slab and Mantle Wedge Dynamics

Science.gov (United States)

Ishise, Motoko; Kawakatsu, Hitoshi; Morishige, Manabu; Shiomi, Katsuhiko

2018-05-01

We investigate slab and mantle structure of the NE Japan subduction zone from P wave azimuthal and radial anisotropy using travel time tomography. Trench normal E-W-trending azimuthal anisotropy (AA) and radial anisotropy (RA) with VPV > VPH are found in the mantle wedge, which supports the existence of small-scale convection in the mantle wedge with flow-induced LPO of mantle minerals. In the subducting Pacific slab, trench parallel N-S-trending AA and RA with VPH > VPV are obtained. Considering the effect of dip of the subducting slab on apparent anisotropy, we suggest that both characteristics can be explained by the presence of laminar structure, in addition to AA frozen-in in the subducting plate prior to subduction.

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.

Three-dimensional P velocity structure of the crust and upper mantle under Beijing region

Energy Technology Data Exchange (ETDEWEB)

Quan, A.; Liu, F.; Sun, Y.

1980-04-01

By use of the teleseismic P arrival times at 15 stations of the Beijing network for 120 events distributed over various azimuths, we studied the three-dimensional P velocity structure under the Beijing region. In calculating the theoretic travel time, we adopted the source parameters given in BISC, and used the J-B model as the standard model of earth. On inversion, we adopted singular value decomposition as a generalized inversion package, which can be used for solving very large over-determined systems of equations Gm = t without resorting to normal equations G/sup T/Gm = G/sup T/t. The results are that within the crust and upper mantle under the Beijing region there are clear lateral differences. In the results obtained by use of data from 1972 to 1975, it can be seen that there are three different zones of P-velocity. In the southeast Beijing region, P velocity is lower than that of the normal model by 10 to 14% within the crust, and by 8 to 9% within the upper mantle. The northwest Beijing region is a higher-velocity zone, within which the average P-velocity is faster than that of the normal model by about 9%. It disappears after entering into the upper mantle. The central part of this region is a normal zone. On the surface, the distribution of these P velocity variations corresponds approximately to the distribution of the over-burden. But in the deeper region, the distribution of velocity variation agrees with the distribution of seismicity. It is interesting to note that the hypocenters of several major earthquakes in this region, e.g., the Sanhe-Pinggu earthquake (1679, M = 8), the Shacheng earthquake (1730, M = 6-3/4) and the Tangshan earthquake (1976, M = 7.8), are all located very close to this boundary of these P-velocity variation zones.

Mantle Cell Lymphoma

Science.gov (United States)

... 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 ...

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...

The Glycome of Normal and Malignant Plasma Cells

Science.gov (United States)

Hose, Dirk; Andrulis, Mindaugas; Moreaux, Jèrôme; Hielscher, Thomas; Willhauck-Fleckenstein, Martina; Merling, Anette; Bertsch, Uta; Jauch, Anna; Goldschmidt, Hartmut; Klein, Bernard; Schwartz-Albiez, Reinhard

2013-01-01

The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10) and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i) malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii) be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii) Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14), t(4;14), hyperdiploidy, 1q21-gain and deletion of 13q14. iv) A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v) As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma. PMID:24386263

The glycome of normal and malignant plasma cells.

Directory of Open Access Journals (Sweden)

Thomas M Moehler

Full Text Available The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10 and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14, t(4;14, hyperdiploidy, 1q21-gain and deletion of 13q14. iv A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma.

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.

Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

International Nuclear Information System (INIS)

Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

1988-01-01

Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

Response of cultured normal human mammary epithelial cells to X rays

International Nuclear Information System (INIS)

Yang, T.C.; Stampfer, M.R.; Smith, H.S.

1983-01-01

The effect of X rays on the reproductive death of cultured normal human mammary epithelial cells was examined. Techniques were developed for isolating and culturing normal human mammary epithelial cells which provide sufficient cells at second passage for radiation studies, and an efficient clonogenic assay suitable for measuring radiation survival curves. It was found that the survival curves for epithelial cells from normal breast tissue were exponential and had D 0 values of about 109-148 rad for 225 kVp X rays. No consistent change in cell radiosensitivity with the age of donor was observed, and no sublethal damage repair in these cells could be detected with the split-dose technique

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

Science.gov (United States)

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.

Chronic Lymphocytic Leukemia B-Cell Normal Cellular Counterpart: Clues From a Functional Perspective.

Science.gov (United States)

Darwiche, Walaa; Gubler, Brigitte; Marolleau, Jean-Pierre; Ghamlouch, Hussein

2018-01-01

Chronic lymphocytic leukemia (CLL) is characterized by the clonal expansion of small mature-looking CD19+ CD23+ CD5+ B-cells that accumulate in the blood, bone marrow, and lymphoid organs. To date, no consensus has been reached concerning the normal cellular counterpart of CLL B-cells and several B-cell types have been proposed. CLL B-cells have remarkable phenotypic and gene expression profile homogeneity. In recent years, the molecular and cellular biology of CLL has been enriched by seminal insights that are leading to a better understanding of the natural history of the disease. Immunophenotypic and molecular approaches (including immunoglobulin heavy-chain variable gene mutational status, transcriptional and epigenetic profiling) comparing the normal B-cell subset and CLL B-cells provide some new insights into the normal cellular counterpart. Functional characteristics (including activation requirements and propensity for plasma cell differentiation) of CLL B-cells have now been investigated for 50 years. B-cell subsets differ substantially in terms of their functional features. Analysis of shared functional characteristics may reveal similarities between normal B-cell subsets and CLL B-cells, allowing speculative assignment of a normal cellular counterpart for CLL B-cells. In this review, we summarize current data regarding peripheral B-cell differentiation and human B-cell subsets and suggest possibilities for a normal cellular counterpart based on the functional characteristics of CLL B-cells. However, a definitive normal cellular counterpart cannot be attributed on the basis of the available data. We discuss the functional characteristics required for a cell to be logically considered to be the normal counterpart of CLL B-cells.

Numerical simulations of the mantle lithosphere delamination

Science.gov (United States)

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...

LET effects on normal and radiosensitive cell lines

International Nuclear Information System (INIS)

Geard, C.R.; Travisano, M.

1986-01-01

Charged particles in the track segment mode were produced by the RARAF Van de Graaff accelerator and used to irradiate two CHO cell lines, a radiosensitive hypermutable line EM9 and its normal parent AA8. Asynchronous cells were irradiated attached to 6 micrometer thick Mylar with protons, deuterons and helium-3 particles at LETs ranging from 10 to 150 keV per micrometer. A 50 kVp x-ray tube integrated into the track segment facility provided a low LET comparison. Following irradiation cells were monitored for clonogenicity, and in a separate series of experiments frequencies of sister chromatid exchanges. Up to 9 experiments were carried out at each LET, with a total of 8 radiations of different LETs being compared. The optimally effective LET for cell survival was between 80 and 120 keV per micrometer, with the 150 keV per micrometer particles indicating energy wastage. The differential between the normal and radiosensitive cell lines was maintained at all LETs

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

Science.gov (United States)

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

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

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

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

A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

International Nuclear Information System (INIS)

Koh, Eng-Siew; Paul, Narinder; Hodgson, David C; Tran, Tu Huan; Heydarian, Mostafa; Sachs, Rainer K; Tsang, Richard W; Brenner, David J; Pintilie, Melania; Xu, Tony; Chung, June

2007-01-01

Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment

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)

Sub-cellular force microscopy in single normal and cancer cells

Energy Technology Data Exchange (ETDEWEB)

Babahosseini, H. [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States); Carmichael, B. [Nonlinear Intelligent Structures Laboratory, Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487-0276 (United States); Strobl, J.S. [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States); Mahmoodi, S.N., E-mail: nmahmoodi@eng.ua.edu [Nonlinear Intelligent Structures Laboratory, Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487-0276 (United States); Agah, M., E-mail: agah@vt.edu [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States)

2015-08-07

This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures. - Highlights: • The cells are modeled as a triple-layered structure using Generalized Maxwell model. • The sub-domains include membrane/cortex, cytoplasm/nucleus, and nuclear/integrin. • Biomechanics of corresponding sub-domains are compared among normal and cancer cells. • Viscoelasticity of sub-domains show a decreasing trend from normal to cancer cells. • The decreasing trend becomes most significant in the deeper sub-domain.

Sub-cellular force microscopy in single normal and cancer cells

International Nuclear Information System (INIS)

Babahosseini, H.; Carmichael, B.; Strobl, J.S.; Mahmoodi, S.N.; Agah, M.

2015-01-01

This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures. - Highlights: • The cells are modeled as a triple-layered structure using Generalized Maxwell model. • The sub-domains include membrane/cortex, cytoplasm/nucleus, and nuclear/integrin. • Biomechanics of corresponding sub-domains are compared among normal and cancer cells. • Viscoelasticity of sub-domains show a decreasing trend from normal to cancer cells. • The decreasing trend becomes most significant in the deeper sub-domain

Mast cell distribution in normal adult skin.

Science.gov (United States)

Janssens, A S; Heide, R; den Hollander, J C; Mulder, P G M; Tank, B; Oranje, A P

2005-03-01

To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

Primordial domains in the depleted upper mantle identified by noble gases in MORBs

Science.gov (United States)

Tucker, J.; Mukhopadhyay, S.; Langmuir, C. H.; Hamelin, C.; Fuentes, J.

2017-12-01

The distribution of noble gas isotopic compositions in the mantle provides important constraints on the large-scale mantle evolution, as noble gases can trace the interaction between degassed, or processed, mantle domains and undegassed, or primitive, mantle domains. Data from the radiogenic He, Ne, Ar and Xe isotopic systems have shown that plume-related lavas sample relatively undegassed mantle domains, and the recent identification of isotopic anomalies in the short-lived I-Xe and Hf-W isotopic systems in plume-related lavas further suggests that these domains may be ancient, dating back to Earth's accretion. However, little is known about the potential variability of the heavy noble gas systems and the distribution of undegassed domains in the ambient upper mantle not influenced by plumes. Here, we present new high-precision He, Ne, Ar, and Xe isotopic data for a series of MORBs from a depleted section of the subtropical north Mid-Atlantic Ridge, distant from any known plume influence. Some samples have extremely low (unradiogenic) 4He/3He, 21Ne/22Ne, 40Ar/36Ar, and 129Xe/130Xe ratios, including some of the lowest values ever determined for MORBs. Such unradiogenic compositions are reminiscent of OIBs and plume-influenced E-MORBs, suggesting the presence of a relatively undegassed or primitive reservoir in the source of these depleted MORBs. The He, Ne, and Ar isotopic systems are sensitive to the long-term degassing history, suggesting that this domain in the MORB source is ancient. The 129Xe/130Xe ratio is sensitive to degassing only during the first 100 Ma of Earth history, suggesting that some of the isotopic character of these samples has been preserved since Earth's accretion. Together, these observations suggest that primordial or undegassed material is not only sampled in plumes-related lavas, but also normal, depleted MORBs. Along with data from E-MORBs in the southern EPR (Kurz et al., 2005), southern MAR (Sarda et al., 2000), and equatorial MAR

Seismic imaging of the upper mantle beneath the northern Central Andean Plateau: Implications for surface topography

Science.gov (United States)

Ward, K. M.; Zandt, G.; Beck, S. L.; Wagner, L. S.

2015-12-01

Extending over 1,800 km along the active South American Cordilleran margin, the Central Andean Plateau (CAP) as defined by the 3 km elevation contour is second only to the Tibetan Plateau in geographic extent. The uplift history of the 4 km high Plateau remains uncertain with paleoelevation studies along the CAP suggesting a complex, non-uniform uplift history. As part of the Central Andean Uplift and the Geodynamics of High Topography (CAUGHT) project, we use surface waves measured from ambient noise and two-plane wave tomography to image the S-wave velocity structure of the crust and upper mantle to investigate the upper mantle component of plateau uplift. We observe three main features in our S-wave velocity model including (1), a high velocity slab (2), a low velocity anomaly above the slab where the slab changes dip from near horizontal to a normal dip, and (3), a high-velocity feature in the mantle above the slab that extends along the length of the Altiplano from the base of the Moho to a depth of ~120 km with the highest velocities observed under Lake Titicaca. A strong spatial correlation exists between the lateral extent of this high-velocity feature beneath the Altiplano and the lower elevations of the Altiplano basin suggesting a potential relationship. Non-uniqueness in our seismic models preclude uniquely constraining this feature as an uppermost mantle feature bellow the Moho or as a connected eastward dipping feature extending up to 300 km in the mantle as seen in deeper mantle tomography studies. Determining if the high velocity feature represents a small lithospheric root or a delaminating lithospheric root extending ~300 km into the mantle requires more integration of observations, but either interpretation shows a strong geodynamic connection with the uppermost mantle and the current topography of the northern CAP.

Nuclear localization of the mitochondrial ncRNAs in normal and cancer cells.

Science.gov (United States)

Landerer, Eduardo; Villegas, Jaime; Burzio, Veronica A; Oliveira, Luciana; Villota, Claudio; Lopez, Constanza; Restovic, Franko; Martinez, Ronny; Castillo, Octavio; Burzio, Luis O

2011-08-01

We have previously shown a differential expression of a family of mitochondrial ncRNAs in normal and cancer cells. Normal proliferating cells and cancer cells express the sense mitochondrial ncRNA (SncmtRNA). In addition, while normal proliferating cells express two antisense mitochondrial ncRNAs (ASncmtRNAs-1 and -2), these transcripts seem to be universally down-regulated in cancer cells. In situ hybridization (ISH) of some normal and cancer tissues reveals nuclear localization of these transcripts suggesting that they are exported from mitochondria. FISH and confocal microscopy, in situ digestion with RNase previous to ISH and electron microscopy ISH was employed to confirm the extra-mitochondrial localization of the SncmtRNA and the ASncmtRNAs in normal proliferating and cancer cells of human and mouse. In normal human kidney and mouse testis the SncmtRNA and the ASncmtRNAs were found outside the organelle and especially localized in the nucleus associated to heterochromatin. In cancer cells, only the SncmtRNA was expressed and was found associated to heterochromatin and nucleoli. The ubiquitous localization of these mitochondrial transcripts in the nucleus suggests that they are new players in the mitochondrial-nuclear communication pathway or retrograde signaling. Down regulation of the ASncmtRNAs seems to be an important step on neoplastic transformation and cancer progression.

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.

Gene expression signature of normal cell-of-origin predicts ovarian tumor outcomes.

Directory of Open Access Journals (Sweden)

Melissa A Merritt

Full Text Available The potential role of the cell-of-origin in determining the tumor phenotype has been raised, but not adequately examined. We hypothesized that distinct cells-of-origin may play a role in determining ovarian tumor phenotype and outcome. Here we describe a new cell culture medium for in vitro culture of paired normal human ovarian (OV and fallopian tube (FT epithelial cells from donors without cancer. While these cells have been cultured individually for short periods of time, to our knowledge this is the first long-term culture of both cell types from the same donors. Through analysis of the gene expression profiles of the cultured OV/FT cells we identified a normal cell-of-origin gene signature that classified primary ovarian cancers into OV-like and FT-like subgroups; this classification correlated with significant differences in clinical outcomes. The identification of a prognostically significant gene expression signature derived solely from normal untransformed cells is consistent with the hypothesis that the normal cell-of-origin may be a source of ovarian tumor heterogeneity and the associated differences in tumor outcome.

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...

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

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

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.

The 2016 Case for Mantle Plumes and a Plume-Fed Asthenosphere (Augustus Love Medal Lecture)

Science.gov (United States)

Morgan, Jason P.

2016-04-01

discrepancies between idealized plume/hotspot models and geochronological observations will also be briefly discussed. A further consequence of the existence of strong deep mantle plumes is that hot plume material should preferentially pond at the base of the lithosphere, draining towards and concentrating beneath the regions where the lithosphere is thinnest, and asthenosphere is being actively consumed to make new tectonic plates - mid-ocean ridges. This plume-fed asthenosphere hypothesis makes predictions for the structure of asthenosphere flow and anisotropy, patterns of continental edge-volcanism linked to lateral plume drainage at continental margins, patterns of cratonic uplift and subsidence linked to passage from hotter plume-influenced to cooler non-plume-influenced regions of the upper mantle, and variable non-volcanic versus volcanic modes of continental extension linked to rifting above '~1425K cool normal mantle' versus 'warm plume-fed asthenosphere' regions of upper mantle. These will be briefly discussed. My take-home message is that "Mantle Plumes are almost certainly real". You can safely bet they will be part of any successful paradigm for the structure of mantle convection. While more risky, I would also recommend betting on the potential reality of the paradigm of a plume-fed asthenosphere. This is still a largely unexplored subfield of mantle convection. Current observations remain very imperfect, but seem more consistent with a plume-fed asthenosphere than with alternatives, and computational and geochemical advances are making good, falsifiable tests increasingly feasible. Make one!

EXPRESSION OF CELLULAR ADHESION MOLECULES IN LANGERHANS CELL HISTIOCYTOSIS AND NORMAL LANGERHANS CELLS

NARCIS (Netherlands)

DEGRAAF, JH; TAMMINGA, RYJ; KAMPS, WA; TIMENS, W

1995-01-01

Langerhans cell histiocytosis (LCH) is characterized by lesions with an accumulation and/or proliferation of Langerhans cells (LCs). Little is known of the etiology and pathogenesis of LCH. Although the relation between the LCH cell and normal LCs is currently uncertain, the localizations of the LCH

Crust and mantle of the gulf of Mexico

Science.gov (United States)

Moore, G.W.

1972-01-01

A SEEMING paradox has puzzled investigators of the crustal structure of the Gulf of Mexico since Ewing et al.1 calculated that a unit area of the rather thick crust in the gulf contains less mass than does a combination of the crust and enough of the upper mantle to make a comparable thickness in the Atlantic Ocean. They also noted that the free-air gravity of the gulf is essentially normal and fails by a large factor to be low enough to reflect the mass difference that they calculated. We propose a solution to this problem. ?? 1972 Nature Publishing Group.

Widespread melt/rock interaction and seismic properties of the lithosphere above mantle plumes: A petrological and microstructural study of mantle xenoliths from French Polynesia

Science.gov (United States)

Tommasi, A.; Godard, M.

2002-12-01

In addition to thermal erosion, plume/lithosphere interaction may induce significant changes in the lithosphere chemical composition. To constrain the extent of this process in an oceanic environment and its consequences on the lithosphere seismic properties, we studied the relationship between petrological processes and microstructure in mantle xenoliths from the Austral-Cook, Society and Marquesas islands. Olivine forsterite contents in our sp-peridotites vary continuously from Fo91 to Fo83, the lowest Fo being observed in dunites and wehrlites. Yet, their high Ni content (up to 2500 ppm) precludes a cumulate origin. These rocks are rather interpreted as resulting from melt/rock reactions involving olivine precipitation and pyroxene dissolution, the dunites indicating high melt-rock ratios. Moreover, wehrlites display poikiloblastic diopside enclosing corroded olivines. Late crystallization of clinopyroxene, also observed in lherzolites, may result from a near-solidus melt-freezing reaction occurring at the boundary of a partial melting domain developed at the expenses of lithospheric mantle. These data suggest that the lithosphere above a mantle plume undergoes a complex sequence of magmatic processes that significantly change its composition. Yet, crystal preferred orientations and thus seismic anisotropy are little affected by these processes. Lherzolites and harzburgites, independent from composition, show high-temperature porphyroclastic microstructures and strong olivine CPO. Although dunites and wehrlites display annealing microstructures to which is associated a progressive dispersion of the olivine CPO, very weak CPO are limited to a few dunites and wehrlites, suggesting that CPO destruction is restricted to domains of intense magma-rock interaction due to localized flow or accumulation of magmas. Conversely, the compositional changes result in lower seismic velocities for P- and S-waves. Relative to normal mantle, seismic anomalies may attain -2

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...

The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells.

Science.gov (United States)

Vander Griend, Donald J; Karthaus, Wouter L; Dalrymple, Susan; Meeker, Alan; DeMarzo, Angelo M; Isaacs, John T

2008-12-01

Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.

Prostate-Specific Natural Health Products (Dietary Supplements) Radiosensitize Normal Prostate Cells

International Nuclear Information System (INIS)

Hasan, Yasmin; Schoenherr, Diane; Martinez, Alvaro A.; Wilson, George D.; Marples, Brian

2010-01-01

Purpose: Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines. Methods and Materials: Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity was assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing γH2AX. Results: The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2μg/mL], Trinovin [10μg/mL], and Prostate Rx [50 μg/mL]). However, both Trinovin (10μg/mL) and Prostate Rx (6μg/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair. Conclusion: The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.

Comparison of the circadian variation in cell proliferation in normal and neoplastic colonic epithelial cells.

Science.gov (United States)

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-15

Circadian variations in cell proliferation in normal tissues have been recognised for many years but comparable phenomena in neoplastic tissues appear not to have been reported. Adenomas and carcinomas were induced in mouse colon by injection of dimethylhydrazine (DMH) and cell proliferation in these tumors was measured stathmokinetically. In normal intestine cell proliferation is fastest at night whereas in both adenomas and carcinomas it was found to be slower at night than in the middle of the day. Chemical sympathectomy was found to abolish the circadian variation in tumor cell proliferation.

CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species

International Nuclear Information System (INIS)

Hwang, Chae Young; Lee, Seung-Min; Park, Sung Sup; Kwon, Ki-Sun

2012-01-01

Highlights: ► H 2 O 2 differently adjusted senescence and proliferation in normal and cancer cells. ► H 2 O 2 exposure transiently decreased PCNA levels in normal cells. ► H 2 O 2 exposure transiently increased CDK2 activity in cancer cells. ► p21 Cip1 is likely dispensable when H 2 O 2 induces senescence in normal cells. ► Suggestively, CDK2 and PCNA play critical roles in H 2 O 2 -induced cell fate decision. -- Abstract: Reactive oxygen species modulate cell fate in a context-dependent manner. Sublethal doses of H 2 O 2 decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H 2 O 2 increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation. A CDK2 inhibitor, CVT-313, prevented H 2 O 2 -induced cancer cell proliferation. These results support the notion that the cyclin/CDK2/p21 Cip1 /PCNA complex plays an important role as a regulator of cell fate decisions.

Difference in membrane repair capacity between cancer cell lines and a normal cell line

DEFF Research Database (Denmark)

Frandsen, Stine Krog; McNeil, Anna K.; Novak, Ivana

2016-01-01

repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique...... cancer cell lines (p immortalized cell line (p

Regulation of heme metabolism in normal and sideroblastic bone marrow cells in culture

International Nuclear Information System (INIS)

Ibraham, N.G.; Lutton, J.D.; Hoffman, R.; Levere, R.D.

1985-01-01

Heme metabolism was examined in developing in vitro erythroid colonies (CFUE) and in bone marrow samples taken directly from four normal donors and four patients with sideroblastic anemia. Maximum activities of delta-aminolevulinic acid synthase (ALAS), ALA dehydratase (ALAD), and 14 C-ALA incorporation into heme were achieved in normal marrow CFUE after 8 days of culture, whereas heme oxygenase progressively decreased to low levels of activity during the same period. Assays on nucleated bone marrow cells taken directly from patients revealed that ALAS activity was considerably reduced in idiopathic sideroblastic anemia (IASA) and X-linked sideroblastic anemia (X-SA) bone marrow specimens, whereas the activity increased more than twofold (normal levels) when cells were assayed from 8-day CFUE. In all cases, ALAD activity appeared to be within normal levels. Measurement of heme synthesis revealed that normal levels of 14 C-ALA incorporation into heme were achieved in IASA cells but were reduced in X-SA cells. In marked contrast to levels in normal cells, heme oxygenase was found to be significantly elevated (two- to fourfold) in bone marrow cells taken directly from patients with IASA and X-SA. Results from this study demonstrate that IASA and X-SA bone marrow cells have disturbances in ALAS and heme metabolism, and that erythropoiesis (CFUE) can be restored to normal levels when cells are cultured in methylcellulose

Synthetic receiver function profiles through the upper mantle and the transition zone for upwelling scenarios

Science.gov (United States)

Nagel, Thorsten; Düsterhöft, Erik; Schiffer, Christian

2017-04-01

. This transition causes even lower seismic velocities with greater depth (following an adiabatic gradient), the highly continuous nature of the reaction, however, should produce only a smooth negative conversion. In contrast, a small positive conversion is expected at normal thermal gradients in the same depth range between 500 and 550 kilometers because of the wadsleyite-ringwoodite-transition. Hence, the polarity of the 520 discontinuity also offers a possibility to recognize the thermal state of the upper mantle.

Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy.

Science.gov (United States)

Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei

2015-12-01

The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease.

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

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

Science.gov (United States)

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

Low helium flux from the mantle inferred from simulations of oceanic helium isotope data

Science.gov (United States)

Bianchi, Daniele; Sarmiento, Jorge L.; Gnanadesikan, Anand; Key, Robert M.; Schlosser, Peter; Newton, Robert

2010-09-01

The high 3He/ 4He isotopic ratio of oceanic helium relative to the atmosphere has long been recognized as the signature of mantle 3He outgassing from the Earth's interior. The outgassing flux of helium is frequently used to normalize estimates of chemical fluxes of elements from the solid Earth, and provides a strong constraint to models of mantle degassing. Here we use a suite of ocean general circulation models and helium isotope data obtained by the World Ocean Circulation Experiment to constrain the flux of helium from the mantle to the oceans. Our results suggest that the currently accepted flux is overestimated by a factor of 2. We show that a flux of 527 ± 102 mol year - 1 is required for ocean general circulation models that produce distributions of ocean ventilation tracers such as radiocarbon and chlorofluorocarbons that match observations. This new estimate calls for a reevaluation of the degassing fluxes of elements that are currently tied to the helium fluxes, including noble gases and carbon dioxide.

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

Geochemical nature of sub-ridge mantle and opening dynamics of the South China Sea

Science.gov (United States)

Zhang, Guo-Liang; Luo, Qing; Zhao, Jian; Jackson, Matthew G.; Guo, Li-Shuang; Zhong, Li-Feng

2018-05-01

The Indian-type mantle (i.e., above the north hemisphere reference line on the plot of 208Pb/204Pb vs. 206Pb/204Pb) has been considered as a "Southern Hemisphere" geochemical signature, whose origin remains enigmatic. The South China Sea is an extensional basin formed after rifting of the Euro-Asia continent in the Northern Hemisphere, however, the geochemical nature of the igneous crust remains unexplored. For the first time, IODP Expedition 349 has recovered seafloor basalts covered by the thick sediments in the Southwest sub-basin (Sites U1433 and U1434) and the East sub-basin (Site U1431). The Southwest sub-basin consists of enriched (E)-MORB type basalts, and the East sub-basin consists of both normal (N)-MORB-type and E-MORB-type basalts based on trace element compositions. The basalts of the two sub-basins are Indian-type MORBs based on Sr-Nd-Pb-Hf isotope compositions, and the Southwest sub-basin basalts show isotopic compositions (i.e., 206Pb/204Pb of 17.59-17.89) distinctly different from the East sub-basin (i.e., 206Pb/204Pb of 18.38-18.57), suggesting a sub-basin scale mantle compositional heterogeneity and different histories of mantle compositional evolution. Two different enriched mantle end-members (EM1 and EM2) are responsible for the genesis of the Indian-type mantle in the South China Sea. We have modeled the influences of Hainan mantle plume and lower continental crust based on Sr-Nd-Pb-Hf isotope compositions. The results indicate that the influence of Hainan plume can explain the elevated 206Pb/204Pb of the East sub-basin basalts, and the recycling of lower continental crust can explain the low 206Pb/204Pb of the Southwest sub-basin basalts. Based on the strong geochemical imprints of Hainan plume in the ridge magmatism, we propose that the Hainan plume might have promoted the opening of the South China Sea, during which the Hainan plume contributed enriched component to the sub-ridge mantle and caused thermal erosion and return of lower

Cdx2 modulates proliferation in normal human intestinal epithelial crypt cells

International Nuclear Information System (INIS)

Escaffit, Fabrice; Pare, Frederic; Gauthier, Remy; Rivard, Nathalie; Boudreau, Francois; Beaulieu, Jean-Francois

2006-01-01

The homeobox gene Cdx2 is involved in the regulation of the expression of intestine specific markers such as sucrase-isomaltase and lactase-phlorizin hydrolase. Previous studies performed with immortalized or transformed intestinal cell lines have provided evidence that Cdx2 can promote morphological and functional differentiation in these experimental models. However, no data exist concerning the implication of this factor in normal human intestinal cell physiology. In the present work, we have investigated the role of Cdx2 in normal human intestinal epithelial crypt (HIEC) cells that lack this transcription factor. The establishment of HIEC cells expressing Cdx2 in an inducible manner shows that forced expression of Cdx2 significantly alters the proliferation of intestinal crypt cells and stimulates dipeptidylpeptidase IV expression but is not sufficient to trigger intestinal terminal differentiation. These observations suggest that Cdx2 requires additional factors to activate the enterocyte differentiation program in normal undifferentiated cells

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

Science.gov (United States)

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

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

Membrane associated ion transport enzymes in normal and transformed fibroblasts and epithelial cells

International Nuclear Information System (INIS)

Borek, C.

1982-01-01

In an effort to evaluate membrane changes associated with neoplastic transformation of fibroblasts and epithelial cells by radiation and chemicals, alterations in membrane-associated (Na + + K + )-ATPase and 5'-nucleotidase activities were investigated. Cell cultures consisted of normal and radiation transformed hamster embryo fibroblasts (HE) and mouse C3H 10T 1/2 fibroblasts, normal and chemically transformed adult rat liver epithelial cells (ARL), as well as hepatocarcinoma cells induced by the liver transformants. Transformed fibroblasts demonstrated a 1-2 fold increase in (Na + + K + )-ATPase activity over the normal, while the transformed liver epithelial cells and carcinoma cells showed a 60% and 40% decrease in activity compared to the normal values, respectively. The 5'-nucleotidase activity was 2 to 3 times higher in the transformed fibroblasts

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.

Equation of state fits to the lower mantle and outer core

Science.gov (United States)

Butler, R.; Anderson, D. L.

1978-01-01

The lower mantle and outer core are subjected to tests for homogeneity and adiabaticity. An earth model is used which is based on the inversion of body waves and Q-corrected normal-mode data. Homogeneous regions are found at radii between 5125 and 4825 km, 4600 and 3850 km, and 3200 and 2200 km. The lower mantle and outer core are inhomogeneous on the whole and are only homogeneous in the above local regions. Finite-strain and atomistic equations of state are fit to the homogeneous regions. The apparent convergence of the finite-strain relations is examined to judge their applicability to a given region. In some cases the observed pressure derivatives of the elastic moduli are used as additional constraints. The effect of minor deviations from adiabaticity on the extrapolations is also considered. An ensemble of zero-pressure values of the density and seismic velocities are found for these regions. The range of extrapolated values from these several approaches provides a measure of uncertainties involved.

Distinguishing normal cells from cancer cells via lysosome-targetable pH biomarkers with benzo[a]phenoxazine skeleton

Energy Technology Data Exchange (ETDEWEB)

Zhan, Yan-Hua [College of Chemistry, Chemical Engineering and Material Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, 199 Ren’Ai Road, Suzhou, 215123 (China); Li, Xiao-Jun [School of Radiation Medicine and Protection, Medicine College of Soochow University, Suzhou, 215123 (China); Sun, Ru, E-mail: sunru924@hotmail.com [College of Chemistry, Chemical Engineering and Material Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, 199 Ren’Ai Road, Suzhou, 215123 (China); Xu, Yu-Jie [School of Radiation Medicine and Protection, Medicine College of Soochow University, Suzhou, 215123 (China); Ge, Jian-Feng, E-mail: ge_jianfeng@hotmail.com [College of Chemistry, Chemical Engineering and Material Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, 199 Ren’Ai Road, Suzhou, 215123 (China); Jiangsu Key Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163 (China)

2016-08-24

In this paper, the design of a lysosome-targetable pH probe that has a fluorescent OFF (pH = 4) to ON (pH = 5–6) response is described to identify lysosomes in normal cells. The mechanism of photoinduced electron transfer with a fluorophore-based reaction (FBR-PET) was proposed. Benzo[a]phenoxazines with electro-donating aryl groups were selected, its (2,5-dimethoxyphenyl)imino-, (2-hydroxyphenyl)imino- and (2-hydroxy-5-methoxyphenyl)- imino-derivatives (probes 1a−c) were prepared and their optical responses towards pH were evaluated; their fluorescence pH titration experiments gave regularly changes with the increasing electro-donating abilities at the linked aryl groups, the (2-hydroxy-5-methoxyphenyl)iminobenzo[a]phenoxazine (probe 1c) exhibited a nearly OFF−ON response at 580–800 nm. All probes were reversible, and they showed excellent selectivity toward the proton over other competitive species. Fluorescence confocal images were performed with HeLa, KB cancer cells and V79 normal cells, probes 1a−c are all lysosome-targetable pH probes, and benzo[a]phenoxazine with (2-hydroxy-5-methoxyphenyl)imino-group (probe 1c) has potential applications in selective differentiation of normal cells from cancer cells. - Highlights: • pH probes for lysosome detection in normal cells. • Differentiation of normal cells from cancer cells by lysosome-biomarker. • The PET mechanism promoted by fluorophore based reactions (FBR-PET).

Distinguishing normal cells from cancer cells via lysosome-targetable pH biomarkers with benzo[a]phenoxazine skeleton

International Nuclear Information System (INIS)

Zhan, Yan-Hua; Li, Xiao-Jun; Sun, Ru; Xu, Yu-Jie; Ge, Jian-Feng

2016-01-01

In this paper, the design of a lysosome-targetable pH probe that has a fluorescent OFF (pH = 4) to ON (pH = 5–6) response is described to identify lysosomes in normal cells. The mechanism of photoinduced electron transfer with a fluorophore-based reaction (FBR-PET) was proposed. Benzo[a]phenoxazines with electro-donating aryl groups were selected, its (2,5-dimethoxyphenyl)imino-, (2-hydroxyphenyl)imino- and (2-hydroxy-5-methoxyphenyl)- imino-derivatives (probes 1a−c) were prepared and their optical responses towards pH were evaluated; their fluorescence pH titration experiments gave regularly changes with the increasing electro-donating abilities at the linked aryl groups, the (2-hydroxy-5-methoxyphenyl)iminobenzo[a]phenoxazine (probe 1c) exhibited a nearly OFF−ON response at 580–800 nm. All probes were reversible, and they showed excellent selectivity toward the proton over other competitive species. Fluorescence confocal images were performed with HeLa, KB cancer cells and V79 normal cells, probes 1a−c are all lysosome-targetable pH probes, and benzo[a]phenoxazine with (2-hydroxy-5-methoxyphenyl)imino-group (probe 1c) has potential applications in selective differentiation of normal cells from cancer cells. - Highlights: • pH probes for lysosome detection in normal cells. • Differentiation of normal cells from cancer cells by lysosome-biomarker. • The PET mechanism promoted by fluorophore based reactions (FBR-PET).

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.

Three-dimensional telomere architecture of esophageal squamous cell carcinoma: comparison of tumor and normal epithelial cells.

Science.gov (United States)

Sunpaweravong, S; Sunpaweravong, P; Sathitruangsak, C; Mai, S

2016-05-01

Telomeres are repetitive nucleotide sequences (TTAGGG)n located at the ends of chromosomes that function to preserve chromosomal integrity and prevent terminal end-to-end fusions. Telomere loss or dysfunction results in breakage-bridge-fusion cycles, aneuploidy, gene amplification and chromosomal rearrangements, which can lead to genomic instability and promote carcinogenesis. Evaluating the hypothesis that changes in telomeres contribute to the development of esophageal squamous cell carcinoma (ESCC) and to determine whether there are differences between young and old patients, we compared the three-dimensional (3D) nuclear telomere architecture in ESCC tumor cells with that of normal epithelial cells obtained from the same patient. Patients were equally divided by age into two groups, one comprising those less than 45 years of age and the other consisting of those over 80 years of age. Tumor and normal epithelial cells located at least 10 cm from the border of the tumor were biopsied in ESCC patients. Hematoxylin and eosin staining was performed for each sample to confirm and identify the cancer and normal epithelial cells. This study was based on quantitative 3D fluorescence in situ hybridization (Q-FISH), 3D imaging and 3D analysis of paraffin-embedded slides. The 3D telomere architecture data were computer analyzed using 100 nuclei per slide. The following were the main parameters compared: the number of signals (number of telomeres), signal intensity (telomere length), number of telomere aggregates, and nuclear volume. Tumor and normal epithelial samples from 16 patients were compared. The normal epithelial cells had more telomere signals and higher intensities than the tumor cells, with P-values of P architecture and found no statistically significant differences in any parameter tested between the young and old patients in either the tumor or epithelial cells. The 3D nuclear telomeric signature was able to detect differences in telomere architecture

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

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.)

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.

Normalization of cell responses in cat striate cortex

Science.gov (United States)

Heeger, D. J.

1992-01-01

Simple cells in the striate cortex have been depicted as half-wave-rectified linear operators. Complex cells have been depicted as energy mechanisms, constructed from the squared sum of the outputs of quadrature pairs of linear operators. However, the linear/energy model falls short of a complete explanation of striate cell responses. In this paper, a modified version of the linear/energy model is presented in which striate cells mutually inhibit one another, effectively normalizing their responses with respect to stimulus contrast. This paper reviews experimental measurements of striate cell responses, and shows that the new model explains a significantly larger body of physiological data.

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,

Radiosensitivity of normal human epidermal cells in culture

International Nuclear Information System (INIS)

Dover, R.; Potten, C.S.

1983-01-01

Using an in vitro culture system the authors have derived #betta#-radiation survival curves over a dose range 0-8 Gy for the clonogenic cells of normal human epidermis. The culture system used allows the epidermal cells to stratify and form a multi-layered sheet of keratinizing cells. The cultures appear to be a very good model for epidermis in vivo. The survival curves show a population which is apparently more sensitive than murine epidermis in vivo. It remains unclear whether this is an intrinsic difference between the species or is a consequence of the in vitro cultivation of the human cells. (author)

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

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

Plurihormonal cells of normal anterior pituitary: Facts and conclusions.

Science.gov (United States)

Mitrofanova, Lubov B; Konovalov, Petr V; Krylova, Julia S; Polyakova, Victoria O; Kvetnoy, Igor M

2017-04-25

plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment.

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

Mantle Serpentinization near the Central Mariana Trench Constrained by Ocean Bottom Surface Wave Observations

Science.gov (United States)

Cai, C.; Wiens, D. A.; Lizarralde, D.; Eimer, M. O.; Shen, W.

2017-12-01

We investigate the crustal and uppermost mantle seismic structure across the Mariana trench by jointly inverting Rayleigh wave phase and group velocities from ambient noise and longer period phase velocities from Helmholtz tomography of teleseismic waveforms. We use data from a temporary deployment in 2012-2013, consisting of 7 island-based stations and 20 broadband ocean bottom seismographs, as well as data from the USGS Northern Mariana Islands Seismograph Network. To avoid any potential bias from the starting model, we use a Bayesian Monte-Carlo algorithm to invert for the azimuthally-averaged SV-wave velocity at each node. This method also allows us to apply prior constraints on crustal thickness and other parameters in a systematic way, and to derive formal estimates of velocity uncertainty. The results show the development of a low velocity zone within the incoming plate beginning about 80 km seaward of the trench axis, consistent with the onset of bending faults from bathymetry and earthquake locations. The maximum depth of the velocity anomaly increases towards the trench, and extends to about 30 km below the seafloor. The low velocities persist after the plate is subducted, as a 20-30 km thick low velocity layer with a somewhat smaller velocity reduction is imaged along the top of the slab beneath the forearc. An extremely low velocity zone is observed beneath the serpentine seamounts in the outer forearc, consistent with 40% serpentinization in the forearc mantle wedge. Azimuthal anisotropy results show trench parallel fast axis within the incoming plate at uppermost mantle depth (2%-4% anisotropy). All these observations suggest the velocity reduction in the incoming plate prior to subduction results from both serpentinized normal faults and water-filled cracks. Water is expelled from the cracks early in subduction, causing a modest increase in the velocity of the subducting mantle, and moves upward and causes serpentinization of the outer forearc

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

Olfactory granule cell development in normal and hyperthyroid rats.

Science.gov (United States)

Brunjes, P C; Schwark, H D; Greenough, W T

1982-10-01

Dendritic development was examined in olfactory bulbs of both normal 7-, 14-, 21- and 60-day-old rats and littermates treated on postnatal days 1-4 with 1 microgram/g body weight of L-thyroxine sodium. Tissue was processed via the Golgi-Cox technique and subjected to quantitative analyses of mitral and internal layer granule cell development. These populations of granule cells were selected because their pattern of late proliferation suggested potentially greater susceptibility to postnatal hormonal alterations. Although neonatal hyperthyroidism induces widespread acceleration of maturation, including precocious chemosensitivity, granule cell development was unaffected relative to littermate controls. Both normal and hyperthyroid groups exhibited an inverted U-shaped pattern of cellular development, with rapid dendritic dendritic growth and expansion occurring during the earliest ages tested, but with loss of processes and dendritic field size occurring after day 21.

Cell renewal of glomerular cell types in normal rats. An autoradiographic analysis

International Nuclear Information System (INIS)

Pabst, R.; Sterzel, R.B.

1983-01-01

Normal adult Sprague-Dawley rats received either a single or repetitive injection of the DNA precursor 3 H-thymidine ( 3 H-TdR). For autoradiography semi-thin sections were prepared 2 hr to 14 days after labeling. The majority of labeled cells noted in glomerular tufts were endothelial cells. Mesangial cells had a lower production rate. Podocytes revealed no evidence of proliferation. Bowman's capsule cells showed a higher labeling index than tuft cells at all times. Neither the urinary nor the vascular pole was found to be a proliferative zone for Bowman's capsule cells. The flash and repetitive labeling experiments demonstrated a constant rate of cell renewal of about 1% per day, resulting in a long life span for endothelial and mesangial cells as well as Bowman's capsule cells. These data provide a basis for cell kinetic studies in models of glomerular diseases

Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells.

Directory of Open Access Journals (Sweden)

Clementina Sansone

Full Text Available Diatoms are an important class of unicellular algae that produce bioactive polyunsaturated aldehydes (PUAs that induce abortions or malformations in the offspring of invertebrates exposed to them during gestation. Here we compare the effects of the PUAs 2-trans,4-trans-decadienal (DD, 2-trans,4-trans-octadienal (OD and 2-trans,4-trans-heptadienal (HD on the adenocarcinoma cell lines lung A549 and colon COLO 205, and the normal lung/brunch epithelial BEAS-2B cell line. Using the viability MTT/Trypan blue assays, we show that PUAs have a toxic effect on both A549 and COLO 205 tumor cells but not BEAS-2B normal cells. DD was the strongest of the three PUAs tested, at all time-intervals considered, but HD was as strong as DD after 48 h. OD was the least active of the three PUAs. The effect of the three PUAs was somewhat stronger for A549 cells. We therefore studied the death signaling pathway activated in A549 showing that cells treated with DD activated Tumor Necrosis Factor Receptor 1 (TNFR1 and Fas Associated Death Domain (FADD leading to necroptosis via caspase-3 without activating the survival pathway Receptor-Interacting Protein (RIP. The TNFR1/FADD/caspase pathway was also observed with OD, but only after 48 h. This was the only PUA that activated RIP, consistent with the finding that OD causes less damage to the cell compared to DD and HD. In contrast, cells treated with HD activated the Fas/FADD/caspase pathway. This is the first report that PUAs activate an extrinsic apoptotic machinery in contrast to other anticancer drugs that promote an intrinsic death pathway, without affecting the viability of normal cells from the same tissue type. These findings have interesting implications also from the ecological viewpoint considering that HD is one of the most common PUAs produced by diatoms.

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

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.

Small copper fixed-point cells of the hybrid type to be used in place of normal larger cells

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Battuello, M.; Girard, F.; Florio, M.

2012-10-01

Two small cells for the realization of the fixed point of copper were constructed and investigated at INRIM. They are of the same hybrid design generally adopted for the eutectic high-temperature fixed-point cells, namely a structure with a sacrificial graphite sleeve and a layer of flexible carbon-carbon composite sheet (C/C sheet). Because of the largely different design with respect to the cells normally adopted for the construction of pure metal fixed points, they were compared and characterized with respect to the normal cells used at INRIM for the ITS-90 realization. Two different furnaces were used to compare hybrid and normal cells. One of the hybrid cells was also used in different configurations, i.e. without the C/C sheet and with two layers of sheet. The cells were compared with different operative conditions, i.e. temperature settings of the furnaces for inducing the freeze, and repeatability and reproducibility were investigated. Freezing temperature and shape of the plateaux obtained under the different conditions were analysed. As expected the duration of the plateaux obtained with the hybrid cells is considerably shorter than with the normal cell, but this does not affect the results in terms of freezing temperature. Measurements with the modified cell showed that the use of a double C/C sheet may improve both repeatability and reproducibility of the plateaux.

Small copper fixed-point cells of the hybrid type to be used in place of normal larger cells

International Nuclear Information System (INIS)

Battuello, M; Girard, F; Florio, M

2012-01-01

Two small cells for the realization of the fixed point of copper were constructed and investigated at INRIM. They are of the same hybrid design generally adopted for the eutectic high-temperature fixed-point cells, namely a structure with a sacrificial graphite sleeve and a layer of flexible carbon–carbon composite sheet (C/C sheet). Because of the largely different design with respect to the cells normally adopted for the construction of pure metal fixed points, they were compared and characterized with respect to the normal cells used at INRIM for the ITS-90 realization. Two different furnaces were used to compare hybrid and normal cells. One of the hybrid cells was also used in different configurations, i.e. without the C/C sheet and with two layers of sheet. The cells were compared with different operative conditions, i.e. temperature settings of the furnaces for inducing the freeze, and repeatability and reproducibility were investigated. Freezing temperature and shape of the plateaux obtained under the different conditions were analysed. As expected the duration of the plateaux obtained with the hybrid cells is considerably shorter than with the normal cell, but this does not affect the results in terms of freezing temperature. Measurements with the modified cell showed that the use of a double C/C sheet may improve both repeatability and reproducibility of the plateaux. (paper)

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

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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

CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

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Mariam El-Ashmawy

Full Text Available Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs. In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF = 1.3, and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

Late Miocene extensional systems in northern Tunisia and their relation with SE directed delamination of the African subcontinental mantle lithosphere

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Booth-Rea, Guillermo; Gaidi, Seif; Melki, Fetheddine; Pérez-Peña, Vicente; Marzougui, Wissem; Azañón, Jose Miguel; Galve, Jorge Pedro

2017-04-01

Recent work has proposed the delamination of the subcontinental mantle lithosphere under northern Tunisia during the late Miocene. This process is required to explain the present location of the Tunisian segment of the African slab, imaged by seismic tomography, hanging under the Gulf of Gabes to the south of Tunisia. Thus, having retreated towards the SE several hundred km from its original position under the Tellian-Atlas nappe contact that crops out along the north of Tunisia. However, no tectonic structures have been described which could be related to this mechanism of lithospheric mantle peeling. Here we describe for the first time extensional fault systems in northern Tunisia that strongly thinned the Tellian nappes, exhuming rocks from the Tunisian Atlas in the core of folded extensional detachments. Two normal fault systems with sub-orthogonal extensional transport occur. These were active during the late Miocene associated to the extrusion of 13 Ma granodiorite and 9 Ma rhyodacite in the footwall of the Nefza detachment. We have differentiated an extensional system formed by low-angle normal faults with NE- and SW-directed transport cutting through the Early to Middle Miocene Tellian nappen stack and a later system of low and high-angle normal faults that cuts down into the underlying Tunisian Atlas units with SE-directed transport, which root in the Nefza detachment. Both normal fault systems have been later folded and cut by thrusts during Plio-Quaternary NW-SE directed compression. These findings change the interpretation of the tectonic evolution of Tunisia that has always been framed in a transpressive to compressive setting, manifesting the extensional effects of Late Miocene lithospheric mantle delamination under northern Tunisia.

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

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Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. Materials and methods We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. Results We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Conclusion Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment. PMID:28418929

Vesicles mimicking normal and cancer cell membranes exhibit differential responses to the cell-penetrating peptide Pep-1.

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Almarwani, Bashiyar; Phambu, Esther Nzuzi; Alexander, Christopher; Nguyen, Ha Aimee T; Phambu, Nsoki; Sunda-Meya, Anderson

2018-06-01

The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the blue shift of its maximal emission wavelength. DSC data show that Pep-1 induces segregation of lipids. At high peptide concentration, IR data indicate that the interaction of Pep-1 is relatively stronger with normal cell membrane than with cancer cell membrane through the phosphate groups, while the interaction is weaker with normal cell membrane than with cancer cell membrane through the carbonyl groups. TGA and DSC data reveal that vesicles of normal cell membrane are thermally more stable than vesicles of cancer cell membrane. This suggests that the additional lipid PS included in cancer cell membrane has a destabilizing effect on the membrane structure. SEM images reveal that Pep-1 form superstructures including spherical particles and fibrils in the presence of both model membranes. PS seems to enhance peptide transport across cellular membranes. The biophysical techniques in this study provide valuable insights into the properties of CPPs in drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Whole-mantle P-wave velocity structure and azimuthal anisotropy

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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

Water Distribution in the Continental and Oceanic Upper Mantle

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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

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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.

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

International Nuclear Information System (INIS)

Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

2012-01-01

Highlights: ► Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. ► Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. ► Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. ► Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.

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

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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?

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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

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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".

Raman Spectroscopy of DNA Packaging in Individual Human Sperm Cells distinguishes Normal from Abnormal Cells

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Huser, T; Orme, C; Hollars, C; Corzett, M; Balhorn, R

2009-03-09

Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

RON kinase isoforms demonstrate variable cell motility in normal cells.

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Greenbaum, Alissa; Rajput, Ashwani; Wan, Guanghua

2016-09-01

Aberrant RON (Recepteur d'Origine Nantais) tyrosine kinase activation causes the epithelial cell to evade normal growth pathways, resulting in unregulated cell proliferation, increased cell motility and decreased apoptosis. Wildtype (wt) RON has been shown to play a role in metastasis of epithelial malignancies. It presents an important potential therapeutic target for colorectal, breast, gastric and pancreatic cancer. Little is known about functional differences amongst RON isoforms RON155, RON160 and RON165. The purpose of this study was to determine the effect of various RON kinase isoforms on cell motility. Cell lines with stable expression of wtRON were generated by inserting the coding region of RON in pTagRFP (tagged red fluorescence protein plasmid). The expression constructs of RON variants (RON155, RON160 and RON165) were generated by creating a mutagenesis-based wtRON-pTag RFP plasmid and stably transfected into HEK 293 cells. The wound closure scratch assay was used to investigate the effect on cell migratory capacity of wild type RON and its variants. RON transfected cells demonstrated increased cell motility compared to HEK293 control cells. RON165 cell motility was significantly increased compared to RON160 (mean percentage of wound covered 37.37% vs. 32.40%; p = 0.03). RON tyrosine kinase isoforms have variable cell motility. This may reflect a difference in the behavior of malignant epithelial cells and their capacity for metastasis.

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

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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

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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

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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

The morphological classification of normal and abnormal red blood cell using Self Organizing Map

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Rahmat, R. F.; Wulandari, F. S.; Faza, S.; Muchtar, M. A.; Siregar, I.

2018-02-01

Blood is an essential component of living creatures in the vascular space. For possible disease identification, it can be tested through a blood test, one of which can be seen from the form of red blood cells. The normal and abnormal morphology of the red blood cells of a patient is very helpful to doctors in detecting a disease. With the advancement of digital image processing technology can be used to identify normal and abnormal blood cells of a patient. This research used self-organizing map method to classify the normal and abnormal form of red blood cells in the digital image. The use of self-organizing map neural network method can be implemented to classify the normal and abnormal form of red blood cells in the input image with 93,78% accuracy testing.

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

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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.

New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.

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Ghada Allan

Full Text Available sp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4, cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21(Waf1/Cip1. In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer.

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.)

Bioactive form of resveratrol in glioblastoma cells and its safety for normal brain cells

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Xiao-Hong Shu

2013-05-01

Full Text Available ABSTRACTBackground: Resveratrol, a plant polyphenol existing in grapes and many other natural foods, possesses a wide range of biological activities including cancer prevention. It has been recognized that resveratrol is intracellularly biotransformed to different metabolites, but no direct evidence has been available to ascertain its bioactive form because of the difficulty to maintain resveratrol unmetabolized in vivo or in vitro. It would be therefore worthwhile to elucidate the potential therapeutic implications of resveratrol metabolism using a reliable resveratrol-sensitive cancer cells.Objective: To identify the real biological form of trans-resveratrol and to evaluate the safety of the effective anticancer dose of resveratrol for the normal brain cells.Methods: The samples were prepared from the condition media and cell lysates of human glioblastoma U251 cells, and were purified by solid phase extraction (SPE. The samples were subjected to high performance liquid chromatography (HPLC and liquid chromatography/tandem mass spectrometry (LC/MS analysis. According to the metabolite(s, trans-resveratrol was biotransformed in vitro by the method described elsewhere, and the resulting solution was used to treat U251 cells. Meanwhile, the responses of U251 and primarily cultured rat normal brain cells (glial cells and neurons to 100μM trans-resveratrol were evaluated by multiple experimental methods.Results: The results revealed that resveratrol monosulfate was the major metabolite in U251 cells. About half fraction of resveratrol monosulfate was prepared in vitro and this trans-resveratrol and resveratrol monosulfate mixture showed little inhibitory effect on U251 cells. It is also found that rat primary brain cells (PBCs not only resist 100μM but also tolerate as high as 200μM resveratrol treatment.Conclusions: Our study thus demonstrated that trans-resveratrol was the bioactive form in glioblastoma cells and, therefore, the biotransforming

Continental smokers couple mantle degassing and distinctive microbiology within continents

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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

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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

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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

Thermally-Driven Mantle Plumes Reconcile Hot-spot Observations

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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.

Distinct p53 genomic binding patterns in normal and cancer-derived human cells

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Botcheva K.; McCorkle S. R.; McCombie W. R.; Dunn J. J.; Anderson C. W.

2011-12-15

We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

The effects of environmental deuterium on normal and neoplastic cultured cell development

International Nuclear Information System (INIS)

Bild, W.; Schuller, T.; Zhihai, Qin; Blankenstein, T.; Nastasa, V.; Haulica, I.

2000-01-01

The powdered culture media (RPMI - 1640) were reconstituted either with normal distilled water (150 ppm deuterium) either with deuterium - depleted water (DDW) in various concentrations (30, 60, 90 ppm) and sterilized by filtration with 0.2 μm filters. The cell lines used were NIH (normal mouse fibroblasts), RAG (mouse renal carcinoma) and TS/A (mouse mammary adenocarcinoma). In auxiliary tests, BAIBC mouse splenocytes in direct culture were used, stimulated for growth with concanavalin A or LPS (bacterial lipopolysaccharide). The estimation of the growth was made using the MTT assay or direct counting with trypan blue exclusion. The following results were obtained: Deuterium - depleted water had a stimulating effect on cell growth, the most important stimulating action being from the 90 ppm deuterium-water. The growth curves show, in a first phase, a stimulation of the rapid -growing neoplastic cells, followed by a slower growth of the normal cells. Amiloride 100 mM blocking of the Na + /K + membrane pump did not affect the cell growth curves, while the lansoprazole 100 mM blocking of the K + /H + ATP-ase brought the growth curves at the level of those with normal water. This might show an eventual involvement of the K + /H + antiport in the stimulating effects of the DDW. (authors)

Study of nuclear proteins in normal and xeroderma pigmentosum lymphoblastoid cells

International Nuclear Information System (INIS)

Amari, N.M.B.

1985-01-01

Nuclear histone and nonhistone (NHP) proteins from normal human and xeroderma pigmentosum, complementation group A (XP-A) lymphoblastoid cells were compared both qualitatively, quantitatively and for binding affinity for DNA. Histones and four NHP fractions (NHP/sub 1-4/) were isolated from purified cell nuclei. Binding affinity to [ 3 H] melanoma DNA of histones and each NHP fraction was then determined using gradient dialysis followed by a filter assay. Histones and each NHP fraction were then sub-fractionated by polyacrylamide gel electrophoresis. Densitometric scans of the separation of these proteins on the gels were qualitatively, and quantitatively analyzed and compared between the two cell lines. No qualitative or quantitative differences were observed between histones from XP-A or normal cells

Lithology and temperature: How key mantle variables control rift volcanism

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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

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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

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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

Natural killer activity and suppressor cells in irradiated mice repopulated with a mixture of cells from normal and 89Sr-treated donors

International Nuclear Information System (INIS)

Levy, E.M.; Kumar, V.; Bennett, M.

1981-01-01

Mice that have been injected with 89 Sr have fairly normal B and T cell function, but are abnormal in that they lack natural killer (NK) activity and other functions that require an intact bone marrow. These mice also have an increased potential for suppressor cell activity. We had previously shown that spleen cells from 89 Sr-treated mice could transfer low NK activity and increased suppressor cell function to lethally irradiated syngeneic recipients. To investigate the mechanisms involved in perpetuating these defects, groups of normal spleen or bone marrow cells. Recipients were assayed for their NK activity and suppressor cell function 5 to 14 wk later. it was found that the addition of normal cells in the donor inoculum resulted in normal NK activity. This indicates that low NK activity in 89 Sr-treated mice was not due to the presence of a suppressor cell that prevented NK cell generation. It was additionally found that low NK activity in recipient mice could be boosted by interferon inducers. This would indicate that NK activity in the recipients was not due to a lack of interferon-sensitive pre-NK cells. Suppressor cell function in recipient mice depended on the type and number of normal cells in the donor inoculum. Bone marrow cells were very efficient in overcoming the tendency to produce suppressor cells. It took approximately 20 times more normal spleen cells to produce the same results. The implications of these findings are discussed

Quantifying mantle structure and dynamics using plume tracing in seismic tomography

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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

Continental basalts record the crust-mantle interaction in oceanic subduction channel: A geochemical case study from eastern China

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Xu, Zheng; Zheng, Yong-Fei

2017-09-01

Continental basalts, erupted in either flood or rift mode, usually show oceanic island basalts (OIB)-like geochemical compositions. Although their depletion in Sr-Nd isotope compositions is normally ascribed to contributions from the asthenospheric mantle, their enrichment in large ion lithophile elements (LILE) and light rare earth elements (LREE) is generally associated with variable enrichments in the Sr-Nd isotope compositions. This indicates significant contributions from crustal components such as igneous oceanic crust, lower continental crust and seafloor sediment. Nevertheless, these crustal components were not incorporated into the mantle sources of continental basalts in the form of solidus rocks. Instead they were processed into metasomatic agents through low-degree partial melting in order to have the geochemical fractionation of the largest extent to achieve the enrichment of LILE and LREE in the metasomatic agents. Therefore, the mantle sources of continental basalts were generated by metasomatic reaction of the depleted mid-ocean ridge basalts (MORB) mantle with hydrous felsic melts. Nevertheless, mass balance considerations indicate differential contributions from the mantle and crustal components to the basalts. While the depleted MORB mantle predominates the budget of major elements, the crustal components predominate the budget of melt-mobile incompatible trace elements and their pertinent radiogenic isotopes. These considerations are verified by model calculations that are composed of four steps in an ancient oceanic subduction channel: (1) dehydration of the subducting crustal rocks at subarc depths, (2) anataxis of the dehydrated rocks at postarc depths, (3) metasomatic reaction of the depleted MORB mantle peridotite with the felsic melts to generate ultramafic metasomatites in the lower part of the mantle wedge, and (4) partial melting of the metasomatites for basaltic magmatism. The composition of metasomatites is quantitatively dictated by

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

CD4+ T Cell Activation and Vascular Normalization: Two Sides of the Same Coin?

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De Palma, Michele; Jain, Rakesh K

2017-05-16

Normalization of tumor blood vessels enhances the infiltration and functions of T cells. Tian et al. (2017) report that effector CD4 + T cells, in turn, support vascular normalization, highlighting intertwined roles for blood vessels and T cells in cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Obliquity histories of Earth and Mars: Influence of inertial and dissipative core-mantle coupling

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Bills, Bruce G.

1990-01-01

For both the Earth and Mars, secular variations in the angular separation of the spin axis from the orbit normal are suspected of driving major climatic changes. There is considerable interest in determining the amplitude and timing of these obliquity variations. If the orientation of the orbital plane were inertially fixed, and the planet were to act as a rigid body in it response to precessional torques, the spin axis would simply precess around the orbit at a fixed obliquity and at a uniform angular rate. The precession rate parameter depends on the principal moments of inertia and rotation rate of the perturbed body, and on the gravitational masses and semiminor axes of the perturbing bodies. For Mars, the precession rate is not well known, but probably lies in the interval 8 to 10 arcsec/year. Gravitational interactions between the planets lead to secular motions of the orbit planes. In the rigid body case, the spin axis still attempts to precess about the instantaneous orbit normal, but now the obliquity varies. The hydrostatic figure of a planet represents a compromise between gravitation, which attempts to attain spherical symmetry, and rotation, which prefers cylindrical symmetry. Due to their higher mean densities the cores of the Earth and Mars will be more nearly spherical than the outer layers of these planets. On short time scales it is appropriate to consider the core to be an inviscid fluid constrained to move with the ellipsoidal region bounded by the rigid mantle. The inertial coupling provided by this mechanism is effective whenever the ellipticicy of the container exceeds the ratio of precessional to rotational rates. If the mantle were actually rigid, this would be an extremely effective type of coupling. However, on sufficiently long time scales, the mantle will deform viscously and can accommodate the motions of the core fluid. A fundamentally different type of coupling is provided by electromagnetic or viscous torques. This type of coupling

A comparative study on the mast cells count in oral squamous cell carcinoma and normal oral mucosa

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Mahsa Dastpak

2015-03-01

Full Text Available Introduction: Oral squamous cell carcinoma (OSCC is one of the 10 most common malignant tumors and SCC accounts 94% of all oral malignancies. Mast cells are regarded as complex and multifunctional cells, playing a significant role in immunopathology . The aim of this study is to evaluate the number of mast cells in tissue sections of oral squamous cell carcinoma (OSCC in comparison with normal mucosa. Materials & Methods: Sixty paraffin-embedded specimens were obtained from the archives of the Department of Oral and Maxillofacial Pathology,dental school of Babol university of medical science (15 high grade,15 low grade and 30 Iritation Fibroma. Classification of OSCC cases was according to the BRODER`S malignancy grading system. Hematoxylin and Eosin-stained slides were re-evaluated before entering the samples in our study. Toluidine blue(1% staining was used to identify Mast cells in samples . We used SPSS software version 18 and one way ANOVA test for analyzing data. Results: The highest mast cell count was seen in normal tissue and it was higher in low grade OSCC in comparison with high grade, but the differences between groups weren’t statistically significant. The Mean count of mast cell between OSCC and normal oral mucosa was statistically significant different(p=0.019.We didn’t observe any statistically significant difference between Mast cell counts of control group and low grade OSCC . The same result was seen between high garde and low grade OSCC . The Mean mast cell count difference between male and female groups weren’t statistically significant. The Mean mast cell count difference between high grade OSCC and control group was significant (p<0.05. Conclusion: According to the results, the average amount of mast cells decreased in OSCC in comparison with normal oral mucosa . It does not seem that mast cells play an important role in tumor progression, although further study is needed. 

Long non-coding RNA profile in mantle cell lymphoma identifies a functional lncRNA ROR1-AS1 associated with EZH2/PRC2 complex

Science.gov (United States)

Hu, Guangzhen; Gupta, Shiv K.; Troska, Tammy P.; Nair, Asha; Gupta, Mamta

2017-01-01

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed. As a result, several novel lncRNAs were found significantly overexpressed in the MCL samples with lncRNA ROR1-AS1 the most significant one. We cloned the ROR1-AS1 lncRNA in expression vector and ectopically transfected in MCL cell lines. Results showed that overexpression of ROR1-AS1 lncRNA promoted growth of MCL cells while decreased sensitivity to the treatment with drugs ibrutinib and dexamethasone. ROR-AS1 overexpression also decreased the mRNA expression of P16 (P = 0.21), and SOX11 (p = 0.017), without much effect on P53, ATM and P14 mRNA. RNA-immunoprecipitation assays demonstrated high affinity binding of lncRNA ROR1-AS1 with EZH2 and SUZ12 proteins of the polycomb repressive complex-2 (PRC2). Suppressing EZH2 activity with pharmacological inhibitor GSK343 abolished binding of ROR1-AS1 with EZH2. Taken together, this study identified a functional lncRNA ROR-AS1 involved with regulation of gene transcription via associating with PRC2 complex, and may serve as a novel biomarker in MCL patients. PMID:29113297

Crustal and upper mantle investigations of the Caribbean-South American plate boundary

Science.gov (United States)

Bezada, Maximiliano J.

The evolution of the Caribbean --- South America plate boundary has been a matter of vigorous debate for decades and many questions remain unresolved. In this work, and in the framework of the BOLIVAR project, we shed light on some aspects of the present state and the tectonic history of the margin by using different types of geophysical data sets and techniques. An analysis of controlled-source traveltime data collected along a boundary-normal profile at ˜65°W was used to build a 2D P-wave velocity model. The model shows that the Caribbean Large Igenous Province is present offshore eastern Venezuela and confirms the uniformity of the velocity structure along the Leeward Antilles volcanic belt. In contrast with neighboring profiles, at this longitude we see no change in velocity structure or crustal thickness across the San Sebastian - El Pilar fault system. A 2D gravity modeling methodology that uses seismically derived initial density models was developed as part of this research. The application of this new method to four of the BOLIVAR boundary-normal profiles suggests that the uppermost mantle is denser under the South American continental crust and the island arc terranes than under the Caribbean oceanic crust. Crustal rocks of the island arc and extended island arc terranes of the Leeward Antilles have a relatively low density, given their P-wave velocity. This may be caused by low iron content, relative to average magmatic arc rocks. Finally, an analysis of teleseismic traveltimes with frequency-dependent kernels produced a 3D P-wave velocity perturbation model. The model shows the structure of the mantle lithosphere under the study area and clearly images the subduction of the Atlantic slab and associated partial removal of the lower lithosphere under northern South America. We also image the subduction of a section of the Caribbean plate under South America with an east-southeast direction. Both the Atlantic and Caribbean subducting slabs penetrate the

Executive Summary: “Mantle Frontier” Workshop

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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.

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

MUC-1-ESA+ progenitor cells in normal benign and malignant human breast epithelial cells

OpenAIRE

Lu, Xinquan; Li, Huixiang; Xu, Kejia; Nesland, Jahn M.; Suo, Zhenhe

2009-01-01

The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer ce...

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

Amniotic Fluid Cells Proliferation in Normal and Down Syndrome Subjects

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Honcea Adina

2016-02-01

Full Text Available Down Syndrome/Trisomy 21 is the most common chromosomal anomaly, and it represents the most common congenital cause of infants’ intellectual disability. Subjects with this syndrome are affected by degenerative processes caused by accelerated aging or unknown ethyologies. In recent years, accumulating evidence revealed increased potential of amniotic fluid-derived stem cells to be used in regenerative therapy. Our aim was to assess differences in immunophenotype, cell morphology and proliferation of amniotic fluid cells from normal and Down Syndrome pregnancies using a quantitative cytometry approach. Results revealed the emergence of a population of small sized cells in Down Syndrome derived amniotic fluid cells that are readily visible upon microscopic inspection. Hence, the fluorescence–based quantitative image cytometry determinations showed a tendency of decrease in both cell and nuclei size in trisomy, with no significant modification in nuclei circularity, as measured following actin cytoskeleton and nuclei labeling. The propensity of Ki67 positive cells was found to be increased in Down Syndrome derived cells (48.92% as compared to normal specimens (28.68%. However, cells in S and G2/M cell cycle phases decreased from 32.91% to 4.49% in diseased cells. Further studies are devoted to understanding the molecular basis of the observed differences in the proliferation ability of Down Syndrome amniotic cells, in order to evaluate the potential therapeutic effect of amniotic fluid stem cells for tissue regeneration in subjects with trisomy and to find correlations between amniotic cells phenotype and patient prognosis.

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

Single cell analysis of normal and leukemic hematopoiesis.

Science.gov (United States)

Povinelli, Benjamin J; Rodriguez-Meira, Alba; Mead, Adam J

2018-02-01

The hematopoietic system is well established as a paradigm for the study of cellular hierarchies, their disruption in disease and therapeutic use in regenerative medicine. Traditional approaches to study hematopoiesis involve purification of cell populations based on a small number of surface markers. However, such population-based analysis obscures underlying heterogeneity contained within any phenotypically defined cell population. This heterogeneity can only be resolved through single cell analysis. Recent advances in single cell techniques allow analysis of the genome, transcriptome, epigenome and proteome in single cells at an unprecedented scale. The application of these new single cell methods to investigate the hematopoietic system has led to paradigm shifts in our understanding of cellular heterogeneity in hematopoiesis and how this is disrupted in disease. In this review, we summarize how single cell techniques have been applied to the analysis of hematopoietic stem/progenitor cells in normal and malignant hematopoiesis, with a particular focus on recent advances in single-cell genomics, including how these might be utilized for clinical application. Copyright © 2017. Published by Elsevier Ltd.

Culture of normal human blood cells in a diffusion chamber system II. Lymphocyte and plasma cell kinetics

International Nuclear Information System (INIS)

Chikkappa, G.; Carsten, A.L.; Chanana, A.D.; Cronkite, E.P.

1979-01-01

Normal human blood leukocytes were cultured in Millipore diffusion chambers implanted into the peritoneal cavities of irradiated mice. The evaluation of survival and proliferation kinetics of cells in lymphyocytic series suggested that the lymphoid cells are formed from transition of small and/or large lymphocytes, and the lymphoblasts from the lymphoid cells. There was also evidence indicating that some of the cells in these two compartments are formed by proliferation. The evaluation of plasmacytic series suggested that the plasma cells are formed from plasmacytoid-lymphocytes by transition, and the latter from the transition of lymphocytes. In addition, relatively a small fraction of cells in these two compartments are formed by proliferation. mature plasma cells do not and immature plasma cells do proliferate. Estimation of magnitude of plasma cells formed in the cultures at day 18 indicated that at least one plasma cell is formed for every 6 normal human blood lymphocytes introduced into the culture

Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

NARCIS (Netherlands)

Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

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

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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.

Duchenne muscular dystrophy: normal ATP turnover in cultured cells

International Nuclear Information System (INIS)

Fox, I.H.; Bertorini, T.; Palmieri, G.M.A.; Shefner, R.

1986-01-01

This paper examines ATP metabolism in cultured muscle cells and fibroblasts from patients with Duchenne dystrophy. ATP and ADP levels were the same in cultured cells from normal subjects and patients and there was no difference in ATP synthesis or degradation. The ATP synthesis was measured by the incorporation of C 14-U-adenine into aTP and ADP. although there was a significant decrease in radioactively labelled ATP after incubation with deoxyglucose in Duchenne muscle cells, there was no difference in ATP concentration of ADP metabolism

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

GC-MS-Based Endometabolome Analysis Differentiates Prostate Cancer from Normal Prostate Cells

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Ana Rita Lima

2018-03-01

Full Text Available Prostate cancer (PCa is an important health problem worldwide. Diagnosis and management of PCa is very complex because the detection of serum prostate specific antigen (PSA has several drawbacks. Metabolomics brings promise for cancer biomarker discovery and for better understanding PCa biochemistry. In this study, a gas chromatography–mass spectrometry (GC-MS based metabolomic profiling of PCa cell lines was performed. The cell lines include 22RV1 and LNCaP from PCa with androgen receptor (AR expression, DU145 and PC3 (which lack AR expression, and one normal prostate cell line (PNT2. Regarding the metastatic potential, PC3 is from an adenocarcinoma grade IV with high metastatic potential, DU145 has a moderate metastatic potential, and LNCaP has a low metastatic potential. Using multivariate analysis, alterations in levels of several intracellular metabolites were detected, disclosing the capability of the endometabolome to discriminate all PCa cell lines from the normal prostate cell line. Discriminant metabolites included amino acids, fatty acids, steroids, and sugars. Six stood out for the separation of all the studied PCa cell lines from the normal prostate cell line: ethanolamine, lactic acid, β-Alanine, L-valine, L-leucine, and L-tyrosine.

Survival of human osteosarcoma cells and normal human fibroblasts following alpha particle irradiation

International Nuclear Information System (INIS)

Lloyd, E.L.; Gemmell, M.A.

1981-01-01

Cell survival of human osteosarcoma cells in culture following alpha particle irradiation is reported here for the first time. The osteosarcoma cell line (TE-85) is found to be less sensitive to inactivation by 5.6 MeV alpha particles (LET 86 keV/μm) than normal diploid human fibroblasts (NFS). Values for the mean lethal doses were estimated to be 103 rads for the TE-85 cells compared with 68 rads for the NFS cultures irradiated under identical conditions. It is postulated that the aneuploidy of the tumor cells with increased DNA chromosomal material may confer a selective advantage for the survival of tumor cells relative to normal cells with diploid chromosomes

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

Analysis of epothilone B-induced cell death in normal ovarian cells.

Science.gov (United States)

Rogalska, Aneta; Gajek, Arkadiusz; Marczak, Agnieszka

2013-12-01

We have investigated the mode of cell death induced by a new microtubule-stabilizing agent, epothilone B (EpoB, patupilone), and a clinically used medicine, paclitaxel (PTX), in normal ovarian cells. Using fluorescence microscopy, polyacrylamide gel electrophoresis preceding Western blot analysis, as well as spectrofluorimetric and colorimetric detection, we demonstrate that, compared to EpoB, PTX induced high time-dependent morphological and biochemical changes typical of apoptosis. Induction of apoptosis followed an early increase in p53 levels. Apoptosis reached its maximum at 24-48 h. At the same time, there was a significant increase in caspase-9 and -3 activity and PARP fragmentation, which suggests that an intrinsic path was involved. Apoptosis in MM14 cells was increased more by PTX than EpoB, and also induced more necrosis responsible for inflammation (1.4-fold) than EpoB. © 2013 International Federation for Cell Biology.

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

Seismic anisotropy and compositionally induced velocity anomalies in the lithosphere above mantle plumes: a petrological and microstructural study of mantle xenoliths from French Polynesia

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Tommasi, Andréa; Godard, Marguerite; Coromina, Guilhem; Dautria, Jean-Marie; Barsczus, Hans

2004-11-01

In addition to thermal erosion, plume/lithosphere interaction may induce significant changes in the lithosphere chemical composition. To constrain the extent of this process in an oceanic environment and its consequences on the lithosphere seismic properties, we investigated the relationship between petrological processes and microstructure in mantle xenoliths from different hotspots tracks in South Pacific Superswell region: the Austral-Cook, Society, and Marquesas islands in French Polynesia. Olivine forsterite contents in the studied spinel peridotites vary continuously from Fo91 to Fo83. Dunites and wehrlites display the lowest forsterite contents. Their microstructure and high Ni contents preclude a cumulate origin, suggesting that these rocks result from melt/rock reactions involving olivine precipitation and pyroxene dissolution. In addition, lherzolites and wehrlites display evidence of late crystallization of clinopyroxene, which may result from a near-solidus melt-freezing reaction. These data suggest that the lithosphere above a mantle plume undergoes a complex sequence of magmatic processes that significantly change its composition. These compositional changes, particularly iron enrichment in olivine, result in lower P- and S-waves velocities. Relative to normal lithospheric mantle, compositionally induced seismic anomalies may attain -2.2% for S-waves and -1% for P-waves. Smaller negative anomalies for P-waves are due to a higher sensitivity to modal composition. Conversely, crystal-preferred orientations (CPO) and seismic anisotropy are little affected by these processes. Lherzolites and harzburgites, independent from composition, show high-temperature porphyroclastic microstructures and strong olivine CPO. Dunites and wehrlites display annealing microstructures to which is associated a progressive dispersion of the olivine CPO. Very weak, almost random olivine CPO is nevertheless rare, suggesting that CPO destruction is restricted to domains of

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

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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.

Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas.

Science.gov (United States)

Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

2017-10-01

Pancreatic stellate cells (PSCs) play a central role as source of fibrogenic cells in pancreatic cancer and chronic pancreatitis. In contrast to quiescent hepatic stellate cells (qHSCs), a specific marker for quiescent PSCs (qPSCs) that can be used in formalin-fixed and paraffin embedded (FFPE) normal human pancreatic tissue has not been identified. The aim of this study was to identify a marker enabling the identification of qPSCs in normal human FFPE pancreatic tissue. Immunohistochemical (IHC), double-IHC, immunofluorescence (IF) and double-IF analyses were carried out using a tissue microarray consisting of cores with normal human pancreatic tissue. Cores with normal human liver served as control. Antibodies directed against adipophilin, α-SMA, CD146, CRBP-1, cytoglobin, desmin, GFAP, nestin, S100A4 and vinculin were examined, with special emphasis on their expression in periacinar cells in the normal human pancreas and perisinusoidal cells in the normal human liver. The immunolabelling capacity was evaluated according to a semiquantitative scoring system. Double-IF of the markers of interest together with markers for other periacinar cells was performed. Moreover, the utility of histochemical stains for the identification of human qPSCs was examined, and their ultrastructure was revisited by electron microscopy. Adipophilin, CRBP-1, cytoglobin and vinculin were expressed in qHSCs in the liver, whereas cytoglobin and adipophilin were expressed in qPSCs in the pancreas. Adipophilin immunohistochemistry was highly dependent on the preanalytical time interval (PATI) from removal of the tissue to formalin fixation. Cytoglobin, S100A4 and vinculin were expressed in periacinar fibroblasts (FBs). The other examined markers were negative in human qPSCs. Our data indicate that cytoglobin and adipophilin are markers of qPSCs in the normal human pancreas. However, the use of adipophilin as a qPSC marker may be limited due to its high dependence on optimal PATI

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.

Protection from intracellular oxidative stress by cytoglobin in normal and cancerous oesophageal cells.

Directory of Open Access Journals (Sweden)

Fiona E McRonald

Full Text Available Cytoglobin is an intracellular globin of unknown function that is expressed mostly in cells of a myofibroblast lineage. Possible functions of cytoglobin include buffering of intracellular oxygen and detoxification of reactive oxygen species. Previous work in our laboratory has demonstrated that cytoglobin affords protection from oxidant-induced DNA damage when over expressed in vitro, but the importance of this in more physiologically relevant models of disease is unknown. Cytoglobin is a candidate for the tylosis with oesophageal cancer gene, and its expression is strongly down-regulated in non-cancerous oesophageal biopsies from patients with TOC compared with normal biopsies. Therefore, oesophageal cells provide an ideal experimental model to test our hypothesis that downregulation of cytoglobin expression sensitises cells to the damaging effects of reactive oxygen species, particularly oxidative DNA damage, and that this could potentially contribute to the TOC phenotype. In the current study, we tested this hypothesis by manipulating cytoglobin expression in both normal and oesophageal cancer cell lines, which have normal physiological and no expression of cytoglobin respectively. Our results show that, in agreement with previous findings, over expression of cytoglobin in cancer cell lines afforded protection from chemically-induced oxidative stress but this was only observed at non-physiological concentrations of cytoglobin. In addition, down regulation of cytoglobin in normal oesophageal cells had no effect on their sensitivity to oxidative stress as assessed by a number of end points. We therefore conclude that normal physiological concentrations of cytoglobin do not offer cytoprotection from reactive oxygen species, at least in the current experimental model.

Sub-cellular force microscopy in single normal and cancer cells.

Science.gov (United States)

Babahosseini, H; Carmichael, B; Strobl, J S; Mahmoodi, S N; Agah, M

2015-08-07

This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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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.

Patterns of proliferation and differentiation of irradiated haemopoietic stem cells cultured on normal 'stromal' cell colonies in vitro

International Nuclear Information System (INIS)

Mori, K.J.

1981-01-01

Experiments were designed to elucidate whether or not the irradiated bone marrow cells receive any stimulation for the self-replication and differentiation from normal 'stromal' cell colonies in the bone marrow cell culture in vitro. When irradiated or unirradiated bone marrow cells were overlaid on the normal adherent cell colonies, the proliferation of haemopoietic stem cells was supported, the degree of the stimulation depending on the starting cellular concentration. There was, however, no significant changes in the concentration of either CFUs or CFUc regardless of the dose of irradiation on the bone marrow cells overlaid. This was a great contrast to the dose-dependent decrease of CFUs or CFUc within the culture in which both the stem cells and stromal cells were simultaneously irradiated. These results suggest that the balance of self-replication and differentiation of the haemopoietic stem cells is affected only when haemopoietic microenvironment is perturbed. (author)

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

DEFF Research Database (Denmark)

Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

2014-01-01

to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

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)

Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells.

Science.gov (United States)

Burzio, Verónica A; Villota, Claudio; Villegas, Jaime; Landerer, Eduardo; Boccardo, Enrique; Villa, Luisa L; Martínez, Ronny; Lopez, Constanza; Gaete, Fancy; Toro, Viviana; Rodriguez, Ximena; Burzio, Luis O

2009-06-09

We reported the presence in human cells of a noncoding mitochondrial RNA that contains an inverted repeat (IR) of 815 nucleotides (nt) covalently linked to the 5' end of the mitochondrial 16S RNA (16S mtrRNA). The transcript contains a stem-loop structure and is expressed in human proliferating cells but not in resting cells. Here, we demonstrate that, in addition to this transcript, normal human proliferating cells in culture express 2 antisense mitochondrial transcripts. These transcripts also contain stem-loop structures but strikingly they are down-regulated in tumor cell lines and tumor cells present in 17 different tumor types. The differential expression of these transcripts distinguishes normal from tumor cells and might contribute a unique vision on cancer biology and diagnostics.

visnormsc: A Graphical User Interface to Normalize Single-cell RNA Sequencing Data.

Science.gov (United States)

Tang, Lijun; Zhou, Nan

2017-12-26

Single-cell RNA sequencing (RNA-seq) allows the analysis of gene expression with high resolution. The intrinsic defects of this promising technology imports technical noise into the single-cell RNA-seq data, increasing the difficulty of accurate downstream inference. Normalization is a crucial step in single-cell RNA-seq data pre-processing. SCnorm is an accurate and efficient method that can be used for this purpose. An R implementation of this method is currently available. On one hand, the R package possesses many excellent features from R. On the other hand, R programming ability is required, which prevents the biologists who lack the skills from learning to use it quickly. To make this method more user-friendly, we developed a graphical user interface, visnormsc, for normalization of single-cell RNA-seq data. It is implemented in Python and is freely available at https://github.com/solo7773/visnormsc . Although visnormsc is based on the existing method, it contributes to this field by offering a user-friendly alternative. The out-of-the-box and cross-platform features make visnormsc easy to learn and to use. It is expected to serve biologists by simplifying single-cell RNA-seq normalization.

Corneal endothelial cell density and morphology in normal Iranian eyes

Directory of Open Access Journals (Sweden)

Fallah Mohammad

2006-03-01

Full Text Available Abstract Background We describe corneal endothelial cell density and morphology in normal Iranian eyes and compare endothelial cell characteristics in the Iranian population with data available in the literature for American and Indian populations. Methods Specular microscopy was performed in 525 eyes of normal Iranian people aged 20 to 85 years old. The studied parameters including mean endothelial cell density (MCD, mean cell area (MCA and coefficient of variation (CV in cell area were analyzed in all of the 525 eyes. Results MCD was 1961 ± 457 cell/mm2 and MCA was 537.0 ± 137.4 μm2. There was no statistically significant difference in MCD, MCA and CV between genders (Student t-test, P = 0.85, P = 0.97 and P = 0.15 respectively. There was a statistically significant decrease in MCD with age (P r = -0.64. The rate of cell loss was 0.6% per year. There was also a statistically significant increase in MCA (P r = 0.56 and CV (P r = 0.30 from 20 to 85 years of age. Conclusion The first normative data for the endothelium of Iranian eyes seems to confirm that there are no differences in MCD, MCA and CV between genders. Nevertheless, the values obtained in Iranian eyes seem to be different to those reported by the literature in Indian and American populations.

Studies by radioiodination of normal adult, fetal and leukemic cell membranes

Energy Technology Data Exchange (ETDEWEB)

Kannourakis, G; Cauchi, M N [Department of Pathology and Immunology, Monash Medical School, Melbourne, Australia

1978-01-01

A comparison was made between cord blood lymphocytes, normal adult lymphocytes and leukemic cells after membrane iodination with lactoperoxidase. A double-labeling technique using lactoperoxidase iodination with /sup 125/I and /sup 131/I followed by analysis on polyacrylamide gel electrophoresis revealed a number of membrane differences between leukemic, normal and fetal cells. There was a reduction in the 70,000 molecular weight component in cord blood cells compared to adult lymphocytes, and an increase in membrane peptides with molecular weights of 35,000, 20,000, 9,000 and 4,000. Although smaller molecular weight peptides were also present in chronic lymphatic leukemia as well as acute myeloid leukemia, these were shown to be distinct from fetal type membrane components.

Clinical and Pathologic Study of Feline Merkel Cell Carcinoma With Immunohistochemical Characterization of Normal and Neoplastic Merkel Cells.

Science.gov (United States)

Dohata, A; Chambers, J K; Uchida, K; Nakazono, S; Kinoshita, Y; Nibe, K; Nakayama, H

2015-11-01

The authors herein describe the morphologic and immunohistochemical features of normal Merkel cells as well as the clinicopathologic findings of Merkel cell carcinoma in cats. Merkel cells were characterized as vacuolated clear cells and were individually located in the epidermal basal layer of all regions examined. Clusters of Merkel cells were often observed adjacent to the sinus hair of the face and carpus. Immunohistochemically, Merkel cells were positive for cytokeratin (CK) 20, CK18, p63, neuron-specific enolase, synaptophysin, and protein gene product 9.5. Merkel cell carcinoma was detected as a solitary cutaneous mass in 3 aged cats (13 to 16 years old). On cytology, large lymphocyte-like cells were observed in all cases. Histologic examinations of surgically resected tumors revealed nests of round cells separated by various amounts of a fibrous stroma. Tumor cells were commonly immunopositive for CK20, CK18, p63, neuron-specific enolase, and synaptophysin, representing the characteristics of normal Merkel cells. © The Author(s) 2015.

Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy.

Science.gov (United States)

Canetta, Elisabetta; Riches, Andrew; Borger, Eva; Herrington, Simon; Dholakia, Kishan; Adya, Ashok K

2014-05-01

Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute viral infection.

Science.gov (United States)

Raué, Hans-Peter; Slifka, Mark K

2007-05-01

Previous studies have shown that T cells, which are genetically deficient in CTLA-4/CD152 expression, will proliferate uncontrollably, resulting in lethal autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical role in the negative regulation of effector T cell function. In contrast to expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression was associated with normal or even enhanced in vivo proliferation of virus-specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo, CTLA-4+ T cells also exhibited normal antiviral effector functions following stimulation with peptide-coated cells, virus-infected cells, plate-bound anti-CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector functions, at least not under the normal physiological conditions associated with either of these two acute viral infections.

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

Science.gov (United States)

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.

Science.gov (United States)

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.

JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.

Science.gov (United States)

McMurtry, Vanity; Saavedra, Joseph E; Nieves-Alicea, René; Simeone, Ann-Marie; Keefer, Larry K; Tari, Ana M

2011-04-01

Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC50s of JS-K against the breast cancer cells ranged from 0.8 to 3 µM. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-µM concentration, and HMECs were unaffected by 10 µM JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective anti-tumor activity of JS-K warrants its further investigation in breast tumors.

RF Breakdown in Normal Conducting Single-cell Structures

CERN Document Server

Dolgashev, Valery A; Higo, Toshiyasu; Nantista, Christopher D; Tantawi, Sami G

2005-01-01

Operating accelerating gradient in normal conducting accelerating structures is often limited by rf breakdown. The limit depends on multiple parameters, including input rf power, rf circuit, cavity shape and material. Experimental and theoretical study of the effects of these parameters on the breakdown limit in full scale structures is difficult and costly. We use 11.4 GHz single-cell traveling wave and standing wave accelerating structures for experiments and modeling of rf breakdown behavior. These test structures are designed so that the electromagnetic fields in one cell mimic the fields in prototype multicell structures for the X-band linear collider. Fields elsewhere in the test structures are significantly lower than that of the single cell. The setup uses matched mode converters that launch the circular TM01 mode into short test structures. The test structures are connected to the mode launchers with vacuum rf flanges. This setup allows economic testing of different cell geometries, cell materials an...

Early episodes of high-pressure core formation preserved in plume mantle

Science.gov (United States)

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.

Modelling the possible interaction between edge-driven convection and the Canary Islands mantle plume

Science.gov (United States)

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

Normal endometrial stromal cells regulate 17β-estradiol-induced epithelial-mesenchymal transition via slug and E-cadherin in endometrial adenocarcinoma cells in vitro.

Science.gov (United States)

Zhang, Hui; Li, Hongyan; Qi, Shasha; Liu, Zhao; Fu, Yibing; Li, Mingjiang; Zhao, Xingbo

2017-01-01

Stroma-tumor communication participates in the pathogenesis of endometrial carcinomas. In previous studies, we found that normal stromal cells inhibited the growth of endometrial carcinoma cells. Here, we investigated the role of normal stromal cells in the epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells and explored the possible mechanism implied. We found that conditioned medium (CM) by normal endometrial stromal cells (NSC) reduced cell growth and induced cell apoptosis in Ishikawa cells. CM by NSC inhibited 17β-estradiol-induced cell growth and apoptosis decrease in Ishikawa cells. Moreover, CM by NSC inhibited the migration and invasion, and 17β-estradiol-induced migration and invasion in Ishikawa cells. Meanwhile, CM by NSC decreased Slug expression and 17β-estradiol-induced Slug expression, increased E-cadherin expression and abolished 17β-estradiol-induced E-cadherin reduction in Ishikawa cells. In conclusion, normal stromal factors can inhibit 17β-estradiol-induced cell proliferation and apoptosis inhibition, and abolished 17β-estradiol-induced EMT in endometrial cancer cell via regulating E-cadherin and Slug expression.

Ibrutinib Treatment of Mantle Cell Lymphoma Relapsing at Central Nervous System: A Case Report and Literature Review

Directory of Open Access Journals (Sweden)

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

Science.gov (United States)

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

Science.gov (United States)

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.

Gamma-ray excision repair in normal and diseased human cells

International Nuclear Information System (INIS)

Cerutti, P.A.; Remsen, J.F.

1976-01-01

Radiation products of the 5,6-dihydroxy-dihydrothymine type (t') are efficiently removed from the DNA during postirradiation incubation of bacterial and mammalian cells. In this chapter we describe the t'-excision system contained in normal human cells, in human carcinoma HeLa S-3 cells, and in skin fibroblasts from xeroderma pigmentosum (XP) and Fanconi's anemia (FA) patients. The latter diseases are characterized among other symptoms by a genetically increased susceptibility for the development of cancer

Phase transition and thermal equations of state of (Fe,Al)-bridgmanite and post-perovskite: Implication for the chemical heterogeneity at the lowermost mantle

Science.gov (United States)

Sun, Ningyu; Wei, Wei; Han, Shunjie; Song, Junhao; Li, Xinyang; Duan, Yunfei; Prakapenka, Vitali B.; Mao, Zhu

2018-05-01

In this study, we have determined the phase boundary between Mg0.735Fe0.21Al0.07Si0.965O3-Bm and PPv and the thermal equations of state of both phases up to 202 GPa and 2600 K using synchrotron X-ray diffraction in laser heated diamond anvil cells. Our experimental results have shown that the combined effect of Fe and Al produces a wide two-phase coexistence region with a thickness of 26 GPa (410 km) at 2200 K, and addition of Fe lowers the onset transition pressure to 98 GPa at 2000 K, consistent with previous experimental results. Furthermore, addition of Fe was noted to reduce the density (ρ) and bulk sound velocity (VΦ) contrasts across the Bm-PPv phase transition, which is in contrast to the effect of Al. Using the obtained phase diagram and thermal equations of state of Bm and PPv, we have also examined the effect of composition variations on the ρ and VΦ profiles of the lowermost mantle. Our modeling results have shown that the pyrolitic lowermost mantle should be highly heterogeneous in composition and temperature laterally to match the observed variations in the depth and seismic signatures of the D″ discontinuity. Normal mantle in a pyrolitic composition with ∼10% Fe and Al in Bm and PPv will lack clear seismic signature of the D″ discontinuity because the broad phase boundary could smooth the velocity contrast between Bm and PPv. On the other hand, Fe-enriched regions close to the cold slabs may show a seismic signature with a change in the velocity slope of the D″ discontinuity, consistent with recent seismic observations beneath the eastern Alaska. Only regions depleted in Fe and Al near the cold slabs would show a sharp change in velocity. Fe in such regions could be removed to the outer core by strong core-mantle interactions or partitions together with Al to the high-pressure phases in the subduction mid ocean ridge basalts. Our results thus have profound implication for the composition of the lowermost mantle.

The viscosity of Earth's lower mantle inferred from sinking speed of subducted lithosphere

NARCIS (Netherlands)

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

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

Energy Technology Data Exchange (ETDEWEB)

Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

2012-03-09

Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

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.

Cell adhesion-mediated radioresistance (CAM-RR). Extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro

International Nuclear Information System (INIS)

Cordes, N.; Meineke, V.

2003-01-01

Background: Cell-extracellular matrix (ECM) contact is thought to have great impact on cellular mechanisms resulting in increased cell survival upon exposure to ionizing radiation. Several human tumor cell lines and normal human fibroblastic cell strains of different origin, all of them expressing the wide-spread and important integrin subunit β1, were irradiated, and clonogenic cell survival, β1-integrin cell surface expression, and adhesive functionality were investigated. Material and Methods: Human tumor cell lines A172 (glioblastoma), PATU8902 (pancreas carcinoma), SKMES1 (lung carcinoma), A549 (lung carcinoma), and IPC298 (melanoma) as well as normal human skin (HSF1) and lung fibroblasts (CCD32) and human keratinocytes (HaCaT) were irradiated with 0-8 Gy. Besides colony formation assays, β1-integrin cell surface expression by flow cytometry and adhesive functionality by adhesion assays were analyzed. Results: All cell lines showed improved clonogenic survival after irradiation in the presence of fibronectin as compared to plastic. Irradiated cells exhibited a significant, dose-dependent increase in β1-integrin cell surface expression following irradiation. As a parameter of the adhesive functionality of the β1-integrin, a radiation-dependent elevation of cell adhesion to fibronectin in comparison with adhesion to plastic was demonstrated. Conclusion: The in vitro cellular radiosensitivity is highly influenced by fibronectin according to the phenomenon of cell adhesion-mediated radioresistance. Additionally, our emerging data question the results of former and current in vitro cytotoxicity studies performed in the absence of an ECM. These findings might also be important for the understanding of malignant transformation, anchorage-independent cell growth, optimization of radiotherapeutic regimes and the prevention of normal tissue side effects on the basis of experimental radiobiological data. (orig.)

Identification and Characterization of Plasma Cells in Normal Human Bone Marrow by High-Resolution Flow Cytometry

NARCIS (Netherlands)

Terstappen, Leonardus Wendelinus Mathias Marie; Johnsen, Steen; Segers-Nolten, Gezina M.J.; Loken, Michael R.

1990-01-01

The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma

Generation of hiPSTZ16 (ISMMSi003-A cell line from normal human foreskin fibroblasts

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Marion Dejosez

2018-01-01

Full Text Available Human foreskin fibroblasts from a commercial source were reprogrammed into induced pluripotent stem cells to establish a clonal stem cell line, hiPSTZ16 (ISMMSi003-A. These cells show a normal karyotype and full differentiation potential in teratoma assays. The described cells provide a useful resource in combination with other iPS cell lines generated from normal human foreskin fibroblasts to study source- and reprogramming method-independent effects in downstream applications.

The upper-mantle transition zone beneath the Chile-Argentina flat subduction zone

Science.gov (United States)

Bagdo, Paula; Bonatto, Luciana; Badi, Gabriela; Piromallo, Claudia

2016-04-01

The main objective of the present work is the study of the upper mantle structure of the western margin of South America (between 26°S and 36°S) within an area known as the Chile-Argentina flat subduction zone. For this purpose, we use teleseismic records from temporary broad band seismic stations that resulted from different seismic experiments carried out in South America. This area is characterized by on-going orogenic processes and complex subduction history that have profoundly affected the underlying mantle structure. The detection and characterization of the upper mantle seismic discontinuities are useful to understand subduction processes and the dynamics of mantle convection; this is due to the fact that they mark changes in mantle composition or phase changes in mantle minerals that respond differently to the disturbances caused by mantle convection. The discontinuities at a depth of 410 km and 660 km, generally associated to phase changes in olivine, vary in width and depth as a result of compositional and temperature anomalies. As a consequence, these discontinuities are an essential tool to study the thermal and compositional structure of the mantle. Here, we analyze the upper-mantle transition zone discontinuities at a depth of 410 km and 660 km as seen from Pds seismic phases beneath the Argentina-Chile flat subduction.

Mantle viscosity structure constrained by joint inversions of seismic velocities and density

Science.gov (United States)

Rudolph, M. L.; Moulik, P.; Lekic, V.

2017-12-01

The viscosity structure of Earth's deep mantle affects the thermal evolution of Earth, the ascent of mantle upwellings, sinking of subducted oceanic lithosphere, and the mixing of compositional heterogeneities in the mantle. Modeling the long-wavelength dynamic geoid allows us to constrain the radial viscosity profile of the mantle. Typically, in inversions for the mantle viscosity structure, wavespeed variations are mapped into density variations using a constant- or depth-dependent scaling factor. Here, we use a newly developed joint model of anisotropic Vs, Vp, density and transition zone topographies to generate a suite of solutions for the mantle viscosity structure directly from the seismologically constrained density structure. The density structure used to drive our forward models includes contributions from both thermal and compositional variations, including important contributions from compositionally dense material in the Large Low Velocity Provinces at the base of the mantle. These compositional variations have been neglected in the forward models used in most previous inversions and have the potential to significantly affect large-scale flow and thus the inferred viscosity structure. We use a transdimensional, hierarchical, Bayesian approach to solve the inverse problem, and our solutions for viscosity structure include an increase in viscosity below the base of the transition zone, in the shallow lower mantle. Using geoid dynamic response functions and an analysis of the correlation between the observed geoid and mantle structure, we demonstrate the underlying reason for this inference. Finally, we present a new family of solutions in which the data uncertainty is accounted for using covariance matrices associated with the mantle structure models.

The Interaction Between Supercontinent Cycles and Compositional Variations in the Deep Mantle

Science.gov (United States)

Lowman, J. P.; Trim, S. J.

2015-12-01

Earth is the only planet known to currently feature active plate tectonics. Two features that may influence the Earth's ability to sustain plate-like surface motion are the presence of continents and the inferred chemical piles lying on the core mantle boundary. In our previous study that modelled thermochemical convection in the mantle with evolving plates, it was shown that upwellings that form on top of chemical piles are relatively weak and make a diminished contribution to lithospheric stress. Yet, surface yielding is required in order to maintain plate tectonics and form new plate boundaries. Consequently an intrinsically dense layer in the lower mantle can decrease the vigour of convection and the likelihood of surface failure. In contrast to the mantle upwellings that form above the chemically dense provinces in our models, particularly vigorous plumes form where the ambient mantle lies adjacent to the core mantle boundary and at the edges of the chemically dense piles. Continents also affect surface mobility, due to their inherent buoyancy and their distinct yield strength. In this study we employ numerical models of mantle convection featuring both tectonic plates and compositional variation in the mantle and lithosphere. Plate-like surface motion is dynamically modelled using a force-balance method that determines plate velocities based upon lithospheric stresses. Oceanic and continental margins evolve in response to the plate velocities and specified lithospheric yield stresses. Compositional variations in the deep mantle are tracked using the tracer ratio method. For a range of ratios of the ambient mantle density to the density of the compositionally enriched material, we examine the the impact of mantle compositional variation on plate evolution, the effect of continents on planetary surface mobility and the frequency of supercontinent assembly versus the mobility of compositional provinces.

Receiver Function Imaging of Mantle Transition Zone Discontinuities Beneath Alaska

Science.gov (United States)

Dahm, Haider Hassan Faraj

Subduction of tectonic plates is one of the most important tectonic processes, yet many aspects of subduction zone geodynamics remain unsolved and poorly understood, such as the depth extent of the subducted slab and its geometry. The Alaska subduction zone, which is associated with the subduction of the Pacific Plate beneath the North America plate, has a complex tectonic setting and carries a series of subduction episodes, and represents an excellent target to study such plate tectonic processes. Previous seismological studies in Alaska have proposed different depth estimations and geometry for the subducted slab. The Mantle transition zone discontinuities of the 410km and the 660 km provide independent constraints on the depth extent of the subducted slabs. We conducted a receiver function study to map the topography of the 410 km and the 660 km discontinuities beneath Alaska and its adjacent areas by taking advantage of the teleseismic data from the new USArray deployment in Alaska and northwestern Canada. Stacking over 75,000 high-quality radial receiver functions recorded in Alaska with more than 40 years of recording period, the topographies of the 410 km and 660 km are mapped. The depths of both d410 and d660 show systematic spatial variations, the mean depth of d410 and d660 are within 6 km and 6 km from the global average, respectively. The mean MTZ thickness of the entire study area is within -2 km from the global average of 250 km, suggesting normal MTZ conditions on average. Central and south-central Alaska are characterized by a larger than normal MTZ thickness, suggesting that the subducting Pacific slab is thermally interacted with the MTZ. This study shows that lateral upper mantle velocity variations contribute the bulk of the observed apparent undulations of the MTZ discontinuities.

Coupling surface and mantle dynamics: A novel experimental approach

Science.gov (United States)

Kiraly, Agnes; Faccenna, Claudio; Funiciello, Francesca; Sembroni, Andrea

2015-05-01

Recent modeling shows that surface processes, such as erosion and deposition, may drive the deformation of the Earth's surface, interfering with deeper crustal and mantle signals. To investigate the coupling between the surface and deep process, we designed a three-dimensional laboratory apparatus, to analyze the role of erosion and sedimentation, triggered by deep mantle instability. The setup is constituted and scaled down to natural gravity field using a thin viscous sheet model, with mantle and lithosphere simulated by Newtonian viscous glucose syrup and silicon putty, respectively. The surface process is simulated assuming a simple erosion law producing the downhill flow of a thin viscous material away from high topography. The deep mantle upwelling is triggered by the rise of a buoyant sphere. The results of these models along with the parametric analysis show how surface processes influence uplift velocity and topography signals.

On the Role of Mantle Overturn during Magma Ocean Solidification

Science.gov (United States)

Boukaré, C. E.; Parmentier, E.; Parman, S. W.

2017-12-01

Solidification of potential global magma ocean(s) (MO) early in the history of terrestrial planets may play a key role in the evolution of planetary interiors by setting initial conditions for their long-term evolution. Constraining this initial structure of solid mantles is thus crucial but remains poorly understood. MO fractional crystallization has been proposed to generate gravitationally unstable Fe-Mg chemical stratification capable of driving solid-state mantle overturn. Fractional solidification and overturn hypothesis, while only an ideal limiting case, can explain important geochemical features of both the Moon and Mars. Current overturn models consider generally post-MO overturn where the cumulate pile remains immobile until the end of MO solidification. However, if the cumulate pile overturns during MO solidification, the general picture of early planet evolution might differ significantly from the static crystallization models. We show that the timing of mantle overturn can be characterized with a dimensionless number measuring the ratio of the MO solidification time and the purely compositional overturn timescale. Syn-solidification overturn occurs if this dimensionless parameter, Rc, exceeds a critical value. Rc is mostly affected by the competition between the MO solidification time and mantle viscosity. Overturn that occurs during solidification can result in smaller scales of mantle chemical heterogeneity that could persist for long times thus influencing the whole evolution of a planetary body. We will discuss the effects of compaction/percolation on mantle viscosity. If partially molten cumulate do not have time to compact during MO solidification, viscosity of cumulates would be significantly lower as the interstitcial melt fraction would be large. Both solid mantle remelting during syn-solidification overturn and porous convection of melt retained with the cumulates are expected to reduce the degree of fractional crystallization. Syn

Universal single grain amphibole thermobarometer for mantle rocks - preliminary calibration.

Science.gov (United States)

Ashchepkov, Igor

2017-04-01

Calibration of S-Al- K-Na-Ca distribution in the structure of the mantle amphiboles (Cr- hornblende, pargasite, kaersutite) using experimental data (Niida, Green, 1999; Wallace Green, 1991, Conceicao, Green, 2004; Medard et al, 2006; Safonov, Butvina, 2013; 2016; Pirard, Hermann, 2015 etc) allows to obtain an equation for pressure estimates in 0.5 - 4.5 GPa interval. Regression calculated pressures with experimental values (R 0.82) and precision 5 kbar allow to use barometer for a wide range of mantle rocks from peridotite to pyroxenites and megacrystals. For the higher pressures (Cr- pargasite richterite) calibration is carried by the cross- correlations with the estimates calculated for the natural associations obtained using clino- and orthopyroxene. IT was used KD =Si/(8-Al-2.2*Ti)*(Na+K))/Ca for the following equation: P(GPa)=0.0035*(4+K/(Na+K))*2*Mg)/Fe+3.75*(K+Na)/Ca))*KD*ToK**0.75/ (1+3.32*Fe)-ln(1273/ToK*5*(8*Mg-Al*2 +3*Ti+8*Cr+3*K)/10 Th advantage of this barometer comparing with the previous (Ridolfi, Renzulli, 2012) is that is working with all mantle amphibole types. For the calculations of the PT parameters of the natural xenocrysts it was used monomineral version of Gar-Amph termometer (Ravna et al., 2000) in combination with the received barometer. Contents of Ca- Mg and Fe in associated garnets were calculated usinf the regressions obtained from natural and experimental associations. Aplication of the mantle amphibole thermobarometry for the reconstruction of sections of the cratonic mantle lithosphere of Yakutia show that amphibloles are distributed in various parts of mantle sections in deifferent mantle terranes of Yakutia. The most abundant amphoboles from Alakite region are distributed within all mantle section. In the SCLM beneat Yubileyaya pipe thehalf of them belong to the spinel garnet facie refering to the upper pyroxenitic suit and Cr- hornblende - mica viens. The second group reffer to the eclogite pyroxenite layer in the middle part of

Analysis of the flow structure and heat transfer in a vertical mantle heat exchanger

DEFF Research Database (Denmark)

Knudsen, Søren; Morrison, GL; Behnia, M

2005-01-01

initially mixed and initially stratified inner tank and mantle. The analysis of the heat transfer showed that the flow in the mantle near the inlet is mixed convection flow and that the heat transfer is dependent on the mantle inlet temperature relative to the core tank temperature at the mantle level. (C......The flow structure inside the inner tank and inside the mantle of a vertical mantle heat exchanger was investigated using a full-scale tank designed to facilitate flow visualisation. The flow structure and velocities in the inner tank and in the mantle were measured using a Particle Image...... Velocimetry (PIV) system. A Computational Fluid Dynamics (CFD) model of the vertical mantle heat exchanger was also developed for a detailed evaluation of the heat flux at the mantle wall and at the tank wall. The flow structure was evaluated for both high and low temperature incoming flows and for both...

Mixing properties of thermal convection in the earth's mantle

NARCIS (Netherlands)

Schmalzl, J.T.

1996-01-01

The structure of mantle convection will greatly influence the generation and the survival of compositional heterogeneities. Conversely, geochemical observations can be used to obtain information about heterogeneities in the mantle and then, with certain model assumptions, information about the

Metasomatized mantle as the source of Mid-Miocene-Quaternary volcanism in NW-Iranian Azerbaijan: Geochronological and geochemical evidence

Science.gov (United States)

Lechmann, Anna; Burg, Jean-Pierre; Ulmer, Peter; Guillong, Marcel; Faridi, Mohammad

2018-04-01

Middle Miocene to Quaternary volcanic rocks cover large areas of the Azerbaijan Province in NW Iran. This study reports two separate age clusters out of 23 new LA-ICP-MS U-Pb zircon ages: (1) Middle Miocene (16.2-10.6 Ma) and (2) Latest Miocene-Late Pleistocene (5.5-0.4 Ma). Major and trace element bulk rock geochemistry and initial Sr, Nd, Pb radiogenic isotope data on the dated rocks provide new constraints on the Mid-Miocene to Quaternary volcanism in this region. The analyses are distributed over a large compositional range from low-K to high-K calc-alkaline andesites and dacites/rhyolites to more alkaline trachybasalts and dacites with shoshonitic affinities. Chondrite-normalized REE patterns are steep with significant enrichment in LREE and low abundances of HREE indicating a garnet control. Plots of primitive mantle-normalized trace elements show negative Ti and Nb-Ta anomalies indicative of an arc signature. The wide compositional range and the ubiquitous presence of an arc signature reveal that the source mantle is heterogeneous and metasomatically altered. Sr, Nd and Pb radiogenic isotope data further point towards an enriched mantle source and/or crustal contamination. Crustal contamination is best recognized by inherited zircon cores, which yield Late Neoproterozoic to Early Cambrian ages typical for the Iranian basement. The occurrence of adakite-like compositions with elevated magnesium numbers, Cr and Ni concentrations argue against a fractionation-driven process but point to a subcrustal origin. Overall, the analyzed lavas show no spatial and temporal relation to a potential subduction zone, confirming the dated volcanics to be post-collisional and not related to singular processes such as slab retreat or delamination of a continuous lower crustal sliver. We propose three hypotheses to explain the reported disparity in distribution, age and composition and favour small-scale sublithospheric convection or incorporation of crustal material into the

Plate Tectonic Cycling and Whole Mantle Convection Modulate Earth's 3He/22Ne Ratio

Science.gov (United States)

Dygert, N. J.; Jackson, C.; Hesse, M. A.; Tremblay, M. M.; Shuster, D. L.; Gu, J.

2016-12-01

3He and 22Ne are not produced in the mantle or fractionated by partial melting, and neither isotope is recycled back into the mantle by subduction of oceanic basalt or sediment. Thus, it is a surprise that large 3He/22Ne variations exist within the mantle and that the mantle has a net elevated 3He/22Ne ratio compared to volatile-rich planetary precursor materials. Depleted subcontinental lithospheric mantle and mid-ocean ridge basalt (MORB) mantle have distinctly higher 3He/22Ne compared to ocean island basalt (OIB) sources ( 4-12.5 vs. 2.5-4.5, respectively) [1,2]. The low 3He/22Ne of OIBs approaches chondritic ( 1) and solar nebula values ( 1.5). The high 3He/22Ne of the MORB mantle is not similar to solar sources or any known family of meteorites, requiring a mechanism for fractionating He from Ne in the mantle and suggesting isolation of distinct mantle reservoirs throughout geologic time. We model the formation of a MORB source with elevated and variable 3He/22Ne though diffusive exchange between dunite channel-hosted basaltic liquids and harzburgite wallrock beneath mid-ocean ridges. Over timescales relevant to mantle upwelling beneath spreading centers, He may diffuse tens to hundreds of meters into wallrock while Ne is relatively immobile, producing a regassed, depleted mantle lithosphere with elevated 3He/22Ne. Subduction of high 3He/22Ne mantle would generate a MORB source with high 3He/22Ne. Regassed, high 3He/22Ne mantle lithosphere has He concentrations 2-3 orders of magnitude lower than undegassed mantle. To preserve the large volumes of high 3He/22Ne mantle required by the MORB source, mixing between subducted and undegassed mantle reservoirs must have been limited throughout geologic time. Using the new 3He/22Ne constraints, we ran a model similar to [3] to quantify mantle mixing timescales, finding they are on the order of Gyr assuming physically reasonable seafloor spreading rates, and that Earth's convecting mantle has lost >99% of its primordial

The evolution of grain mantles and silicate dust growth at high redshift

Science.gov (United States)

Ceccarelli, Cecilia; Viti, Serena; Balucani, Nadia; Taquet, Vianney

2018-05-01

In dense molecular clouds, interstellar grains are covered by mantles of iced molecules. The formation of the grain mantles has two important consequences: it removes species from the gas phase and promotes the synthesis of new molecules on the grain surfaces. The composition of the mantle is a strong function of the environment that the cloud belongs to. Therefore, clouds in high-zeta galaxies, where conditions - like temperature, metallicity, and cosmic ray flux - are different from those in the Milky Way, will have different grain mantles. In the last years, several authors have suggested that silicate grains might grow by accretion of silicon-bearing species on smaller seeds. This would occur simultaneously with the formation of the iced mantles and be greatly affected by its composition as a function of time. In this work, we present a numerical study of the grain mantle formation in high-zeta galaxies, and we quantitatively address the possibility of silicate growth. We find that the mantle thickness decreases with increasing redshift, from about 120 to 20 layers for z varying from 0 to 8. Furthermore, the mantle composition is also a strong function of the cloud redshift, with the relative importance of CO, CO2, ammonia, methane, and methanol highly varying with z. Finally, being Si-bearing species always a very minor component of the mantle, the formation of silicates in molecular clouds is practically impossible.

Plate tectonics, mantle convection and D'' seismic structures

Science.gov (United States)

Wen, Lianxing

This thesis adopts multidisciplinary (geodynamical and seismological) approaches toward understanding dynamics of the Earth's mantle. My geodynamical approach is directed at understanding the relationship between large-scale surface observables (geoid, topography, plate motions) and mantle rheology and convection of the present-day Earth. In chapter 2, I remove shallow mantle structure of various tectonic features to generate "residual tomography." In chapter 3, I show that the pattern, spectrum and amplitude of the "residual topography" are consistent with shallow origin of the "Earth surface dynamic topography;" the long wavelength geoid and topography (l = 2-3) are successfully explained by density models inferred from the "residual tomography," assuming layered mantle convection stratified at the "920 km seismic discontinuity." In chapter 4, I develop a new method to calculate mantle flow with lateral variation of viscosity. The viscosity contrast between continental and oceanic regions is identified to have dominating effects on both the observed poloidal/toroidal ratio and pattern of toroidal motions at long wavelengths. My seismological approach is focused on exploring fine structures near the core-mantle boundary (CMB) and developing new seismic techniques. I discuss the method development and strategies to explore fine structures in the following chapters. In chapter 5, I develop a hybrid method, a combination of analytical and numerical methods, with numerical methods applied in heterogeneous regions only. In chapter 6, I constrain the general structures of the ultra low velocity zones (ULVZ) near the CMB under the south-east Pacific and Iceland. The SKS-SPdKS data are explained by ULVZ with P-velocity reduction of 10%, horizontal length-scales of about 250 km and height of about 40 km. S-velocity reduction of 30% is consistent with the data. In chapter 7, I constrain the detailed structures of the ULVZ near the CMB from observed broadband PKP precursors

Lower Mantle S-wave Velocity Model under the Western United States

Science.gov (United States)

Nelson, P.; Grand, S. P.

2016-12-01

Deep mantle plumes created by thermal instabilities at the core-mantle boundary has been an explanation for intraplate volcanism since the 1970's. Recently, broad slow velocity conduits in the lower mantle underneath some hotspots have been observed (French and Romanowicz, 2015), however the direct detection of a classical thin mantle plume using seismic tomography has remained elusive. Herein, we present a seismic tomography technique designed to image a deep mantle plume under the Yellowstone Hotspot located in the western United States utilizing SKS and SKKS waves in conjunction with finite frequency tomography. Synthetic resolution tests show the technique can resolve a 235 km diameter lower mantle plume with a 1.5% Gaussian velocity perturbation even if a realistic amount of random noise is added to the data. The Yellowstone Hotspot presents a unique opportunity to image a thin plume because it is the only hotspot with a purported deep origin that has a large enough aperture and density of seismometers to accurately sample the lower mantle at the length scales required to image a plume. Previous regional tomography studies largely based on S wave data have imaged a cylindrically shaped slow anomaly extending down to 900km under the hotspot, however they could not resolve it any deeper (Schmandt et al., 2010; Obrebski et al., 2010).To test if the anomaly extends deeper, we measured and inverted over 40,000 SKS and SKKS waves' travel times in two frequency bands recorded at 2400+ stations deployed during 2006-2012. Our preliminary model shows narrow slow velocity anomalies in the lower mantle with no fast anomalies. The slow anomalies are offset from the Yellowstone hotspot and may be diapirs rising from the base of the mantle.

Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells.

Directory of Open Access Journals (Sweden)

Yukihiro Nishikawa

Full Text Available Withaferin A (WA, a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD. WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L. Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death.

Subcellular localization of YKL-40 in normal and malignant epithelial cells of the breast

DEFF Research Database (Denmark)

Roslind, A.; Balslev, E.; Kruse, H.

2008-01-01

. YKL-40 protein expression was redistributed in carcinoma versus normal glandular tissue of the breast. A reduced expression of YKL-40 in relation to intermediate filaments and desmosomes was found in tumor cells. Changes in YKL-40 expression suggest that the function of YKL-40 in cells of epithelial......YKL-40 is a new prognostic biomarker in cancer. The biological function is only poorly understood. This study aimed at determining the subcellular localization of YKL-40, using immunogold labeling, in normal epithelial cells and in malignant tumor cells of the breast by immunoelectron microscopy...

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

Science.gov (United States)

Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

2014-08-01

The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sulfur in Earth's Mantle and Its Behavior During Core Formation

Science.gov (United States)

Chabot, Nancy L.; Righter,Kevin

2006-01-01

The density of Earth's outer core requires that about 5-10% of the outer core be composed of elements lighter than Fe-Ni; proposed choices for the "light element" component of Earth's core include H, C, O, Si, S, and combinations of these elements [e.g. 1]. Though samples of Earth's core are not available, mantle samples contain elemental signatures left behind from the formation of Earth's core. The abundances of siderophile (metal-loving) elements in Earth's mantle have been used to gain insight into the early accretion and differentiation history of Earth, the process by which the core and mantle formed, and the composition of the core [e.g. 2-4]. Similarly, the abundance of potential light elements in Earth's mantle could also provide constraints on Earth's evolution and core composition. The S abundance in Earth's mantle is 250 ( 50) ppm [5]. It has been suggested that 250 ppm S is too high to be due to equilibrium core formation in a high pressure, high temperature magma ocean on early Earth and that the addition of S to the mantle from the subsequent accretion of a late veneer is consequently required [6]. However, this earlier work of Li and Agee [6] did not parameterize the metalsilicate partitioning behavior of S as a function of thermodynamic variables, limiting the different pressure and temperature conditions during core formation that could be explored. Here, the question of explaining the mantle abundance of S is revisited, through parameterizing existing metal-silicate partitioning data for S and applying the parameterization to core formation in Earth.

RF Breakdown in Normal Conducting Single-Cell Structures

International Nuclear Information System (INIS)

Dolgashev, V.A.; Nantista, C.D.; Tantawi, S.G.; Higashi, Y.; Higo, T.

2006-01-01

Operating accelerating gradient in normal conducting accelerating structures is often limited by rf breakdown. The limit depends on multiple parameters, including input rf power, rf circuit, cavity shape and material. Experimental and theoretical study of the effects of these parameters on the breakdown limit in full scale structures is difficult and costly. We use 11.4 GHz single-cell traveling wave and standing wave accelerating structures for experiments and modeling of rf breakdown behavior. These test structures are designed so that the electromagnetic fields in one cell mimic the fields in prototype multicell structures for the X-band linear collider. Fields elsewhere in the test structures are significantly lower than that of the single cell. The setup uses matched mode converters that launch the circular TM 01 mode into short test structures. The test structures are connected to the mode launchers with vacuum rf flanges. This setup allows economic testing of different cell geometries, cell materials and preparation techniques with short turn-around time. Simple 2D geometry of the test structures simplifies modeling of the breakdown currents and their thermal effects

Dosimetric considerations in treating mediastinal disease with mantle fields: Characterization of the dose under mantle blocks

International Nuclear Information System (INIS)

Miller, R.W.; Geijn, J. van de; Okunieff, P.

1995-01-01

While the rationale for using mantle fields is well understood and the prescription of these fields is straightforward, the underlying complexity of the dose distributions that result is not generally appreciated. This is especially true in the choice of lung block design, which affects the dose to both the target volume as well as to the normal lung tissue. The key to the design of optimal lung blocks is the physician's perception of the complex relationship between the geometric and dosimetric aspects of heavily modified fields, as well as how the physical and anatomical properties of the target volume and the shape of the patient's lungs relate to the images visualized on simulator films. Depth doses and cross-beam profiles of blocks ranging in width from 1 cm to 10 cm were taken using an automated beam scanning system. These data were then converted to open-quotes shadow fields.close quotes Shadow fields behave quite similarly to small, open fields in terms of x-ray-light field congruence, flatness, symmetry, and penumbra. There is a 2-3 mm rim between the edge of the block and the point at which it becomes nominally effective. The dose at the center of a block, which gives the normalization of the shadow fields, is given by a block transmission factor (BTF), which produces results in excellent agreement with measurements over a wide variety of block sizes and tissue depths. The radiation dose under shielding blocks can be considerably higher than expected, and care must be exercised when drawing blocks close to critical structures. The effects of blocks can be described in terms of normalized shadow fields, which behave similar to narrow, open fields, but with a divergence characteristic of their position relative to the radiation source. The normalization value for these fields, which gives the relative dose under the block, can be obtained from a straightforward analytical expression, the BTF. 33 refs., 9 figs., 4 tabs

Mantle dynamics in Mars and Venus: Influence of an immobile lithosphere on three-dimensional mantle convection

International Nuclear Information System (INIS)

Schubert, G.; Bercovici; Glatzmaier, G.A.

1990-01-01

Numerical calculations of fully three-dimensional convection in constant viscosity, compressible spherical shells are interpreted in terms of possible convective motions in the mantles of Venus and Mars. The shells are heated both internally and from below to account for radiogenic heating, secular cooling, and heat flow from the core. The lower boundary of each of the shells is isothermal and shear stress free, as appropriate to the interface between a mantle and a liquid outer core. The upper boundary of each of the shells is rigid and isothermal, as appropriate to the base of a thick immobile lithosphere. Calculations with shear stress-free upper boundaries are also carried out to assess the role of the rigid surface condition. The ratio of the inner radius of each shell to its outer radius is in accordance with possible core sizes in both Venus and Mars. A calculation is also carried out for a Mars model with a small core to simulate mantle convection during early core formation. Different relative proportions of internal and bottom heating are investigated, ranging from nearly complete heating from within to almost all heating from below. The Rayleigh numbers of all the cases are approximately 100 times the critical Rayleigh numbers for the onset of convection. Cylindrical plumes are the prominent form of upwelling in the models independent of the surface boundary condition so long as sufficient heat derives from the core. Thus major volcanic centers on Mars, such as Tharsis and Elysium, and the coronae and some equatorial highlands on Venus may be the surface expressions of cylindrical mantle plumes

Androgen receptor signalling in peritubular myoid cells is essential for normal differentiation and function of adult Leydig cells

DEFF Research Database (Denmark)

Welsh, M.; Moffat, L.; Belling, Kirstine Christensen

2012-01-01

Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number, but res......Testosterone synthesis depends on normal Leydig cell (LC) development, but the mechanisms controlling this development remain unclear. We recently demonstrated that androgen receptor (AR) ablation from a proportion of testicular peritubular myoid cells (PTM-ARKO) did not affect LC number......’ subpopulation that had arrested development and only weakly expressed INSL3, luteinizing hormone receptor, and several steroidogenic enzymes. Furthermore, unlike ‘normal’ LCs in PTM-ARKOs, the ‘abnormal’ LCs did not involute as expected in response to exogenous testosterone. Differential function of these LC...... sub-populations is likely to mean that the ‘normal’ LCs work harder to compensate for the ‘abnormal’ LCs to maintain normal serum testosterone. These findings reveal new paracrine mechanisms underlying adult LC development, which can be further investigated using PTM-ARKOs....

Diverse, discrete, mantle-derived batches of basalt erupted along a short normal fault zone: The Poison Lake chain, southernmost Cascades

Science.gov (United States)

Muffler, L.J.P.; Clynne, M.A.; Calvert, A.T.; Champion, D.E.

2011-01-01

The Poison Lake chain consists of small, monogenetic, calc-alkaline basaltic volcanoes located east of the Cascade arc axis, 30 km ENE of Lassen Peak in northeastern California. This chain consists of 39 distinguishable units in a 14-km-long and 2-kmwide zone trending NNW, parallel to nearby Quaternary normal faults. The 39 units fall into nine coherent groups based on stratigraphy, field characteristics, petrography, and major-element compositions. Petrographic differences among groups are expressed by different amounts and proportions of phenocrysts. MgO-SiO 2, K 2O-SiO 2, and TiO 2-SiO 2 variation diagrams illustrate clear differences in compatible and incompatible elements among the groups. Variation of K 2O/ TiO 2 and K 2O/P 2O 5 with MgO indicates that most of the basalts of the Poison Lake chain cannot be related by crystal fractionation at different pressures and that compositions have not been affected significantly by incorporation of low-degree silicic crustal melt or interaction with sialic crust. Limited traceelement and whole-rock isotopic data also suggest little if any incorporation of uppercrustal material, and that compositional variation among groups primarily reflects source compositional differences. Precise 40Ar/ 39Ar determinations show that the lavas were erupted between 100 and 110 ka. The migration of paleomagnetic remanent directions over 30?? suggests that the entire Poison Lake chain could represent three short-lived episodes of volcanism within a period as brief as 500 yr. The diverse geologic, petrographic, chemical, paleomagnetic, and age data indicate that each of the nine groups represents a small, discrete magma batch generated in the mantle and stored briefly in the lower crust. A NNW normal fault zone provided episodic conduits that allowed rapid ascent of these batches to the surface, where they erupted as distinct volcanic groups, each aligned along a segment of the Poison Lake chain. Compositional diversity of these primitive

HIV-Specific ADCC Improves After Antiretroviral Therapy and Correlates With Normalization of the NK Cell Phenotype

DEFF Research Database (Denmark)

Jensen, Sanne S; Hartling, Hans J; Tingstedt, Jeanette L

2015-01-01

analyzed. RESULTS: The ability of NK cells to mediate ADCC was significantly increased after only 6 months of HAART and was not explained by a normalization of NK cell subsets (CD56 CD16 and CD56 CD16 NK cells) but rather by normalization in the frequency of NK cells expressing CCR7 and CD27...

Mast cells and atopic dermatitis. Stereological quantification of mast cells in atopic dermatitis and normal human skin

DEFF Research Database (Denmark)

Damsgaard, T E; Olesen, A B; Sørensen, Flemming Brandt

1997-01-01

Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or the fixative influenced the results...... of the determination of the mast cell profile numbers. The punch biopsies were taken from the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out...... yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly increased number of mast cell profiles per millimetre squared was found...

Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas

DEFF Research Database (Denmark)

Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

2017-01-01

cells in the normal human pancreas and perisinusoidal cells in the normal human liver. The immunolabelling capacity was evaluated according to a semiquantitative scoring system. Double-IF of the markers of interest together with markers for other periacinar cells was performed. Moreover, the utility...... of histochemical stains for the identification of human qPSCs was examined, and their ultrastructure was revisited by electron microscopy. Adipophilin, CRBP-1, cytoglobin and vinculin were expressed in qHSCs in the liver, whereas cytoglobin and adipophilin were expressed in qPSCs in the pancreas. Adipophilin...... are markers of qPSCs in the normal human pancreas. However, the use of adipophilin as a qPSC marker may be limited due to its high dependence on optimal PATI. Cytoglobin, on the other hand, is a sensitive marker for qPSCs but is expressed in FBs as well....

Constraining Mantle Differentiation Processes with La-Ce and Sm-Nd Isotope Systematics

Science.gov (United States)

Willig, M.; Stracke, A.

2016-12-01

Cerium (Ce) and Neodymium (Nd) isotopic ratios in oceanic basalts reflect the time integrated La-Ce and Sm-Nd ratios, and hence the extent of light rare earth element element (LREE) depletion or enrichment of their mantle sources. New high precision Ce-Nd isotope data from several ocean islands define a tight array in ԑCe-ԑNd space with ԑNd = -8.2±0.4 ԑCe + 1.3±0.9 (S.D.), in good agreement with previous data [1, 2]. The slope of the ԑCe-ԑNd array and the overall isotopic range are sensitive indicators of the processes that govern the evolution of the mantle's LREE composition. A Monte Carlo approach is employed to simulate continuous mantle-crust differentiation by partial melting and recycling of crustal materials. Partial melting of mantle peridotites produces variably depleted mantle and oceanic crust, which evolve for different time periods, before the oceanic crust is recycled back into the mantle including small amounts of continental crust (GLOSS [3]). Subsequently, depleted mantle and recycled materials of variable age and composition melt, and the respective melts mix in different proportions. Mixing lines strongly curve towards depleted mantle, and tend to be offset from the data for increasingly older and more depleted mantle. Observed ԑCe-ԑNd in ridge [1] and ocean island basalts and the slope of the ԑCe-ԑNd array therefore define upper limits for the extent and age of LREE depletion preserved in mantle peridotites. Very old average mantle depletion ages (> ca. 1-2 Ga) for the bulk of the mantle are difficult to reconcile with the existing ԑCe-ԑNd data, consistent with the range of Nd-Hf-Os model ages in abyssal peridotites [4-6]. Moreover, unless small amounts of continental crust are included in the recycled material, it is difficult to reproduce the relatively shallow slope of the ԑCe-ԑNd array, consistent with constraints from the ԑNd - ԑHf mantle array [7]. [1] Makishima and Masuda, 1994 Chem. Geol. 118, 1-8. [2] Doucelance et al

Cell biological effects of total body irradiation on growth and differentiation of acute myelogenous leukemia cells compared to normal bone marrow

Energy Technology Data Exchange (ETDEWEB)

Greenberger, J S; Weichselbaum, R R; Botnick, L E; Sakakeeny, M; Moloney, W C

1979-01-01

Radiation therapy is used as total body treatment in preparation of the acute myelogenous leukemia (AML) patient for bone marrow transplantation. Many AML patients will have residual leukemia cells at the time of total body irradiation (TBI). In the present study, the effect of TBI on leukemic myeloid cells was compared to the effect on normal marrow granulocytic stem cells (CFUc) in vitro. Little difference from that of normal CFUc was found in the radiosensitivity of two mouse myeloid leukemia cell lines. The effect of TBI on growth of WEHI-3 or J774 cells in millipore diffusion chambers was stimulatory. These AML cell lines as well as others derived from Friend or Abelson virus infected in vitro long term mouse marrow cultures showed some morphologic differentiation by 7 days growth in diffusion chambers in irradiated heterologous rat hosts, but immature cells predominated by day 21. Thus, evidence in murine models of AML indicates that residual AML cells surviving chemotherapy will show no greater susceptibility to radiation killing compared to normal stem cells and will rapidly repopulate the irradiated host.

Comparison of radiosensitivity between tumor and normal tissue in terms of cell population kinetics

International Nuclear Information System (INIS)

Sugahara, Tsutomu; Utsumi, Hiroshi

1975-01-01

Puck and Marcus in 1956 established the in vitro colony formation of mammalian cells and demonstrated a dose-survival curve of mammalian cells well fitted to the target theory. Since then almost all of the work on the radiosensitivity of malignant and normal cells has been based on the reproductive integrity of cells. However, in the author's laboratory, a recent work was done on the effect of ionizing radiation on the differentiative trait, using clonal cell cultures developed by Coon (1966) in chick embryonic cartilage cells. This work demonstrated clearly that the differentiative trait is more radiosensitive than is reproduction. Based on this finding a new compartment model is proposed for a cell renewal system which demonstrates the difference between normal and malignant tissue. (author)

Search for methylation-sensitive amplification polymorphisms associated with the mantled variant phenotype in oil palm (Elaeis guineensis Jacq).

Science.gov (United States)

Jaligot, E; Beulé, T; Baurens, F-C; Billotte, N; Rival, A

2004-02-01

The methylation-sensitive amplification polymorphism (MSAP) technique has been employed on somatic embryo-derived oil palms (Elaeis guineensis Jacq.) to identify methylation polymorphisms correlated with the "mantled" somaclonal variation. The variant phenotype displays an unstable feminization of male organs in both male and female flowers. Using MSAP, the methylation status of CCGG sites was compared in three normal versus three mantled regenerants sampled in clonal populations obtained through somatic embryogenesis from four genotypically distinct mother palms. Overall, 64 selective primer combinations were used and they have amplified 23 markers exhibiting a differential methylation pattern between the two phenotypes. Our results indicate that CCGG sites are poorly affected by the considerable decrease in global DNA methylation that has been previously associated with the mantled phenotype. Each of the 23 markers isolated in the present study could discriminate between the two phenotypes only when they were from the same genetic origin. This result hampers at the moment the direct use of MSAP markers for the early detection of variants, even though valuable information on putative target sequences will be obtained from a further characterization of these polymorphic markers.

Elasticity of superhydrous phase B at the mantle temperature and pressure: Implications for 800-km discontinuity and water flow into lower mantle

Science.gov (United States)

Yang, D.; Wang, W.; Wu, Z.

2017-12-01

Plate subduction can transport the water to the Earth's interior by forming hydrous phases and water can exert important effects on global dynamics and many processes within the deep Earth. Superhydrous phase B (ShyB), as an important candidate for transporting water into the mantle transition zone and lower mantle, is stable up to 31 GPa and will decompose into bridgmanite, periclase and water at a depth of 800 km [Komabayashi and Omori, 2006]. The decomposition of ShyB may be related to the seismic discontinuity at the depth of 800 km in Western-Pacific Subduction Zones [Liu et al., 2016; Porritt and Yoshioka, 2016]. The detail discussions on this topic require the elasticity of ShyB at the P-T conditions of the transition zone and lower mantle. In this contribution, we obtained the thermal elasticity of ShyB using first-principles calculations. ShyB shows a very low velocity and density compared to the bridgmanite and periclase, the major minerals in the lower mantle. The accumulation of ShyB will generate the low-velocity anomaly in the uppermost lower mantle. The dehydration of ShyB will cause the Vp, Vs, and density increase by 7.5%, 15.0% and 12%, respectively. It means that a slab with 10% ShyB could cause an impedance contrast of 2.7% at a depth of 800 km for shear wave. Furthermore, the released waters by the dehydration of ShyB probably migrate upward and promote the partial melt to reduce the sound velocity at shallower depth, which can further explain the low-velocity zones just above 800-km discontinuity in Western-Pacific Subduction Zones [Liu et al., 2016]. Komabayashi, T., and S. Omori (2006), Internally consistent thermodynamic data set for dense hydrous magnesium silicates up to 35GPa, 1600°C: Implications for water circulation in the Earth's deep mantle, Physics of the Earth and Planetary Interiors, 156(1-2), 89-107. Liu, Z., J. Park, and S. I. Karato (2016), Seismological detection of low-velocity anomalies surrounding the mantle transition

Molecular dynamics study of lipid bilayers modeling the plasma membranes of normal murine thymocytes and leukemic GRSL cells.

Science.gov (United States)

Andoh, Yoshimichi; Okazaki, Susumu; Ueoka, Ryuichi

2013-04-01

Molecular dynamics (MD) calculations for the plasma membranes of normal murine thymocytes and thymus-derived leukemic GRSL cells in water have been performed under physiological isothermal-isobaric conditions (310.15K and 1 atm) to investigate changes in membrane properties induced by canceration. The model membranes used in our calculations for normal and leukemic thymocytes comprised 23 and 25 kinds of lipids, respectively, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, lysophospholipids, and cholesterol. The mole fractions of the lipids adopted here were based on previously published experimental values. Our calculations clearly showed that the membrane area was increased in leukemic cells, and that the isothermal area compressibility of the leukemic plasma membranes was double that of normal cells. The calculated membranes of leukemic cells were thus considerably bulkier and softer in the lateral direction compared with those of normal cells. The tilt angle of the cholesterol and the conformation of the phospholipid fatty acid tails both showed a lower level of order in leukemic cell membranes compared with normal cell membranes. The lateral radial distribution function of the lipids also showed a more disordered structure in leukemic cell membranes than in normal cell membranes. These observations all show that, for the present thymocytes, the lateral structure of the membrane is considerably disordered by canceration. Furthermore, the calculated lateral self-diffusion coefficient of the lipid molecules in leukemic cell membranes was almost double that in normal cell membranes. The calculated rotational and wobbling autocorrelation functions also indicated that the molecular motion of the lipids was enhanced in leukemic cell membranes. Thus, here we have demonstrated that the membranes of thymocyte leukemic cells are more disordered and more fluid than normal cell membranes. Copyright © 2013

Topography of upper mantle seismic discontinuities beneath the North Atlantic: the Azores, Canary and Cape Verde plumes

Science.gov (United States)

Saki, Morvarid; Thomas, Christine; Nippress, Stuart E. J.; Lessing, Stephan

2015-04-01

We are mapping the topography of upper mantle seismic discontinuities beneath the North Atlantic and surrounding regions by using precursor arrivals to PP and SS seismic waves that reflect off the seismic discontinuities. Many source-receiver combinations have been used in order to collect a large dataset of reflection points beneath our investigating area. We analyzed over 1700 seismograms from MW>5.8 events using array seismic methods to enhance the signal to noise ratio. The measured time lag between PP (SS) arrivals and their corresponding precursors on robust stacks are used to measure the depth of the transition zone boundaries. The reflectors' depths show a correlation between the location of hotspots and a significantly depressed 410 km discontinuity indicating a temperature increase of 200-300 K compared to the surrounding mantle. For the 660 km discontinuity three distinct behaviours are visible: i) normal depths beneath Greenland and at a distance of a few hundred kilometres away from the hotspots and ii) shallower 660 km discontinuity compared with the global average value near hotspots closer to the Mid-Atlantic Ridge and iii) very few observations of a 660 km discontinuity at the hotspot locations. We interpret our observations as a large upwelling beneath the southern parts of our study region, possibly due to the South Atlantic convection cell. The thermal anomaly may be blocked by endothermic phase transformation and likely does not extend through the top of the transition zone as whole except for those branches which appear as the Azores, Canaries and Cape Verde hotspots at the surface.

Wnt/β-catenin Signaling in Normal and Cancer Stem Cells

Directory of Open Access Journals (Sweden)

Kenneth C. Valkenburg

2011-04-01

Full Text Available The ability of Wnt ligands to initiate a signaling cascade that results in cytoplasmic stabilization of, and nuclear localization of, β-catenin underlies their ability to regulate progenitor cell differentiation. In this review, we will summarize the current knowledge of the mechanisms underlying Wnt/β-catenin signaling and how the pathway regulates normal differentiation of stem cells in the intestine, mammary gland, and prostate. We will also discuss how dysregulation of the pathway is associated with putative cancer stem cells and the potential therapeutic implications of regulating Wnt signaling.

Ubiquitous expression of MAKORIN-2 in normal and malignant hematopoietic cells and its growth promoting activity.

Directory of Open Access Journals (Sweden)

King Yiu Lee

Full Text Available Makorin-2 (MKRN2 is a highly conserved protein and yet its functions are largely unknown. We investigated the expression levels of MKRN2 and RAF1 in normal and malignant hematopoietic cells, and leukemia cell lines. We also attempted to delineate the role of MKRN2 in umbilical cord blood CD34+ stem/progenitor cells and K562 cell line by over-expression and inhibition of MKRN2 through lentivirus transduction and shRNA nucleofection, respectively. Our results provided the first evidence on the ubiquitous expression of MKRN2 in normal hematopoietic cells, embryonic stem cell lines, primary leukemia and leukemic cell lines of myeloid, lymphoid, erythroid and megakaryocytic lineages. The expression levels of MKRN2 were generally higher in primary leukemia samples compared with those in age-matched normal BM cells. In all leukemia subtypes, there was no significant correlation between expression levels of MKRN2 and RAF1. sh-MKRN2-silenced CD34+ cells had a significantly lower proliferation capacity and decreased levels of the early stem/progenitor subpopulation (CFU-GEMM compared with control cultures. Over-expression of MKRN2 in K562 cells increased cell proliferation. Our results indicated possible roles of MKRN2 in normal and malignant hematopoiesis.

A reconnaissance view of tungsten reservoirs in some crustal and mantle rocks: Implications for interpreting W isotopic compositions and crust-mantle W cycling

Science.gov (United States)

Liu, Jingao; Pearson, D. Graham; Chacko, Thomas; Luo, Yan

2018-02-01

High-precision measurements of W isotopic ratios have enabled increased exploration of early Earth processes. However, when applying W isotopic data to understand the geological processes, it is critical to recognize the potential mobility of W and hence evaluate whether measured W contents and isotopic compositions reflect the primary petrogenetic processes or instead are influenced by the effects of secondary inputs/mobility. Furthermore, if we are to better understand how W is partitioned between different minerals during melting and metasomatic processes it is important to document the likely sinks for W during these processes. In addition, an understanding of the main hosts for W in the crust and mantle is critically important to constrain how W is cycled and stored in the crust-mantle geochemical cycle. As a first step to investigate these issues, we have carried out in situ concentration measurements of W and other HFSEs in mineral phases within a broad spectrum of crustal and mantle rocks, along with whole-rock concentration measurements. Mass balance shows that for tonalitic gneiss and amphibolite, the major rock-forming minerals can adequately account for the bulk W budget, and for the pristine ultramafic rocks, olivine and orthopyroxene are the major controlling phases for W whereas for metasomatized ultramafic rocks, significant W is hosted in Ti-bearing trace phases (e.g., rutile, lindsleyite) along grain boundaries or is inferred to reside in cryptic W-bearing trace phases. Formation or decomposition of these phases during secondary processes could cause fractionation of W from other HFSEs, and also dramatically modify bulk W concentrations in rocks. For rocks that experienced subsequent W enrichment/alteration, their W isotopic compositions may not necessarily represent their mantle sources, but could reflect later inputs. The relatively small suite of rocks analyzed here serves as a reconnaissance study but allows some preliminary speculations on

Tomographic and Geodynamic Constraints on Convection-Induced Mixing in Earth's Deep Mantle

Science.gov (United States)

Hafter, D. P.; Forte, A. M.; Bremner, P. M.; Glisovic, P.

2017-12-01

Seismological studies reveal two large low-shear-velocity provinces (LLSVPs) in the lowermost mantle (e.g., Su et al. 1994; Wang & Wen 2007; He & Wen 2012), which may represent accumulations of subducted slabs at the CMB (Tan & Gurnis 2005; Christensen & Hoffman 1994) or primordial material generated in the early differentiation of Earth (e.g. Li et al. 2014). The longevity or stability of these large-scale heterogeneities in the deep mantle depends on the vigor and spatial distribution of the convective circulation, which is in turn dependent on the distribution of mantle buoyancy and viscosity (e.g. Glisovic & Forte 2015). Here we explore the state of convective mixing in the mantle using the ASPECT convection code (Kronbichler et al. 2012). A series of experiments are conducted to consider the geochemical and dynamical contributions of LLSVPs to deep-mantle upwellings and corresponding plume-sourced volcanism. The principal feature of these experiments is the use of particle tracers to track geochemical changes in the LLSVPs and mantle plumes in addition to identifying those parts of the mantle that may remain unmixed. We employ 3-D mantle density anomalies derived from joint inversions of seismic, geodynamic and mineral physics constraints and geodynamically-constrained viscosity distributions (Glisovic et al. 2015) to ensure that the predicted flow fields yield a good match to key geophysical constraints (e.g. heat flow, global gravity anomalies and plate velocities).

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

Science.gov (United States)

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

The A-myb transcription factor in neoplastic and normal B cells.

Science.gov (United States)

Golay, J; Facchinetti, V; Ying, G; Introna, M

1997-07-01

The myb family of transcription factors has been strongly implicated in the regulation of cell growth and differentiation in the haematopoietic system. The v-myb oncogene, carried by avian defective retroviruses, causes leukaemias in the chicken and transforms haematopoietic cells in vitro. Its normal cellular equivalent c-myb, has been shown to promote the proliferation and block the differentiation of haematopoietic cells in several experimental models and is required for fetal haematopoiesis. Two other members of the family have been cloned more recently, A-myb and B-myb, which show sequence homology with c-myb in several domains, of which the DNA binding domain as well as other regulatory domains. Both have been shown to be transcription factors. B-myb is also involved in the control of proliferation and differentiation, but, unlike c-myb, it is expressed in many cell types. The third member of the family, A-myb, shows the most restricted pattern of expression, suggesting a very specific role for this transcription factor. A-myb is expressed in a subpopulation of normal B lymphocytes activated in vivo and localised in the germinal center of peripheral lymphoid organs and is not detected at significant levels in all other mature or immature haematopoietic populations studied, including bone marrow cells, T lymphocytes, granulocytes, monocytes, either at rest or after in vitro activation. These studies indicate that A-myb plays a role during a narrow window of normal B cell differentiation. A-myb expression has also been studied in a wide range of neoplastic B cells, representing the whole spectrum of B cell differentiation. A-myb is strongly expressed in Burkitt's lymphomas (BL) and slg+ B-acute lymphoblastic leukaemias (B-ALL) and not in all other leukaemias/lymphomas tested, with the exception of a subset of CLL (about 25% of cases). It is intriguing that the A-myb genome has been localised relatively close to the c-myc gene on chromosome 8, suggesting that

Effects of mantle rheologies on viscous heating induced by glacial isostatic adjustment

NARCIS (Netherlands)

Huang, Ping Ping; Wu, Patrick; van der Wal, W.

2018-01-01

It has been argued that viscous dissipation from mantle flow in response to surface loading during glacial cycles can result in short-term heating and thus trigger transient volcanism or changes in mantle properties, which may in turn affect mantle dynamics. Furthermore, heating near the Earth's

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

Energy Technology Data Exchange (ETDEWEB)

Poljanc, Karin [Atominstitut der Osterreichischen Universitaeten, Vienna University of Technology, Stadionallee 2, 1020 Vienna (Austria); Steinhauser, Georg [Atominstitut der Osterreichischen Universitaeten, Vienna University of Technology, Stadionallee 2, 1020 Vienna (Austria)]. E-mail: georg.steinhauser@ati.ac.at; Sterba, Johannes H. [Atominstitut der Osterreichischen Universitaeten, Vienna University of Technology, Stadionallee 2, 1020 Vienna (Austria); Buchtela, Karl [Atominstitut der Osterreichischen Universitaeten, Vienna University of Technology, Stadionallee 2, 1020 Vienna (Austria); Bichler, Max [Atominstitut der Osterreichischen Universitaeten, Vienna University of Technology, Stadionallee 2, 1020 Vienna (Austria)

2007-03-01

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), {gamma}-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 {sup 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.

Comparative histochemical study of Bowen’s disease and actinic keratosis: preserved normal basal cells in Bowen’s disease

Directory of Open Access Journals (Sweden)

H Ishida

2009-12-01

Full Text Available The degree of DNA-instability as revealed by immunohistochemical staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test has been recently used as a marker of malignancy. This technique was applied to examine 17 skin tissue samples of Bowen’s disease, 47 of actinic keratosis, 15 of squamous cell carcinoma, 5 of seborrheic keratosis, and 10 of normal skin. All benign neoplastic cells of seborrheic keratosis and normal epidermal cells were negative. On the other hand, all cancer cells were positive with the DNA-instability test, indicating their malignancy, but all basal cells in Bowen’s disease were completely negative. Compatible with this result, the basal cells in Bowen’s disease were characteristically normal as evident in other histochemical examinations. Thus, they were negative with p53 immunohistochemistry, with normal signals of chromosome 17 in situ hybridisation and argyrophilic nucleolar organiser region, and showed slightly enhanced proliferative activity as revealed by proliferating cell nuclear antigen immunohistochemistry. Immunohistochemical staining with 34 ß E12 (monoclonal antibody against cytokeratins 1, 5, 10, and 14, which stains all normal epidermal keratinocytes including basal cells, showed that only the basal cells of Bowen’s disease stained strongly and homogeneously, while all cancer cells in the upper layers of Bowen’s disease and all layers of actinic keratosis were only sporadically or weakly stained. Staining with 34 ß B4 (monoclonal antibody against cytokeratin 1, which recognises the whole epidermis except for the basal layer in the normal epidermis, showed that the basal cells in the Bowen’s disease were completely negative, and lower layer cells in the actinic keratosis and upper layer cells in Bowen’s disease were only sporadically stained positive, although the superficial layer cells in actinic keratosis stained strongly and homogeneously. Our findings clearly

Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

International Nuclear Information System (INIS)

Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

2011-01-01

Highlights: → Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. → The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. → Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

2-dimensional triplicated waveform modeling of the mantle transition zone beneath Northeast Asia

Science.gov (United States)

Lai, Y.; Chen, L.; Wang, T.

2017-12-01

The Mantle Transition Zone (MTZ) of Northeast Asia has long been investigated by geoscientists for its critical importance where the subducted Pacific slab is stagnant above the 660km discontinuity, accompanied by complicated mantle processes. Taking advantages of the frequent occurrent deep earthquakes in subduction zone and dense seismic arrays in Northeast China, we successfully constructed the fine-scale P and SH velocity structure of a narrow azimuthal fan area based on 2-Dimensional (2D) triplicated waveform modeling for three deep close earthquakes, in which the triplicated waveforms are very sensitive to MTZ velocity structure in general, particularly the morphology of the stagnant slab in Northeast Asia. In our 2D triplication study, for the first time, we show a quite consistent feature of a high velocity layer for both Vp and Vs with the thickness of 140km and the length of 1200km just atop the 660km discontinuity, the western edge of the stagnant slab intersect with the North-South Gravity Lineament in China and has the subducting age of 30 Ma. Compared with a quite normal Vp, the Shear wave velocity reduction of -0.5% in the slab and -2.5% in the upper MTZ is required to reconcile the SH waves featured by the broad BOD. The high Vp/Vs ratio beneath Northeast Asia may imply a water-rich MTZ with the H2O content of 0.1-0.3 wt%. Particularly, a low velocity anomaly of about 150km wide was detected in the overall high-velocity stagnant slab by both P and SH triplicated waveform modeling, with the velocity anomaly value of -1% and -3%, respectively. The gap/window in the stagnant slab may provide a passage for hot deeper mantle materials to penetrate through the thick slab and feed the surface Changbaishan volcano. We also speculate that the existence of such a gap can be the manifestation of the original heterogeneity in the subducted slab and will further exacerbatethe impending gravitational instability and speed up mantle avalanche.

BurnMan: A lower mantle mineral physics toolkit

KAUST Repository

Cottaar, Sanne; Heister, Timo; Rose, Ian; Unterborn, Cayman

2014-01-01

We present BurnMan, an open-source mineral physics toolbox to determine elastic properties for specified compositions in the lower mantle by solving an Equation of State (EoS). The toolbox, written in Python, can be used to evaluate seismic velocities of new mineral physics data or geodynamic models, and as the forward model in inversions for mantle composition. The user can define the composition from a list of minerals provided for the lower mantle or easily include their own. BurnMan provides choices in methodology, both for the EoS and for the multiphase averaging scheme. The results can be visually or quantitatively compared to observed seismic models. Example user scripts show how to go through these steps. This paper includes several examples realized with BurnMan: First, we benchmark the computations to check for correctness. Second, we exemplify two pitfalls in EoS modeling: using a different EoS than the one used to derive the mineral physical parameters or using an incorrect averaging scheme. Both pitfalls have led to incorrect conclusions on lower mantle composition and temperature in the literature. We further illustrate that fitting elastic velocities separately or jointly leads to different Mg/Si ratios for the lower mantle. However, we find that, within mineral physical uncertainties, a pyrolitic composition can match PREM very well. Finally, we find that uncertainties on specific input parameters result in a considerable amount of variation in both magnitude and gradient of the seismic velocities. © 2014. American Geophysical Union. All Rights Reserved.

BurnMan: A lower mantle mineral physics toolkit

KAUST Repository

Cottaar, Sanne

2014-04-01

We present BurnMan, an open-source mineral physics toolbox to determine elastic properties for specified compositions in the lower mantle by solving an Equation of State (EoS). The toolbox, written in Python, can be used to evaluate seismic velocities of new mineral physics data or geodynamic models, and as the forward model in inversions for mantle composition. The user can define the composition from a list of minerals provided for the lower mantle or easily include their own. BurnMan provides choices in methodology, both for the EoS and for the multiphase averaging scheme. The results can be visually or quantitatively compared to observed seismic models. Example user scripts show how to go through these steps. This paper includes several examples realized with BurnMan: First, we benchmark the computations to check for correctness. Second, we exemplify two pitfalls in EoS modeling: using a different EoS than the one used to derive the mineral physical parameters or using an incorrect averaging scheme. Both pitfalls have led to incorrect conclusions on lower mantle composition and temperature in the literature. We further illustrate that fitting elastic velocities separately or jointly leads to different Mg/Si ratios for the lower mantle. However, we find that, within mineral physical uncertainties, a pyrolitic composition can match PREM very well. Finally, we find that uncertainties on specific input parameters result in a considerable amount of variation in both magnitude and gradient of the seismic velocities. © 2014. American Geophysical Union. All Rights Reserved.

Normal function of immunologic stem cells from aged mice

International Nuclear Information System (INIS)

Harrison, D.E.; Doubleday, J.W.

1975-01-01

Marrow or spleen grafts from aged donor mice produced antibody-forming cells as effectively as did grafts from younger controls in recipients tested 3 to 10 months after the transplantation. All recipients were lethally irradiated, and the T6 chromosome marker was used to demonstrate that they were populated by donor cell lines. Recipients of aged or younger control grafts gave similar responses when stimulated with varying doses of antigen and when tested at different times after the transplantation except in two cases. Recipients of aged spleen grafts gave significantly lower responses than younger controls for the first few weeks after the transplantation. If recipients had been thymectomized before lethal irradiation, aged cell lines (pooled marrow and spleen cells) gave only 37 percent of the responses of younger controls. Given sufficient time and intact young recipients, immunologic stem cell lines from old donors populated recipients with cells having normal immune responses. These results suggest that age-related immunologic defects are not intrinsically timed in the precursor cell lines that populate the immune system. (U.S.)

Length-scales of Slab-induced Asthenospheric Deformation from Geodynamic Modeling, Mantle Deformation Fabric, and Synthetic Shear Wave Splitting

Science.gov (United States)

Jadamec, M. A.; MacDougall, J.; Fischer, K. M.

2017-12-01

The viscosity structure of the Earth's interior is critically important, because it places a first order constraint on plate motion and mantle flow rates. Geodynamic models using a composite viscosity based on experimentally derived flow laws for olivine aggregates show that lateral viscosity variations emerge in the upper mantle due to the subduction dynamics. However, the length-scale of this transition is still not well understood. Two-dimensional numerical models of subduction are presented that investigate the effect of initial slab dip, maximum yield stress (slab strength), and viscosity formulation (Newtonian versus composite) on the emergent lateral viscosity variations in the upper-mantle and magnitude of slab-driven mantle flow velocity. Significant viscosity reductions occur in regions of large flow velocity gradients due to the weakening effect of the dislocation creep deformation mechanism. The dynamic reductions in asthenospheric viscosity (less than 1018 Pa s) occur within approximately 500 km from driving force of the slab, with peak flow velocities occurring in models with a lower yield stress (weaker slab) and higher stress exponent. This leads to a sharper definition of the rheological base of the lithosphere and implies lateral variability in tractions along the base of the lithosphere. As the dislocation creep mechanism also leads to mantle deformation fabric, we then examine the spatial variation in the LPO development in the asthenosphere and calculate synthetic shear wave splitting. The models show that olivine LPO fabric in the asthenosphere generally increases in alignment strength with increased proximity to the slab, but can be transient and spatially variable on small length scales. The vertical flow fields surrounding the slab tip can produce shear-wave splitting variations with back-azimuth that deviate from the predictions of uniform trench-normal anisotropy, a result that bears on the interpretation of complexity in shear

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

Science.gov (United States)

Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

2011-01-01

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

Experimental investigation of flow-induced fabrics in rocks at upper-mantle pressures: Application to understanding mantle dynamics and seismic anisotropy

Energy Technology Data Exchange (ETDEWEB)

Kohlstedt, David L. [Univ. of Minnesota, Minneapolis, MN (United States)

2016-04-26

The goal of this collaborative research effort between W.B. Durham at the Massachusetts Institute of Technology (MIT) and D.L. Kohlstedt and S. Mei at the University of Minnesota (UMN) was to exploit a newly developed technology for high-pressure, high-temperature deformation experimentation, namely, the deformation DIA (D-DIA) to determine the deformation behavior of a number of important upper mantle rock types including olivine, garnet, enstatite, and periclase. Experiments were carried out under both hydrous and anhydrous conditions and at both lithospheric and asthenospheric stress and temperature conditions. The result was a group of flow laws for Earth’s upper mantle that quantitatively describe the viscosity of mantle rocks from shallow depths (the lithosphere) to great depths (the asthenosphere). These flow laws are fundamental for modeling the geodynamic behavior and heat transport from depth to Earth’s surface.

Experimental investigation of flow-induced fabrics in rocks at upper-mantle pressures. Application to understanding mantle dynamics and seismic anisotropy

Energy Technology Data Exchange (ETDEWEB)

Durham, William B. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

2016-05-02

The goal of this collaborative research effort between W.B. Durham at the Massachusetts Institute of Technology (MIT) and D.L. Kohlstedt and S. Mei at the University of Minnesota (UMN) was to exploit a newly developed technology for high-pressure, high-temperature deformation experimentation, namely, the deformation DIA (D-DIA), to determine the deformation behavior of a number of important upper mantle rock types including olivine, garnet, enstatite, and periclase. Experiments were carried out under both hydrous and anhydrous conditions and at both lithospheric and asthenospheric stress and temperature conditions. The result was a group of flow laws for Earth’s upper mantle that quantitatively describe the viscosity of mantle rocks from shallow depths (the lithosphere) to great depths (the asthenosphere). These flow laws are fundamental for modeling the geodynamic behavior and heat transport from depth to Earth’s surface.-

Re - Os isotopic constraints on the origin of volcanic rocks, Gorgona Island, Colombia: Os isotopic evidence for ancient heterogeneities in the mantle

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