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Sample records for multiple nodal cells

  1. Prognostic impact of the level of nodal involvement: retrospective analysis of patients with advanced oral squamous cell carcinoma.

    Science.gov (United States)

    Murakami, R; Nakayama, H; Semba, A; Hiraki, A; Nagata, M; Kawahara, K; Shiraishi, S; Hirai, T; Uozumi, H; Yamashita, Y

    2017-01-01

    We retrospectively evaluated the prognostic impact of the level of nodal involvement in patients with advanced oral squamous cell carcinoma (SCC). Between 2005 and 2010, 105 patients with clinical stage III or IV oral SCC had chemoradiotherapy preoperatively. Clinical (cN) and pathological nodal (pN) involvement was primarily at levels Ib and II. We defined nodal involvement at levels Ia and III-V as anterior and inferior extensions, respectively, and recorded such findings as extensive. With respect to pretreatment variables (age, clinical stage, clinical findings of the primary tumour, and nodal findings), univariate analysis showed that extensive cN was the only significant factor for overall survival (hazard ratio [HR], 3.27; 95% CI 1.50 to 7.13; p=0.001). Univariate analysis showed that all pN findings, including the nodal classification (invaded nodes, multiple, and contralateral) and extensive involvement were significant, and multivariate analysis confirmed that extensive pN (HR 4.71; 95% CI 1.85 to 11.97; p=0.001) and multiple pN (HR 2.59; 95% CI 1.10 to 6.09; p=0.029) were independent predictors of overall survival. Assessment based on the level of invaded neck nodes may be a better predictor of survival than the current nodal classification. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. In vitro mass multiplication of pomegranate from cotyledonary nodal ...

    African Journals Online (AJOL)

    Maria

    2013-05-15

    May 15, 2013 ... Key words: Establishment, multiplication, rooting, acclimatization, Punica granatum. INTRODUCTION. Pomegranate Punica granatum L. belongs to the family. Punicaceae which comprises only one genus (Punica) and only two species, P. granatum and P. proptopunica. This is popularly known as anar, ...

  3. Regional nodal relapse in surgically staged Merkel cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoeller, Ulrike; Mueller, Thomas; Schubert, Tina; Budach, Volker; Ghadjar, Pirus [Charite Universitaetsmedizin Berlin, Department of Radiation Oncology, Berlin (Germany); Brenner, Winfried [Charite Universitaetsmedizin Berlin, Department of Nuclear Medicine, Berlin (Germany); Kiecker, Felix [Charite Universitaetsmedizin Berlin, Department of Dermatology, Berlin (Germany); Schicke, Bernd [Tumor Center Berlin, Berlin (Germany); Haase, Oliver [Charite Universitaetsmedizin Berlin, Department of Surgery, Berlin (Germany)

    2014-10-08

    The nodal relapse pattern of surgically staged Merkel cell carcinoma (MCC) with/without elective nodal radiotherapy (RT) was studied in a single institution. A total of 51 patients with MCC, 33 % UICC stage I, 14 % II, 53 % III (4 lymph node metastases of unknown primary) were eligible. All patients had surgical staging: 23 patients sentinel node biopsy (SNB), 22 patients SNB followed by lymphadenectomy (LAD) and 6 patients LAD. In all, 94 % of the primary tumors (PT) were completely resected; 57 % of patients received RT, 51 % of known PT sites, 33 % (8/24 patients) regional RT to snN0 nodes and 68 % (17/27 patients) to pN+ nodes, mean reference dose 51.5 and 50 Gy, respectively. Mean follow-up was 6 years (range 2-14 years). A total of 22 % (11/51) patients developed regional relapses (RR); the 5-year RR rate was 27 %. In snN0 sites (stage I/II), relapse occurred in 5 of 14 nonirradiated vs. none of 8 irradiated sites (p = 0.054), resulting in a 5-year RR rate of 33 % versus 0 % (p = 0.16). The crude RR rate was lower in stage I (12 %, 2/17 patients) than for stage II (43 %, 3/7 patients). In stage III (pN+), RR appeared to be less frequent in irradiated sites (18 %, 3/14 patients) compared with nonirradiated sites (33 %, 3/10 patients, p = 0.45) with 5-year RR rates of 23 % vs. 34 %, respectively. Our data suggest that adjuvant nodal RT plays a major role even if the sentinel nodes were negative. Adjuvant RT of the lymph nodes in patients with stage IIa tumors and RT after LAD in stage III tumors is proposed and should be evaluated prospectively. (orig.) [German] Untersucht wurde das regionaere Rezidivmuster des Merkelzell-Karzinoms (MCC) nach chirurgischem Staging und stadienadaptierter Therapie. Eingeschlossen wurden 51 Patienten mit lokalisiertem MCC: 33 % hatten UICC-Stadium-I-, 14 % -II-, 53 % -III-Tumoren (davon 4 Lymphknotenmetastasen eines unbekannten Primaertumors). Alle Patienten erhielten ein chirurgisches Staging: 23 Waechterlymphknotenbiopsien (SNB

  4. Churchill regulates cell movement and mesoderm specification by repressing Nodal signaling

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    Mentzer Laura

    2007-11-01

    Full Text Available Abstract Background Cell movements are essential to the determination of cell fates during development. The zinc-finger transcription factor, Churchill (ChCh has been proposed to regulate cell fate by regulating cell movements during gastrulation in the chick. However, the mechanism of action of ChCh is not understood. Results We demonstrate that ChCh acts to repress the response to Nodal-related signals in zebrafish. When ChCh function is abrogated the expression of mesodermal markers is enhanced while ectodermal markers are expressed at decreased levels. In cell transplant assays, we observed that ChCh-deficient cells are more motile than wild-type cells. When placed in wild-type hosts, ChCh-deficient cells often leave the epiblast, migrate to the germ ring and are later found in mesodermal structures. We demonstrate that both movement of ChCh-compromised cells to the germ ring and acquisition of mesodermal character depend on the ability of the donor cells to respond to Nodal signals. Blocking Nodal signaling in the donor cells at the levels of Oep, Alk receptors or Fast1 inhibited migration to the germ ring and mesodermal fate change in the donor cells. We also detect additional unusual movements of transplanted ChCh-deficient cells which suggests that movement and acquisition of mesodermal character can be uncoupled. Finally, we demonstrate that ChCh is required to limit the transcriptional response to Nodal. Conclusion These data establish a broad role for ChCh in regulating both cell movement and Nodal signaling during early zebrafish development. We show that chch is required to limit mesodermal gene expression, inhibit Nodal-dependant movement of presumptive ectodermal cells and repress the transcriptional response to Nodal signaling. These findings reveal a dynamic role for chch in regulating cell movement and fate during early development.

  5. F18 FDG positron emission tomography revelation of primary testicular lymphoma with concurrent multiple extra nodal involvement

    International Nuclear Information System (INIS)

    Vamsy, Mohana; Dattatreya, P.S.; Parakh, Megha; Dayal, Monal; Prabhakar Rao, V.V.S.

    2013-01-01

    Primary testicular lymphoma (PTL) a relatively rare disease of non-Hodgkin's lymphomas occurring with a lesser incidence of 1-2% has a propensity to occur at later ages above 50 years. PTL spreads to extra nodal sites due to deficiency of extra cellular adhesion molecules. We present detection of multiple sites of extra nodal involvement of PTL by F-18 positron emission tomography/computed tomography study aiding early detection of the dissemination thus aiding in staging and management. (author)

  6. MicroRNA expression in nodal and extranodal Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Mandrup, Charlotte; Petersen, Anders; Højfeldt, Anne Dirks

    MicroRNA expression in nodal and extranodal Diffuse Large B-cell Lymphoma   C. Mandrup1, A. Petersen1, A. D. Hoejfeldt1, H. F. Thomsen1, J. Madsen1, J. Dahlgaard1, P. Johansen2, A. Bukh1, K. Dybkaer1 and H. E Johnsen1. 1Department of Hematology, 2Pathological Institute, Aalborg Hospital, Aarhus...... University Hospital, Aalborg, Denmark Introduction: The aim of this project was to analyse microRNA (miRNA) expression in nodal and extranodal diffuse large B-cell lymphoma (DLBCL). Manifestation at diagnosis may be nodal and/or extranodal. At present, there are no known determinants for none...... of the manifestations, and no way to predict the potential progression from nodal to extranodal disease. miRNA are small regulatory RNA molecules with core function to repress/cleave sequence complementary mRNA targets. Abnormalities in miRNA genetics and expression are known to affect initiation and development...

  7. Tumor microvessel density–associated mast cells in canine nodal lymphoma

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    Moges Woldemeskel

    2014-11-01

    Full Text Available Objective: Mast cells are associated in angiogenesis in various human and animal neoplasms. However, association of mast cells with tumor microvessel density in canine lymphoma was not previously documented. The objective of the study is to determine if mast cells are increased in canine nodal lymphomas and to evaluate their correlation with tumor microvessel density and grading of lymphomas. Methods: Nodal lymphomas from 33 dogs were studied and compared with nonneoplastic lymph nodes from 6 dogs as control. Mast cell count was made on Toluidine blue stained sections. Immunohistochemistry using antibody against Factor VIII was employed to visualize and determine microvessel density. Results: The mast cell count in lymphoma (2.95 ± 2.4 was significantly higher (p < 0.05 than that in the control (0.83 ± 0.3 and was positively correlated with tumor microvessel density (r = 0.44, p = 0.009. Significant difference was not observed in mast cell count and tumor microvessel density among different gradings of lymphomas. Conclusions: Mast cells are associated with tumor microvessel density in canine nodal lymphoma with no significant difference among gradings of lymphomas. Mast cells may play an important role in development of canine nodal lymphomas. Further detailed investigation on the role of mast cells as important part of tumor microenvironment in canine nodal lymphomas is recommended.

  8. Tumor microvessel density–associated mast cells in canine nodal lymphoma

    Science.gov (United States)

    Mann, Elizabeth; Whittington, Lisa

    2014-01-01

    Objective: Mast cells are associated in angiogenesis in various human and animal neoplasms. However, association of mast cells with tumor microvessel density in canine lymphoma was not previously documented. The objective of the study is to determine if mast cells are increased in canine nodal lymphomas and to evaluate their correlation with tumor microvessel density and grading of lymphomas. Methods: Nodal lymphomas from 33 dogs were studied and compared with nonneoplastic lymph nodes from 6 dogs as control. Mast cell count was made on Toluidine blue stained sections. Immunohistochemistry using antibody against Factor VIII was employed to visualize and determine microvessel density. Results: The mast cell count in lymphoma (2.95 ± 2.4) was significantly higher (p < 0.05) than that in the control (0.83 ± 0.3) and was positively correlated with tumor microvessel density (r = 0.44, p = 0.009). Significant difference was not observed in mast cell count and tumor microvessel density among different gradings of lymphomas. Conclusions: Mast cells are associated with tumor microvessel density in canine nodal lymphoma with no significant difference among gradings of lymphomas. Mast cells may play an important role in development of canine nodal lymphomas. Further detailed investigation on the role of mast cells as important part of tumor microenvironment in canine nodal lymphomas is recommended. PMID:26770752

  9. TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways

    International Nuclear Information System (INIS)

    Sun, Jing; Liu, Su-zhi; Lin, Yan; Cao, Xiao-pan; Liu, Jia-ming

    2014-01-01

    Highlights: •TGF-β promoted Nodal expression in glioma cells. •TGF-β promoted Nodal expression via activating Smad and ERK1/2 pathways. •TGF-β promotes glioma cell growth via activating Nodal expression. -- Abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy

  10. Exclusion of elective nodal irradiation is associated with minimal elective nodal failure in non-small cell lung cancer

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    Cox James D

    2009-01-01

    Full Text Available Abstract Background Controversy still exists regarding the long-term outcome of patients whose uninvolved lymph node stations are not prophylactically irradiated for non-small cell lung cancer (NSCLC treated with definitive radiotherapy. To determine the frequency of elective nodal failure (ENF and in-field failure (IFF, we examined a large cohort of patients with NSCLC staged with positron emission tomography (PET/computed tomography (CT and treated with 3-dimensional conformal radiotherapy (3D-CRT that excluded uninvolved lymph node stations. Methods We retrospectively reviewed the records of 115 patients with non-small cell lung cancer treated at our institution with definitive radiation therapy with or without concurrent chemotherapy (CHT. All patients were treated with 3D-CRT, including nodal regions determined by CT or PET to be disease involved. Concurrent platinum-based CHT was administered for locally advanced disease. Patients were analyzed in follow-up for survival, local regional recurrence, and distant metastases (DM. Results The median follow-up time was 18 months (3 to 44 months among all patients and 27 months (6 to 44 months among survivors. The median overall survival, 2-year actuarial overall survival and disease-free survival were 19 months, 38%, and 28%, respectively. The majority of patients died from DM, the overall rate of which was 36%. Of the 31 patients with local regional failure, 26 (22.6% had IFF, 5 (4.3% had ENF and 2 (1.7% had isolated ENF. For 88 patients with stage IIIA/B, the frequencies of IFF, any ENF, isolated ENF, and DM were 23 (26%, 3 (9%, 1 (1.1% and 36 (40.9%, respectively. The comparable rates for the 22 patients with early stage node-negative disease (stage IA/IB were 3 (13.6%, 1(4.5%, 0 (0%, and 5 (22.7%, respectively. Conclusion We observed only a 4.3% recurrence of any ENF and a 1.7% recurrence of isolated ENF in patients with NSCLC treated with definitive 3D-CRT without prophylactic irradiation of

  11. Exclusion of elective nodal irradiation is associated with minimal elective nodal failure in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Sulman, Erik P; Komaki, Ritsuko; Klopp, Ann H; Cox, James D; Chang, Joe Y

    2009-01-01

    Controversy still exists regarding the long-term outcome of patients whose uninvolved lymph node stations are not prophylactically irradiated for non-small cell lung cancer (NSCLC) treated with definitive radiotherapy. To determine the frequency of elective nodal failure (ENF) and in-field failure (IFF), we examined a large cohort of patients with NSCLC staged with positron emission tomography (PET)/computed tomography (CT) and treated with 3-dimensional conformal radiotherapy (3D-CRT) that excluded uninvolved lymph node stations. We retrospectively reviewed the records of 115 patients with non-small cell lung cancer treated at our institution with definitive radiation therapy with or without concurrent chemotherapy (CHT). All patients were treated with 3D-CRT, including nodal regions determined by CT or PET to be disease involved. Concurrent platinum-based CHT was administered for locally advanced disease. Patients were analyzed in follow-up for survival, local regional recurrence, and distant metastases (DM). The median follow-up time was 18 months (3 to 44 months) among all patients and 27 months (6 to 44 months) among survivors. The median overall survival, 2-year actuarial overall survival and disease-free survival were 19 months, 38%, and 28%, respectively. The majority of patients died from DM, the overall rate of which was 36%. Of the 31 patients with local regional failure, 26 (22.6%) had IFF, 5 (4.3%) had ENF and 2 (1.7%) had isolated ENF. For 88 patients with stage IIIA/B, the frequencies of IFF, any ENF, isolated ENF, and DM were 23 (26%), 3 (9%), 1 (1.1%) and 36 (40.9%), respectively. The comparable rates for the 22 patients with early stage node-negative disease (stage IA/IB) were 3 (13.6%), 1(4.5%), 0 (0%), and 5 (22.7%), respectively. We observed only a 4.3% recurrence of any ENF and a 1.7% recurrence of isolated ENF in patients with NSCLC treated with definitive 3D-CRT without prophylactic irradiation of uninvolved lymph node stations. Thus

  12. Primary nodal peripheral T-cell lymphomas: diagnosis and therapeutic considerations

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    Luis Alberto de Pádua Covas Lage

    2015-08-01

    Full Text Available Nodal peripheral T-cell lymphomas are a rare group of neoplasms derived from post-thymic and activated T lymphocytes. A review of scientific articles listed in PubMed, Lilacs, and the Cochrane Library databases was performed using the term "peripheral T-cell lymphomas". According to the World Health Organization classification of hematopoietic tissue tumors, this group of neoplasms consists of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, angioimmunoblastic T-cell lymphoma (AITL, anaplastic large cell lymphoma-anaplastic lymphoma kinase positive (ALCL-ALK+, and a provisional entity called anaplastic large cell lymphoma-anaplastic lymphoma kinase negative (ALCL-ALK-. Because the treatment and prognoses of these neoplasms involve different principles, it is essential to distinguish each one by its clinical, immunophenotypic, genetic, and molecular features. Except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, which has no adverse international prognostic index, the prognosis of nodal peripheral T-cell lymphomas is worse than that of aggressive B-cell lymphomas. Chemotherapy based on anthracyclines provides poor outcomes because these neoplasms frequently have multidrug-resistant phenotypes. Based on this, the current tendency is to use intensified cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP regimens with the addition of new drugs, and autologous hematopoietic stem cell transplantation. This paper describes the clinical features and diagnostic methods, and proposes a therapeutic algorithm for nodal peripheral T-cell lymphoma patients.

  13. Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: management and outcomes of a rare entity.

    Science.gov (United States)

    Kotteas, E A; Pavlidis, N

    2015-04-01

    Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine tumour with distinct clinical and biological behaviour. We conducted a review of retrospective data extracted from 90 patients focusing on the management and outcome of this disease. We also compared life expectancy of these patients with the outcome of patients with known Merkel primaries and with neuroendocrine cancers of unidentifiable primary. There is a limited body of data for this type of malignancy, however, patients with Merkel cell nodal carcinoma of unknown primary site, seem to have better survival when treated aggressively than patients with cutaneous Merkel tumours of the same stage and equal survival with patients with low-grade neuroendocrine tumour of unknown origin. The lack of prospective trials, and the inadequate data, hamper the management of these tumours. Establishment of treatment guidelines is urgently needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Primary Germ Cell Tumor of Testes with Extensive Lymph Nodal and Splenic Metastases Masquerading Lymphoma on 18-F-FDG PET/CT

    Science.gov (United States)

    Tripathy, Sarthak; Mukherjee, Anirban; Bal, Chandrasekhar; Tripathi, Madhavi; Mallick, Saumyaranjan; Shamim, Shamim Ahmed

    2017-01-01

    Germ cell tumors (GCT) account for the 95% of the malignancies associated with testes. They are the most common solid malignancies affecting the males in the age group of 15–35 years. It is known to be bilateral in 3% of cases. We herein present FDG PET-CT findings of a case with biopsy proven GCT with multiple lymph nodal and splenic metastases mimicking lymphomatous neoplasm. PMID:28533651

  15. Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus.

    Science.gov (United States)

    Onozawa, Masakatsu; Nihei, Keiji; Ishikura, Satoshi; Minashi, Keiko; Yano, Tomonori; Muto, Manabu; Ohtsu, Atsushi; Ogino, Takashi

    2009-08-01

    There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer. Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI. One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence. In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed.

  16. Comparison of treatment outcomes between involved-field and elective nodal irradiation in limited-stage small cell lung cancer

    International Nuclear Information System (INIS)

    Han, Tae-Jin; Kim, Hak-Jae; Wu, Hong-Gyun; Heo, Dae-Seog; Kim, Young-Whan; Lee, Se-Hoon

    2012-01-01

    The present study was performed to assess the usefulness of involved-field irradiation and the impact of 18 F-fluorodeoxyglucose-positron emission tomography-based staging on treatment outcomes in limited-stage small cell lung cancer. Eighty patients who received definitive chemoradiotherapy for limited-stage small cell lung cancer were retrospectively analyzed. Fifty patients were treated with involved-field irradiation, which means that the radiotherapy portal includes only clinically identifiable tumors. The other 30 patients were irradiated with a comprehensive portal, including uninvolved mediastinal and/or supraclavicular lymph nodes, so-called elective nodal irradiation. No significant difference was seen in clinical factors between the two groups. At a median follow-up of 27 months (range, 5-75 months), no significant differences were observed in 3 year overall survival (44.6 vs. 54.1%, P=0.220) and 3 year progression-free survival (24.4 vs. 42.8%, P=0.133) between the involved-field irradiation group and the elective nodal irradiation group, respectively. For patients who did not undergo positron emission tomography scans, 3 year overall survival (29.3 vs. 56.3%, P=0.022) and 3 year progression-free survival (11.0 vs. 50.0%, P=0.040) were significantly longer in the elective nodal irradiation group. Crude incidences of isolated nodal failure were 6.0% in the involved-field irradiation group and 0% in the elective nodal irradiation group, respectively. All isolated nodal failures were developed in patients who had not undergone positron emission tomography scans in their initial work-ups. If patients did not undergo positron emission tomography-based staging, the omission of elective nodal irradiation resulted in impaired survival outcomes and raised the risk of isolated nodal failure. Therefore, involved-field irradiation for limited-stage small cell lung cancer might be reasonable only with positron emission tomography scan implementation. (author)

  17. Concurrent chemoradiotherapy with S-1 in patients with stage III-IV oral squamous cell carcinoma: A retrospective analysis of nodal classification based on the neck node level.

    Science.gov (United States)

    Murakami, Ryuji; Semba, Akiko; Kawahara, Kenta; Matsuyama, Keiya; Hiraki, Akimitsu; Nagata, Masashi; Toya, Ryo; Yamashita, Yasuyuki; Oya, Natsuo; Nakayama, Hideki

    2017-07-01

    The aim of the present study was to retrospectively evaluate the treatment outcomes of concurrent chemoradiotherapy (CCRT) with S-1, an oral fluoropyrimidine anticancer agent, for advanced oral squamous cell carcinoma (SCC). The study population consisted of 47 patients with clinical stage III or IV oral SCC, who underwent CCRT with S-1. Pretreatment variables, including patient age, clinical stage, T classification, midline involvement of the primary tumor and nodal status, were analyzed as predictors of survival. In addition to the N classification (node-positive, multiple and contralateral), the prognostic impact of the level of nodal involvement was assessed. Nodal involvement was mainly observed at levels Ib and II; involvement at levels Ia and III-V was considered to be anterior and inferior extension, respectively, and was recorded as extensive nodal involvement (ENI). The 3-year overall survival (OS) and progression-free survival (PFS) rates were 37 and 27%, respectively. A finding of ENI was a significant factor for OS [hazard ratio (HR)=2.16; 95% confidence interval (CI): 1.03-4.55; P=0.038] and PFS (HR=2.65; 95% CI: 1.32-5.33; P=0.005); the 3-year OS and PFS rates in patients with vs. those without ENI were 23 vs. 50% and 9 vs. 43%, respectively. The other variables were not significant. Therefore, CCRT with S-1 may be an alternative treatment for advanced oral SCC; favorable outcomes are expected in patients without ENI.

  18. Efficacy of elective nodal irradiation in skin squamous cell carcinoma of the face, ears, and scalp

    OpenAIRE

    Wray, Justin; Amdur, Robert J.; Morris, Christopher G.; Werning, John; Mendenhall, William M.

    2015-01-01

    Background In patients at high risk for regional node metastasis from squamous cell carcinoma (SCC) of the skin of the face, ear, or scalp, radiotherapy to the regional nodes is an alternative to parotid or neck surgery. Data on the efficacy of elective nodal radiotherapy in this setting are scarce such that there is no publication specifically addressing the subject. The purpose of our study is to fill this void in the skin cancer literature. Methods This is a single-institution study of out...

  19. F-18 fluorodeoxyglucose positron emission tomography in the mediastinal nodal staging of non-small cell lung carcinoma

    International Nuclear Information System (INIS)

    Berlangieri, S.U.; Scott, A.M.; Knight, S.; Fitt, G.J.; Hess, E.M.; Pathmaraj, K.; Hennessy, O.F.; Tochon-Danguy, H.J.; Chan, J.G.; Egan, G.F.; Sinclair, R.A.; Clarke, C.P.; McKay, W.J.; St Vincents Hospital, Fitzroy, VIC

    1998-01-01

    Full text: Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG), as a metabolic tumour marker, has been proposed for staging of oncological disease. To determine its role in the mediastinal staging of lung cancer, a prospective comparison of FDG PET with surgery was performed in patients with suspected non-small cell lung carcinoma. The analysis group consists of 70 patients, 49 men and 21 women, mean age 64 yrs (range 41-83 yrs). The PET study was acquired on a Siemens 951/31R scanner over 3 bed positions, 45 minutes following 400MBq FDG. The emission scan was attenuation corrected using measured transmission data. The FDG PET were interpreted by a nuclear physician blinded to the clinical data and the results of the patients' CT scan. On PET, nodes were graded qualitatively on a 5 point scale with scores 4 or greater, positive for tumour involvement. Surgical specimens were obtained in all patients by thoracotomy or mediastinoscopy. The PET metabolic studies and pathology were mapped according to the American Thoracic Society nodal classification resulting in a total of 277 nodal stations evaluated. The PET studies analysed N2 or N3 tumour involvement by nodal station in comparison to histology of pathological specimens or direct visual assessment of the nodal stations at surgery. All patients had proven non-small cell lung carcinoma, except two, in whom, a tissue confirmation of the suspected diagnosis was not attained. PET excluded tumour in 237 of 246 nodal stations (specificity 96%). PET correctly identified 23 of 31 nodal stations with disease (sensitivity 74%). PET correctly staged 260 of 277 nodal stations (accuracy 94%) for disease. FDG PET is an accurate non-invasive functional imaging modality for the mediastinal staging of non-small cell lung cancer and has an important clinical role in the preoperative staging of lung cancer patients

  20. Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus

    International Nuclear Information System (INIS)

    Onozawa, Masakatsu; Nihei, Keiji; Ishikura, Satoshi; Minashi, Keiko; Yano, Tomonori; Muto, Manabu; Ohtsu, Atsushi; Ogino, Takashi

    2009-01-01

    Background and purpose: There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer. Materials and methods: Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI. Results: One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence. Conclusion: In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed.

  1. Isolated cutaneous involvement in a child with nodal anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Vibhu Mendiratta

    2016-01-01

    Full Text Available Non-Hodgkin lymphoma is a common childhood T-cell and B-cell neoplasm that originates primarily from lymphoid tissue. Cutaneous involvement can be in the form of a primary extranodal lymphoma, or secondary to metastasis from a non-cutaneous location. The latter is uncommon, and isolated cutaneous involvement is rarely reported. We report a case of isolated secondary cutaneous involvement from nodal anaplastic large cell lymphoma (CD30 + and ALK + in a 7-year-old boy who was on chemotherapy. This case is reported for its unusual clinical presentation as an acute febrile, generalized papulonodular eruption that mimicked deep fungal infection, with the absence of other foci of systemic metastasis.

  2. T-cell receptor (TCR) phenotype of nodal Epstein-Barr virus (EBV)-positive cytotoxic T-cell lymphoma (CTL): a clinicopathologic study of 39 cases.

    Science.gov (United States)

    Kato, Seiichi; Asano, Naoko; Miyata-Takata, Tomoko; Takata, Katsuyoshi; Elsayed, Ahmed Ali; Satou, Akira; Takahashi, Emiko; Kinoshita, Tomohiro; Nakamura, Shigeo

    2015-04-01

    Among Epstein-Barr virus (EBV)-positive cytotoxic T/NK-cell lymphoma, there are only a few reports on the clinicopathologic features of patients with primary nodal presentation (nodal EBV cytotoxic T-cell lymphoma [CTL]). Here, we compared the clinicopathologic profiles of 39 patients with nodal EBV CTL with those of 27 cases of "extranasal" NK/T-cell lymphoma of nasal type (ENKTL), especially addressing their T-cell receptor (TCR) phenotype. Histologically, 22 of 39 nodal EBV CTL cases (56%) were unique in having centroblastoid appearance, which was contrasted with the lower incidence of this feature in ENKTL (15%, P=0.001). In contrast, pleomorphic appearance was more frequently seen in ENKTL than in nodal EBV CTL (67% vs. 23%, P=0.001). Thirty-three of 39 nodal EBV CTL cases (85%) were of T-cell lineage on the basis of TCR expression and/or TCRγ gene rearrangement; in detail, 18 cases (46%) were TCRβ positive (αβ T), 5 (13%) were TCRγ and/or δ positive (γδ T), and 10 (26%) were TCR-silent type with clonal TCRγ gene rearrangement but no expression of TCRβ, γ, or δ. These results were clearly contrasted by a lower incidence of T-cell lineage in ENKTL (7 cases, 26%, P<0.001). Notably, the survival time of the 5 nodal lymphoma patients with γδ T-cell phenotype was within 3 months, which was inferior to those of αβ T and TCR-silent types (P=0.003), and 3 of those with available clinical information were all found to be associated with autoimmune diseases. These data suggest that nodal EBV CTL is distinct from ENKTL.

  3. Multiple interactions between maternally-activated signalling pathways control Xenopus nodal-related genes.

    Science.gov (United States)

    Rex, Maria; Hilton, Emma; Old, Robert

    2002-03-01

    We have investigated the induction of the six Xenopus nodal-related genes, Xnr1-Xnr6, by maternal determinants. The beta-catenin pathway was modelled by stimulation using Xwnt8, activin-like signalling was modelled by activin, and VegT action was studied by overexpression in animal cap explants. Combinations of factors were examined, and previously unrecognised interactions were revealed in animal caps and whole embryos. For the induction of Xnr5 and Xnr6 in whole embryos, using a beta-catenin antisense morpholino oligonucleotide or a dominant negative XTcf3, we have demonstrated an absolute permissive requirement for the beta-catenin/Tcf pathway, in addition to the requirement for VegT action. In animal caps Xnr5 and Xnr6 are induced in response to VegT overexpression, and this induction is dependent upon the concomitant activation of the beta-catenin pathway that VegT initiates in animal caps. For the induction of Xnr3, VegT interacts negatively so as to inhibit the induction otherwise observed with wnt-signalling alone. The negative effect of VegT is not the result of a general inhibition of wnt-signalling, and does not result from an inhibition of wnt-induced siamois expression. A 294 bp proximal promoter fragment of the Xnr3 gene is sufficient to mediate the negative effect of VegT. Further experiments, employing cycloheximide to examine the dependence of Xnr gene expression upon proteins translated after the mid-blastula stage, demonstrated that Xnrs 4, 5 and 6 are 'primary' Xnr genes whose expression in the late blastula is solely dependent upon factors present before the mid-blastula stage.

  4. Experimental discovery of nodal chains

    Science.gov (United States)

    Yan, Qinghui; Liu, Rongjuan; Yan, Zhongbo; Liu, Boyuan; Chen, Hongsheng; Wang, Zhong; Lu, Ling

    2018-05-01

    Three-dimensional Weyl and Dirac nodal points1 have attracted widespread interest across multiple disciplines and in many platforms but allow for few structural variations. In contrast, nodal lines2-4 can have numerous topological configurations in momentum space, forming nodal rings5-9, nodal chains10-15, nodal links16-20 and nodal knots21,22. However, nodal lines are much less explored because of the lack of an ideal experimental realization23-25. For example, in condensed-matter systems, nodal lines are often fragile to spin-orbit coupling, located away from the Fermi level, coexist with energy-degenerate trivial bands or have a degeneracy line that disperses strongly in energy. Here, overcoming all these difficulties, we theoretically predict and experimentally observe nodal chains in a metallic-mesh photonic crystal having frequency-isolated linear band-touching rings chained across the entire Brillouin zone. These nodal chains are protected by mirror symmetry and have a frequency variation of less than 1%. We use angle-resolved transmission measurements to probe the projected bulk dispersion and perform Fourier-transformed field scans to map out the dispersion of the drumhead surface state. Our results establish an ideal nodal-line material for further study of topological line degeneracies with non-trivial connectivity and consequent wave dynamics that are richer than those in Weyl and Dirac materials.

  5. Immunoarchitectural patterns in nodal marginal zone B-cell lymphoma: a study of 51 cases.

    Science.gov (United States)

    Salama, Mohamed E; Lossos, Izidore S; Warnke, Roger A; Natkunam, Yasodha

    2009-07-01

    Nodal marginal zone lymphoma (NMZL) represents a rare and heterogeneous group that lacks markers specific for the diagnosis. We evaluated morphologic and immunoarchitectural features of 51 NMZLs, and the following immunostains were performed: CD20, CD21, CD23, CD5, CD3, CD43, CD10, Ki-67, BCL1, BCL2, BCL6, HGAL, and LMO2. Four immunoarchitectural patterns were evident: diffuse (38 [75%]), well-formed nodular/follicular (5 [10%]), interfollicular (7 [14%]), and perifollicular (1 [2%]). Additional features included a monocytoid component (36 [71%]), admixed large cells (20 [39%]), plasma cells (24 [47%]), compartmentalizing stromal sclerosis (13 [25%]), and prominent blood vessel sclerosis (10 [20%]). CD21 highlighted disrupted follicular dendritic cell meshwork in 35 (71%) of 49 cases, and CD43 coexpression was present in 10 (24%) of 42 cases. A panel of germinal center-associated markers was helpful in eliminating cases of diffuse follicle center lymphoma. Our results highlight the histologic and immunoarchitectural spectrum of NMZL and the usefulness of immunohistochemical analysis for CD43, CD23, CD21, BCL6, HGAL, and LMO2 in the diagnosis of NMZL.

  6. Programming and isolation of highly pure physiologically and pharmacologically functional sinus-nodal bodies from pluripotent stem cells.

    Science.gov (United States)

    Jung, Julia Jeannine; Husse, Britta; Rimmbach, Christian; Krebs, Stefan; Stieber, Juliane; Steinhoff, Gustav; Dendorfer, Andreas; Franz, Wolfgang-Michael; David, Robert

    2014-05-06

    Therapeutic approaches for "sick sinus syndrome" rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via "biological pacemakers" derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300-400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro.

  7. De Novo Nodal Diffuse Large B-Cell Lymphoma: Identification of Biologic Prognostic Factors

    International Nuclear Information System (INIS)

    Abd El-Hameed, A.

    2005-01-01

    Diffuse large B-cell Lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma (NHL). Although combination chemotherapy has improved the outcome, long-term cure is now possible for approximately 50% of all patients. making the search for parameters identifying patients at high risk particularly needed. The presence of bcl-2 gene rearrangement in de novo DLBCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior. This study investigated the frequency and prognostic significance of t( 14; 18) translocation and bcl-2 protein overexpression in a cohort of patients with de novo nodal DLBCL who where uniformly evaluated and treated. Material and Methods: A total of 40 patients with de novo nodal DLBCL treated at National Cancer Institute (NCI), Cairo University were investigated. Formal infixed, paraffin-embedded sections were analyzed for: I) bcl-2 gene rearrangement including major break point region (mbr) and minor cluster region (mcr) by polymerase chain reaction (PCR). and 2) bcl-2 protein expression by immunohistochemistry using Dako 124 clone. Results were correlated with the clinical features and subsequent clinical course. Bcl-2 gene rearrangement was detected in 8 cases (20%). 2 cases at mbr, and 6 cases at mcr. Bcl-2 protein (> I 0%) was expressed in 24 cases (60%), irrespective of the presence of t( 14; 18) translocation. The t( 14; 18), and bcl-2 protein overexpression were more frequently associated with failure to achieve a complete response to therapy (ρ=0.008. and 0.04. respectively). DLBCL patients with t(14;18), and bcl-2 protein expression had a significantly reduced 5-year disease free survival (ρ=0.04, and 0.01, respectively). The t( 14; 18) translocation, and bcl-2 protein expression define a group of DLBCL patients with a poor prognosis, and could be used to tailor treatment, and to identify candidates for therapeutic approaches. Geographic differences in t(14;18) may be related to the

  8. A proposal for combined MRI and PET/CT interpretation criteria for preoperative nodal staging in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Kim, Yoo Na; Yi, Chin A.; Lee, Kyung Soo; Lee, Ho Yun; Kim, Tae Sung; Chung, Myung Jin; Kwon, O.Jung; Chung, Man Pyo; Kim, Byung-Tae; Choi, Joon Young; Kim, Seon Woo; Han, Joungho; Shim, Young Mog

    2012-01-01

    To determine the positive reading criteria for malignant nodes when interpreting combined MRI and PET/CT images for preoperative nodal staging in non-small-cell lung cancer (NSCLC). Forty-nine patients with biopsy-proven NSCLC underwent both PET/CT and thoracic MRI [diffusion weighted imaging (DWI)]. Each nodal station was evaluated for the presence of metastasis by applying either inclusive (positive if either one read positive) or exclusive (positive if both read positive) criteria in the combined interpretation of PET/CT and MRI. Nodal stage was confirmed pathologically. The combined diagnostic accuracy of PET/CT and MRI was determined on per-nodal station and per-patient bases and compared with that of PET/CT alone. In 49 patients, 39 (19%) of 206 nodal stations harboured malignant cells. Out of 206 nodal stations, 186 (90%) had concordant readings, while the rest (10%) had discordant readings. Inclusive criteria of combined PET/CT and MRI helped increase sensitivity for detecting nodal metastasis (69%) compared with PET/CT alone (46%; P = 0.003), while specificity was not significantly decreased. Inclusive criteria in combined MRI and PET/CT readings help improve significantly the sensitivity for detecting nodal metastasis compared with PET/CT alone and may decrease unnecessary open thoracotomy. (orig.)

  9. CHOEP-21 chemotherapy for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs) in Maharaj Nakorn Chiang Mai Hospital.

    Science.gov (United States)

    Rattarittamrong, Ekarat; Norasetthada, Lalita; Tantiworawit, Adisak; Chai-Adisaksopha, Chatree; Nawarawong, Weerasak

    2013-11-01

    To determine the effectiveness and tolerability of the combination of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with the addition of etoposide (CHOEP-21) for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs). Between January 2009 and October 2011, patients aged 18 to 60 years with newly diagnosed nodal PTCLs at the Maharaj Nakorn Chiang Mai Hospital were enrolled to receive CHOEP-21 every three weeks for eight cycles. G-CSF prophylaxis was given to all patients. Twenty-four patients were enrolled. Twenty of them were male with a median age of 49 years. The majority of patients (66.7%) had PTCL, not otherwise specified (PTCL, NOS), and 95.8% of the patients were in stage III or IV. The overall response rate was 58% with 42% having complete response. The response rates were better among patients with ALK-negative anaplastic large cell lymphoma (ALCL; 100%) and angioimmunoblastic T-cell lymphoma (AITL; 85%) than those with PTCL, NOS (44%). With a median follow-up of 21 months, the patients had an estimated 2-year event-free survival, and an overall survival rate of 37.6% and 54.4%, respectively. The most common adverse effects were infection and hematologic toxicities that was manageable. Although CHOEP-21 induced favorable responses in patients with ALK-negative ALCL and AITL, the responses were not durable and further therapy is mandated in management of patients with nodal PTCL.

  10. Preoperative nodal staging of non-small cell lung cancer using 99mTc-sestamibi spect/ct imaging

    Directory of Open Access Journals (Sweden)

    Juliana Muniz Miziara

    2011-01-01

    Full Text Available OBJECTIVES: The proper nodal staging of non-small cell lung cancer is important for choosing the best treatment modality. Although computed tomography remains the first-line imaging test for the primary staging of lung cancer, its limitations for mediastinum nodal staging are well known. The aim of this study is to evaluate the accuracy of hybrid single-photon emission computed tomography and computed tomography using 99mTc-sestamibi in the nodal staging of patients with non-small cell lung cancer and to identify potential candidates for surgical treatment. METHODS: Prospective data were collected for 41 patients from December 2006 to February 2009. The patients underwent chest computed tomography and single-photon emission computed tomography/computed tomography examinations with 99mTc-sestamibi within a 30-day time period before surgery. Single-photon emission computed tomography/computed tomography was considered positive when there was focal uptake of sestamibi in the mediastinum, and computed tomography scan when there was lymph nodes larger than 10 mm in short axis. The results of single-photon emission computed tomography and computed tomography were correlated with pathology findings after surgery. RESULTS: Single-photon emission computed tomography/computed tomography correctly identified six out of 19 cases involving hilar lymph nodes and one out of seven cases involving nodal metastases in the mediastinum. The sensitivity, specificity, positive predictive value, and negative predictive value for 99mTc-sestamibi single-photon emission computed tomography/computed tomography in the hilum assessment were 31.6%, 95.5%, 85.7%, and 61.8%, respectively. The same values for the mediastinum were 14.3%, 97.1%, 50%, and 84.6%, respectively. For the hilar and mediastinal lymph nodes, chest tomography showed sensitivity values of 47.4% and 57.1%, specificity values of 95.5% and 91.2%, positive predictive values of 90% and 57.1% and negative

  11. Preoperative nodal staging of non-small cell lung cancer using 99mTc-sestamibi SPECT/CT imaging

    International Nuclear Information System (INIS)

    Miziara, Juliana Muniz; Rocha, Euclides Timoteo da; Miziara, Jose Elias Abrao; Garcia, Gustavo Fabene; Simoes, Maria Izilda Previato; Lopes, Marco Antonio; Kerr, Ligia Maria; Buchpiguel, Carlos Alberto

    2011-01-01

    Objectives: The proper nodal staging of non-small cell lung cancer is important for choosing the best treatment modality. Although computed tomography remains the first-line imaging test for the primary staging of lung cancer, its limitations for mediastinum nodal staging are well known. The aim of this study is to evaluate the accuracy of hybrid single-photon emission computed tomography and computed tomography using 99m Tc-sestamibi in the nodal staging of patients with non-small cell lung cancer and to identify potential candidates for surgical treatment. Methods: Prospective data were collected for 41 patients from December 2006 to February 2009. The patients underwent chest computed tomography and single-photon emission computed tomography/computed tomography examinations with 99m Tc-sestamibi within a 30-day time period before surgery. Single-photon emission computed tomography/computed tomography was considered positive when there was focal uptake of sestamibi in the mediastinum, and computed tomography scan when there was lymph nodes larger than 10 mm in short axis. The results of single-photon emission computed tomography and computed tomography were correlated with pathology findings after surgery. Results: Single-photon emission computed tomography/computed tomography correctly identified six out of 19 cases involving hilar lymph nodes and one out of seven cases involving nodal metastases in the mediastinum. The sensitivity, specificity, positive predictive value, and negative predictive value for 99m Tc-sestamibi single-photon emission computed tomography/computed tomography in the hilum assessment were 31.6%, 95.5%, 85.7%, and 61.8%, respectively. The same values for the mediastinum were 14.3%, 97.1%, 50%, and 84.6%, respectively. For the hilar and mediastinal lymph nodes, chest tomography showed sensitivity values of 47.4% and 57.1%, specificity values of 95.5% and 91.2%, positive predictive values of 90% and 57.1% and negative predictive values of 67

  12. Retrospective analysis of outcome differences in preoperative concurrent chemoradiation with or without elective nodal irradiation for esophageal squamous cell carcinoma.

    Science.gov (United States)

    Hsu, Feng-Ming; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Tsai, Yu-Chieh; Lee, Yung-Chie; Chia-Hsien Cheng, Jason

    2011-11-15

    To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor

  13. Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Feng-Ming [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan (China); Lee, Jang-Ming; Huang, Pei-Ming [Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Lin, Chia-Chi; Hsu, Chih-Hung; Tsai, Yu-Chieh [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Lee, Yung-Chie [Department of Surgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Chia-Hsien Cheng, Jason, E-mail: jasoncheng@ntu.edu.tw [Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan (China)

    2011-11-15

    Purpose: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. Methods and Materials: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. Results: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. Conclusions: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal

  14. Nodal enhances the activity of FoxO3a and its synergistic interaction with Smads to regulate cyclin G2 transcription in ovarian cancer cells.

    Science.gov (United States)

    Fu, G; Peng, C

    2011-09-15

    Nodal, a member of the transforming growth factor-β superfamily, has been recently shown to suppress cell proliferation and to stimulate the expression of cyclin G2 (CCNG2) in human epithelial ovarian cancer cells. However, the precise mechanisms underlying these events are not fully understood. In this study, we investigated the transcriptional regulation of CCNG2 by the Nodal signaling pathway. In ovarian cancer cells, overexpression of Nodal or its receptors, activin receptor-like kinase 7 (ALK7) or ALK4, resulted in an increase in the CCNG2 promoter activity. Several putative Forkhead box class O (FoxO)3a-binding sites are present in the human CCNG2 promoter and overexpression of FoxO3a enhanced the CCNG2 promoter activity. The functional FoxO3a-binding element (FBE) was mapped to a proximal region located between -398 and -380 bp (FBE1) through deletion and mutation analyses, as well as chromatin immunoprecipitation (IP) assay. Interestingly, mutation of the FBE1 not only abolished the effect of FoxO3a, but also blocked Nodal-induced CCNG2 transcription. Nodal stimulated FoxO3a mRNA and protein expression through the canonical Smad pathway and suppressed FoxO3a inactivation by inhibiting AKT activity. Silencing of FoxO3a using small interfering RNA significantly reduced the effect of Nodal on the CCNG2 promoter activity. On the other hand, overexpression of Smad2 and Smad3 enhanced the FoxO3a-induced CCNG2 promoter activity whereas knockdown of Smad4 blocked the activity of FoxO3a. Furthermore, IP assays revealed that FoxO3a formed complexes with Smad proteins and that Nodal enhanced the binding of FoxO3a to the CCNG2 promoter. Finally, silencing of FoxO3a reversed the inhibitory effect of Nodal on cell proliferation. Taken together, these findings demonstrated that Nodal signaling promotes CCNG2 transcription by upregulating FoxO3a expression, inhibiting FoxO3a phosphorylation and enhancing its synergistic interaction with Smads. These results also suggest

  15. Selective Nodal Irradiation on Basis of 18FDG-PET Scans in Limited-Disease Small-Cell Lung Cancer: A Prospective Study

    International Nuclear Information System (INIS)

    Loon, Judith van; De Ruysscher, Dirk; Wanders, Rinus; Boersma, Liesbeth; Simons, Jean; Oellers, Michel; Dingemans, Anne-Marie C.; Hochstenbag, Monique; Bootsma, Gerben; Geraedts, Wiel; Pitz, Cordula; Teule, Jaap; Rhami, Ali; Thimister, Willy; Snoep, Gabriel; Dehing-Oberije, Cary; Lambin, Philippe

    2010-01-01

    Purpose: To evaluate the results of selective nodal irradiation on basis of 18 F-deoxyglucose positron emission tomography (PET) scans in patients with limited-disease small-cell lung cancer (LD-SCLC) on isolated nodal failure. Methods and Materials: A prospective study was performed of 60 patients with LD-SCLC. Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy, concurrent with carboplatin and etoposide chemotherapy. Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated. A chest computed tomography (CT) scan was performed 3 months after radiotherapy completion and every 6 months thereafter. Results: A difference was seen in the involved nodal stations between the pretreatment 18 F-deoxyglucose PET scans and computed tomography scans in 30% of patients (95% confidence interval, 20-43%). Of the 60 patients, 39 (65%; 95% confidence interval [CI], 52-76%) developed a recurrence; 2 patients (3%, 95% CI, 1-11%) experienced isolated regional failure. The median actuarial overall survival was 19 months (95% CI, 17-21). The median actuarial progression-free survival was 14 months (95% CI, 12-16). 12% (95% CI, 6-22%) of patients experienced acute Grade 3 (Common Terminology Criteria for Adverse Events, version 3.0) esophagitis. Conclusion: PET-based selective nodal irradiation for LD-SCLC resulted in a low rate of isolated nodal failures (3%), with a low percentage of acute esophagitis. These findings are in contrast to those from our prospective study of CT-based selective nodal irradiation, which resulted in an unexpectedly high percentage of isolated nodal failures (11%). Because of the low rate of isolated nodal failures and toxicity, we believe that our data support the use of PET-based SNI for LD-SCLC.

  16. Multiple passage cells theory

    International Nuclear Information System (INIS)

    Riva, R.

    1983-01-01

    A review of the main concepts envolved in non astigmatic multiple passes cells is presented. It is shown that these concepts can be extended to ring cavities in which the analysis of the ray propagation (in the paraxial approaching) in two separated plans is accomplished. The concepts developed are applyed to a simple ring cavity (one curve mirror and two plane ones) showing that the acquired pattern of the rays on the mirrors is the one of a Lissajours figure which allows a better use of the mirror's area and consequently a larger number of passes. The cavity has applications in optical delay lines, measurements of mirrors reflectivities and possibly in passive optical gyroscopes. (Author) [pt

  17. Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

    Energy Technology Data Exchange (ETDEWEB)

    Varlotto, John M., E-mail: john.varlotto@umassmemorial.org [Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts (United States); Yao, Aaron N. [Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia (United States); DeCamp, Malcolm M. [Division of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Chicago, Illinois (United States); Northwestern University School of Medicine, Chicago, Illinois (United States); Ramakrishna, Satvik [Northwestern University School of Medicine, Chicago, Illinois (United States); Recht, Abe [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Flickinger, John [Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Andrei, Adin [Northwestern University, Chicago, Illinois (United States); Reed, Michael F. [Pennsylvania State University College of Medicine, Hershey, Pennsylvania (United States); Heart and Vascular Institute, Pennsylvania State University-Hershey, Hershey, Pennsylvania (United States); Toth, Jennifer W. [Pennsylvania State University College of Medicine, Hershey, Pennsylvania (United States); Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Pennsylvania State University-Hershey, Hershey, Pennsylvania (United States); Fizgerald, Thomas J. [Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts (United States); Higgins, Kristin [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Zheng, Xiao [Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia (United States); Shelkey, Julie [Department of Anesthesiology, Columbia University, New York, New York (United States); and others

    2015-03-15

    Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective

  18. Prognostic implications of occult nodal tumour cells in stage I and II colon cancer: The correlation between micrometastasis and disease recurrence

    NARCIS (Netherlands)

    Sloothaak, D. A. M.; van der Linden, R. L. A.; van de Velde, C. J. H.; Bemelman, W. A.; Lips, D. J.; van der Linden, J. C.; Doornewaard, H.; Tanis, P. J.; Bosscha, K.; van der Zaag, E. S.; Buskens, C. J.

    2017-01-01

    Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer. The objective of this retrospective multicenter study

  19. Activin/Nodal Signaling Supports Retinal Progenitor Specification in a Narrow Time Window during Pluripotent Stem Cell Neuralization

    Directory of Open Access Journals (Sweden)

    Michele Bertacchi

    2015-10-01

    Full Text Available Retinal progenitors are initially found in the anterior neural plate region known as the eye field, whereas neighboring areas undertake telencephalic or hypothalamic development. Eye field cells become specified by switching on a network of eye field transcription factors, but the extracellular cues activating this network remain unclear. In this study, we used chemically defined media to induce in vitro differentiation of mouse embryonic stem cells (ESCs toward eye field fates. Inhibition of Wnt/β-catenin signaling was sufficient to drive ESCs to telencephalic, but not retinal, fates. Instead, retinal progenitors could be generated from competent differentiating mouse ESCs by activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Activin also promoted eye field gene expression in differentiating human ESCs. Our results reveal insights into the mechanisms of eye field specification and open new avenues toward the generation of retinal progenitors for translational medicine.

  20. Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes

    International Nuclear Information System (INIS)

    Fernandes, Annemarie T.; Shen, Jason; Finlay, Jarod; Mitra, Nandita; Evans, Tracey; Stevenson, James; Langer, Corey; Lin, Lilie; Hahn, Stephen; Glatstein, Eli; Rengan, Ramesh

    2010-01-01

    Background: Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. Methods: We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Results: Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Conclusions: Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients.

  1. Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer--evidence from a phase II trial.

    Science.gov (United States)

    Colaco, Rovel; Sheikh, Hamid; Lorigan, Paul; Blackhall, Fiona; Hulse, Paul; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nicholas; Faivre-Finn, Corinne

    2012-04-01

    Omitting elective nodal irradiation (ENI) in limited-stage disease small cell lung cancer (LD-SCLC) is expected to result in smaller radiation fields. We report on data from a randomised phase II trial that omitted ENI in patients receiving concurrent chemo-radiotherapy for LD-SCLC. 38 patients with LD-SCLC were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy (RT). 3D-conformal RT was given concurrently with cisplatin and etoposide starting with the second cycle of a total of four cycles. The gross tumour volume was defined as primary tumour with involved lymph nodes (nodes ≥1 cm in short axis) identifiable with CT imaging. ENI was not used. Six recurrence patterns were identified: recurrence within planning target volume (PTV) only, recurrence within PTV+regional nodal recurrence and/or distant recurrence, isolated nodal recurrence outside PTV, nodal recurrence outside PTV+distant recurrence, distant metastases only and no recurrence. At median follow-up 16.9 months, 31/38 patients were evaluable and 14/31 patients had relapsed. There were no isolated nodal recurrences. Eight patients relapsed with intra-thoracic disease: 2 within PTV only, 4 within PTV and distantly and 2 with nodal recurrence outside PTV plus distant metastases. Rates of grade 3+ acute oesophagitis and pneumonitis in the 31 evaluable patients were 23 and 3% respectively. In our study of LD-SCLC, omitting ENI based on CT imaging was not associated with a high risk of isolated nodal recurrence, although further prospective studies are needed to confirm this. Routine ENI omission will be further evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes.

    Science.gov (United States)

    Fernandes, Annemarie T; Shen, Jason; Finlay, Jarod; Mitra, Nandita; Evans, Tracey; Stevenson, James; Langer, Corey; Lin, Lilie; Hahn, Stephen; Glatstein, Eli; Rengan, Ramesh

    2010-05-01

    Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  3. Involved-Field Radiotherapy versus Elective Nodal Irradiation in Combination with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study

    Science.gov (United States)

    Chen, Ming; Bao, Yong; Ma, Hong-Lian; Wang, Jin; Wang, Yan; Peng, Fang; Zhou, Qi-Chao; Xie, Cong-Hua

    2013-01-01

    This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study. PMID:23762840

  4. Planar cell polarity enables posterior localization of nodal cilia and left-right axis determination during mouse and Xenopus embryogenesis.

    Directory of Open Access Journals (Sweden)

    Dragana Antic

    2010-02-01

    Full Text Available Left-right asymmetry in vertebrates is initiated in an early embryonic structure called the ventral node in human and mouse, and the gastrocoel roof plate (GRP in the frog. Within these structures, each epithelial cell bears a single motile cilium, and the concerted beating of these cilia produces a leftward fluid flow that is required to initiate left-right asymmetric gene expression. The leftward fluid flow is thought to result from the posterior tilt of the cilia, which protrude from near the posterior portion of each cell's apical surface. The cells, therefore, display a morphological planar polarization. Planar cell polarity (PCP is manifested as the coordinated, polarized orientation of cells within epithelial sheets, or as directional cell migration and intercalation during convergent extension. A set of evolutionarily conserved proteins regulates PCP. Here, we provide evidence that vertebrate PCP proteins regulate planar polarity in the mouse ventral node and in the Xenopus gastrocoel roof plate. Asymmetric anterior localization of VANGL1 and PRICKLE2 (PK2 in mouse ventral node cells indicates that these cells are planar polarized by a conserved molecular mechanism. A weakly penetrant Vangl1 mutant phenotype suggests that compromised Vangl1 function may be associated with left-right laterality defects. Stronger functional evidence comes from the Xenopus GRP, where we show that perturbation of VANGL2 protein function disrupts the posterior localization of motile cilia that is required for leftward fluid flow, and causes aberrant expression of the left side-specific gene Nodal. The observation of anterior-posterior PCP in the mouse and in Xenopus embryonic organizers reflects a strong evolutionary conservation of this mechanism that is important for body plan determination.

  5. Reappraisal of nodal Epstein-Barr Virus-negative cytotoxic T-cell lymphoma: identification of indolent CD5+ diseases.

    Science.gov (United States)

    Yamashita, Daisuke; Shimada, Kazuyuki; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Kohno, Kei; Satou, Akira; Sakakibara, Ayako; Nakamura, Shigeo; Asano, Naoko; Kato, Seiichi

    2018-05-29

    Nodal cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein-Barr virus (EBV)-negative CTL to 48 patients with EBV-positive CTL. The two groups did not differ in histopathology, T-cell receptor (TCR) expression or rearrangement incidences, or survival curves. However, patients with EBV-negative CTL less frequently showed hepatic involvement (P = 0.007), B symptoms (P = 0.020), hemophagocytosis (P = 0.024), and detectable CD4 (P = 0.002) and CD5 (P = 0.009). Univariate and multivariate analyses identified three factors that independently predicted favorable survival, onset age diseases: CD5 + TCRαβ (n = 13), and CD5 + NK-cell type lacking TCR expression or clonal TCRγ rearrangement (n = 4). The survival curves for these two groups were significantly superior to others (n = 29, P diseases appear to be unique in their indolent clinical behavior, and should be managed differently from other diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Involved field radiotherapy (IFRT) versus elective nodal irradiation (ENI) for locally advanced non-small cell lung cancer: a meta-analysis of incidence of elective nodal failure (ENF).

    Science.gov (United States)

    Li, Ruijian; Yu, Liang; Lin, Sixiang; Wang, Lina; Dong, Xin; Yu, Lingxia; Li, Weiyi; Li, Baosheng

    2016-09-21

    The use of involved field radiotherapy (IFRT) has generated concern about the increasing incidence of elective nodal failure (ENF) in contrast to elective nodal irradiation (ENI). This meta-analysis aimed to provide more reliable and up-to-date evidence on the incidence of ENF between IFRT and ENI. We searched three databases for eligible studies where locally advanced non-small cell lung cancer (NSCLC) patients received IFRT or ENI. Outcome of interest was the incidence of ENF. The fixed-effects model was used to pool outcomes across the studies. There were 3 RCTs and 3 cohort studies included with low risk of bias. There was no significant difference in incidence of ENF between IFRT and ENI either among RCTs (RR = 1.38, 95 % CI: 0.59-3.25, p = 0.46) or among cohort studies (RR = 0.99, 95 % CI: 0.46-2.10, p = 0.97). There was also no significant difference in incidence of ENF between IFRT and ENI when RCTs and cohort studies were combined (RR = 1.15, 95 % CI: 0.65-2.01, p = 0.64). I 2 of test for heterogeneity was 0 %. This meta-analysis provides more reliable and stable evidence that there is no significant difference in incidence of ENF between IFRT and ENI.

  7. Unilateral cervical nodal metastasis is an independent prognostic factor for esophageal squamous cell carcinoma patients undergoing chemoradiotherapy: a retrospective study.

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    Full Text Available To determine the prognostic significance of unilateral cervical lymph nodal metastasis (CLNM in patients with inoperable thoracic esophageal squamous cell carcinoma (SCC and to identify significant prognostic factors in these patients.This retrospective study involved 395 patients with inoperable esophageal SCC treated with concurrent chemoradiotherapy. The patients were classified into three groups according to their cervical lymph node status: group A, no evidence of CLNM; group B, unilateral CLNM; group C, other distant metastases. Overall survival (OS and progression-free survival (PFS were calculated. Significant prognostic factors were identified using univariate and multivariate analyses.The 3-year OS rates in groups A, B and C were 46.7%, 33.5% and 8.3%, respectively (p<0.001, log-rank test. The corresponding PFS rates were 40.7%, 26.4% and 4.7% (p<0.001, log-rank test. Group B had a similar prognosis to that of group A and better 3-year OS (p = 0.009 and PFS (p = 0.006 rates than those of group C. Multivariate analysis demonstrated that T stage, chemotherapy regimen and cervical lymph node involvement were independent prognostic factors affecting OS and PFS.Compared to other distant metastases, unilateral CLNM is associated with longer OS in esophageal SCC and should be regarded as a regional disease. Sex, T stage, concurrent chemotherapy modality and cervical lymph node involvement are independent predictors of survival in esophageal SCC.

  8. KEK NODAL user's guide

    International Nuclear Information System (INIS)

    Akiyama, Atsuyoshi; Katoh, Tadahiko; Kikutani, Eiji; Koiso, Haruyo; Kurokawa, Shin-ichi; Oide, Katsunobu.

    1984-06-01

    NODAL is an interpreter language for accelerator control developed at CERN SPS and has been used successfully since 1974. At present NODAL or NODAL-like languages are used at DESY PETRA and CERN CPS. At KEK, we have also adopted NODAL for the control of TRISTAN, a 30 GeV x 30 GeV electron-positron colliding beam facility. The KEK version of NODAL has the following improvements on the SPS NODAL: (1) the fast execution speed due to the compiler-interpreter scheme, and (2) the full-screen editing facility. This manual explains how to use the KEK NODAL. It is based on the manual of the SPS NODAL, THE NODAL SYSTEM FOR THE SPS, by M.C. Crowley-Milling and G.C. Shering, CERN 78-07. We have made some additions and modifications to make the manual more appropriate for the KEK NODAL system, paying attention to retaining the good features of the original SPS NODAL manual. We acknowledge Professor M.C. Crowley-Milling, Dr G.C. Shering and CERN for their kind permission for this modification. (author)

  9. KEK NODAL system

    International Nuclear Information System (INIS)

    Kurokawa, S.; Abe, K.; Akiyama, A.; Katoh, T.; Kikutani, E.; Koiso, H.; Kurihara, N.; Oide, K.; Shinomoto, M.

    1985-01-01

    The KEK NODAL system, which is based on the NODAL devised at the CERN SPS, works on an optical-fiber token ring network of twenty-four minicomputers (Hitachi HIDIC 80's) to control the TRISTAN accelerator complex, now being constructed at KEK. KEK NODAL retains main features of the original NODAL: the interpreting scheme, the multi-computer programming facility, and the data-module concept. In addition, it has the following characteristics: fast execution due to the compiler-interpreter method, a multicomputer file system, a full-screen editing facility, and a dynamic linkage scheme of data modules and NODAL functions. The structure of the KEK NODAL system under PMS, a real-time multitasking operating system of HIDIC 80, is described; the NODAL file system is also explained

  10. Three-dimensional conformal radiation may deliver considerable dose of incidental nodal irradiation in patients with early stage node-negative non-small cell lung cancer when the tumor is large and centrally located

    International Nuclear Information System (INIS)

    Zhao Lujun; Chen Ming; Haken, Randall ten; Chetty, Indrin; Chapet, Olivier; Hayman, James A.; Kong Fengming

    2007-01-01

    Background and purpose: To determine the dose to regional nodal stations in patients with T 1-3 N 0 M 0 non-small cell lung cancer (NSCLC) treated with three-dimensional conformal radiation therapy (3DCRT) without intentional elective nodal irradiation (ENI). Materials and methods: Twenty-three patients with medically inoperable T 1-3 N 0 M 0 NSCLC were treated with 3DCRT without ENI. Hilar and mediastinal nodal regions were contoured on planning CT. The prescription dose was normalized to 70 Gy. Equivalent uniform dose (EUD) and other dosimetric parameters (e.g., V 40 ) were calculated for each nodal station. Results: The median EUD for the whole group ranged from 0.4 to 4.4 Gy for all elective nodal regions. Gross tumor volume (GTV) and the relationship between GTV and hilum were significantly correlated with irradiation dose to ipsilateral hilar nodal regions (P 3 (diameter ∼ 4 cm) and or having any overlap with hilum, the median EUDs were 9.6, 22.6, and 62.9 Gy for ipsilateral lower paratracheal, subcarinal, and ipsilateral hilar regions, respectively. The corresponding median V 40 were 32.5%, 39.3%, and 97.6%, respectively. Conclusions: Although incidental nodal irradiation dose is low in the whole group, the dose to high-risk nodal regions is considerable in patients with T 1-3 N 0 NSCLC when the primary is large and/or centrally located

  11. Maternal Nodal inversely affects NODAL and STOX1 expression in the fetal placenta

    Directory of Open Access Journals (Sweden)

    Hari Krishna Thulluru

    2013-08-01

    Full Text Available Nodal, a secreted signaling protein from the TGFβ-super family plays a vital role during early embryonic development. Recently, it was found that maternal decidua-specific Nodal knockout mice show intrauterine growth restriction (IUGR and preterm birth. As the chromosomal location of NODAL is in the same linkage area as the susceptibility gene STOX1, associated with the familial form of early-onset, IUGR-complicated pre-eclampsia, their potential maternal-fetal interaction was investigated. Pre-eclamptic mothers with children who carried the STOX1 susceptibility allele themselves all carried the NODAL H165R SNP, which causes a 50% reduced activity. Surprisingly, in decidua Nodal knockout mice the fetal placenta showed up-regulation of STOX1 and NODAL expression. Conditioned media of human first trimester decidua and a human endometrial stromal cell line (T-HESC treated with siRNAs against NODAL or carrying the H165R SNP were also able to induce NODAL and STOX1 expression when added to SGHPL-5 first trimester extravillous trophoblast cells. Finally, a human TGFß-BMP-Signaling-Pathway PCR-Array on decidua and the T-HESC cell line with Nodal knockdown revealed upregulation of Activin-A, which was confirmed in conditioned media by ELISA. We show that maternal decidua Nodal knockdown gives upregulation of NODAL and STOX1 mRNA expression in fetal extravillous trophoblast cells, potentially via upregulation of Activin-A in the maternal decidua. As both Activin-A and Nodal have been implicated in pre-eclampsia, being increased in serum of pre-eclamptic women and upregulated in pre-eclamptic placentas respectively, this interaction at the maternal-fetal interface might play a substantial role in the development of pre-eclampsia.

  12. Sub-cell balanced nodal expansion methods using S4 eigenfunctions for multi-group SN transport problems in slab geometry

    International Nuclear Information System (INIS)

    Hong, Ser Gi; Lee, Deokjung

    2015-01-01

    A highly accurate S 4 eigenfunction-based nodal method has been developed to solve multi-group discrete ordinate neutral particle transport problems with a linearly anisotropic scattering in slab geometry. The new method solves the even-parity form of discrete ordinates transport equation with an arbitrary S N order angular quadrature using two sub-cell balance equations and the S 4 eigenfunctions of within-group transport equation. The four eigenfunctions from S 4 approximation have been chosen as basis functions for the spatial expansion of the angular flux in each mesh. The constant and cubic polynomial approximations are adopted for the scattering source terms from other energy groups and fission source. A nodal method using the conventional polynomial expansion and the sub-cell balances was also developed to be used for demonstrating the high accuracy of the new methods. Using the new methods, a multi-group eigenvalue problem has been solved as well as fixed source problems. The numerical test results of one-group problem show that the new method has third-order accuracy as mesh size is finely refined and it has much higher accuracies for large meshes than the diamond differencing method and the nodal method using sub-cell balances and polynomial expansion of angular flux. For multi-group problems including eigenvalue problem, it was demonstrated that the new method using the cubic polynomial approximation of the sources could produce very accurate solutions even with large mesh sizes. (author)

  13. Does Tumor Depth Affect Nodal Upstaging in Squamous Cell Carcinoma of the Head and Neck?

    DEFF Research Database (Denmark)

    Alkureishi, Lee; Ross, Gary; Shoaib, Taimur

    2007-01-01

    AND METHODS:: One hundred seventy-two patients with cT1/2 N0 squamous cell carcinoma (SCC) of the oral cavity/oropharynx undergoing primary resection and either sentinel node biopsy (SNB) or SNB-assisted neck dissection as a staging tool for the cN0 neck. Harvested nodes were examined with hematoxylin...

  14. Single-Cell Network Analysis Identifies DDIT3 as a Nodal Lineage Regulator in Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Cristina Pina

    2015-06-01

    Full Text Available We explore cell heterogeneity during spontaneous and transcription-factor-driven commitment for network inference in hematopoiesis. Since individual genes display discrete OFF states or a distribution of ON levels, we compute and combine pairwise gene associations from binary and continuous components of gene expression in single cells. Ddit3 emerges as a regulatory node with positive linkage to erythroid regulators and negative association with myeloid determinants. Ddit3 loss impairs erythroid colony output from multipotent cells, while forcing Ddit3 in granulo-monocytic progenitors (GMPs enhances self-renewal and impedes differentiation. Network analysis of Ddit3-transduced GMPs reveals uncoupling of myeloid networks and strengthening of erythroid linkages. RNA sequencing suggests that Ddit3 acts through development or stabilization of a precursor upstream of GMPs with inherent Meg-E potential. The enrichment of Gata2 target genes in Ddit3-dependent transcriptional responses suggests that Ddit3 functions in an erythroid transcriptional network nucleated by Gata2.

  15. Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells.

    Science.gov (United States)

    Sirenko, Syevda G; Yang, Dongmei; Maltseva, Larissa A; Kim, Mary S; Lakatta, Edward G; Maltsev, Victor A

    2017-01-01

    Uptake and release calcium from the sarcoplasmic reticulum (SR) (dubbed "calcium clock"), in the form of spontaneous, rhythmic, local diastolic calcium releases (LCRs), together with voltage-sensitive ion channels (membrane clock) form a coupled system that regulates the action potential (AP) firing rate. LCRs activate Sodium/Calcium exchanger (NCX) that accelerates diastolic depolarization and thus participating in regulation of the time at which the next AP will occur. Previous studies in rabbit SA node cells (SANC) demonstrated that the basal AP cycle length (APCL) is tightly coupled to the basal LCR period (time from the prior AP-induced Ca2+ transient to the diastolic LCR occurrence), and that this coupling is further modulated by autonomic receptor stimulation. Although spontaneous LCRs during diastolic depolarization have been reported in SANC of various species (rabbit, cat, mouse, toad), prior studies have failed to detect LCRs in spontaneously beating SANC of guinea-pig, a species that has been traditionally used in studies of cardiac pacemaker cell function. We performed a detailed investigation of whether guinea-pig SANC generate LCRs and whether they play a similar key role in regulation of the AP firing rate. We used two different approaches, 2D high-speed camera and classical line-scan confocal imaging. Positioning the scan-line beneath sarcolemma, parallel to the long axis of the cell, we found that rhythmically beating guinea-pig SANC do, indeed, generate spontaneous, diastolic LCRs beneath the surface membrane. The average key LCR characteristics measured in confocal images in guinea-pig SANC were comparable to rabbit SANC, both in the basal state and in the presence of β-adrenergic receptor stimulation. Moreover, the relationship between the LCR period and APCL was subtended by the same linear function. Thus, LCRs in guinea-pig SANC contribute to the diastolic depolarization and APCL regulation. Our findings indicate that coupled-clock system

  16. Preoperative nodal staging of non-small cell lung cancer using {sup 99m}Tc-sestamibi SPECT/CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Miziara, Juliana Muniz; Rocha, Euclides Timoteo da; Miziara, Jose Elias Abrao; Garcia, Gustavo Fabene; Simoes, Maria Izilda Previato; Lopes, Marco Antonio; Kerr, Ligia Maria [Hospital de Cancer de Barretos, Barretos, SP (Brazil); Buchpiguel, Carlos Alberto, E-mail: julimiziara@ig.com.br [Faculdade de Medicina da Universidade da Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, SP (Brazil)

    2011-07-01

    Objectives: The proper nodal staging of non-small cell lung cancer is important for choosing the best treatment modality. Although computed tomography remains the first-line imaging test for the primary staging of lung cancer, its limitations for mediastinum nodal staging are well known. The aim of this study is to evaluate the accuracy of hybrid single-photon emission computed tomography and computed tomography using {sup 99m}Tc-sestamibi in the nodal staging of patients with non-small cell lung cancer and to identify potential candidates for surgical treatment. Methods: Prospective data were collected for 41 patients from December 2006 to February 2009. The patients underwent chest computed tomography and single-photon emission computed tomography/computed tomography examinations with {sup 99m}Tc-sestamibi within a 30-day time period before surgery. Single-photon emission computed tomography/computed tomography was considered positive when there was focal uptake of sestamibi in the mediastinum, and computed tomography scan when there was lymph nodes larger than 10 mm in short axis. The results of single-photon emission computed tomography and computed tomography were correlated with pathology findings after surgery. Results: Single-photon emission computed tomography/computed tomography correctly identified six out of 19 cases involving hilar lymph nodes and one out of seven cases involving nodal metastases in the mediastinum. The sensitivity, specificity, positive predictive value, and negative predictive value for {sup 99m}Tc-sestamibi single-photon emission computed tomography/computed tomography in the hilum assessment were 31.6%, 95.5%, 85.7%, and 61.8%, respectively. The same values for the mediastinum were 14.3%, 97.1%, 50%, and 84.6%, respectively. For the hilar and mediastinal lymph nodes, chest tomography showed sensitivity values of 47.4% and 57.1%, specificity values of 95.5% and 91.2%, positive predictive values of 90% and 57.1% and negative

  17. Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-beta/Activin/Nodal signaling using SB-431542

    DEFF Research Database (Denmark)

    Mahmood, Amer; Harkness, Linda; Schrøder, Henrik Daa

    2010-01-01

    Directing differentiation of human embryonic stem cells (hESC) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESC in regenerative medicine procedures. Here, we report a protocol for directing the differentiation of hESC into mesenchymal...... in vivo. Interestingly, SB-OG cells cultured in 10% fetal bovine serum (FBS) developed into a homogeneous population of mesenchymal progenitors that expressed CD markers characteristic of mesenchymal stem cells (MSC): CD44(+) (100%), CD73(+) (98%), CD146(+) (96%) and CD166(+) (88%) with the ability...... progenitor cells. We demonstrate that inhibition of TGF-beta/Activin/Nodal signaling during embryoid bodies (EB) formation using SB-431542 (SB) in serum free medium, markedly up-regulated paraxial mesodermal markers (TBX6, TBX5), and several myogenic developmental markers including early myogenic...

  18. Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head-and-Neck Squamous Cell Carcinoma Patients With Nodal Metastases

    International Nuclear Information System (INIS)

    Shukla-Dave, Amita; Lee, Nancy Y.; Jansen, Jacobus F.A.; Thaler, Howard T.; Stambuk, Hilda E.; Fury, Matthew G.; Patel, Snehal G.; Moreira, Andre L.; Sherman, Eric; Karimi, Sasan; Wang, Ya; Kraus, Dennis; Shah, Jatin P.; Pfister, David G.

    2012-01-01

    Purpose: Dynamic contrast-enhanced MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of this study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery. Methods and Materials: Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using the Tofts model. DCE-MRI parameters were related to treatment outcome (progression-free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD), or dead of other causes (DOC). Prognostic significance was assessed using the log-rank test for single variables and Cox proportional hazards regression for combinations of variables. Results: At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. K trans is volume transfer constant. In a stepwise Cox regression, skewness of K trans (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p trans was the strongest predictor of PFS and OS in Stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter K trans as a predictor of outcome in these patients.

  19. Long-term results of high-dose conformal radiotherapy for patients with medically inoperable T1-3N0 non-small-cell lung cancer: Is low incidence of regional failure due to incidental nodal irradiation?

    International Nuclear Information System (INIS)

    Chen Ming; Hayman, James A.; Haken, Randall K. ten; Tatro, Daniel; Fernando, Shaneli; Kong, F.-M.

    2006-01-01

    Purpose: To report the results of high-dose conformal irradiation and examine incidental nodal irradiation and nodal failure in patients with inoperable early-stage non-small-cell lung cancer (NSCLC). Methods and Materials: This analysis included patients with inoperable CT-staged T1-3N0M0 NSCLC treated on our prospective dose-escalation trial. Patients were treated with radiation alone (total dose, 63-102.9 Gy in 2.1-Gy daily fractions) with a three-dimensional conformal technique without intentional nodal irradiation. Bilateral highest mediastinal and upper/lower paratracheal, prevascular and retrotracheal, sub- and para-aortic, subcarinal, paraesophageal, and ipsilateral hilar regions were delineated individually. Nodal failure and doses of incidental irradiation were studied. Results: The potential median follow-up was 104 months. For patients who completed protocol treatment, median survival was 31 months. The actuarial overall survival rate was 86%, 61%, 43%, and 21% and the cause-specific survival rate was 89%, 70%, 53%, and 35% at 1, 2, 3, and 5 years, respectively. Weight loss (p = 0.008) and radiation dose in Gy (p = 0.013) were significantly associated with overall survival. In only 22% and 13% of patients examined did ipsilateral hilar and paratracheal (and subaortic for left-sided tumor) nodal regions receive a dose of ≥40 Gy, respectively. Less than 10% of all other nodal regions received a dose of ≥40 Gy. No patients failed initially at nodal sites. Conclusions: Radiation dose is positively associated with overall survival in patients with medically inoperable T1-3N0 NSCLC, though long-term results remain poor. The nodal failure rate is low and does not seem to be due to high-dose incidental irradiation

  20. A comparison of two nodal codes : Advanced nodal code (ANC) and analytic function expansion nodal (AFEN) code

    International Nuclear Information System (INIS)

    Chung, S.K.; Hah, C.J.; Lee, H.C.; Kim, Y.H.; Cho, N.Z.

    1996-01-01

    Modern nodal methods usually employs the transverse integration technique in order to reduce a multi-dimensional diffusion equation to one-dimensional diffusion equations. The use of the transverse integration technique requires two major approximations such as a transverse leakage approximation and a one-dimensional flux approximation. Both the transverse leakage and the one-dimensional flux are approximated by polynomials. ANC (Advanced Nodal Code) developed by Westinghouse employs a modern nodal expansion method for the flux calculation, the equivalence theory for the homogenization error reduction and a group theory for pin power recovery. Unlike the conventional modern nodal methods, AFEN (Analytic Function Expansion Nodal) method expands homogeneous flux distributions within a node into non-separable analytic basis functions, which eliminate two major approximations of the modern nodal methods. A comparison study of AFEN with ANC has been performed to see the applicability of AFEN to commercial PWR and different types of reactors such as MOX fueled reactor. The qualification comparison results demonstrate that AFEN methodology is accurate enough to apply for commercial PWR analysis. The results show that AFEN provides very accurate results (core multiplication factor and assembly power distribution) for cores that exhibit strong flux gradients as in a MOX loaded core. (author)

  1. The value of regional nodal radiotherapy (dose/volume) in the treatment of unresectable non-small cell lung cancer: an RTOG analysis

    International Nuclear Information System (INIS)

    Emami, Bahman; Scott, Charles; Byhardt, Roger; Graham, Mary V.; Andras, E. James; John, Madhu; Herskovic, Arnold; Urtasun, Raul C.; Asbell, Sucha O.; Perez, Carlos A.; Cox, James

    1996-01-01

    PURPOSE/OBJECTIVE: To evaluate whether or not the traditional practice of including all thoracic regional nodal areas in the radiotherapy volume in the treatment of unresectable lung cancer is of any therapeutic benefit. MATERIALS AND METHODS: A total of 1,705 patients from four large RTOG trials (78-11, 79-17, 83-11, 84-07) were analyzed for this purpose. Each of these trials had data on dose delivered to the nodal regions and assessment of nodal borders. The nodes were separated into mediastinal, contralateral hilar, ipsilateral hilar, and supraclavicular. Each node site was assessed for progression, defined as in-field or out-of-field, at the node site. In patients with adequate nodal field borders, the results were also analyzed according to the dose delivered. RESULTS: The majority (74%) of patients were between the age of 55 to 75. Forty-six percent of patients had KPS of 60 to 80 and 52% KPS of 90 to 100. Sixty percent of patients had a weight loss of less than 5%, and 40% had a weight loss of over 5% six months prior to diagnosis. Major variations from protocol in defining field borders (unacceptable field borders) were lowest for ipsilateral hilum ((42(727))) and the highest for mediastinal borders ((158(743))). Three groups had statistically significant differences in outcome (progression) between the per protocol and the unacceptable per protocol: ipsilateral hilar nodes (field borders), 14% versus 26% (p = 0.03); dose to mediastinal nodes in CALGB eligible patients, 9% versus 19% (p = 0.02); and ipsilateral hilar nodes (field borders) for high-dose patients assigned to greater than or equal to 69.6 Gy, 14% versus 31% (p = 0.007). CONCLUSION: These data suggest that inclusion of the ipsilateral hilar and mediastinal nodes affect outcome in unresectable non-small cell lung cancer. Exclusion of the other thoracic lymph node regions did not affect outcome in this study. These findings have important implications for combined modality therapy and three

  2. Risk of isolated nodal failure for non-small cell lung cancer (NSCLC) treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) techniques - A retrospective analysis

    International Nuclear Information System (INIS)

    Kepka, Lucyna; Bujko, Krzysztof; Zolciak-Siwinska, Agnieszka

    2008-01-01

    Purpose. To estimate retrospectively the rate of isolated nodal failures (INF) in NSCLC patients treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT). Materials/methods. One hundred and eighty-five patients with I-IIIB stage treated with 3D-CRT in consecutive clinical trials differing in an extent of the ENI were analyzed. According to the extent of the ENI, two groups were distinguished: extended (n=124) and limited (n=61) ENI. INF was defined as regional nodal failure occurring without local progression. Cumulative Incidence of INF (CIINF) was evaluated by univariate and multivariate analysis with regard to prognostic factors. Results. With a median follow up of 30 months, the two-year actuarial overall survival was 35%. The two-year CIINF rate was 12%. There were 16 (9%) INF, eight (6%) for extended and eight (13%) for limited ENI. In the univariate analysis bulky mediastinal disease (BMD), left side, higher N stage, and partial response to RT had a significant negative impact on the CIINF. BMD was the only independent predictor of the risk of incidence of the INF (p=0.001). Conclusions. INF is more likely to occur in case of more advanced nodal status

  3. Risk of isolated nodal failure for non-small cell lung cancer (NSCLC) treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) techniques--a retrospective analysis.

    Science.gov (United States)

    Kepka, Lucyna; Bujko, Krzysztof; Zolciak-Siwinska, Agnieszka

    2008-01-01

    To estimate retrospectively the rate of isolated nodal failures (INF) in NSCLC patients treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT). One hundred and eighty-five patients with I-IIIB stage treated with 3D-CRT in consecutive clinical trials differing in an extent of the ENI were analyzed. According to the extent of the ENI, two groups were distinguished: extended (n = 124) and limited (n = 61) ENI. INF was defined as regional nodal failure occurring without local progression. Cumulative Incidence of INF (CIINF) was evaluated by univariate and multivariate analysis with regard to prognostic factors. With a median follow up of 30 months, the two-year actuarial overall survival was 35%. The two-year CIINF rate was 12%. There were 16 (9%) INF, eight (6%) for extended and eight (13%) for limited ENI. In the univariate analysis bulky mediastinal disease (BMD), left side, higher N stage, and partial response to RT had a significant negative impact on the CIINF. BMD was the only independent predictor of the risk of incidence of the INF (p = 0.001). INF is more likely to occur in case of more advanced nodal status.

  4. Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells

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    Vedavathi Madhu

    2016-01-01

    Full Text Available Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-β and BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally, in vitro subcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair.

  5. Regional nodal staging with 18F-FDG PET–CT in non-small cell lung cancer: Additional diagnostic value of CT attenuation and dual-time-point imaging

    International Nuclear Information System (INIS)

    Li, Meng; Wu, Ning; Liu, Ying; Zheng, Rong; Liang, Ying; Zhang, Wenjie; Zhao, Ping

    2012-01-01

    Background: [Fluorine-18]-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET–CT) is widely performed in the regional nodal staging of non-small cell lung cancer (NSCLC). However, the uptake of 18 F-FDG by tubercular granulomatous tissues may lead to false-positive diagnosis. This is of special concern in China, where tubercular granulomatous disease is epidemic. Herein, we evaluated the efficacy of an additional CT attenuation and a dual-time-point scan in determining the status of lymph nodes. Methods: Eighty NSCLC patients underwent curative surgical resection after 18 F-FDG PET–CT and separate breath-hold CT examinations. The initial images were analyzed by two methods. In method 1, nodal status was determined by 18 F-FDG uptake only. In Method 2, nodal status was determined by 18 F-FDG uptake associated with CT attenuation. For dual-time-point imaging, the retention index (RI) of benign and malignant nodal groups with positive uptake in the initial scan was examined. Results: A total of 265 nodal groups were documented. On a per-nodal-group basis, the diagnostic sensitivity, specificity, and accuracy of Method 1 were 66.7%, 89.7%, and 85.3%, respectively, whereas those of Method 2 were 64.7%, 96.7%, and 90.6%, respectively. The improvement in diagnostic specificity and accuracy associated with the addition of CT attenuation in Method 2 as compared to Method 1 was statistically significant (p 0.05). Conclusion: 18 F-FDG PET–CT has high diagnostic value for preoperative lymph-node (N) staging of NSCLC patients. We show that 18 F-FDG uptake combined with CT attenuation improves the diagnostic specificity and accuracy of nodal diagnosis in NSCLC. For the lymph nodes with positive uptake in the initial scan, dual-time-point imaging has limited effect in differentiation.

  6. Fusion positron emission/computed tomography underestimates the presence of hilar nodal metastases in patients with resected non-small cell lung cancer.

    Science.gov (United States)

    Carrillo, Sergio A; Daniel, Vincent C; Hall, Nathan; Hitchcock, Charles L; Ross, Patrick; Kassis, Edmund S

    2012-05-01

    The 5-year survival for patients with resected stage II (N1) non-small cell lung cancer ranges from 40% to 55%. No data exist addressing the benefit of neoadjuvant therapy for patients with stage II disease. This is largely in part due to the lack of a reliable, minimally invasive method to assess hilar nodes. This study is aimed at determining the ability of fusion positron emission/computed tomography (PET/CT) to identify hilar metastases in patients with resected non-small cell lung cancer. A retrospective review of surgically resected patients with fusion PET/CT within 30 days of resection was performed. The sensitivity, specificity, positive predictive value, and negative predictive value for PET/CT in detecting hilar nodal metastases was calculated for a range of maximum standardized uptake values (SUVmax). Hilar nodes from patients with falsely positive PET/CT scans were analyzed for the presence of histoplasmosis. Additionally, the impact of hilar node size greater than 1 centimeter on the calculated values was assessed. There were 119 patients evaluated. The number of lymph nodes resected ranged from 1 to 12 (X=2.98). There was decreased sensitivity and increased specificity with higher SUVmax cutoff values. At the standard SUVmax value of 2.5, the sensitivity and specificity were only 48.5% and 80.2%. The addition of size of hilar node by CT led to a modest improvement in sensitivity at all SUVmax cutoff values. Fusion PET/CT lacks sensitivity and specificity in identifying hilar nodal metastasis in patients with resected non-small cell lung cancer. Further prospective studies assessing the utility of PET/CT versus alternative sampling techniques are warranted. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Intensity-modulated proton therapy for elective nodal irradiation and involved-field radiation in the definitive treatment of locally advanced non-small-cell lung cancer: a dosimetric study.

    Science.gov (United States)

    Kesarwala, Aparna H; Ko, Christine J; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E; O'Meara, William P; Simone, Charles B; Rengan, Ramesh

    2015-05-01

    Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT. Published by Elsevier Inc.

  8. Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Dosimetric Study

    Science.gov (United States)

    Kesarwala, Aparna H.; Ko, Christine J.; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E.; O’Meara, William P.; Simone, Charles B.; Rengan, Ramesh

    2015-01-01

    Background Photon involved-field radiation therapy (IFRT), the standard for locally advanced non-small cell lung cancer (LA-NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Given the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Materials and Methods IMPT IFRT plans were generated to the same total dose of 66.6–72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 CGE to elective nodal (EN) planning treatment volumes (PTV) plus 24 CGE to involved field (IF)-PTVs. Results Proton IFRT and ENI both improved D95 involved field (IF)-PTV coverage by 4% (pENI. Mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all pENI. Potential decreased toxicity indicates IMPT could allow ENI while maintaining a favorable therapeutic ratio compared to photon IFRT. PMID:25604729

  9. Applications of a systematic homogenization theory for nodal diffusion methods

    International Nuclear Information System (INIS)

    Zhang, Hong-bin; Dorning, J.J.

    1992-01-01

    The authors recently have developed a self-consistent and systematic lattice cell and fuel bundle homogenization theory based on a multiple spatial scales asymptotic expansion of the transport equation in the ratio of the mean free path to the reactor characteristics dimension for use with nodal diffusion methods. The mathematical development leads naturally to self-consistent analytical expressions for homogenized diffusion coefficients and cross sections and flux discontinuity factors to be used in nodal diffusion calculations. The expressions for the homogenized nuclear parameters that follow from the systematic homogenization theory (SHT) are different from those for the traditional flux and volume-weighted (FVW) parameters. The calculations summarized here show that the systematic homogenization theory developed recently for nodal diffusion methods yields accurate values for k eff and assembly powers even when compared with the results of a fine mesh transport calculation. Thus, it provides a practical alternative to equivalence theory and GET (Ref. 3) and to simplified equivalence theory, which requires auxiliary fine-mesh calculations for assemblies embedded in a typical environment to determine the discontinuity factors and the equivalent diffusion coefficient for a homogenized assembly

  10. Encapsulation of nodal segments of lobelia chinensis

    Directory of Open Access Journals (Sweden)

    Weng Hing Thong

    2015-04-01

    Full Text Available Lobelia chinensis served as an important herb in traditional chinese medicine. It is rare in the field and infected by some pathogens. Therefore, encapsulation of axillary buds has been developed for in vitro propagation of L. chinensis. Nodal explants of L. chinensis were used as inclusion materials for encapsulation. Various combinations of calcium chloride and sodium alginate were tested. Encapsulation beads produced by mixing 50 mM calcium chloride and 3.5% sodium alginate supported the optimal in vitro conversion potential. The number of multiple shoots formed by encapsulated nodal segments was not significantly different from the average of shoots produced by non-encapsulated nodal segments. The encapsulated nodal segments regenerated in vitro on different medium. The optimal germination and regeneration medium was Murashige-Skoog medium. Plantlets regenerated from the encapsulated nodal segments were hardened, acclimatized and established well in the field, showing similar morphology with parent plants. This encapsulation technology would serve as an alternative in vitro regeneration system for L. chinensis.

  11. Nodal-chain metals.

    Science.gov (United States)

    Bzdušek, Tomáš; Wu, QuanSheng; Rüegg, Andreas; Sigrist, Manfred; Soluyanov, Alexey A

    2016-10-06

    The band theory of solids is arguably the most successful theory of condensed-matter physics, providing a description of the electronic energy levels in various materials. Electronic wavefunctions obtained from the band theory enable a topological characterization of metals for which the electronic spectrum may host robust, topologically protected, fermionic quasiparticles. Many of these quasiparticles are analogues of the elementary particles of the Standard Model, but others do not have a counterpart in relativistic high-energy theories. A complete list of possible quasiparticles in solids is lacking, even in the non-interacting case. Here we describe the possible existence of a hitherto unrecognized type of fermionic excitation in metals. This excitation forms a nodal chain-a chain of connected loops in momentum space-along which conduction and valence bands touch. We prove that the nodal chain is topologically distinct from previously reported excitations. We discuss the symmetry requirements for the appearance of this excitation and predict that it is realized in an existing material, iridium tetrafluoride (IrF 4 ), as well as in other compounds of this class of materials. Using IrF 4 as an example, we provide a discussion of the topological surface states associated with the nodal chain. We argue that the presence of the nodal-chain fermions will result in anomalous magnetotransport properties, distinct from those of materials exhibiting previously known excitations.

  12. Analysis of Incidental Radiation Dose to Uninvolved Mediastinal/Supraclavicular Lymph Nodes in Patients with Limited-Stage Small Cell Lung Cancer Treated Without Elective Nodal Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Irfan; DeMarco, Marylou; Stevens, Craig W. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, FL (United States); Fulp, William J. [Biostatistics Core, H. Lee Moffitt Cancer Center, Tampa, FL (United States); Dilling, Thomas J., E-mail: Thomas.Dilling@moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center, Tampa, FL (United States)

    2011-01-01

    Classic teaching states that treatment of limited-stage small cell lung cancer (L-SCLC) requires large treatment fields covering the entire mediastinum. However, a trend in modern thoracic radiotherapy is toward more conformal fields, employing positron emission tomography/computed tomography (PET/CT) scans to determine the gross tumor volume (GTV). This analysis evaluates the dosimetric results when using selective nodal irradiation (SNI) to treat a patient with L-SCLC, quantitatively comparing the results to standard Intergroup treatment fields. Sixteen consecutive patients with L-SCLC and central mediastinal disease who also underwent pretherapy PET/CT scans were studied in this analysis. For each patient, we created SNI treatment volumes, based on the PET/CT-based criteria for malignancy. We also created 2 ENI plans, the first without heterogeneity corrections, as per the Intergroup 0096 study (ENI{sub off}) and the second with heterogeneity corrections while maintaining constant the number of MUs delivered between these latter 2 plans (ENI{sub on}). Nodal stations were contoured using published guidelines, then placed into 4 'bins' (treated nodes, 1 echelon away, >1 echelon away within the mediastinum, contralateral hilar/supraclavicular). These were aggregated across the patients in the study. Dose to these nodal bins and to tumor/normal structures were compared among these plans using pairwise t-tests. The ENI{sub on} plans demonstrated a statistically significant degradation in dose coverage compared with the ENI{sub off} plans. ENI and SNI both created a dose gradient to the lymph nodes across the mediastinum. Overall, the gradient was larger for the SNI plans, although the maximum dose to the '1 echelon away' nodes was not statistically different. Coverage of the GTV and planning target volume (PTV) were improved with SNI, while simultaneously reducing esophageal and spinal cord dose though at the expense of modestly reduced dose to

  13. Analysis of incidental radiation dose to uninvolved mediastinal/supraclavicular lymph nodes in patients with limited-stage small cell lung cancer treated without elective nodal irradiation.

    Science.gov (United States)

    Ahmed, Irfan; DeMarco, Marylou; Stevens, Craig W; Fulp, William J; Dilling, Thomas J

    2011-01-01

    Classic teaching states that treatment of limited-stage small cell lung cancer (L-SCLC) requires large treatment fields covering the entire mediastinum. However, a trend in modern thoracic radiotherapy is toward more conformal fields, employing positron emission tomography/computed tomography (PET/CT) scans to determine the gross tumor volume (GTV). This analysis evaluates the dosimetric results when using selective nodal irradiation (SNI) to treat a patient with L-SCLC, quantitatively comparing the results to standard Intergroup treatment fields. Sixteen consecutive patients with L-SCLC and central mediastinal disease who also underwent pretherapy PET/CT scans were studied in this analysis. For each patient, we created SNI treatment volumes, based on the PET/CT-based criteria for malignancy. We also created 2 ENI plans, the first without heterogeneity corrections, as per the Intergroup 0096 study (ENI(off)) and the second with heterogeneity corrections while maintaining constant the number of MUs delivered between these latter 2 plans (ENI(on)). Nodal stations were contoured using published guidelines, then placed into 4 "bins" (treated nodes, 1 echelon away, >1 echelon away within the mediastinum, contralateral hilar/supraclavicular). These were aggregated across the patients in the study. Dose to these nodal bins and to tumor/normal structures were compared among these plans using pairwise t-tests. The ENI(on) plans demonstrated a statistically significant degradation in dose coverage compared with the ENI(off) plans. ENI and SNI both created a dose gradient to the lymph nodes across the mediastinum. Overall, the gradient was larger for the SNI plans, although the maximum dose to the "1 echelon away" nodes was not statistically different. Coverage of the GTV and planning target volume (PTV) were improved with SNI, while simultaneously reducing esophageal and spinal cord dose though at the expense of modestly reduced dose to anatomically distant lymph nodes

  14. Update on nodal staging in non-small cell lung cancer with integrated positron emission tomography/computed tomography: a meta-analysis.

    Science.gov (United States)

    Pak, Kyoungjune; Park, Sohyun; Cheon, Gi Jeong; Kang, Keon Wook; Kim, In-Joo; Lee, Dong Soo; Kim, E Edmund; Chung, June-Key

    2015-06-01

    Nowadays, the number of primary studies on fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been increasing rapidly. Thus, we updated meta-analysis to evaluate the test performance of FDG PET/CT for nodal staging in non-small cell lung cancer (NSCLC) including the most recent studies. We performed a systematic search of MEDLINE and EMBASE for English publications using keywords "positron emission tomography", "lung cancer", and "lymph node". All searches were limited to human studies. Inclusion criteria were studies of the initial nodal staging of NSCLC with PET/CT. The reasons for exclusion are as follows: (1) studies with PET, (2) previous therapy before PET/CT, (3) nodal staging not confirmed by histology, and (4) reviews, abstracts, and editorial materials. 786 articles were identified through database searching. 28 studies including 3,255 patients and 11,887 lymph nodes (LN) were eligible for this study. The pooled sensitivity was 0.62 (95% CI 0.54-0.70), widely ranging from 0.13 to 0.98. The specificity ranged between 0.72 and 0.98 with an overall estimated specificity of 0.92 (0.88-0.95) for node-based data. The pooled sensitivity, specificity, positive and negative likelihood ratio were 0.67 (0.54-0.79), 0.87 (0.82-0.91), 5.20 (3.59-7.54), and 0.37 (0.25-0.55) for patient-based data. Studies from tuberculosis (Tb) endemic countries showed lower sensitivity (0.56 vs 0.68, p = 0.03) for node-based data and lower specificity (0.83 vs 0.89, p < 0.01) for patient-based ones. PET/CT has a high specificity, but low sensitivity for detecting LN metastasis in patients with NSCLC. Tb might be one of the main reasons for lower sensitivity of PET/CT in several countries. The primary clinicians of lung cancer should be aware of the possibility of hidden metastatic LNs in bilateral FDG uptake of mediastinal and hilar LNs, especially in the Tb endemic countries.

  15. Diffusion-weighted MR imaging for postoperative nodal recurrence of esophageal squamous cell cancer in comparison with FDG-PET

    International Nuclear Information System (INIS)

    Shuto, Kiyohiko; Saito, Hiroshige; Ohira, Gaku

    2009-01-01

    We evaluated the power of diffusion-weighted MR imaging with background body signal suppression (DWIBS) in patients with postoperative lymph node recurrence of esophageal cancer and compared with fluorodeoxyglucose-positron emission tomography (FDG-PET) findings. Forty-seven suspected lesions by multi detector row CT (MDCT) were enrolled. No significant difference between DWIBS and PET was observed in sensitivity (95% vs 97%), positive predictive value (PPV) (83% vs 90%) and overall accuracy rate (81% vs 87%). The apparent diffusion coefficients (ADCs) (x 10 -3 mm 2 /s) of recurrent nodes, primary cancer and normal esophagus were 1.124, 1.058 and 2.079, respectively. ADCs of recurrent nodes were significantly lower than those of normal esophagus (p<0.0001). The cut-off ADC line of 1.5 revealed 100% overall accuracy for separating the recurrent lesion from normal esophagus. Noninvasive DWIBS may become a valid modality to discriminate nodal recurrence of esophageal cancer by no means inferior to PET. (author)

  16. Optimizing bone morphogenic protein 4-mediated human embryonic stem cell differentiation into trophoblast-like cells using fibroblast growth factor 2 and transforming growth factor-β/activin/nodal signalling inhibition.

    Science.gov (United States)

    Koel, Mariann; Võsa, Urmo; Krjutškov, Kaarel; Einarsdottir, Elisabet; Kere, Juha; Tapanainen, Juha; Katayama, Shintaro; Ingerpuu, Sulev; Jaks, Viljar; Stenman, Ulf-Hakan; Lundin, Karolina; Tuuri, Timo; Salumets, Andres

    2017-09-01

    Several studies have demonstrated that human embryonic stem cells (hESC) can be differentiated into trophoblast-like cells if exposed to bone morphogenic protein 4 (BMP4) and/or inhibitors of fibroblast growth factor 2 (FGF2) and the transforming growth factor beta (TGF-β)/activin/nodal signalling pathways. The goal of this study was to investigate how the inhibitors of these pathways improve the efficiency of hESC differentiation when compared with basic BMP4 treatment. RNA sequencing was used to analyse the effects of all possible inhibitor combinations on the differentiation of hESC into trophoblast-like cells over 12 days. Genes differentially expressed compared with untreated cells were identified at seven time points. Additionally, expression of total human chorionic gonadotrophin (HCG) and its hyperglycosylated form (HCG-H) were determined by immunoassay from cell culture media. We showed that FGF2 inhibition with BMP4 activation up-regulates syncytiotrophoblast-specific genes (CGA, CGB and LGALS16), induces several molecular pathways involved in embryo implantation and triggers HCG-H production. In contrast, inhibition of the TGF-β/activin/nodal pathway decreases the ability of hESC to form trophoblast-like cells. Information about the conditions needed for hESC differentiation toward trophoblast-like cells helps us to find an optimal model for studying the early development of human trophoblasts in normal and in complicated pregnancy. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  17. Trichoepithelioma And Multiple Basal Cell Epithelioma

    Directory of Open Access Journals (Sweden)

    Dey S.K

    1996-01-01

    Full Text Available A combination of multiple trichoepithelioma and basal cell epithelioma is reported. Although malignant degeneration of trichoepithelioma is debated, clinical and histopathological studies, in our case, hint at that. The case is reported for its rarity.

  18. Avoided intersections of nodal lines

    International Nuclear Information System (INIS)

    Monastra, Alejandro G; Smilansky, Uzy; Gnutzmann, Sven

    2003-01-01

    We consider real eigenfunctions of the Schroedinger operator in 2D. The nodal lines of separable systems form a regular grid, and the number of nodal crossings equals the number of nodal domains. In contrast, for wavefunctions of non-integrable systems nodal intersections are rare, and for random waves, the expected number of intersections in any finite area vanishes. However, nodal lines display characteristic avoided crossings which we study in this work. We define a measure for the avoidance range and compute its distribution for the random wave ensemble. We show that the avoidance range distribution of wavefunctions of chaotic systems follows the expected random wave distributions, whereas for wavefunctions of classically integrable but quantum non-separable systems, the distribution is quite different. Thus, the study of the avoidance distribution provides more support to the conjecture that nodal structures of chaotic systems are reproduced by the predictions of the random wave ensemble

  19. Pathology of nodal marginal zone lymphomas.

    Science.gov (United States)

    Pileri, Stefano; Ponzoni, Maurilio

    Nodal marginal zone B cell lymphomas (NMZLs) are a rare group of lymphoid disorders part of the spectrum of marginal zone B-cell lymphomas, which encompass splenic marginal one B-cell lymphoma (SMZL) and extra nodal marginal zone of B-cell lymphoma (EMZL), often of MALT-type. Two clinicopathological forms of NMZL are recognized: adult-type and pediatric-type, respectively. NMZLs show overlapping features with other types of MZ, but distinctive features as well. In this review, we will focus on the salient distinguishing features of NMZL mostly under morphological/immunophenotypical/molecular perspectives in views of the recent acquisitions and forthcoming updated 2016 WHO classification of lymphoid malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Efficacy of pegaspargase in extra nodal natural killer/T-cell lymphoma nasal type: A case report from China

    Directory of Open Access Journals (Sweden)

    Xingan Xiong

    2015-01-01

    Full Text Available Extranodal natural killer (NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. There is no known satisfactory treatment. The author herein to report one case of L-asparaginase extranodal NK/T-cell lymphoma primary treated with L-asparaginase methotrexate and dexamethasone.

  1. Diagnostic accuracy of FDG PET/CT in mediastinal lymph nodal staging of the non-small cell lung cancer: prospective study with PET/CT of 182 cases

    International Nuclear Information System (INIS)

    Lee, J. W.; Kang, W. J.; Kim, B. S.; Lee, D. S.; Jeong, J. K.; Lee, M. C.

    2007-01-01

    This study was performed to assess the accuracy of fluorodeoxyglucose - positron emission tomography/computed tomography (FDG-PET/CT) in the mediastinal lymph nodal staging of non-small cell lung cancer as compared with CT. Between March 2004 and February 2006, 182 patients (126 men and 56 women; mean age, 60.7 y) with non-small cell lung cancer underwent FDG PET/CT and enhanced chest CT. PET/CT and CT images were acquired in a prospective manner. These images were evaluated separately by 2 different physicians and nodal stages were determined by using American Joint Committee on Cancer staging systems. The maxSUV, location, size, calcification and pattern of FDG uptake of lymph nodes were considered. Surgical and histological findings served as the reference standard. A total of 182 patients with 778 mediastinal nodal stations were evaluated. Among them, metastases were found in 36 patients with 53 nodal stations. The respective values for sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mediastinal lymph node staging were 36%, 80%, 30%, 84% and 71% with CT and 75%, 89%, 63%, 94% and 86% with PET/CT on per-patient basis, and 23%, 92%, 18%, 94% and 88% with CT and 66%, 96%, 54%, 98% and 94% with PET/CT on per-nodal-station basis. The maxSUVs of metastatic lymph nodes were significantly higher than those of benign nodes (p = 0.0008). Seventy seven percent (27/35) of the metastatic lymph nodes on FDG-PET/CT images were less than a 1cm in the short axis. Moreover, some benign lymph node patterns, such as bilateral symmetric nodes with similar FDG uptake, benign pattern of nodal calcification and small-sized lymph node with much higher maxSUV than primary tumor, were noted during the evaluation of FDG-PET/CT images. This prospective study suggests that FDG-PET/CT is more accurately stage the mediastinal lymph node staging than CT, and that it provides high specificity and a negative predictive value

  2. An eleven gene molecular signature for extra-capsular spread in oral squamous cell carcinoma serves as a prognosticator of outcome in patients without nodal metastases.

    Science.gov (United States)

    Wang, Weining; Lim, Weng Khong; Leong, Hui Sun; Chong, Fui Teen; Lim, Tony K H; Tan, Daniel S W; Teh, Bin Tean; Iyer, N Gopalakrishna

    2015-04-01

    Extracapsular spread (ECS) is an important prognostic factor for oral squamous cell carcinoma (OSCC) and is used to guide management. In this study, we aimed to identify an expression profile signature for ECS in node-positive OSCC using data derived from two different sources: a cohort of OSCC patients from our institution (National Cancer Centre Singapore) and The Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) cohort. We also sought to determine if this signature could serve as a prognostic factor in node negative cancers. Patients with a histological diagnosis of OSCC were identified from an institutional database and fresh tumor samples were retrieved. RNA was extracted and gene expression profiling was performed using the Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. RNA sequence data and corresponding clinical data for the TCGA HNSCC cohort were downloaded from the TCGA Data Portal. All data analyses were conducted using R package and SPSS. We identified an 11 gene signature (GGH, MTFR1, CDKN3, PSRC1, SMIM3, CA9, IRX4, CPA3, ZSCAN16, CBX7 and ZFP3) which was robust in segregating tumors by ECS status. In node negative patients, patients harboring this ECS signature had a significantly worse overall survival (p=0.04). An eleven gene signature for ECS was derived. Our results also suggest that this signature is prognostic in a separate subset of patients with no nodal metastasis Further validation of this signature on other datasets and immunohistochemical studies are required to establish utility of this signature in stratifying early stage OSCC patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Multiple cell CPV nickel-hydrogen battery

    Science.gov (United States)

    Jones, Ken R.; Zagrodnik, Jeffrey P.

    1991-01-01

    Johnson Controls, Inc. has developed a multiple cell CPV nickel hydrogen battery that offers significant weight, volume, and cost advantages for aerospace applications. The baseline design was successfully demonstrated through the testing of a 26-cell prototype, which completed over 7000 44 percent depth-of-discharge low earth orbit cycles. Prototype designs using both nominal 5 and 10 inch diameter vessels are currently being developed for a variety of customers and applications.

  4. The SINTRAN III NODAL system

    International Nuclear Information System (INIS)

    Skaali, T.B.

    1980-10-01

    NODAL is a high level programming language based on FOCAL and SNOBOL4, with some influence from BASIC. The language was developed to operate on the computer network controlling the SPS accelerator at CERN. NODAL is an interpretive language designed for interactive use. This is the most important aspect of the language, and is reflected in its structure. The interactive facilities make it possible to write, debug and modify programs much faster than with compiler based languages like FORTRAN and ALGOL. Apart from a few minor modifications, the basic part of the Oslo University NODAL system does not differ from the CERN version. However, the Oslo University implementation has been expanded with new functions which enable the user to execute many of the SINTRAN III monitor calls from the NODAL level. In particular the most important RT monitor calls have been implemented in this way, a property which renders possible the use of NODAL as a RT program administrator. (JIW)

  5. Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells

    Science.gov (United States)

    Dombrowski, Mary A.; Sasaki, Masanori; Lankford, Karen L.; Kocsis, Jeffery D.; Radtke, Christine

    2009-01-01

    Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome. Mechanisms suggested to account for this functional improvement include axonal regeneration, remyelination and neuroprotection. OECs transplanted into transected peripheral nerve have been shown to modify peripheral axonal regeneration and functional outcome. However, little is known of the detailed integration of OECs at the transplantation site in peripheral nerve. To address this issue cells populations enriched in OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesion which transects all axons. Five weeks to six months after transplantation the nerves were studied histologically. GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. The internodal regions of individual teased fibers distal to the transection site were characterized by GFP expression in the cytoplasmic and nuclear compartments of cells surrounding the axons. Immuno-electron microscopy for GFP indicated that the transplanted OECs formed peripheral type myelin. Immunostaining for sodium channel and Caspr revealed a high density of Nav1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve and form myelin on regenerated peripheral nerve fibers, and that nodes of Ranvier of these axons display proper sodium channel organization. PMID:17112480

  6. Hematopoietic stem cell transplantation in multiple sclerosis

    DEFF Research Database (Denmark)

    Rogojan, C; Frederiksen, J L

    2009-01-01

    Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...

  7. B Cells and Autoantibodies in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Anne-Katrin Pröbstel

    2015-07-01

    Full Text Available While over the past decades T cells have been considered key players in the pathogenesis of multiple sclerosis (MS, it has only recently become evident that B cells have a major contributing role. Our understanding of the role of B cells has evolved substantially following the clinical success of B cell-targeting therapies and increasing experimental evidence for significant B cell involvement. Rather than mere antibody-producing cells, it is becoming clear that they are team players with the capacity to prime and regulate T cells, and function both as pro- and anti-inflammatory mediators. However, despite tremendous efforts, the target antigen(s of B cells in MS have yet to be identified. The first part of this review summarizes the clinical evidence and results from animal studies pointing to the relevance of B cells in the pathogenesis of MS. The second part gives an overview of the currently known potential autoantigen targets. The third part recapitulates and critically appraises the currently available B cell-directed therapies.

  8. Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

    Science.gov (United States)

    Wu, Shi-Xiu; Wang, Lv-Hua; Luo, Hong-Lei; Xie, Cong-Ying; Zhang, Xue-Bang; Hu, Wei; Zheng, An-Ping; Li, Duo-Jie; Zhang, Hong-Yan; Xie, Cong-Hua; Lian, Xi-Long; Du, De-Xi; Chen, Ming; Bian, Xiu-Hua; Tan, Bang-Xian; Jiang, Hao; Zhang, Hong-Bo; Wang, Jian-Hua; Jing, Zhao; Xia, Bing; Zhang, Ni; Zhang, Ping; Li, Wen-Feng; Zhao, Fu-Jun; Tian, Zhi-Feng; Liu, Hui; Huang, Ke-Wei; Hu, Jin; Xie, Rui-Fei; Du, Lin; Li, Gang

    2018-04-01

    This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m 2  day 1 and cisplatin 20 mg/m 2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Dopamine, T cells and multiple sclerosis (MS).

    Science.gov (United States)

    Levite, Mia; Marino, Franca; Cosentino, Marco

    2017-05-01

    Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in

  10. NODAL interpreter for CP/M

    International Nuclear Information System (INIS)

    Oide, Katsunobu.

    1982-11-01

    A NODAL interpreter which works under CP/M operating system is made for microcomputers. This interpreter language named NODAL-80 has a similar structure to the NODAL of SPS, but its commands, variables, and expressions are modified to increase the flexibility of programming. NODAL-80 also uses a simple intermediate code to make the execution speed fast without imposing any restriction on the dynamic feature of NODAL language. (author)

  11. Numerical solution of the Neutron Transport Equation using discontinuous nodal methods at X-Y geometry

    International Nuclear Information System (INIS)

    Delfin L, A.

    1996-01-01

    The purpose of this work is to solve the neutron transport equation in discrete-ordinates and X-Y geometry by developing and using the strong discontinuous and strong modified discontinuous nodal finite element schemes. The strong discontinuous and modified strong discontinuous nodal finite element schemes go from two to ten interpolation parameters per cell. They are describing giving a set D c and polynomial space S c corresponding for each scheme BDMO, RTO, BL, BDM1, HdV, BDFM1, RT1, BQ and BDM2. The solution is obtained solving the neutron transport equation moments for each nodal scheme by developing the basis functions defined by Pascal triangle and the Legendre moments giving in the polynomial space S c and, finally, looking for the non singularity of the resulting linear system. The linear system is numerically solved using a computer program for each scheme mentioned . It uses the LU method and forward and backward substitution and makes a partition of the domain in cells. The source terms and angular flux are calculated, using the directions and weights associated to the S N approximation and solving the angular flux moments to find the effective multiplication constant. The programs are written in Fortran language, using the dynamic allocation of memory to increase efficiently the available memory of the computing equipment. (Author)

  12. Time-dependent patterning of the mesoderm and endoderm by Nodal signals in zebrafish

    Directory of Open Access Journals (Sweden)

    Dougan Scott T

    2007-03-01

    Full Text Available Abstract Background The vertebrate body plan is generated during gastrulation with the formation of the three germ layers. Members of the Nodal-related subclass of the TGF-β superfamily induce and pattern the mesoderm and endoderm in all vertebrates. In zebrafish, two nodal-related genes, called squint and cyclops, are required in a dosage-dependent manner for the formation of all derivatives of the mesoderm and endoderm. These genes are expressed dynamically during the blastula stages and may have different roles at different times. This question has been difficult to address because conditions that alter the timing of nodal-related gene expression also change Nodal levels. We utilized a pharmacological approach to conditionally inactivate the ALK 4, 5 and 7 receptors during the blastula stages without disturbing earlier signaling activity. This permitted us to directly examine when Nodal signals specify cell types independently of dosage effects. Results We show that two drugs, SB-431542 and SB-505124, completely block the response to Nodal signals when added to embryos after the mid-blastula transition. By blocking Nodal receptor activity at later stages, we demonstrate that Nodal signaling is required from the mid-to-late blastula period to specify sequentially, the somites, notochord, blood, Kupffer's vesicle, hatching gland, heart, and endoderm. Blocking Nodal signaling at late times prevents specification of cell types derived from the embryo margin, but not those from more animal regions. This suggests a linkage between cell fate and length of exposure to Nodal signals. Confirming this, cells exposed to a uniform Nodal dose adopt progressively more marginal fates with increasing lengths of exposure. Finally, cell fate specification is delayed in squint mutants and accelerated when Nodal levels are elevated. Conclusion We conclude that (1 Nodal signals are most active during the mid-to-late blastula stages, when nodal-related gene

  13. Identify multiple myeloma stem cells: Utopia?

    Science.gov (United States)

    Saltarella, Ilaria; Lamanuzzi, Aurelia; Reale, Antonia; Vacca, Angelo; Ria, Roberto

    2015-01-26

    Multiple myeloma (MM) is a hematologic malignancy of monoclonal plasma cells which remains incurable despite recent advances in therapies. The presence of cancer stem cells (CSCs) has been demonstrated in many solid and hematologic tumors, so the idea of CSCs has been proposed for MM, even if MM CSCs have not been define yet. The existence of myeloma CSCs with clonotypic B and clonotypic non B cells was postulated by many groups. This review aims to focus on these distinct clonotypic subpopulations and on their ability to develop and sustain MM. The bone marrow microenvironment provides to MM CSCs self-renewal, survival and drug resistance thanks to the presence of normal and cancer stem cell niches. The niches and CSCs interact each other through adhesion molecules and the interplay between ligands and receptors activates stemness signaling (Hedgehog, Wnt and Notch pathways). MM CSCs are also supposed to be responsible for drug resistance that happens in three steps from the initial cancer cell homing microenvironment-mediated to development of microenvironment-independent drug resistance. In this review, we will underline all these aspects of MM CSCs.

  14. Involvement of multiple cell lineages in atherogenesis | Ogeng'o ...

    African Journals Online (AJOL)

    Involvement of multiple cell lineages in atherogenesis. ... mast cells, dendritic cells, macrophages and immigrant cells usually found in blood, namely ... which influence inflammation, migration, proliferation and secretory activity of each other in ...

  15. Incidence of isolated nodal failure in non-small cell lung cancer patients included in a prospective study of the value of PET–CT

    International Nuclear Information System (INIS)

    Kolodziejczyk, Milena; Bujko, Krzysztof; Michalski, Wojciech; Kepka, Lucyna

    2012-01-01

    Purpose: Elective nodal irradiation (ENI) is not recommended in PET–CT-based radiotherapy for NSCLC despite a low level of evidence to support such guidelines. The aim of this investigation is to find out whether omitting ENI is safe. Materials and methods: Sixty-seven patients treated within a frame of a previously published prospective trial of the value of PET–CT were included in the analysis. Seventeen (25%) patients received ENI due to higher initial nodal involvement and in the remaining 50 patients (75%) with N0-N1 or single N2 disease ENI was omitted. Isolated nodal failure (INF) was recorded if relapse occurred in the initially uninvolved regional lymph node without previous or simultaneous local recurrence regardless of the status of distant metastases. Results: With a median follow-up of 32 months, the estimated 3-year overall survival was 42%, local progression-free interval was 55%, and distant metastases-free interval was 62%. Three patients developed INF; all had ENI omitted from treatment, giving a final result of three INFs in 50 (6%) patients treated without ENI. In this group of patients, the 3-year cause-specific cumulative incidence of INF was 6.4% (95% confidence interval: 0–17%). Conclusions: The omission of ENI appears to be not as safe as suggested by current recommendations.

  16. Incidence of isolated nodal failure in non-small cell lung cancer patients included in a prospective study of the value of PET-CT.

    Science.gov (United States)

    Kolodziejczyk, Milena; Bujko, Krzysztof; Michalski, Wojciech; Kepka, Lucyna

    2012-07-01

    Elective nodal irradiation (ENI) is not recommended in PET-CT-based radiotherapy for NSCLC despite a low level of evidence to support such guidelines. The aim of this investigation is to find out whether omitting ENI is safe. Sixty-seven patients treated within a frame of a previously published prospective trial of the value of PET-CT were included in the analysis. Seventeen (25%) patients received ENI due to higher initial nodal involvement and in the remaining 50 patients (75%) with N0-N1 or single N2 disease ENI was omitted. Isolated nodal failure (INF) was recorded if relapse occurred in the initially uninvolved regional lymph node without previous or simultaneous local recurrence regardless of the status of distant metastases. With a median follow-up of 32 months, the estimated 3-year overall survival was 42%, local progression-free interval was 55%, and distant metastases-free interval was 62%. Three patients developed INF; all had ENI omitted from treatment, giving a final result of three INFs in 50 (6%) patients treated without ENI. In this group of patients, the 3-year cause-specific cumulative incidence of INF was 6.4% (95% confidence interval: 0-17%). The omission of ENI appears to be not as safe as suggested by current recommendations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Nodal metastasis in thyroid cancer

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

    The biological behavior and hence the prognosis of thyroid cancer (TC) depends among other factors on the extent of spread of the disease outside the thyroid bed. This effect is controversial, especially for nodal metastasis of well differentiated thyroid carcinoma (WDC). Nodal metastasis at the time of initial diagnosis behaves differently depending on the histology, age of the patient, presence of extrathyroidal extension, and the sex of the individual. The type of the surgery, administration of 131 I and thyroxin suppression also to some extent influence the rate of recurrence and mortality. Experience has shown that it is not as innocuous as a small intrathyroidal tumor without any invasion outside the thyroid bed and due consideration should be accorded to the management strategies for handling patients with nodal metastasis

  18. The adjoint variational nodal method

    International Nuclear Information System (INIS)

    Laurin-Kovitz, K.; Lewis, E.E.

    1993-01-01

    The widespread use of nodal methods for reactor core calculations in both diffusion and transport approximations has created a demand for the corresponding adjoint solutions as a prerequisite for performing perturbation calculations. With some computational methods, however, the solution of the adjoint problem presents a difficulty; the physical adjoint obtained by discretizing the adjoint equation is not the same as the mathematical adjoint obtained by taking the transpose of the coefficient matrix, which results from the discretization of the forward equation. This difficulty arises, in particular, when interface current nodal methods based on quasi-one-dimensional solution of the diffusion or transport equation are employed. The mathematical adjoint is needed to perform perturbation calculations. The utilization of existing nodal computational algorithms, however, requires the physical adjoint. As a result, similarity transforms or related techniques must be utilized to relate physical and mathematical adjoints. Thus far, such techniques have been developed only for diffusion theory

  19. Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma--a retrospective analysis.

    Science.gov (United States)

    Yamashita, Hideomi; Okuma, Kae; Wakui, Reiko; Kobayashi-Shibata, Shino; Ohtomo, Kuni; Nakagawa, Keiichi

    2011-02-01

    To describe patterns of recurrence of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal squamous cell carcinoma (SqCC) using 3D-conformal radiotherapy. One hundred and twenty-six consecutive patients with stages I-IVB thoracic esophageal SqCC newly diagnosed between June 2000 and July 2009 and treated with 3D-CRT in our institution were recruited from our database. Definitive CRT consisted of two cycles of nedaplatin/5FU repeated every 4 weeks, with concurrent radiation therapy of 50-50.4 Gy in 25-28 fractions. Until completion, radiotherapy was delivered to the N1 and M1a lymph nodes as ENI in addition to gross tumor volume. All 126 patients were included in this analysis, and their tumors were staged as follows: T1/T2/T3/T4, 28/18/54/26; N0/N1, 50/76; M0/M1a/M1b, 91/5/30. The mean follow-up period for the 63 surviving patients was 28.3 (±22.8) months. Eighty-seven patients (69%) achieved complete response (CR) without any residual tumor at least once after completion of CRT. After achieving CR, each of 40 patients experienced failures (local=20 and distant=20) and no patient experienced elective nodal failure without having any other site of recurrence. The upper thoracic esophageal carcinoma showed significantly more (34%) relapses at the local site than the middle (9%) or lower thoracic (11%) carcinomas. The 2-year and 3-year overall survival was 56% and 43%, respectively. The 1-year, 2-year and 3-year disease-free survival was 46%, 38% and 33%, respectively. In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. The upper thoracic esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction.

    Science.gov (United States)

    Park, C B; Dufort, D

    2011-03-01

    Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF-β) superfamily, has established roles in vertebrate development. However, components of the Nodal signaling pathway are also expressed at the maternal-fetal interface and have been implicated in many processes of mammalian reproduction. Emerging evidence indicates that Nodal and its extracellular inhibitor Lefty are expressed in the uterus and complex interactions between the two proteins mediate menstruation, decidualization and embryo implantation. Furthermore, several studies have shown that Nodal from both fetal and maternal sources may regulate trophoblast cell fate and facilitate placentation as both embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted placenta morphology. Here we review the established and prospective roles of Nodal signaling in facilitating successful pregnancy, including recent evidence supporting a potential link to parturition and preterm birth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Nodal in computerized control systems of accelerators

    International Nuclear Information System (INIS)

    Kagarmanov, A.A.; Koval'tsov, V.I.; Korobov, S.A.

    1994-01-01

    Brief description of the Nodal language programming structure is presented. Its possibilities as high-level programming language for accelerator control systems are considered. The status of the Nodal language in the HEPI is discussed. 3 refs

  2. A variational synthesis nodal discrete ordinates method

    International Nuclear Information System (INIS)

    Favorite, J.A.; Stacey, W.M.

    1999-01-01

    A self-consistent nodal approximation method for computing discrete ordinates neutron flux distributions has been developed from a variational functional for neutron transport theory. The advantage of the new nodal method formulation is that it is self-consistent in its definition of the homogenized nodal parameters, the construction of the global nodal equations, and the reconstruction of the detailed flux distribution. The efficacy of the method is demonstrated by two-dimensional test problems

  3. On the Nodal Lines of Eisenstein Series on Schottky Surfaces

    Science.gov (United States)

    Jakobson, Dmitry; Naud, Frédéric

    2017-04-01

    On convex co-compact hyperbolic surfaces {X=Γ backslash H2}, we investigate the behavior of nodal curves of real valued Eisenstein series {F_λ(z,ξ)}, where {λ} is the spectral parameter, {ξ} the direction at infinity. Eisenstein series are (non-{L^2}) eigenfunctions of the Laplacian {Δ_X} satisfying {Δ_X F_λ=(1/4+λ^2)F_λ}. As {λ} goes to infinity (the high energy limit), we show that, for generic {ξ}, the number of intersections of nodal lines with any compact segment of geodesic grows like {λ}, up to multiplicative constants. Applications to the number of nodal domains inside the convex core of the surface are then derived.

  4. Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

  5. Radiotherapy of adult nodal non Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Gamen, G.; Thirion, P.

    1999-01-01

    The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. For easy-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10 year disease-free survival rate of 50 % and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. For 'new' nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods. (authors)

  6. Discontinuous nodal schemes applied to the bidimensional neutron transport equation

    International Nuclear Information System (INIS)

    Delfin L, A.; Valle G, E. Del; Hennart B, J.P.

    1996-01-01

    In this paper several strong discontinuous nodal schemes are described, starting from the one that has only two interpolation parameters per cell to the one having ten. Their application to the spatial discretization of the neutron transport equation in X-Y geometry is also described, giving, for each one of the nodal schemes, the approximation for the angular neutron flux that includes the set of interpolation parameters and the corresponding polynomial space. Numerical results were obtained for several test problems presenting here the problem with the highest degree of difficulty and their comparison with published results 1,2 . (Author)

  7. Investigation on generalized Variational Nodal Methods for heterogeneous nodes

    International Nuclear Information System (INIS)

    Wang, Yongping; Wu, Hongchun; Li, Yunzhao; Cao, Liangzhi; Shen, Wei

    2017-01-01

    Highlights: • We developed two heterogeneous nodal methods based on the Variational Nodal Method. • Four problems were solved to evaluate the two heterogeneous nodal methods. • The function expansion method is good at treating continuous-changing heterogeneity. • The finite sub-element method is good at treating discontinuous-changing heterogeneity. - Abstract: The Variational Nodal Method (VNM) is generalized for heterogeneous nodes and applied to four kinds of problems including Molten Salt Reactor (MSR) core problem with continuous cross section profile, Pressurized Water Reactor (PWR) control rod cusping effect problem, PWR whole-core pin-by-pin problem, and heterogeneous PWR core problem without fuel-coolant homogenization in each pin cell. Two approaches have been investigated for the treatment of the nodal heterogeneity in this paper. To concentrate on spatial heterogeneity, diffusion approximation was adopted for the angular variable in neutron transport equation. To provide demonstrative numerical results, the codes in this paper were developed in slab geometry. The first method, named as function expansion (FE) method, expands nodal flux by orthogonal polynomials and the nodal cross sections are also expressed as spatial depended functions. The second path, named as finite sub-element (FS) method, takes advantage of the finite-element method by dividing each node into numbers of homogeneous sub-elements and expanding nodal flux into the combination of linear sub-element trial functions. Numerical tests have been carried out to evaluate the ability of the two nodal (coarse-mesh) heterogeneous VNMs by comparing with the fine-mesh homogeneous VNM. It has been demonstrated that both heterogeneous approaches can handle heterogeneous nodes. The FE method is good at continuous-changing heterogeneity as in the MSR core problem, while the FS method is good at discontinuous-changing heterogeneity such as the PWR pin-by-pin problem and heterogeneous PWR core

  8. NESTLE: A nodal kinetics code

    International Nuclear Information System (INIS)

    Al-Chalabi, R.M.; Turinsky, P.J.; Faure, F.-X.; Sarsour, H.N.; Engrand, P.R.

    1993-01-01

    The NESTLE nodal kinetics code has been developed for utilization as a stand-alone code for steady-state and transient reactor neutronic analysis and for incorporation into system transient codes, such as TRAC and RELAP. The latter is desirable to increase the simulation fidelity over that obtained from currently employed zero- and one-dimensional neutronic models and now feasible due to advances in computer performance and efficiency of nodal methods. As a stand-alone code, requirements are that it operate on a range of computing platforms from memory-limited personal computers (PCs) to supercomputers with vector processors. This paper summarizes the features of NESTLE that reflect the utilization and requirements just noted

  9. Nodal lymphomas of the abdomen

    International Nuclear Information System (INIS)

    Bruneton, J.N.; Caramella, E.; Manzino, J.J.

    1986-01-01

    Modern imaging modalities have greatly contributed to current knowledge about intra-abdominal nodal lymphomas. Since both intra and retroperitoneal node involvement can be demonstrated by computed tomography (CT) and ultrasonography, it seems legitimate to treat these two sites together in the same chapter, particularly since the older separation between intraperitoneal and retroperitoneal nodal disease was based to a large degree on the limitations of lymphography. Hodgkin's disease (HD) has benefited less from recent technological advances. The diversity in the incidence of nodal involvement between HD and NHL, the diagnostic capabilities of modern imaging techniques, and the histopathological features of lymphomatous non-Hodgkin and Hodgkin nodes, justify adoption of an investigatory approach which takes all of these factors into account. Details of this investigative strategy are discussed in this paper following a review of available imaging modalities. In current practice, the four main methods for the exploration of abdominal lymph nodes are lymphography, ultrasonography, CT, and radionuclide studies. The first three techniques are also utilized to guide biopsies for staging purposes and for the evaluation of response to treatment

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Numerical solution of the Neutron Transport Equation using discontinuous nodal methods at X-Y geometry; Solucion numerica de la ecuacion de transporte de neutrones usando metodos nodales discontinuos en geometria X-Y

    Energy Technology Data Exchange (ETDEWEB)

    Delfin L, A

    1997-12-31

    The purpose of this work is to solve the neutron transport equation in discrete-ordinates and X-Y geometry by developing and using the strong discontinuous and strong modified discontinuous nodal finite element schemes. The strong discontinuous and modified strong discontinuous nodal finite element schemes go from two to ten interpolation parameters per cell. They are describing giving a set D{sub c} and polynomial space S{sub c} corresponding for each scheme BDMO, RTO, BL, BDM1, HdV, BDFM1, RT1, BQ and BDM2. The solution is obtained solving the neutron transport equation moments for each nodal scheme by developing the basis functions defined by Pascal triangle and the Legendre moments giving in the polynomial space S{sub c} and, finally, looking for the non singularity of the resulting linear system. The linear system is numerically solved using a computer program for each scheme mentioned . It uses the LU method and forward and backward substitution and makes a partition of the domain in cells. The source terms and angular flux are calculated, using the directions and weights associated to the S{sub N} approximation and solving the angular flux moments to find the effective multiplication constant. The programs are written in Fortran language, using the dynamic allocation of memory to increase efficiently the available memory of the computing equipment. (Author).

  12. Nodal parameters of FDG PET/CT performed during radiotherapy for locally advanced mucosal primary head and neck squamous cell carcinoma can predict treatment outcomes: SUVmean and response rate are useful imaging biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Peter [Liverpool Hospital, Department of Nuclear Medicine and PET, Liverpool BC, NSW (Australia); University of New South Wales, South Western Sydney Clinical School, Sydney, NSW (Australia); Western Sydney University, Sydney, NSW (Australia); Min, Myo; Forstner, Dion [University of New South Wales, South Western Sydney Clinical School, Sydney, NSW (Australia); Liverpool Hospital, Cancer Therapy Centre, Liverpool, NSW (Australia); Ingham Institute of Applied Medical Research, Liverpool, NSW (Australia); Lee, Mark [University of New South Wales, South Western Sydney Clinical School, Sydney, NSW (Australia); Liverpool Hospital, Cancer Therapy Centre, Liverpool, NSW (Australia); Holloway, Lois [University of New South Wales, South Western Sydney Clinical School, Sydney, NSW (Australia); Western Sydney University, Sydney, NSW (Australia); Liverpool Hospital, Cancer Therapy Centre, Liverpool, NSW (Australia); Ingham Institute of Applied Medical Research, Liverpool, NSW (Australia); Bray, Victoria; Fowler, Allan [Liverpool Hospital, Cancer Therapy Centre, Liverpool, NSW (Australia)

    2017-05-15

    To evaluate the prognostic utility of nodal metabolic parameters derived from FDG PET/CT performed before radiotherapy (prePET) and during the third week of radiotherapy (iPET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC). This analysis included 75 patients with newly diagnosed locally advanced node-positive MPHNSCC treated with radical radiotherapy and concurrent systemic therapy who underwent prePET and iPET: N1 11 patients, N2a 38, N2b 12, N2c 9, N3 5. The median follow-up was 28 months (9 - 70 months). The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of the index lymph node (node with the highest TLG) and the combined total lymph nodes, and their percentage reductions on iPET were determined, and the results were correlated with 3-year Kaplan-Meier locoregional, regional and distant metastatic failure-free survival (FFS), disease-free survival (DFS) and overall survival (OS). Optimal cut-off values were derived from receiver operating characteristic curves. Cox regression univariate and multivariate analyses with clinical covariates were performed. Based on assessment of residual nodal metabolic burden during treatment, the iPET index node SUVmean (optimal cut-off value 2.95 g/ml) and the total node SUVmean (optimal cut-off value 3.25) were the best independent predictors of outcome in the multivariate analysis: index node SUVmean for DFS and OS p = 0.033 and 0.003, respectively, and the total node SUVmean for locoregional FFS, DFS and OS p = 0.028, 0.025 and 0.014, respectively. Based on the assessment of response rates during treatment, a reduction of more than 50 % in the total node TLG was the best biomarker for locoregional and regional FFS, DFS and OS in the multivariate analysis (p = 0.001, 0.016, 0.001 and 0.004, respectively), and reduction in the total node MTV for locoregional FFS, DFS and OS (p = 0.026, 0.003 and 0

  13. Analytic function expansion nodal method for nuclear reactor core design

    International Nuclear Information System (INIS)

    Noh, Hae Man

    1995-02-01

    deriving the nodal coupling equations, it does not suffer from the limitations caused by the transverse integration, such as the need of transverse leakage approximation and the singularity arising in non-rectangular node geometries. And because of the use of analytic basis functions, the method accurately models large localized flux gradients in the vicinity of nodal corner points as well as nodal interfaces. To demonstrate its accuracy and applicability to realistic problems, the AFEN method was tested to several benchmark problems in both the rectangular and the hexagonal geometry, including MOX fuel problems, and the initial core of Ulchin Unit 1. The results show that the AFEN method significantly improves the accuracy in the nodal flux distribution and the core multiplication factor compared to the nodal methods which use the transverse integration. The method also facilitates pinwise flux reconstruction since the homogeneous flux distributions obtained from the nodal calculation are very accurate and can be used directly in the reconstruction. Encouraged by the success of the AFEN method, we also developed two other nodal methods in this study, which can be classified as variations of the AFEN method. The first one is the Polynomial Expansion Nodal (PEN) method. This method retains all the features of the AFEN method except expanding the intranodal flux distribution into a nonseparable high-order polynomial instead of the analytic function. The results of benchmark problems indicate mixed performance of the method. For the conventional light water reactor cores loaded with the conventional UO 2 fuel assembly, the performance of the method is similar to that of the AFEN method, but for the reactor cores loaded with the MOX fuel assemblies, the PEN method is poorer than the AFEN method. The poor performance of the PEN method for the MOX fuel loaded cores is due to the fact that the polynomial is less accurate for the representation of the intranodal flux distribution

  14. Multiple gastrointestinal metastases of Merkel cell carcinoma.

    Science.gov (United States)

    Poškus, Eligijus; Platkevičius, Gediminas; Simanskaitė, Vilma; Rimkevičiūtė, Ernesta; Petrulionis, Marius; Strupas, Kestutis

    2016-01-01

    Merkel cell carcinoma is an aggressive skin malignancy. Primary Merkel cell carcinomas are treated by wide radical excision with or without adjuvant radiotherapy, while benefits of adjuvant chemotherapy remain doubtful. There are only several cases of gastrointestinal metastases of Merkel cell carcinoma reported so far. We report a case of recurrent Merkel cell carcinoma with metastases to the stomach and the small intestines after wide excision of primary Merkel cell carcinoma. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Optical cell sorting with multiple imaging modalities

    DEFF Research Database (Denmark)

    Banas, Andrew; Carrissemoux, Caro; Palima, Darwin

    2017-01-01

    healthy cells. With the richness of visual information, a lot of microscopy techniques have been developed and have been crucial in biological studies. To utilize their complementary advantages we adopt both fluorescence and brightfield imaging in our optical cell sorter. Brightfield imaging has...... the advantage of being non-invasive, thus maintaining cell viability. Fluorescence imaging, on the other hand, takes advantages of the chemical specificity of fluorescence markers and can validate machine vision results from brightfield images. Visually identified cells are sorted using optical manipulation...

  16. Using nodal expansion method in calculation of reactor core with square fuel assemblies

    International Nuclear Information System (INIS)

    Abdollahzadeh, M. Y.; Boroushaki, M.

    2009-01-01

    A polynomial nodal method is developed to solve few-group neutron diffusion equations in cartesian geometry. In this article, the effective multiplication factor, group flux and power distribution based on the nodal polynomial expansion procedure is presented. In addition, by comparison of the results the superiority of nodal expansion method on finite-difference and finite-element are fully demonstrated. The comparison of the results obtained by these method with those of the well known benchmark problems have shown that they are in very good agreement.

  17. Cell-based therapeutic strategies for multiple sclerosis

    DEFF Research Database (Denmark)

    Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C

    2017-01-01

    and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities......, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved...

  18. Development of nodal interface conditions for a PN approximation nodal model

    International Nuclear Information System (INIS)

    Feiz, M.

    1993-01-01

    A relation was developed for approximating higher order odd-moments from lower order odd-moments at the nodal interfaces of a Legendre polynomial nodal model. Two sample problems were tested using different order P N expansions in adjacent nodes. The developed relation proved to be adequate and matched the nodal interface flux accurately. The development allows the use of different order expansions in adjacent nodes, and will be used in a hybrid diffusion-transport nodal model. (author)

  19. SPANDOM - source projection analytic nodal discrete ordinates method

    International Nuclear Information System (INIS)

    Kim, Tae Hyeong; Cho, Nam Zin

    1994-01-01

    We describe a new discrete ordinates nodal method for the two-dimensional transport equation. We solve the discrete ordinates equation analytically after the source term is projected and represented in polynomials. The method is applied to two fast reactor benchmark problems and compared with the TWOHEX code. The results indicate that the present method accurately predicts not only multiplication factor but also flux distribution

  20. Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines

    NARCIS (Netherlands)

    van den Berg, Henk; Schreuder, Willem Hans; Jongmans, Marjolijn; van Bommel-Slee, Danielle; Witsenburg, Bart; de Lange, Jan

    2016-01-01

    A patient with Noonan syndrome with multiple lentigines (NSML) and multiple giant cell lesions (MGCL) in mandibles and maxillae is described. A mutation p.Thr468Met in the PTPN11-gene was found. This is the second reported NSML patient with MGCL. Our case adds to the assumption that, despite a

  1. involvement of multiple cell lineages in atherogenesis

    African Journals Online (AJOL)

    2017-07-12

    Jul 12, 2017 ... Elucidation of all ... molecular mechanisms which underly this .... intima. Monocyte chemoattractant protein-1 ... cell interaction, release of microparticles, pro – ..... Monocytes and macrophages dynamics during atherogenesis.

  2. Systematic assembly homogenization and local flux reconstruction for nodal method calculations of fast reactor power distributions

    International Nuclear Information System (INIS)

    Dorning, J.J.

    1991-01-01

    A simultaneous pin lattice cell and fuel bundle homogenization theory has been developed for use with nodal diffusion calculations of practical reactors. The theoretical development of the homogenization theory, which is based on multiple-scales asymptotic expansion methods carried out through fourth order in a small parameter, starts from the transport equation and systematically yields: a cell-homogenized bundled diffusion equation with self-consistent expressions for the cell-homogenized cross sections and diffusion tensor elements; and a bundle-homogenized global reactor diffusion equation with self-consistent expressions for the bundle-homogenized cross sections and diffusion tensor elements. The continuity of the angular flux at cell and bundle interfaces also systematically yields jump conditions for the scaler flux or so-called flux discontinuity factors on the cell and bundle interfaces in terms of the two adjacent cell or bundle eigenfunctions. The expressions required for the reconstruction of the angular flux or the 'de-homogenization' theory were obtained as an integral part of the development; hence the leading order transport theory angular flux is easily reconstructed throughout the reactor including the regions in the interior of the fuel bundles or computational nodes and in the interiors of the pin lattice cells. The theoretical development shows that the exact transport theory angular flux is obtained to first order from the whole-reactor nodal diffusion calculations, done using the homogenized nuclear data and discontinuity factors, is a product of three computed quantities: a ''cell shape function''; a ''bundle shape function''; and a ''global shape function''. 10 refs

  3. The Nudo, Rollo, Melon codes and nodal correlations

    International Nuclear Information System (INIS)

    Perlado, J.M.; Aragones, J.M.; Minguez, E.; Pena, J.

    1975-01-01

    Analysis of nodal calculation and checking results by the reference reactor experimental data. Nudo code description, adapting experimental data to nodal calculations. Rollo, Melon codes as improvement in the cycle life calculations of albedos, mixing parameters and nodal correlations. (author)

  4. Heterogeneous treatment in the variational nodal method

    International Nuclear Information System (INIS)

    Fanning, T.H.

    1995-01-01

    The variational nodal transport method is reduced to its diffusion form and generalized for the treatment of heterogeneous nodes while maintaining nodal balances. Adapting variational methods to heterogeneous nodes requires the ability to integrate over a node with discontinuous cross sections. In this work, integrals are evaluated using composite gaussian quadrature rules, which permit accurate integration while minimizing computing time. Allowing structure within a nodal solution scheme avoids some of the necessity of cross section homogenization, and more accurately defines the intra-nodal flux shape. Ideally, any desired heterogeneity can be constructed within the node; but in reality, the finite set of basis functions limits the practical resolution to which fine detail can be defined within the node. Preliminary comparison tests show that the heterogeneous variational nodal method provides satisfactory results even if some improvements are needed for very difficult, configurations

  5. Novel human multiple myeloma cell line UHKT-893

    Czech Academy of Sciences Publication Activity Database

    Uherková, L.; Vančurová, I.; Vyhlídalová, I.; Pleschnerová, M.; Špička, I.; Mihalová, R.; Březinová, J.; Hodný, Zdeněk; Čermáková, K.; Polanská, V.; Marinov, I.; Jedelský, P.L.; Kuželová, K.; Stöckbauer, P.

    2013-01-01

    Roč. 37, č. 3 (2013), s. 320-326 ISSN 0145-2126 Institutional support: RVO:68378050 Keywords : human myeloma cell line * human multiple myeloma * plasma cell * IL-6 dependence * immunoglobulin * free light chain Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.692, year: 2013

  6. 2-Aminopurine overrides multiple cell cycle checkpoints in BHK cells.

    OpenAIRE

    Andreassen, P R; Margolis, R L

    1992-01-01

    BHK cells blocked at any of several points in the cell cycle override their drug-induced arrest and proceed in the cycle when exposed concurrently to the protein kinase inhibitor 2-aminopurine (2-AP). For cells arrested at various points in interphase, 2-AP-induced cell cycle progression is made evident by arrival of the drug-treated cell population in mitosis. Cells that have escaped from mimosine G1 arrest, from hydroxyurea or aphidicolin S-phase arrest, or from VM-26-induced G2 arrest subs...

  7. Cell elasticity with altered cytoskeletal architectures across multiple cell types.

    Science.gov (United States)

    Grady, Martha E; Composto, Russell J; Eckmann, David M

    2016-08-01

    The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Cell-based therapeutic strategies for multiple sclerosis.

    Science.gov (United States)

    Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

    2017-11-01

    The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  9. Nodal pricing in a coupled electricity market

    OpenAIRE

    Bjørndal, Endre; Bjørndal, Mette; Cai, Hong

    2014-01-01

    This paper investigates a pricing model for an electricity market with a hybrid congestion management method, i.e. part of the system applies a nodal pricing scheme and the rest applies a zonal pricing scheme. The model clears the zonal and nodal pricing areas simultaneously. The nodal pricing area is affected by the changes in the zonal pricing area since it is directly connected to the zonal pricing area by commercial trading. The model is tested on a 13-node power system. Within the area t...

  10. Alpha-particles induce autophagy in multiple myeloma cells

    Directory of Open Access Journals (Sweden)

    Joelle Marcelle Gaschet

    2015-10-01

    Full Text Available Objectives: Radiations emitted by the radionuclides in radioimmunotherapy (RIT approaches induce direct killing of the targeted cells as well as indirect killing through bystander effect. Our research group is dedicated to the development of α-RIT, i.e RIT using α-particles especially for the treatment of multiple myeloma (MM. γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by 213Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of 213Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation.Methods: Murine 5T33 and human LP-1 multiple myeloma (MM cell lines were used to study the effects of such α-particles. We first examined the effects of 213Bi on proliferation rate, double strand DNA breaks, cell cycle and cell death. Then, we investigated autophagy after 213Bi irradiation. Finally, a co-culture of dendritic cells (DC with irradiated tumour cells or their culture media was performed to test whether it would induce DC activation.Results: We showed that 213Bi induces DNA double strand breaks, cell cycle arrest and autophagy in both cell lines but we detected only slight levels of early apoptosis within the 120 hours following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented 213Bi induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s, however no increase in membrane or extracellular expression of danger associated molecular patterns (DAMPs was observed after irradiation.Conclusion: This study demonstrates that 213Bi induces mainly necrosis in MM cells, low levels of apoptosis and also autophagy that might be involved in tumor cell death.

  11. Multiple exciton generation in quantum dot-based solar cells

    Science.gov (United States)

    Goodwin, Heather; Jellicoe, Tom C.; Davis, Nathaniel J. L. K.; Böhm, Marcus L.

    2018-01-01

    Multiple exciton generation (MEG) in quantum-confined semiconductors is the process by which multiple bound charge-carrier pairs are generated after absorption of a single high-energy photon. Such charge-carrier multiplication effects have been highlighted as particularly beneficial for solar cells where they have the potential to increase the photocurrent significantly. Indeed, recent research efforts have proved that more than one charge-carrier pair per incident solar photon can be extracted in photovoltaic devices incorporating quantum-confined semiconductors. While these proof-of-concept applications underline the potential of MEG in solar cells, the impact of the carrier multiplication effect on the device performance remains rather low. This review covers recent advancements in the understanding and application of MEG as a photocurrent-enhancing mechanism in quantum dot-based photovoltaics.

  12. Quantum oscillations in nodal line systems

    Science.gov (United States)

    Yang, Hui; Moessner, Roderich; Lim, Lih-King

    2018-04-01

    We study signatures of magnetic quantum oscillations in three-dimensional nodal line semimetals at zero temperature. The extended nature of the degenerate bands can result in a Fermi surface geometry with topological genus one, as well as a Fermi surface of electron and hole pockets encapsulating the nodal line. Moreover, the underlying two-band model to describe a nodal line is not unique, in that there are two classes of Hamiltonian with distinct band topology giving rise to the same Fermi-surface geometry. After identifying the extremal cyclotron orbits in various magnetic field directions, we study their concomitant Landau levels and resulting quantum oscillation signatures. By Landau-fan-diagram analyses, we extract the nontrivial π Berry phase signature for extremal orbits linking the nodal line.

  13. Sensitivity of SBLOCA analysis to model nodalization

    International Nuclear Information System (INIS)

    Lee, C.; Ito, T.; Abramson, P.B.

    1983-01-01

    The recent Semiscale test S-UT-8 indicates the possibility for primary liquid to hang up in the steam generators during a SBLOCA, permitting core uncovery prior to loop-seal clearance. In analysis of Small Break Loss of Coolant Accidents with RELAP5, it is found that resultant transient behavior is quite sensitive to the selection of nodalization for the steam generators. Although global parameters such as integrated mass loss, primary inventory and primary pressure are relatively insensitive to the nodalization, it is found that the predicted distribution of inventory around the primary is significantly affected by nodalization. More detailed nodalization predicts that more of the inventory tends to remain in the steam generators, resulting in less inventory in the reactor vessel and therefore causing earlier and more severe core uncovery

  14. Twisted Vector Bundles on Pointed Nodal Curves

    Indian Academy of Sciences (India)

    Abstract. Motivated by the quest for a good compactification of the moduli space of -bundles on a nodal curve we establish a striking relationship between Abramovich's and Vistoli's twisted bundles and Gieseker vector bundles.

  15. Concomitant occurrence of sinus histiocytosis with massive lymphadenopathy and nodal marginal zone lymphoma.

    Science.gov (United States)

    Pang, Changlee S; Grier, David D; Beaty, Michael W

    2011-03-01

    Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, is a rare self-limiting disorder of histiocytes with unknown etiology. Sinus histiocytosis with massive lymphadenopathy is most common in children and young adults and is characterized by painless lymphadenopathy. Histologically there is a proliferation of sinus histiocytes with lymphophagocytosis or emperipolesis. On rare occasions, SHML has been associated with lymphoma, usually involving different anatomic sites and developing at different times. We report a case of concomitant SHML and nodal marginal zone lymphoma involving the same lymph node without involvement of other nodal or extranodal sites. The presence of concomitant SHML within the lymph node involved by nodal marginal zone lymphoma may represent the responsiveness of SHML histiocytes to B-cell-derived cytokines in lymphoproliferative disorders. To our knowledge, this is the first description of concomitant occurrence of SHML and nodal marginal zone lymphoma.

  16. The role of radiation therapy for stage IIIB non-small cell lung cancer. Impact of clinical nodal stage on survival

    International Nuclear Information System (INIS)

    Hayakawa, Kazushige; Mitsuhashi, Norio; Furuta, Masaya; Saito, Yoshihiro; Nakayama, Yuko; Katano, Susumu; Ohno, Tatsuya; Niibe, Hideo

    1996-01-01

    From 1976 through 1989, 46 patients with stage IIIB non-small cell lung cancer (NSCLC) without malignant effusion were treated with definitive radiation therapy (RT) at Gunma University Hospital. All patients were treated with 10 MV x-rays using antero posterior parallel opposed fields. The total dose ranged from 60 Gy to 70 Gy (mean dose; 66 Gy) with once daily standard fractionation. The actuarial two and five-year survival rates of the entire group were 22% and 10% respectively with a median survival time (MST) of 10 months. The survival of 18 patients with stage N0-2 disease was significantly better than the 28 patients with stage N3 disease (MST 21 versus 9 months; p<0.05). There were no significant differences in survival based on age and sex. However, there was a borderline difference in survival rates between patients with a performance status of 0-1 and those with status of 2-3 (p=0.06). Three patients with squamous cell carcinoma were alive after 5 years and were without disease progression. No patients with non-squamous cell carcinoma were free of disease after 5 years. These results provide support for the use of definitive RT to manage those patients with limited stage IIIB squamous cell carcinoma not extending to N3 stage. (author)

  17. Competitive Stem Cell Recruitment by Multiple Cytotactic Cues

    Science.gov (United States)

    Mendelson, Avital; Cheung, Yukkee; Paluch, Kamila; Chen, Mo; Kong, Kimi; Tan, Jiali; Dong, Ziming; Sia, Samuel K.; Mao, Jeremy J.

    2014-01-01

    A multitude of cytotactic cues direct cell migration in development, cancer metastasis and wound healing. However, our understanding of cell motility remains fragmented partially because current migration devices only allow the study of independent factors. We developed a cell motility assay that allows competitive recruitment of a given cell population simultaneously by gradients of multiple cytotactic cues, observable under real-time imaging. Well-defined uniform gradients of cytotactic cues can be independently generated and sustained in each channel. As a case study, bone marrow mesenchymal stem/stromal cells (MSCs) were exposed to 15 cytokines that are commonly present in arthritis. Cytokines that induced robust recruitment of MSCs in multiple groups were selected to ‘compete’ in a final round to yield the most chemotactic factor(s) based on cell migration numbers, distances, migration indices and motility over time. The potency of a given cytokine in competition frequently differed from its individual action, substantiating the need to test multiple cytokines concurrently due to synergistic or antagonistic effects. This new device has the rare capacity to screen molecules that induce cell migration in cancer therapy, drug development and tissue regeneration. PMID:23364311

  18. The NODAL system for the SPS

    International Nuclear Information System (INIS)

    Crowley-Milling, M.C.; Shering, G.C.

    1978-01-01

    A comprehensive description is given of the NODAL system used for computer control of the CERN Super-Proton Synchrotron. Details are given of NODAL, a high-level programming language based on FOCAL and SNOBOL4, designed for interactive use. It is shown how this interpretive language is used with a network of computers and how it can be extended by adding machine-code modules. The report updates and replaces an earlier one published in 1974. (Auth.)

  19. Nodal coupling by response matrix principles

    International Nuclear Information System (INIS)

    Ancona, A.; Becker, M.; Beg, M.D.; Harris, D.R.; Menezes, A.D.; VerPlanck, D.M.; Pilat, E.

    1977-01-01

    The response matrix approach has been used in viewing a reactor node in isolation and in characterizing the node by reflection and trans-emission factors. These are then used to generate invariant imbedding parameters, which in turn are used in a nodal reactor simulator code to compute core power distributions in two and three dimensions. Various nodal techniques are analyzed and converted into a single invariant imbedding formalism

  20. Hybrid microscopic depletion model in nodal code DYN3D

    International Nuclear Information System (INIS)

    Bilodid, Y.; Kotlyar, D.; Shwageraus, E.; Fridman, E.; Kliem, S.

    2016-01-01

    Highlights: • A new hybrid method of accounting for spectral history effects is proposed. • Local concentrations of over 1000 nuclides are calculated using micro depletion. • The new method is implemented in nodal code DYN3D and verified. - Abstract: The paper presents a general hybrid method that combines the micro-depletion technique with correction of micro- and macro-diffusion parameters to account for the spectral history effects. The fuel in a core is subjected to time- and space-dependent operational conditions (e.g. coolant density), which cannot be predicted in advance. However, lattice codes assume some average conditions to generate cross sections (XS) for nodal diffusion codes such as DYN3D. Deviation of local operational history from average conditions leads to accumulation of errors in XS, which is referred as spectral history effects. Various methods to account for the spectral history effects, such as spectral index, burnup-averaged operational parameters and micro-depletion, were implemented in some nodal codes. Recently, an alternative method, which characterizes fuel depletion state by burnup and 239 Pu concentration (denoted as Pu-correction) was proposed, implemented in nodal code DYN3D and verified for a wide range of history effects. The method is computationally efficient, however, it has applicability limitations. The current study seeks to improve the accuracy and applicability range of Pu-correction method. The proposed hybrid method combines the micro-depletion method with a XS characterization technique similar to the Pu-correction method. The method was implemented in DYN3D and verified on multiple test cases. The results obtained with DYN3D were compared to those obtained with Monte Carlo code Serpent, which was also used to generate the XS. The observed differences are within the statistical uncertainties.

  1. Magnonic triply-degenerate nodal points

    Science.gov (United States)

    Owerre, S. A.

    2017-12-01

    We generalize the concept of triply-degenerate nodal points to non-collinear antiferromagnets. Here, we introduce this concept to insulating quantum antiferromagnets on the decorated honeycomb lattice, with spin-1 bosonic quasiparticle excitations known as magnons. We demonstrate the existence of magnonic surface states with constant energy contours that form pairs of magnonic arcs connecting the surface projection of the magnonic triple nodal points. The quasiparticle excitations near the triple nodal points represent three-component bosons beyond that of magnonic Dirac, Weyl, and nodal-line cases. They can be regarded as a direct reflection of the intrinsic spin carried by magnons. Furthermore, we show that the magnonic triple nodal points can split into magnonic Weyl points, as the system transits from a non-collinear spin structure to a non-coplanar one with a non-zero scalar spin chirality. Our results not only apply to insulating antiferromagnets, but also provide a platform to seek for triple nodal points in metallic antiferromagnets.

  2. Illegitimate WNT signaling promotes proliferation of multiple myeloma cells

    Science.gov (United States)

    Derksen, Patrick W. B.; Tjin, Esther; Meijer, Helen P.; Klok, Melanie D.; Mac Gillavry, Harold D.; van Oers, Marinus H. J.; Lokhorst, Henk M.; Bloem, Andries C.; Clevers, Hans; Nusse, Roel; van der Neut, Ronald; Spaargaren, Marcel; Pals, Steven T.

    2004-01-01

    The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also influenced by signals from the environment. In multiple myeloma (MM), the factors and signals coming from the bone marrow microenvironment are possibly even essential for the growth of the tumor cells. As targets for intervention, these signals may be equally important as mutated oncogenes. Given their oncogenic potential, WNT signals form a class of paracrine growth factors that could act to influence MM cell growth. In this paper, we report that MM cells have hallmarks of active WNT signaling, whereas the cells have not undergone detectable mutations in WNT signaling genes such as adenomatous polyposis coli and β-catenin (CTNNB1). We show that the malignant MM plasma cells overexpress β-catenin, including its N-terminally unphosphorylated form, suggesting active β-catenin/T cell factor-mediated transcription. Further accumulation and nuclear localization of β-catenin, and/or increased cell proliferation, was achieved by stimulation of WNT signaling with either Wnt3a, LiCl, or the constitutively active S33Y mutant of β-catenin. In contrast, by blocking WNT signaling by dominant-negative T cell factor, we can interfere with the growth of MM cells. We therefore suggest that MM cells are dependent on an active WNT signal, which may have important implications for the management of this incurable form of cancer. PMID:15067127

  3. Alpha Particles Induce Autophagy in Multiple Myeloma Cells.

    Science.gov (United States)

    Gorin, Jean-Baptiste; Gouard, Sébastien; Ménager, Jérémie; Morgenstern, Alfred; Bruchertseifer, Frank; Faivre-Chauvet, Alain; Guilloux, Yannick; Chérel, Michel; Davodeau, François; Gaschet, Joëlle

    2015-01-01

    Radiation emitted by the radionuclides in radioimmunotherapy (RIT) approaches induce direct killing of the targeted cells as well as indirect killing through the bystander effect. Our research group is dedicated to the development of α-RIT, i.e., RIT using α-particles especially for the treatment of multiple myeloma (MM). γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by (213)Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of (213)Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation. Murine 5T33 and human LP-1 MM cell lines were used to study the effects of such α-particles. We first examined the effects of (213)Bi on proliferation rate, double-strand DNA breaks, cell cycle, and cell death. Then, we investigated autophagy after (213)Bi irradiation. Finally, a coculture of dendritic cells (DCs) with irradiated tumor cells or their culture media was performed to test whether it would induce DC activation. We showed that (213)Bi induces DNA double-strand breaks, cell cycle arrest, and autophagy in both cell lines, but we detected only slight levels of early apoptosis within the 120 h following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented (213)Bi-induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s); however, no increase in membrane or extracellular expression of danger-associated molecular patterns was observed after irradiation. This study demonstrates that (213)Bi induces mainly necrosis in MM cells, low levels of apoptosis, and autophagy that might be involved in tumor cell death.

  4. Histologic assessment of tumor budding in preoperative biopsies to predict nodal metastasis in squamous cell carcinoma of the tongue and floor of the mouth.

    Science.gov (United States)

    Seki, Mai; Sano, Takaaki; Yokoo, Satoshi; Oyama, Tetsunari

    2016-04-01

    In squamous cell carcinoma (SCC) of the tongue and the floor of the mouth (FOM), it is important to predict lymph node metastasis, including occult metastasis, before operating. The purpose of this study was for us to determine practical histopathologic parameters as predictive factors for lymph node metastasis in preoperative SCC biopsy specimens. We examined 91 cases of SCC for conventional histopathologic assessment and a new factor, tumor budding, and their relationship with lymph node metastasis. Significant factors via univariate analysis (p factoring into the decision as to whether neck dissection is indicated. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1582-E1590, 2016. © 2015 Wiley Periodicals, Inc.

  5. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  6. Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: A Groupe d'Etude des Lymphomes de l'Adulte (GELA) study.

    Science.gov (United States)

    Dupuis, Jehan; Emile, Jean-François; Mounier, Nicolas; Gisselbrecht, Christian; Martin-Garcia, Nadine; Petrella, Tony; Bouabdallah, Reda; Berger, Françoise; Delmer, Alain; Coiffier, Bertrand; Reyes, Félix; Gaulard, Philippe

    2006-12-15

    Peripheral T-cell lymphomas (PTCLs) are rare and have a dismal prognosis. The most frequent subtype is PTCL, unspecified. Epstein-Barr virus (EBV) has been detected in around 40% of cases, but its prognostic significance is not fully established. Lymph node samples from 110 patients with PTCL, unspecified included in LNH87 and LNH93 trials were available. EBV status was studied by EBV-encoded small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45 (41%) of 110 patients. Pretreatment characteristics were comparable between positive and negative cases, except for male sex (80% versus 60%, respectively, P = .02). Only 50% of patients achieved complete remission with a 5-year event-free survival (EFS) and overall survival (OS) of 21% and 30%, respectively. EBER-ISH positivity was the sole factor linked with worse EFS, with a 5-year probability of 11% for positive patients. In univariate analysis, factors affecting OS were EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate analysis, EBER-ISH was associated with a worse OS in the elderly population. Time-dependent analysis showed that the negative impact of EBV was essentially seen in the first 2 years following diagnosis. These results warrant further studies regarding pathogenesis and specific treatment approaches for EBV-associated PTCL patients.

  7. Viability in holder of irradiated cells: distinguish between repair and cell multiplication

    International Nuclear Information System (INIS)

    Araujo, A.C. de.

    1980-01-01

    In experiments in which liquid holding recovery (LHR) was measured, the majority of cellular population is formed by non-viable cells and cell multiplication may be important for LHR expression. In order to distinguish between recuperation of viability (true LHR) and cell multiplication, it was necessary to employ improved plating techniques and a fluctuation test based on Poisson distribution. Our results are an indication that this fluctuation test, used together with the traditional method, is a good tool to distinguish repair from cell multiplication. (author)

  8. Feasibility of Elective Nodal Irradiation (ENI) and Involved Field Irradiation (IFI) in Radiotherapy for the Elderly Patients (Aged ≥ 70 Years) with Esophageal Squamous Cell Cancer: A Retrospective Analysis from a Single Institute.

    Science.gov (United States)

    Jing, Wang; Zhu, Hui; Guo, Hongbo; Zhang, Yan; Shi, Fang; Han, Anqin; Li, Minghuan; Kong, Li; Yu, Jinming

    2015-01-01

    We conducted a retrospective analysis to assess the feasibility of involved field irradiation (IFI) in elderly patients with esophageal squamous cell cancer (ESCC). We performed a retrospective review of the records of elderly patients (≥ 70 years) with unresectable ESCC and no distant metastases who received treatment with radiotherapy between January 2009 and March 2013. According to the irradiation volume, patients were allocated into either the elective nodal irradiation (ENI) group or the IFI group. Overall survival (OS), progression-free survival (PFS) and treatment-related toxicities were compared between the two groups. A total of 137 patients were enrolled. Fifty-four patients (39.4%) were allocated to the ENI group and 83 patients (60.6%) to the IFI group, the median doses in the two groups were 60 Gy and 59.4 Gy, respectively. For the entire group, the median survival time (MST) and PFS were 16 months and 12 months, respectively. The median PFS and 3-year PFS rate in the ENI group were 13 months and 20.6%, compared to 11 months and 21.0% in the IFI groups (p = 0.61). The MST and 3-year OS rate in the ENI and IFI groups were 17 months and 26.4% and 15.5 months and 21.7%, respectively (p = 0.25). The rate of grade ≥ 3 acute irradiation esophagitis in the ENI group was significantly higher than that in the IFI group (18.5% vs. 6.0%; p = 0.027). Other grade ≥ 3 treatment-related toxicities did not significantly differ between the two groups. IFI resulted in decreased irradiation toxicities without sacrificing OS in elderly patients with ESCC.

  9. Automated platform for designing multiple robot work cells

    Science.gov (United States)

    Osman, N. S.; Rahman, M. A. A.; Rahman, A. A. Abdul; Kamsani, S. H.; Bali Mohamad, B. M.; Mohamad, E.; Zaini, Z. A.; Rahman, M. F. Ab; Mohamad Hatta, M. N. H.

    2017-06-01

    Designing the multiple robot work cells is very knowledge-intensive, intricate, and time-consuming process. This paper elaborates the development process of a computer-aided design program for generating the multiple robot work cells which offer a user-friendly interface. The primary purpose of this work is to provide a fast and easy platform for less cost and human involvement with minimum trial and errors adjustments. The automated platform is constructed based on the variant-shaped configuration concept with its mathematical model. A robot work cell layout, system components, and construction procedure of the automated platform are discussed in this paper where integration of these items will be able to automatically provide the optimum robot work cell design according to the information set by the user. This system is implemented on top of CATIA V5 software and utilises its Part Design, Assembly Design, and Macro tool. The current outcomes of this work provide a basis for future investigation in developing a flexible configuration system for the multiple robot work cells.

  10. Multiple jaw cysts not associated with basal cell nevus syndrome

    International Nuclear Information System (INIS)

    Yoon, Suk Ja; Kang, Byung Cheol

    2003-01-01

    We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

  11. New type of cells with multiple chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail: dom@blood.ru

    2010-04-15

    A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

  12. New type of cells with multiple chromosome rearrangements

    International Nuclear Information System (INIS)

    Aseeva, E.A.; Domracheva, E.V.; Neverova, A.L; Bogomazova, A.N.; Snigiryova, G.P.; Novitskaya, N.N.; Khazins, E.D.

    2008-01-01

    Full text: A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. MAC were found in most of the examined groups and they were absent in the control population. A highest MAC frequency was observed in people exposed to alpha radiation (Pu, Ra). This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the FISH method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods is discussed

  13. Multiple jaw cysts not associated with basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Suk Ja; Kang, Byung Cheol [Chonnam National University College of Medicine, Kwangju (Korea, Republic of)

    2003-09-15

    We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

  14. Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer.

    Science.gov (United States)

    Noorlag, Rob; Boeve, Koos; Witjes, Max J H; Koole, Ronald; Peeters, Ton L M; Schuuring, Ed; Willems, Stefan M; van Es, Robert J J

    2017-02-01

    Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017. © 2016 Wiley Periodicals, Inc.

  15. Cilia are required for asymmetric nodal induction in the sea urchin embryo.

    Science.gov (United States)

    Tisler, Matthias; Wetzel, Franziska; Mantino, Sabrina; Kremnyov, Stanislav; Thumberger, Thomas; Schweickert, Axel; Blum, Martin; Vick, Philipp

    2016-08-23

    Left-right (LR) organ asymmetries are a common feature of metazoan animals. In many cases, laterality is established by a conserved asymmetric Nodal signaling cascade during embryogenesis. In most vertebrates, asymmetric nodal induction results from a cilia-driven leftward fluid flow at the left-right organizer (LRO), a ciliated epithelium present during gastrula/neurula stages. Conservation of LRO and flow beyond the vertebrates has not been reported yet. Here we study sea urchin embryos, which use nodal to establish larval LR asymmetry as well. Cilia were found in the archenteron of embryos undergoing gastrulation. Expression of foxj1 and dnah9 suggested that archenteron cilia were motile. Cilia were polarized to the posterior pole of cells, a prerequisite of directed flow. High-speed videography revealed rotating cilia in the archenteron slightly before asymmetric nodal induction. Removal of cilia through brief high salt treatments resulted in aberrant patterns of nodal expression. Our data demonstrate that cilia - like in vertebrates - are required for asymmetric nodal induction in sea urchin embryos. Based on these results we argue that the anterior archenteron represents a bona fide LRO and propose that cilia-based symmetry breakage is a synapomorphy of the deuterostomes.

  16. Correlation of proliferative and clonogenic tumor cells in multiple myeloma

    International Nuclear Information System (INIS)

    Karp, J.E.; Burke, P.J.; Saylor, P.L.; Humphrey, R.L.

    1984-01-01

    To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [ 3 H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [ 3 H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [ 3 H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity

  17. FDG PET/CT and Mediastinal Nodal Metastasis Detection in Stage T1 Non-Small Cell Lung Cancer: Prognostic Implications

    International Nuclear Information System (INIS)

    Shin, Kyung Min; Lee, Kyung Soo; Shim, Young Mog; Kim, Jhin Gook; Kim, Byung Tae; Kwon, O Jung; Park, Keun Chil

    2008-01-01

    We aimed to compare the prognoses of patients with pathologically true negative (P-TN) N2 and PET/CT false negative (FN) results in stage T1 nonsmall cell lung cancer (NSCLC). Our institutional review board approved this retrospective study with a waiver of informed consent. The study included 184 patients (124 men and 60 women; mean age, 59 years) with stage T1 NSCLC who underwent an integrated PET/CT and surgery. After estimating the efficacy of PET/CT for detecting N2 disease, we determined and compared disease-free survival (DFS) rates in three groups (P-TN [n = 161], PET/CT FN [n = 12], and PET/CT true positive [TP, n = 11]) using the Kaplan-Meier analysis and log-rank test. Pathologic N2 disease was observed in 23 (12%) patients. PET/CT had an N2 disease detection sensitivity of 48% (11 of 23 patients), a specificity of 95% (153 of 161), and an accuracy of 89% (164 of 184). The 3-year DFS rate in the PET/CT FN group (31%, 95% confidence interval [CI]; 13.6-48.0%) was similar to that of the TP group (16%, 95% CI; 1.7-29.5%) (p = 0.649), but both groups had significantly shorter DFS rates than the P-TN group (77%, 95% CI; 72.0- 81.2%) (p < 0.001). The PET/CT shows a high specificity, but low sensitivity for detecting N2 disease in stage T1 NSCLC. Patients with PET/CT FN N2 disease have survival rates similar to PET/CT TP N2 disease patients, which are both substantially shorter than the survival rate of P-TN patients

  18. The analytic nodal method in cylindrical geometry

    International Nuclear Information System (INIS)

    Prinsloo, Rian H.; Tomasevic, Djordje I.

    2008-01-01

    Nodal diffusion methods have been used extensively in nuclear reactor calculations, specifically for their performance advantage, but also for their superior accuracy. More specifically, the Analytic Nodal Method (ANM), utilising the transverse integration principle, has been applied to numerous reactor problems with much success. In this work, a nodal diffusion method is developed for cylindrical geometry. Application of this method to three-dimensional (3D) cylindrical geometry has never been satisfactorily addressed and we propose a solution which entails the use of conformal mapping. A set of 1D-equations with an adjusted, geometrically dependent, inhomogeneous source, is obtained. This work describes the development of the method and associated test code, as well as its application to realistic reactor problems. Numerical results are given for the PBMR-400 MW benchmark problem, as well as for a 'cylindrisized' version of the well-known 3D LWR IAEA benchmark. Results highlight the improved accuracy and performance over finite-difference core solutions and investigate the applicability of nodal methods to 3D PBMR type problems. Results indicate that cylindrical nodal methods definitely have a place within PBMR applications, yielding performance advantage factors of 10 and 20 for 2D and 3D calculations, respectively, and advantage factors of the order of 1000 in the case of the LWR problem

  19. Smart Energy Management of Multiple Full Cell Powered Applications

    Energy Technology Data Exchange (ETDEWEB)

    Mohammad S. Alam

    2007-04-23

    In this research project the University of South Alabama research team has been investigating smart energy management and control of multiple fuel cell power sources when subjected to varying demands of electrical and thermal loads together with demands of hydrogen production. This research has focused on finding the optimal schedule of the multiple fuel cell power plants in terms of electric, thermal and hydrogen energy. The optimal schedule is expected to yield the lowest operating cost. Our team is also investigating the possibility of generating hydrogen using photoelectrochemical (PEC) solar cells through finding materials for efficient light harvesting photoanodes. The goal is to develop an efficient and cost effective PEC solar cell system for direct electrolysis of water. In addition, models for hydrogen production, purification, and storage will be developed. The results obtained and the data collected will be then used to develop a smart energy management algorithm whose function is to maximize energy conservation within a managed set of appliances, thereby lowering O/M costs of the Fuel Cell power plant (FCPP), and allowing more hydrogen generation opportunities. The Smart Energy Management and Control (SEMaC) software, developed earlier, controls electrical loads in an individual home to achieve load management objectives such that the total power consumption of a typical residential home remains below the available power generated from a fuel cell. In this project, the research team will leverage the SEMaC algorithm developed earlier to create a neighborhood level control system.

  20. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis.

    LENUS (Irish Health Repository)

    Fletcher, J M

    2012-02-01

    Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS), which involves autoimmune responses to myelin antigens. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have provided convincing evidence that T cells specific for self-antigens mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However more recent studies have highlighted an important pathogenic role for CD4(+) T cells that secrete interleukin (IL)-17, termed Th17, but also IL-17-secreting gammadelta T cells in EAE as well as other autoimmune and chronic inflammatory conditions. This has prompted intensive study of the induction, function and regulation of IL-17-producing T cells in MS and EAE. In this paper, we review the contribution of Th1, Th17, gammadelta, CD8(+) and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes.

  1. T–CELL VACCINE PREPARATION FOR MULTIPLE SCLEROSIS TREATMENT

    Directory of Open Access Journals (Sweden)

    I. P. Ivanova

    2005-01-01

    Full Text Available Abstract. A two–stage technology of preparation of T–cell vaccine designated for multiple sclerosis treatment is described. At the first stage myelin–specific lymphocytes undergoe antigen–dependent cultural selection, whereas at the second stage they are grown by means of non–specific stimulation. The vaccine prepared in this way was found to induce specific anti–idiotypic immune response, directed against myelin–reactive T–lymphocytes. The results of 1–year follow–up of 18 vaccinated patients with a cerebral–spinal type of multiple sclerosis indicated the absence of side effects of T–cell vaccination, and suggest the possibility of effective application of this treatment within early stages of disease. (Med. Immunol., 2005, vol.7, № 1, pp 27532

  2. Effect of failures and repairs on multiple cell production lines

    Energy Technology Data Exchange (ETDEWEB)

    Legato, P.; Bobbio, A.; Roberti, L.

    1989-01-01

    This paper examines a production line composed of multiple stages, or cells, which are passed in sequential order to arrive to the final product. Two possible coordination disciplines are considered, namely: the classical tandem arrangement of sequential working centers with input buffer and the kanban scheme, considered the Japanese shop floor realization of the Just-In-Time (JIT) manifacturing approach. The production line is modelled and analysed by means of Stochastic Petri Nets (SPN). Finally an analysis is made of the possibility that the working cells can incur failure/repair cycles perturbing the production flow of the line and thus reduce performance indices.

  3. Tuning Cell and Tissue Development by Combining Multiple Mechanical Signals.

    Science.gov (United States)

    Sinha, Ravi; Verdonschot, Nico; Koopman, Bart; Rouwkema, Jeroen

    2017-10-01

    Mechanical signals offer a promising way to control cell and tissue development. It has been established that cells constantly probe their mechanical microenvironment and employ force feedback mechanisms to modify themselves and when possible, their environment, to reach a homeostatic state. Thus, a correct mechanical microenvironment (external forces and mechanical properties and shapes of cellular surroundings) is necessary for the proper functioning of cells. In vitro or in the case of nonbiological implants in vivo, where cells are in an artificial environment, addition of the adequate mechanical signals can, therefore, enable the cells to function normally as in vivo. Hence, a wide variety of approaches have been developed to apply mechanical stimuli (such as substrate stretch, flow-induced shear stress, substrate stiffness, topography, and modulation of attachment area) to cells in vitro. These approaches have not just revealed the effects of the mechanical signals on cells but also provided ways for probing cellular molecules and structures that can provide a mechanistic understanding of the effects. However, they remain lower in complexity compared with the in vivo conditions, where the cellular mechanical microenvironment is the result of a combination of multiple mechanical signals. Therefore, combinations of mechanical stimuli have also been applied to cells in vitro. These studies have had varying focus-developing novel platforms to apply complex combinations of mechanical stimuli, observing the co-operation/competition between stimuli, combining benefits of multiple stimuli toward an application, or uncovering the underlying mechanisms of their action. In general, they provided new insights that could not have been predicted from previous knowledge. We present here a review of several such studies and the insights gained from them, thereby making a case for such studies to be continued and further developed.

  4. Complex models of nodal nuclear data

    International Nuclear Information System (INIS)

    Dufek, Jan

    2011-01-01

    During the core simulations, nuclear data are required at various nodal thermal-hydraulic and fuel burnup conditions. The nodal data are also partially affected by thermal-hydraulic and fuel burnup conditions in surrounding nodes as these change the neutron energy spectrum in the node. Therefore, the nodal data are functions of many parameters (state variables), and the more state variables are considered by the nodal data models the more accurate and flexible the models get. The existing table and polynomial regression models, however, cannot reflect the data dependences on many state variables. As for the table models, the number of mesh points (and necessary lattice calculations) grows exponentially with the number of variables. As for the polynomial regression models, the number of possible multivariate polynomials exceeds the limits of existing selection algorithms that should identify a few dozens of the most important polynomials. Also, the standard scheme of lattice calculations is not convenient for modelling the data dependences on various burnup conditions since it performs only a single or few burnup calculations at fixed nominal conditions. We suggest a new efficient algorithm for selecting the most important multivariate polynomials for the polynomial regression models so that dependences on many state variables can be considered. We also present a new scheme for lattice calculations where a large number of burnup histories are accomplished at varied nodal conditions. The number of lattice calculations being performed and the number of polynomials being analysed are controlled and minimised while building the nodal data models of a required accuracy. (author)

  5. Hybrid nodal methods in the solution of the diffusion equations in X Y geometry; Metodos nodales hibridos en la solucion de las ecuaciones de difusion en geometria XY

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez M, N. [CFE, Carretera Cardel-Nautla Km. 43.5, 91680 Veracruz (Mexico); Alonso V, G.; Valle G, E. del [IPN-ESFM, 07738 Mexico D.F. (Mexico)]. e-mail: nhmiranda@mexico.com

    2003-07-01

    In 1979, Hennart and collaborators applied several schemes of classic finite element in the numerical solution of the diffusion equations in X Y geometry and stationary state. Almost two decades then, in 1996, himself and other collaborators carried out a similar work but using nodal schemes type finite element. Continuing in this last direction, in this work a group it is described a set of several Hybrid Nodal schemes denominated (NH) as well as their application to solve the diffusion equations in multigroup in stationary state and X Y geometry. The term hybrid nodal it means that such schemes interpolate not only Legendre moments of face and of cell but also the values of the scalar flow of neutrons in the four corners of each cell or element of the spatial discretization of the domain of interest. All the schemes here considered are polynomials like they were it their predecessors. Particularly, its have developed and applied eight different hybrid nodal schemes that its are very nearby related with those developed by Hennart and collaborators in the past. It is treated of schemes in those that nevertheless that decreases the number of interpolation parameters it is conserved the accurate in relation to the bi-quadratic and bi-cubic schemes. Of these eight, three were described and applied in a previous work. It is the bi-lineal classic scheme as well as the hybrid nodal schemes, bi-quadratic and bi-cubic for that here only are described the other 5 hybrid nodal schemes although they are provided numerical results for several test problems with all them. (Author)

  6. Nodal Structure of the Electronic Wigner Function

    DEFF Research Database (Denmark)

    Schmider, Hartmut; Dahl, Jens Peder

    1996-01-01

    On the example of several atomic and small molecular systems, the regular behavior of nodal patterns in the electronic one-particle reduced Wigner function is demonstrated. An expression found earlier relates the nodal pattern solely to the dot-product of the position and the momentum vector......, if both arguments are large. An argument analogous to the ``bond-oscillatory principle'' for momentum densities links the nuclear framework in a molecule to an additional oscillatory term in momenta parallel to bonds. It is shown that these are visible in the Wigner function in terms of characteristic...

  7. Th17 cells in the pathogenesis of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Marek Juszczak

    2009-10-01

    Full Text Available Th17 cells are a recently described subset of T helper lymphocytes characterized by the production of IL-17 (IL-17A. Since their discovery in 2003, studies on Th17 cells have become increasingly popular among immunologists and they have emerged as key players in the pathogenesis of multiple sclerosis (MS and other autoimmune disorders traditionally attributed to Th1 cells. Murine Th17 lymphocytes differentiate from naive CD4 cells in a specific cytokine environment, which includes TGF- and IL-6 or IL-21, whereas human Th17 cell development requires TGF-, IL-1, and IL-2 in combination with IL-6, IL-21, or IL-23. Th17-related response is additionally enhanced by osteopontin, TNF, and PGE2 and suppressed by IL-25, IL-27, IL-35, and IL-10. Apart from their main cytokine, Th17 cells can also express IL-17F, IL-21, IL-22, TNF, CCL20, and, in humans, IL-26. All of these mediators may contribute to the proinflammatory action of Th17 .cells both in the clearance of various pathogens and in autoimmunity. At least some of these functions are exerted through the induction of neutrophil-recruiting chemokines (CXCL1, CXCL2, CXCL8 by IL-17. Accumulating evidence from studies on mice and humans indicates an important role of Th17 cells in mediating autoimmune neuroinflammation. This has led some immunologists to question the previously exhibited importance of Th1 cells in MS pathology. However, more recent data suggest that both these T-cell subsets are capable of inducing and promoting the disease. Further investigation is required to clarify the role of Th17 cells in the pathogenesis of MS since some of the Th17-related molecules appear as attractive targets for future therapeutic strategies

  8. Efficient cascade multiple heterojunction organic solar cells with inverted structure

    Science.gov (United States)

    Guo, Tingting; Li, Mingtao; Qiao, Zhenfang; Yu, Leiming; Zhao, Jianhong; Feng, Nianjun; Shi, Peiguang; Wang, Xiaoyan; Pu, Xiaoyun; Wang, Hai

    2018-05-01

    In this work, we demonstrate an efficient cascade multiple heterojunction organic solar cell with inverted structure. By using two donor materials, poly(3-hexylthiosphene) (P3HT) and titanyl phthalocyanine (TiOPc), as well as two acceptor materials, [6,6]-phenyl C61 butyric acid methyl ester (PCBM) and C60, the cascade multiple heterojunctions of P3HT:PCBM/TiOPc:C60/C60 have been constructed. Applying the optimized inverted configuration of FTO/Zinc Tin Oxide (ZTO)/C60 (30 nm)/TiOPc:C60 (1:1.5, 25 nm)/P3HT:PCBM (1:0.8, 100 nm)/MoO3 (4 nm)/Ag, the considerably enhanced open circuit voltage (VOC) and short circuit current (JSC) can be harvested together, and the power conversion efficiency (PCE) is three times higher than that of the control cell with conventional structure. The significant improvements of the inverted cell are mostly due to the broadened spectral absorption and high efficient multi-interface exciton dissociation in the cascade multiple heterojunctions, indicating that the optimized cascade heterojunctions match the inverted structure well.

  9. Stationary Size Distributions of Growing Cells with Binary and Multiple Cell Division

    Science.gov (United States)

    Rading, M. M.; Engel, T. A.; Lipowsky, R.; Valleriani, A.

    2011-10-01

    Populations of unicellular organisms that grow under constant environmental conditions are considered theoretically. The size distribution of these cells is calculated analytically, both for the usual process of binary division, in which one mother cell produces always two daughter cells, and for the more complex process of multiple division, in which one mother cell can produce 2 n daughter cells with n=1,2,3,… . The latter mode of division is inspired by the unicellular algae Chlamydomonas reinhardtii. The uniform response of the whole population to different environmental conditions is encoded in the individual rates of growth and division of the cells. The analytical treatment of the problem is based on size-dependent rules for cell growth and stochastic transition processes for cell division. The comparison between binary and multiple division shows that these different division processes lead to qualitatively different results for the size distribution and the population growth rates.

  10. Segregated nodal domains of two-dimensional multispecies Bose-Einstein condensates

    Science.gov (United States)

    Chang, Shu-Ming; Lin, Chang-Shou; Lin, Tai-Chia; Lin, Wen-Wei

    2004-09-01

    In this paper, we study the distribution of m segregated nodal domains of the m-mixture of Bose-Einstein condensates under positive and large repulsive scattering lengths. It is shown that components of positive bound states may repel each other and form segregated nodal domains as the repulsive scattering lengths go to infinity. Efficient numerical schemes are created to confirm our theoretical results and discover a new phenomenon called verticillate multiplying, i.e., the generation of multiple verticillate structures. In addition, our proposed Gauss-Seidel-type iteration method is very effective in that it converges linearly in 10-20 steps.

  11. Impact of [18F]fluorodeoxyglucose PET-CT staging on treatment planning in radiotherapy incorporating elective nodal irradiation for non-small-cell lung cancer: a prospective study.

    Science.gov (United States)

    Kolodziejczyk, Milena; Kepka, Lucyna; Dziuk, Miroslaw; Zawadzka, Anna; Szalus, Norbert; Gizewska, Agnieszka; Bujko, Krzysztof

    2011-07-15

    To evaluate prospectively how positron emission tomography (PET) information changes treatment plans for non-small-cell lung cancer (NSCLC) patients receiving or not receiving elective nodal irradiation (ENI). One hundred consecutive patients referred for curative radiotherapy were included in the study. Treatment plans were carried out with CT data sets only. For stage III patients, mediastinal ENI was planned. Then, patients underwent PET-CT for diagnostic/planning purposes. PET/CT was fused with the CT data for final planning. New targets were delineated. For stage III patients with minimal N disease (N0-N1, single N2), the ENI was omitted in the new plans. Patients were treated according to the PET-based volumes and plans. The gross tumor volume (GTV)/planning tumor volume (PTV) and doses for critical structures were compared for both data sets. The doses for areas of potential geographical misses derived with the CT data set alone were compared in patients with and without initially planned ENI. In the 75 patients for whom the decision about curative radiotherapy was maintained after PET/CT, there would have been 20 cases (27%) with potential geographical misses by using the CT data set alone. Among them, 13 patients would receive ENI; of those patients, only 2 patients had the PET-based PTV covered by 90% isodose by using the plans based on CT alone, and the mean of the minimum dose within the missed GTV was 55% of the prescribed dose, while for 7 patients without ENI, it was 10% (p = 0.006). The lung, heart, and esophageal doses were significantly lower for plans with ENI omission than for plans with ENI use based on CT alone. PET/CT should be incorporated in the planning of radiotherapy for NSCLC, even in the setting of ENI. However, if PET/CT is unavailable, ENI may to some extent compensate for an inadequate dose coverage resulting from diagnostic uncertainties. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Impact of [18F]Fluorodeoxyglucose PET-CT Staging on Treatment Planning in Radiotherapy Incorporating Elective Nodal Irradiation for Non-Small-Cell Lung Cancer: A Prospective Study

    International Nuclear Information System (INIS)

    Kolodziejczyk, Milena; Kepka, Lucyna; Dziuk, Miroslaw; Zawadzka, Anna; Szalus, Norbert; Gizewska, Agnieszka; Bujko, Krzysztof

    2011-01-01

    Purpose: To evaluate prospectively how positron emission tomography (PET) information changes treatment plans for non-small-cell lung cancer (NSCLC) patients receiving or not receiving elective nodal irradiation (ENI). Methods and Materials: One hundred consecutive patients referred for curative radiotherapy were included in the study. Treatment plans were carried out with CT data sets only. For stage III patients, mediastinal ENI was planned. Then, patients underwent PET-CT for diagnostic/planning purposes. PET/CT was fused with the CT data for final planning. New targets were delineated. For stage III patients with minimal N disease (N0-N1, single N2), the ENI was omitted in the new plans. Patients were treated according to the PET-based volumes and plans. The gross tumor volume (GTV)/planning tumor volume (PTV) and doses for critical structures were compared for both data sets. The doses for areas of potential geographical misses derived with the CT data set alone were compared in patients with and without initially planned ENI. Results: In the 75 patients for whom the decision about curative radiotherapy was maintained after PET/CT, there would have been 20 cases (27%) with potential geographical misses by using the CT data set alone. Among them, 13 patients would receive ENI; of those patients, only 2 patients had the PET-based PTV covered by 90% isodose by using the plans based on CT alone, and the mean of the minimum dose within the missed GTV was 55% of the prescribed dose, while for 7 patients without ENI, it was 10% (p = 0.006). The lung, heart, and esophageal doses were significantly lower for plans with ENI omission than for plans with ENI use based on CT alone. Conclusions: PET/CT should be incorporated in the planning of radiotherapy for NSCLC, even in the setting of ENI. However, if PET/CT is unavailable, ENI may to some extent compensate for an inadequate dose coverage resulting from diagnostic uncertainties.

  13. Cost-effectiveness of FDG-PET for the management of potentially operable non-small cell lung cancer: priority for a PET-based strategy after nodal-negative CT results

    International Nuclear Information System (INIS)

    Dietlein, M.; Weber, K.; Moka, D.; Theissen, P.; Schicha, H.

    2000-01-01

    Decision analysis is used here to establish the most cost-effective strategy for management of potentially operable non-small cell lung cancers (NSCLCs). The strategies compared were conventional staging (strategy A), dedicated systems of positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) in patients with normal-sized (strategy B) or in patients with enlarged mediastinal lymph nodes (part of strategy C), and FDG-PET followed by exclusion from surgical procedures when both computed tomography (CT) and PET were positive for mediastinal lymph nodes (strategy D) or when PET alone was positive (strategy E). Based on published data, the sensitivity and specificity of FDG-PET were estimated at 0.74 and 0.96 for detecting metastasis in normal-sized mediastinal lymph nodes, and at 0.95 and 0.76 when these lymph nodes were enlarged. The calculated probability of up-staging to M1 by using PET was 0.05. The costs quoted correspond to the cost reimbursed in 1999 by the public health provider in Germany. The incremental cost-effectiveness ratio (ICER) of strategy B was much more favourable (143 EUR/LYS; LYS = life year saved) than the ICER of strategy C (36,667 EUR/LYS). In strategy B, the use of PET did not raise the overall costs because the costs of PET were almost balanced by a better selection of patients for beneficial cancer resection. The exclusion from biopsy confirmation in strategies D and E led to cost savings that did not justify the expected reduction in life expectancy. In sensitivity analyses, the ICERs of strategy B were robust to the pretest likelihood of N2/N3, to penalized test parameters of PET and to reimbursement of PET. However, the ICER of strategy B would be raised to 28,000 EUR/LYS through use of thoracic PET without whole-body scanning. To conclude, the implementation of whole-body PET with a full ring of detectors in the preoperative staging of patients with NSCLC and normal-sized lymph nodes is clearly cost

  14. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells

    DEFF Research Database (Denmark)

    Standal, Therese; Seidel, Carina; Hjertner, Øyvind

    2002-01-01

    Multiple myeloma (MM) is a hematologic malignancy characterized by accumulation of plasma cells in the bone marrow (BM). Bone destruction is a complication of the disease and is usually associated with severe morbidity. The balance between receptor activator of nuclear factor-kappaB (NF-kappaB......) ligand and osteoprotegerin (OPG) is of major importance in bone homeostasis. We have recently shown that serum OPG levels are lower in patients with myeloma than in healthy individuals. Here we show that myeloma cells can bind, internalize, and degrade OPG, thereby providing a possible explanation...... for the lower levels of OPG in the BM of patients with MM. This process is dependent on interaction of OPG with heparan sulfates on the myeloma cells. The results suggest a novel biologic mechanism for the bone disease associated with MM and that treatment of the bone disease with OPG lacking the heparin...

  15. Multiple cell common pressure vessel nickel hydrogen battery

    Science.gov (United States)

    Zagrodnik, Jeffrey P.; Jones, Kenneth R.

    1991-01-01

    A multiple cell common pressure vessel (CPV) nickel hydrogen battery was developed that offers significant weight, volume, cost, and interfacing advantages over the conventional individual pressure vessel (IPV) nickel hydrogen configuration that is currently used for aerospace applications. The baseline CPV design was successfully demonstrated though the testing of a 26 cell prototype, which completed over 7,000 44 percent depth of discharge LEO cycles. Two-cell boilerplate batteries have now exceeded 12,500 LEO cycles in ongoing laboratory tests. CPV batteries using both nominal 5 and 10 inch diameter vessels are currently available. The flexibility of the design allows these diameters to provide a broad capability for a variety of space applications.

  16. Isospectral graphs with identical nodal counts

    International Nuclear Information System (INIS)

    Oren, Idan; Band, Ram

    2012-01-01

    According to a recent conjecture, isospectral objects have different nodal count sequences (Gnutzmann et al 2005 J. Phys. A: Math. Gen. 38 8921–33). We study generalized Laplacians on discrete graphs, and use them to construct the first non-trivial counterexamples to this conjecture. In addition, these examples demonstrate a surprising connection between isospectral discrete and quantum graphs. (paper)

  17. Comparison of neutronic transport equation resolution nodal methods

    International Nuclear Information System (INIS)

    Zamonsky, O.M.; Gho, C.J.

    1990-01-01

    In this work, some transport equation resolution nodal methods are comparatively studied: the constant-constant (CC), linear-nodal (LN) and the constant-quadratic (CQ). A nodal scheme equivalent to finite differences has been used for its programming, permitting its inclusion in existing codes. Some bidimensional problems have been solved, showing that linear-nodal (LN) are, in general, obtained with accuracy in CPU shorter times. (Author) [es

  18. Fluorine-18-Fluorodeoxyglucose PET in the mediastinal nodal staging of bronchogenic carcinoma.

    Energy Technology Data Exchange (ETDEWEB)

    Berlangieri, S.U.; Scott, A.M.; Knight, S.; Pointon, O.; Thomas, D.L.; O``Keefe, G.; Chan, J.G.; Egen, G.F.; Tochon-Danguy, H.J.; Clarke, C.P.; McKay, W.J. [Austin Hospital, Melbourne, VIC (Australia). Centre for Positron Emission Tomography and the Departments of Nuclear Medicine and Thoracic Surgery

    1998-03-01

    Full text: Non-invasive methods of pre-operative staging of non-small cell bronchogenic carcinoma are inaccurate. To determine the clinical role of positron emission tomography (PET) in the mediastinal staging of lung carcinoma, {sup 18}F-fluorodeoxyglucose (FDG) studies were performed in 25 patients with suspected non-small cell bronchogenic carcinoma and correlated with pathology. The patients comprised 20 men and 5 women (mean age 63; range 43-78 y). All patients had proven non-small cell lung carcinoma, except two, one patient with benign inflammatory disease and the other with small cell carcinoma. The FDG PET studies were acquired on a Siemens 951131R body tomography over 2-3 bed positions to include the thorax and mediastinum. The PET images were interpreted for tumour involvement of mediastinal nodes according to the American Thoracic Society classification and scored for confidence of tumour presence on a 5 point scale. The intensity of glucose metabolism was compared to mediastinal blood pool activity and graded on a 4 point scale. FDG PET correctly excluded ipsilateral mediastinal nodal (N2) disease in 16 of 16 patients. Six of nine patients with N2 disease were correctly identified by FDG PET. Of the three patients with N2 nodal involvement not detected by PET, each had single station nodal disease, and in two patients the primary lesions abutted the involved nodal group. A total of 104 nodal stations were sampled or examined at surgery. FDG PET correctly excluded disease in 83/83 (100% specificity) negative nodal stations. FDG PET is a promising non-invasive functional imaging modality for the mediastinal staging of bronchogenic carcinoma.

  19. Mechanism for multiplicity of steady states with distinct cell concentration in continuous culture of mammalian cells.

    Science.gov (United States)

    Yongky, Andrew; Lee, Jongchan; Le, Tung; Mulukutla, Bhanu Chandra; Daoutidis, Prodromos; Hu, Wei-Shou

    2015-07-01

    Continuous culture for the production of biopharmaceutical proteins offers the possibility of steady state operations and thus more consistent product quality and increased productivity. Under some conditions, multiplicity of steady states has been observed in continuous cultures of mammalian cells, wherein with the same dilution rate and feed nutrient composition, steady states with very different cell and product concentrations may be reached. At those different steady states, cells may exhibit a high glycolysis flux with high lactate production and low cell concentration, or a low glycolysis flux with low lactate and high cell concentration. These different steady states, with different cell concentration, also have different productivity. Developing a mechanistic understanding of the occurrence of steady state multiplicity and devising a strategy to steer the culture toward the desired steady state is critical. We establish a multi-scale kinetic model that integrates a mechanistic intracellular metabolic model and cell growth model in a continuous bioreactor. We show that steady state multiplicity exists in a range of dilution rate in continuous culture as a result of the bistable behavior in glycolysis. The insights from the model were used to devise strategies to guide the culture to the desired steady state in the multiple steady state region. The model provides a guideline principle in the design of continuous culture processes of mammalian cells. © 2015 Wiley Periodicals, Inc.

  20. Nestin Reporter Transgene Labels Multiple Central Nervous System Precursor Cells

    Directory of Open Access Journals (Sweden)

    Avery S. Walker

    2010-01-01

    Full Text Available Embryonic neuroepithelia and adult subventricular zone (SVZ stem and progenitor cells express nestin. We characterized a transgenic line that expresses enhanced green fluorescent protein (eGFP specified to neural tissue by the second intronic enhancer of the nestin promoter that had several novel features. During embryogenesis, the dorsal telencephalon contained many and the ventral telencephalon few eGFP+ cells. eGFP+ cells were found in postnatal and adult neurogenic regions. eGFP+ cells in the SVZ expressed multiple phenotype markers, glial fibrillary acidic protein, Dlx, and neuroblast-specific molecules suggesting the transgene is expressed through the lineage. eGFP+ cell numbers increased in the SVZ after cortical injury, suggesting this line will be useful in probing postinjury neurogenesis. In non-neurogenic regions, eGFP was strongly expressed in oligodendrocyte progenitors, but not in astrocytes, even when they were reactive. This eGFP+ mouse will facilitate studies of proliferative neuroepithelia and adult neurogenesis, as well as of parenchymal oligodendrocytes.

  1. Characterization of nodal/TGF-lefty signaling pathway gene variants for possible roles in congenital heart diseases.

    Directory of Open Access Journals (Sweden)

    Xia Deng

    Full Text Available BACKGROUND: Nodal/TGF-Lefty signaling pathway has important effects at early stages of differentiation of human embryonic stem cells in directing them to differentiate into different embryonic lineages. LEFTY, one of transforming growth factors in the Nodal/TGF-Lefty signaling pathway, plays an important role in the development of heart. The aim of this work was to find evidence on whether Lefty variations are associated with congenital heart diseases (CHD. METHODS: We sequenced the Lefty gene for 230 Chinese Han CHD patients and evaluated SNPs rs2295418, rs360057 and g.G169A, which are located within the translated regions of the genes. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0. The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE, and multiple-sequence alignments of LEFTY proteins were carried out using the Vector NTI software. RESULTS: Two heterozygous variants in Lefty1 gene, g.G169A and g.A1035C, and one heterozygous variant in Lefty2 gene, g.C925A, were identified. Statistical analyses showed that the rs2295418 (g.C925A variant in Lefty2 gene was obviously associated with the risk of CHD (P value = 0.0160.05. CONCLUSIONS: The SNP rs2295418 in the Lefty2 gene is associated with CHD in Chinese Han populations.

  2. The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yuji Mishima

    2017-04-01

    Full Text Available The development of sensitive and non-invasive “liquid biopsies” presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs is prognostic in multiple myeloma (MM, but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs.

  3. Solution of the transport equation in stationary state, in one and two dimensions, for BWR assemblies using nodal methods; Solucion de la ecuacion de transporte en estado estacionario, en 1 y 2 dimensiones, para ensambles tipo BWR usando metodos nodales

    Energy Technology Data Exchange (ETDEWEB)

    Xolocostli M, J V

    2002-07-01

    . In this geometry nodal, continuous and discontinuous schemes were used. For the continuos schemes, only the Bi Quadratic (BiQ) and the Bi Cubic (BiC) were considered. In the case of the discontinuous ones two nodal schemes were considered, namely the Discontinuous Bi Linear (DBiL) and Discontinuous Bi Quadratic (DBiQ). The nodal schemes applied use from 4 up to 16 interpolation parameters per cell. These schemes are-defined for a set D{sub c} of interpolation parameters and a polynomial space S{sub h} corresponding to each one of the nodal schemes considered. All these four nodal hybrid schemes were implemented in a computer program called TNHXY starting from the computer program TNXY developed in previous thesis works. Several subroutines wae added to calculate the average neutron flux for each cell and for each energy group, generating two versions, one for the continuous schemes and one for the discontinuous schemes. For this geometry, two benchmark problems of the ANL-7416 document were analyzed. They are 7x7 BWR fuel assemblies, one without control rod and the other one with control rod. The computer program was also applied to a MOX assembly proposed by the Nuclear Energy Agency and it is considered as a reference problem. The results obtained for the one-dimensional problems using TNX for the effective multiplication factor were compared with the ones obtained with the code ANISN/PC. TNX code shows a faster convergence within four significant figures for the case with no control rod and three significant figures for the case with control rod (using double precision). These results suggest TNX is a very useful tool for this kind of calculations. For X Y geometry, the results obtained with TNHXY were compared with those calculated with the code TWOTRAN. To get these results, several spatial (1x1, 2x2, 4x4 per cell) and angular meshes (S{sub 2}, S{sub 4}, S{sub 6}, and S{sub 8}) were used. The results for the problem with no control rod were practically the same

  4. Solution of the transport equation in stationary state, in one and two dimensions, for BWR assemblies using nodal methods; Solucion de la ecuacion de transporte en estado estacionario, en 1 y 2 dimensiones, para ensambles tipo BWR usando metodos nodales

    Energy Technology Data Exchange (ETDEWEB)

    Xolocostli M, J.V

    2002-07-01

    . In this geometry nodal, continuous and discontinuous schemes were used. For the continuos schemes, only the Bi Quadratic (BiQ) and the Bi Cubic (BiC) were considered. In the case of the discontinuous ones two nodal schemes were considered, namely the Discontinuous Bi Linear (DBiL) and Discontinuous Bi Quadratic (DBiQ). The nodal schemes applied use from 4 up to 16 interpolation parameters per cell. These schemes are-defined for a set D{sub c} of interpolation parameters and a polynomial space S{sub h} corresponding to each one of the nodal schemes considered. All these four nodal hybrid schemes were implemented in a computer program called TNHXY starting from the computer program TNXY developed in previous thesis works. Several subroutines wae added to calculate the average neutron flux for each cell and for each energy group, generating two versions, one for the continuous schemes and one for the discontinuous schemes. For this geometry, two benchmark problems of the ANL-7416 document were analyzed. They are 7x7 BWR fuel assemblies, one without control rod and the other one with control rod. The computer program was also applied to a MOX assembly proposed by the Nuclear Energy Agency and it is considered as a reference problem. The results obtained for the one-dimensional problems using TNX for the effective multiplication factor were compared with the ones obtained with the code ANISN/PC. TNX code shows a faster convergence within four significant figures for the case with no control rod and three significant figures for the case with control rod (using double precision). These results suggest TNX is a very useful tool for this kind of calculations. For X Y geometry, the results obtained with TNHXY were compared with those calculated with the code TWOTRAN. To get these results, several spatial (1x1, 2x2, 4x4 per cell) and angular meshes (S{sub 2}, S{sub 4}, S{sub 6}, and S{sub 8}) were used. The results for the problem with no control rod were practically the same

  5. Hereditary bone dysplasia with pathological fractures and nodal osteoarthropathy

    International Nuclear Information System (INIS)

    Arendse, Regan; Brink, Paul; Beighton, Peter

    2009-01-01

    A father and daughter both had multiple pathological fractures and nodal osteoarthropathy. The father, aged 50 years, had at least 20 healed fractures of the axial and appendicular skeleton, sustained by minor trauma over his 50-year lifespan, many of which had been surgically fixed prior to his first presentation to us. Fractures of the clavicles, thoracic cage and long bones of the arms and legs, had healed with malalignment and deformity. Healed fractures were complicated by ankylosis of the cervical vertebrae and both elbows. He also had osteoarthritis of the hands, with exuberant osteophytosis, and profound perceptive deafness. His general health was good, his intellect and facies were normal, and his sclerae were white. The daughter, aged 27 years, had sustained at least seven fractures of the axial and appendicular skeleton following trivial injuries, in distribution similar to those of the father. She had also experienced painful swelling of the fingers, which preceded progressive development of nodal osteoarthropathy. Her hearing was normal. In both individuals, biochemical and immunological investigations yielded normal results. It was not possible for molecular studies to be undertaken. Pedigree data were consistent with autosomal dominant transmission, and this disorder appeared to be a previously undocumented heritable skeletal dysplasia. (orig.)

  6. Hereditary bone dysplasia with pathological fractures and nodal osteoarthropathy

    Energy Technology Data Exchange (ETDEWEB)

    Arendse, Regan [University of Stellenbosch, Department of Medicine, Tygerberg Hospital, Stellenbosch (South Africa); University of Cape Town, Division of Rheumatology, Groote Schuur Hospital, Cape Town (South Africa); Brink, Paul [University of Stellenbosch, Department of Medicine, Tygerberg Hospital, Stellenbosch (South Africa); Beighton, Peter [University of Cape Town, Division of Human Genetics, Faculty of Health Sciences, Cape Town (South Africa)

    2009-12-15

    A father and daughter both had multiple pathological fractures and nodal osteoarthropathy. The father, aged 50 years, had at least 20 healed fractures of the axial and appendicular skeleton, sustained by minor trauma over his 50-year lifespan, many of which had been surgically fixed prior to his first presentation to us. Fractures of the clavicles, thoracic cage and long bones of the arms and legs, had healed with malalignment and deformity. Healed fractures were complicated by ankylosis of the cervical vertebrae and both elbows. He also had osteoarthritis of the hands, with exuberant osteophytosis, and profound perceptive deafness. His general health was good, his intellect and facies were normal, and his sclerae were white. The daughter, aged 27 years, had sustained at least seven fractures of the axial and appendicular skeleton following trivial injuries, in distribution similar to those of the father. She had also experienced painful swelling of the fingers, which preceded progressive development of nodal osteoarthropathy. Her hearing was normal. In both individuals, biochemical and immunological investigations yielded normal results. It was not possible for molecular studies to be undertaken. Pedigree data were consistent with autosomal dominant transmission, and this disorder appeared to be a previously undocumented heritable skeletal dysplasia. (orig.)

  7. Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

    Science.gov (United States)

    van den Brand, Michiel; van Krieken, J. Han J.M.

    2013-01-01

    The diagnosis of nodal marginal zone lymphoma is one of the remaining problem areas in hematopathology. Because no established positive markers exist for this lymphoma, it is frequently a diagnosis of exclusion, making distinction from other low-grade B-cell lymphomas difficult or even impossible. This systematic review summarizes and discusses the current knowledge on nodal marginal zone lymphoma, including clinical features, epidemiology and etiology, histology, and cytogenetic and molecular features. In particular, recent advances in diagnostics and pathogenesis are discussed. New immunohistochemical markers have become available that could be used as positive markers for nodal marginal zone lymphoma. These markers could be used to ensure more homogeneous study groups in future research. Also, recent gene expression studies and studies describing specific gene mutations have provided clues to the pathogenesis of nodal marginal zone lymphoma, suggesting deregulation of the nuclear factor kappa B pathway. Nevertheless, nodal marginal zone lymphoma remains an enigmatic entity, requiring further study to define its pathogenesis to allow an accurate diagnosis and tailored treatment. However, recent data indicate that it is not related to splenic or extranodal lymphoma, and that it is also not related to lymphoplasmacytic lymphoma. Thus, even though the diagnosis is not always easy, it is clearly a separate entity. PMID:23813646

  8. Endothelial progenitor cells display clonal restriction in multiple myeloma

    International Nuclear Information System (INIS)

    Braunstein, Marc; Özçelik, Tayfun; Bağişlar, Sevgi; Vakil, Varsha; Smith, Eric LP; Dai, Kezhi; Akyerli, Cemaliye B; Batuman, Olcay A

    2006-01-01

    In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (V H ). In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with V H primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI

  9. Detection and Characterization of Circulating Tumour Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Liangxuan Zhang

    2016-06-01

    Full Text Available Multiple myeloma (MM remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease manage‐ ment and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluores‐ cence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6 as a readout for PI3K/AKT pathway activation. Clinical feasi‐ bility of the assay was established by testing blood samples from a small cohort of patients, where we detected popu‐ lations of both CD138pos and CD138neg MM CTCs. In this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.

  10. Detection and Characterization of Circulating Tumour Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Liangxuan Zhang

    2016-01-01

    Full Text Available Multiple myeloma (MM remains an incurable disease despite recent therapeutic improvements. The ability to detect and characterize MM circulating tumour cells (CTCs in peripheral blood provides an alternative to replace or augment invasive bone marrow (BM biopsies with a simple blood draw, providing real-time, clinically relevant information leading to improved disease management and therapy selection. Here we have developed and qualified an enrichment-free, cell-based immunofluorescence MM CTC assay that utilizes an automated digital pathology algorithm to distinguish MM CTCs from white blood cells (WBCs on the basis of CD138 and CD45 expression levels, as well as a number of morphological parameters. These MM CTCs were further characterized for expression of phospho-ribosomal protein S6 (pS6 as a readout for PI3K/AKT pathway activation. Clinical feasibility of the assay was established by testing blood samples from a small cohort of patients, where we detected populations of both CD138 pos and CD138 neg MM CTCs. In this study, we developed an immunofluorescent cell-based assay to detect and characterize CTCs in MM.

  11. Multiple squamous cell carcinomas within the head and neck region

    International Nuclear Information System (INIS)

    Sato, Katsuro; Hanazawa, Hideyuki; Sato, Yuichiro; Takahashi, Sugata

    2004-01-01

    Clinical features of multiple squamous cell carcinoma (SCC) cases within the head and neck that were treated in our department during the recent 10 years are discussed. Multiple SCCs arose in 6.6% of the cases with primary SCC; 67% of the cases had two carcinomas, and 33% had more than three carcinomas. The most common site of the multiple SCCs was the oral cavity (54%). The most frequent interval between treatment of previous carcinoma and diagnosis of subsequent carcinoma was simultaneous, but more than 5 years' interval was observed in 36% of the patients. The most common initial treatment of the carcinoma was irradiation, but the ratio of surgery increased for subsequent carcinomas. Prognosis of the patients with more than three carcinomas was not worse than that of patients with two carcinomas. Therefore, early diagnosis of the subsequent carcinomas based on careful long-term observation in the head and neck is necessary for follow-up of the patients with SCC of the head and neck. Treatment strategies considering the treatment of subsequent carcinomas are needed for the patients with primary head and neck SCC. (author)

  12. Solution of the transport equation in stationary state, in one and two dimensions, for BWR assemblies using nodal methods

    International Nuclear Information System (INIS)

    Xolocostli M, J.V.

    2002-01-01

    . In this geometry nodal, continuous and discontinuous schemes were used. For the continuos schemes, only the Bi Quadratic (BiQ) and the Bi Cubic (BiC) were considered. In the case of the discontinuous ones two nodal schemes were considered, namely the Discontinuous Bi Linear (DBiL) and Discontinuous Bi Quadratic (DBiQ). The nodal schemes applied use from 4 up to 16 interpolation parameters per cell. These schemes are-defined for a set D c of interpolation parameters and a polynomial space S h corresponding to each one of the nodal schemes considered. All these four nodal hybrid schemes were implemented in a computer program called TNHXY starting from the computer program TNXY developed in previous thesis works. Several subroutines wae added to calculate the average neutron flux for each cell and for each energy group, generating two versions, one for the continuous schemes and one for the discontinuous schemes. For this geometry, two benchmark problems of the ANL-7416 document were analyzed. They are 7x7 BWR fuel assemblies, one without control rod and the other one with control rod. The computer program was also applied to a MOX assembly proposed by the Nuclear Energy Agency and it is considered as a reference problem. The results obtained for the one-dimensional problems using TNX for the effective multiplication factor were compared with the ones obtained with the code ANISN/PC. TNX code shows a faster convergence within four significant figures for the case with no control rod and three significant figures for the case with control rod (using double precision). These results suggest TNX is a very useful tool for this kind of calculations. For X Y geometry, the results obtained with TNHXY were compared with those calculated with the code TWOTRAN. To get these results, several spatial (1x1, 2x2, 4x4 per cell) and angular meshes (S 2 , S 4 , S 6 , and S 8 ) were used. The results for the problem with no control rod were practically the same as those obtained with

  13. Multiple modes of proepicardial cell migration require heartbeat.

    Science.gov (United States)

    Plavicki, Jessica S; Hofsteen, Peter; Yue, Monica S; Lanham, Kevin A; Peterson, Richard E; Heideman, Warren

    2014-05-15

    The outermost layer of the vertebrate heart, the epicardium, forms from a cluster of progenitor cells termed the proepicardium (PE). PE cells migrate onto the myocardium to give rise to the epicardium. Impaired epicardial development has been associated with defects in valve development, cardiomyocyte proliferation and alignment, cardiac conduction system maturation and adult heart regeneration. Zebrafish are an excellent model for studying cardiac development and regeneration; however, little is known about how the zebrafish epicardium forms. We report that PE migration occurs through multiple mechanisms and that the zebrafish epicardium is composed of a heterogeneous population of cells. Heterogeneity is first observed within the PE and persists through epicardium formation. Using in vivo imaging, histology and confocal microscopy, we show that PE cells migrate through a cellular bridge that forms between the pericardial mesothelium and the heart. We also observed the formation of PE aggregates on the pericardial surface, which were released into the pericardial cavity. It was previously reported that heartbeat-induced pericardiac fluid advections are necessary for PE cluster formation and subsequent epicardium development. We manipulated heartbeat genetically and pharmacologically and found that PE clusters clearly form in the absence of heartbeat. However, when heartbeat was inhibited the PE failed to migrate to the myocardium and the epicardium did not form. We isolated and cultured hearts with only a few epicardial progenitor cells and found a complete epicardial layer formed. However, pharmacologically inhibiting contraction in culture prevented epicardium formation. Furthermore, we isolated control and silent heart (sih) morpholino (MO) injected hearts prior to epicardium formation (60 hpf) and co-cultured these hearts with "donor" hearts that had an epicardium forming (108 hpf). Epicardial cells from donor hearts migrated on to control but not sih MO

  14. HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell.

    Directory of Open Access Journals (Sweden)

    Mikaël Boullé

    2016-11-01

    Full Text Available Cell-to-cell spread of HIV, a directed mode of viral transmission, has been observed to be more rapid than cell-free infection. However, a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. Here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of HIV gene expression in a fluorescent reporter cell line, as well as single cell staining for infection over time in primary cells. We compared cell-to-cell spread of HIV to cell-free infection, and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. The mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free HIV infection. Neither factors secreted by infected cells, nor contact with infected cells in the absence of transmission, detectably changed onset. We recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. Surprisingly, the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. Instead, more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses.

  15. Hybrid nodal methods in the solution of the diffusion equations in X Y geometry

    International Nuclear Information System (INIS)

    Hernandez M, N.; Alonso V, G.; Valle G, E. del

    2003-01-01

    In 1979, Hennart and collaborators applied several schemes of classic finite element in the numerical solution of the diffusion equations in X Y geometry and stationary state. Almost two decades then, in 1996, himself and other collaborators carried out a similar work but using nodal schemes type finite element. Continuing in this last direction, in this work a group it is described a set of several Hybrid Nodal schemes denominated (NH) as well as their application to solve the diffusion equations in multigroup in stationary state and X Y geometry. The term hybrid nodal it means that such schemes interpolate not only Legendre moments of face and of cell but also the values of the scalar flow of neutrons in the four corners of each cell or element of the spatial discretization of the domain of interest. All the schemes here considered are polynomials like they were it their predecessors. Particularly, its have developed and applied eight different hybrid nodal schemes that its are very nearby related with those developed by Hennart and collaborators in the past. It is treated of schemes in those that nevertheless that decreases the number of interpolation parameters it is conserved the accurate in relation to the bi-quadratic and bi-cubic schemes. Of these eight, three were described and applied in a previous work. It is the bi-lineal classic scheme as well as the hybrid nodal schemes, bi-quadratic and bi-cubic for that here only are described the other 5 hybrid nodal schemes although they are provided numerical results for several test problems with all them. (Author)

  16. Quantum anomalies in nodal line semimetals

    Science.gov (United States)

    Burkov, A. A.

    2018-04-01

    Topological semimetals are a new class of condensed matter systems with nontrivial electronic structure topology. Their unusual observable properties may often be understood in terms of quantum anomalies. In particular, Weyl and Dirac semimetals, which have point band-touching nodes, are characterized by the chiral anomaly, which leads to the Fermi arc surface states, anomalous Hall effect, negative longitudinal magnetoresistance, and planar Hall effect. In this paper, we explore analogous phenomena in nodal line semimetals. We demonstrate that such semimetals realize a three-dimensional analog of the parity anomaly, which is a known property of two-dimensional Dirac semimetals arising, for example, on the surface of a three-dimensional topological insulator. We relate one of the characteristic properties of nodal line semimetals, namely, the drumhead surface states, to this anomaly, and derive the field theory, which encodes the corresponding anomalous response.

  17. Temporal quadratic expansion nodal Green's function method

    International Nuclear Information System (INIS)

    Liu Cong; Jing Xingqing; Xu Xiaolin

    2000-01-01

    A new approach is presented to efficiently solve the three-dimensional space-time reactor dynamics equation which overcomes the disadvantages of current methods. In the Temporal Quadratic Expansion Nodal Green's Function Method (TQE/NGFM), the Quadratic Expansion Method (QEM) is used for the temporal solution with the Nodal Green's Function Method (NGFM) employed for the spatial solution. Test calculational results using TQE/NGFM show that its time step size can be 5-20 times larger than that of the Fully Implicit Method (FIM) for similar precision. Additionally, the spatial mesh size with NGFM can be nearly 20 times larger than that using the finite difference method. So, TQE/NGFM is proved to be an efficient reactor dynamics analysis method

  18. Acceleration of the FERM nodal program

    International Nuclear Information System (INIS)

    Nakata, H.

    1985-01-01

    It was tested three acceleration methods trying to reduce the number of outer iterations in the FERM nodal program. The results obtained indicated that the Chebychev polynomial acceleration method with variable degree results in a economy of 50% in the computer time. Otherwise, the acceleration method by source asymptotic extrapolation or by zonal rebalance did not result in economy of the global computer time, however some acceleration had been verified in outer iterations. (M.C.K.) [pt

  19. Acceleration of the nodal program FERM

    International Nuclear Information System (INIS)

    Nakata, H.

    1985-01-01

    Acceleration of the nodal FERM was tried by three acceleration schemes. Results of the calculations showed the best acceleration with the Tchebyshev method where the savings in the computing time were of the order of 50%. Acceleration with the Assymptotic Source Extrapoltation Method and with the Coarse-Mesh Rebalancing Method did not result in any improvement on the global computational time, although a reduction in the number of outer iterations was observed. (Author) [pt

  20. Nodal method for fast reactor analysis

    International Nuclear Information System (INIS)

    Shober, R.A.

    1979-01-01

    In this paper, a nodal method applicable to fast reactor diffusion theory analysis has been developed. This method has been shown to be accurate and efficient in comparison to highly optimized finite difference techniques. The use of an analytic solution to the diffusion equation as a means of determining accurate coupling relationships between nodes has been shown to be highly accurate and efficient in specific two-group applications, as well as in the current multigroup method

  1. Nodal methods in numerical reactor calculations

    International Nuclear Information System (INIS)

    Hennart, J.P.; Valle, E. del

    2004-01-01

    The present work describes the antecedents, developments and applications started in 1972 with Prof. Hennart who was invited to be part of the staff of the Nuclear Engineering Department at the School of Physics and Mathematics of the National Polytechnic Institute. Since that time and up to 1981, several master theses based on classical finite element methods were developed with applications in point kinetics and in the steady state as well as the time dependent multigroup diffusion equations. After this period the emphasis moved to nodal finite elements in 1, 2 and 3D cartesian geometries. All the thesis were devoted to the numerical solution of the neutron multigroup diffusion and transport equations, few of them including the time dependence, most of them related with steady state diffusion equations. The main contributions were as follows: high order nodal schemes for the primal and mixed forms of the diffusion equations, block-centered finite-differences methods, post-processing, composite nodal finite elements for hexagons, and weakly and strongly discontinuous schemes for the transport equation. Some of these are now being used by several researchers involved in nuclear fuel management. (Author)

  2. Nodal methods in numerical reactor calculations

    Energy Technology Data Exchange (ETDEWEB)

    Hennart, J P [UNAM, IIMAS, A.P. 20-726, 01000 Mexico D.F. (Mexico); Valle, E del [National Polytechnic Institute, School of Physics and Mathematics, Department of Nuclear Engineering, Mexico, D.F. (Mexico)

    2004-07-01

    The present work describes the antecedents, developments and applications started in 1972 with Prof. Hennart who was invited to be part of the staff of the Nuclear Engineering Department at the School of Physics and Mathematics of the National Polytechnic Institute. Since that time and up to 1981, several master theses based on classical finite element methods were developed with applications in point kinetics and in the steady state as well as the time dependent multigroup diffusion equations. After this period the emphasis moved to nodal finite elements in 1, 2 and 3D cartesian geometries. All the thesis were devoted to the numerical solution of the neutron multigroup diffusion and transport equations, few of them including the time dependence, most of them related with steady state diffusion equations. The main contributions were as follows: high order nodal schemes for the primal and mixed forms of the diffusion equations, block-centered finite-differences methods, post-processing, composite nodal finite elements for hexagons, and weakly and strongly discontinuous schemes for the transport equation. Some of these are now being used by several researchers involved in nuclear fuel management. (Author)

  3. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

    Science.gov (United States)

    Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

    2017-08-01

    Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  4. Amelioration of NK cell function driven by Vα24+ invariant NKT cell activation in multiple myeloma.

    Science.gov (United States)

    Iyoda, Tomonori; Yamasaki, Satoru; Hidaka, Michihiro; Kawano, Fumio; Abe, Yu; Suzuki, Kenshi; Kadowaki, Norimitsu; Shimizu, Kanako; Fujii, Shin-Ichiro

    2018-02-01

    NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells. The expression of NKG2D on CD56 dim CD16 + NK cells and DNAM-1 on CD56 bright CD16 - NK cells increased after NKT cell activation. Apparently, NK cell-mediated anti-tumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus, NK cell function in patients could be ameliorated, beyond the effect of immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could represent a potential new treatment modality. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. On the non-uniqueness of the nodal mathematical adjoint

    International Nuclear Information System (INIS)

    Müller, Erwin

    2014-01-01

    Highlights: • We evaluate three CMFD schemes for computing the nodal mathematical adjoint. • The nodal mathematical adjoint is not unique and can be non-positive (nonphysical). • Adjoint and forward eigenmodes are compatible if produced by the same CMFD method. • In nodal applications the excited eigenmodes are purely mathematical entities. - Abstract: Computation of the neutron adjoint flux within the framework of modern nodal diffusion methods is often facilitated by reducing the nodal equation system for the forward flux into a simpler coarse-mesh finite-difference form and then transposing the resultant matrix equations. The solution to the transposed problem is known as the nodal mathematical adjoint. Since the coarse-mesh finite-difference reduction of a given nodal formulation can be obtained in a number of ways, different nodal mathematical adjoint solutions can be computed. This non-uniqueness of the nodal mathematical adjoint challenges the credibility of the reduction strategy and demands a verdict as to its suitability in practical applications. This is the matter under consideration in this paper. A selected number of coarse-mesh finite-difference reduction schemes are described and compared. Numerical calculations are utilised to illustrate the differences in the adjoint solutions as well as to appraise the impact on such common applications as the computation of core point kinetics parameters. Recommendations are made for the proper application of the coarse-mesh finite-difference reduction approach to the nodal mathematical adjoint problem

  6. Impacts of Contingency Reserve on Nodal Price and Nodal Reliability Risk in Deregulated Power Systems

    DEFF Research Database (Denmark)

    Zhao, Qian; Wang, Peng; Goel, Lalit

    2013-01-01

    The deregulation of power systems allows customers to participate in power market operation. In deregulated power systems, nodal price and nodal reliability are adopted to represent locational operation cost and reliability performance. Since contingency reserve (CR) plays an important role...... in reliable operation, the CR commitment should be considered in operational reliability analysis. In this paper, a CR model based on customer reliability requirements has been formulated and integrated into power market settlement. A two-step market clearing process has been proposed to determine generation...

  7. Plasma cell morphology in multiple myeloma and related disorders.

    Science.gov (United States)

    Ribourtout, B; Zandecki, M

    2015-06-01

    Normal and reactive plasma cells (PC) are easy to ascertain on human bone marrow films, due to their small mature-appearing nucleus and large cytoplasm, the latter usually deep blue after Giemsa staining. Cytoplasm is filled with long strands of rough endoplasmic reticulum and one large Golgi apparatus (paranuclear hof), demonstrating that PC are dedicated mainly to protein synthesis and excretion (immunoglobulin). Deregulation of the genome may induce clonal expansion of one PC that will lead to immunoglobulin overproduction and eventually to one among the so-called PC neoplasms. In multiple myeloma (MM), the number of PC is over 10% in most patients studied. Changes in the morphology of myeloma PC may be inconspicuous as compared to normal PC (30-50% patients). In other instances PC show one or several morphological changes. One is related to low amount of cytoplasm, defining lymphoplasmacytoid myeloma (10-15% patients). In other cases (40-50% patients), named immature myeloma cases, nuclear-cytoplasmic asynchrony is observed: presence of one nucleolus, finely dispersed chromatin and/or irregular nuclear contour contrast with a still large and blue (mature) cytoplasm. A peculiar morphological change, corresponding to the presence of very immature PC named plasmablasts, is observed in 10-15% cases. Several prognostic morphological classifications have been published, as mature myeloma is related to favorable outcome and immature myeloma, peculiarly plasmablastic myeloma, is related to dismal prognosis. However, such classifications are no longer included in current prognostic schemes. Changes related to the nucleus are very rare in monoclonal gammopathy of unknown significance (MGUS). In contrast, anomalies related to the cytoplasm of PC, including color (flaming cells), round inclusions (Mott cells, Russell bodies), Auer rod-like or crystalline inclusions, are reported in myeloma cases as well as in MGUS and at times in reactive disorders. They do not correspond

  8. Tumour thickness as a predictor of nodal metastases in oral cancer: comparison between tongue and floor of mouth subsites.

    Science.gov (United States)

    Balasubramanian, Deepak; Ebrahimi, Ardalan; Gupta, Ruta; Gao, Kan; Elliott, Michael; Palme, Carsten E; Clark, Jonathan R

    2014-12-01

    To identify whether tumour thickness as a predictor of nodal metastases in oral squamous cell carcinoma differs between tongue and floor of mouth (FOM) subsites. Retrospective review of 343 patients treated between 1987 and 2012. The neck was considered positive in the presence of pathologically proven nodal metastases on neck dissection or during follow-up. There were 222 oral tongue and 121 FOM tumours. In patients with FOM tumours 2.1-4mm thick, the rate of nodal metastases was 41.7%. In contrast, for tongue cancers of a similar thickness the rate was only 11.2%. This increased to 38.5% in patients with tongue cancers that were 4.1-6mm thick. Comparing these two subsites, FOM cancers cross the critical 20% threshold of probability for nodal metastases between 1 and 2mm whereas tongue cancers cross the 20% threshold just under 4mm thickness. On logistic regression adjusting for relevant covariates, there was a significant difference in the propensity for nodal metastases based on tumour thickness according to subsite (p=0.028). Thin FOM tumours (2.1-4mm) have a high rate of nodal metastases. Elective neck dissection is appropriate in FOM tumours ⩾2mm thick and in tongue tumours ⩾4mm thick. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Depletion Calculations for MTR Core Using MCNPX and Multi-Group Nodal Diffusion Methods

    International Nuclear Information System (INIS)

    Jaradata, Mustafa K.; Park, Chang Je; Lee, Byungchul

    2013-01-01

    In order to maintain a self-sustaining steady-state chain reaction, more fuel than is necessary in order to maintain a steady state chain reaction must be loaded. The introduction of this excess fuel increases the net multiplication capability of the system. In this paper MCNPX and multi-group nodal diffusion theory will be used for depletion calculations for MTR core. The eigenvalue and power distribution in the core will be compared for different burnup. Multi-group nodal diffusion theory with combination of NEWT-TRITON system was used to perform depletion calculations for 3Χ3 MTR core. 2G and 6G approximations were used and compared with MCNPX results for 2G approximation the maximum difference from MCNPX was 40 mk and for 6G approximation was 6 mk which is comparable to the MCNPX results. The calculated power using nodal code was almost the same MCNPX results. Finally the results of the multi-group nodal theory were acceptable and comparable to the calculated using MCNPX

  10. Topological surface states in nodal superconductors.

    Science.gov (United States)

    Schnyder, Andreas P; Brydon, Philip M R

    2015-06-24

    Topological superconductors have become a subject of intense research due to their potential use for technical applications in device fabrication and quantum information. Besides fully gapped superconductors, unconventional superconductors with point or line nodes in their order parameter can also exhibit nontrivial topological characteristics. This article reviews recent progress in the theoretical understanding of nodal topological superconductors, with a focus on Weyl and noncentrosymmetric superconductors and their protected surface states. Using selected examples, we review the bulk topological properties of these systems, study different types of topological surface states, and examine their unusual properties. Furthermore, we survey some candidate materials for topological superconductivity and discuss different experimental signatures of topological surface states.

  11. Twisted vector bundles on pointed nodal curves

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    by identifying the points p1 and p2. If m ≥ 2, let R1,...,Rm−1 be m − 1 copies of the projective line P1 and let xi,yi be two distinct points in Ri. Let R be the nodal curve which arises from the union. R0 ⊔ R1 ⊔···⊔ Rm−1 ⊔ Rm by identifying p1 ∈ R0 and p2 ∈ Rm with x1 ∈ R1 and ym−1 ∈ Rm−1 respectively and by identifying ...

  12. Space-angle approximations in the variational nodal method

    International Nuclear Information System (INIS)

    Lewis, E. E.; Palmiotti, G.; Taiwo, T.

    1999-01-01

    The variational nodal method is formulated such that the angular and spatial approximations maybe examined separately. Spherical harmonic, simplified spherical harmonic, and discrete ordinate approximations are coupled to the primal hybrid finite element treatment of the spatial variables. Within this framework, two classes of spatial trial functions are presented: (1) orthogonal polynomials for the treatment of homogeneous nodes and (2) bilinear finite subelement trial functions for the treatment of fuel assembly sized nodes in which fuel-pin cell cross sections are represented explicitly. Polynomial and subelement trial functions are applied to benchmark water-reactor problems containing MOX fuel using spherical harmonic and simplified spherical harmonic approximations. The resulting accuracy and computing costs are compared

  13. Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

    Science.gov (United States)

    Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

    2016-10-01

    Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

  14. High throughput single-cell and multiple-cell micro-encapsulation.

    Science.gov (United States)

    Lagus, Todd P; Edd, Jon F

    2012-06-15

    Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement from a bulk fluid environment with applications in high throughput screening, cytometry, and mass spectrometry. We describe a method to not only encapsulate single cells, but to repeatedly capture a set number of cells (here we demonstrate one- and two-cell encapsulation) to study both isolation and the interactions between cells in groups of controlled sizes. By combining drop generation techniques with cell and particle ordering, we demonstrate controlled encapsulation of cell-sized particles for efficient, continuous encapsulation. Using an aqueous particle suspension and immiscible fluorocarbon oil, we generate aqueous drops in oil with a flow focusing nozzle. The aqueous flow rate is sufficiently high to create ordering of particles which reach the nozzle at integer multiple frequencies of the drop generation frequency, encapsulating a controlled number of cells in each drop. For representative results, 9.9 μm polystyrene particles are used as cell surrogates. This study shows a single-particle encapsulation efficiency P(k=1) of 83.7% and a double-particle encapsulation efficiency P(k=2) of 79.5% as compared to their respective Poisson efficiencies of 39.3% and 33.3%, respectively. The effect of consistent cell and particle concentration is demonstrated to be of major importance for efficient encapsulation, and dripping to jetting transitions are also addressed. Continuous media aqueous cell suspensions share a common fluid environment which allows cells to interact in parallel and also homogenizes the effects of specific cells in measurements from the media. High-throughput encapsulation of cells into picoliter-scale drops confines the samples to protect drops from cross-contamination, enable a measure of cellular diversity within samples, prevent dilution of reagents and expressed biomarkers, and amplify

  15. Robust doubly charged nodal lines and nodal surfaces in centrosymmetric systems

    Science.gov (United States)

    Bzdušek, Tomáš; Sigrist, Manfred

    2017-10-01

    Weyl points in three spatial dimensions are characterized by a Z -valued charge—the Chern number—which makes them stable against a wide range of perturbations. A set of Weyl points can mutually annihilate only if their net charge vanishes, a property we refer to as robustness. While nodal loops are usually not robust in this sense, it has recently been shown using homotopy arguments that in the centrosymmetric extension of the AI symmetry class they nevertheless develop a Z2 charge analogous to the Chern number. Nodal loops carrying a nontrivial value of this Z2 charge are robust, i.e., they can be gapped out only by a pairwise annihilation and not on their own. As this is an additional charge independent of the Berry π -phase flowing along the band degeneracy, such nodal loops are, in fact, doubly charged. In this manuscript, we generalize the homotopy discussion to the centrosymmetric extensions of all Atland-Zirnbauer classes. We develop a tailored mathematical framework dubbed the AZ +I classification and show that in three spatial dimensions such robust and multiply charged nodes appear in four of such centrosymmetric extensions, namely, AZ +I classes CI and AI lead to doubly charged nodal lines, while D and BDI support doubly charged nodal surfaces. We remark that no further crystalline symmetries apart from the spatial inversion are necessary for their stability. We provide a description of the corresponding topological charges, and develop simple tight-binding models of various semimetallic and superconducting phases that exhibit these nodes. We also indicate how the concept of robust and multiply charged nodes generalizes to other spatial dimensions.

  16. Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

    Science.gov (United States)

    Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

    2018-01-01

    Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

  17. Error estimation for variational nodal calculations

    International Nuclear Information System (INIS)

    Zhang, H.; Lewis, E.E.

    1998-01-01

    Adaptive grid methods are widely employed in finite element solutions to both solid and fluid mechanics problems. Either the size of the element is reduced (h refinement) or the order of the trial function is increased (p refinement) locally to improve the accuracy of the solution without a commensurate increase in computational effort. Success of these methods requires effective local error estimates to determine those parts of the problem domain where the solution should be refined. Adaptive methods have recently been applied to the spatial variables of the discrete ordinates equations. As a first step in the development of adaptive methods that are compatible with the variational nodal method, the authors examine error estimates for use in conjunction with spatial variables. The variational nodal method lends itself well to p refinement because the space-angle trial functions are hierarchical. Here they examine an error estimator for use with spatial p refinement for the diffusion approximation. Eventually, angular refinement will also be considered using spherical harmonics approximations

  18. Plasma Cell Neoplasms (Including Multiple Myeloma)—Health Professional Version

    Science.gov (United States)

    There are several types of plasma cell neoplasms, including monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma. Find evidence-based information on plasma cell neoplasms treatment, research, and statistics.

  19. FogBank: a single cell segmentation across multiple cell lines and image modalities.

    Science.gov (United States)

    Chalfoun, Joe; Majurski, Michael; Dima, Alden; Stuelten, Christina; Peskin, Adele; Brady, Mary

    2014-12-30

    sheets with high accuracy. It can be applied to microscopy images of multiple cell lines and a variety of imaging modalities. The code for the segmentation method is available as open-source and includes a Graphical User Interface for user friendly execution.

  20. Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Hesse, D; Limborg, S

    2012-01-01

    , monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA. Methods: Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25high and CD26high cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS......Background: Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist. Objective: To study the activation of CD4+ T cells...... (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05–1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers...

  1. Torsionfree Sheaves over a Nodal Curve of Arithmetic Genus One

    Indian Academy of Sciences (India)

    We classify all isomorphism classes of stable torsionfree sheaves on an irreducible nodal curve of arithmetic genus one defined over C C . Let be a nodal curve of arithmetic genus one defined over R R , with exactly one node, such that does not have any real points apart from the node. We classify all isomorphism ...

  2. Regulatory T cells in multiple sclerosis and myasthenia gravis.

    Science.gov (United States)

    Danikowski, K M; Jayaraman, S; Prabhakar, B S

    2017-06-09

    Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs). Tregs are thought to play a critical role in the maintenance of peripheral immune tolerance. It is believed that Tregs function by suppressing the effector CD4+ T cell subsets that mediate autoimmune responses. Dysregulation of suppressive and migratory markers on Tregs have been linked to the pathogenesis of both MS and MG. For example, genetic abnormalities have been found in Treg suppressive markers CTLA-4 and CD25, while others have shown a decreased expression of FoxP3 and IL-10. Furthermore, elevated levels of pro-inflammatory cytokines such as IL-6, IL-17, and IFN-γ secreted by T effectors have been noted in MS and MG patients. This review provides several strategies of treatment which have been shown to be effective or are proposed as potential therapies to restore the function of various Treg subsets including Tr1, iTr35, nTregs, and iTregs. Strategies focusing on enhancing the Treg function find importance in cytokines TGF-β, IDO, interleukins 10, 27, and 35, and ligands Jagged-1 and OX40L. Likewise, strategies which affect Treg migration involve chemokines CCL17 and CXCL11. In pre-clinical animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune myasthenia gravis (EAMG), several strategies

  3. The essential role of t cells in multiple sclerosis: A reappraisal

    Directory of Open Access Journals (Sweden)

    Cris S Constantinescu

    2014-04-01

    Full Text Available Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which destruction of myelin and nerve axons has been shown to be mediated by immune mechanisms. Although the focus of research has been traditionally on T cells as key mediators of the immunopathology, more recent efforts at understanding this complex disorder have been directed increasingly at other cellular and humoral elements of the immune response. This review is a reappraisal of the crucial role of T cells, in particular the CD4+ helper T-cell subset, in multiple sclerosis. Recent evidence is discussed underlining the predominant contribution of T-cell-associated genes to the genome-wide association study results of multiple sclerosis susceptibility, the loss of T-cell quiescence in the conversion from clinically isolated syndrome to clinically definite multiple sclerosis, and the fact that T cells represent the main target of effective immunomodulatory and immunosuppressive treatments in multiple sclerosis.

  4. Molecular pathogenesis of splenic and nodal marginal zone lymphoma.

    Science.gov (United States)

    Spina, Valeria; Rossi, Davide

    Genomic studies have improved our understanding of the biological basis of splenic (SMZL) and nodal (NMZL) marginal zone lymphoma by providing a comprehensive and unbiased view of the genes/pathways that are deregulated in these diseases. Consistent with the physiological involvement of NOTCH, NF-κB, B-cell receptor and toll-like receptor signaling in mature B-cells differentiation into the marginal zone B-cells, many oncogenic mutations of genes involved in these pathways have been identified in SMZL and NMZL. Beside genetic lesions, also epigenetic and post-transcriptional modifications contribute to the deregulation of marginal zone B-cell differentiation pathways in SMZL and NMZL. This review describes the progress in understanding the molecular mechanism underlying SMZL and NMZL, including molecular and post-transcriptional modifications, and discusses how information gained from these efforts has provided new insights on potential targets of diagnostic, prognostic and therapeutic relevance in SMZL and NMZL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Faisal [University of Utah School of Medicine, Salt Lake City, UT (United States); Loma Linda University Medical Center, Department of Radiation Oncology, Loma Linda, CA (United States); Sarkar, Vikren; Gaffney, David K.; Salter, Bill [Department of Radiation Oncology, University of Utah, Salt Lake City, UT (United States); Poppe, Matthew M., E-mail: matthew.poppe@hci.utah.edu [Department of Radiation Oncology, University of Utah, Salt Lake City, UT (United States)

    2016-10-01

    evaluating individual IGRT sessions, we found that 6 patients had an estimated minimal nodal CTV dose less than 90% (range: 78 to 99%) of that planned. With a median follow-up of 42.5 months, 2 patients experienced systemic disease progression at an average of 19.6 months. One patient was found to have a local or regional failure with an average follow-up of 42 months. Conclusion: Using only 3 dimensional IGRT corrections in gynecological radiation allows excellent coverage of the primary target volume and good average nodal CTV coverage. If IGRT corrections are based on alignment to the primary tumor volume, and is only able to be corrected in 3 degrees, this can create situations in which nodal volumes may be under dosed. Utilizing multiple IGRT sessions appears to average out dose discrepancies over the course of treatment. The implication of underdosing in a single IGRT session needs further evaluation in future studies. Based on the concern of minimum dose to a nodal target volume, these findings may signal caution when using IGRT and IMRT in gynecological radiation patients. Possible techniques to overcome this situation may include averaging shifts between tumor and nodal volume, use of a treatment couch with 6° of freedom, deformable registration, or adaptive planning.

  6. A review on stem cell therapy for multiple sclerosis: special focus on human embryonic stem cells.

    Science.gov (United States)

    Shroff, Geeta

    2018-01-01

    Multiple sclerosis (MS), a complex disorder of the central nervous system (CNS), is characterized with axonal loss underlying long-term progressive disability. Currently available therapies for its management are able to slow down the progression but fail to treat it completely. Moreover, these therapies are associated with major CNS and cardiovascular adverse events, and prolonged use of these treatments may cause life-threatening diseases. Recent research has shown that cellular therapies hold a potential for CNS repair and may be able to provide protection from inflammatory damage caused after injury. Human embryonic stem cell (hESC) transplantation is one of the promising cell therapies; hESCs play an important role in remyelination and help in preventing demylenation of the axons. In this study, an overview of the current knowledge about the unique properties of hESC and their comparison with other cell therapies has been presented for the treatment of patients with MS.

  7. Nuclear movement regulated by non-Smad Nodal signaling via JNK is associated with Smad signaling during zebrafish endoderm specification.

    Science.gov (United States)

    Hozumi, Shunya; Aoki, Shun; Kikuchi, Yutaka

    2017-11-01

    Asymmetric nuclear positioning is observed during animal development, but its regulation and significance in cell differentiation remain poorly understood. Using zebrafish blastulae, we provide evidence that nuclear movement towards the yolk syncytial layer, which comprises extraembryonic tissue, occurs in the first cells fated to differentiate into the endoderm. Nodal signaling is essential for nuclear movement, whereas nuclear envelope proteins are involved in movement through microtubule formation. Positioning of the microtubule-organizing center, which is proposed to be crucial for nuclear movement, is regulated by Nodal signaling and nuclear envelope proteins. The non-Smad JNK signaling pathway, which is downstream of Nodal signaling, regulates nuclear movement independently of the Smad pathway, and this nuclear movement is associated with Smad signal transduction toward the nucleus. Our study provides insight into the function of nuclear movement in Smad signaling toward the nucleus, and could be applied to the control of TGFβ signaling. © 2017. Published by The Company of Biologists Ltd.

  8. A nodalization study of steam separator in real time simulation

    International Nuclear Information System (INIS)

    Horugshyang, Lein; Luh, R.T.J.; Zen-Yow, Wang

    1999-01-01

    The motive of this paper is to investigate the influence of steam separator nodalization on reactor thermohydraulics in terms of stability and level response. Three different nodalizations of steam separator are studied by using THEATRE and REMARK Code in a BWR simulator. The first nodalization is the traditional one with two nodes for steam separator. In this nodalization, the steam separation is modeled in the outer node, i.e., upper downcomer. Separated steam enters the Steen dome node and the liquid goes to the feedwater node. The second nodalization is similar to the first one with the steam separation modeled in the inner node. There is one additional junction connecting steam dome node and the inner node. The liquid fallback junction connects the inner node and feedwater node. The third nodalization is a combination of the former two with an integrated node for steam separator. Boundary conditions in this study are provided by a simplified feedwater and main steam driver. For comparison purpose, three tests including full power steady state initialisation, recirculation pumps runback and reactor scram are conducted. Major parameters such as reactor pressure, reactor level, void fractions, neutronic power and junction flows are recorded for analysis. Test results clearly show that the first nodalization is stable for steady state initialisation. However it has too responsive level performance in core flow reduction transients. The second nodalization is the closest representation of real plant structure, but not the performance. Test results show that an instability occurs in the separator region for both steady state initialisation and transients. This instability is caused by an unbalanced momentum in the dual loop configuration. The magnitude of the oscillation reduces as the power decreases. No superiority to the other nodalizations is shown in the test results. The third nodalization shows both stability and responsiveness in the tests. (author)

  9. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. Multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are different types of plasma cell neoplasms. Find out about risk factors, symptoms, diagnostic tests, prognosis, and treatment for these diseases.

  10. Role of CT/PET in predicting nodal disease in head and neck cancers

    International Nuclear Information System (INIS)

    Singham, S.; Iyer, G.; Clark, J.

    2009-01-01

    Full text:Introduction: Pre-treatment evaluation of the presence of cervical nodal metastases is important in head and neck cancers and has major prognostic implications. In this study, we aim to determine the accuracy of CT/PET as a tool for identifying such metastases. Methods: All patients from Royal Prince Alfred and Liverpool Hospitals, who underwent CT/PET for any cancer arising from the head and neck, and who underwent subsequent surgery (which included a neck dissection) within 8 weeks of the CT/PET were included. Nodal staging was undertaken by utilising imaging-based nodal classification, and comparison with pathologic data from the surgical specimen was made. PET was considered positive if the SUV was greater than 2. Results: We identified 111 patients from the above criteria. 80 of such patients were treated for squamous cell carcinoma (SCC). CT/PET identified unsuspected metastatic disease in 6 patients. Correlation of CT/PET findings and the presence of disease at the primary site: sensitivity: 98%, specificity: 93%, positive predictive value (PPV): 98% and negative predictive value (NPV): 93%. Correlating CT/PET findings with the presence of nodal disease at any level: sensitivity: 95%, specificity: 88%, PPV: 95% and NPV: 88%. CT/PET was anatomically accurate in predicting the site of metastases in 62/74 (84%). Conclusion: PET is accurate in predicting both presence of nodal metastases and the level of involvement. CT/PET should be undertaken as a pre-operative tool to assist in planning the extent of surgery required in head and neck cancers.

  11. Topological surface states in nodal superconductors

    International Nuclear Information System (INIS)

    Schnyder, Andreas P; Brydon, Philip M R

    2015-01-01

    Topological superconductors have become a subject of intense research due to their potential use for technical applications in device fabrication and quantum information. Besides fully gapped superconductors, unconventional superconductors with point or line nodes in their order parameter can also exhibit nontrivial topological characteristics. This article reviews recent progress in the theoretical understanding of nodal topological superconductors, with a focus on Weyl and noncentrosymmetric superconductors and their protected surface states. Using selected examples, we review the bulk topological properties of these systems, study different types of topological surface states, and examine their unusual properties. Furthermore, we survey some candidate materials for topological superconductivity and discuss different experimental signatures of topological surface states. (topical review)

  12. Nodal aberration theory applied to freeform surfaces

    Science.gov (United States)

    Fuerschbach, Kyle; Rolland, Jannick P.; Thompson, Kevin P.

    2014-12-01

    When new three-dimensional packages are developed for imaging optical systems, the rotational symmetry of the optical system is often broken, changing its imaging behavior and making the optical performance worse. A method to restore the performance is to use freeform optical surfaces that compensate directly the aberrations introduced from tilting and decentering the optical surfaces. In order to effectively optimize the shape of a freeform surface to restore optical functionality, it is helpful to understand the aberration effect the surface may induce. Using nodal aberration theory the aberration fields induced by a freeform surface in an optical system are explored. These theoretical predications are experimentally validated with the design and implementation of an aberration generating telescope.

  13. Activin- and Nodal-related factors control antero-posterior patterning of the zebrafish embryo.

    Science.gov (United States)

    Thisse, B; Wright, C V; Thisse, C

    2000-01-27

    Definition of cell fates along the dorso-ventral axis depends on an antagonistic relationship between ventralizing transforming growth factor-beta superfamily members, the bone morphogenetic proteins and factors secreted from the dorsal organizer, such as Noggin and Chordin. The extracellular binding of the last group to the bone morphogenetic proteins prevents them from activating their receptors, and the relative ventralizer:antagonist ratio is thought to specify different dorso-ventral cell fates. Here, by taking advantage of a non-genetic interference method using a specific competitive inhibitor, the Lefty-related gene product Antivin, we provide evidence that cell fate along the antero-posterior axis of the zebrafish embryo is controlled by the morphogenetic activity of another transforming growth factor-beta superfamily subgroup--the Activin and Nodal-related factors. Increasing antivin doses progressively deleted posterior fates within the ectoderm, eventually resulting in the removal of all fates except forebrain and eyes. In contrast, overexpression of activin or nodal-related factors converted ectoderm that was fated to be forebrain into more posterior ectodermal or mesendodermal fates. We propose that modulation of intercellular signalling by Antivin/Activin and Nodal-related factors provides a mechanism for the graded establishment of cell fates along the antero-posterior axis of the zebrafish embryo.

  14. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lao, Louis [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Auckland City Hospital, Auckland (New Zealand); Hope, Andrew J. [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Maganti, Manjula [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Cho, B. C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

    2014-09-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

  15. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    International Nuclear Information System (INIS)

    Lao, Louis; Hope, Andrew J.; Maganti, Manjula; Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander; Cho, B. C. John

    2014-01-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT

  16. Radiofrequency Catheter Ablation of Coexistent Idiopathic Left Ventricular Tachycardia and Atrioventricular Nodal Reentrant Tachycardia

    Directory of Open Access Journals (Sweden)

    Ken-Pen Weng

    2005-10-01

    Full Text Available A healthy 15-year-old male patient presented with a 6-month history of recurrent attacks of palpitations. On multiple emergency room visits, a sustained wide QRS complex tachycardia with a right bundle branch block and northwest axis deviation was documented. The tachycardia was not terminated by intravenous adenosine, but was suppressed with intravenous verapamil. There was no evidence of structural heart disease, myocarditis, long QT syndrome, or electrolyte imbalance after a series of standard examinations. Idiopathic left ventricular tachycardia (ILVT was suspected. Electrophysiologic studies revealed 2 inducible tachycardias, which were shown to represent atrioventricular nodal reentrant tachycardia (AVNRT and ILVT. Transformation from AVNRT to ILVT occurred spontaneously following atrial pacing. Successful ablation of ILVT and the slow atrioventricular nodal pathway resulted in cure of the double tachycardia.

  17. Increased T cell expression of CD154 (CD40-ligand) in multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, J; Krakauer, M; Sellebjerg, F

    2001-01-01

    CD154 (CD40-ligand, gp39), expressed on activated T cells, is crucial in T cell-dependent immune responses and may be involved in the pathogenesis of multiple sclerosis (MS). We studied cerebro-spinal fluid and peripheral blood T cell expression of CD154 in MS by flow cytometry. Patients with sec......CD154 (CD40-ligand, gp39), expressed on activated T cells, is crucial in T cell-dependent immune responses and may be involved in the pathogenesis of multiple sclerosis (MS). We studied cerebro-spinal fluid and peripheral blood T cell expression of CD154 in MS by flow cytometry. Patients...

  18. Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  19. Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

    Science.gov (United States)

    ... cancer treatment is also called biotherapy or immunotherapy. Immunomodulators are a type of biologic therapy. Thalidomide , lenalidomide , and pomalidomide are immunomodulators used to treat multiple myeloma and other plasma ...

  20. Generation of multiple cell types in Bacillus subtilis.

    Science.gov (United States)

    Lopez, Daniel; Vlamakis, Hera; Kolter, Roberto

    2009-01-01

    Bacillus subtilis is a Gram-positive bacterium that is well known for its ability to differentiate into metabolically inactive spores that are highly resistant to environmental stresses. In fact, populations of genetically identical B. subtilis comprise numerous distinct cell types. In addition to spores, cells can become genetically competent, motile, produce extracellular matrix or degradative enzymes, or secrete toxins that allow them to cannibalize their neighbors. Many of the cell fates listed above appear to be mutually exclusive. In this review, we discuss how individual cells within a population control their gene expression to ensure that proper regulation of differentiation occurs. These different cell fates are regulated by an intricate network that relies primarily on the activity of three major transcriptional regulators: Spo0A, DegU, and ComK. While individual cells must choose distinct cell fates, the population as a whole exhibits a spectrum of phenotypes whose diversity may increase fitness.

  1. A nodal expansion method using conformal mapping for hexagonal geometry

    International Nuclear Information System (INIS)

    Chao, Y.A.; Shatilla, Y.A.

    1993-01-01

    Hexagonal nodal methods adopting the same transverse integration process used for square nodal methods face the subtle theoretical problem that this process leads to highly singular nonphysical terms in the diffusion equation. Lawrence, in developing the DIF3D-N code, tried to approximate the singular terms with relatively simple polynomials. In the HEX-NOD code, Wagner ignored the singularities to simplify the diffusion equation and introduced compensating terms in the nodal equations to restore the nodal balance relation. More recently developed hexagonal nodal codes, such as HEXPE-DITE and the hexagonal version of PANTHER, used methods similar to Wagner's. It will be shown that for light water reactor applications, these two different approximations significantly degraded the accuracy of the respective method as compared to the established square nodal methods. Alternatively, the method of conformal mapping was suggested to map a hexagon to a rectangle, with the unique feature of leaving the diffusion operator invariant, thereby fundamentally resolving the problems associated with transverse integration. This method is now implemented in the Westinghouse hexagonal nodal code ANC-H. In this paper we report on the results of comparing the three methods for a variety of problems via benchmarking against the fine-mesh finite difference code

  2. Benchmarking with high-order nodal diffusion methods

    International Nuclear Information System (INIS)

    Tomasevic, D.; Larsen, E.W.

    1993-01-01

    Significant progress in the solution of multidimensional neutron diffusion problems was made in the late 1970s with the introduction of nodal methods. Modern nodal reactor analysis codes provide significant improvements in both accuracy and computing speed over earlier codes based on fine-mesh finite difference methods. In the past, the performance of advanced nodal methods was determined by comparisons with fine-mesh finite difference codes. More recently, the excellent spatial convergence of nodal methods has permitted their use in establishing reference solutions for some important bench-mark problems. The recent development of the self-consistent high-order nodal diffusion method and its subsequent variational formulation has permitted the calculation of reference solutions with one node per assembly mesh size. In this paper, we compare results for four selected benchmark problems to those obtained by high-order response matrix methods and by two well-known state-of-the-art nodal methods (the open-quotes analyticalclose quotes and open-quotes nodal expansionclose quotes methods)

  3. Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model.

    Science.gov (United States)

    Swift, Brenna E; Williams, Brent A; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A; Viswanathan, Sowmya; Martinez-Lopez, Joaquin; Keating, Armand

    2012-07-01

    Novel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. The cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. Three multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2- to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89-99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. This study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma

  4. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease

    OpenAIRE

    Shroff, Geeta

    2016-01-01

    Case series Patient: Male, 42 ? Female, 30 Final Diagnosis: Human embryonic stem cells showed good therapeutic potential for treatment of multiple sclerosis with lyme disease Symptoms: Fatigue ? weakness in limbs Medication: ? Clinical Procedure: Human embryonic stem cells transplantation Specialty: Transplantology Objective: Rare disease Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause dela...

  5. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    International Nuclear Information System (INIS)

    Huang, Er-Wen; Xue, Sheng-Jiang; Li, Xiao-Yan; Xu, Suo-Wen; Cheng, Jian-Ding; Zheng, Jin-Xiang; Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong; Li, Jie; Liu, Chao

    2014-01-01

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma

  6. EEN regulates the proliferation and survival of multiple myeloma cells by potentiating IGF-1 secretion

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Er-Wen [Guangzhou Institute of Forensic Science, Guangzhou (China); Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Xue, Sheng-Jiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Li, Xiao-Yan [Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Xu, Suo-Wen [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Cheng, Jian-Ding; Zheng, Jin-Xiang [Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou (China); Shi, He; Lv, Guo-Li; Li, Zhi-Gang; Li, Yue; Liu, Chang-Hui; Chen, Xiao-Hui; Liu, Hong [Guangzhou Institute of Forensic Science, Guangzhou (China); Li, Jie, E-mail: mdlijie@sina.com [Department of Anaesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Liu, Chao, E-mail: liuchaogaj@21cn.com [Guangzhou Institute of Forensic Science, Guangzhou (China)

    2014-05-02

    Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.

  7. MULTIPLE MALIGNANT TUMORS IN 8-YEARS OLD BOY WITH XERODERMA PIGMENTOSUM: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    V. I. Al’banova

    2014-01-01

    Full Text Available This case report describes xeroderma pigmentosum in an 8-year old boy. At the age of 4 he was diagnosed with aggressive keratinizing squamous cell carcinoma. Surgical treatment, close-focus radiotherapy, isotretinoin and cyclosporine were ineffective. At the age of 8 he had multiple tumors on the face and concha of the ear, with destruction of adjacent bone and cartilage and regional nodal metastasing.

  8. A Hennart nodal method for the diffusion equation

    International Nuclear Information System (INIS)

    Lesaint, P.; Noceir, S.; Verwaerde, D.

    1995-01-01

    A modification of the Hennart nodal method for neutron diffusion problems is presented. The final system of equations obtained by this method is not positive definite. However, a flux elimination technique leads to a simple positive definite system, which can be solved by the traditional iterative methods. Calculations of a two-dimensional International Atomic Energy Agency benchmark problem are performed and compared with results of the original Hennart nodal method and some finite element methods. The high computational efficiency of this modified nodal method is clearly demonstrated

  9. Modifying nodal pricing method considering market participants optimality and reliability

    Directory of Open Access Journals (Sweden)

    A. R. Soofiabadi

    2015-06-01

    Full Text Available This paper develops a method for nodal pricing and market clearing mechanism considering reliability of the system. The effects of components reliability on electricity price, market participants’ profit and system social welfare is considered. This paper considers reliability both for evaluation of market participant’s optimality as well as for fair pricing and market clearing mechanism. To achieve fair pricing, nodal price has been obtained through a two stage optimization problem and to achieve fair market clearing mechanism, comprehensive criteria has been introduced for optimality evaluation of market participant. Social welfare of the system and system efficiency are increased under proposed modified nodal pricing method.

  10. Autologous bone marrow Th cells can support multiple myeloma cell proliferation in vitro and in xenografted mice.

    Science.gov (United States)

    Wang, D; Fløisand, Y; Myklebust, C V; Bürgler, S; Parente-Ribes, A; Hofgaard, P O; Bogen, B; Taskén, K; Tjønnfjord, G E; Schjesvold, F; Dalgaard, J; Tveita, A; Munthe, L A

    2017-10-01

    Multiple myeloma (MM) is a plasma cell malignancy where MM cell growth is supported by the bone marrow (BM) microenvironment with poorly defined cellular and molecular mechanisms. MM cells express CD40, a receptor known to activate autocrine secretion of cytokines and elicit proliferation. Activated T helper (Th) cells express CD40 ligand (CD40L) and BM Th cells are significantly increased in MM patients. We hypothesized that activated BM Th cells could support MM cell growth. We here found that activated autologous BM Th cells supported MM cell growth in a contact- and CD40L-dependent manner in vitro. MM cells had retained the ability to activate Th cells that reciprocated and stimulated MM cell proliferation. Autologous BM Th cells supported MM cell growth in xenografted mice and were found in close contact with MM cells. MM cells secreted chemokines that attracted Th cells, secretion was augmented by CD40-stimulation. Within 14 days of culture of whole BM aspirates in autologous serum, MM cells and Th cells mutually stimulated each other, and MM cells required Th cells for further expansion in vitro and in mice. The results suggest that Th cells may support the expansion of MM cells in patients.

  11. Ras proteins have multiple functions in vegetative cells of Dictyostelium.

    Science.gov (United States)

    Bolourani, Parvin; Spiegelman, George; Weeks, Gerald

    2010-11-01

    During the aggregation of Dictyostelium cells, signaling through RasG is more important in regulating cyclic AMP (cAMP) chemotaxis, whereas signaling through RasC is more important in regulating the cAMP relay. However, RasC is capable of substituting for RasG for chemotaxis, since rasG⁻ cells are only partially deficient in chemotaxis, whereas rasC⁻/rasG⁻ cells are totally incapable of chemotaxis. In this study we have examined the possible functional overlap between RasG and RasC in vegetative cells by comparing the vegetative cell properties of rasG⁻, rasC⁻, and rasC⁻/rasG⁻ cells. In addition, since RasD, a protein not normally found in vegetative cells, is expressed in vegetative rasG⁻ and rasC⁻/rasG⁻ cells and appears to partially compensate for the absence of RasG, we have also examined the possible functional overlap between RasG and RasD by comparing the properties of rasG⁻ and rasC⁻/rasG⁻ cells with those of the mutant cells expressing higher levels of RasD. The results of these two lines of investigation show that RasD is capable of totally substituting for RasG for cytokinesis and growth in suspension, whereas RasC is without effect. In contrast, for chemotaxis to folate, RasC is capable of partially substituting for RasG, but RasD is totally without effect. Finally, neither RasC nor RasD is able to substitute for the role that RasG plays in regulating actin distribution and random motility. These specificity studies therefore delineate three distinct and none-overlapping functions for RasG in vegetative cells.

  12. Regeneration of three sweet potato (Ipomea batatas (L.)) accessions via meristem, Nodal and callus induction

    International Nuclear Information System (INIS)

    Addae-Frimpomaah, F.

    2012-11-01

    In vitro regeneration of three sweet potato accessions UE007, UK-BNARI and SA-BNARI using meristem, nodal cuttings or callus induction was studied. Meristematic explants cultured on Murashige and Skoog (1962) basal medium supplemented with low concentration of benzylaminopurine (BAP) or kinetin resulted in callus with or without shoot development which delayed shoot emergence. The degree of callus development increased as the concentration of the cytokinin in the culture medium increased. Although, callus development was comparatively lower on kinetin amended medium than BAP amended medium, Murashige and Skoog medium supplemented with 0.25mg/1BAP had the highest shoot induction (80%). For further differentiation of callus or shoots into distinct stem and leaves, the culture were transferred into fresh MS medium supplemented with 0.25mg/1 BAP, 0.1 mg/1 NAA and 0.1 mg/1 Gibberellic acid (GA 3 . To overcome the delay in shoot initiation using meristem culture, nodal cuttings of sweet potato were used as explants and cultured on MS medium amended with 0.3 - 0.9mg/1 BAP. All explants cultured on 0.3 or 0.6mg/1 BAP developed shoots. Furthermore, liquid MS medium amended with 0.25mg/1 BAP, 0.1mg/I NAA, and 0.1mg/1 GA 3 also enhanced early shoot development from nodal cutting explants compared to solid culture. Post flask acclimatisation of meristem or nodal cutting-derived plantlets showed that meristem derived plantlets were better acclimatised than nodal cutting plants due to vigorous root development leading to higher percentage survival in pots and subsequent tuber production. Callusogenesis was achieved when leaf lobe explants were cultured on CLC/ Ipomoea medium supplemented with 1.0 - 4.0mg/1 2,4-D with 4.0mg/1 2,4-D being the optimal concentration. However, the calli were non-embryogenic and therefore could not produce embryos when transferred to 0.1mg/1 BAP amended medium but rather produced either single or multiple shoots. The highest percentage shoot (83

  13. Treatment Results of Postoperative Radiotherapy on Squamous Cell Carcinoma of the Oral Cavity: Coexistence of Multiple Minor Risk Factors Results in Higher Recurrence Rates

    International Nuclear Information System (INIS)

    Fan, Kang-Hsing; Wang, Hung-Ming; Kang, Chung-Jan

    2010-01-01

    Purpose: The aim of this study was to investigate the treatment results of postoperative radiotherapy (PORT) on squamous cell carcinoma of the oral cavity (OSCC). Materials and Methods: This study included 302 OSCC patients who were treated by radical surgery and PORT. Indications for PORT include Stage III or IV OSCC according to the 2002 criteria of the American Joint Committee on Cancer, the presence of perineural invasion or lymphatic invasion, the depth of tumor invasion, or a close surgical margin. Patients with major risk factors, such as multiple nodal metastases, a positive surgical margin, or extracapsular spreading, were excluded. The prescribed dose of PORT ranged from 59.4 to 66.6Gy (median, 63Gy). Results: The 3-year overall and recurrence-free survival rates were 73% and 70%, respectively. Univariate analysis revealed that differentiation, perineural invasion, lymphatic invasion, bone invasion, location (hard palate and retromolar trigone), invasion depths ≥10mm, and margin distances ≤4mm were significant prognostic factors. The presence of multiple significant factors of univariate analysis correlated with disease recurrence. The 3-year recurrence-free survival rates were 82%, 76%, and 45% for patients with no risk factors, one or two risk factors, and three or more risk factors, respectively. After multivariate analysis, the number of risk factors and lymphatic invasion were significant prognostic factors. Conclusion: PORT may be an adequate adjuvant therapy for OSCC patients with one or two risk factors of recurrence. The presence of multiple risk factors and lymphatic invasion correlated with poor prognosis, and more aggressive treatment may need to be considered.

  14. Different aspects of thalidomide treatment and stem cell transplantation in multiple myeloma patients

    NARCIS (Netherlands)

    Marion, A.M.W. van

    2006-01-01

    Multiple myeloma (MM) is an haematological malignancy caused by an unrestrained proliferation of plasma cells (monoclonally differentiated B-cells), and part of the white blood cell count. This proliferation infiltrates the blood forming skeletal bone marrow, producing osteoclastic factors, causing

  15. Activation of endogenous neural stem cells for multiple sclerosis therapy

    NARCIS (Netherlands)

    Michailidou, I.; de Vries, H.E.; Hol, E.M.; van Strien, M.E.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic

  16. Micropropagation of Calophyllum brasiliense (Cambess.) from nodal segments.

    Science.gov (United States)

    Silveira, S S; Cordeiro-Silva, R; Degenhardt-Goldbach, J; Quoirin, M

    2016-05-03

    Micropropagation of Calophyllum brasiliense Cambess. (Clusiaceae) is a way to overcome difficulties in achieving large-scale plant production, given the recalcitrant nature of the seeds, irregular fructification and absence of natural vegetative propagation of the species. Cultures were established using nodal segments 2 cm in length, obtained from 1-2 year old seedlings, maintained in a greenhouse. Mercury chloride and Plant Preservative Mixture™ were used in the surface sterilizing stage, better results being achieved with Plant Preservative Mixture™ incorporation in culture medium, at any concentration. Polyvinylpyrrolidone, activated charcoal, cysteine, ascorbic acid or citric acid were added to the culture medium to avoid oxidation. After 30 days of culture, polyvinylpirrolidone and ascorbic acid gave better results, eliminating oxidation in most explants. For shoot multiplication, benzylaminopurine was used in concentrations of 4.4 and 8.8 µM in Woody Plant Medium, resulting in an average of 4.43 and 4.68 shoots per explant, respectively, after 90 days. Indole-3-butyric acid and α-naphthalene acetic acid were used to induce root formation, reaching a maximum rooting rate of 24% with 20µM α-naphthalene acetic acid. For acclimatization. the rooted plants were transferred to Plantmax® substrate and cultured in a greenhouse, reaching 79% of survival after 30 days and 60% after one year.

  17. Romidepsin targets multiple survival signaling pathways in malignant T cells

    International Nuclear Information System (INIS)

    Valdez, B C; Brammer, J E; Li, Y; Murray, D; Liu, Y; Hosing, C; Nieto, Y; Champlin, R E; Andersson, B S

    2015-01-01

    Romidepsin is a cyclic molecule that inhibits histone deacetylases. It is Food and Drug Administration-approved for treatment of cutaneous and peripheral T-cell lymphoma, but its precise mechanism of action against malignant T cells is unknown. To better understand the biological effects of romidepsin in these cells, we exposed PEER and SUPT1 T-cell lines, and a primary sample from T-cell lymphoma patient (Patient J) to romidepsin. We then examined the consequences in some key oncogenic signaling pathways. Romidepsin displayed IC 50 values of 10.8, 7.9 and 7.0 nm in PEER, SUPT1 and Patient J cells, respectively. Strong inhibition of histone deacetylases and demethylases, increased production of reactive oxygen species and decreased mitochondrial membrane potential were observed, which may contribute to the observed DNA-damage response and apoptosis. The stress-activated protein kinase/c-Jun N-terminal kinase signaling pathway and unfolded protein response in the endoplasmic reticulum were activated, whereas the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) and β-catenin pro-survival pathways were inhibited. The decreased level of β-catenin correlated with the upregulation of its inhibitor SFRP1 through romidepsin-mediated hypomethylation of its gene promoter. Our results provide new insights into how romidepsin invokes malignant T-cell killing, show evidence of its associated DNA hypomethylating activity and offer a rationale for the development of romidepsin-containing combination therapies

  18. CT simulation in nodal positive breast cancer

    International Nuclear Information System (INIS)

    Horst, E.; Schuck, A.; Moustakis, C.; Schaefer, U.; Micke, O.; Kronholz, H.L.; Willich, N.

    2001-01-01

    Background: A variety of solutions are used to match tangential fields and opposed lymph node fields in irradiation of nodal positive breast cancer. The choice is depending on the technical equipment which is available and the clinical situation. The CT simulation of a non-monoisocentric technique was evaluated in terms of accuracy and reproducibility. Patients, Material and Methods: The field match parameters were adjusted virtually at CT simulation and were compared with parameters derived mathematically. The coordinate transfer from the CT simulator to the conventional simulator was analyzed in 25 consecutive patients. Results: The angles adjusted virtually for a geometrically exact coplanar field match corresponded with the angles calculated for each set-up. The mean isocenter displacement was 5.7 mm and the total uncertainty of the coordinate transfer was 6.7 mm (1 SD). Limitations in the patient set-up became obvious because of the steep arm abduction necessary to fit the 70 cm CT gantry aperture. Required modifications of the arm position and coordinate transfer errors led to a significant shift of the marked matchline of >1.0 cm in eight of 25 patients (32%). Conclusion: The virtual CT simulation allows a precise and graphic definition of the field match parameters. However, modifications of the virtual set-up basically due to technical limitations were required in a total of 32% of cases, so that a hybrid technique was adapted at present that combines virtual adjustment of the ideal field alignment parameters with conventional simulation. (orig.) [de

  19. Present Status of GNF New Nodal Simulator

    International Nuclear Information System (INIS)

    Iwamoto, T.; Tamitani, M.; Moore, B.

    2001-01-01

    This paper presents core simulator consolidation work done at Global Nuclear Fuel (GNF). The unified simulator needs to supercede the capabilities of past simulator packages from the original GNF partners: GE, Hitachi, and Toshiba. At the same time, an effort is being made to produce a simulation package that will be a state-of-the-art analysis tool when released, in terms of the physics solution methodology and functionality. The core simulator will be capable and qualified for (a) high-energy cycles in the U.S. markets, (b) mixed-oxide (MOX) introduction in Japan, and (c) high-power density plants in Europe, etc. The unification of the lattice physics code is also in progress based on a transport model with collision probability methods. The AETNA core simulator is built upon the PANAC11 software base. The goal is to essentially replace the 1.5-energy-group model with a higher-order multigroup nonlinear nodal solution capable of the required modeling fidelity, while keeping highly automated library generation as well as functionality. All required interfaces to PANAC11 will be preserved, which minimizes the impact on users and process automation. Preliminary results show statistical accuracy improvement over the 1.5-group model

  20. BEACON: An application of nodal methods for operational support

    International Nuclear Information System (INIS)

    Boyd, W.A.; Nguyen, T.Q.

    1992-01-01

    A practical application of nodal methods is on-line plant operational support. However, to enable plant personnel to take full advantage of a nodal model to support plant operations, (a) a core nodal model must always be up to date with the current core history and conditions, (b) the nodal methods must be fast enough to allow numerous core calculations to be performed in minutes to support engineering decisions, and (c) the system must be easily accessible to engineering personnel at the reactor, their offices, or any other location considered appropriate. A core operational support package developed by Westinghouse called BEACON (best estimate analysis of core operations - nuclear) has been installed at several plants. Results from these plants and numerous in-core flux maps analyzed have demonstrated the accuracy of the model and the effectiveness of the methodology

  1. Aircraft Nodal Data Acquisition System (ANDAS), Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Development of an Aircraft Nodal Data Acquisition System (ANDAS) based upon the short haul Zigbee networking standard is proposed. It employs a very thin (135 um)...

  2. Hybrid nodal loop metal: Unconventional magnetoresponse and material realization

    Science.gov (United States)

    Zhang, Xiaoming; Yu, Zhi-Ming; Lu, Yunhao; Sheng, Xian-Lei; Yang, Hui Ying; Yang, Shengyuan A.

    2018-03-01

    A nodal loop is formed by a band crossing along a one-dimensional closed manifold, with each point on the loop a linear nodal point in the transverse dimensions, and can be classified as type I or type II depending on the band dispersion. Here, we propose a class of nodal loops composed of both type-I and type-II points, which are hence termed as hybrid nodal loops. Based on first-principles calculations, we predict the realization of such loops in the existing electride material Ca2As . For a hybrid loop, the Fermi surface consists of coexisting electron and hole pockets that touch at isolated points for an extended range of Fermi energies, without the need for fine-tuning. This leads to unconventional magnetic responses, including the zero-field magnetic breakdown and the momentum-space Klein tunneling observable in the magnetic quantum oscillations, as well as the peculiar anisotropy in the cyclotron resonance.

  3. A nodal method based on matrix-response method

    International Nuclear Information System (INIS)

    Rocamora Junior, F.D.; Menezes, A.

    1982-01-01

    A nodal method based in the matrix-response method, is presented, and its application to spatial gradient problems, such as those that exist in fast reactors, near the core - blanket interface, is investigated. (E.G.) [pt

  4. Nodal prices determination with wind integration for radial ...

    African Journals Online (AJOL)

    With competitive electricity market operation, open access to the transmission and distribution network is essential ... The results have been obtained for IEEE 33 ...... The value of intermittent wind DG under nodal prices and amp – mile tariffs.

  5. Nodal aberration theory for wild-filed asymmetric optical systems

    Science.gov (United States)

    Chen, Yang; Cheng, Xuemin; Hao, Qun

    2016-10-01

    Nodal Aberration Theory (NAT) was used to calculate the zero field position in Full Field Display (FFD) for the given aberration term. Aiming at wide-filed non-rotational symmetric decentered optical systems, we have presented the nodal geography behavior of the family of third-order and fifth-order aberrations. Meanwhile, we have calculated the wavefront aberration expressions when one optical element in the system is tilted, which was not at the entrance pupil. By using a three-piece-cellphone lens example in optical design software CodeV, the nodal geography is testified under several situations; and the wavefront aberrations are calculated when the optical element is tilted. The properties of the nodal aberrations are analyzed by using Fringe Zernike coefficients, which are directly related with the wavefront aberration terms and usually obtained by real ray trace and wavefront surface fitting.

  6. Extension of the analytic nodal method to four energy groups

    International Nuclear Information System (INIS)

    Parsons, D.K.; Nigg, D.W.

    1985-01-01

    The Analytic Nodal Method is one of several recently-developed coarse mesh numerical methods for efficiently and accurately solving the multidimensional static and transient neutron diffusion equations. This summary describes a mathematically rigorous extension of the Analytic Nodal Method to the frequently more physically realistic four-group case. A few general theoretical considerations are discussed, followed by some calculated results for a typical steady-state two-dimensional PWR quarter core application. 8 refs

  7. Extra-nodal lymphoma. A survey of Japan lymphoma radiation therapy group

    International Nuclear Information System (INIS)

    Oguchi, Masahiko; Ikeda, Hiroshi; Nakamura, Shigeo

    2002-01-01

    The purpose of this study was to examine, retrospectively, national-wide clinical data of patients with localized extranodal non-Hodgkin's lymphoma (NHL) who were treated by radiation therapy with or without chemotherapy. The survey was carried out at 25 radiation oncology institutions in Japan in 1998. In 1999, according to the Revised European American Lymphoma (REAL) classification, central pathological review conducted at Aichi cancer center was carried out for the data from 7 radiation oncology institutions. The 5-year progression free survival rates (PFS) were calculated to identify prognostic factors. Survey: Data from 1, 141 patients with stage I and II NHL were recruited from 1988 through 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate and high-grade lymphomas in Working Formulation, constituted the core of this study. Primary tumors arose mainly from extra-nodal organs (71%) in the head and neck (Waldeyer's ring: 41%, thyroid gland: 7%, nasal cavities: 5%, oral cavities: 4%, sinus: 3%, orbital structures: 3%, skin: 2% and etc.). The median age of 60 years for patients with extra-nodal NHL was higher than that of 56 years for patients with nodal NHL (p<0.01). Female were dominant in incidence of extra-nodal NHL arising from the thyroid gland, skin and gastrointestinal tract. The percentage of stage I to the extra-nodal NHL from orbit, sino-nasal presentation was higher than that of other NHLs. The percentage of stage II to the extra-nodal NHL from Waldeyer's ring and thyroid gland was higher than that of other NHLs. Central pathological review was carried out for pathological data from 79 patients (Waldeyer's ring: 45, thyroid gland: 19, sinonasal cavities: 15). Of these, diffuse large B cell lymphoma (DLBCL) composed 63% of all patients, mucosa associated lyumphoid tissue lymphoma (MALT-L): 16%, Natural Killer/T cell lymphoma (NK/T-L): 11%, and mantle cell lymphoma: 5% in REAL

  8. Bilinear nodal transport method in weighted diamond difference form

    International Nuclear Information System (INIS)

    Azmy, Y.Y.

    1987-01-01

    Nodal methods have been developed and implemented for the numerical solution of the discrete ordinates neutron transport equation. Numerical testing of these methods and comparison of their results to those obtained by conventional methods have established the high accuracy of nodal methods. Furthermore, it has been suggested that the linear-linear approximation is the most computationally efficient, practical nodal approximation. Indeed, this claim has been substantiated by comparing the accuracy in the solution, and the CPU time required to achieve convergence to that solution by several nodal approximations, as well as the diamond difference scheme. Two types of linear-linear nodal methods have been developed in the literature: analytic linear-linear (NLL) methods, in which the transverse-leakage terms are derived analytically, and approximate linear-linear (PLL) methods, in which these terms are approximated. In spite of their higher accuracy, NLL methods result in very complicated discrete-variable equations that exhibit a high degree of coupling, thus requiring special solution algorithms. On the other hand, the sacrificed accuracy in PLL methods is compensated for by the simple discrete-variable equations and diamond-difference-like solution algorithm. In this paper the authors outline the development of an NLL nodal method, the bilinear method, which can be written in a weighted diamond difference form with one spatial weight per dimension that is analytically derived rather than preassigned in an ad hoc fashion

  9. Red Cell Alloantibodies in Multiple Transfused Thalassaemia Patients.

    Science.gov (United States)

    Chaudhari, C N

    2011-01-01

    Thalassaemia major patients require lifelong transfusion support due to which they are prone for alloimmunization to foreign RBCs. Alloimmunization can be prevented by extended phenotype match blood transfusion. The study was conducted to know the extent of problem of alloimmunization and to find important red cell antibodies in thalassaemia patients. A cross-sectional study was conducted. A total of 32 thalassaemia patients were enrolled. The specimen was subjected to red cell alloantibody and autoantibody by column gel agglutination technique. R 1 (w) R 1 , R 2 R 2 , rr (papaine and non papain) and 11 cell panel reagent cells were used in screening and identification of alloantibodies respectively. Six (18.8 %) subjects were alloimmunized. All alloimmunized subjects were recipient of more than 20 units of transfusion. Total seven clinically significant alloantibodies were identified. Anti E and anti c were commonest antibodies in four (12.5%) patients. Red cell alloimmunization is an important risk in thalassaemia patient. 71.4% of alloantibodies were anti E and anti c type. Extended phenotype match blood transfusion for Rh-c and Rh-E antigens or level 2 antigen matching stringency needs to be explored in preventing alloimmunization in thalassaemia patients.

  10. HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

    Science.gov (United States)

    Pai, Vaibhav P; Willocq, Valerie; Pitcairn, Emily J; Lemire, Joan M; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A; Levin, Michael

    2017-10-15

    Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels ( I h currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal , Lefty , and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. © 2017. Published by The Company of Biologists Ltd.

  11. Incorporating Multiple Energy Relay Dyes in Liquid Dye-Sensitized Solar Cells

    KAUST Repository

    Yum, Jun-Ho; Hardin, Brian E.; Hoke, Eric T.; Baranoff, Etienne; Zakeeruddin, Shaik M.; Nazeeruddin, Mohammad K.; Torres, Tomas; McGehee, Michael D.; Grä tzel, Michael

    2011-01-01

    Panchromatic response is essential to increase the light-harvesting efficiency in solar conversion systems. Herein we show increased light harvesting from using multiple energy relay dyes inside dye-sensitized solar cells. Additional photoresponse

  12. Significance of adipose tissue-derived stem cells regulate CD4+ T cell immune in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Yong-lin XIE

    2014-10-01

    Full Text Available Adipose tissue-derived stem cells (ADSCs are genetically engineered seed cells with immunomodulatory effects, widely used in the treatment of autoimmune diseases. This article focuses on the immunomodulatory effects of adipose tissue-derived stem cells on CD4+ T cell subsets, including T helper cell (Th 1, 2, 17 and regulatory T cell (Treg, and its clinical significance in the treatment of multiple sclerosis. doi: 10.3969/j.issn.1672-6731.2014.10.005

  13. Uniqueness Theorem for the Inverse Aftereffect Problem and Representation the Nodal Points Form

    Directory of Open Access Journals (Sweden)

    A. Neamaty

    2015-03-01

    Full Text Available In this paper, we consider a boundary value problem with aftereffect on a finite interval. Then, the asymptotic behavior of the solutions, eigenvalues, the nodal points and the associated nodal length are studied. We also calculate the numerical values of the nodal points and the nodal length. Finally, we prove the uniqueness theorem for the inverse aftereffect problem by applying any dense subset of the nodal points.

  14. Uniqueness Theorem for the Inverse Aftereffect Problem and Representation the Nodal Points Form

    OpenAIRE

    A. Neamaty; Sh. Akbarpoor; A. Dabbaghian

    2015-01-01

    In this paper, we consider a boundary value problem with aftereffect on a finite interval. Then, the asymptotic behavior of the solutions, eigenvalues, the nodal points and the associated nodal length are studied. We also calculate the numerical values of the nodal points and the nodal length. Finally, we prove the uniqueness theorem for the inverse aftereffect problem by applying any dense subset of the nodal points.

  15. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition.

    Science.gov (United States)

    Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara Mª; Teixidó, Montserrat; Gimenez, Mª Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Bladé, Joan; de Larrea, Carlos Fernández

    2017-06-01

    The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6-9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×10 9 /L vs 214×10 9 /L, P <0.0001) and higher bone marrow plasma cells (median 53% vs 36%, P =0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia. Copyright© Ferrata Storti Foundation.

  16. Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells

    NARCIS (Netherlands)

    Maldonado, Paloma P; Angulo, María Cecilia

    The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity

  17. Relevance of regional nodal management in multimodality esophageal cancer treatment

    International Nuclear Information System (INIS)

    Wong, J.; Perez-Tamayo, C.; Takasugi, B.; Orringer, M.B.; Flint, A.; Lichter, A.S.

    1986-01-01

    A prospective study has been undertaken at the University of Michigan Hospital, where patients with distal esophageal carcinoma receive concurrent radiation therapy (3,750 cGy delivered in 15 fractions) and systemic chemotherapy (cisplatin, Velban, 5-FU), followed by blunt esophagectomy with exploration and lymph node sampling. Strict pathologic screening and handling of nodal tissue and esophagectomy specimens were analyzed. Eighteen patients with distal esophageal lesions ranging from 5 to 12 cm (average, 7 cm) detected on the initial barium swallow study have been seen to date. In three of these patients celiac axis involvement has been demonstrated on CT. All primary lesions were confirmed by biopsy. Five were found to be squamous cell carcinoma and thirteen were adenocarcinomas. One of 15 of the presently evaluable patients (5%) had microscopic involvement of a celiac node at surgery. Celiac, lesser curvature, and superior gastric nodes where all encompassed in the radiation therapy portals to the aforementioned dose. CT scan planning was done in all patients. This added volume was well tolerated by the patients without morbidity

  18. Multiple mesodermal lineage differentiation of Apodemus sylvaticus embryonic stem cells in vitro

    Directory of Open Access Journals (Sweden)

    Yu Weihua

    2010-06-01

    Full Text Available Abstract Background Embryonic stem (ES cells have attracted significant attention from researchers around the world because of their ability to undergo indefinite self-renewal and produce derivatives from the three cell lineages, which has enormous value in research and clinical applications. Until now, many ES cell lines of different mammals have been established and studied. In addition, recently, AS-ES1 cells derived from Apodemus sylvaticus were established and identified by our laboratory as a new mammalian ES cell line. Hence further research, in the application of AS-ES1 cells, is warranted. Results Herein we report the generation of multiple mesodermal AS-ES1 lineages via embryoid body (EB formation by the hanging drop method and the addition of particular reagents and factors for induction at the stage of EB attachment. The AS-ES1 cells generated separately in vitro included: adipocytes, osteoblasts, chondrocytes and cardiomyocytes. Histochemical staining, immunofluorescent staining and RT-PCR were carried out to confirm the formation of multiple mesodermal lineage cells. Conclusions The appropriate reagents and culture milieu used in mesodermal differentiation of mouse ES cells also guide the differentiation of in vitro AS-ES1 cells into distinct mesoderm-derived cells. This study provides a better understanding of the characteristics of AS-ES1 cells, a new species ES cell line and promotes the use of Apodemus ES cells as a complement to mouse ES cells in future studies.

  19. Usefulness of FDG PET for nodal staging using a dual head coincidence camera in patients with lung cancer

    International Nuclear Information System (INIS)

    Yoon, Seok Nam; Park, Chan H.; Lee, Myoung Hoon; Hwang, Kyung Hoon; Hwang, Kyung Hoon

    2001-01-01

    Staging of lung cancer requires an accurate evaluation of the mediastinum. Positron imaging with dual head cameras may be not as sensitive as dedicated PET. Therefore, the purpose of the study was to evaluated the usefulness of F-18 FDG coincidence (CoDe) PET using a dual-head gamma camera in the nodal staging of the lung cancer. CoDe-PET studies were performed in 51 patients with histologically proven non small cell lung cancer. CoDe-PET began 60 minutes after the injection of 111-185 MBq of F-18 FDG. CoDe-PET was performed using a dual-head gamma camera equipped with coincidence detection circuitry (Elscints Varicam, Haifa, lsrael). There was no attenuation correction made and reconstruction was done using a filtered back-projection. Surgery was performed in 49 patients CoDe-PET studies were evaluated visually. Any focal increased uptake was considered abnormal. The nodal stating of CoDe-PET studies were evaluated visually. Any focal increased uptake was considered abnormal. The nodal staging of CoDe-PET and of CT were compared with the nodal stating of surgical (49) and mediastinoscopical (2) pathology. All primary lung lesions were hypermetabolic and easily visualized. Compared with surgical nodal staging as a gold standard, false positives occurred in 13 CoDe PET and 17 CT studies and false negative occurred in 5 CoDe-PET and 4 CT studies. Assessment of lymph node involvement by CoDe-PET depicted a sensitivity of 67%, specificity of 64% and accuracy of 65%. CT revealed a sensitivity of 73%, specificity of 53% and accuracy of 59% in the assessment of lymph node involvement. The detection of primary lesions were 100% but nodal staging was suboptimal for routine clinical use. This is mainly due to limited resolution of our system

  20. Multiple bubbles in a Hele-Shaw cell

    International Nuclear Information System (INIS)

    Vasconcelos, G.L.

    1994-01-01

    A new class of exact solutions is reported for an infinite stream of identical groups of bubbles moving with a constant velocity U in a Hele-Shaw cell when surface tension is neglected. It is suggested that the existence of these solutions might explain some of the complex behavior observed in recent experiments on rising bubbles in a Hele-Shaw cell. Solutions for a finite number of bubbles in a channel are also obtained. In this case, it is shown that solutions with an arbitrary bubble velocity U>V, where V is the fluid velocity at infinity, can in general be obtained from a simple transformation of the solutions for U=2V

  1. Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Trude G. Simonsen

    2016-06-01

    Full Text Available INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases.

  2. Autologous hematopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: comparison with secondary progressive multiple sclerosis.

    Science.gov (United States)

    Casanova, Bonaventura; Jarque, Isidro; Gascón, Francisco; Hernández-Boluda, Juan Carlos; Pérez-Miralles, Francisco; de la Rubia, Javier; Alcalá, Carmen; Sanz, Jaime; Mallada, Javier; Cervelló, Angeles; Navarré, Arantxa; Carcelén-Gadea, María; Boscá, Isabel; Gil-Perotin, Sara; Solano, Carlos; Sanz, Miguel Angel; Coret, Francisco

    2017-07-01

    The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS ≥ 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

  3. PET-NECK: a multicentre randomised Phase III non-inferiority trial comparing a positron emission tomography-computerised tomography-guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell head and neck cancer.

    Science.gov (United States)

    Mehanna, Hisham; McConkey, Chris C; Rahman, Joy K; Wong, Wai-Lup; Smith, Alison F; Nutting, Chris; Hartley, Andrew Gj; Hall, Peter; Hulme, Claire; Patel, Dharmesh K; Zeidler, Sandra Ventorin von; Robinson, Max; Sanghera, Bal; Fresco, Lydia; Dunn, Janet A

    2017-04-01

    Planned neck dissection (ND) after radical chemoradiotherapy (CRT) for locally advanced nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. Thirty per cent of ND specimens show histological evidence of tumour. Consequently, a significant proportion of clinicians still practise planned ND. Fludeoxyglucose positron emission tomography (PET)-computerised tomography (CT) scanning demonstrated high negative predictive values for persistent nodal disease, providing a possible alternative paradigm to ND. Evidence is sparse and drawn mainly from retrospective single-institution studies, illustrating the need for a prospective randomised controlled trial. To determine the efficacy and cost-effectiveness of PET-CT-guided surveillance, compared with planned ND, in a multicentre, prospective, randomised setting. A pragmatic randomised non-inferiority trial comparing PET-CT-guided watch-and-wait policy with the current planned ND policy in HNSCC patients with locally advanced nodal metastases and treated with radical CRT. Patients were randomised in a 1 : 1 ratio. Primary outcomes were overall survival (OS) and cost-effectiveness [incremental cost per incremental quality-adjusted life-year (QALY)]. Cost-effectiveness was assessed over the trial period using individual patient data, and over a lifetime horizon using a decision-analytic model. Secondary outcomes were recurrence in the neck, complication rates and quality of life. The recruitment of 560 patients was planned to detect non-inferior OS in the intervention arm with a 90% power and a type I error of 5%, with non-inferiority defined as having a hazard ratio (HR) of no higher than 1.50. An intention-to-treat analysis was performed by Cox's proportional hazards model. Thirty-seven head and neck cancer-treating centres (43 NHS hospitals) throughout the UK. Patients with locally advanced nodal metastases of oropharynx, hypopharynx, larynx, oral or occult HNSCC receiving

  4. Familial atrioventricular nodal re-entrant tachycardia: A case seriers and a systematic review

    Directory of Open Access Journals (Sweden)

    Muthiah Subramanian

    2017-11-01

    Full Text Available Multiple reports of familial clustering suggest that genetic factors may contribute in the pathogenesis of atrioventricular nodal re-entrant tachycardia (AVNRT. We report three cases of AVNRT in a father and his two sons along with a review of literature of other similar cases. Electrophysiological studies induced typical AVNRT, which was successfully eliminated by radiofrequency ablation in all of them. Of the 22 reported cases, 96% had typical (slow-fast variant of AVNRT. The predominant pattern of inheritance appears to be autosomal dominant, though other patterns may exist. Further research is needed to understand the genetic influence of AVNRT and its pathophysiology. Keywords: Familial, AVNRT, Tachycardia

  5. A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Jutta Ries

    2009-01-01

    Full Text Available Objective: Melanoma associated antigens-A (MAGE-A expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC.

  6. NODAL and SHH dose-dependent double inhibition promotes an HPE-like phenotype in chick embryos

    Directory of Open Access Journals (Sweden)

    Sandra Mercier

    2013-03-01

    Holoprosencephaly (HPE is a common congenital defect that results from failed or incomplete forebrain cleavage. HPE is characterized by a wide clinical spectrum, with inter- and intrafamilial variability. This heterogeneity is not well understood and it has been suggested that HPE involves a combination of multiple gene mutations. In this model, several mutated alleles or modifying factors are presumed to act in synergy to cause and determine the severity of HPE. This could explain the various clinical phenotypes. Screening for HPE-associated genes in humans suggests the involvement of NODAL or SHH signaling, or both. To test this multigenic hypothesis, we investigated the effects of chemical inhibition of these two main HPE signaling pathways in a chick embryo model. SB-505124, a selective inhibitor of transforming growth factor-B type I receptors was used to inhibit the NODAL pathway. Cyclopamine was used to inhibit the SHH pathway. We report that both inhibitors caused HPE-like defects that were dependent on the drug concentration and on the developmental stage at the time of treatment. We also investigated double inhibition of NODAL and SHH pathways from the onset of gastrulation by using subthreshold inhibitor concentrations. The inhibitors of the NODAL and SHH pathways, even at low concentration, acted synergistically to promote an HPE-like phenotype. These findings support the view that genetic heterogeneity is important in the etiology of HPE and may contribute to the phenotypic variability.

  7. Characterization of CD4+ T cell-mediated cytotoxicity in patients with multiple myeloma.

    Science.gov (United States)

    Zhang, Xiaole; Gao, Lei; Meng, Kai; Han, Chunting; Li, Qiang; Feng, Zhenjun; Chen, Lei

    2018-05-01

    Multiple myeloma (MM) is an incurable cancer characterized by the development of malignant plasma cells. The CD8 T cell-mediated cytotoxicity is considered a major player in antitumor immunity, but in MM patients, the CD8 T cells displayed senescence markers and were functionally impaired. To investigate whether cytotoxic CD4 T cells could act as a treatment alternative in MM, we examined the frequency and function of naturally occurring cytotoxic CD4 T cells in MM patients. The cytotoxic CD4 T cells were identified as granzyme-A, granzyme B-, and perforin-expressing CD4 T cells, and their frequencies were significantly upregulated in MM patients when compared with healthy controls. The frequencies of cytotoxic CD4 T cells in MM patients were not associated with the frequencies of cytotoxic CD8 T cells, but were negatively associated with disease severity. Interestingly, the expression levels of inhibitory molecules, including PD-1 and CTLA-4, were significantly lower in cytotoxic CD4 T cells than in cytotoxic CD8 T cells. When co-incubated with autologous CD38 + CD138 + plasma cells, CD4 T cells were capable of eliminating plasma cells with varying degrees of efficacy. In MM patients, the frequency of circulating plasma cells was negatively correlated with the frequency of cytotoxic CD4 T cells. Therefore, CD4 T cell-mediated cytotoxicity existed naturally in MM patients and could potentially act as an option in antitumor therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. A CASE REPORT OF MULTIPLE PRIMARY SQUAMOUS CELL CARCINOMAS OF THE OVARY AND SIGMOID COLON

    Directory of Open Access Journals (Sweden)

    A. B. Villert

    2016-01-01

    Full Text Available Squamous cell ovarian and sigmoid colon carcinomas are extremely rare malignancies. Because of their rarity, it is difficult to investigate the clinical characteristics and prognosis of patients with theses malignancies, and therefore, the increased interest in each clinical case report is highly relevant. Multiple primary squamous cell ovarian and sigmoid colon carcinomas are the subject of discussion and differential diagnosis of sigmoid colon cancer with secondary ovarian cancer. Histopathological and clinical characteristics of the tumors were present and evidences in favor of the multiple primary malignancies were given. The association of squamous cell ovarian and sigmoid colon carcinomas with human papilloma virus type 16 was shown.

  9. Multiple loci are associated with white blood cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Michael A Nalls

    2011-06-01

    Full Text Available White blood cell (WBC count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2, including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across

  10. Individual motile CD4+ T cells can participate in efficient multi-killing through conjugation to multiple tumor cells

    Science.gov (United States)

    Liadi, Ivan; Singh, Harjeet; Romain, Gabrielle; Rey-Villamizar, Nicolas; Merouane, Amine; Adolacion, Jay R T.; Kebriaei, Partow; Huls, Helen; Qiu, Peng; Roysam, Badrinath; Cooper, Laurence J.N.; Varadarajan, Navin

    2015-01-01

    T cells genetically modified to express a CD19-specific chimeric antigen receptor (CAR) for the investigational treatment of B-cell malignancies comprise a heterogeneous population, and their ability to persist and participate in serial killing of tumor cells is a predictor of therapeutic success. We implemented Timelapse Imaging Microscopy In Nanowell Grids (TIMING) to provide direct evidence that CD4+CAR+ T cells (CAR4 cells) can engage in multi-killing via simultaneous conjugation to multiple tumor cells. Comparisons of the CAR4 cells and CD8+CAR+ T cells (CAR8 cells) demonstrate that while CAR4 cells can participate in killing and multi-killing, they do so at slower rates, likely due to the lower Granzyme B content. Significantly, in both sets of T cells, a minor sub-population of individual T cells identified by their high motility, demonstrated efficient killing of single tumor cells. By comparing both the multi-killer and single killer CAR+ T cells it appears that the propensity and kinetics of T-cell apoptosis was modulated by the number of functional conjugations. T cells underwent rapid apoptosis, and at higher frequencies, when conjugated to single tumor cells in isolation and this effect was more pronounced on CAR8 cells. Our results suggest that the ability of CAR+ T cells to participate in multi-killing should be evaluated in the context of their ability to resist activation induced cell death (AICD). We anticipate that TIMING may be utilized to rapidly determine the potency of T-cell populations and may facilitate the design and manufacture of next-generation CAR+ T cells with improved efficacy. PMID:25711538

  11. Multiple Modes of Communication between Neurons and Oligodendrocyte Precursor Cells.

    Science.gov (United States)

    Maldonado, Paloma P; Angulo, María Cecilia

    2015-06-01

    The surprising discovery of bona fide synapses between neurons and oligodendrocytes precursor cells (OPCs) 15 years ago placed these progenitors as real partners of neurons in the CNS. The role of these synapses has not been established yet, but a main hypothesis is that neuron-OPC synaptic activity is a signaling pathway controlling OPC proliferation/differentiation, influencing the myelination process. However, new evidences describing non-synaptic mechanisms of communication between neurons and OPCs have revealed that neuron-OPC interactions are more complex than expected. The activation of extrasynaptic receptors by ambient neurotransmitter or local spillover and the ability of OPCs to sense neuronal activity through a potassium channel suggest that distinct modes of communication mediate different functions of OPCs in the CNS. This review discusses different mechanisms used by OPCs to interact with neurons and their potential roles during postnatal development and in brain disorders. © The Author(s) 2014.

  12. T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

    Science.gov (United States)

    van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

    2018-05-01

    Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4

  13. Multiple co morbid conditions in patient with Mast Cell Activation Syndrome

    Science.gov (United States)

    2017-10-26

    conditions in patient \\\\·ith Mast Cell Activation Syndron1e Sb. GRANT NUMBER Sc. PROGRAM.ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER Maj Sofia...13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple co-n1orhid conditions in patient \\Vith Mast Cell Activation Syndrotne Sofia M. Szari.MD. and James...Defense. !NTR()D{JCT!ON: Mast cell activation disorders {MCAD) have been associated \\Vilh Connective Tissue Disorders (CTD) and orthostatic

  14. Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration

    OpenAIRE

    Nabissi, Massimo; Morelli, Maria Beatrice; Offidani, Massimo; Amantini, Consuelo; Gentili, Silvia; Soriani, Alessandra; Cardinali, Claudio; Leoni, Pietro; Santoni, Giorgio

    2016-01-01

    Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with ?9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggest...

  15. Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

    Science.gov (United States)

    Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

    2017-07-01

    Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Nodal methods for problems in fluid mechanics and neutron transport

    International Nuclear Information System (INIS)

    Azmy, Y.Y.

    1985-01-01

    A new high-accuracy, coarse-mesh, nodal integral approach is developed for the efficient numerical solution of linear partial differential equations. It is shown that various special cases of this general nodal integral approach correspond to several high efficiency nodal methods developed recently for the numerical solution of neutron diffusion and neutron transport problems. The new approach is extended to the nonlinear Navier-Stokes equations of fluid mechanics; its extension to these equations leads to a new computational method, the nodal integral method which is implemented for the numerical solution of these equations. Application to several test problems demonstrates the superior computational efficiency of this new method over previously developed methods. The solutions obtained for several driven cavity problems are compared with the available experimental data and are shown to be in very good agreement with experiment. Additional comparisons also show that the coarse-mesh, nodal integral method results agree very well with the results of definitive ultra-fine-mesh, finite-difference calculations for the driven cavity problem up to fairly high Reynolds numbers

  17. Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad

    2006-01-01

    OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12 healthy controls by flow cytometry in CD4+ and CD8+ T...... cells expressing CCR5 and CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas expression in activated CD4+ CCR5+ T cells might contribute to disease pathogenesis by prolonging cell survival and favoring...

  18. A critical examination of the numerology of antigen-binding cells: evidence for multiple receptor specificities on single cells.

    Science.gov (United States)

    Miller, A

    1977-01-01

    The data available from other laboratories as well as our own on the frequency of cells recognizing major histocompatibility antigens or conventional protein and hapten antigens is critically evaluated. The frequency of specific binding for a large number of antigens is sufficiently high to support the idea that at least part of the antigen-binding cell population must have multiple specificities. Our results suggest that these multiple specific cells result from single cells synthesizing and displaying as many as 50-100 species of receptor, each at a frequency of 10(4) per cell. A model involving gene expansion of constant-region genes is suggested and some auxilliary evidence consistent with such C-gene expansion is presented.

  19. Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.

    2015-01-01

    Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...... for disseminated disease. Methods: From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse......, compared with patients treated with only orchiectomy, had an increased risk for a second cancer (hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.5), major cardiovascular disease (HR, 1.9; 95% CI, 1.0 to 3.3), pulmonary disease (HR, 2.0; 95% CI, 1.0 to 3.8), GI disease (HR, 7.3; 95% CI, 3.6 to 14.8), renal...

  20. Dystroglycan versatility in cell adhesion: a tale of multiple motifs

    Directory of Open Access Journals (Sweden)

    Winder Steve J

    2010-02-01

    Full Text Available Abstract Dystroglycan is a ubiquitously expressed heterodimeric adhesion receptor. The extracellular α-subunit makes connections with a number of laminin G domain ligands including laminins, agrin and perlecan in the extracellular matrix and the transmembrane β-subunit makes connections to the actin filament network via cytoskeletal linkers including dystrophin, utrophin, ezrin and plectin, depending on context. Originally discovered as part of the dystrophin glycoprotein complex of skeletal muscle, dystroglycan is an important adhesion molecule and signalling scaffold in a multitude of cell types and tissues and is involved in several diseases. Dystroglycan has emerged as a multifunctional adhesion platform with many interacting partners associating with its short unstructured cytoplasmic domain. Two particular hotspots are the cytoplasmic juxtamembrane region and at the very carboxy terminus of dystroglycan. Regions which between them have several overlapping functions: in the juxtamembrane region; a nuclear localisation signal, ezrin/radixin/moesin protein, rapsyn and ERK MAP Kinase binding function, and at the C terminus a regulatory tyrosine governing WW, SH2 and SH3 domain interactions. We will discuss the binding partners for these motifs and how their interactions and regulation can modulate the involvement of dystroglycan in a range of different adhesion structures and functions depending on context. Thus dystroglycan presents as a multifunctional scaffold involved in adhesion and adhesion-mediated signalling with its functions under exquisite spatio-temporal regulation.

  1. POOR HEMOPOIETIC STEM CELL MOBILIZERS IN MULTIPLE MYELOMA : A SINGLE INSTITUTION EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Guillermo Jose Ruiz-Delgado

    2010-06-01

    Full Text Available In a single institution, in a group of 28 myeloma patients deemed eligible for autologous transplant, stem cell mobilization was attempted using filgrastim: 26 individuals were given 31 autografts employing 1-4 (median three apheresis sessions, to obtain a target stem cell dose of 1 x 106 CD34 viable cells / Kg of the recipient. The median number of grafted CD34 cells was 7.56 x 106  / Kg of the recipient; the range being 0.92 to 14.8.  By defining as poor mobilizers individuals in which a cell collection of 1 x 106 CD34 viable cells / Kg was better (80% at 80 months than those grafted with < 1 x 106 CD34 viable cells / Kg (67% at 76 months. Methods to improve stem cell mobilization are needed and may result in obtaining better results when autografting multiple myeloma patients.

  2. A computational study of nodal-based tetrahedral element behavior.

    Energy Technology Data Exchange (ETDEWEB)

    Gullerud, Arne S.

    2010-09-01

    This report explores the behavior of nodal-based tetrahedral elements on six sample problems, and compares their solution to that of a corresponding hexahedral mesh. The problems demonstrate that while certain aspects of the solution field for the nodal-based tetrahedrons provide good quality results, the pressure field tends to be of poor quality. Results appear to be strongly affected by the connectivity of the tetrahedral elements. Simulations that rely on the pressure field, such as those which use material models that are dependent on the pressure (e.g. equation-of-state models), can generate erroneous results. Remeshing can also be strongly affected by these issues. The nodal-based test elements as they currently stand need to be used with caution to ensure that their numerical deficiencies do not adversely affect critical values of interest.

  3. A theoretical study on a convergence problem of nodal methods

    Energy Technology Data Exchange (ETDEWEB)

    Shaohong, Z.; Ziyong, L. [Shanghai Jiao Tong Univ., 1954 Hua Shan Road, Shanghai, 200030 (China); Chao, Y. A. [Westinghouse Electric Company, P. O. Box 355, Pittsburgh, PA 15230-0355 (United States)

    2006-07-01

    The effectiveness of modern nodal methods is largely due to its use of the information from the analytical flux solution inside a homogeneous node. As a result, the nodal coupling coefficients depend explicitly or implicitly on the evolving Eigen-value of a problem during its solution iteration process. This poses an inherently non-linear matrix Eigen-value iteration problem. This paper points out analytically that, whenever the half wave length of an evolving node interior analytic solution becomes smaller than the size of that node, this non-linear iteration problem can become inherently unstable and theoretically can always be non-convergent or converge to higher order harmonics. This phenomenon is confirmed, demonstrated and analyzed via the simplest 1-D problem solved by the simplest analytic nodal method, the Analytic Coarse Mesh Finite Difference (ACMFD, [1]) method. (authors)

  4. Super-nodal methods for space-time kinetics

    Science.gov (United States)

    Mertyurek, Ugur

    The purpose of this research has been to develop an advanced Super-Nodal method to reduce the run time of 3-D core neutronics models, such as in the NESTLE reactor core simulator and FORMOSA nuclear fuel management optimization codes. Computational performance of the neutronics model is increased by reducing the number of spatial nodes used in the core modeling. However, as the number of spatial nodes decreases, the error in the solution increases. The Super-Nodal method reduces the error associated with the use of coarse nodes in the analyses by providing a new set of cross sections and ADFs (Assembly Discontinuity Factors) for the new nodalization. These so called homogenization parameters are obtained by employing consistent collapsing technique. During this research a new type of singularity, namely "fundamental mode singularity", is addressed in the ANM (Analytical Nodal Method) solution. The "Coordinate Shifting" approach is developed as a method to address this singularity. Also, the "Buckling Shifting" approach is developed as an alternative and more accurate method to address the zero buckling singularity, which is a more common and well known singularity problem in the ANM solution. In the course of addressing the treatment of these singularities, an effort was made to provide better and more robust results from the Super-Nodal method by developing several new methods for determining the transverse leakage and collapsed diffusion coefficient, which generally are the two main approximations in the ANM methodology. Unfortunately, the proposed new transverse leakage and diffusion coefficient approximations failed to provide a consistent improvement to the current methodology. However, improvement in the Super-Nodal solution is achieved by updating the homogenization parameters at several time points during a transient. The update is achieved by employing a refinement technique similar to pin-power reconstruction. A simple error analysis based on the relative

  5. A comparison of Nodal methods in neutron diffusion calculations

    Energy Technology Data Exchange (ETDEWEB)

    Tavron, Barak [Israel Electric Company, Haifa (Israel) Nuclear Engineering Dept. Research and Development Div.

    1996-12-01

    The nuclear engineering department at IEC uses in the reactor analysis three neutron diffusion codes based on nodal methods. The codes, GNOMERl, ADMARC2 and NOXER3 solve the neutron diffusion equation to obtain flux and power distributions in the core. The resulting flux distributions are used for the furl cycle analysis and for fuel reload optimization. This work presents a comparison of the various nodal methods employed in the above codes. Nodal methods (also called Coarse-mesh methods) have been designed to solve problems that contain relatively coarse areas of homogeneous composition. In the nodal method parts of the equation that present the state in the homogeneous area are solved analytically while, according to various assumptions and continuity requirements, a general solution is sought out. Thus efficiency of the method for this kind of problems, is very high compared with the finite element and finite difference methods. On the other hand, using this method one can get only approximate information about the node vicinity (or coarse-mesh area, usually a feel assembly of a 20 cm size). These characteristics of the nodal method make it suitable for feel cycle analysis and reload optimization. This analysis requires many subsequent calculations of the flux and power distributions for the feel assemblies while there is no need for detailed distribution within the assembly. For obtaining detailed distribution within the assembly methods of power reconstruction may be applied. However homogenization of feel assembly properties, required for the nodal method, may cause difficulties when applied to fuel assemblies with many absorber rods, due to exciting strong neutron properties heterogeneity within the assembly. (author).

  6. Nodal Control and Surgical Salvage after Primary Radiotherapy in 1,782 Patients with Laryngeal and Pharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Vendelbo Johansen, Lars; Grau, Cai; Overgaard, Jens

    2004-01-01

    The purpose of this study was to evaluate the ultimate neck control after primary radiotherapy and surgical salvage in laryngeal and pharyngeal cancer patients. Some 1,782 consecutive patients with squamous cell carcinoma were treated by radiotherapy. At presentation 26% of the patients had metastatic lymph nodes. A total of 298 primary or secondary nodal recurrences were seen, 159 were treated, and 53 (∼18%) were controlled. Isolated N-recurrence was fatal in 2.7% (36/1,324) of the N0 patients. Univariate actuarial analysis of nodal control demonstrated that the region of origin, T-classification, T-size, N-classification, tumor stage, differentiation, hemoglobin, and radiation time were significant prognostic factors. In a Cox analysis the independent significant parameters were gender, region of origin, N-classification, and differentiation. The conclusions were that in patients with nodal recurrence a little over half were treated and of these a third of the nodal recurrences were controlled. Significant prognostic factors in multivariate analysis were gender, region of origin, N-classification, and tumor differentiation

  7. Improvement of neutron kinetics module in TRAC-BF1code: one-dimensional nodal collocation method

    Energy Technology Data Exchange (ETDEWEB)

    Jambrina, Ana; Barrachina, Teresa; Miro, Rafael; Verdu, Gumersindo, E-mail: ajambrina@iqn.upv.es, E-mail: tbarrachina@iqn.upv.es, E-mail: rmiro@iqn.upv.es, E-mail: gverdu@iqn.upv.es [Universidade Politecnica de Valencia (UPV), Valencia (Spain); Soler, Amparo, E-mail: asoler@iberdrola.es [SEA Propulsion S.L., Madrid (Spain); Concejal, Alberto, E-mail: acbe@iberdrola.es [Iberdrola Ingenieria y Construcion S.A.U., Madrid (Spain)

    2013-07-01

    The TRAC-BF1 one-dimensional kinetic model is a formulation of the neutron diffusion equation in the two energy groups' approximation, based on the analytical nodal method (ANM). The advantage compared with a zero-dimensional kinetic model is that the axial power profile may vary with time due to thermal-hydraulic parameter changes and/or actions of the control systems but at has the disadvantages that in unusual situations it fails to converge. The nodal collocation method developed for the neutron diffusion equation and applied to the kinetics resolution of TRAC-BF1 thermal-hydraulics, is an adaptation of the traditional collocation methods for the discretization of partial differential equations, based on the development of the solution as a linear combination of analytical functions. It has chosen to use a nodal collocation method based on a development of Legendre polynomials of neutron fluxes in each cell. The qualification is carried out by the analysis of the turbine trip transient from the NEA benchmark in Peach Bottom NPP using both the original 1D kinetics implemented in TRAC-BF1 and the 1D nodal collocation method. (author)

  8. Statistics and methodology of multiple cell upset characterization under heavy ion irradiation

    International Nuclear Information System (INIS)

    Zebrev, G.I.; Gorbunov, M.S.; Useinov, R.G.; Emeliyanov, V.V.; Ozerov, A.I.; Anashin, V.S.; Kozyukov, A.E.; Zemtsov, K.S.

    2015-01-01

    Mean and partial cross-section concepts and their connections to multiplicity and statistics of multiple cell upsets (MCUs) in highly-scaled digital memories are introduced and discussed. The important role of the experimental determination of the upset statistics is emphasized. It was found that MCU may lead to quasi-linear dependence of cross-sections on linear energy transfer (LET). A new form of function for interpolation of mean cross-section dependences on LET has been proposed

  9. Nodal spectrum method for solving neutron diffusion equation

    International Nuclear Information System (INIS)

    Sanchez, D.; Garcia, C. R.; Barros, R. C. de; Milian, D.E.

    1999-01-01

    Presented here is a new numerical nodal method for solving static multidimensional neutron diffusion equation in rectangular geometry. Our method is based on a spectral analysis of the nodal diffusion equations. These equations are obtained by integrating the diffusion equation in X, Y directions and then considering flat approximations for the current. These flat approximations are the only approximations that are considered in this method, as a result the numerical solutions are completely free from truncation errors. We show numerical results to illustrate the methods accuracy for coarse mesh calculations

  10. Oddness of least energy nodal solutions on radial domains

    Directory of Open Access Journals (Sweden)

    Christopher Grumiau

    2010-07-01

    Full Text Available In this article, we consider the Lane-Emden problem $$displaylines{ Delta u(x + |{u(x}mathclose|^{p-2}u(x=0, quad hbox{for } xinOmega,cr u(x=0, quad hbox{for } xinpartialOmega, }$$ where $2 < p < 2^{*}$ and $Omega$ is a ball or an annulus in $mathbb{R}^{N}$, $Ngeq 2$. We show that, for p close to 2, least energy nodal solutions are odd with respect to an hyperplane -- which is their nodal surface. The proof ingredients are a constrained implicit function theorem and the fact that the second eigenvalue is simple up to rotations.

  11. Development and validation of a nodal code for core calculation

    International Nuclear Information System (INIS)

    Nowakowski, Pedro Mariano

    2004-01-01

    The code RHENO solves the multigroup three-dimensional diffusion equation using a nodal method of polynomial expansion.A comparative study has been made between this code and present internationals nodal diffusion codes, resulting that the RHENO is up to date.The RHENO has been integrated to a calculation line and has been extend to make burnup calculations.Two methods for pin power reconstruction were developed: modulation and imbedded. The modulation method has been implemented in a program, while the implementation of the imbedded method will be concluded shortly.The validation carried out (that includes experimental data of a MPR) show very good results and calculation efficiency

  12. Nodal algorithm derived from a new variational principle

    International Nuclear Information System (INIS)

    Watson, Fernando V.

    1995-01-01

    As a by-product of the research being carried on by the author on methods of recovering pin power distribution of PWR cores, a nodal algorithm based on a modified variational principle for the two group diffusion equations has been obtained. The main feature of the new algorithm is the low dimensionality achieved by the reduction of the original diffusion equations to a system of algebraic Eigen equations involving the average sources only, instead of sources and interface group currents used in conventional nodal methods. The advantage of this procedure is discussed and results generated by the new algorithm and by a finite difference code are compared. (author). 2 refs, 7 tabs

  13. Nodal approximations in space and time for neutron kinetics

    International Nuclear Information System (INIS)

    Grossman, L.M.; Hennart, J.P.

    2005-01-01

    A general formalism is described of the nodal type in time and space for the neutron kinetics equations. In space, several nodal methods are given of the Raviart-Thomas type (RT0 and RT1), of the Brezzi-Douglas-Marini type (BDM0 and BDM1) and of the Brezzi-Douglas-Fortin-Marini type (BDFM 1). In time, polynomial and analytical approximations are derived. In the analytical case, they are based on the inclusion of an exponential term in the basis function. They can be continuous or discontinuous in time, leading in particular to the well-known Crank-Nicolson, Backward Euler and θ schemes

  14. Regional Nodal Irradiation in Early-Stage Breast Cancer.

    Science.gov (United States)

    Whelan, Timothy J; Olivotto, Ivo A; Parulekar, Wendy R; Ackerman, Ida; Chua, Boon H; Nabid, Abdenour; Vallis, Katherine A; White, Julia R; Rousseau, Pierre; Fortin, Andre; Pierce, Lori J; Manchul, Lee; Chafe, Susan; Nolan, Maureen C; Craighead, Peter; Bowen, Julie; McCready, David R; Pritchard, Kathleen I; Gelmon, Karen; Murray, Yvonne; Chapman, Judy-Anne W; Chen, Bingshu E; Levine, Mark N

    2015-07-23

    Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

  15. Killing multiple myeloma cells with the small molecule 3-bromopyruvate: implications for therapy.

    Science.gov (United States)

    Majkowska-Skrobek, Grażyna; Augustyniak, Daria; Lis, Paweł; Bartkowiak, Anna; Gonchar, Mykhailo; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

    2014-07-01

    The small molecule 3-bromopyruvate (3-BP), which has emerged recently as the first member of a new class of potent anticancer agents, was tested for its capacity to kill multiple myeloma (MM) cancer cells. Human MM cells (RPMI 8226) begin to lose viability significantly within 8 h of incubation in the presence of 3-BP. The Km (0.3 mmol/l) for intracellular accumulation of 3-BP in MM cells is 24 times lower than that in control cells (7.2 mmol/l). Therefore, the uptake of 3-BP by MM cells is significantly higher than that by peripheral blood mononuclear cells. Further, the IC50 values for human MM cells and control peripheral blood mononuclear cells are 24 and 58 µmol/l, respectively. Therefore, specificity and selectivity of 3-BP toward MM cancer cells are evident on the basis of the above. In MM cells the transcription levels of the gene encoding the monocarboxylate transporter MCT1 is significantly amplified compared with control cells. The level of intracellular ATP in MM cells decreases by over 90% within 1 h after addition of 100 µmol/l 3-BP. The cytotoxicity of 3-BP, exemplified by a marked decrease in viability of MM cells, is potentiated by the inhibitor of glutathione synthesis buthionine sulfoximine. In addition, the lack of mutagenicity and its superior capacity relative to Glivec to kill MM cancer cells are presented in this study.

  16. Coordinated learning of grid cell and place cell spatial and temporal properties: multiple scales, attention and oscillations.

    Science.gov (United States)

    Grossberg, Stephen; Pilly, Praveen K

    2014-02-05

    A neural model proposes how entorhinal grid cells and hippocampal place cells may develop as spatial categories in a hierarchy of self-organizing maps (SOMs). The model responds to realistic rat navigational trajectories by learning both grid cells with hexagonal grid firing fields of multiple spatial scales, and place cells with one or more firing fields, that match neurophysiological data about their development in juvenile rats. Both grid and place cells can develop by detecting, learning and remembering the most frequent and energetic co-occurrences of their inputs. The model's parsimonious properties include: similar ring attractor mechanisms process linear and angular path integration inputs that drive map learning; the same SOM mechanisms can learn grid cell and place cell receptive fields; and the learning of the dorsoventral organization of multiple spatial scale modules through medial entorhinal cortex to hippocampus (HC) may use mechanisms homologous to those for temporal learning through lateral entorhinal cortex to HC ('neural relativity'). The model clarifies how top-down HC-to-entorhinal attentional mechanisms may stabilize map learning, simulates how hippocampal inactivation may disrupt grid cells, and explains data about theta, beta and gamma oscillations. The article also compares the three main types of grid cell models in the light of recent data.

  17. Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

    Institute of Scientific and Technical Information of China (English)

    Akira Hokama; Nobuyuki Takasu; Jiro Fujita; Takeaki Tomoyose; Yu-ichi Yamamoto; Takako Watanabe; Tetsuo Hirata; Fukunori Kinjo; Seiya Kato; Koichi Ohshima; Hiroshi Uezato

    2008-01-01

    Multiple lymphomatous polyposis (HLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL is reviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

  18. CD4 T cell activation and disease activity at onset of multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, J; Langkilde, Annika Reynberg; Fenst, C

    2004-01-01

    We studied CD4 T cell activation in patients with clinically isolated syndromes (CIS) suggesting an initial attack of multiple sclerosis. The percentage of blood CD26+ CD4 T cells was increased in these patients, and correlated with magnetic resonance imaging disease activity and clinical disease...... severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states...

  19. Concept of multiple-cell cavity for axion dark matter search

    Science.gov (United States)

    Jeong, Junu; Youn, SungWoo; Ahn, Saebyeok; Kim, Jihn E.; Semertzidis, Yannis K.

    2018-02-01

    In cavity-based axion dark matter search experiments exploring high mass regions, multiple-cavity design is under consideration as a method to increase the detection volume within a given magnet bore. We introduce a new idea, referred to as a multiple-cell cavity, which provides various benefits including a larger detection volume, simpler experimental setup, and easier phase-matching mechanism. We present the characteristics of this concept and demonstrate the experimental feasibility with an example of a double-cell cavity.

  20. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Borsi, Enrica, E-mail: enrica.borsi2@unibo.it [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy); Perrone, Giulia [Fondazione IRCCS Istituto Nazionale dei Tumori, Hematology Department, Via Venezian 1, 20133 Milano (Italy); Terragna, Carolina; Martello, Marina; Zamagni, Elena; Tacchetti, Paola; Pantani, Lucia; Brioli, Annamaria; Dico, Angela Flores; Zannetti, Beatrice Anna; Rocchi, Serena; Cavo, Michele [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy)

    2014-11-01

    Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma.

  1. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology.

    Science.gov (United States)

    Xu, Tao; Zhao, Weixin; Zhu, Jian-Ming; Albanna, Mohammad Z; Yoo, James J; Atala, Anthony

    2013-01-01

    This study was designed to develop a versatile method for fabricating complex and heterogeneous three-dimensional (3D) tissue constructs using simultaneous ink-jetting of multiple cell types. Human amniotic fluid-derived stem cells (hAFSCs), canine smooth muscle cells (dSMCs), and bovine aortic endothelial cells (bECs), were separately mixed with ionic cross-linker calcium chloride (CaCl(2)), loaded into separate ink cartridges and printed using a modified thermal inkjet printer. The three cell types were delivered layer-by-layer to pre-determined locations in a sodium alginate-collagen composite located in a chamber under the printer. The reaction between CaCl(2) and sodium alginate resulted in a rapid formation of a solid composite gel and the printed cells were anchored in designated areas within the gel. The printing process was repeated for several cycles leading to a complex 3D multi-cell hybrid construct. The biological functions of the 3D printed constructs were evaluated in vitro and in vivo. Each of the printed cell types maintained their viability and normal proliferation rates, phenotypic expression, and physiological functions within the heterogeneous constructs. The bioprinted constructs were able to survive and mature into functional tissues with adequate vascularization in vivo. These findings demonstrate the feasibility of fabricating complex heterogeneous tissue constructs containing multiple cell types using inkjet printing technology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    International Nuclear Information System (INIS)

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-01-01

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

  3. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  4. Production of Multiple Growth Factors by a Newly Established Human Thyroid Carcinoma Cell Line

    Science.gov (United States)

    Yoshida, Yataro; Ohashi, Kensaku; Sano, Emiko; Kobayashi, Hisataka; Endo, Keigo; Naruto, Masanobu; Nakamura, Toru

    1992-01-01

    A multiple growth factor‐producing tumor cell line (NIM‐1) was newly established from a patient with thyroid cancer and remarkable neutrophilia. NIM‐1 cells also caused severe neutrophilia in nude mice bearing tumors. NIM‐1‐conditioned medium (NIM‐1CM) contained activities that supported not only granulocyte, macrophage and eosinophil colony formation of human bone marrow cells but also the growth of colony‐stimulating factor (CSF)‐dependent cell lines, NFS60‐KX and TF‐1. Northern blot hybridization analysis revealed the constitutive expression of granulocyte‐CSF (G‐CSF), granulocyte/macrophage‐CSF (GM‐CSF) and interleukin(IL)‐6 mRNAs in NIM‐1 cells. Enzyme‐linked immunosorbent assays (ELISA) using NIM‐1CM also confirmed the production of IL‐la and a small amount of IL‐1β besides G‐CSF, GM‐CSF and IL‐6 in NIM‐1 cells. In addition, unexpected production of IL‐11 in NIM‐1 cells was detected by northern blot hybridization analysis and by bioassay using an IL‐11‐dependent cell line. Therefore, NIM‐1 cell line is shown to produce multiple cytokines including potentially megakaryopoietic growth factors such as GM‐CSF, IL‐6 and IL‐11. PMID:1372885

  5. Elaboration of a nodal method to solve the steady state multigroup diffusion equation. Study and use of the multigroup diffusion code DAHRA

    International Nuclear Information System (INIS)

    Halilou, A.; Lounici, A.

    1981-01-01

    The subject is divided in two parts: In the first part a nodal method has been worked out to solve the steady state multigroup diffusion equation. This method belongs to the same set of nodal methods currently used to calculate the exact fission powers and neutron fluxes in a very short computing time. It has been tested on a two dimensional idealized reactors. The effective multiplication factor and the fission powers for each fuel element have been calculated. The second part consists in studying and mastering the multigroup diffusion code DAHRA - a reduced version of DIANE - a two dimensional code using finite difference method

  6. Systematic identification of yeast cell cycle transcription factors using multiple data sources

    Directory of Open Access Journals (Sweden)

    Li Wen-Hsiung

    2008-12-01

    Full Text Available Abstract Background Eukaryotic cell cycle is a complex process and is precisely regulated at many levels. Many genes specific to the cell cycle are regulated transcriptionally and are expressed just before they are needed. To understand the cell cycle process, it is important to identify the cell cycle transcription factors (TFs that regulate the expression of cell cycle-regulated genes. Results We developed a method to identify cell cycle TFs in yeast by integrating current ChIP-chip, mutant, transcription factor binding site (TFBS, and cell cycle gene expression data. We identified 17 cell cycle TFs, 12 of which are known cell cycle TFs, while the remaining five (Ash1, Rlm1, Ste12, Stp1, Tec1 are putative novel cell cycle TFs. For each cell cycle TF, we assigned specific cell cycle phases in which the TF functions and identified the time lag for the TF to exert regulatory effects on its target genes. We also identified 178 novel cell cycle-regulated genes, among which 59 have unknown functions, but they may now be annotated as cell cycle-regulated genes. Most of our predictions are supported by previous experimental or computational studies. Furthermore, a high confidence TF-gene regulatory matrix is derived as a byproduct of our method. Each TF-gene regulatory relationship in this matrix is supported by at least three data sources: gene expression, TFBS, and ChIP-chip or/and mutant data. We show that our method performs better than four existing methods for identifying yeast cell cycle TFs. Finally, an application of our method to different cell cycle gene expression datasets suggests that our method is robust. Conclusion Our method is effective for identifying yeast cell cycle TFs and cell cycle-regulated genes. Many of our predictions are validated by the literature. Our study shows that integrating multiple data sources is a powerful approach to studying complex biological systems.

  7. Analysis of multiple types of human cells subsequent to bioprinting with electrospraying technology.

    Science.gov (United States)

    Xin, Yu; Chai, Gang; Zhang, Ting; Wang, Xiangsheng; Qu, Miao; Tan, Andy; Bogari, Melia; Zhu, Ming; Lin, Li; Hu, Qingxi; Liu, Yuanyuan; Zhang, Yan

    2016-12-01

    The aim of the present study was to investigate bioprinting with electrospraying technology using multiple types of human cell suspensions as bio-ink, in order to lay the initial foundations for the application of the bioprinting technology in tissue engineering. In the current study, six types of human cells were selected and cultured, including human fibroblasts, human adipose-derived stem cells (hADSCs), human periodontal ligament cells (HPDLCs), adult human retinal pigment epithelial cells (ARPE-19), human umbilical vascular endothelial cells (HUVECs) and human gastric epithelial cell line (GES-1). Each cell type was divided into two groups, the experimental and control group. All the experimental group cells were electrosprayed using an electrospraying printer (voltage, 15 kV; flow rate, 150 µl/min) and collected in a petri dish placed 15 cm away from the needle (needle diameter, 0.5 mm). Subsequently, cell viability was detected by flow cytometry with a Live/Dead Viability kit. In addition, the cell morphological characteristics were observed with a phase-contrast microscope after 6 h of culturing in order to obtain adherent cells, while cell proliferation was analyzed using a Cell Counting Kit-8 assay. The control groups, without printing, were subjected to the same procedures as the experimental groups. The results of the cell viability and proliferation assays indicated a statistically significant difference after printing between the experiments and control groups only for the hADSCs (P0.05). In addition, there were no observable differences between all experimental and the control groups at any examined time point in the terms of cell morphological characteristics. In conclusion, bioprinting based on electrospraying technology demonstrated no distinct negative effect on cell vitality, proliferation and morphology in the present study, and thus the application of this novel technology to cell printing may provide a promising method in tissue engineering.

  8. A Case of Mature Natural Killer-Cell Neoplasm Manifesting Multiple Choroidal Lesions: Primary Intraocular Natural Killer-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Yoshiaki Tagawa

    2015-11-01

    Full Text Available Purpose: Natural killer (NK cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. It usually emerges from the nose and appears in the ocular tissue as a metastasis. Herein, we describe a case of NK-cell neoplasm in which the eye was considered to be the primary organ. Case: A 50-year-old female displayed bilateral anterior chamber cells, vitreous opacity, bullous retinal detachment, and multiple white choroidal mass lesions. Although malignant lymphoma or metastatic tumor was suspected, various systemic examinations failed to detect any positive results. A vitrectomy was performed OS; however, histocytological analyses from the vitreous sample showed no definite evidence of malignancy, and IL-10 concentration was low. Enlarged choroidal masses were fused together. Three weeks after the first visit, the patient suddenly developed an attack of fever, night sweat, and hepatic dysfunction, and 5 days later, she passed away due to multiple organ failure. Immunohistochemisty and in situ hybridization revealed the presence of atypical cells positive for CD3, CD56, and Epstein-Barr virus-encoded RNAs, resulting in the diagnosis of NK-cell neoplasm. With the characteristic clinical course, we concluded that this neoplasm was a primary intraocular NK-cell lymphoma. Conclusions: This is the first report to describe primary intraocular NK-cell neoplasm. When we encounter atypical choroidal lesions, we should consider the possibility of NK-cell lymphoma, even though it is a rare disease.

  9. Extension of the linear nodal method to large concrete building calculations

    International Nuclear Information System (INIS)

    Childs, R.L.; Rhoades, W.A.

    1985-01-01

    The implementation of the linear nodal method in the TORT code is described, and the results of a mesh refinement study to test the effectiveness of the linear nodal and weighted diamond difference methods available in TORT are presented

  10. High Throughput Single-cell and Multiple-cell Micro-encapsulation

    OpenAIRE

    Lagus, Todd P.; Edd, Jon F.

    2012-01-01

    Microfluidic encapsulation methods have been previously utilized to capture cells in picoliter-scale aqueous, monodisperse drops, providing confinement from a bulk fluid environment with applications in high throughput screening, cytometry, and mass spectrometry. We describe a method to not only encapsulate single cells, but to repeatedly capture a set number of cells (here we demonstrate one- and two-cell encapsulation) to study both isolation and the interactions between cells in groups of ...

  11. SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture.

    Science.gov (United States)

    Arhoma, A; Chantry, A D; Haywood-Small, S L; Cross, N A

    2017-11-15

    Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell

  12. Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells

    OpenAIRE

    Urue?a, Claudia; Cifuentes, Claudia; Casta?eda, Diana; Arango, Amparo; Kaur, Punit; Asea, Alexzander; Fiorentino, Susana

    2008-01-01

    Abstract Background There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Methods Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], flow cytometry, cytosk...

  13. Effects of Voltage-Gated K+ Channel on Cell Proliferation in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2014-01-01

    Full Text Available Objective. To study the effects and underlying mechanisms of voltage-gated K+ channels on the proliferation of multiple myeloma cells. Methods. RPMI-8226 MM cell line was used for the experiments. Voltage-gated K+ currents and the resting potential were recorded by whole-cell patch-clamp technique. RT-PCR detected Kv channel mRNA expression. Cell viability was analyzed with MTT assay. Cell counting system was employed to monitor cell proliferation. DNA contents and cell volume were analyzed by flow cytometry. Results. Currents recorded in RPMI-8226 cells were confirmed to be voltage-gated K+ channels. A high level of Kv1.3 mRNA was detected but no Kv3.1 mRNA was detected in RPMI-8226 cells. Voltage-gated K+ channel blocker 4-aminopyridine (4-AP (2 mM depolarized the resting potential from −42 ± 1.7 mV to −31.8 ± 2.8 mV (P0.05. Conclusions. In RPMI-8226, voltage-gated K+ channels are involved in proliferation and cell cycle progression its influence on the resting potential and cell volume may be responsible for this process; the inhibitory effect of the voltage-gated K+ channel blocker on RPMI-8226 cell proliferation is a phase-specific event.

  14. Neutron transport in hexagonal reactor cores modeled by trigonal-geometry diffusion and simplified P{sub 3} nodal methods

    Energy Technology Data Exchange (ETDEWEB)

    Duerigen, Susan

    2013-05-15

    The superior advantage of a nodal method for reactor cores with hexagonal fuel assemblies discretized as cells consisting of equilateral triangles is its mesh refinement capability. In this thesis, a diffusion and a simplified P{sub 3} (or SP{sub 3}) neutron transport nodal method are developed based on trigonal geometry. Both models are implemented in the reactor dynamics code DYN3D. As yet, no other well-established nodal core analysis code comprises an SP{sub 3} transport theory model based on trigonal meshes. The development of two methods based on different neutron transport approximations but using identical underlying spatial trigonal discretization allows a profound comparative analysis of both methods with regard to their mathematical derivations, nodal expansion approaches, solution procedures, and their physical performance. The developed nodal approaches can be regarded as a hybrid NEM/AFEN form. They are based on the transverse-integration procedure, which renders them computationally efficient, and they use a combination of polynomial and exponential functions to represent the neutron flux moments of the SP{sub 3} and diffusion equations, which guarantees high accuracy. The SP{sub 3} equations are derived in within-group form thus being of diffusion type. On this basis, the conventional diffusion solver structure can be retained also for the solution of the SP{sub 3} transport problem. The verification analysis provides proof of the methodological reliability of both trigonal DYN3D models. By means of diverse hexagonal academic benchmark and realistic detailed-geometry full-transport-theory problems, the superiority of the SP{sub 3} transport over the diffusion model is demonstrated in cases with pronounced anisotropy effects, which is, e.g., highly relevant to the modeling of fuel assemblies comprising absorber material.

  15. Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis.

    Science.gov (United States)

    Lovato, Laura; Willis, Simon N; Rodig, Scott J; Caron, Tyler; Almendinger, Stefany E; Howell, Owain W; Reynolds, Richard; O'Connor, Kevin C; Hafler, David A

    2011-02-01

    In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.

  16. The Nodal Location of Metastases in Melanoma Sentinel Lymph Nodes

    DEFF Research Database (Denmark)

    Riber-Hansen, Rikke; Nyengaard, Jens; Hamilton-Dutoit, Stephen

    2009-01-01

    BACKGROUND: The design of melanoma sentinel lymph node (SLN) histologic protocols is based on the premise that most metastases are found in the central parts of the nodes, but the evidence for this belief has never been thoroughly tested. METHODS: The nodal location of melanoma metastases in 149...

  17. Real-time control of power systems using nodal prices

    NARCIS (Netherlands)

    Jokic, A.; Lazar, M.; Bosch, van den P.P.J.

    2009-01-01

    This article presents a novel control scheme for achieving optimal power balancing and congestion management in electrical power systems via nodal prices. We develop a dynamic controller that guarantees economically optimal steady-state operation while respecting all line flow constraints in

  18. Topological transport in Dirac nodal-line semimetals

    Science.gov (United States)

    Rui, W. B.; Zhao, Y. X.; Schnyder, Andreas P.

    2018-04-01

    Topological nodal-line semimetals are characterized by one-dimensional Dirac nodal rings that are protected by the combined symmetry of inversion P and time-reversal T . The stability of these Dirac rings is guaranteed by a quantized ±π Berry phase and their low-energy physics is described by a one-parameter family of (2+1)-dimensional quantum field theories exhibiting the parity anomaly. Here we study the Berry-phase supported topological transport of P T -invariant nodal-line semimetals. We find that small inversion breaking allows for an electric-field-induced anomalous transverse current, whose universal component originates from the parity anomaly. Due to this Hall-like current, carriers at opposite sides of the Dirac nodal ring flow to opposite surfaces when an electric field is applied. To detect the topological currents, we propose a dumbbell device, which uses surface states to filter charges based on their momenta. Suggestions for experiments and device applications are discussed.

  19. Hyoid bone chondrosarcoma with cervical nodal metastasis: A case ...

    African Journals Online (AJOL)

    Background: Hyoid bone chondrosarcoma is a very rare condition. This study presents a case report of low-grade chondrosarcoma of hyoid bone with cervical nodal metastasis. The study also presents preoperative radiological investigations, pathological examination and the follow-up of the case. Case presentation: A 42 ...

  20. Note on the nodal line of the p-Laplacian

    Directory of Open Access Journals (Sweden)

    Abdel R. El Amrouss

    2006-09-01

    Full Text Available In this paper, we prove that the length of the nodal line of the eigenfunctions associated to the second eigenvalue of the problem $$ -Delta_p u = lambda ho (x |u|^{p-2}u quad hbox{in } Omega $$ with the Dirichlet conditions is not bounded uniformly with respect to the weight.

  1. A nodal method based on the response-matrix method

    International Nuclear Information System (INIS)

    Cunha Menezes Filho, A. da; Rocamora Junior, F.D.

    1983-02-01

    A nodal approach based on the Response-Matrix method is presented with the purpose of investigating the possibility of mixing two different allocations in the same problem. It is found that the use of allocation of albedo combined with allocation of direct reflection produces good results for homogeneous fast reactor configurations. (Author) [pt

  2. CRY 1AB trangenic cowpea obtained by nodal electroporation ...

    African Journals Online (AJOL)

    Electroporation-mediated genetic transformation was used to introduce Cry 1 Ab insecticidal gene into cowpea. Nodal buds were electroporated in planta with a plasmid carrying the Cry 1Ab and antibiotic resistance npt II genes driven by a 35S CaMV promoter. T1 seeds derived from electroporated branches were selected ...

  3. Multiple Modes of Cell Death Discovered in a Prokaryotic (Cyanobacterial Endosymbiont.

    Directory of Open Access Journals (Sweden)

    Weiwen Zheng

    Full Text Available Programmed cell death (PCD is a genetically-based cell death mechanism with vital roles in eukaryotes. Although there is limited consensus on similar death mode programs in prokaryotes, emerging evidence suggest that PCD events are operative. Here we present cell death events in a cyanobacterium living endophytically in the fern Azolla microphylla, suggestive of PCD. This symbiosis is characterized by some unique traits such as a synchronized development, a vertical transfer of the cyanobacterium between plant generations, and a highly eroding cyanobacterial genome. A combination of methods was used to identify cell death modes in the cyanobacterium. Light- and electron microscopy analyses showed that the proportion of cells undergoing cell death peaked at 53.6% (average 20% of the total cell population, depending on the cell type and host developmental stage. Biochemical markers used for early and late programmed cell death events related to apoptosis (Annexin V-EGFP and TUNEL staining assays, together with visualization of cytoskeleton alterations (FITC-phalloidin staining, showed that all cyanobacterial cell categories were affected by cell death. Transmission electron microscopy revealed four modes of cell death: apoptotic-like, autophagic-like, necrotic-like and autolytic-like. Abiotic stresses further enhanced cell death in a dose and time dependent manner. The data also suggest that dynamic changes in the peptidoglycan cell wall layer and in the cytoskeleton distribution patterns may act as markers for the various cell death modes. The presence of a metacaspase homolog (domain p20 further suggests that the death modes are genetically programmed. It is therefore concluded that multiple, likely genetically programmed, cell death modes exist in cyanobacteria, a finding that may be connected with the evolution of cell death in the plant kingdom.

  4. Multiple Modes of Cell Death Discovered in a Prokaryotic (Cyanobacterial) Endosymbiont

    Science.gov (United States)

    Zheng, Weiwen; Rasmussen, Ulla; Zheng, Siping; Bao, Xiaodong; Chen, Bin; Gao, Yuan; Guan, Xiong; Larsson, John; Bergman, Birgitta

    2013-01-01

    Programmed cell death (PCD) is a genetically-based cell death mechanism with vital roles in eukaryotes. Although there is limited consensus on similar death mode programs in prokaryotes, emerging evidence suggest that PCD events are operative. Here we present cell death events in a cyanobacterium living endophytically in the fern Azolla microphylla, suggestive of PCD. This symbiosis is characterized by some unique traits such as a synchronized development, a vertical transfer of the cyanobacterium between plant generations, and a highly eroding cyanobacterial genome. A combination of methods was used to identify cell death modes in the cyanobacterium. Light- and electron microscopy analyses showed that the proportion of cells undergoing cell death peaked at 53.6% (average 20%) of the total cell population, depending on the cell type and host developmental stage. Biochemical markers used for early and late programmed cell death events related to apoptosis (Annexin V-EGFP and TUNEL staining assays), together with visualization of cytoskeleton alterations (FITC-phalloidin staining), showed that all cyanobacterial cell categories were affected by cell death. Transmission electron microscopy revealed four modes of cell death: apoptotic-like, autophagic-like, necrotic-like and autolytic-like. Abiotic stresses further enhanced cell death in a dose and time dependent manner. The data also suggest that dynamic changes in the peptidoglycan cell wall layer and in the cytoskeleton distribution patterns may act as markers for the various cell death modes. The presence of a metacaspase homolog (domain p20) further suggests that the death modes are genetically programmed. It is therefore concluded that multiple, likely genetically programmed, cell death modes exist in cyanobacteria, a finding that may be connected with the evolution of cell death in the plant kingdom. PMID:23822984

  5. Development of a computer code for neutronic calculations of a hexagonal lattice of nuclear reactor using the flux expansion nodal method

    Directory of Open Access Journals (Sweden)

    Mohammadnia Meysam

    2013-01-01

    Full Text Available The flux expansion nodal method is a suitable method for considering nodalization effects in node corners. In this paper we used this method to solve the intra-nodal flux analytically. Then, a computer code, named MA.CODE, was developed using the C# programming language. The code is capable of reactor core calculations for hexagonal geometries in two energy groups and three dimensions. The MA.CODE imports two group constants from the WIMS code and calculates the effective multiplication factor, thermal and fast neutron flux in three dimensions, power density, reactivity, and the power peaking factor of each fuel assembly. Some of the code's merits are low calculation time and a user friendly interface. MA.CODE results showed good agreement with IAEA benchmarks, i. e. AER-FCM-101 and AER-FCM-001.

  6. Imaging of multiple myeloma and related monoclonal plasma cell diseases. An update

    International Nuclear Information System (INIS)

    Weber, Marc-Andre; Delorme, Stefan; Hillengass, Jens

    2014-01-01

    Multiple myeloma is a hematologic disorder characterized by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. The main symptoms are hypercalcemia, renal impairment, cytopenia/anemia and bone disease - summarized as CRAB-criteria. Symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of hematopoiesis, renal function and mineralized bone. In the last decade the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. Cross sectional imaging like MRI and CT is currently replacing conventional radiological surveys in the initial work-up and follow-up of patients with monoclonal plasma cell diseases. The added value of MRI is to improve initial staging by unraveling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. Furthermore, a complete remission of myeloma confirmed by MRI and CT goes along with a better prognosis compared to a complete response based only on serological parameters.

  7. Yessotoxin as a Tool to Study Induction of Multiple Cell Death Pathways

    Directory of Open Access Journals (Sweden)

    Mónica Suárez Korsnes

    2012-07-01

    Full Text Available This work proposes to use the marine algal toxin yessotoxin (YTX to establish reference model experiments to explore medically valuable effects from induction of multiple cell death pathways. YTX is one of few toxins reported to make such induction. It is a small molecule compound which at low concentrations can induce apoptosis in primary cultures, many types of cells and cell lines. It can also induce a non-apoptotic form of programmed cell death in BC3H1 myoblast cell lines. The present contribution reviews arguments that this type of induction may have principal interest outside this particular example. One principal effect of medical interest may be that cancer cells will not so easily adapt to the synergistic effects from induction of more than one death pathway as compared to induction of only apoptosis.

  8. Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines

    Science.gov (United States)

    Franco, Domenico; Trusso, Sebastiano; Fazio, Enza; Allegra, Alessandro; Musolino, Caterina; Speciale, Antonio; Cimino, Francesco; Saija, Antonella; Neri, Fortunato; Nicolò, Marco S.; Guglielmino, Salvatore P. P.

    2017-12-01

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM.1R and U266/BTZ-R subtypes, resistant to dexamethasone and bortezomib, respectively. Then, micro-Raman spectroscopy provides an easily accurate and noninvasive method for cancer detection for both research and clinical environments. Characteristic peaks, mostly due to different DNA/RNA ratio, nucleic acids, lipids and protein concentrations, allow for discerning the sensitive and resistant subtypes. We also explored principal component analysis (PCA) for resistant cell identification and classification. Sensitive and resistant cells form distinct clusters that can be defined using just two principal components. The identification of drug-resistant cells by confocal micro-Raman spectroscopy is thus proposed as a clinical tool to assess the development of resistance to glucocorticoids and proteasome inhibitors in myeloma cells.

  9. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, Richard W. J.; de Rooij, Martin F. M.; Kocemba, Kinga A.; Reijmers, Rogier M.; de Haan-Kramer, Anneke; Overdijk, Marije B.; Aalders, Linda; Rozemuller, Henk; Martens, Anton C. M.; Bergsagel, P. Leif; Kersten, Marie José; Pals, Steven T.; Spaargaren, Marcel

    2011-01-01

    Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow microenvironment plays

  10. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, R.W.J.; de Rooij, M.F.M.; Kocemba, K.A.; Reijmers, R.M.; de Haan-Kramer, A.; Overdijk, M.B.; Aalders, L.; Rozemuller, H.; Martens, A.C.M.; Bergsagel, P.L.; Kersten, M.J.; Pals, S.T.; Spaargaren, M.

    2011-01-01

    Background Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow

  11. Optimization of carrier multiplication for more effcient solar cells: the case of Sn quantum dots.

    Science.gov (United States)

    Allan, Guy; Delerue, Christophe

    2011-09-27

    We present calculations of impact ionization rates, carrier multiplication yields, and solar-power conversion efficiencies in solar cells based on quantum dots (QDs) of a semimetal, α-Sn. Using these results and previous ones on PbSe and PbS QDs, we discuss a strategy to select QDs with the highest carrier multiplication rate for more efficient solar cells. We suggest using QDs of materials with a close to zero band gap and a high multiplicity of the bands in order to favor the relaxation of photoexcited carriers by impact ionization. Even in that case, the improvement of the maximum solar-power conversion efficiency appears to be a challenging task. © 2011 American Chemical Society

  12. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Science.gov (United States)

    2010-10-01

    ... Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may be... 47 Telecommunication 5 2010-10-01 2010-10-01 false Digital Electronic Message Service Nodal Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY...

  13. PWR in-core nuclear fuel management optimization utilizing nodal (non-linear NEM) generalized perturbation theory

    International Nuclear Information System (INIS)

    Maldonado, G.I.; Turinsky, P.J.; Kropaczek, D.J.

    1993-01-01

    The computational capability of efficiently and accurately evaluate reactor core attributes (i.e., k eff and power distributions as a function of cycle burnup) utilizing a second-order accurate advanced nodal Generalized Perturbation Theory (GPT) model has been developed. The GPT model is derived from the forward non-linear iterative Nodal Expansion Method (NEM) strategy, thereby extending its inherent savings in memory storage and high computational efficiency to also encompass GPT via the preservation of the finite-difference matrix structure. The above development was easily implemented into the existing coarse-mesh finite-difference GPT-based in-core fuel management optimization code FORMOSA-P, thus combining the proven robustness of its adaptive Simulated Annealing (SA) multiple-objective optimization algorithm with a high-fidelity NEM GPT neutronics model to produce a powerful computational tool used to generate families of near-optimum loading patterns for PWRs. (orig.)

  14. Characterization of γδ regulatory T cells from peripheral blood in patients with multiple myeloma

    International Nuclear Information System (INIS)

    Ma, Yongyong; Lei, Huyi; Tan, Jie; Xuan, Li; Wu, Xiuli; Liu, Qifa

    2016-01-01

    γδ regulatory T cells are able to inhibit the activation and function of T cells involved in antigen-specific immune responses. This study aimed to investigate the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in patients diagnosed as multiple myeloma (MM). We measured the levels of γδ T cells, the distribution and clonally amplified TCR Vγ and VδT cells in peripheral blood of healthy donors, patients recently diagnosed with MM, and MM patients in remission cohorts. In addition, we evaluated the ability of γδ regulatory T cells to inhibit the proliferation of CD4+CD25- T cells and detected the expression of immunoregulatory-associated molecules. We found that the levels of γδ regulatory T cells from the peripheral blood in patients of MM were significantly higher than those in healthy donors. Comparison of γδT regulatory cells function in MM and healthy donors showed similarly inhibitory effects on the proliferation of T cells. Additionally, TLR8 expression level increased significantly in MM patients compared to healthy donors, while the expression levels of Foxp3, CD25, CTLA4, GITR, GATA3 and Tbet in MM patients and healthy donors showed no significant difference. Taken together, our study reveals the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in MM patients.

  15. Micropropagation of Dianthus deltoides L. through shoot tip and nodal cuttings culture

    Directory of Open Access Journals (Sweden)

    Marković Marija

    2013-01-01

    Full Text Available Micropropagation (shoot tip and nodal cuttings culture was used for the rapid propagation of the non-invasive, decorative, native plants of maiden pink (Dianthus deltoides L. in order to preserve their genetic diversity. In vitro culture was successfully established on Murashige and Skoog medium (MS using seeds as the initial material. In the shoot multiplication phase, the explants were cultured on MS medium supplemented with different concentrations of 6-benzylaminopurine (BAP and naphthaleneacetic acid (NAA. The highest multiplication rate was achieved on a medium containing 0.1 mgL-1 of BAP and 0.1 mgL-1 of NAA. The rooting was successful on a hormone-free medium (100%, and the highest percentage of microplant acclimatization (97% was recorded in a 4: 1 mixture of peat and sand. [Projekat Ministarstva nauke Republike Srbije, br. TR 31041: Establishment of wood plantations intended for a forestation of Serbia

  16. T-cell libraries allow simple parallel generation of multiple peptide-specific human T-cell clones.

    Science.gov (United States)

    Theaker, Sarah M; Rius, Cristina; Greenshields-Watson, Alexander; Lloyd, Angharad; Trimby, Andrew; Fuller, Anna; Miles, John J; Cole, David K; Peakman, Mark; Sewell, Andrew K; Dolton, Garry

    2016-03-01

    Isolation of peptide-specific T-cell clones is highly desirable for determining the role of T-cells in human disease, as well as for the development of therapies and diagnostics. However, generation of monoclonal T-cells with the required specificity is challenging and time-consuming. Here we describe a library-based strategy for the simple parallel detection and isolation of multiple peptide-specific human T-cell clones from CD8(+) or CD4(+) polyclonal T-cell populations. T-cells were first amplified by CD3/CD28 microbeads in a 96U-well library format, prior to screening for desired peptide recognition. T-cells from peptide-reactive wells were then subjected to cytokine-mediated enrichment followed by single-cell cloning, with the entire process from sample to validated clone taking as little as 6 weeks. Overall, T-cell libraries represent an efficient and relatively rapid tool for the generation of peptide-specific T-cell clones, with applications shown here in infectious disease (Epstein-Barr virus, influenza A, and Ebola virus), autoimmunity (type 1 diabetes) and cancer. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Targeting poly (ADP-ribose polymerase partially contributes to bufalin-induced cell death in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    He Huang

    Full Text Available Despite recent pharmaceutical advancements in therapeutic drugs, multiple myeloma (MM remains an incurable disease. Recently, ploy(ADP-ribose polymerase 1 (PARP1 has been shown as a potentially promising target for MM therapy. A previous report suggested bufalin, a component of traditional Chinese medicine ("Chan Su", might target PARP1. However, this hypothesis has not been verified. We here showed that bufalin could inhibit PARP1 activity in vitro and reduce DNA-damage-induced poly(ADP-ribosylation in MM cells. Molecular docking analysis revealed that the active site of bufalin interaction is within the catalytic domain of PAPR1. Thus, PARP1 is a putative target of bufalin. Furthermore, we showed, for the first time that the proliferation of MM cell lines (NCI-H929, U266, RPMI8226 and MM.1S and primary CD138(+ MM cells could be inhibited by bufalin, mainly via apoptosis and G2-M phase cell cycle arrest. MM cell apoptosis was confirmed by apoptotic cell morphology, Annexin-V positive cells, and the caspase3 activation. We further evaluated the role of PARP1 in bufalin-induced apoptosis, discovering that PARP1 overexpression partially suppressed bufalin-induced cell death. Moreover, bufalin can act as chemosensitizer to enhance the cell growth-inhibitory effects of topotecan, camptothecin, etoposide and vorinostat in MM cells. Collectively, our data suggest that bufalin is a novel PARP1 inhibitor and a potentially promising therapeutic agent against MM alone or in combination with other drugs.

  18. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma.

    Science.gov (United States)

    Mark, Tomer; Stern, Jessica; Furst, Jessica R; Jayabalan, David; Zafar, Faiza; LaRow, April; Pearse, Roger N; Harpel, John; Shore, Tsiporah; Schuster, Michael W; Leonard, John P; Christos, Paul J; Coleman, Morton; Niesvizky, Ruben

    2008-07-01

    A total of 28 treatment-naïve patients with stage II or III multiple myeloma (MM) were treated with the combination of clarithromycin, lenalidomide, and dexamethasone (BiRD). Stem cells were collected following granulocyte-colony stimulating factor (G-CSF) or cyclophosphamide (Cy) plus G-CSF mobilization at maximum response. Sufficient stem cells for 2 autologous stem cell transplants were collected from all patients mobilized with Cy plus G-CSF, versus 33% mobilized with G-CSF alone (P < .0001). The duration of prior lenalidomide therapy did not correlate with success of stem cell harvests (P = .91). In conclusion, Cy can be added to G-CSF for stem cell mobilization to successfully overcome the suppressive effect of prior treatment with lenalidomide.

  19. Gemcitabine radiosensitizes multiple myeloma cells to low let, but not high let, irradiation

    International Nuclear Information System (INIS)

    Supiot, Stephane; Thillays, Francois; Rio, Emmanuel; Gouard, Sebastien; Morgenstern, Alfred; Bruchertseifer, Frank; Mahe, Marc-Andre; Chatal, Jean-Francois; Davodeau, Francois; Cherel, Michel

    2007-01-01

    The radiosensitizing properties of gemcitabine in relation to low Linear Energy Transfer (LET) particles (Cobalt 60) and high-LET particles (alpha-RIT 213 Bi-radiolabeled CHX-DTPA-B-B4) were analyzed. Three multiple myeloma cell lines (LP1, RPMI 8226, U266) were irradiated with or without 10 nM gemcitabine 24 h prior to radiation. Gemcitabine led to radiosensitization of LP1 and U266 cells with low-LET (Radiation Enhancement Ratio: 1.55 and 1.49, respectively) but did not radiosensitize any cell line when combined with high-LET

  20. Multiple growth hormone-binding proteins are expressed on insulin-producing cells

    DEFF Research Database (Denmark)

    Møldrup, A; Billestrup, N; Thorn, N A

    1989-01-01

    The insulin-producing rat islet tumor cell line, RIN-5AH, expresses somatogen binding sites and responds to GH by increased proliferation and insulin production. Affinity cross-linking shows that RIN-5AH cells contain two major GH-binding subunits of Mr 100-130K (110K), which appear to exist as d....... It is concluded that the RIN-5AH cells have multiple GH-binding proteins which may mediate signals for either proliferation and/or insulin production....

  1. Rationale of chemotherapy for Nodal Disease

    International Nuclear Information System (INIS)

    Zwelling, L.A.; Silberman, L.; Estey, E.

    1987-01-01

    Defining biochemical differences between malignant and normal cells or between drug-sensitive and drug-resistant cells may lead to the discovery of pharmacologically exploitable pathways by which to treat human cancer. Systems in which active antineoplastic agents display different cytotoxic effects allow biochemical study of the basis for these differences. The interaction between topoisomerase II and active, anti-neoplastic DNA intercalating agents may be the way these active drugs kill cells. Details of the biochemical mechanisms and their effects on cellular events await precise description, but the principles learned in studies of this unique drug-protein-DNA interaction may be applicable to the treatment of locally advanced and diffusely disseminated human malignancies

  2. Apoptotic effects of non-edible parts of Punica granatum on human multiple myeloma cells.

    Science.gov (United States)

    Kiraz, Yağmur; Neergheen-Bhujun, Vidushi S; Rummun, Nawraj; Baran, Yusuf

    2016-02-01

    Multiple myeloma is of great concern since existing therapies are unable to cure this clinical condition. Alternative therapeutic approaches are mandatory, and the use of plant extracts is considered interesting. Punica granatum and its derived products were suggested as potential anticancer agents due to the presence of bioactive compounds. Thus, polypenolic-rich extracts of the non-edible parts of P. granatum were investigated for their antiproliferative and apoptotic effects on U266 multiple myeloma cells. We demonstrated that there were dose-dependent decreases in the proliferation of U266 cells in response to P. granatum extracts. Also, exposure to the extracts triggered apoptosis with significant increases in loss of mitochondrial membrane potential in U266 cells exposed to the leaves and stem extracts, while the flower extract resulted in slight increases in loss of MMP. These results were confirmed by Annexin-V analysis. These results documented the cytotoxic and apoptotic effects of P. granatum extracts on human U266 multiple myeloma cells via disruption of mitochondrial membrane potential and increasing cell cycle arrest. The data suggest that the extracts can be envisaged in cancer chemoprevention and call for further exploration into the potential application of these plant parts.

  3. PET-CT-Based Auto-Contouring in Non-Small-Cell Lung Cancer Correlates With Pathology and Reduces Interobserver Variability in the Delineation of the Primary Tumor and Involved Nodal Volumes

    International Nuclear Information System (INIS)

    Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth; Buijsen, Jeroen; Wanders, Stofferinus; Hochstenbag, Monique; Suylen, Robert-Jan van; Dekker, Andre; Dehing-Oberije, Cary; Houben, Ruud; Bentzen, Soren M.; Kroonenburgh, Marinus van; Lambin, Philippe; Ruysscher, Dirk de

    2007-01-01

    Purpose: To compare source-to-background ratio (SBR)-based PET-CT auto-delineation with pathology in non-small-cell lung cancer (NSCLC) and to investigate whether auto-delineation reduces the interobserver variability compared with manual PET-CT-based gross tumor volume (GTV) delineation. Methods and Materials: Source-to-background ratio-based auto-delineation was compared with macroscopic tumor dimensions to assess its validity in 23 tumors. Thereafter, GTVs were delineated manually on 33 PET-CT scans by five observers for the primary tumor (GTV-1) and the involved lymph nodes (GTV-2). The delineation was repeated after 6 months with the auto-contour provided. This contour was edited by the observers. For comparison, the concordance index (CI) was calculated, defined as the ratio of intersection and the union of two volumes (A intersection B)/(A union B). Results: The maximal tumor diameter of the SBR-based auto-contour correlated strongly with the macroscopic diameter of primary tumors (correlation coefficient = 0.90) and was shown to be accurate for involved lymph nodes (sensitivity 67%, specificity 95%). The median auto-contour-based target volumes were smaller than those defined by manual delineation for GTV-1 (31.8 and 34.6 cm 3 , respectively; p = 0.001) and GTV-2 (16.3 and 21.8 cm 3 , respectively; p 0.02). The auto-contour-based method showed higher CIs than the manual method for GTV-1 (0.74 and 0.70 cm 3 , respectively; p 3 , respectively; p = 0.11). Conclusion: Source-to-background ratio-based auto-delineation showed a good correlation with pathology, decreased the delineated volumes of the GTVs, and reduced the interobserver variability. Auto-contouring may further improve the quality of target delineation in NSCLC patients

  4. Influence of Pathological Nodal Status and Maximal Standardized Uptake Value of the Primary Tumor and Regional Lymph Nodes on Treatment Plans in Patients With Advanced Oral Cavity Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Liao, C.-T.; Wang, H.-M.; Chang, Joseph Tung-Chieh; Lin, C.-Y.; Ng, S.-H.; Huang, S.-F.; Chen, I.-H.; Hsueh Chuen; Lee, L.-Y.; Lin, C.-H.

    2010-01-01

    Purpose: A better understanding of the prognostic factors in oral cavity squamous cell carcinoma (OSCC) may optimize the therapeutic approach. In this study, we sought to investigate whether the combination of clinical information, pathologic results, and preoperative maximal standardized uptake value (SUVmax) at the primary tumor and regional lymph nodes might improve the prognostic stratification in this patient group. Methods and Materials: A total of 347 consecutive OSCC patients were investigated. All participants underwent fluorodeoxyglucose-positron emission tomography within 2 weeks before surgery and neck dissection. The duration of follow-up was at least 24 months in all surviving patients. The optimal cutoff values for SUVmax at the primary tumor (SUVtumor-max) and regional lymph nodes (SUVnodal-max) were selected according to the 5-year disease-free survival (DFS) rate. Independent prognosticators were identified by Cox regression analysis. Results: In multivariate analysis, a cutoff SUVtumor-max of 8.6, a cutoff SUVnodal-max of 5.7, and the presence of pathologic lymph node metastases were found to be significant prognosticators for the 5-year DFS. A scoring system using these three prognostic factors was formulated to define distinct prognostic groups. The 5-year rates for patients with a score between 0 and 3 were as follows: neck control, 94%, 86%, 77%, 59% (p < 0.0001); distant metastases, 1%, 7%, 22%, 47% (p < 0.0001); disease-specific survival, 93%, 85%, 61%, 36%, respectively (p < 0.0001). Conclusion: Based on the study findings, the combined evaluation of pathologic node status and SUVmax at the primary tumor and regional lymph nodes may improve prognostic stratification in OSCC patients.

  5. In vitro clonal propagation of Achyranthes aspera L. and Achyranthes bidentata Blume using nodal explants.

    Science.gov (United States)

    Gnanaraj, Wesely Edward; Antonisamy, Johnson Marimuthu; R B, Mohanamathi; Subramanian, Kavitha Marappampalyam

    2012-01-01

    plants were established in the field. The results have shown that use of nodal buds is an alternative reproducible and dependable method for clonal propagation of A. aspera and A. bidentata. The high rate of direct shoot-root multiplication and their high rate of post-hardening survival indicate that this protocol can be easily adopted for commercial large scale cultivation.

  6. Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis

    NARCIS (Netherlands)

    Thiruvalluvan, Arun; Czepiel, Marcin; Kap, Yolanda A.; Mantingh-Otter, Ietje; Vainchtein, Ilia; Kuipers, Jeroen; Bijlard, Marjolein; Baron, Wia; Giepmans, Ben; Brueck, Wolfgang; 'T Hart, Bert A.; Boddeke, Erik; Copray, Sjef

    2016-01-01

    : Fast remyelination by endogenous oligodendrocyte precursor cells (OPCs) is essential to prevent axonal and subsequent retrograde neuronal degeneration in demyelinating lesions in multiple sclerosis (MS). In chronic lesions, however, the remyelination capacity of OPCs becomes insufficient. Cell

  7. Ratio of mediastinal lymph node SUV to primary tumor SUV in {sup 18}F-FDG PET/CT for nodal staging in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Hyuk; Choe, Jae Gol; Pahk, Kisoo; Choi, Sun Ju; Kwon, Hye Ryeong; Kim, Sun Geun [Dept. of Nuclear Medicine, Korea University Anam Hospital, Seoul (Korea, Republic of); Eo, Jae Seon; Seo, Hyo Jung [Dept. of Nuclear Medicine, Korea University Guro Hospital, Seoul (Korea, Republic of); Kim, Chul Han [Dept. of Nuclear Medicine, Korea University Ansan Hospital, Ansan (Korea, Republic of)

    2017-06-15

    Following determination of the maximum standardized uptake values (SUVmax) of the mediastinal lymph nodes (SUV-LN) and of the primary tumor (SUV-T) on 18F-FDG PET/CT in patients with non-small-cell lung cancer (NSCLC), the aim of the study was to determine the value of the SUV-LN/SUV-T ratio in lymph node staging in comparison with that of SUV-LN. We retrospectively reviewed a total of 289 mediastinal lymph node stations from 98 patients with NSCLC who were examined preoperatively for staging and subsequently underwent pathologic studies of the mediastinal lymph nodes. We determined SUV-LN and SUV-R for each lymph node station on 18F-FDG PET/CT and then classified each station into one of three groups based on SUV-T (low, medium and high SUV-T groups). Diagnostic performance was assessed based on receiver operating characteristic (ROC) curve analysis, and the optimal cut-off values that would best discriminate metastatic from benign lymph nodes were determined for each method. The average of SUV-R of malignant lymph nodes was significantly higher than that of benign lymph nodes (0.79 ± 0.45 vs. 0.36 ± 0.23, P < 0.0001). In the ROC curve analysis, the area under the curve (AUC) of SUV-R was significantly higher than that of SUV-LN in the low SUV-T group (0.885 vs. 0.810, P = 0.019). There were no significant differences between the AUCs of SUV-LN and of SUV-R in the medium and high SUV-T groups. The optimal cut-off value for SUV-R in the low SUV-T group was 0.71 (sensitivity 87.5 %, specificity 85.9 %). The SUV-R performed well in distinguishing between metastatic and benign lymph nodes. In particular, SUV-R was found to have a better diagnostic performance than SUV-LN in the low SUV-T group.

  8. CALCULUS FROM THE PAST: MULTIPLE DELAY SYSTEMS ARISING IN CANCER CELL MODELLING

    KAUST Repository

    WAKE, G. C.; BYRNE, H. M.

    2013-01-01

    Nonlocal calculus is often overlooked in the mathematics curriculum. In this paper we present an interesting new class of nonlocal problems that arise from modelling the growth and division of cells, especially cancer cells, as they progress through the cell cycle. The cellular biomass is assumed to be unstructured in size or position, and its evolution governed by a time-dependent system of ordinary differential equations with multiple time delays. The system is linear and taken to be autonomous. As a result, it is possible to reduce its solution to that of a nonlinear matrix eigenvalue problem. This method is illustrated by considering case studies, including a model of the cell cycle developed recently by Simms, Bean and Koeber. The paper concludes by explaining how asymptotic expressions for the distribution of cells across the compartments can be determined and used to assess the impact of different chemotherapeutic agents. Copyright © 2013 Australian Mathematical Society.

  9. Multiple dendritic cell populations activate CD4+ T cells after viral stimulation.

    Directory of Open Access Journals (Sweden)

    Adele M Mount

    2008-02-01

    Full Text Available Dendritic cells (DC are a heterogeneous cell population that bridge the innate and adaptive immune systems. CD8alpha DC play a prominent, and sometimes exclusive, role in driving amplification of CD8(+ T cells during a viral infection. Whether this reliance on a single subset of DC also applies for CD4(+ T cell activation is unknown. We used a direct ex vivo antigen presentation assay to probe the capacity of flow cytometrically purified DC populations to drive amplification of CD4(+ and CD8(+ T cells following infection with influenza virus by different routes. This study examined the contributions of non-CD8alpha DC populations in the amplification of CD8(+ and CD4(+ T cells in cutaneous and systemic influenza viral infections. We confirmed that in vivo, effective immune responses for CD8(+ T cells are dominated by presentation of antigen by CD8alpha DC but can involve non-CD8alpha DC. In contrast, CD4(+ T cell responses relied more heavily on the contributions of dermal DC migrating from peripheral lymphoid tissues following cutaneous infection, and CD4 DC in the spleen after systemic infection. CD4(+ T cell priming by DC subsets that is dependent upon the route of administration raises the possibility that vaccination approaches could be tailored to prime helper T cell immunity.

  10. Study of flow over object problems by a nodal discontinuous Galerkin-lattice Boltzmann method

    Science.gov (United States)

    Wu, Jie; Shen, Meng; Liu, Chen

    2018-04-01

    The flow over object problems are studied by a nodal discontinuous Galerkin-lattice Boltzmann method (NDG-LBM) in this work. Different from the standard lattice Boltzmann method, the current method applies the nodal discontinuous Galerkin method into the streaming process in LBM to solve the resultant pure convection equation, in which the spatial discretization is completed on unstructured grids and the low-storage explicit Runge-Kutta scheme is used for time marching. The present method then overcomes the disadvantage of standard LBM for depending on the uniform meshes. Moreover, the collision process in the LBM is completed by using the multiple-relaxation-time scheme. After the validation of the NDG-LBM by simulating the lid-driven cavity flow, the simulations of flows over a fixed circular cylinder, a stationary airfoil and rotating-stationary cylinders are performed. Good agreement of present results with previous results is achieved, which indicates that the current NDG-LBM is accurate and effective for flow over object problems.

  11. Solution of the Neutron transport equation in hexagonal geometry using strongly discontinuous nodal schemes

    International Nuclear Information System (INIS)

    Mugica R, C.A.; Valle G, E. del

    2005-01-01

    In 2002, E. del Valle and Ernest H. Mund developed a technique to solve numerically the Neutron transport equations in discrete ordinates and hexagonal geometry using two nodal schemes type finite element weakly discontinuous denominated WD 5,3 and WD 12,8 (of their initials in english Weakly Discontinuous). The technique consists on representing each hexagon in the union of three rhombuses each one of which it is transformed in a square in the one that the methods WD 5,3 and WD 12,8 were applied. In this work they are solved the mentioned equations of transport using the same discretization technique by hexagon but using two nodal schemes type finite element strongly discontinuous denominated SD 3 and SD 8 (of their initials in english Strongly Discontinuous). The application in each case as well as a reference problem for those that results are provided for the effective multiplication factor is described. It is carried out a comparison with the obtained results by del Valle and Mund for different discretization meshes so much angular as spatial. (Author)

  12. Development of a New core/reflector model for coarse-mesh nodal methods

    International Nuclear Information System (INIS)

    Pogosbekyan, Leonid; Cho, Jin Young; Kim, Young Il; Kim, Young Jin; Joo, Hyung Kuk; Chang, Moon Hee.

    1997-10-01

    This work presents two approaches for reflector simulation in coarse-mesh nodal methods. The first approach is called Interface Matrix Technique (IMT), which simulates the baffle as a banishingly thin layer having the property of reflection and transmission. We applied this technique within the frame of AFEN (Analytic Function Expansion Nodal) method, and developed the AFEN-IM (Interface Matrix) method. AFEN-IM method shows 1.24% and 0.42 % in maximum and RMS (Root Mean Square) assemblywise power error for ZION-1 benchmark problem. The second approach is L-shaped reflector homogenization method. This method is based on the integral response conservation along the L-shaped core-reflector interface. The reference reflector response is calculated from 2-dimensional spectral calculation and the response of the homogenized reflector is derived from the one-node 2-dimensional AFEN problem solution. This method shows 5 times better accuracy than the 1-dimensional homogenization technique in the assemblywise power. Also, the concept of shroud/reflector homogenization for hexagonal core have been developed. The 1-dimensional spectral calculation was used for the determination of 2 group cross sections. The essence of homogenization concept consists in the calculation of equivalent shroud width, which preserve albedo for the fast neutrons in 2-dimensional reflector. This method shows a relative error less than 0.42% in assemblywise power and a difference of 9x10 -5 in multiplication factor for full-core model. (author). 9 refs., 3 tabs., 28 figs

  13. In vitro establishment of nodal segments of Annona muricata L. young plants

    Directory of Open Access Journals (Sweden)

    Leyanis García-Águila

    2012-10-01

    Full Text Available The use of tissue in vitro culture for plant propagation of soursop (Annona muricata L. promissory trees can help increasing the availability of plants for developing field plantations. Considering these aspect, this work aimed to establish in vitro nodal segments of young plants of soursop. Nodal segments with 1.5 cm of length were superficially disinfected with 70% ethanol during one minute and with sodium hypochlorite (0.5, 1.0, 1.5 and 2.0% during 15 minutes. The presence of microbial contamination and the number of segments with axillary buds were evaluated after 15 and 25 days of culture. The length (cm of buds was also determined. Results showed a low incidence of microbial contamination in the explants because the presence of fungi in treatments was not observed. However, 3.8% segments were contaminated with bacteria in the treatment with lower concentration of sodium hypochlorite. Axillary shoots were observed in 73.0% of explants when 1.0% of sodium hypochlorite was used, without significant differences using 1.5%. Shoots development with first expanded leaves and a length ranged between 0.8 and 1.5 cm was observed after 25 days of culture. Increasing culture time, plants showed leaf abscission. These results demonstrate that in vitro culture can be used for the propagation of soursop. However, we must make emphasis in the study of the culture conditions for the multiplication phase. Key words: in vitro culture, microbial contamination, phenolic oxidation, shoot production.

  14. Transforming growth factor alpha (TGFα regulates granulosa cell tumor (GCT cell proliferation and migration through activation of multiple pathways.

    Directory of Open Access Journals (Sweden)

    Cheng Wang

    Full Text Available Granulosa cell tumors (GCTs are the most common ovarian estrogen producing tumors, leading to symptoms of excessive estrogen such as endometrial hyperplasia and endometrial adenocarcinoma. These tumors have malignant potential and often recur. The etiology of GCT is unknown. TGFα is a potent mitogen for many different cells. However, its function in GCT initiation, progression and metastasis has not been determined. The present study aims to determine whether TGFα plays a role in the growth of GCT cells. KGN cells, which are derived from an invasive GCT and have many features of normal granulosa cells, were used as the cellular model. Immunohistochemistry, Western blot and RT-PCR results showed that the ErbB family of receptors is expressed in human GCT tissues and GCT cell lines. RT-PCR results also indicated that TGFα and EGF are expressed in the human granulosa cells and the GCT cell lines, suggesting that TGFα might regulate GCT cell function in an autocrine/paracrine manner. TGFα stimulated KGN cell DNA synthesis, cell proliferation, cell viability, cell cycle progression, and cell migration. TGFα rapidly activated EGFR/PI3K/Akt and mTOR pathways, as indicated by rapid phosphorylation of Akt, TSC2, Rictor, mTOR, P70S6K and S6 proteins following TGFα treatment. TGFα also rapidly activated the EGFR/MEK/ERK pathway, and P38 MAPK pathways, as indicated by the rapid phosphorylation of EGFR, MEK, ERK1/2, P38, and CREB after TGFα treatment. Whereas TGFα triggered a transient activation of Akt, it induced a sustained activation of ERK1/2 in KGN cells. Long-term treatment of KGN cells with TGFα resulted in a significant increase in cyclin D2 and a decrease in p27/Kip1, two critical regulators of granulosa cell proliferation and granulosa cell tumorigenesis. In conclusion, TGFα, via multiple signaling pathways, regulates KGN cell proliferation and migration and may play an important role in the growth and metastasis of GCTs.

  15. Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

    Science.gov (United States)

    Chinen, Yoshiaki; Kuroda, Junya; Shimura, Yuji; Nagoshi, Hisao; Kiyota, Miki; Yamamoto-Sugitani, Mio; Mizutani, Shinsuke; Sakamoto, Natsumi; Ri, Masaki; Kawata, Eri; Kobayashi, Tsutomu; Matsumoto, Yosuke; Horiike, Shigeo; Iida, Shinsuke; Taniwaki, Masafumi

    2014-12-15

    Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells. In the clinical setting, PDPK1 was active in myeloma cells of approximately 90% of symptomatic patients at diagnosis, and the smaller population of patients with multiple myeloma exhibiting myeloma cells without active PDPK1 showed a significantly less frequent proportion of the disease stage III by the International Staging System and a significantly more favorable prognosis, including the longer overall survival period and the longer progression-free survival period by bortezomib treatment, than patients with active PDPK1, suggesting that PDPK1 activation accelerates the disease progression and the resistance to treatment in multiple myeloma. Our study demonstrates that PDPK1 is a potent and a universally targetable signaling mediator in multiple myeloma regardless of the types of cytogenetic/molecular profiles. ©2014 American Association for Cancer Research.

  16. Stem Cell Physics. Multiple-Laser-Beam Treatment of Parkinson's Disease

    Science.gov (United States)

    Stefan, V.

    2013-03-01

    A novel method for the treatment of Parkinson's disease is proposed. Pluripotent stem cells are laser cultured, using ultrashort wavelength, (around 0.1 micron-ultraviolet radiation-with intensities of a few mW/cm2) , multiple laser beams.[2] The multiple-energy laser photons[3] interact with the neuron DNA molecules to be cloned. The laser created dopaminergic substantia nigra neurons can be, (theoretically), laser transplanted, (a higher focusing precision as compared to a syringe method), into the striatum or substantia nigra regions of the brain, or both. Supported by Nikola Tesla Labs, Stefan University.

  17. T cells in multiple myeloma display features of exhaustion and senescence at the tumor site

    Directory of Open Access Journals (Sweden)

    Claudia Zelle-Rieser

    2016-11-01

    Full Text Available Abstract Background Multiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments. In addition, T cell function concerning proliferation and expression of T-bet, IL-2, IFNγ, and CD107a was investigated after in vitro stimulation by CD3/CD28. Finally, data was compared to healthy, age-matched donor T cells from both compartments. Methods Multicolor flow cytometry was utilized for the analyses of surface molecules, intracellular staining of cytokines was also performed by flow cytometry, and proliferation was assessed by 3H-thymidine incorporation. Statistical analyses were performed utilizing unpaired T test and Mann-Whitney U test. Results We observed enhanced T cell exhaustion and senescence especially at the tumor site. CD8+ T cells expressed several molecules associated with T cell exhaustion (PD-1, CTLA-4, 2B4, CD160 and T cell senescence (CD57, lack of CD28. This phenotype was associated with lower proliferative capacity and impaired function. Despite a high expression of the transcription factor T-bet, CD8+ T cells from the tumor site failed to produce IFNγ after CD3/CD28 in vitro restimulation and displayed a reduced ability to degranulate in response to T cell stimuli. Notably, the percentage of senescent CD57+CD28− CD8+ T cells was significantly lower in treated myeloma patients when compared to untreated patients. Conclusions T cells from the bone marrow of myeloma

  18. Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway.

    Science.gov (United States)

    Gao, Hui; Wang, Jianrong

    2016-02-01

    Andrographolide is an active component from the extract of Andrographis paniculata [(Burm.f) Nees], a medicinal plant from the Acanthaceae family. Pharmacological studies have revealed that andrographolide possesses anti-bacterial, anti-inflammatory, anti-viral, immune regulatory and hepatoprotective properties, and is efficacious in the treatment of cardiovascular diseases, while exhibiting low toxicity and low cost. The present study aimed to determine the inhibitory effects of andrographolide on the growth of multiple myeloma (MM) cells and its possible impact on the Toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway. Cell proliferation was detected using an MTT assay, cellular apoptosis was measured using flow cytometry, and caspase-9/3 activation were assessed using colorimetric assay kits. Furthermore, TLR4 and NF-κB protein expression was determined by western blot analysis. The results revealed that andrographolide reduced the proliferation, while increasing cellular apoptosis and caspase-9/3 activation of MM cells, in addition to downregulating the expression of TLR4 and NF-κB protein. Of note, TLR4- or NF-κB-targeting small-interfering (si)RNA enhanced the andrographolide-induced inhibition of cell proliferation and induction of apoptosis of MM cells. The results of the present study therefore suggested that andrographolide inhibited multiple myeloma cells via the TLR4/NF-κB signaling pathway.

  19. Online unsupervised formation of cell assemblies for the encoding of multiple cognitive maps.

    Science.gov (United States)

    Salihoglu, Utku; Bersini, Hugues; Yamaguchi, Yoko; Molter, Colin

    2009-01-01

    Since their introduction sixty years ago, cell assemblies have proved to be a powerful paradigm for brain information processing. After their introduction in artificial intelligence, cell assemblies became commonly used in computational neuroscience as a neural substrate for content addressable memories. However, the mechanisms underlying their formation are poorly understood and, so far, there is no biologically plausible algorithms which can explain how external stimuli can be online stored in cell assemblies. We addressed this question in a previous paper [Salihoglu, U., Bersini, H., Yamaguchi, Y., Molter, C., (2009). A model for the cognitive map formation: Application of the retroaxonal theory. In Proc. IEEE international joint conference on neural networks], were, based on biologically plausible mechanisms, a novel unsupervised algorithm for online cell assemblies' creation was developed. The procedure involved simultaneously, a fast Hebbian/anti-Hebbian learning of the network's recurrent connections for the creation of new cell assemblies, and a slower feedback signal which stabilized the cell assemblies by learning the feedforward input connections. Here, we first quantify the role played by the retroaxonal feedback mechanism. Then, we show how multiple cognitive maps, composed by a set of orthogonal input stimuli, can be encoded in the network. As a result, when facing a previously learned input, the system is able to retrieve the cognitive map it belongs to. As a consequence, ambiguous inputs which could belong to multiple cognitive maps can be disambiguated by the knowledge of the context, i.e. the cognitive map.

  20. Isolation and Multiple Differentiation Potential Assessment of Human Gingival Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2014-11-01

    Full Text Available The aim of this study was to isolate human mesenchymal stem cells (MSCs from the gingiva (GMSCs and confirm their multiple differentiation potentials, including the odontogenic lineage. GMSCs, periodontal ligament stem cells (PDLSCs and dermal stem cells (DSCs cultures were analyzed for cell shape, cell cycle, colony-forming unit-fibroblast (CFU-F and stem cell markers. Cells were then induced for osteogenic and adipogenic differentiation and analyzed for differentiation markers (alkaline phosphatase (ALP activity, mineralization nodule formation and Runx2, ALP, osteocalcin (OCN and collagen I expressions for the osteogenic differentiation, and lipid vacuole formation and PPARγ-2 expression for the adipogenic differentiation. Besides, the odontogenic differentiation potential of GMSCs induced with embryonic tooth germ cell-conditioned medium (ETGC-CM was observed. GMSCs, PDLSCs and DSCs were all stromal origin. PDLSCs showed much higher osteogenic differentiation ability but lower adipogenic differentiation potential than DSCs. GMSCs showed the medial osteogenic and adipogenic differentiation potentials between those of PDLSCs and DSCs. GMSCs were capable of expressing the odontogenic genes after ETGC-CM induction. This study provides evidence that GMSCs can be used in tissue engineering/regeneration protocols as an approachable stem cell source.

  1. Simultaneous Measurement of Multiple Mechanical Properties of Single Cells Using AFM by Indentation and Vibration.

    Science.gov (United States)

    Zhang, Chuang; Shi, Jialin; Wang, Wenxue; Xi, Ning; Wang, Yuechao; Liu, Lianqing

    2017-12-01

    The mechanical properties of cells, which are the main characteristics determining their physical performance and physiological functions, have been actively studied in the fields of cytobiology and biomedical engineering and for the development of medicines. In this study, an indentation-vibration-based method is proposed to simultaneously measure the mechanical properties of cells in situ, including cellular mass (m), elasticity (k), and viscosity (c). The proposed measurement method is implemented based on the principle of forced vibration stimulated by simple harmonic force using an atomic force microscope (AFM) system integrated with a piezoelectric transducer as the substrate vibrator. The corresponding theoretical model containing the three mechanical properties is derived and used to perform simulations and calculations. Living and fixed human embryonic kidney 293 (HEK 293) cells were subjected to indentation and vibration to measure and compare their mechanical parameters and verify the proposed approach. The results that the fixed sample cells are more viscous and elastic than the living sample cells and the measured mechanical properties of cell are consistent within, but not outside of the central region of the cell, are in accordance with the previous studies. This work provides an approach to simultaneous measurement of the multiple mechanical properties of single cells using an integrated AFM system based on the principle force vibration and thickness-corrected Hertz model. This study should contribute to progress in biomedical engineering, cytobiology, medicine, early diagnosis, specific therapy and cell-powered robots.

  2. The novel immunotoxin HM1.24-ETA′ induces apoptosis in multiple myeloma cells

    International Nuclear Information System (INIS)

    Staudinger, M; Glorius, P; Burger, R; Kellner, C; Klausz, K; Günther, A; Repp, R; Klapper, W; Gramatzki, M; Peipp, M

    2014-01-01

    Despite new treatment modalities, the clinical outcome in a substantial number of patients with multiple myeloma (MM) has yet to be improved. Antibody-based targeted therapies for myeloma patients could make use of the HM1.24 antigen (CD317), a surface molecule overexpressed on malignant plasma cells and efficiently internalized. Here, a novel immunotoxin, HM1.24-ETA′, is described. HM1.24-ETA′ was generated by genetic fusion of a CD317-specific single-chain Fv (scFv) antibody and a truncated variant of Pseudomonas aeruginosa exotoxin A (ETA′). HM1.24-ETA′ inhibited growth of interleukin 6 (IL-6)-dependent and -independent myeloma cell lines. Half-maximal growth inhibition was observed at concentrations as low as 0.3 nM. Target cell killing occurred via induction of apoptosis and was unaffected in co-culture experiments with bone marrow stromal cells. HM1.24-ETA′ efficiently triggered apoptosis of freshly isolated/cryopreserved cells of patients with plasma cell leukemia and MM and was active in a preclinical severe combined immunodeficiency (SCID) mouse xenograft model. Importantly, HM1.24-ETA′ was not cytotoxic against CD317-positive cells from healthy tissue (monocytes, human umbilical vein endothelial cells). These results indicate that CD317 may represent a promising target structure for specific and efficient immunotoxin therapy for patients with plasma cell tumors

  3. B cells are multifunctional players in multiple sclerosis pathogenesis: insights from therapeutic interventions

    Directory of Open Access Journals (Sweden)

    Nele eClaes

    2015-12-01

    Full Text Available Multiple sclerosis (MS is a severe disease of the central nervous system (CNS characterized by autoimmune inflammation and neurodegeneration. Historically, damage to the CNS was thought to be mediated predominantly by activated pro-inflammatory T cells. B cell involvement in the pathogenesis of MS was solely attributed to autoantibody production. The first clues for the involvement of antibody-independent B cell functions in MS pathology came from positive results in clinical trials of the B cell depleting treatment rituximab in patients with relapsing-remitting (RR MS. The survival of antibody-secreting plasma cells and decrease in T cell numbers indicated the importance of other B cell functions in MS such as antigen presentation, costimulation and cytokine production. Rituximab provided us with an example of how clinical trials can lead to new research opportunities concerning B cell biology. Moreover, analysis of the antibody-independent B cell functions in MS has gained interest since these trials. Limited information is present on the effects of current immunomodulatory therapies on B cell functions, although effects of both first-line (interferon, glatiramer acetate, dimethyl fumarate and teriflunomide, second-line (fingolimod, natalizumab and even third-line (monoclonal antibody therapies treatments on B cell subtype distribution, expression of functional surface markers and secretion of different cytokines by B cells have been studied to some extent. In this review, we summarize the effects of different MS related treatments on B cell functions that have been described up to now in order to find new research opportunities and contribute to the understanding of the pathogenesis of MS.

  4. Characterisation of cellular adhesion reinforcement by multiple bond force spectroscopy in alveolar epithelial cells.

    Science.gov (United States)

    Nguyen, Ngoc-Minh; Angely, Christelle; Andre Dias, Sofia; Planus, Emmanuelle; Filoche, Marcel; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2017-07-01

    Integrin-mediated adhesion is a key process by which cells physically connect with their environment, and express sensitivity and adaptation through mechanotransduction. A critical step of cell adhesion is the formation of the first bonds which individually generate weak contacts (∼tens pN) but can sustain thousand times higher forces (∼tens nN) when associated. We propose an experimental validation by multiple bond force spectroscopy (MFS) of a stochastic model predicting adhesion reinforcement permitted by non-cooperative, multiple bonds on which force is homogeneously distributed (called parallel bond configuration). To do so, spherical probes (diameter: 6.6 μm), specifically coated by RGD-peptide to bind integrins, are used to statically indent and homogenously stretch the multiple bonds created for short contact times (2 s) between the bead and the surface of epithelial cells (A549). Using different separation speeds (v = 2, 5, 10 μm/s) and measuring cellular Young's modulus as well as the local stiffness preceding local rupture events, we obtain cell-by-cell the effective loading rates both at the global cell level and at the local level of individual constitutive bonds. Local rupture forces are in the range: f*=60-115 pN , whereas global rupture (detachment) forces reach F*=0.8-1.7 nN . Global and local rupture forces both exhibit linear dependencies with the effective loading rate, the slopes of these two linear relationships providing an estimate of the number of independent integrin bonds constituting the tested multiple bond structure (∼12). The MFS method enables to validate the reinforcement of integrin-mediated adhesion induced by the multiple bond configuration in which force is homogeneously distributed amongst parallel bonds. Local rupture events observed in the course of a spectroscopy manoeuver (MFS) lead to rupture force values considered in the literature as single-integrin bonds. Adhesion reinforcement permitted by the parallel

  5. Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo

    International Nuclear Information System (INIS)

    Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

    2012-01-01

    In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM

  6. Cell characteristics of a multiple alloy nano-dots memory structure

    International Nuclear Information System (INIS)

    Bea, Ji Chel; Lee, Kang-Wook; Tanaka, Tetsu; Koyanagi, Mitsumasa; Song, Yun Heub; Lee, Gae-Hun

    2009-01-01

    A multiple alloy metal nano-dots memory using FN tunneling was investigated in order to confirm its structural possibility for future flash memory. In this work, a multiple FePt nano-dots device with a high work function (∼5.2 eV) and extremely high dot density (∼1.2 × 10 13 cm −2 ) was fabricated. Its structural effect for multiple layers was evaluated and compared to the one with a single layer in terms of the cell characteristics and reliability. We confirm that MOS capacitor structures with two to four multiple FePt nano-dot layers provide a larger threshold voltage window and better retention characteristics. Furthermore, it was also revealed that several process parameters for block oxide and inter-tunnel oxide between the nano-dot layers are very important to improve the efficiency of electron injection into multiple nano-dots. From these results, it is expected that a multiple FePt nano-dots memory using Fowler–Nordheim (FN) tunneling could be a candidate structure for future flash memory

  7. NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Haiwen Ni

    Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

  8. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

    DEFF Research Database (Denmark)

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio

    2015-01-01

    of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further...... and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels...

  9. Cyclic AMP induces apoptosis in multiple myeloma cells and inhibits tumor development in a mouse myeloma model

    International Nuclear Information System (INIS)

    Follin-Arbelet, Virginie; Hofgaard, Peter O; Hauglin, Harald; Naderi, Soheil; Sundan, Anders; Blomhoff, Rune; Bogen, Bjarne; Blomhoff, Heidi K

    2011-01-01

    Multiple myeloma is an incurable disease requiring the development of effective therapies which can be used clinically. We have elucidated the potential for manipulating the cAMP signaling pathway as a target for inhibiting the growth of multiple myeloma cells. As a model system, we primarily used the murine multiple myeloma cell line MOPC315 which can be grown both in vivo and in vitro. Human multiple myeloma cell lines U266, INA-6 and the B-cell precursor acute lymphoblastic leukemia cell line Reh were used only for in vitro studies. Cell death was assessed by flow cytometry and western blot analysis after treatment with cAMP elevating agents (forskolin, prostaglandin E2 and rolipram) and cAMP analogs. We followed tumor growth in vivo after forskolin treatment by imaging DsRed-labelled MOPC315 cells transplanted subcutaneously in BALB/c nude mice. In contrast to the effect on Reh cells, 50 μM forskolin more than tripled the death of MOPC315 cells after 24 h in vitro. Forskolin induced cell death to a similar extent in the human myeloma cell lines U266 and INA-6. cAMP-mediated cell death had all the typical hallmarks of apoptosis, including changes in the mitochondrial membrane potential and cleavage of caspase 3, caspase 9 and PARP. Forskolin also inhibited the growth of multiple myeloma cells in a mouse model in vivo. Elevation of intracellular levels of cAMP kills multiple myeloma cells in vitro and inhibits development of multiple myeloma in vivo. This strongly suggests that compounds activating the cAMP signaling pathway may be useful in the field of multiple myeloma

  10. New procedure for criticality search using coarse mesh nodal methods

    International Nuclear Information System (INIS)

    Pereira, Wanderson F.; Silva, Fernando C. da; Martinez, Aquilino S.

    2011-01-01

    The coarse mesh nodal methods have as their primary goal to calculate the neutron flux inside the reactor core. Many computer systems use a specific form of calculation, which is called nodal method. In classical computing systems that use the criticality search is made after the complete convergence of the iterative process of calculating the neutron flux. In this paper, we proposed a new method for the calculation of criticality, condition which will be over very iterative process of calculating the neutron flux. Thus, the processing time for calculating the neutron flux was reduced by half compared with the procedure developed by the Nuclear Engineering Program of COPPE/UFRJ (PEN/COPPE/UFRJ). (author)

  11. New procedure for criticality search using coarse mesh nodal methods

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Wanderson F.; Silva, Fernando C. da; Martinez, Aquilino S., E-mail: wneto@con.ufrj.b, E-mail: fernando@con.ufrj.b, E-mail: Aquilino@lmp.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEN/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear

    2011-07-01

    The coarse mesh nodal methods have as their primary goal to calculate the neutron flux inside the reactor core. Many computer systems use a specific form of calculation, which is called nodal method. In classical computing systems that use the criticality search is made after the complete convergence of the iterative process of calculating the neutron flux. In this paper, we proposed a new method for the calculation of criticality, condition which will be over very iterative process of calculating the neutron flux. Thus, the processing time for calculating the neutron flux was reduced by half compared with the procedure developed by the Nuclear Engineering Program of COPPE/UFRJ (PEN/COPPE/UFRJ). (author)

  12. The variational nodal method: history and recent accomplishments

    International Nuclear Information System (INIS)

    Lewis, E.E.

    2004-01-01

    The variational nodal method combines spherical harmonics expansions in angle with hybrid finite element techniques is space to obtain multigroup transport response matrix algorithms applicable to both deep penetration and reactor core physics problems. This survey briefly recounts the method's history and reviews its capabilities. The variational basis for the approach is presented and two methods for obtaining discretized equations in the form of response matrices are detailed. The first is that contained the widely used VARIANT code, while the second incorporates newly developed integral transport techniques into the variational nodal framework. The two approaches are combined with a finite sub element formulation to treat heterogeneous nodes. Applications are presented for both a deep penetration problem and to an OECD benchmark consisting of LWR MOX fuel assemblies. Ongoing work is discussed. (Author)

  13. Radiological signs of extra nodal abdominal involvements in lymphoma

    International Nuclear Information System (INIS)

    Carro, A.I.; Alegre, N.; Cervera, J.L.; Montero, A.I.

    1998-01-01

    To assess abdominal CT images in lymphoma patients for the study of extra nodal abdominal involvement. Ninety-two patients diagnosed as having lymphoma were studied retrospectively. All the patients underwent abdominopelvic CT with oral and intravenous contrast (except in one patient who was allergic). In every case, the diagnosis was confirmed by biopsy or radiological follow-up after treatment had been completed. Fifty-two patients (56.5%) presented infiltration of extra nodal organs. The organs most frequently involved were liver and spleen, followed by the gastrointestinal tract, the musculoskeletal system and the genitourinary tract. The findings in this study coincide with those reported elsewhere with the exception of the splenic involvement the incidence of which was lower in the present series. (Author) 17 refs

  14. On the nodal structure of atomic and molecular Wigner functions

    International Nuclear Information System (INIS)

    Dahl, J.P.; Schmider, H.

    1996-01-01

    In previous work on the phase-space representation of quantum mechanics, we have presented detailed pictures of the electronic one-particle reduced Wigner function for atoms and small molecules. In this communication, we focus upon the nodal structure of the function. On the basis of the simplest systems, we present an expression which relates the oscillatory decay of the Wigner function solely to the dot product of the position and momentum vector, if both arguments are large. We then demonstrate the regular behavior of nodal patterns for the larger systems. For the molecular systems, an argument analogous to the open-quotes bond-oscillatory principleclose quotes for momentum densities links the nuclear framework to an additional oscillatory term in momenta parallel to bonds. It is shown that these are visible in the Wigner function in terms of characteristic nodes

  15. An alternative solver for the nodal expansion method equations - 106

    International Nuclear Information System (INIS)

    Carvalho da Silva, F.; Carlos Marques Alvim, A.; Senra Martinez, A.

    2010-01-01

    An automated procedure for nuclear reactor core design is accomplished by using a quick and accurate 3D nodal code, aiming at solving the diffusion equation, which describes the spatial neutron distribution in the reactor. This paper deals with an alternative solver for nodal expansion method (NEM), with only two inner iterations (mesh sweeps) per outer iteration, thus having the potential to reduce the time required to calculate the power distribution in nuclear reactors, but with accuracy similar to the ones found in conventional NEM. The proposed solver was implemented into a computational system which, besides solving the diffusion equation, also solves the burnup equations governing the gradual changes in material compositions of the core due to fuel depletion. Results confirm the effectiveness of the method for practical purposes. (authors)

  16. Topological and trivial magnetic oscillations in nodal loop semimetals

    Science.gov (United States)

    Oroszlány, László; Dóra, Balázs; Cserti, József; Cortijo, Alberto

    2018-05-01

    Nodal loop semimetals are close descendants of Weyl semimetals and possess a topologically dressed band structure. We argue by combining the conventional theory of magnetic oscillation with topological arguments that nodal loop semimetals host coexisting topological and trivial magnetic oscillations. These originate from mapping the topological properties of the extremal Fermi surface cross sections onto the physics of two dimensional semi-Dirac systems, stemming from merging two massless Dirac cones. By tuning the chemical potential and the direction of magnetic field, a sharp transition is identified from purely trivial oscillations, arising from the Landau levels of a normal two dimensional (2D) electron gas, to a phase where oscillations of topological and trivial origin coexist, originating from 2D massless Dirac and semi-Dirac points, respectively. These could in principle be directly identified in current experiments.

  17. Ischemic stroke associated with radio frequency ablation for nodal reentry

    International Nuclear Information System (INIS)

    Diaz M, Juan C; Duran R, Carlos E; Perafan B, Pablo; Pava M, Luis F

    2010-01-01

    Atrioventricular nodal reentry tachycardia is the most common type of paroxysmal supraventricular tachycardia. In those patients in whom drug therapy is not effective or not desired, radio frequency ablation is an excellent therapeutic method. Although overall these procedures are fast and safe, several complications among which ischemic stroke stands out, have been reported. We present the case of a 41 year old female patient with repetitive episodes of tachycardia due to nodal reentry who was treated with radiofrequency ablation. Immediately after the procedure she presented focal neurologic deficit consistent with ischemic stroke in the right medial cerebral artery territory. Angiography with angioplastia and abxicimab was performed and then tissue plasminogen activator (rtPA) was locally infused, with appropriate clinical and angiographic outcome.

  18. RELAP 4/MOD 6 boiling water nodalization study

    International Nuclear Information System (INIS)

    Sonneck, G.; Pfau, H.

    1985-09-01

    The risk of nuclear steam supply systems is dominated by the core melt accidents. The first step to a realistic assessment of these sequences is the successful prediction of a loss of coolant event in a test loop. One of the codes for that is RELAP 4/MOD 6 and one of the important options in this code is the nodalization. The base of this work is the test LOCA No. 1 FIX II in Studsvik (Sweden) which also served as the OECD International Standard Problem 15. This report discusses the influence of different nodalizations, of different distributions of pressure, water and structural heat as well as of different bubble rise options, break flow coefficients, and heat transfer time steps. The most important result is that a simple RELAP 4/MOD6 model with less than 10 volumes is able to predict an experiment as LOCA No. 1 in FIX II successfully using only a fraction of the usual computing time. (Author)

  19. A nodal model for the simulation of a PWR core

    International Nuclear Information System (INIS)

    Souza Pinto, R. de.

    1981-06-01

    A computer program FORTRAN language was developed to simulate the neutronic and thermal-hydraulic transient behaviour of a PWR reactor core. The reator power is calculated using a point kinectics model with six groups of delayed neutron precursors. The fission product decay heat was considered assuming three effective decay heat groups. A nodal model was employed for the treatment of heat transfer in the fuel rod, with integration of the heat equation by the lumped parameter technique. Axial conduction was neglected. A single-channel nodal model was developed for the thermo-hydrodynamic simulation using mass and energy conservation equations for the control volumes. The effect of the axial pressure variation was neglected. The computer program was tested, with good results, through the simulation of the transient behaviour of postulated accidents in a typical PWR. (Author) [pt

  20. The variational nodal method: some history and recent activity

    International Nuclear Information System (INIS)

    Lewis, E.E.; Smith, M.A.; Palmiotti, G.

    2005-01-01

    The variational nodal method combines spherical harmonics expansions in angle with hybrid finite element techniques in space to obtain multigroup transport response matrix algorithms applicable to a wide variety of reactor physics problems. This survey briefly recounts the method's history and reviews its capabilities. Two methods for obtaining discretized equations in the form of response matrices are compared. The first is that contained the widely used VARIANT code, while the second incorporates more recently developed integral transport techniques into the variational nodal framework. The two approaches are combined with a finite sub-element formulation to treat heterogeneous nodes. Results are presented for application to a deep penetration problem and to an OECD benchmark consisting of LWR Mox fuel assemblies. Ongoing work is discussed. (authors)

  1. Localized extramedullary relapse after autologous hematopoietic stem cell transplantation in multiple myeloma

    International Nuclear Information System (INIS)

    Erkus, Muhan; Meteoglu, Ibrahim; Bolaman, Zahit; Kadikoylu, Gurhan

    2005-01-01

    Extramedullary plasmacytomas are rare manifestation of plasma cell malignancies. After hematopoietic stem cell transplantation HSCT, presentation of localized plasmacytoma with extramedullary growth is very unusual. We report a case of a 56-year-old woman with Dune-Salmon stage IIIA immunoglobulin A-kappa multiple myeloma, which presented 120 days after autologous HSCT with extramedullary plasmacytoma arising from a lymph node in supraclavicular region. The patient had no pretransplant-history related with extramedullary disease. There was no increase of plasma cells in bone marrow or monoclonal protein in urine or serum. Aspiration smears of lymph node revealed a population of plasmacytoid cells at various stages of maturation. The patient was successfully treated with local radiotherapy and has remained progression-free for more than 20 months. (author)

  2. T regulatory cells are markers of disease activity in multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Dacia Dalla Libera

    Full Text Available FoxP3⁺ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS, an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis.

  3. Modifications of S-phase cell distribution in the intestinal crypts after multiple daily fractionation

    Energy Technology Data Exchange (ETDEWEB)

    Becciolini, A; Cremonini, D; Fabbrica, D; Balzi, M [Florence Univ. (Italy). Ist. di Radiologia

    1983-01-01

    The effects obtained by multiple daily fractionation (3 Gy x2 or 3 Gy x2x2) on the distribution of S-phase cells along the crypt of the small intestine were investigated. The frequency of labelled cell distribution was reduced at early intervals; then the proliferating compartment gradually extended to the villus junctions. During recovery labelled cell frequency in the lower half of the crypts returned to control levels, while labelled cells were present in the differentiating area. With lower total dose modifications were milder and, as early as 72 h before exposure, distribution was already similar to controls. Invertase activity showed an initial increase and a higher reduction during acute damage when fractionation with higher doses was used. A lack of return to normal activity was present even 11 days after exposure when, however, the characteristic circadian pattern was observed.

  4. Encapsulation of Multiple Microalgal Cells via a Combination of Biomimetic Mineralization and LbL Coating

    Directory of Open Access Journals (Sweden)

    Minjeong Kim

    2018-02-01

    Full Text Available The encapsulation of living cells is appealing for its various applications to cell-based sensors, bioreactors, biocatalysts, and bioenergy. In this work, we introduce the encapsulation of multiple microalgal cells in hollow polymer shells of rhombohedral shape by the following sequential processes: embedding of microalgae in CaCO3 crystals; layer-by-layer (LbL coating of polyelectrolytes; and removal of sacrificial crystals. The microcapsule size was controlled by the alteration of CaCO3 crystal size, which is dependent on CaCl2/Na2CO3 concentration. The microalgal cells could be embedded in CaCO3 crystals by a two-step process: heterogeneous nucleation of crystal on the cell surface followed by cell embedment by the subsequent growth of crystal. The surfaces of the microalgal cells were highly favorable for the crystal growth of calcite; thus, micrometer-sized microalgae could be perfectly occluded in the calcite crystal without changing its rhombohedral shape. The surfaces of the microcapsules, moreover, could be decorated with gold nanoparticles, Fe3O4 magnetic nanoparticles, and carbon nanotubes (CNTs, by which we would expect the functionalities of a light-triggered release, magnetic separation, and enhanced mechanical and electrical strength, respectively. This approach, entailing the encapsulation of microalgae in semi-permeable and hollow polymer microcapsules, has the potential for application to microbial-cell immobilization for high-biomass-concentration cultivation as well as various other bioapplications.

  5. Encapsulation of Multiple Microalgal Cells via a Combination of Biomimetic Mineralization and LbL Coating.

    Science.gov (United States)

    Kim, Minjeong; Choi, Myoung Gil; Ra, Ho Won; Park, Seung Bin; Kim, Yong-Joo; Lee, Kyubock

    2018-02-13

    The encapsulation of living cells is appealing for its various applications to cell-based sensors, bioreactors, biocatalysts, and bioenergy. In this work, we introduce the encapsulation of multiple microalgal cells in hollow polymer shells of rhombohedral shape by the following sequential processes: embedding of microalgae in CaCO₃ crystals; layer-by-layer (LbL) coating of polyelectrolytes; and removal of sacrificial crystals. The microcapsule size was controlled by the alteration of CaCO₃ crystal size, which is dependent on CaCl₂/Na₂CO₃ concentration. The microalgal cells could be embedded in CaCO₃ crystals by a two-step process: heterogeneous nucleation of crystal on the cell surface followed by cell embedment by the subsequent growth of crystal. The surfaces of the microalgal cells were highly favorable for the crystal growth of calcite; thus, micrometer-sized microalgae could be perfectly occluded in the calcite crystal without changing its rhombohedral shape. The surfaces of the microcapsules, moreover, could be decorated with gold nanoparticles, Fe₃O₄ magnetic nanoparticles, and carbon nanotubes (CNTs), by which we would expect the functionalities of a light-triggered release, magnetic separation, and enhanced mechanical and electrical strength, respectively. This approach, entailing the encapsulation of microalgae in semi-permeable and hollow polymer microcapsules, has the potential for application to microbial-cell immobilization for high-biomass-concentration cultivation as well as various other bioapplications.

  6. Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

    Science.gov (United States)

    Al-Habib, Mey; Yu, Zongdong

    2013-01-01

    One fundamental issue regarding stem cells for regenerative medicine is the maintenance of stem cell stemness. The purpose of the study was to test whether small molecules can enhance stem cell properties of mesenchymal stem cells (MSCs) derived from human dental pulp (hDPSCs), which have potential for multiple clinical applications. We identified the effects of small molecules (Pluripotin (SC1), 6-bromoindirubin-3-oxime and rapamycin) on the maintenance of hDPSC properties in vitro and the mechanisms involved in exerting the effects. Primary cultures of hDPSCs were exposed to optimal concentrations of these small molecules. Treated hDPSCs were analyzed for their proliferation, the expression levels of pluripotent and MSC markers, differentiation capacities, and intracellular signaling activations. We found that small molecule treatments decreased cell proliferation and increased the expression of STRO-1, NANOG, OCT4, and SOX2, while diminishing cell differentiation into odonto/osteogenic, adipogenic, and neurogenic lineages in vitro. These effects involved Ras-GAP-, ERK1/2-, and mTOR-signaling pathways, which may preserve the cell self-renewal capacity, while suppressing differentiation. We conclude that small molecules appear to enhance the immature state of hDPSCs in culture, which may be used as a strategy for adult stem cell maintenance and extend their capacity for regenerative applications. PMID:23573877

  7. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

    Science.gov (United States)

    Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo; Giavaresi, Gianluca; Alessandro, Riccardo

    2015-01-01

    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix Metalloproteinases 9 (MMP9) and Tartrate-resistant Acid Phosphatase (TRAP). Pre-osteoclast treated with MM cell-derived exosomes differentiate in multinuclear OCs able to excavate authentic resorption lacunae. Similar results were obtained with exosomes derived from MM patient's sera. Our data indicate that MM-exosomes modulate OCs function and differentiation. Further studies are needed to identify the OCs activating factors transported by MM cell-derived exosomes. PMID:25944696

  8. HEXAN - a hexagonal nodal code for solving the diffusion equation

    International Nuclear Information System (INIS)

    Makai, M.

    1982-07-01

    This report describes the theory of and provides a user's manual for the HEXAN program, which is a nodal program for the solution of the few-group diffusion equation in hexagonal geometry. Based upon symmetry considerations, the theory provides an analytical solution in a homogeneous node. WWER and HTGR test problem solutions are presented. The equivalence of the finite-difference scheme and the response matrix method is proven. The properties of a symmetric node's response matrix are investigated. (author)

  9. Cerebral blood flow and red cell delivery in normal subjects and in multiple sclerosis

    International Nuclear Information System (INIS)

    Swank, R.L.; Roth, J.G.; Woody, D.C. Jr.

    1983-01-01

    Regional cerebral blood flow (rCBF) was determined in 77 normal females and 53 normal males of different ages and in 26 men and 45 women with multiple sclerosis by the inhalation of radioactive Xe133 method. In the normal subjects the CBF was relatively high in the teens and fell, at first rapidly and then slowly in both sexes with age. During adult life the flow in females was significantly higher than in males. The delivery of packed red cells (RCD) was determined by multiplying the CBF by the percentage concentration of red cells (HCT). The RCD for both sexes was nearly the same. In the patients with multiple sclerosis there occurred a progressive generalized decrease in CBF and in RCD with age which was significantly greater than observed in normal subjects. The rate of decrease in CBF and RCD correlated directly with the rate of progress of the disease

  10. Twelve-year survival after multiple recurrences and repeated metastasectomies for renal cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Wang Jue

    2011-11-01

    Full Text Available Abstract Background Metastatic renal cell carcinoma (RCC presents a therapeutic challenge for clinicians because of the unpredictable clinical course, resistance to chemotherapy or radiotherapy and the limited response to immunotherapy. Patients and Methods We report a case of a 62-year-old woman who underwent nephrectomy for T4N0 RCC, clear cell type, Fuhrman grade 3/4 in 1999. The patinet subsequently had multiple tumor recurrences. Results The patient underwent eight metastasectomies, including multiple partial left nephrectomies, right adrenalectomy, a complete left nephrectomy, and distal pancreatectomy. She remains well and tumor free 12 years after initial diagnosis. Conclusion Repeated resections after initial metastasectomy can be carried out safely and provide long-term survival in selected patients with recurrent metastasis from RCC. The findings from our case indicate that close follow-up for the early detection of recurrence and complete resection of metastases can improve the results after repeated resection.

  11. Multiple Synchronous Central Giant Cell Granulomas of the Maxillofacial Region: A Case Report

    International Nuclear Information System (INIS)

    Kang, Min Seok; Kim, Hak Jin

    2010-01-01

    Multifocal central giant cell granulomas (CGCG) in the maxillofacial region are suggestive of systemic disease such as hyperparathyroidism or an inherited syndrome such as Noonan-like multiple giant cell lesion syndrome. Only 5 cases of multifocal CGCGs in the maxillofacial region without any concomitant systemic disease have currently been reported. We report here on an unusual case of 17-year-old man who presented with multifocal CGCGs of the bilateral posterior mandible and right maxilla and he was without any concomitant systemic disease

  12. Multiple Synchronous Central Giant Cell Granulomas of the Maxillofacial Region: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Min Seok; Kim, Hak Jin [Pusan National University Hospital, Busan (Korea, Republic of)

    2010-01-15

    Multifocal central giant cell granulomas (CGCG) in the maxillofacial region are suggestive of systemic disease such as hyperparathyroidism or an inherited syndrome such as Noonan-like multiple giant cell lesion syndrome. Only 5 cases of multifocal CGCGs in the maxillofacial region without any concomitant systemic disease have currently been reported. We report here on an unusual case of 17-year-old man who presented with multifocal CGCGs of the bilateral posterior mandible and right maxilla and he was without any concomitant systemic disease

  13. Merkel cell carcinoma with fingolimod treatment for multiple sclerosis: A case report.

    Science.gov (United States)

    Mahajan, Kedar R; Ko, Jennifer S; Tetzlaff, Michael T; Hudgens, Courtney W; Billings, Steven D; Cohen, Jeffrey A

    2017-10-01

    Neoplasms and reactivation of latent viruses have been observed in individuals taking fingolimod. Merkel cell carcinoma (MCC), a rare neuroendocrine skin cancer, is associated with immunosuppression and can be triggered by the oncogenic Merkel cell polyoma virus (MCPyV). We report a case of a 61-year-old man with multiple sclerosis who developed MCPyV-positive MCC 4 years after starting fingolimod. This is the second report of MCC associated with MCPyV in an individual on fingolimod. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Multiple growths of epitaxial lift-off solar cells from a single InP substrate

    International Nuclear Information System (INIS)

    Lee, Kyusang; Shiu, Kuen-Ting; Zimmerman, Jeramy D.; Forrest, Stephen R.; Renshaw, Christopher K.

    2010-01-01

    We demonstrate multiple growths of flexible, thin-film indium tin oxide-InP Schottky-barrier solar cells on a single InP wafer via epitaxial lift-off (ELO). Layers that protect the InP parent wafer surface during the ELO process are subsequently removed by selective wet-chemical etching, with the active solar cell layers transferred to a thin, flexible plastic host substrate by cold welding at room temperature. The first- and second-growth solar cells exhibit no performance degradation under simulated Atmospheric Mass 1.5 Global (AM 1.5G) illumination, and have a power conversion efficiency of η p =14.4±0.4% and η p =14.8±0.2%, respectively. The current-voltage characteristics for the solar cells and atomic force microscope images of the substrate indicate that the parent wafer is undamaged, and is suitable for reuse after ELO and the protection-layer removal processes. X-ray photoelectron spectroscopy, reflection high-energy electron diffraction observation, and three-dimensional surface profiling show a surface that is comparable or improved to the original epiready wafer following ELO. Wafer reuse over multiple cycles suggests that high-efficiency; single-crystal thin-film solar cells may provide a practical path to low-cost solar-to-electrical energy conversion.

  15. Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells

    Directory of Open Access Journals (Sweden)

    Kaur Punit

    2008-11-01

    Full Text Available Abstract Background There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Methods Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide], flow cytometry, cytoskeleton organization analysis, cell cycle, mitochondria membrane depolarization, clonogenicity test, DNA fragmentation test and differential protein expression by HPLC-Chip/MS analysis. F4 fraction characterization was made by HPLC-MS. Results Petiveria alliacea fraction characterized by de-replication was found to alter actin cytoskeleton organization, induce G2 cell cycle arrest and cause apoptotic cell death in a mitochondria independent way. In addition, we found down regulation of cytoskeleton, chaperone, signal transduction proteins, and proteins involved in metabolic pathways. Finally up regulation of proteins involved in translation and intracellular degradation was also observed. Conclusion The results of this study indicate that Petiveria alliacea exerts multiple biological activities in vitro consistent with cytotoxicity. Further studies in animal models are needed but Petiveria alliacea appears to be a good candidate to be used as an antitumor agent.

  16. Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development.

    Science.gov (United States)

    Lentucci, Claudia; Belkina, Anna C; Cederquist, Carly T; Chan, Michelle; Johnson, Holly E; Prasad, Sherry; Lopacinski, Amanda; Nikolajczyk, Barbara S; Monti, Stefano; Snyder-Cappione, Jennifer; Tanasa, Bogdan; Cardamone, M Dafne; Perissi, Valentina

    2017-02-17

    Non-proteolytic ubiquitin signaling mediated by Lys 63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNFα signaling and lipid metabolism in the adipose tissue through modulation of Lys 63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Petiveria alliacea extracts uses multiple mechanisms to inhibit growth of human and mouse tumoral cells.

    Science.gov (United States)

    Urueña, Claudia; Cifuentes, Claudia; Castañeda, Diana; Arango, Amparo; Kaur, Punit; Asea, Alexzander; Fiorentino, Susana

    2008-11-18

    There is ethnopharmacological evidence that Petiveria alliacea can have antitumor activity; however, the mechanism of its cytotoxic activity is not well understood. We assessed multiple in vitro biological activities of an ethyl acetate soluble plant fraction over several tumor cell lines. Tumor cell lines were evaluated using the following tests: trypan blue exclusion test, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide], flow cytometry, cytoskeleton organization analysis, cell cycle, mitochondria membrane depolarization, clonogenicity test, DNA fragmentation test and differential protein expression by HPLC-Chip/MS analysis. F4 fraction characterization was made by HPLC-MS. Petiveria alliacea fraction characterized by de-replication was found to alter actin cytoskeleton organization, induce G2 cell cycle arrest and cause apoptotic cell death in a mitochondria independent way. In addition, we found down regulation of cytoskeleton, chaperone, signal transduction proteins, and proteins involved in metabolic pathways. Finally up regulation of proteins involved in translation and intracellular degradation was also observed. The results of this study indicate that Petiveria alliacea exerts multiple biological activities in vitro consistent with cytotoxicity. Further studies in animal models are needed but Petiveria alliacea appears to be a good candidate to be used as an antitumor agent.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  19. Treatment of multiple unresectable basal cell carcinomas from Gorlin-Goltz syndrome: a case report.

    Science.gov (United States)

    Ojevwe, Fidelis O; Ojevwe, Cindy D; Zacny, James P; Dudek, Arkadiusz Z; Lin, Amy; Kohlitz, Patrick

    2015-03-01

    Nevoid basal cell carcinoma syndrome (NBCCS), which is also known by other names, including Gorlin-Goltz syndrome and multiple basal-cell carcinoma (BCC) syndrome, is a rare multi-systemic disease inherited in a dominant autosomal manner with complete penetrance and variable expressivity. The main clinical manifestations include multiple BCCs, odontogenic keratocysts of the jaw, hyperkeratosis of the palms and soles, skeletal abnormalities, intracranial calcifications and facial deformities. A 31-year-old male diagnosed with Gorlin-Goltz syndrome with multiple unresectable facial BCCs was treated with the Hedgehog inhibitor vismodegib. After one month of therapy on vismodegib, there were significant reductions in the size of multiple BCCs on the patient's face. The patient remains on this therapy. Hedgehog pathway inhibition is an effective strategy to treat unresectable BCCs from Gorlin-Goltz syndrome. Although vismodegib shows some promising clinical results in the early phase of its use, there are concerns of possible resistance developing within months. Duration of therapy, role of maintenance treatment and drug modification to reduce resistance need to be explored in future case studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Altered 67Ga citrate distribution in patients with multiple red blood cell transfusions

    International Nuclear Information System (INIS)

    Engelstad, B.; Luk, S.S.; Hattner, R.S.

    1982-01-01

    Gallium-67 citrate studies from four patients who received multiple red blood cell transfusions were reviewed. Increased kidney, bladder, or bone localization was associated with decreased liver and colon activity. The findings suggest altered distribution due to competition with iron for receptor binding. Identification of inflammatory disease in two patients was possible. However, the effect of transfusions on detection of inflammatory or neoplastic diseases requires further evaluation

  1. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation

    OpenAIRE

    Raimondi, Lavinia; De Luca, Angela; Amodio, Nicola; Manno, Mauro; Raccosta, Samuele; Taverna, Simona; Bellavia, Daniele; Naselli, Flores; Fontana, Simona; Schillaci, Odessa; Giardino, Roberto; Fini, Milena; Tassone, Pierfrancesco; Santoro, Alessandra; De Leo, Giacomo

    2015-01-01

    Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs ...

  2. NOMAD: a nodal microscopic analysis method for nuclear fuel depletion

    International Nuclear Information System (INIS)

    Rajic, H.L.; Ougouag, A.M.

    1987-01-01

    Recently developed assembly homogenization techniques made possible very efficient global burnup calculations based on modern nodal methods. There are two possible ways of modeling the global depletion process: macroscopic and microscopic depletion models. Using a microscopic global depletion approach NOMAD (NOdal Microscopic Analysis Method for Nuclear Fuel Depletion), a multigroup, two- and three-dimensional, multicycle depletion code was devised. The code uses the ILLICO nodal diffusion model. The formalism of the ILLICO methodology is extended to treat changes in the macroscopic cross sections during a depletion cycle without recomputing the coupling coefficients. This results in a computationally very efficient method. The code was tested against a well-known depletion benchmark problem. In this problem a two-dimensional pressurized water reactor is depleted through two cycles. Both cycles were run with 1 x 1 and 2 x 2 nodes per assembly. It is obvious that the one node per assembly solution gives unacceptable results while the 2 x 2 solution gives relative power errors consistently below 2%

  3. Flow-based market coupling. Stepping stone towards nodal pricing?

    International Nuclear Information System (INIS)

    Van der Welle, A.J.

    2012-07-01

    For achieving one internal energy market for electricity by 2014, market coupling is deployed to integrate national markets into regional markets and ultimately one European electricity market. The extent to which markets can be coupled depends on the available transmission capacities between countries. Since interconnections are congested from time to time, congestion management methods are deployed to divide the scarce available transmission capacities over market participants. For further optimization of the use of available transmission capacities while maintaining current security of supply levels, flow-based market coupling (FBMC) will be implemented in the CWE region by 2013. Although this is an important step forward, important hurdles for efficient congestion management remain. Hence, flow based market coupling is compared to nodal pricing, which is often considered as the most optimal solution from theoretical perspective. In the context of decarbonised power systems it is concluded that advantages of nodal pricing are likely to exceed its disadvantages, warranting further development of FBMC in the direction of nodal pricing.

  4. An iterative algorithm for solving the multidimensional neutron diffusion nodal method equations on parallel computers

    International Nuclear Information System (INIS)

    Kirk, B.L.; Azmy, Y.Y.

    1992-01-01

    In this paper the one-group, steady-state neutron diffusion equation in two-dimensional Cartesian geometry is solved using the nodal integral method. The discrete variable equations comprise loosely coupled sets of equations representing the nodal balance of neutrons, as well as neutron current continuity along rows or columns of computational cells. An iterative algorithm that is more suitable for solving large problems concurrently is derived based on the decomposition of the spatial domain and is accelerated using successive overrelaxation. This algorithm is very well suited for parallel computers, especially since the spatial domain decomposition occurs naturally, so that the number of iterations required for convergence does not depend on the number of processors participating in the calculation. Implementation of the authors' algorithm on the Intel iPSC/2 hypercube and Sequent Balance 8000 parallel computer is presented, and measured speedup and efficiency for test problems are reported. The results suggest that the efficiency of the hypercube quickly deteriorates when many processors are used, while the Sequent Balance retains very high efficiency for a comparable number of participating processors. This leads to the conjecture that message-passing parallel computers are not as well suited for this algorithm as shared-memory machines

  5. In Silico Prediction Analysis of Idiotope-Driven T–B Cell Collaboration in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Rune A. Høglund

    2017-10-01

    Full Text Available Memory B cells acting as antigen-presenting cells are believed to be important in multiple sclerosis (MS, but the antigen they present remains unknown. We hypothesized that B cells may activate CD4+ T cells in the central nervous system of MS patients by presenting idiotopes from their own immunoglobulin variable regions on human leukocyte antigen (HLA class II molecules. Here, we use bioinformatics prediction analysis of B cell immunoglobulin variable regions from 11 MS patients and 6 controls with other inflammatory neurological disorders (OINDs, to assess whether the prerequisites for such idiotope-driven T–B cell collaboration are present. Our findings indicate that idiotopes from the complementarity determining region (CDR 3 of MS patients on average have high predicted affinities for disease associated HLA-DRB1*15:01 molecules and are predicted to be endosomally processed by cathepsin S and L in positions that allows such HLA binding to occur. Additionally, complementarity determining region 3 sequences from cerebrospinal fluid (CSF B cells from MS patients contain on average more rare T cell-exposed motifs that could potentially escape tolerance and stimulate CD4+ T cells than CSF B cells from OIND patients. Many of these features were associated with preferential use of the IGHV4 gene family by CSF B cells from MS patients. This is the first study to combine high-throughput sequencing of patient immune repertoires with large-scale prediction analysis and provides key indicators for future in vitro and in vivo analyses.

  6. N-way FRET microscopy of multiple protein-protein interactions in live cells.

    Directory of Open Access Journals (Sweden)

    Adam D Hoppe

    Full Text Available Fluorescence Resonance Energy Transfer (FRET microscopy has emerged as a powerful tool to visualize nanoscale protein-protein interactions while capturing their microscale organization and millisecond dynamics. Recently, FRET microscopy was extended to imaging of multiple donor-acceptor pairs, thereby enabling visualization of multiple biochemical events within a single living cell. These methods require numerous equations that must be defined on a case-by-case basis. Here, we present a universal multispectral microscopy method (N-Way FRET to enable quantitative imaging for any number of interacting and non-interacting FRET pairs. This approach redefines linear unmixing to incorporate the excitation and emission couplings created by FRET, which cannot be accounted for in conventional linear unmixing. Experiments on a three-fluorophore system using blue, yellow and red fluorescent proteins validate the method in living cells. In addition, we propose a simple linear algebra scheme for error propagation from input data to estimate the uncertainty in the computed FRET images. We demonstrate the strength of this approach by monitoring the oligomerization of three FP-tagged HIV Gag proteins whose tight association in the viral capsid is readily observed. Replacement of one FP-Gag molecule with a lipid raft-targeted FP allowed direct observation of Gag oligomerization with no association between FP-Gag and raft-targeted FP. The N-Way FRET method provides a new toolbox for capturing multiple molecular processes with high spatial and temporal resolution in living cells.

  7. Tackling Energy Loss for High-Efficiency Organic Solar Cells with Integrated Multiple Strategies.

    Science.gov (United States)

    Zuo, Lijian; Shi, Xueliang; Jo, Sae Byeok; Liu, Yun; Lin, Fracis; Jen, Alex K-Y

    2018-04-01

    Limited by the various inherent energy losses from multiple channels, organic solar cells show inferior device performance compared to traditional inorganic photovoltaic techniques, such as silicon and CuInGaSe. To alleviate these fundamental limitations, an integrated multiple strategy is implemented including molecular design, interfacial engineering, optical manipulation, and tandem device construction into one cell. Considering the close correlation among these loss channels, a sophisticated quantification of energy-loss reduction is tracked along with each strategy in a perspective to reach rational overall optimum. A novel nonfullerene acceptor, 6TBA, is synthesized to resolve the thermalization and V OC loss, and another small bandgap nonfullerene acceptor, 4TIC, is used in the back sub-cell to alleviate transmission loss. Tandem architecture design significantly reduces the light absorption loss, and compensates carrier dynamics and thermalization loss. Interfacial engineering further reduces energy loss from carrier dynamics in the tandem architecture. As a result of this concerted effort, a very high power conversion efficiency (13.20%) is obtained. A detailed quantitative analysis on the energy losses confirms that the improved device performance stems from these multiple strategies. The results provide a rational way to explore the ultimate device performance through molecular design and device engineering. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Tbx6 regulates left/right patterning in mouse embryos through effects on nodal cilia and perinodal signaling.

    Directory of Open Access Journals (Sweden)

    Anna-Katerina Hadjantonakis

    Full Text Available BACKGROUND: The determination of left/right body axis during early embryogenesis sets up a developmental cascade that coordinates the development of the viscera and is essential to the correct placement and alignment of organ systems and vasculature. Defective left-right patterning can lead to congenital cardiac malformations, vascular anomalies and other serious health problems. Here we describe a novel role for the T-box transcription factor gene Tbx6 in left/right body axis determination in the mouse. RESULTS: Embryos lacking Tbx6 show randomized embryo turning and heart looping. Our results point to multiple mechanisms for this effect. First, Dll1, a direct target of Tbx6, is down regulated around the node in Tbx6 mutants and there is a subsequent decrease in nodal signaling, which is required for laterality determination. Secondly, in spite of a lack of expression of Tbx6 in the node, we document a profound effect of the Tbx6 mutation on the morphology and motility of nodal cilia. This results in the loss of asymmetric calcium signaling at the periphery of the node, suggesting that unidirectional nodal flow is disrupted. To carry out these studies, we devised a novel method for direct labeling and live imaging cilia in vivo using a genetically-encoded fluorescent protein fusion that labels tubulin, combined with laser point scanning confocal microscopy for direct visualization of cilia movement. CONCLUSIONS: We conclude that the transcription factor gene Tbx6 is essential for correct left/right axis determination in the mouse and acts through effects on notch signaling around the node as well as through an effect on the morphology and motility of the nodal cilia.

  9. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Drent, Esther; Groen, Richard W. J.; Noort, Willy A. Noort

    2016-01-01

    Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy. Prompted by this, we used three different CD38 antibody...... sequences to generate second-generation retroviral CD38- chimeric antigen receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients. We then evaluated the preclinical efficacy and safety of the transduced T cells. Irrespective of the donor and antibody sequence......, CD38-chimeric antigen receptor-transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite...

  10. Electric properties and carrier multiplication in breakdown sites in multi-crystalline silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Schneemann, Matthias; Carius, Reinhard; Rau, Uwe [IEK5-Photovoltaics, Forschungszentrum Jülich, Jülich 52425 (Germany); Kirchartz, Thomas, E-mail: t.kirchartz@fz-juelich.de [IEK5-Photovoltaics, Forschungszentrum Jülich, Jülich 52425 (Germany); Faculty of Engineering and CENIDE, University of Duisburg-Essen, Carl-Benz-Str. 199, Duisburg 47057 (Germany)

    2015-05-28

    This paper studies the effective electrical size and carrier multiplication of breakdown sites in multi-crystalline silicon solar cells. The local series resistance limits the current of each breakdown site and is thereby linearizing the current-voltage characteristic. This fact allows the estimation of the effective electrical diameters to be as low as 100 nm. Using a laser beam induced current (LBIC) measurement with a high spatial resolution, we find carrier multiplication factors on the order of 30 (Zener-type breakdown) and 100 (avalanche breakdown) as new lower limits. Hence, we prove that also the so-called Zener-type breakdown is followed by avalanche multiplication. We explain that previous measurements of the carrier multiplication using thermography yield results higher than unity, only if the spatial defect density is high enough, and the illumination intensity is lower than what was used for the LBIC method. The individual series resistances of the breakdown sites limit the current through these breakdown sites. Therefore, the measured multiplication factors depend on the applied voltage as well as on the injected photocurrent. Both dependencies are successfully simulated using a series-resistance-limited diode model.

  11. Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey

    NARCIS (Netherlands)

    Belkacemi, Y.; Kaidar-Person, O.; Poortmans, P.; Ozsahin, M.; Valli, M.-C.; Russell, N.; Kunkler, I.; Hermans, J.; Kuten, A.; van Tienhoven, G.; Westenberg, H.

    2015-01-01

    Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine

  12. B cell follicle-like structures in multiple sclerosis-with focus on the role of B cell activating factor

    DEFF Research Database (Denmark)

    Morten, Haugen; Frederiksen, Jette L; Vinter, Matilda Degn

    2014-01-01

    B lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). Follicle-like structures (FLS) have recently been found in the subarachnoid space in the leptomeninges in some patients with secondary progressive MS (SPMS). They contain proliferating B lymphocytes, plasma cells......, helper T lymphocytes and a network of follicular dendritic cells. FLS have been shown to correlate with increased cortical demyelination, neuronal loss, meningeal infiltration and central nervous system inflammation, as well as lower age at disease onset and progression to severe disability and death....... In this review, we will discuss the role of FLS in MS pathogenesis and disease course and the possible influence by B cell activating factor (BAFF) and C-X-C motif chemokine 13 (CXCL13)....

  13. Replication of Syngrapha falcifera Multiple-Nuclear Polyhedrosis Virus-D in Different Insect Cells

    Science.gov (United States)

    Khalid Nessr Alhag, Sadeq; Xin, Peng Jian

    Six insect cell lines were tested for susceptibility to Syngrapha falcifera multiple nucleocapsid nucleopolyhedrovirus-D (SfaMNPV-D) infection by use of a typical endpoint assay procedure. Cell lines from Trichoplusia ni (Tn5B1-4), (L105-clone), Spodoptera litura (SL-ZSU-1), Spodoptera frugiperda (IPLB-SF-21), Pieris rapaeb (Pr-E-HNU9) and Helicoverpa zea (BCIRL-HZ-AM1) in 96-well tissue culture plates were infected with dilutions of extra cellular virus suspensions of (SfaMNPV-D). Each cell/virus combination was incubated at temperatures 27°C and wells were scored for positive infection at 2 to 4 day intervals. The resulting data were analyzed by Reed and Muench method, providing virus titers for each combination of virus, cell line. The results were categorized by accuracy and by rapidity of maximum titer. Virus titer of Tn5B-4 was higher than other cell lines TCID50 8.7x108, the lowest level detected in infected was in (Pr-E-HNU9) cells TCID50 2.4x108. No Virions or polyhedral inclusion bodies were detected in infected SL-ZSU-1 cells.

  14. Comparative proteomics analysis of Spodoptera frugiperda cells during Autographa californica multiple nucleopolyhedrovirus infection.

    Science.gov (United States)

    Yu, Qian; Xiong, Youhua; Gao, Hang; Liu, Jianliang; Chen, Zhiqiang; Wang, Qin; Wen, Dongling

    2015-08-04

    Increasing evidence sugggest that in addition of balculovirus controling insect host, host cells also responds to balculovirus infection. However, compared to existing knowledge on virus gene, host cell responses are relatively poorly understood. In this study, Spodoptera frugiperda (Sf9) cells were infected with Autographa californica multiple nucleopolyhedrovirus (AcMNPV). The protein composition and protein changes of Spodoptera frugiperda (Sf9) cells of different infection stages were analysed by isobaric tag for relative and absolute quantification (iTRAQ) techniques. A total of 4004 Sf9 proteins were identified by iTRAQ and 413 proteins were found as more than 1.5-fold changes in abundance. The 413 proteins were categorised according to GO classification for insects and were categorised into: biological process, molecular function and cellular component. The determination of the protein changes in infected Sf9 cells would help to better understanding of host cell responses and facilitate better design of this virus-host cell interaction in pest insect control and other related fields.

  15. Cerebrospinal fluid B cells correlate with early brain inflammation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Bettina Kuenz

    Full Text Available BACKGROUND: There is accumulating evidence from immunological, pathological and therapeutic studies that B cells are key components in the pathophysiology of multiple sclerosis (MS. METHODOLOGY/PRINCIPAL FINDINGS: In this prospective study we have for the first time investigated the differences in the inflammatory response between relapsing and progressive MS by comparing cerebrospinal fluid (CSF cell profiles from patients at the onset of the disease (clinically isolated syndrome, CIS, relapsing-remitting (RR and chronic progressive (CP MS by flow cytometry. As controls we have used patients with other neurological diseases. We have found a statistically significant accumulation of CSF mature B cells (CD19+CD138- and plasma blasts (CD19+CD138+ in CIS and RRMS. Both B cell populations were, however, not significantly increased in CPMS. Further, this accumulation of B cells correlated with acute brain inflammation measured by magnetic resonance imaging and with inflammatory CSF parameters such as the number of CSF leukocytes, intrathecal immunoglobulin M and G synthesis and intrathecal production of matrix metalloproteinase (MMP-9 and the B cell chemokine CxCL-13. CONCLUSIONS: Our data support an important role of CSF B cells in acute brain inflammation in CIS and RRMS.

  16. Cell cycle commitment in budding yeast emerges from the cooperation of multiple bistable switches

    Science.gov (United States)

    Zhang, Tongli; Schmierer, Bernhard; Novák, Béla

    2011-01-01

    The start-transition (START) in the G1 phase marks the point in the cell cycle at which a yeast cell initiates a new round of cell division. Once made, this decision is irreversible and the cell is committed to progressing through the entire cell cycle, irrespective of arrest signals such as pheromone. How commitment emerges from the underlying molecular interaction network is poorly understood. Here, we perform a dynamical systems analysis of an established cell cycle model, which has never been analysed from a commitment perspective. We show that the irreversibility of the START transition and subsequent commitment can be consistently explained in terms of the interplay of multiple bistable molecular switches. By applying an existing mathematical model to a novel problem and by expanding the model in a self-consistent manner, we achieve several goals: we bring together a large number of experimental findings into a coherent theoretical framework; we increase the scope and the applicability of the original model; we give a systems level explanation of how the START transition and the cell cycle commitment arise from the dynamical features of the underlying molecular interaction network; and we make clear, experimentally testable predictions. PMID:22645649

  17. Micropropagation from cultured nodal explants of rose (Rosa hybrida L. cv. ‘Perfume Delight’

    Directory of Open Access Journals (Sweden)

    Kamnoon Kanchanapoom

    2010-01-01

    Full Text Available A method for the micropropagation of rose (Rosa hybrida L. cv. ‘Perfume Delight’ was developed. First to fifth nodal explants from young healthy shoots were excised and cultured on basal medium of Murashige and Skoog (1962, MS containing several concentrations of BA and NAA. Multiple shoot formation of up to 3 shoots was obtained on MS medium supplemented with 3 mg/l BA and 0.003 mg/l NAA. Shoot readily rooted on ¼MS medium devoid of growth regulators.Rooted plantlets were hardened and established in pots at 100% survival. In vitro flowering was observed on rose plantscultured on MS medium containing 3 mg/l BA and 0.003 mg/l NAA.

  18. Geometric knowledge and scientific rigor of digital photography: the case of nodal photography

    Directory of Open Access Journals (Sweden)

    Marco Carpiceci

    2013-10-01

    Full Text Available In the past the formation of the photographic image was almost exclusively delegated to a process of shooting, developing and printing or projecting. Today the picture has so many possibilities that it is difficult to delineate a clear and focused operative boundary. In digital photography, every step offers the opportunity of transformation. However the multiple possibilities offered by digital photography implya required knowledge of all those activities in which the automatisms can prevent user from the realization processes control. As emblem of general cognitive problem, we analyze a significant application field that we define “nodal photography”. It is based on a technique produced from the development of electronics and computer, and that encompasses many aspects of technological innovation we are experiencing.

  19. Multiple origins of spontaneously arising micronuclei in HeLa cells: Direct evidence from long-term live cell imaging

    International Nuclear Information System (INIS)

    Rao Xiaotang; Zhang Yingyin; Yi Qiyi; Hou Heli; Xu Bo; Chu Liang; Huang Yun; Zhang Wenrui; Fenech, Michael; Shi Qinghua

    2008-01-01

    Although micronuclei (MNi) are extensively used to evaluate genotoxic effects and chromosome instability, the most basic issue regarding their origins has not been completely addressed due to limitations of traditional methods. Recently, long-term live cell imaging was developed to monitor the dynamics of single cell in a real-time and high-throughput manner. In the present study, this state-of-the-art technique was employed to examine spontaneous micronucleus (MN) formation in untreated HeLa cells. We demonstrate that spontaneous MNi are derived from incorrectly aligned chromosomes in metaphase (displaced chromosomes, DCs), lagging chromosomes (LCs) and broken chromosome bridges (CBs) in later mitotic stages, but not nuclear buds in S phase. However, most of bipolar mitoses with DCs (91.29%), LCs (73.11%) and broken CBs (88.93%) did not give rise to MNi. Our data also show directly, for the first time, that MNi could originate spontaneously from (1) MNi already presented in the mother cells; (2) nuclear fragments that appeared during mitosis with CB; and (3) chromosomes being extruded into a minicell which fused with one of the daughter cells later. Quantitatively, most of MNi originated from LCs (63.66%), DCs (10.97%) and broken CBs (9.25%). Taken together, these direct evidences show that there are multiple origins for spontaneously arising MNi in HeLa cells and each mechanism contributes to overall MN formation to different extents

  20. Multiple origins of spontaneously arising micronuclei in HeLa cells: Direct evidence from long-term live cell imaging

    Energy Technology Data Exchange (ETDEWEB)

    Rao Xiaotang; Zhang Yingyin; Yi Qiyi; Hou Heli; Xu Bo; Chu Liang; Huang Yun; Zhang Wenrui [Laboratory of Molecular and Cell Genetics, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China); Fenech, Michael [CSIRO Human Nutrition, PO Box 10041, Adelaide BC, Adelaide, SA 5000 (Australia); Shi Qinghua [Laboratory of Molecular and Cell Genetics, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China)], E-mail: qshi@ustc.edu.cn

    2008-11-10

    Although micronuclei (MNi) are extensively used to evaluate genotoxic effects and chromosome instability, the most basic issue regarding their origins has not been completely addressed due to limitations of traditional methods. Recently, long-term live cell imaging was developed to monitor the dynamics of single cell in a real-time and high-throughput manner. In the present study, this state-of-the-art technique was employed to examine spontaneous micronucleus (MN) formation in untreated HeLa cells. We demonstrate that spontaneous MNi are derived from incorrectly aligned chromosomes in metaphase (displaced chromosomes, DCs), lagging chromosomes (LCs) and broken chromosome bridges (CBs) in later mitotic stages, but not nuclear buds in S phase. However, most of bipolar mitoses with DCs (91.29%), LCs (73.11%) and broken CBs (88.93%) did not give rise to MNi. Our data also show directly, for the first time, that MNi could originate spontaneously from (1) MNi already presented in the mother cells; (2) nuclear fragments that appeared during mitosis with CB; and (3) chromosomes being extruded into a minicell which fused with one of the daughter cells later. Quantitatively, most of MNi originated from LCs (63.66%), DCs (10.97%) and broken CBs (9.25%). Taken together, these direct evidences show that there are multiple origins for spontaneously arising MNi in HeLa cells and each mechanism contributes to overall MN formation to different extents.

  1. B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

    International Nuclear Information System (INIS)

    Hengeveld, P J; Kersten, M J

    2015-01-01

    Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key player in this interaction. This review discusses the role of BAFF in the pathophysiology of MM, and the potential of BAFF-inhibitory therapy for the treatment of MM. Multiple studies have shown that BAFF functions as a survival factor for MMCs. Furthermore, MMCs express several BAFF-binding receptors. Of these, only Transmembrane Activator and CAML Interactor (TACI) correlates with the MMC's capability to ligate BAFF. Additionally, the level of expression of TACI correlates with the level of the MMC's BM dependency. Ligation of BAFF receptors on MMCs causes activation of the Nuclear Factor of κ-B (NF-κB) pathway, a crucial pathway for the pathogenesis of many B-cell malignancies. Serum BAFF levels are significantly elevated in MM patients when compared to healthy controls, and correlate inversely with overall survival. BAFF signaling is thus an interesting target for the treatment of MM. Several BAFF-inhibitory drugs are currently under evaluation for the treatment of MM. These include BAFF-monoclonal antibodies (tabalumab) and antibody-drug conjugates (GSK2857916)

  2. A Case of Cushing's Syndrome with Multiple Adrenocortical Adenomas Composed of Compact Cells and Clear Cells.

    Science.gov (United States)

    Asakawa, Masahiro; Yoshimoto, Takanobu; Ota, Mitsutane; Numasawa, Mitsuyuki; Sasahara, Yuriko; Takeuchi, Takato; Nakano, Yujiro; Oohara, Norihiko; Murakami, Masanori; Bouchi, Ryotaro; Minami, Isao; Tsuchiya, Kyoichiro; Hashimoto, Koshi; Izumiyama, Hajime; Kawamura, Naoko; Kihara, Kazunori; Negi, Mariko; Akashi, Takumi; Eishi, Yoshinobu; Sasano, Hironobu; Ogawa, Yoshihiro

    2016-06-01

    A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case.

  3. MESENCHYMAL STEM CELLS AS A THERAPEUTIC STRATEGY FOR MULTIPLE SCLEROSIS: ISSUES AND PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    M. M. Zafranskaya

    2017-01-01

    Full Text Available The ability of mesenchymal stem cells (MSC to influence the regulatory/suppressive effect in the autoimmune process and promote remyelination allows to consider them a new method of multiple sclerosis (MS therapy, by means of modifying the disease activity. Genetic stability, proliferative potential, ability to migrate into the damaged tissue areas and agreed protocols for isolation and culture are the main advantages for successful autologous, as well as allogeneic MSC therapy. Preliminary results from clinical studies using MSC application in MS patients show efficiency and safety of this therapeutic approach. Nevertheless, successful demonstration of the cell therapy in MS is only possible after detailed analysis and understanding of MSC biology and mechanisms of appropriate intercellular interactions. The article reviews general experience in usage of immunomodulatory and neuroprotective properties of MSС in MS, and highlights the issues of validity in cell-based therapy taking into account both in vitro и in vivo studies.

  4. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2012-11-01

    Full Text Available Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  5. Assessment of hydrogen fuel cell applications using fuzzy multiple-criteria decision making method

    International Nuclear Information System (INIS)

    Chang, Pao-Long; Hsu, Chiung-Wen; Lin, Chiu-Yue

    2012-01-01

    Highlights: ► This study uses the fuzzy MCDM method to assess hydrogen fuel cell applications. ► We evaluate seven different hydrogen fuel cell applications based on 14 criteria. ► Results show that fuel cell backup power systems should be chosen for development in Taiwan. -- Abstract: Assessment is an essential process in framing government policy. It is critical to select the appropriate targets to meet the needs of national development. This study aimed to develop an assessment model for evaluating hydrogen fuel cell applications and thus provide a screening tool for decision makers. This model operates by selecting evaluation criteria, determining criteria weights, and assessing the performance of hydrogen fuel cell applications for each criterion. The fuzzy multiple-criteria decision making method was used to select the criteria and the preferred hydrogen fuel cell products based on information collected from a group of experts. Survey questionnaires were distributed to collect opinions from experts in different fields. After the survey, the criteria weights and a ranking of alternatives were obtained. The study first defined the evaluation criteria in terms of the stakeholders, so that comprehensive influence criteria could be identified. These criteria were then classified as environmental, technological, economic, or social to indicate the purpose of each criterion in the assessment process. The selected criteria included 14 indicators, such as energy efficiency and CO 2 emissions, as well as seven hydrogen fuel cell applications, such as forklifts and backup power systems. The results show that fuel cell backup power systems rank the highest, followed by household fuel cell electric-heat composite systems. The model provides a screening tool for decision makers to select hydrogen-related applications.

  6. Human immunodeficiency virus-like particles activate multiple types of immune cells

    International Nuclear Information System (INIS)

    Sailaja, Gangadhara; Skountzou, Ioanna; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo

    2007-01-01

    The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses

  7. Histopathological Parameters predicting Occult Nodal Metastases in Tongue Carcinoma Cases: An Indian Perspective.

    Science.gov (United States)

    Jacob, Tina Elizabeth; Malathi, N; Rajan, Sharada T; Augustine, Dominic; Manish, N; Patil, Shankargouda

    2016-01-01

    It is a well-established fact that in squamous cell carcinoma cases, the presence of lymph node metastases decreased the 5-year survival rate by 50% and also caused the recurrence of the primary tumor with development of distant metastases. Till date, the predictive factors for occult cervical lymph nodes metastases in cases of tongue squamous cell carcinoma remain inconclusive. Therefore, it is imperative to identify patients who are at the greatest risk for occult cervical metastases. This study was thus performed with the aim to identify various histopathologic parameters of the primary tumor that predict occult nodal metastases. The clinicopathologic features of 56 cases of lateral tongue squamous cell carcinoma with cT1NoMo/cT2NoMo as the stage and without prior radiotherapy or chemotherapy were considered. The surgical excision of primary tumor was followed by elective neck dissection. The glossectomy specimen along with the neck nodes were fixed in formalin and 5 urn thick sections were obtained. The hematoxylin & eosin stained sections were then subjected to microscopic examination. The primary tumor characteristics that were analyzed include tumor grade, invading front, depth of tumor, lymphovascular invasion, perineural invasion and inflammatory response. The nodes were examined for possible metastases using hematoxylin & eosin followed by cytokeratin immunohistochemistry. A total of 12 cases were found with positive occult nodal metastases. On performing univariate analysis, the histopathologic parameters that were found to be statistically significant were lymphovascular invasion (p = 0.004) and perineural invasion (p = 0.003) along with a cut-off depth of infiltration more than 5 mm (p = 0.01). Histopathologic assessment of the primary tumor specimen therefore continues to provide information that is central to guide clinical management, particularly in cases of occult nodal metastases. Clinical significance The study highlights the importance of

  8. Plerixafor in non-Hodgkin’s lymphoma and multiple myeloma patients undergoing autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Jan S. Moreb

    2011-10-01

    Full Text Available Autologous stem cell transplantation (ASCT is the standard of care for multiple myeloma (MM and relapsing non-Hodgkin’s lymphoma (NHL patients. Peripheral blood stem cells (PBSC have become the main source of grafts for ASCT due to several advantages over bone marrow grafts. Poor PBSC mobilization and inadequate collection of CD34+ cell dose for safe engraftment is a reality for significant proportion of these patients. For this review, we conducted a PubMed search using the titles plerixafor and AMD3100 as well as poor stem cell mobilization. English-language articles were selected and data were extracted with focus on clinical studies of PBSC mobilization in MM and NHL patients. We discuss predictors of poor PBSC mobilization, the impact of poor mobilization on ASCT outcomes, the available agents that have been routinely used to enhance mobilization to achieve optimal CD34+ cell dose, and the role of plerixafor, the first CXCR4 antagonist to be approved for stem cell mobilization. Studies have shown that plerixafor is effective and safe when given with G-CSF either upfront or as a rescue for patients with MM or NHL. Currently, more patients are getting transplanted because of plerixafor. The challenge now is how to use the drug in the most cost effective way. Several scenarios on how to use the drug in proven or predicted poor mobilizers are proposed in this manuscript; however, validation for some of these approaches is still needed.

  9. miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1

    International Nuclear Information System (INIS)

    Liu, Zengyan; Zhang, Guoqiang; Yu, Wenzheng; Gao, Na; Peng, Jun

    2016-01-01

    MicroRNAs (miRNAs) are small, noncoding ribonucleic acids that regulate gene expression by targeting mRNAs for translational repression and degradation. Accumulating experimental evidence supports a causal role of miRNAs in hematology tumorigenesis. However, the specific functions of miRNAs in the pathogenesis of multiple myeloma (MM) remain to be established. In this study, we demonstrated that miR-186 is commonly downregulated in MM cell lines and patient MM cells. Ectopic expression of miR-186 significantly inhibited cell growth, both in vitro and in vivo, and induced cell cycle G_0/G_1 arrest. Furthermore, miR-186 induced downregulation of Jagged1 protein expression by directly targeting its 3′-untranslated region (3′-UTR). Conversely, overexpression of Jagged1 rescued cells from miR-186-induced growth inhibition. Our collective results clearly indicate that miR-186 functions as a tumor suppressor in MM, supporting its potential as a therapeutic target for the disease. - Highlights: • miR-186 expression is decreased in MM. • miR-186 inhibits MM cell proliferation in vitro and in vivo. • Jagged1 is regulated by miR-186. • Overexpression of Jagged1 reverses the effects of miR-186.

  10. Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways.

    Directory of Open Access Journals (Sweden)

    Boying Dun

    Full Text Available Mycophenolic acid (MPA is the metabolized product and active element of mycophenolate mofetil (MMF that has been widely used for the prevention of acute graft rejection. MPA potently inhibits inosine monophosphate dehydrogenase (IMPDH that is up-regulated in many tumors and MPA is known to inhibit cancer cell proliferation as well as fibroblast and endothelial cell migration. In this study, we demonstrated for the first time MPA's antimigratory and anti-invasion abilities of MPA-sensitive AGS (gastric cancer cells. Genome-wide expression analyses using Illumina whole genome microarrays identified 50 genes with ≥2 fold changes and 15 genes with > 4 fold alterations and multiple molecular pathways implicated in cell migration. Real-time RT-PCR analyses of selected genes also confirmed the expression differences. Furthermore, targeted proteomic analyses identified several proteins altered by MPA treatment. Our results indicate that MPA modulates gastric cancer cell migration through down-regulation of a large number of genes (PRKCA, DOCK1, INF2, HSPA5, LRP8 and PDGFRA and proteins (PRKCA, AKT, SRC, CD147 and MMP1 with promigratory functions as well as up-regulation of a number of genes with antimigratory functions (ATF3, SMAD3, CITED2 and CEAMCAM1. However, a few genes that may promote migration (CYR61 and NOS3 were up-regulated. Therefore, MPA's overall antimigratory role on cancer cells reflects a balance between promigratory and antimigratory signals influenced by MPA treatment.

  11. miR-186 inhibits cell proliferation in multiple myeloma by repressing Jagged1

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zengyan [Department of Hematology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, Shandong 250012 (China); Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603 (China); Zhang, Guoqiang [Department of Thyroid and Breast Surgery, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603 (China); Yu, Wenzheng; Gao, Na [Department of Hematology, Hospital Affiliated to Binzhou Medical University, 661 Second Huanghe Street, Binzhou 256603 (China); Peng, Jun, E-mail: junpeng885@sina.com [Department of Hematology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, Shandong 250012 (China)

    2016-01-15

    MicroRNAs (miRNAs) are small, noncoding ribonucleic acids that regulate gene expression by targeting mRNAs for translational repression and degradation. Accumulating experimental evidence supports a causal role of miRNAs in hematology tumorigenesis. However, the specific functions of miRNAs in the pathogenesis of multiple myeloma (MM) remain to be established. In this study, we demonstrated that miR-186 is commonly downregulated in MM cell lines and patient MM cells. Ectopic expression of miR-186 significantly inhibited cell growth, both in vitro and in vivo, and induced cell cycle G{sub 0}/G{sub 1} arrest. Furthermore, miR-186 induced downregulation of Jagged1 protein expression by directly targeting its 3′-untranslated region (3′-UTR). Conversely, overexpression of Jagged1 rescued cells from miR-186-induced growth inhibition. Our collective results clearly indicate that miR-186 functions as a tumor suppressor in MM, supporting its potential as a therapeutic target for the disease. - Highlights: • miR-186 expression is decreased in MM. • miR-186 inhibits MM cell proliferation in vitro and in vivo. • Jagged1 is regulated by miR-186. • Overexpression of Jagged1 reverses the effects of miR-186.

  12. Mouse androgenetic embryonic stem cells differentiated to multiple cell lineages in three embryonic germ layers in vitro.

    Science.gov (United States)

    Teramura, Takeshi; Onodera, Yuta; Murakami, Hideki; Ito, Syunsuke; Mihara, Toshihiro; Takehara, Toshiyuki; Kato, Hiromi; Mitani, Tasuku; Anzai, Masayuki; Matsumoto, Kazuya; Saeki, Kazuhiro; Fukuda, Kanji; Sagawa, Norimasa; Osoi, Yoshihiko

    2009-06-01

    The embryos of some rodents and primates can precede early development without the process of fertilization; however, they cease to develop after implantation because of restricted expressions of imprinting genes. Asexually developed embryos are classified into parthenote/gynogenote and androgenote by their genomic origins. Embryonic stem cells (ESCs) derived from asexual origins have also been reported. To date, ESCs derived from parthenogenetic embryos (PgESCs) have been established in some species, including humans, and the possibility to be alternative sources for autologous cell transplantation in regenerative medicine has been proposed. However, some developmental characteristics, which might be important for therapeutic applications, such as multiple differentiation capacity and transplantability of the ESCs of androgenetic origin (AgESCs) are uncertain. Here, we induced differentiation of mouse AgESCs and observed derivation of neural cells, cardiomyocytes and hepatocytes in vitro. Following differentiated embryoid body (EB) transplantation in various mouse strains including the strain of origin, we found that the EBs could engraft in theoretically MHC-matched strains. Our results indicate that AgESCs possess at least two important characteristics, multiple differentiation properties in vitro and transplantability after differentiation, and suggest that they can also serve as a source of histocompatible tissues for transplantation.

  13. Spontaneous squamous cell carcinoma of the tongue and multiple bronchioloalveolar carcinomas in a Virginia opossum (Didelphis virginiana).

    Science.gov (United States)

    Kim, D Y; Mitchell, M A; De las Heras, M; Taylor, H W; Cho, D-Y

    2002-01-01

    Two primary tumours, squamous cell carcinoma of the tongue and multiple bronchioloalveolar carcinomas, were diagnosed in a Virginia opossum (Didelphis virginiana). Two oral masses were located in the right ventrolateral surface of the tongue, near the frenulum, and the lungs contained multiple, widely distributed, nodular masses. Microscopically, the oral masses were composed of invasive cords of pleomorphic, polyhedral cells, typical of squamous cells. The multiple pulmonary masses consisted of non-ciliated, cuboidal, columnar, or occasionally polyhedral cells arranged in an alveolar pattern with multifocal areas of necrosis. This is the first report of spontaneous oropharyngeal squamous cell carcinoma in the Virginia opossum. However, multiple pulmonary adenomas have been reported previously in this species, the lesions being similar to those in sheep pulmonary adenomatosis (jaagsiekte). In the present study, immunohistochemical examination of the pulmonary tumours with a rabbit polyclonal antiserum to jaagsiekte retroviral capsid protein proved negative. Copyright Harcourt Publishers Ltd.

  14. Radiotherapy studies and extra-nodal non-Hodgkin lymphomas, progress and challenges

    DEFF Research Database (Denmark)

    Specht, L

    2012-01-01

    Extra-nodal lymphomas may arise in any organ, and different histological subtypes occur in distinct patterns. Prognosis and treatment depend not only on the histological subtype and disease extent, but also on the particular involved extra-nodal organ. The clinical course and response to treatment...... for the more common extra-nodal organs, e.g. stomach, Waldeyer's ring, skin and brain, are fairly well known and show significant variation. A few randomised trials have been carried out testing the role of radiotherapy in these lymphomas. However, for most extra-nodal lymphomas, randomised trials have...... not been carried out, and treatment decisions are made on small patient series and extrapolations from nodal lymphomas. Hopefully, wide international collaboration will make controlled clinical trials possible in the less common extra-nodal lymphomas. Modern highly conformal radiotherapy allows better...

  15. Solution and study of nodal neutron transport equation applying the LTSN-DiagExp method

    International Nuclear Information System (INIS)

    Hauser, Eliete Biasotto; Pazos, Ruben Panta; Vilhena, Marco Tullio de; Barros, Ricardo Carvalho de

    2003-01-01

    In this paper we report advances about the three-dimensional nodal discrete-ordinates approximations of neutron transport equation for Cartesian geometry. We use the combined collocation method of the angular variables and nodal approach for the spatial variables. By nodal approach we mean the iterated transverse integration of the S N equations. This procedure leads to the set of one-dimensional averages angular fluxes in each spatial variable. The resulting system of equations is solved with the LTS N method, first applying the Laplace transform to the set of the nodal S N equations and then obtained the solution by symbolic computation. We include the LTS N method by diagonalization to solve the nodal neutron transport equation and then we outline the convergence of these nodal-LTS N approximations with the help of a norm associated to the quadrature formula used to approximate the integral term of the neutron transport equation. (author)

  16. Five-point form of the nodal diffusion method and comparison with finite-difference

    International Nuclear Information System (INIS)

    Azmy, Y.Y.

    1988-01-01

    Nodal Methods have been derived, implemented and numerically tested for several problems in physics and engineering. In the field of nuclear engineering, many nodal formalisms have been used for the neutron diffusion equation, all yielding results which were far more computationally efficient than conventional Finite Difference (FD) and Finite Element (FE) methods. However, not much effort has been devoted to theoretically comparing nodal and FD methods in order to explain the very high accuracy of the former. In this summary we outline the derivation of a simple five-point form for the lowest order nodal method and compare it to the traditional five-point, edge-centered FD scheme. The effect of the observed differences on the accuracy of the respective methods is established by considering a simple test problem. It must be emphasized that the nodal five-point scheme derived here is mathematically equivalent to previously derived lowest order nodal methods. 7 refs., 1 tab

  17. A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

    Science.gov (United States)

    Noël, Emily S.; Verhoeven, Manon; Lagendijk, Anne Karine; Tessadori, Federico; Smith, Kelly; Choorapoikayil, Suma; den Hertog, Jeroen; Bakkers, Jeroen

    2013-11-01

    Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.

  18. A one-dimensional, one-group absorption-production nodal method for neutron flux and power distributions calculations

    International Nuclear Information System (INIS)

    Ferreira, C.R.

    1984-01-01

    It is presented the absorption-production nodal method for steady and dynamical calculations in one-dimension and one group energy. It was elaborated the NOD1D computer code (in FORTRAN-IV language). Calculations of neutron flux and power distributions, burnup, effective multiplication factors and critical boron concentration were made with the NOD1D code and compared with results obtained through the CITATION code, which uses the finite difference method. The nuclear constants were produced by the LEOPARD code. (M.C.K.) [pt

  19. Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

    Science.gov (United States)

    Nabissi, Massimo; Morelli, Maria Beatrice; Offidani, Massimo; Amantini, Consuelo; Gentili, Silvia; Soriani, Alessandra; Cardinali, Claudio; Leoni, Pietro; Santoni, Giorgio

    2016-11-22

    Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy. In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines. We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis. Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein. Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ. Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration. In summary, these results proved that this combination exerts strong anti-myeloma activities.

  20. ANGUSTIFOLIA mediates one of the multiple SCRAMBLED signaling pathways regulating cell growth pattern in Arabidopsis thaliana.

    Science.gov (United States)

    Kwak, Su-Hwan; Song, Sang-Kee; Lee, Myeong Min; Schiefelbein, John

    2015-09-25

    In Arabidopsis thaliana, an atypical leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), is required for multiple developmental processes including root epidermal cell fate determination, silique dehiscence, inflorescence growth, ovule morphogenesis, and tissue morphology. Previous work suggested that SCM regulates these multiple pathways using distinct mechanisms via interactions with specific downstream factors. ANGUSTIFOLIA (AN) is known to regulate cell and tissue morphogenesis by influencing cortical microtubule arrangement, and recently, the AN protein was reported to interact with the SCM protein. Therefore, we examined whether AN might be responsible for mediating some of the SCM-dependent phenotypes. We discovered that both scm and an mutant lines cause an abnormal spiral or twisting growth of roots, but only the scm mutant affected root epidermal patterning. The siliques of the an and scm mutants also exhibited spiral growth, as previously reported, but only the scm mutant altered silique dehiscence. Interestingly, we discovered that the spiral growth of roots and siliques of the scm mutant is rescued by a truncated SCM protein that lacks its kinase domain, and that a juxtamembrane domain of SCM was sufficient for AN binding in the yeast two-hybrid analysis. These results suggest that the AN protein is one of the critical downstream factors of SCM pathways specifically responsible for mediating its effects on cell/tissue morphogenesis through cortical microtubule arrangement. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Superficial Type of Multiple Basal Cell Carcinomas: Detailed Comparative Study of Its Dermoscopic and Histopathological Findings

    International Nuclear Information System (INIS)

    Hirofuji, A.; Takiguchi, K.; Nakamura, K.; Kuramochi, A.; Tsuchida, T.; Arai, E.; Shimizu, M.

    2011-01-01

    We investigated in detail the dermoscopic and histopathological findings in a case of a superficial type of multiple basal cell carcinomas (BCCs). These multiple lesions (occurring in the chest, neck, and back) showed three different findings, respectively. Dermoscopy of the erythematous and brown-colored patch on the anterior chest showed spoke wheel areas, and the histopathological cross-section revealed vertical spoke wheel structures. In the black- and brown-colored patch at the neck, the dermatoscopy showed a maple leaf-like structure, which was in accordance with the strengthening of the histological lateral connection of the lesion. The brown-colored patch of the lateral back histologically showed irregularly enlarged spoke wheel-like areas with peripheral increased melanin pigments, which correlated with the dark black color of dermoscopic maple leaf-like areas. The vertical spoke wheel areas by dermatoscopy revealed a horizontal spoke wheel structure by histopathology

  2. Superficial Type of Multiple Basal Cell Carcinomas: Detailed Comparative Study of Its Dermoscopic and Histopathological Findings

    Directory of Open Access Journals (Sweden)

    Akiko Hirofuji

    2011-01-01

    Full Text Available We investigated in detail the dermoscopic and histopathological findings in a case of a superficial type of multiple basal cell carcinomas (BCCs. These multiple lesions (occurring in the chest, neck, and back showed three different findings, respectively. Dermoscopy of the erythematous and brown-colored patch on the anterior chest showed spoke wheel areas, and the histopathological cross-section revealed vertical spoke wheel structures. In the black- and brown-colored patch at the neck, the dermatoscopy showed a maple leaf-like structure, which was in accordance with the strengthening of the histological lateral connection of the lesion. The brown-colored patch of the lateral back histologically showed irregularly enlarged spoke wheel-like areas with peripheral increased melanin pigments, which correlated with the dark black color of dermoscopic maple leaf-like areas. The vertical spoke wheel areas by dermatoscopy revealed a horizontal spoke wheel structure by histopathology.

  3. Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple sclerosis.

    Science.gov (United States)

    Mitosek-Szewczyk, Krystyna; Tabarkiewicz, Jacek; Wilczynska, Barbara; Lobejko, Katarzyna; Berbecki, Jerzy; Nastaj, Marcin; Dworzanska, Ewa; Kolodziejczyk, Beata; Stelmasiak, Zbigniew; Rolinski, Jacek

    2013-09-15

    Cladribine causes sustained reduction in peripheral T and B cell populations while sparing other immune cells. We determined two populations of dendritic cells (DCs): namely CD1c(+)/CD19(-) (myeloid DCs) and CD303(+)/CD123(+) (plasmacytoid DCs), CD19(+) B lymphocytes, CD3(+) T lymphocytes and CD4(+) or CD8(+) subpopulations in patients with multiple sclerosis after cladribine therapy. We examined 50 patients with secondary progressive multiple sclerosis (SP MS) according to McDonalds et al.'s criteria, 2001 [15]. Blood samples were collected before the initiation of cladribine therapy and after 1st, 2nd, 3th, 4th and 5th courses of treatment. DC subsets, T and B cells were analyzed by flow cytometry. During cladribine treatment the myeloid DCs CD1c(+)/CD19(-) did not change (p=0.73175), and the plasmacytoid DCs CD303(+)/CD123(+) significantly increased (p=0.00034) which resulted in significant changes in the ratio of myeloid DCs to plasmacytoid DCs (p=0.00273). During therapy, B lymphocyte CD19(+) significantly decreased (p=0.00005) and significant changes in CD4(+) cells (p=0.00191), changes in CD8(+) cells (p=0.05760) and significant changes in CD3(+) (p=0.01822) were found. We noticed significant trend to increase the CD303(+) circulating the dendritic cells. This population produces large amounts of IFN-alfa. We found significant and rapid decrease in B cells and CD4(+) Th cells. Our results suggest two possible ways of beneficial cladribine influence on immune system in MS. Induction of IFN-alfa producing cells and their predominance over BDCA-1(+) DCs, which are associated with cytotoxic response. Additionally, cladribine could influence two populations of lymphocytes: B cells and Th lymphocytes responsible for induction of immune response against myelin antigens. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. A method for multiple sequential analyses of macrophage functions using a small single cell sample

    Directory of Open Access Journals (Sweden)

    F.R.F. Nascimento

    2003-09-01

    Full Text Available Microbial pathogens such as bacillus Calmette-Guérin (BCG induce the activation of macrophages. Activated macrophages can be characterized by the increased production of reactive oxygen and nitrogen metabolites, generated via NADPH oxidase and inducible nitric oxide synthase, respectively, and by the increased expression of major histocompatibility complex class II molecules (MHC II. Multiple microassays have been developed to measure these parameters. Usually each assay requires 2-5 x 10(5 cells per well. In some experimental conditions the number of cells is the limiting factor for the phenotypic characterization of macrophages. Here we describe a method whereby this limitation can be circumvented. Using a single 96-well microassay and a very small number of peritoneal cells obtained from C3H/HePas mice, containing as little as <=2 x 10(5 macrophages per well, we determined sequentially the oxidative burst (H2O2, nitric oxide production and MHC II (IAk expression of BCG-activated macrophages. More specifically, with 100 µl of cell suspension it was possible to quantify H2O2 release and nitric oxide production after 1 and 48 h, respectively, and IAk expression after 48 h of cell culture. In addition, this microassay is easy to perform, highly reproducible and more economical.

  5. Does an NKT-cell-based immunotherapeutic approach have a future in multiple myeloma?

    Science.gov (United States)

    Favreau, Mérédis; Vanderkerken, Karin

    2016-01-01

    Natural killer T (NKT) cells constitute a unique subset of innate-like T lymphocytes which differ from conventional T cells by recognizing lipid antigens presented by the non-polymorphic major histocompatibility complex (MHC) I-like molecule CD1d. Despite being a relatively infrequent population of lymphocytes, NKT cells can respond rapidly upon activation with glycosphingolipids by production of cytokines which aim to polarize different axes of the immune system. Due to their dual effector capacities, NKT cells can play a vital role in cancer immunity, infection, inflammation and autoimmune diseases. It is believed that modulation of their activity towards immune activation can be a useful tool in anti-tumor immunotherapeutic strategies. Here we summarize the characteristics of NKT cells and discuss their involvement in immunosurveillance. Furthermore, an update is given about their role and the progress that has been made in the field of multiple myeloma (MM). Finally, some challenges are discussed that are currently hampering further progress. PMID:26895468

  6. EPMLR: sequence-based linear B-cell epitope prediction method using multiple linear regression.

    Science.gov (United States)

    Lian, Yao; Ge, Meng; Pan, Xian-Ming

    2014-12-19

    B-cell epitopes have been studied extensively due to their immunological applications, such as peptide-based vaccine development, antibody production, and disease diagnosis and therapy. Despite several decades of research, the accurate prediction of linear B-cell epitopes has remained a challenging task. In this work, based on the antigen's primary sequence information, a novel linear B-cell epitope prediction model was developed using the multiple linear regression (MLR). A 10-fold cross-validation test on a large non-redundant dataset was performed to evaluate the performance of our model. To alleviate the problem caused by the noise of negative dataset, 300 experiments utilizing 300 sub-datasets were performed. We achieved overall sensitivity of 81.8%, precision of 64.1% and area under the receiver operating characteristic curve (AUC) of 0.728. We have presented a reliable method for the identification of linear B cell epitope using antigen's primary sequence information. Moreover, a web server EPMLR has been developed for linear B-cell epitope prediction: http://www.bioinfo.tsinghua.edu.cn/epitope/EPMLR/ .

  7. Nanoliter reactors improve multiple displacement amplification of genomes from single cells.

    Directory of Open Access Journals (Sweden)

    Yann Marcy

    2007-09-01

    Full Text Available Since only a small fraction of environmental bacteria are amenable to laboratory culture, there is great interest in genomic sequencing directly from single cells. Sufficient DNA for sequencing can be obtained from one cell by the Multiple Displacement Amplification (MDA method, thereby eliminating the need to develop culture methods. Here we used a microfluidic device to isolate individual Escherichia coli and amplify genomic DNA by MDA in 60-nl reactions. Our results confirm a report that reduced MDA reaction volume lowers nonspecific synthesis that can result from contaminant DNA templates and unfavourable interaction between primers. The quality of the genome amplification was assessed by qPCR and compared favourably to single-cell amplifications performed in standard 50-microl volumes. Amplification bias was greatly reduced in nanoliter volumes, thereby providing a more even representation of all sequences. Single-cell amplicons from both microliter and nanoliter volumes provided high-quality sequence data by high-throughput pyrosequencing, thereby demonstrating a straightforward route to sequencing genomes from single cells.

  8. Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-06-01

    Full Text Available Using a viral model of the demyelinating disease multiple sclerosis (MS, we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.

  9. Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease.

    Science.gov (United States)

    Shroff, Geeta

    2016-12-13

    BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients' conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). CONCLUSIONS Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD.

  10. PKA/AMPK signaling in relation to adiponectin's antiproliferative effect on multiple myeloma cells.

    Science.gov (United States)

    Medina, E A; Oberheu, K; Polusani, S R; Ortega, V; Velagaleti, G V N; Oyajobi, B O

    2014-10-01

    Obesity increases the risk of developing multiple myeloma (MM). Adiponectin is a cytokine produced by adipocytes, but paradoxically decreased in obesity, that has been implicated in MM progression. Herein, we evaluated how prolonged exposure to adiponectin affected the survival of MM cells as well as putative signaling mechanisms. Adiponectin activates protein kinase A (PKA), which leads to decreased AKT activity and increased AMP-activated protein kinase (AMPK) activation. AMPK, in turn, induces cell cycle arrest and apoptosis. Adiponectin-induced apoptosis may be mediated, at least in part, by the PKA/AMPK-dependent decline in the expression of the enzyme acetyl-CoA-carboxylase (ACC), which is essential to lipogenesis. Supplementation with palmitic acid, the preliminary end product of fatty acid synthesis, rescues MM cells from adiponectin-induced apoptosis. Furthermore, 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an ACC inhibitor, exhibited potent antiproliferative effects on MM cells that could also be inhibited by fatty acid supplementation. Thus, adiponectin's ability to reduce survival of MM cells appears to be mediated through its ability to suppress lipogenesis. Our findings suggest that PKA/AMPK pathway activators, or inhibitors of ACC, may be useful adjuvants to treat MM. Moreover, the antimyeloma effect of adiponectin supports the concept that hypoadiponectinemia, as occurs in obesity, promotes MM tumor progression.

  11. AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILDREN WITH SEVERE RESISTANT MULTIPLE SCLEROSIS

    Directory of Open Access Journals (Sweden)

    K. I. Kirgizov

    2013-01-01

    Full Text Available Unique experience of high-dose chemotherapy with consequent autologous hematopoietic stem cell transplantation in children with severe resistant multiple sclerosis (n=7 is shown in this article. At present time there is enough data on chemotherapy with consequent hematopoietic stem cell transplantation in children with severe resistant multiple sclerosis. This method was proved to be efficient and safe with immunoablative conditioning chemotherapy regimen. In patients included in this study the mean rate according to the Expanded Disability Status Scale was 5,94±0,2 (from 3 to 9 points. All the patients had disseminated demyelination loci, accumulating the contrast substance, in the brain and the spinal cord. After cyclophosphamide treatment in combination with anti-monocytes globulin the fast stabilization of the condition and prolonged (the observation period was 3-36 moths clinical and radiologic as well as immunophenotypic remission with marked positive dynamics according to the Expanded Disability Status Scale were noted. No pronounced side-effects and infectious complications were mentioned. The maximal improvement according to the Expanded Disability Status Scale (EDSS was 5,5 points, the mean — 2,7±0,1 (from 2 to 5,5 points accompanied with positive dynamics on the magneto-resonance imaging.  The efficacy of the treatment was also proved by the positive changes in the lymphocytes subpopulation status in peripheral blood. The timely performed high-dose chemotherapy with consequent hematopoietic stem cell transplantation is an effective and safe method to slowdown the autoimmune inflammatory process. This method can be recommended to use in treatment of children with severe resistant multiple sclerosis. 

  12. Strain preservation of experimental animals: vitrification of two-cell stage embryos for multiple mouse strains.

    Science.gov (United States)

    Eto, Tomoo; Takahashi, Riichi; Kamisako, Tsutomu

    2015-04-01

    Strain preservation of experimental animals is crucial for experimental reproducibility. Maintaining complete animal strains, however, is costly and there is a risk for genetic mutations as well as complete loss due to disasters or illness. Therefore, the development of effective vitrification techniques for cryopreservation of multiple experimental animal strains is important. We examined whether a vitrification method using cryoprotectant solutions, P10 and PEPeS, is suitable for preservation of multiple inbred and outbred mouse strains. First, we investigated whether our vitrification method using cryoprotectant solutions was suitable for two-cell stage mouse embryos. In vitro development of embryos exposed to the cryoprotectant solutions was similar to that of fresh controls. Further, the survival rate of the vitrified embryos was extremely high (98.1%). Next, we collected and vitrified two-cell stage embryos of 14 mouse strains. The average number of embryos obtained from one female was 7.3-33.3. The survival rate of vitrified embryos ranged from 92.8% to 99.1%, with no significant differences among mouse strains. In vivo development did not differ significantly between fresh controls and vitrified embryos of each strain. For strain preservation using cryopreserved embryos, two offspring for inbred lines and one offspring for outbred lines must be produced from two-cell stage embryos collected from one female. The expected number of surviving fetuses obtained from embryos collected from one female of either the inbred or outbred strains ranged from 2.9 to 19.5. The findings of the present study indicated that this vitrification method is suitable for strain preservation of multiple mouse strains. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. An Improved Micropropagation Protocol by Ex Vitro Rooting of Passiflora edulis Sims. f. flavicarpa Deg. through Nodal Segment Culture.

    Science.gov (United States)

    Shekhawat, Mahipal S; Manokari, M; Ravindran, C P

    2015-01-01

    A procedure for rapid clonal propagation of Passiflora edulis Sims. f. flavicarpa Deg. (Passifloraceae) has been developed in this study. Nodal explants were sterilized with 0.1% HgCl2 and inoculated on Murashige and Skoog (MS) basal medium. The addition of 2.0 mgL(-1) 6-benzylaminopurine (BAP) to MS medium caused an extensive proliferation of multiple shoots (8.21 ± 1.13) primordial from the nodal meristems. Subculturing of these multiple shoots on the MS medium augmented with 1.0 mgL(-1) of each BAP and Kinetin (Kin) was successful for the multiplication of the shoots in vitro with maximum numbers of shoots (25.73 ± 0.06) within four weeks of incubation. Shoots were rooted best (7.13 ± 0.56 roots/shoots) on half strength MS medium supplemented with 2.0 mgL(-1) indole-3 butyric acid (IBA). All in vitro regenerated shoots were rooted by ex vitro method, and this has achieved 6-7 roots per shoot by pulsing of cut ends of the shoots using 200 as well as 300 mgL(-1) IBA. The plantlets were hardened in the greenhouse for 4-5 weeks. The hardened plantlets were shifted to manure containing nursery polybags after five weeks and then transferred to a sand bed for another four weeks for acclimatization before field planting with 88% survival rate.

  14. Nodal wear model: corrosion in carbon blast furnace hearths

    International Nuclear Information System (INIS)

    Verdeja, L. F.; Gonzalez, R.; Alfonso, A.; Barbes, M. F.

    2003-01-01

    Criteria developed for the Nodal Wear Model (NWM) were applied to estimate the shape of the corrosion profiles that a blast furnace hearth may acquire during its campaign. Taking into account design of the hearth, the boundary conditions, the characteristics of the refractory materials used and the operation conditions of the blast furnace, simulation of wear profiles with central well, mushroom and elephant foot shape were accomplished. The foundations of the NWM are constructed considering that the corrosion of the refractory is a function of the temperature present at each point (node) of the liquid metal-refractory interface and the corresponding physical and chemical characteristics of the corrosive fluid. (Author) 31 refs

  15. Mechanism of polyuria and natriuresis in atrioventricular nodal tachycardia.

    Science.gov (United States)

    Canepa-Anson, R; Williams, M; Marshall, J; Mitsuoka, T; Lightman, S; Sutton, R

    1984-01-01

    A woman with tachycardia associated with polyuria was investigated. Electrophysiological analysis showed that the tachycardia was an atrioventricular nodal re-entrant tachycardia. Programmed stimulation was then used to provoke and sustain the tachycardia for 40 minutes. Polyuria, with an appreciable increase in free water clearance, was observed. This was associated with reduction in plasma and urinary arginine vasopressin concentrations. Appreciable natriuresis also developed. These results support the hypothesis that the polyuria with increased free water clearance and the natriuresis occurring during sustained tachycardia in man are due to inhibition of secretion of vasopressin and the release of natriuretic factor. PMID:6434116

  16. Approximate Schur complement preconditioning of the lowest order nodal discretizations

    Energy Technology Data Exchange (ETDEWEB)

    Moulton, J.D.; Ascher, U.M. [Univ. of British Columbia, Vancouver, British Columbia (Canada); Morel, J.E. [Los Alamos National Lab., NM (United States)

    1996-12-31

    Particular classes of nodal methods and mixed hybrid finite element methods lead to equivalent, robust and accurate discretizations of 2nd order elliptic PDEs. However, widespread popularity of these discretizations has been hindered by the awkward linear systems which result. The present work exploits this awkwardness, which provides a natural partitioning of the linear system, by defining two optimal preconditioners based on approximate Schur complements. Central to the optimal performance of these preconditioners is their sparsity structure which is compatible with Dendy`s black box multigrid code.

  17. Optimal Assignment of Cells in C-RAN Deployments with Multiple BBU Pools

    DEFF Research Database (Denmark)

    Holm, Henrik; Checko, Aleksandra; Al-obaidi, Rami

    2015-01-01

    Cloud Radio Access Network (C-RAN) is receiving increasing attention not only within the research community but also from operators and standardization bodies. However, even a good technology will be deployed only if it is economically viable. In our previous work, for larger scale deployment we...... recommend to divide the area into multiple BBU Pools. In this paper we show how to optimally assign cells to different BBU Pools in such a scenario. By using Integer Linear Programming (ILP) method we derive engineering guidelines for minimizing the CAPital EXpenditure (CAPEX) of C-RAN deployment....

  18. Efficiency dip observed with InGaN-based multiple quantum well solar cells

    KAUST Repository

    Lai, Kunyu; Lin, G. J.; Wu, Yuhrenn; Tsai, Menglun; He, Jr-Hau

    2014-01-01

    The dip of external quantum efficiency (EQE) is observed on In0.15Ga0.85N/GaN multiple quantum well (MQW) solar cells upon the increase of incident optical power density. With indium composition increased to 25%, the EQE dip becomes much less noticeable. The composition dependence of EQE dip is ascribed to the competition between radiative recombination and photocurrent generation in the active region, which are dictated by quantum-confined Stark effect (QCSE) and composition fluctuation in the MQWs.

  19. Interactions between organic anions on multiple transporters in Caco-2 cells

    DEFF Research Database (Denmark)

    Grandvuinet, Anne Sophie; Steffansen, Bente

    2011-01-01

    Caco-2 cell line may be used as an overall model to predict interactions on multiple membrane transporters in the intestine. Taurocholic acid (TCA) and estrone-3-sulfate (E1S) were used as model substrates. Possible inhibitors studied were TCA, E1S, taurolithocholic acid, fluvastatin, and glipizide......-dependent bile acid transporter and the organic solute transporter α/β, and to less extent by the organic anion transporting polypeptide 2B1. However, interactions on efflux transporters were not detected, although they were expected from the literature on the investigated compounds. Biosimulation methods may...

  20. Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome

    OpenAIRE

    Neumann, Thomas E; Allanson, Judith; Kavamura, Ines; Kerr, Bronwyn; Neri, Giovanni; Noonan, Jacqueline; Cordeddu, Viviana; Gibson, Kate; Tzschach, Andreas; Krüger, Gabriele; Hoeltzenbein, Maria; Goecke, Timm O; Kehl, Hans Gerd; Albrecht, Beate; Luczak, Klaudiusz

    2008-01-01

    Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS) are related developmental disorders caused by mutations in genes encoding various components of the RAS-MAPK signaling cascade. NS is associated with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS. the NS phenotype is rarely accompanied by multiple giant cell lesions (MGCL) of the jaw (Noonan-like/MGCL syndrome (NL/MGCLS)). PTPN11 mutations are the only gen...

  1. Familial disseminated plaque type porokeratosis with multiple horns and squamous cell carcinoma involving anal skin

    Directory of Open Access Journals (Sweden)

    Sarma Nilendu

    2009-01-01

    Full Text Available Porokeratosis is a disorder of keratinization showing a well-defined lesion with a hyperkeratotic ridge on the border that contains the coronoid lamella. We report familial (autosomal dominant with reduced penetrance disseminated plaque type (Mibelli′s type porokeratosis in a father and son. In the father, there were multiple horns and a large squamous cell carcinoma in a large lesion over the perianal region that reached up to the squamo-columnar junction of the anal mucosa and even invaded the anal sphincteric muscles. Disseminated lesions of the Mibelli′s type, development of horns, and malignancy in this unusual location have not been previously reported.

  2. Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.; Opresko, Lee; Coffey, Robert J.; Zangar, Richard C.; Wiley, H. S.

    2008-11-14

    REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

  3. Incorporating Multiple Energy Relay Dyes in Liquid Dye-Sensitized Solar Cells

    KAUST Repository

    Yum, Jun-Ho

    2011-01-05

    Panchromatic response is essential to increase the light-harvesting efficiency in solar conversion systems. Herein we show increased light harvesting from using multiple energy relay dyes inside dye-sensitized solar cells. Additional photoresponse from 400-590 nm matching the optical window of the zinc phthalocyanine sensitizer was observed due to Förster resonance energy transfer (FRET) from the two energy relay dyes to the sensitizing dye. The complementary absorption spectra of the energy relay dyes and high excitation transfer efficiencies result in a 35% increase in photovoltaic performance. © 2011 Wiley-VCH Verlag GmbH& Co. KGaA.

  4. Average arterial input function for quantitative dynamic contrast enhanced magnetic resonance imaging of neck nodal metastases

    International Nuclear Information System (INIS)

    Shukla-Dave, Amita; Lee, Nancy; Stambuk, Hilda; Wang, Ya; Huang, Wei; Thaler, Howard T; Patel, Snehal G; Shah, Jatin P; Koutcher, Jason A

    2009-01-01

    The present study determines the feasibility of generating an average arterial input function (Avg-AIF) from a limited population of patients with neck nodal metastases to be used for pharmacokinetic modeling of dynamic contrast-enhanced MRI (DCE-MRI) data in clinical trials of larger populations. Twenty patients (mean age 50 years [range 27–77 years]) with neck nodal metastases underwent pretreatment DCE-MRI studies with a temporal resolution of 3.75 to 7.5 sec on a 1.5T clinical MRI scanner. Eleven individual AIFs (Ind-AIFs) met the criteria of expected enhancement pattern and were used to generate Avg-AIF. Tofts model was used to calculate pharmacokinetic DCE-MRI parameters. Bland-Altman plots and paired Student t-tests were used to describe significant differences between the pharmacokinetic parameters obtained from individual and average AIFs. Ind-AIFs obtained from eleven patients were used to calculate the Avg-AIF. No overall significant difference (bias) was observed for the transfer constant (K trans ) measured with Ind-AIFs compared to Avg-AIF (p = 0.20 for region-of-interest (ROI) analysis and p = 0.18 for histogram median analysis). Similarly, no overall significant difference was observed for interstitial fluid space volume fraction (v e ) measured with Ind-AIFs compared to Avg-AIF (p = 0.48 for ROI analysis and p = 0.93 for histogram median analysis). However, the Bland-Altman plot suggests that as K trans increases, the Ind-AIF estimates tend to become proportionally higher than the Avg-AIF estimates. We found no statistically significant overall bias in K trans or v e estimates derived from Avg-AIF, generated from a limited population, as compared with Ind-AIFs. However, further study is needed to determine whether calibration is needed across the range of K trans . The Avg-AIF obtained from a limited population may be used for pharmacokinetic modeling of DCE-MRI data in larger population studies with neck nodal metastases. Further validation of

  5. Evaluation of the use of nodal methods for MTR neutronic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Reitsma, F.; Mueller, E.Z.

    1997-08-01

    Although modern nodal methods are used extensively in the nuclear power industry, their use for research reactor analysis has been very limited. The suitability of nodal methods for material testing reactor analysis is investigated with the emphasis on the modelling of the core region (fuel assemblies). The nodal approach`s performance is compared with that of the traditional finite-difference fine mesh approach. The advantages of using nodal methods coupled with integrated cross section generation systems are highlighted, especially with respect to data preparation, simplicity of use and the possibility of performing a great variety of reactor calcul