Science.gov

Sample records for anti-cd20 na terapia

  1. Anti-CD20 monoclonal antibodies in multiple sclerosis.

    PubMed

    Moreno Torres, Irene; García-Merino, Antonio

    2017-04-01

    The therapeutic utility of the anti-CD20 monoclonal antibodies (mAbs) is currently being evaluated in multiple sclerosis (MS) in line with the better understanding of the role of B lymphocytes in MS pathogenesis. Area covered: We conducted a literature search using Medline/Pub Med database of basic research and available controlled trials about anti-CD20 mAbs in MS. Additionally, ongoing studies were identified in the ClinicalTrials.gov database. B cells exert multiple inflammatory and regulatory functions playing an important role in MS pathogenesis as is demonstrated by the production of autoantibodies, infiltration of B cells in MS lesions and the formation of ectopic B cell follicle-like structures in meninges, among others. B-cell depletion by anti-CD20 mAbs has been shown to have an impact on these pathogenic mechanisms. The efficacy of three of them, rituximab, ocrelizumab and ofatumumab in MS has been confirmed by placebo-controlled clinical trials demonstrating a significant reduction of the annualized relapsing rate (ARR), new gadolinium-enhancing (GdE) and T2 lesions. There have been no significant safety problems so far but the overall benefit to risk profile is still to be determined. Expert commentary: After recent good results of these agents in MS therapy, questions related to maintenance therapy, markers of response and control of B cells values remain unanswered.

  2. Anti-CD20 monoclonal antibodies: beyond B-cells.

    PubMed

    Avivi, Irit; Stroopinsky, Dina; Katz, Tamar

    2013-09-01

    Anti-CD20 monoclonal antibodies (MoAbs), employed in treating CD20⁺ lymphomas and autoimmune diseases, appear to have broader functions than just eradicating malignant B-cells and decreasing autoantibody production. Rituximab-induced T-cell inactivation, reported both in-vitro and in-vivo, may contribute to the increased risk of T-cell-dependent infections, observed in patients receiving this therapy. T-cell polarization into a suppressive phenotype, often observed in patients receiving rituximab for autoimmune disorders, was reported to be associated with prolonged remissions. Elimination of B-cells serving as antigen-presenting cells, thereby causing impaired T-cell activation, could play a significant role in induction of these changes. Direct binding of rituximab to a CD20dim T-cell population, inducing its depletion, may contribute to the decreased T-cell activation following rituximab therapy. Further investigation of the complex network through which rituximab and new anti-CD20 MoAbs act, would advance the employment of these agents in different clinical settings.

  3. The future of anti-CD20 monoclonal antibodies: are we making progress?

    PubMed

    Alduaij, Waleed; Illidge, Tim M

    2011-03-17

    The anti-CD20 monoclonal antibody (mAb) rituximab has revolutionized the treatment of B-cell malignancies. This unprecedented success has not only substantially changed the mindset of the clinical community about the ability of mAb to improve outcomes but has catalyzed the interest in the pharmaceutical industry to develop the next generation of anti-CD20 mAbs. Since the introduction of rituximab 15 years ago, we have learned much about the potential mechanisms underlying the therapeutic efficacy of anti-CD20 mAbs. In parallel, many novel anti-CD20 mAbs have entered the clinic, each designed with modifications to structure aimed at further improving efficacy. On review of the newer generation of anti-CD20 mAbs entering clinical trials, it appears that the link between the novel mechanistic insights and the development of these next-generation anti-CD20 mAbs is unclear. As we move into an era of personalized medicine, it will become increasingly important for us to develop closer links between the emerging mechanistic insights and the clinical development, to further enhance the potency of anti-CD20 mAbs beyond that achieved with rituximab.

  4. Intrathecal anti-CD20 efficiently depletes meningeal B cells in CNS autoimmunity

    PubMed Central

    Lehmann-Horn, Klaus; Kinzel, Silke; Feldmann, Linda; Radelfahr, Florentine; Hemmer, Bernhard; Traffehn, Sarah; Bernard, Claude C A; Stadelmann, Christine; Brück, Wolfgang; Weber, Martin S

    2014-01-01

    Clinical trials revealed that systemic administration of B-cell-depleting anti-CD20 antibodies can hold lesion formation in the early relapsing-remitting phase of multiple sclerosis (MS). Throughout the secondary-progressive (SP) course of MS, pathogenic B cells may, however, progressively replicate within the central nervous system (CNS) itself, which is largely inaccessible to systemic anti-CD20 treatment. Utilizing the murine MS model of experimental autoimmune encephalomyelitis, we show that intrathecal (i.t.) administration of anti-CD20 alone very efficiently depletes meningeal B cells from established CNS lesions. In SP-MS patients, adding i.t. administration of anti-CD20 to its systemic use may be a valuable strategy to target pathogenic B-cell function. PMID:25356419

  5. Anti-CD20 antibody therapy and susceptibility to Pneumocystis pneumonia.

    PubMed

    Elsegeiny, Waleed; Eddens, Taylor; Chen, Kong; Kolls, Jay K

    2015-05-01

    Anti-CD20 antibody therapy has been a useful medication for managing non-Hodgkin's lymphoma as well as autoimmune diseases characterized by autoantibody generation. CD20 is expressed during most developmental stages of B lymphocytes; thus, CD20 depletion leads to B-lymphocyte deficiency. As the drug has become more widely used, there has been an increase in the number of case reports of patients developing Pneumocystis pneumonia. The role of anti-CD20 in Pneumocystis jirovecii infection is under debate due to the fact that most patients receiving it are on a regimen of multiple immunosuppressive medications. To address the specific role of CD20 depletion in host immunity against Pneumocystis, we examined a murine anti-CD20 depleting antibody. We demonstrated that anti-CD20 alone is permissive for Pneumocystis infection and that anti-CD20 impairs components of type II immunity, such as production of interleukin-4 (IL-4), IL-5, and IL-13 by whole-lung cells, in response to Pneumocystis murina. We also demonstrated that CD4(+) T cells from mice treated with anti-CD20 during Pneumocystis infection are incapable of mounting a protective immune response when transferred into Rag1(-/-) mice. Thus, CD20(+) cells are critical for generating protective CD4(+) T-cell immune responses against this organism.

  6. Molecular mechanisms of the antitumor effects of anti-CD20 antibodies.

    PubMed

    Winiarska, Magdalena; Glodkowska-Mrowka, Eliza; Bil, Jacek; Golab, Jakub

    2011-01-01

    Anti-CD20 monoclonal antibodies (mAbs) have become the mainstay in the treatment of non-Hodgkin's lymphomas and have shown significant activity in patients with B-cell chronic lymphocytic leukemia. Antitumor action of these antibodies results from triggering of indirect effector mechanisms of the immune system that include activation of complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), or phagocytosis. Moreover, some studies indicate direct influence of anti-CD20 mAbs on tumor cells that leads to induction of various types of cell death. Despite the wealth of data on the mechanisms of cytotoxicity that accumulated over the last two decades their relative contribution to the therapeutic outcome is still difficult to predict in individual patients. Elucidation of molecular mechanisms of anti-CD20 mAbs action is necessary to deliver their maximal activity in rationally designed combinations with other therapeutic approaches and to design next generation anti-CD20 mAb with improved ability to eliminate tumor cells.

  7. Veterans health administration hepatitis B testing and treatment with anti-CD20 antibody administration

    PubMed Central

    Hunt, Christine M; Beste, Lauren A; Lowy, Elliott; Suzuki, Ayako; Moylan, Cynthia A; Tillmann, Hans L; Ioannou, George N; Lim, Joseph K; Kelley, Michael J; Provenzale, Dawn

    2016-01-01

    AIM: To evaluate pretreatment hepatitis B virus (HBV) testing, vaccination, and antiviral treatment rates in Veterans Affairs patients receiving anti-CD20 Ab for quality improvement. METHODS: We performed a retrospective cohort study using a national repository of Veterans Health Administration (VHA) electronic health record data. We identified all patients receiving anti-CD20 Ab treatment (2002-2014). We ascertained patient demographics, laboratory results, HBV vaccination status (from vaccination records), pharmacy data, and vital status. The high risk period for HBV reactivation is during anti-CD20 Ab treatment and 12 mo follow up. Therefore, we analyzed those who were followed to death or for at least 12 mo after completing anti-CD20 Ab. Pretreatment serologic tests were used to categorize chronic HBV (hepatitis B surface antigen positive or HBsAg+), past HBV (HBsAg-, hepatitis B core antibody positive or HBcAb+), resolved HBV (HBsAg-, HBcAb+, hepatitis B surface antibody positive or HBsAb+), likely prior vaccination (isolated HBsAb+), HBV negative (HBsAg-, HBcAb-), or unknown. Acute hepatitis B was defined by the appearance of HBsAg+ in the high risk period in patients who were pretreatment HBV negative. We assessed HBV antiviral treatment and the incidence of hepatitis, liver failure, and death during the high risk period. Cumulative hepatitis, liver failure, and death after anti-CD20 Ab initiation were compared by HBV disease categories and differences compared using the χ2 test. Mean time to hepatitis peak alanine aminotransferase, liver failure, and death relative to anti-CD20 Ab administration and follow-up were also compared by HBV disease group. RESULTS: Among 19304 VHA patients who received anti-CD20 Ab, 10224 (53%) had pretreatment HBsAg testing during the study period, with 49% and 43% tested for HBsAg and HBcAb, respectively within 6 mo pretreatment in 2014. Of those tested, 2% (167/10224) had chronic HBV, 4% (326/7903) past HBV, 5% (427

  8. Production of an active anti-CD20-hIL-2 immunocytokine in Nicotiana benthamiana.

    PubMed

    Marusic, Carla; Novelli, Flavia; Salzano, Anna M; Scaloni, Andrea; Benvenuto, Eugenio; Pioli, Claudio; Donini, Marcello

    2016-01-01

    Anti-CD20 murine or chimeric antibodies (Abs) have been used to treat non-Hodgkin lymphomas (NHLs) and other diseases characterized by overactive or dysfunctional B cells. Anti-CD20 Abs demonstrated to be effective in inducing regression of B-cell lymphomas, although in many cases patients relapse following treatment. A promising approach to improve the outcome of mAb therapy is the use of anti-CD20 antibodies to deliver cytokines to the tumour microenvironment. In particular, IL-2-based immunocytokines have shown enhanced antitumour activity in several preclinical studies. Here, we report on the engineering of an anti-CD20-human interleukin-2 (hIL-2) immunocytokine (2B8-Fc-hIL2) based on the C2B8 mAb (Rituximab) and the resulting ectopic expression in Nicotiana benthamiana. The scFv-Fc-engineered immunocytokine is fully assembled in plants with minor degradation products as assessed by SDS-PAGE and gel filtration. Purification yields using protein-A affinity chromatography were in the range of 15-20 mg/kg of fresh leaf weight (FW). Glycopeptide analysis confirmed the presence of a highly homogeneous plant-type glycosylation. 2B8-Fc-hIL2 and the cognate 2B8-Fc antibody, devoid of hIL-2, were assayed by flow cytometry on Daudi cells revealing a CD20 binding activity comparable to that of Rituximab and were effective in eliciting antibody-dependent cell-mediated cytotoxicity of human PBMC versus Daudi cells, demonstrating their functional integrity. In 2B8-Fc-hIL2, IL-2 accessibility and biological activity were verified by flow cytometry and cell proliferation assay. To our knowledge, this is the first example of a recombinant immunocytokine based on the therapeutic Rituximab antibody scaffold, whose expression in plants may be a valuable tool for NHLs treatment.

  9. Reassessment of Anti-CD20 Therapy in Lymphoid Malignancies: Impact, Limitations, and New Directions.

    PubMed

    Reagan, Patrick M; Friedberg, Jonathan W

    2017-05-15

    The addition of anti-CD20 monoclonal antibodies to the treatment of B-cell malignancies has dramatically affected the field as well as the lives of patients. Rituximab in particular has been combined safely with conventional chemotherapy and has resulted in improved overall survival in major histologic subtypes of B-cell lymphoma and chronic lymphocytic leukemia. It is incorporated into the standard initial treatment of nearly all of these diseases. Novel anti-CD20 antibodies are currently under development. Two of these agents, ofatumumab and obinutuzumab, have been approved for use in certain clinical settings. Research comparing these newer antibodies with rituximab is ongoing. As these newer antibodies are further studied and developed, improvements in response and progression-free survival need to be considered in the context of clinical benefit as well as toxicity, especially in indolent diseases. Research involving rituximab biosimilars is ongoing as well, and recent preliminary data demonstrate similar efficacy and tolerability when compared with rituximab. An additional focus of ongoing research is the use of extended schedules of anti-CD20 monoclonal antibodies, as the optimal duration of therapy remains ill-defined in many histologic subtypes. To maximize the use of these agents, well-validated clinical trial endpoints will need to be carefully considered.

  10. A non-radioactive complement-dependent cytotoxicity assay for anti-CD20 monoclonal antibody.

    PubMed

    Gazzano-Santoro, H; Ralph, P; Ryskamp, T C; Chen, A B; Mukku, V R

    1997-03-28

    A simple and non-radioactive complement-dependent cytotoxicity assay was developed to determine the relative potency of an anti-CD20 mAb, IDEC-C2B8. The assay measures the relative number of viable cells based on the uptake and metabolism of the redox dye, Alamar blue. A linear relationship between the relative fluorescence unit generated and the number of viable cells was demonstrated. The assay is simple, has high throughput (performed in 96-well microtiter plates), and shows reproducible dose-response curves in the concentration range of 0.02-3.3 micrograms/ml. With intra-assay variability of 5-12%, interassay variability of 6-10% and spike recoveries of 101-109%, the assay has high precision and accuracy. Specificity was demonstrated by the lack of activity of immunoglobulins that do not bind CD20, or anti-CD20 antibody isotype (gamma 4) which does not bind complement. The assay is able to detect degradative changes in the molecule caused by heat, light and proteolytic treatments, suggesting its use as a stability-indicating method. Finally, the Alamar blue method compared favorably with other more conventional methods used to assess cell viability. The assay has the desired properties for use as a potency assay for quality control testing of anti-CD20 mAb.

  11. Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori).

    PubMed

    Tada, Minoru; Tatematsu, Ken-ichiro; Ishii-Watabe, Akiko; Harazono, Akira; Takakura, Daisuke; Hashii, Noritaka; Sezutsu, Hideki; Kawasaki, Nana

    2015-01-01

    In response to the successful use of monoclonal antibodies (mAbs) in the treatment of various diseases, systems for expressing recombinant mAbs using transgenic animals or plants have been widely developed. The silkworm (Bombyx mori) is a highly domesticated insect that has recently been used for the production of recombinant proteins. Because of their cost-effective breeding and relatively easy production scale-up, transgenic silkworms show great promise as a novel production system for mAbs. In this study, we established a transgenic silkworm stably expressing a human-mouse chimeric anti-CD20 mAb having the same amino acid sequence as rituximab, and compared its characteristics with rituximab produced by Chinese hamster ovary (CHO) cells (MabThera®). The anti-CD20 mAb produced in the transgenic silkworm showed a similar antigen-binding property, but stronger antibody-dependent cell-mediated cytotoxicity (ADCC) and weaker complement-dependent cytotoxicity (CDC) compared to MabThera. Post-translational modification analysis was performed by peptide mapping using liquid chromatography/mass spectrometry. There was a significant difference in the N-glycosylation profile between the CHO- and the silkworm-derived mAbs, but not in other post-translational modifications including oxidation and deamidation. The mass spectra of the N-glycosylated peptide revealed that the observed biological properties were attributable to the characteristic N-glycan structures of the anti-CD20 mAbs produced in the transgenic silkworms, i.e., the lack of the core-fucose and galactose at the non-reducing terminal. These results suggest that the transgenic silkworm may be a promising expression system for the tumor-targeting mAbs with higher ADCC activity.

  12. Characterization of anti-CD20 monoclonal antibody produced by transgenic silkworms (Bombyx mori)

    PubMed Central

    Tada, Minoru; Tatematsu, Ken-Ichiro; Ishii-Watabe, Akiko; Harazono, Akira; Takakura, Daisuke; Hashii, Noritaka; Sezutsu, Hideki; Kawasaki, Nana

    2015-01-01

    In response to the successful use of monoclonal antibodies (mAbs) in the treatment of various diseases, systems for expressing recombinant mAbs using transgenic animals or plants have been widely developed. The silkworm (Bombyx mori) is a highly domesticated insect that has recently been used for the production of recombinant proteins. Because of their cost-effective breeding and relatively easy production scale-up, transgenic silkworms show great promise as a novel production system for mAbs. In this study, we established a transgenic silkworm stably expressing a human-mouse chimeric anti-CD20 mAb having the same amino acid sequence as rituximab, and compared its characteristics with rituximab produced by Chinese hamster ovary (CHO) cells (MabThera®). The anti-CD20 mAb produced in the transgenic silkworm showed a similar antigen-binding property, but stronger antibody-dependent cell-mediated cytotoxicity (ADCC) and weaker complement-dependent cytotoxicity (CDC) compared to MabThera. Post-translational modification analysis was performed by peptide mapping using liquid chromatography/mass spectrometry. There was a significant difference in the N-glycosylation profile between the CHO− and the silkworm-derived mAbs, but not in other post-translational modifications including oxidation and deamidation. The mass spectra of the N-glycosylated peptide revealed that the observed biological properties were attributable to the characteristic N-glycan structures of the anti-CD20 mAbs produced in the transgenic silkworms, i.e., the lack of the core-fucose and galactose at the non-reducing terminal. These results suggest that the transgenic silkworm may be a promising expression system for the tumor-targeting mAbs with higher ADCC activity. PMID:26261057

  13. Novel designs of multivalent anti-CD20 humanized antibodies as improved lymphoma therapeutics.

    PubMed

    Rossi, Edmund A; Goldenberg, David M; Cardillo, Thomas M; Stein, Rhona; Wang, Yang; Chang, Chien-Hsing

    2008-10-15

    Multivalent antibodies, either monospecific or bispecific, may improve the efficacy of current therapeutic interventions involving a single monoclonal antibody (mAb). We have applied the Dock-and-Lock (DNL) method, a new platform technology for the site-specific and covalent assembly of modular components into stably tethered complexes of defined composition, to prepare a hexavalent, anti-CD20 antibody, designated Hex-hA20, which comprises six Fabs with one Fc. We show that Hex-hA20 retains the binding activity of all six Fabs, associates with CD20 in lipid rafts, affects antibody-dependent cell-mediated cytotoxicity, but not complement-dependent cytotoxicity, and inhibits proliferation of Daudi, Raji, and Ramos cells in vitro at subnanomolar concentrations without the need for a cross-linking antibody. In addition, Hex-hA20 induces strong homotypical adhesion and is inefficient in stimulating calcium mobilization. Thus, Hex-hA20 exhibits biological properties attributable to both type I and type II anti-CD20 mAbs, as exemplified by rituximab and tositumomab, respectively. Although Hex-hA20 has a short serum half-life, it shows antitumor efficacy in tumor-bearing mice comparable with veltuzumab at equivalent doses. The versatile DNL method was also applied to generate two other multivalent anti-CD20 antibodies without the Fc region, Tri-hA20 and Tetra-hA20, comprising three and four Fabs of veltuzumab, respectively. Similar to Hex-hA20, these were purified to near homogeneity and shown to have potent antiproliferative activity in vitro, thus indicating the need for clustering three or more CD20 molecules on the cell surface to induce growth inhibition.

  14. NOTE: Monte Carlo microdosimetry of 188Re- and 131I-labelled anti-CD20

    NASA Astrophysics Data System (ADS)

    Torres-García, E.; Garnica-Garza, H. M.; Ferro-Flores, G.

    2006-10-01

    The radiolabelled monoclonal antibody anti-CD20 has the property of binding to the CD20 antigen expressed on the cell surface of B-lymphocytes, thus making it a useful tool in the treatment of non-Hodgkin's lymphoma. In this work, the event-by-event Monte Carlo code NOREC is used to calculate the single-event distribution function f1(z) in the cell nucleus using the beta spectra of the 188Re and 131I radionuclides. The simulated geometry consists of two concentric spheres representing the nucleus and the cell surface embedded in a semi-infinite water medium. An isotropic point source was placed on the cell surface to simulate the binding of the anti-CD20 labelled with either 188Re or 131I. The simulations were carried out for two combinations of cell surface and nucleus radii. A method was devised that allows one to calculate the contribution of betas of energy greater than 1 MeV, which cannot be simulated by the NOREC code, to the single-event distribution function. It is shown that disregarding this contribution leads to an overestimation of the frequency-mean specific energy of the order of 9 12%. In general, the antibody radiolabelled with 131I produces single-event distribution functions that yield higher frequency-mean specific energies.

  15. Monte Carlo microdosimetry of 188Re- and 131I-labelled anti-CD20.

    PubMed

    Torres-García, E; Garnica-Garza, H M; Ferro-Flores, G

    2006-10-07

    The radiolabelled monoclonal antibody anti-CD20 has the property of binding to the CD20 antigen expressed on the cell surface of B-lymphocytes, thus making it a useful tool in the treatment of non-Hodgkin's lymphoma. In this work, the event-by-event Monte Carlo code NOREC is used to calculate the single-event distribution function f(1)(z) in the cell nucleus using the beta spectra of the (188)Re and (131)I radionuclides. The simulated geometry consists of two concentric spheres representing the nucleus and the cell surface embedded in a semi-infinite water medium. An isotropic point source was placed on the cell surface to simulate the binding of the anti-CD20 labelled with either (188)Re or (131)I. The simulations were carried out for two combinations of cell surface and nucleus radii. A method was devised that allows one to calculate the contribution of betas of energy greater than 1 MeV, which cannot be simulated by the NOREC code, to the single-event distribution function. It is shown that disregarding this contribution leads to an overestimation of the frequency-mean specific energy of the order of 9-12%. In general, the antibody radiolabelled with (131)I produces single-event distribution functions that yield higher frequency-mean specific energies.

  16. Assessment of cell death mechanisms triggered by (177)Lu-anti-CD20 in lymphoma cells.

    PubMed

    Azorín-Vega, E; Rojas-Calderón, E; Martínez-Ventura, B; Ramos-Bernal, J; Serrano-Espinoza, L; Jiménez-Mancilla, N; Ordaz-Rosado, D; Ferro-Flores, G

    2017-04-12

    The aim of this research was to evaluate the cell cycle redistribution and activation of early and late apoptotic pathways in lymphoma cells after treatment with (177)Lu-anti-CD20. Experimental and computer models were used to calculate the radiation absorbed dose to cancer cell nuclei. The computer model (Monte Carlo, PENELOPE) consisted of twenty spheres representing cells with an inner sphere (cell nucleus) embedded in culture media. Radiation emissions of the radiopharmaceutical located in cell membranes and in culture media were considered for nuclei dose calculations. Flow cytometric analyses demonstrated that doses as low as 4.8Gy are enough to induce cell cycle arrest and activate late apoptotic pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging

    PubMed Central

    Montalvao, Fabricio; Garcia, Zacarias; Celli, Susanna; Breart, Béatrice; Deguine, Jacques; Van Rooijen, Nico; Bousso, Philippe

    2013-01-01

    Anti-CD20 Ab therapy has proven successful for treating B cell malignancies and a number of autoimmune diseases. However, how anti-CD20 Abs operate in vivo to mediate B cell depletion is not fully understood. In particular, the anatomical location, the type of effector cells, and the mechanism underlying anti-CD20 therapy remain uncertain. Here, we found that the liver is a major site for B cell depletion and that recirculation accounts for the decrease in B cell numbers observed in secondary lymphoid organs. Using intravital imaging, we established that, upon anti-CD20 treatment, Kupffer cells (KCs) mediate the abrupt arrest and subsequent engulfment of B cells circulating in the liver sinusoids. KCs were also effective in depleting malignant B cells in a model of spontaneous lymphoma. Our results identify Ab-dependent cellular phagocytosis by KCs as a primary mechanism of anti-CD20 therapy and provide an experimental framework for optimizing the efficacy of therapeutic Abs. PMID:24177426

  18. Highly potent anti-CD20-RLI immunocytokine targeting established human B lymphoma in SCID mouse

    PubMed Central

    Vincent, Marie; Teppaz, Géraldine; Lajoie, Laurie; Solé, Véronique; Bessard, Anne; Maillasson, Mike; Loisel, Séverine; Béchard, David; Clémenceau, Béatrice; Thibault, Gilles; Garrigue-Antar, Laure; Jacques, Yannick; Quéméner, Agnès

    2014-01-01

    Rituximab (RTX), a chimeric IgG1 monoclonal antibody directed against the CD20 antigen, has revolutionized the treatment of B-cell malignancies. Nevertheless, the relapsed/refractory rates are still high. One strategy to increase the clinical effectiveness of RTX is based on antibody-cytokine fusion protein (immunocytokine; ICK) vectorizing together at the tumor site the antibody effector activities and the cytokine co-signal required for the generation of cytotoxic cellular immunity. Such ICKs linking various antibody formats to interleukin (IL)-2 are currently being investigated in clinical trials and have shown promising results in cancer therapies. IL-15, a structurally-related cytokine, is now considered as having a better potential than IL-2 in antitumor immunotherapeutic strategies. We have previously engineered the fusion protein RLI, linking a soluble form of human IL-15Rα-sushi+ domain to human IL-15. Compared with IL-15, RLI displayed better biological activities in vitro and higher antitumor effects in vivo in murine and human cancer models. In this study, we investigated the advantages of fusing RLI to RTX. Anti-CD20-RLI kept its binding capacity to CD20, CD16 and IL-15 receptor and therefore fully retained both antibody effector functions (ADCC and CDC), and the cytokine potential of RLI. In a severe combined immunodeficiency (SCID) mouse model of disseminated residual lymphoma, anti-CD20-RLI was found to induce long-term survival of 90% of mice up to at least 120 days whereas RLI and RTX, alone or in combination, just delayed the disease onset (100% of death at 28, 40 and 51 days respectively). These findings suggest that such ICK could improve the clinical efficacy of RTX, particularly in patients with refractory B-cell lymphoma. PMID:25072059

  19. Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

    PubMed Central

    Capolla, Sara; Garrovo, Chiara; Zorzet, Sonia; Lorenzon, Andrea; Rampazzo, Enrico; Spretz, Ruben; Pozzato, Gabriele; Núñez, Luis; Tripodo, Claudio; Macor, Paolo; Biffi, Stefania

    2015-01-01

    The expectations of nanoparticle (NP)-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conflicting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacokinetic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together, drug delivery and imaging probe represents a promising theranostics tool for targeting B-cell malignancies. PMID:26124662

  20. Anti-CD20 treatment of giant cell hepatitis with autoimmune hemolytic anemia.

    PubMed

    Paganelli, Massimiliano; Patey, Natacha; Bass, Lee M; Alvarez, Fernando

    2014-10-01

    Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare autoimmune disease of infancy characterized by severe liver disease associated with Coombs-positive hemolytic anemia. We recently showed that GCH-AHA is probably caused by a humoral immune mechanism. Such data support the use of rituximab, an anti-CD-20 monoclonal antibody specifically targeting B lymphocytes, as a treatment for GCH-AHA. We describe here the detailed clinical evolution of 4 children with GCH-AHA who showed a complete response to rituximab. All patients shared a severe course of the disease with poor control on standard and aggressive immunosuppression. Rituximab was well tolerated, and no side effects or infections were registered. Several doses were needed to induce remission, and 5 to 11 additional maintenance injections were necessary in the 2 more severe cases. Weaning from corticosteroids was achieved in all subjects. A steroid-sparing effect was noted in the 3 children who started rituximab early in the course of the disease. Overall, we show here that there is a strong rationale for treating GCH-AHA with rituximab. Early treatment could reduce the use of corticosteroids. Nevertheless, short-term steroids should be initially associated with rituximab to account for autoantibodies' half-life. Repeated injections are needed to treat and prevent relapses, but the best frequency and duration of treatment remain to be defined.

  1. Expression and biological characterization of an anti-CD20 biosimilar candidate antibody: a case study.

    PubMed

    Dorvignit, Denise; Palacios, Julio L; Merino, Maylin; Hernández, Tays; Sosa, Katya; Casaco, Angel; López-Requena, Alejandro; Mateo de Acosta, Cristina

    2012-01-01

    The CD20 molecule is a non-glycosylated protein expressed mainly on the surface of B lymphocytes. In some pathogenic B cells, it shows an increased expression, thus becoming an attractive target for diagnosis and therapy. Rituximab is a chimeric antibody that specifically recognizes the human CD20 molecule. This antibody is indicated for the treatment of non-Hodgkin lymphomas and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. In this work, we describe the stable expression and biological evaluation of an anti-CD20 biosimilar antibody. While rituximab is produced in fed-batch culture of recombinant Chinese hamster ovary (CHO) cells, our biosimilar antibody expression process consists of continuous culture of recombinant murine NS0 myeloma cells. The ability of the purified biosimilar antibody to recognize the CD20 molecule on human tumor cell lines, as well as on peripheral blood mononuclear cells from humans and primates, was demonstrated by flow cytometry. The biosimilar antibody induced complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity and apoptosis on human cell lines with high expression of CD20. In addition, this antibody depleted CD20-positive B lymphocytes from peripheral blood in monkeys. These results indicate that the biological properties of the biosimilar antibody compare favorably with those of the innovator product, and that it should be evaluated in future clinical trials.

  2. Successful treatment of steroid-refractory autoimmune thrombocytopenia associated with Castleman disease with anti-CD-20 antibody (rituximab).

    PubMed

    Ibrahim, Khalid; Maghfoor, Irfan; Elghazaly, Assem; Bakshi, Nasir; Mohamed, Said Y; Aljurf, Mahmoud

    2011-01-01

    Multicentric Castleman disease (MCD) is a lymphoproliferative disorder of incompletely understood etiology and with various clinical presentations. The best therapeutic option for this disease is not well established. MCD is known to be associated with autoimmune phenomena. A 70-year-old female patient of MCD with progressive nodal disease associated with autoimmune thrombocytopenia failed steroid treatment and showed a transient response to intravenous immunoglobulin. The patient achieved complete recovery of her platelet count and a very good response in nodal disease after 3 weekly doses of anti-CD-20 antibody (rituximab). Anti-CD20 antibody treatment could be a good therapeutic option for MCD, mainly when associated with immune-related disorders.

  3. Specific energy from Auger and conversion electrons of 131I, 188Re-anti-CD20 to a lymphocyte's nucleus

    NASA Astrophysics Data System (ADS)

    Torres-García, E.; Carrillo-Cazares, T. A.

    2011-01-01

    The typical radionuclides used to label anti-CD20 in the treatment of non-Hodgkin's lymphoma are 90Y, 131I, and 188Re, with the emission of beta particles, Auger electrons, and conversion electrons for the latter two. The aim of the present work was to calculate the contribution of high linear energy transfer radiation as Auger electrons (AE) and conversion electrons (CE) of 131I and 188Re-anti-CD20 to mean specific energy into the cell nucleus by Monte Carlo simulation (MCS), so as to infer therapeutic effectiveness on a dosimetric basis. MCS was used to quantify the frequency-mean specific energy into the cell nucleus, where the cell was modeled by two concentric spheres, considering two cell models. The results showed that 10% and 33% of the mean-specific energies (z¯) per disintegration imparted to the cell nucleus for both geometries are due to AE and CE; on the other hand, if the hit of AE and CE occurs, the contribution to (z¯) is about 64% and 86% for 131I and 188Re, respectively. According to the amount of specific energy from AE and CE into the cell nucleus by positive event, they can cause catastrophic effects in the nuclear DNA in the treatment of non-Hodgkin's lymphoma with 131I, 188Re-anti-CD20.

  4. Potential of Optimal Preloading in Anti-CD20 Antibody Radioimmunotherapy: An Investigation Based on Pharmacokinetic Modeling

    PubMed Central

    Kletting, Peter; Meyer, Christoph; Reske, Sven N.

    2010-01-01

    Abstract Recently, it has been suggested that the concept of preloading is limited by using a standard amount of unlabeled antibody. To identify the potential of optimal preloading, a pharmacokinetic model that describes the biodistribution of anti-CD20 antibody was developed. Simulations were conducted for different tumor burdens, spleen sizes, and tumor permeabilities. The optimal amount of unlabeled antibody was determined for each scenario. These simulations show that the currently administered standard amount is not optimal. A preload of 150 mg or lower would result in equal or higher tumor uptake in all cases. For tumors with high permeability, the uptake of labeled antibody could be increased by a factor of 8.5 using the considerably reduced optimal preload. The most sensitive parameter for the choice of the optimal amount of unlabeled antibody is the tumor uptake index. The results indicate that a personalized approach for radioimmunotherapy (RIT) with anti-CD20 antibody is required to account for the interpatient variability. The optimal amount of unlabeled antibody, which has to be determined by using a pharmacokinetic model, could substantially improve tumor uptake and thus RIT with anti-CD20 antibody. PMID:20578833

  5. Human neutrophils mediate trogocytosis rather than phagocytosis of CLL B-cells opsonized with anti-CD20 antibodies.

    PubMed

    Valgardsdottir, Rut; Cattaneo, Irene; Klein, Christian; Introna, Martino; Figliuzzi, Marina; Golay, Josée

    2017-03-13

    Polymorphonuclear neutrophils (PMN) have previously been reported to mediate phagocytosis of anti-CD20 opsonized B-cells from CLL patients. However recent data have suggested that PMN, like macrophages, can also mediate trogocytosis. We have performed experiments to more precisely investigate this point and discriminate between trogocytosis and phagocytosis. In live cell time-lapse microscopy experiments, we could not detect any significant phagocytosis by purified PMN of anti-CD20-opsonized CLL B-cells, but only the repeated close contact between effectors and targets, suggesting trogocytosis. Similarly, in flow cytometry assays using CLL B-cell targets labeled with the membrane dye PKH67 and opsonized with rituximab or obinutuzumab, we could show that a mean of 50% and 75% of PMN had taken a fraction of the dye from CLL B-cells at 3 and 20 hours, respectively, with no significant decrease in absolute live or total CLL B-cell numbers, confirming that trogocytosis takes place, rather than phagocytosis. Trogocytosis was accompanied by loss of membrane CD20 from CLL B-cells, which was evident with rituximab but not obinutuzumab. We conclude that PMN mediate mostly trogocytosis rather than phagocytosis of anti-CD20-opsonized CLL B-cells and discuss the implications of this finding in CLL patients treated with rituximab or obinutuzumab in vivo.

  6. Structural comparison of two anti-CD20 monoclonal antibody drug products using middle-down mass spectrometry.

    PubMed

    Wang, Bo; Gucinski, Ashley C; Keire, David A; Buhse, Lucinda F; Boyne, Michael T

    2013-05-21

    Liquid chromatography-mass spectrometry (LC-MS) is an information rich analytical tool that can provide fast, robust and sensitive characterization of protein therapeutics for quality assurance and structural comparison. Herein, structural characterization of two anti-CD20 monoclonal antibodies obtained from two different sources was performed using a middle-down LC-MS strategy to determine if they can be analytically differentiated. Through the use of a specific enzymatic digestion method using IdeS with subsequent LC-MS analysis, we show that the anti-CD20 monoclonal antibody that has been approved by the FDA can be partially characterized and differentiated analytically from an Indian sourced product that lacks FDA approval. In comparison to the FDA-approved product, differential modifications to both the N- and C-termini result in increased charge heterogeneity for the Indian product. In addition, significant differences in the intensities of the observed glycoforms between the two antibodies were detected. While this study assesses only one lot of each of a FDA approved drug product and the Indian sourced drug product, the observed differences may represent process specific fingerprints that could be useful for surveillance purposes.

  7. Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes.

    PubMed

    Hu, Changyun; Ding, Heyuan; Zhang, Xiaojun; Wong, F Susan; Wen, Li

    2013-08-01

    Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease, although B cells also play an important role in T1D development. Both T cell- and B cell-directed immunotherapies have shown efficacy in the prevention and reversal of T1D. However, whether the combined strategy of targeting both T and B cells could further improve therapeutic efficacy remains to be explored. We show that combined treatment with intravenous antihuman CD20 (hCD20) and oral anti-CD3 significantly delays diabetes development in prediabetic hCD20 transgenic NOD mice. More importantly, the combined treatment reverses diabetes in >60% of mice newly diagnosed with diabetes. Further mechanistic studies demonstrated that the addition of oral anti-CD3 to the B-cell depletion therapy synergistically enhances the suppressive function of regulatory T cells. Of note, the oral anti-CD3 treatment induced a fraction of interleukin (IL)-10-producing CD4 T cells in the small intestine through IL-10- and IL-27-producing dendritic cells. Thus, the findings demonstrate that combining anti-CD20 and oral anti-CD3 is superior to anti-CD20 monotherapy for restoring normoglycemia in diabetic NOD mice, providing important preclinical evidence for the optimization of B cell-directed therapy for T1D.

  8. Anti-CD137 enhances anti-CD20 therapy of systemic B-cell lymphoma with altered immune homeostasis but negligible toxicity

    PubMed Central

    Souza-Fonseca-Guimaraes, Fernando; Blake, Stephen J.; Makkouk, Amani; Chester, Cariad; Kohrt, Holbrook E.; Smyth, Mark J.

    2016-01-01

    ABSTRACT Studies of sequential anti-CD137/anti-CD20 therapy have previously shown that the efficacy of anti-CD20 was heavily reliant upon anti-CD137; however, the exact mechanism of the anti-B-cell lymphoma efficacy, and whether this correlates with enhanced adverse effects or toxicity, had not been elucidated. Here, we observed that sequential anti-CD137 administration with anti-CD20 resulted in a synergistic therapy, largely dependent upon Fc receptors (FcR), to prolong survival in an experimental B-cell lymphoma therapy model. Tumor suppression was accompanied by B cell depletion, which was not dependent on one activating FcR. Surprisingly, the B-cell activating factor (BAFF) was elevated in the plasma of mice receiving anti-CD137 alone or in combination with anti-CD20, while a selective increase in some plasma cytokines was also noted and triggered by anti-CD137. These effects were independent of activating FcR. Sustained treatment of advanced lymphoma revealed increased lymphocyte infiltrates into the liver and a significant decrease in the metabolic capability of the liver in mice receiving anti-CD137. Importantly, these effects were not exacerbated in mice receiving the anti-CD20/CD137 combination, and elevations in classical liver damage markers such as alanine aminotransferase (ALT) were less than that caused by the lymphoma itself. Thus, combined anti-CD20/anti-CD137 treatment increases the therapeutic index of anti-CD20 or anti-CD137 alone. These mouse data were corroborated by ongoing clinical development studies to assess safety, tolerability and pharmacodynamic activity of human patients treated by this approach. Together, these data support the use of this sequential antibody therapeutic strategy to improve the efficacy of rituximab in B-cell lymphoma patients. PMID:27622048

  9. [One amino acid mutation in an anti-CD20 antibody fragment that affects the yield bacterial secretion and the affinity].

    PubMed

    Liu, Yin-Xing; Xiong, Dong-Sheng; Fan, Dong-Mei; Shao, Xiao-Feng; Xu, Yuan-Fu; Zhu, Zhen-Ping; Yang, Chun-Zheng

    2003-05-01

    Monoclonal antibodies (mAb) directed against CD20, either unmodified or in radiolabeled forms, have been successfully exploited in clinic as effective therapeutic agents in the management of non-Hodgkin's B-cell lymphoma. The antibody fragment is a potential agent in image and therapy of tumor. To further improve the soluble expression of anti-CD20 antibody Fab' fragment, PCR was used to mutate the anti-CD20 VL and VH genes and its biological activity was identified. The expression vector of chimeric antibody Fab' was constructed and expressed in E. coli. The data of mutant clone DNA sequence showed that the amino acid of light chain gene of the parent anti-CD20 antibody (H47) was successful mutated as Ser (GAG)-Asn (CAG). The soluble expression of mutated anti-CD20 Fab' (CD20-7) was 3.8 mg/g dry cell weight, while the parent (CD20-2) was 1.3 mg/g dry cell weight. The affinity constant Ka of CD20-7 was 2.2 x 10(9) L/mol. The primary results of competitive assays by FACS showed that CD20-7 could partially block the sites through which parent antibody (HI47) bind to Raji cells. There was difference in the Raji cells (CD20+)-binding activity between the mutant CD20-7 and parent CD20-2. The site mutation of anti-CD20 Fab' gene make it possible that the anti-CD20 antibody fragment was succeeded to obtain higher expression. In this thesis, we succeeded in completing mutation and expression of anti-CD20 Fab' genes, distinguishing its biological activity, and obtaining its highly expression. These period results will lay a foundation for development of other kind of anti-CD20 engineering antibody (for instance: Fab' Diabody and miniantibody), and make it possible for anti-CD20 antibody to be applied to tumor therapy in civil in the future.

  10. γδ T-cell killing of primary follicular lymphoma cells is dramatically potentiated by GA101, a type II glycoengineered anti-CD20 monoclonal antibody.

    PubMed

    Braza, Mounia Sabrina; Klein, Bernard; Fiol, Geneviève; Rossi, Jean-François

    2011-03-01

    Anti-CD20 monoclonal antibodies are major therapeutic agents for patients with follicular lymphoma and work through complement-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. Optimization of antibody-dependent cellular cytotoxicity, in particular by amplifying its effectors, could further increase the efficacy of anti-CD20 monoclonal antibodies. We investigated the cytotoxic activity of Vγ9Vδ2 T cells against follicular lymphoma cells and whether this killing could be increased by promoting antibody-dependent cellular cytotoxicity with anti-CD20 monoclonal antibodies, in particular a type-II glycoengineered anti-CD20. Vγ9Vδ2 T cells were expanded in vitro in the presence of bromohydrin pyrophosphate (Phosphostim) and interleukin-2 and their ability to kill follicular lymphoma primary cells or cell lines was evaluated by flow cytometry cytotoxic T-lymphocyte assays in the presence or absence of three anti-CD20 monoclonal antibodies: the afucosylated GA101, the chimeric rituximab or the humanized ofatumumab. The ability of these cells to release perforin/granzyme and secrete interferon-γ when co-cultured with follicular lymphoma primary cells or cell lines in the presence or not of the three anti-CD20 monoclonal antibodies was also evaluated by CD107a staining and Elispot assays. Phosphostim and interleukin-2 expanded Vγ9Vδ2 T cells were cytotoxic to primary follicular lymphoma cells and their cytotoxic potential was dramatically increased by GA101, a type II glycoengineered anti-CD20 monoclonal antibody, and to a lesser extent, by rituximab and ofatumumab. The increased cytotoxicity was associated with increased secretion of perforin/granzyme and interferon-γ. In-vitro expanded Vγ9Vδ2 T cells efficiently kill primary follicular lymphoma cells and express CD16; anti-CD20 monoclonal antibodies, in particular GA101, dramatically increase the cytotoxic activity of expanded Vγ9Vδ2 T cells. These preclinical results prompt the development

  11. Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies

    PubMed Central

    Grandjean, Capucine L.; Montalvao, Fabricio; Celli, Susanna; Michonneau, David; Breart, Beatrice; Garcia, Zacarias; Perro, Mario; Freytag, Olivier; Gerdes, Christian A.; Bousso, Philippe

    2016-01-01

    Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment. Relying on intravital two-photon imaging of human CD20-expressing mice, we provide evidence that ADP by Kupffer cells (KC) is a major mechanism for rituximab-mediated B cell depletion. Notably, a glycoengineered anti-mouse CD20 Ab but not its wild-type counterpart triggered potent KC-mediated B cell depletion at low doses. Finally, distinct thresholds for KC phagocytosis were also observed for GA101 (obinutuzumab), a humanized glycoengineered type II anti-CD20 Ab and rituximab. Thus, we propose that enhanced phagocytosis of circulating B cells by KC represents an important in vivo mechanism underlying the improved activity of glycoengineered anti-CD20 mAbs. PMID:27698437

  12. Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies.

    PubMed

    Grandjean, Capucine L; Montalvao, Fabricio; Celli, Susanna; Michonneau, David; Breart, Beatrice; Garcia, Zacarias; Perro, Mario; Freytag, Olivier; Gerdes, Christian A; Bousso, Philippe

    2016-10-04

    Anti-CD20 monoclonal antibodies (mAbs) represent an effective treatment for a number of B cell malignancies and autoimmune disorders. Glycoengineering of anti-CD20mAb may contribute to increased anti-tumor efficacy through enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADP) as reported by in vitro studies. However, where and how glycoengineered Ab may potentiate therapeutic responses in vivo is yet to be elucidated. Here, we have performed mouse liver transplants to demonstrate that the liver is sufficient to mediate systemic B cells depletion after anti-CD20 treatment. Relying on intravital two-photon imaging of human CD20-expressing mice, we provide evidence that ADP by Kupffer cells (KC) is a major mechanism for rituximab-mediated B cell depletion. Notably, a glycoengineered anti-mouse CD20 Ab but not its wild-type counterpart triggered potent KC-mediated B cell depletion at low doses. Finally, distinct thresholds for KC phagocytosis were also observed for GA101 (obinutuzumab), a humanized glycoengineered type II anti-CD20 Ab and rituximab. Thus, we propose that enhanced phagocytosis of circulating B cells by KC represents an important in vivo mechanism underlying the improved activity of glycoengineered anti-CD20 mAbs.

  13. Follicular B cells in thyroids of mice with spontaneous autoimmune thyroiditis contribute to disease pathogenesis and are targets of anti-CD20Ab therapy

    PubMed Central

    Hong, So-Hee; Braley-Mullen, Helen

    2014-01-01

    B cells are required for development of spontaneous autoimmune thyroiditis (SAT) in NOD.H-2h4 mice where they function as important antigen presenting cells (APCs) for activation of CD4+ T cells. Depletion of B cells using anti-CD20 effectively inhibits SAT development. The goals of this study were to characterize the B cells that migrate to thyroids in SAT, and determine if anti-CD20 effectively targets those B cells in mice with established SAT. The results showed that most thyroid infiltrating B cells in mice with SAT are follicular (FO) B cells. Expression of CD80, CD86 and CD40 was significantly increased on follicular (FO), but not marginal zone (MZ) splenic B cells after SAT development. Thyroid-infiltrating and peripheral blood B cells had lower expresion of CD20 and CD24 compared to splenic and LN FO B cells. Despite reduced CD20 expression, anti-CD20 depleted most B cells in thyroids of mice with established SAT within 3 days. B cell depletion in thyroids of mice given anti-CD20 was more complete and longer lasting than in spleen and LN and was comparable to that in blood. Circulation of B cells was required for effective and rapid removal of B cells in thyroids since preventing lymphocyte egress by administration of FTY20 abrogated the effects of anti-CD20 on thyroid B cells. Therefore the FO subset of B cells preferentially contributes to SAT development and persistence, and anti-CD20 targeting of FO B cells effectively eliminates B cells in the target organ even though thyroid B cells have decreased CD20 expression. PMID:24376265

  14. Administration Of Anti-CD20 mAb Is Highly Effective In Preventing But Ineffective In Treating Chronic GVHD While Preserving Strong GVL Effects

    PubMed Central

    Johnston, Heather F.; Xu, Yajing; Racine, Jeremy J.; Cassady, Kaniel; Ni, Xiong; Wu, Tao; Chan, Andrew; Forman, Stephen; Zeng, Defu

    2014-01-01

    Chronic graft-versus-host disease (cGVHD) is an autoimmune-like syndrome, and donor B cells play important roles in augmenting its pathogenesis. B cell-depleting anti-CD20 mAb has been administered before or after cGVHD onset for preventing or treating cGVHD in clinic. Although administration before onset appeared to be more effective, the effect is variable and sometimes minimal. Here, we used two mouse cGVHD models to evaluate the preventive and therapeutic effect of anti-CD20 mAb. With the model of DBA/2 donor to MHC-matched BALB/c recipient, one intravenous injection of anti-CD20 mAb (40 mg/kg) the following day or on day 7 after HCT when serum autoantibodies were undetectable effectively prevented induction of cGVHD and preserved strong graft-versus-leukemia (GVL) effect. The separation of GVL effect from GVHD was associated with a significant reduction of donor CD4+ T cell proliferation and expansion, and protection of host thymic medullary epithelial cells. Anti-CD20 mAb administration also prevented expansion of donor T cells and induction of cGVHD in another mouse model of C57BL/6 donor to MHC-mismatched BALB/c recipients. In contrast, administration of anti-CD20 mAb after GVHD onset was not able to effectively deplete donor B cells or ameliorate cGVHD in either model. These results indicate that administration of anti-CD20 mAb prior to signs of cGVHD can prevent induction of autoimmune-like cGVHD while preserving GVL effect; there is little effect if administered after cGVHD onset. This provides new insights into clinical prevention and therapy of cGVHD with B cell-depleting reagents. PMID:24796279

  15. Primary central nervous system lymphoma: current state of anti-CD20 therapy and appraisal of reported response criteria.

    PubMed

    Siegal, Tali

    2014-05-01

    Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin's lymphoma which is confined to the central nervous system and may also affect intraocular structures. Despite high initial rates of response to methotrexate-based chemotherapy, more than 50% of patients will experience relapse and about 10% have disease that is refractory to chemotherapy. Outcome in patients who fail treatment is very poor, and therefore new therapeutic approaches that may increase the rate of complete response and the proportion of durable remission are sought. Based on the pivotal role that anti-CD20 therapy now plays in the treatment outcome of aggressive systemic B-cell lymphomas, a similar approach is commonly being adapted for PCNSL despite the lack of evidence for its effectiveness. This review examines the current status and level of evidence for the use of monoclonal antibodies against the CD20 surface antigen, which is present on normal and malignant B-cells in PCNSL. The review covers both systemic and local (intracerebrospinal fluid or intravitreal) administration of CD20 monoclonal antibodies in PCNSL. In addition, it scrutinizes the response criteria commonly reported for evaluation of treatment outcome. The importance of differentiating unconfirmed complete response from partial response is outlined and the lack of consensus on response criteria for atypical imaging presentations of PCNSL is delineated. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Properties and structure-function relationships of veltuzumab (hA20), a humanized anti-CD20 monoclonal antibody

    PubMed Central

    Rossi, Edmund A.; Stein, Rhona; Cardillo, Thomas M.; Czuczman, Myron S.; Hernandez-Ilizaliturri, Francisco J.; Hansen, Hans J.; Chang, Chien-Hsing

    2009-01-01

    Veltuzumab is a humanized anti-CD20 monoclonal antibody with complementarity-determining regions (CDRs) identical to rituximab, except for one residue at the 101st position (Kabat numbering) in CDR3 of the variable heavy chain (VH), having aspartic acid (Asp) instead of asparagine (Asn), with framework regions of epratuzumab, a humanized anti-CD22 antibody. When compared with rituximab, veltuzumab has significantly reduced off-rates in 3 human lymphoma cell lines tested, aswell as increased complement-dependent cytotoxicity in 1 of 3 cell lines, but no other in vitro differences. Mutation studies confirmed that the differentiation of the off-rate between veltuzumab and rituximab is related to the single amino acid change in CDR3-VH. Studies of intraperitoneal and subcutaneous doses in mouse models of human lymphoma and in normal cynomolgus monkeys disclosed that low doses of veltuzumab control tumor growth or deplete circulating or sessile B cells. Low- and high-dose veltuzumab were significantly more effective in vivo than rituximab in 3 lymphoma models. These findings are consistent with activity in patients with non-Hodgkin lymphoma given low intravenous or subcutaneous doses of veltuzumab. Thus, changing Asn101 to Asp101 in CDR3-VH of rituximab is responsible for veltuzumab's lower off-rate and apparent improved potency in preclinical models that could translate into advantages in patients. PMID:18941114

  17. Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD).

    PubMed

    Oertel, S H K; Verschuuren, E; Reinke, P; Zeidler, K; Papp-Váry, M; Babel, N; Trappe, R U; Jonas, S; Hummel, M; Anagnostopoulos, I; Dörken, B; Riess, H B

    2005-12-01

    Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation. Treatment with rituximab, a humanized anti-CD20 monoclonal antibody, has proved to be a promising approach and shown a low toxicity profile. Between February 1999 and April 2002, we conducted a multicentre phase II trial investigating rituximab as single agent in 17 patients with PTLD. Transplanted organs were heart (n = 5), kidney (n = 4), lung (n = 4) and liver (n = 4). Patients were treated with four weekly doses of 375 mg/m(2) of rituximab. The mean follow-up time is 24.2 months. Histology was distributed in 10 diffuse large cell-, 2 marginal zone-, 1 Burkitt-like lymphoma, 1 Hodgkin-like PTLD and 3 polymorphic lymphoproliferations. Therapy was well tolerated and no severe adverse events were observed. The mean overall survival period is 37.0 months with 11 patients still living. In total, 9 patients (52.9%) achieved a complete remission, with a mean duration of 17.8 months. Partial remission was observed in 1 patient, minor remission in 2 patients, no change in 3 patients and 1 patient experienced progressive disease. Two patients relapsed, at intervals 3 and 5 months after obtaining complete remission. Rituximab proved to be well tolerated and effective in the treatment of PTLD.

  18. Subcutaneous injections of low doses of humanized anti-CD20 veltuzumab: a phase I study in chronic lymphocytic leukemia.

    PubMed

    Kalaycio, Matt E; George Negrea, O; Allen, Steven L; Rai, Kanti R; Abbasi, Rashid M; Horne, Heather; Wegener, William A; Goldenberg, David M

    2016-01-01

    To evaluate the potential of subcutaneous (SC) injections with anti-CD20 antibody veltuzumab in chronic lymphocytic leukemia (CLL), 21 patients received 80, 160, or 320 mg injections every 2 weeks × 4 doses (n = 11) or 160 or 320 mg twice-weekly × 16 doses (n = 10). Treatment was well tolerated with only occasional, mild-moderate, transient injection reactions. Lymphocytosis decreased in all patients (maximum decrease, 5-91%), with 12 patients obtaining >50% decreases. Of 14 patients with lymphadenopathy on CT imaging, 5 (36%) achieved 14-61% reductions (sum of perpendicular diameters). By NCI-WG criteria, two patients achieved partial responses (10%). SC veltuzumab appeared active in all dose groups, with no obvious exposure-response relationship, despite cumulative doses ranging from 320-5120 mg. Overall median progression-free survival was 7.7 months; three patients remained progression-free >1 year (2 ongoing at 2-year study completion). These data suggest further studies of SC veltuzumab in CLL are warranted.

  19. Refractory relapsing polychondritis in a child treated with antiCD20 monoclonal antibody (rituximab): first case report.

    PubMed

    Abdwani, Reem; Kolethekkat, Arif Ali; Al Abri, Rashid

    2012-07-01

    To report the first case of refractory relapsing polychondritis in a child who was treated with the biological agent, rituximab, an antiCD20 monoclonal antibody. The case is reported with a review of the literature on the use of biological agents in the treatment of refractory relapsing polychondritis. A 10-year-old boy presented with relapsing polychondritis who was treated initially with prednisolone and methotrexate. As there was no response to the treatment, anti TNF antagonist infliximab was given but with a failed response. A subsequent therapy with rituximab produced significant clinical remission with no recurrence at 1 year. Relapsing polychondritis unresponsive to primary treatment modalities but treated with various biological agents in adult have been well described in adults but not reported in children age below 13 yrs. Hence we present this case report. Biological agents such as rituximab has promising role in children when primary treatment fails as reported in our case. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies.

    PubMed

    Sun, Liping L; Ellerman, Diego; Mathieu, Mary; Hristopoulos, Maria; Chen, Xiaocheng; Li, Yijin; Yan, Xiaojie; Clark, Robyn; Reyes, Arthur; Stefanich, Eric; Mai, Elaine; Young, Judy; Johnson, Clarissa; Huseni, Mahrukh; Wang, Xinhua; Chen, Yvonne; Wang, Peiyin; Wang, Hong; Dybdal, Noel; Chu, Yu-Waye; Chiorazzi, Nicholas; Scheer, Justin M; Junttila, Teemu; Totpal, Klara; Dennis, Mark S; Ebens, Allen J

    2015-05-13

    Bispecific antibodies and antibody fragments in various formats have been explored as a means to recruit cytolytic T cells to kill tumor cells. Encouraging clinical data have been reported with molecules such as the anti-CD19/CD3 bispecific T cell engager (BiTE) blinatumomab. However, the clinical use of many reported T cell-recruiting bispecific modalities is limited by liabilities including unfavorable pharmacokinetics, potential immunogenicity, and manufacturing challenges. We describe a B cell-targeting anti-CD20/CD3 T cell-dependent bispecific antibody (CD20-TDB), which is a full-length, humanized immunoglobulin G1 molecule with near-native antibody architecture constructed using "knobs-into-holes" technology. CD20-TDB is highly active in killing CD20-expressing B cells, including primary patient leukemia and lymphoma cells both in vitro and in vivo. In cynomolgus monkeys, CD20-TDB potently depletes B cells in peripheral blood and lymphoid tissues at a single dose of 1 mg/kg while demonstrating pharmacokinetic properties similar to those of conventional monoclonal antibodies. CD20-TDB also exhibits activity in vitro and in vivo in the presence of competing CD20-targeting antibodies. These data provide rationale for the clinical testing of CD20-TDB for the treatment of CD20-expressing B cell malignancies. Copyright © 2015, American Association for the Advancement of Science.

  1. Plasmapheresis, CMV hyperimmune globulin, and anti-CD20 allow ABO-incompatible renal transplantation without splenectomy.

    PubMed

    Sonnenday, Christopher J; Warren, Daniel S; Cooper, Mathew; Samaniego, Milagros; Haas, Mark; King, Karen E; Shirey, R Sue; Simpkins, Christopher E; Montgomery, Robert A

    2004-08-01

    The majority of preconditioning protocols developed to allow ABO-incompatible (ABOi) renal transplantation include concurrent splenectomy as a prerequisite to successful engraftment. Our center has developed a preconditioning protocol that includes plasmapheresis (PP), low-dose CMV hyperimmune globulin (CMVIg), and anti-CD20 monoclonal antibody (rituximab) to allow ABOi renal transplantation without splenectomy. Our initial experience has included treatment of six recipients and successful transplantation from blood group A(1), A(2), and group B living donors. Mean (+/- SD) serum creatinine was 1.3 +/- 0.1 mg/dL among the six recipients and no episodes of antibody-mediated rejection (AMR) occurred at a median follow-up of 12 months. ABO antibody titers have remained below pretreatment levels. The absence of AMR and stable allograft function in this series show the potential of this preconditioning protocol to increase ABOi renal transplantation. The use of rituximab, allowing avoidance of splenectomy, may further remove one of the significant disincentives to ABOi transplantation, and eliminate the risk of post-splenectomy infections.

  2. Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies.

    PubMed

    Tipton, Thomas R W; Roghanian, Ali; Oldham, Robert J; Carter, Matthew J; Cox, Kerry L; Mockridge, C Ian; French, Ruth R; Dahal, Lekh N; Duriez, Patrick J; Hargreaves, Philip G; Cragg, Mark S; Beers, Stephen A

    2015-03-19

    Following the success of rituximab, 2 other anti-CD20 monoclonal antibodies (mAbs), ofatumumab and obinutuzumab, have entered clinical use. Ofatumumab has enhanced capacity for complement-dependent cytotoxicity, whereas obinutuzumab, a type II mAb, lacks the ability to redistribute into lipid rafts and is glycoengineered for augmented antibody-dependent cellular cytotoxicity (ADCC). We previously showed that type I mAbs such as rituximab have a propensity to undergo enhanced antigenic modulation compared with type II. Here we assessed the key effector mechanisms affected, comparing type I and II antibodies of various isotypes in ADCC and antibody-dependent cellular-phagocytosis (ADCP) assays. Rituximab and ofatumumab depleted both normal and leukemic human CD20-expressing B cells in the mouse less effectively than glycoengineered and wild-type forms of obinutuzumab, particularly when human immunoglobulin G1 (hIgG1) mAbs were compared. In contrast to mouse IgG2a, hIgG1 mAbs were ineffective in ADCC assays with murine natural killer cells as effectors, whereas ADCP was equivalent for mouse IgG2a and hIgG1. However, rituximab's ability to elicit both ADCC and ADCP was reduced by antigenic modulation, whereas type II antibodies remained unaffected. These data demonstrate that ADCP and ADCC are impaired by antigenic modulation and that ADCP is the main effector function employed in vivo.

  3. Anti-CD3ε induces splenic B220lo B-cell expansion following anti-CD20 treatment in a mouse model of allosensitization.

    PubMed

    Todo, Tsuyoshi; Wu, Gordon; Chai, Ning-ning; He, Yao; Martins, Gislaine; Gupta, Ankur; Fair, Jeffrey; Liu, Nai-you; Jordan, Stanley; Klein, Andrew

    2012-08-01

    Antibodies targeting T cells and B cells are increasingly used for immunosuppression in clinical transplantation. However, the impact of T-cell depletion by antibodies on B-cell homeostasis is poorly understood. Using a mouse model of allosensitization with skin allograft, we investigated whether targeting T cells by anti-CD3ε alters peripheral B-cell homeostasis and alloantibody responses following B-cell depletion by anti-CD20. We found that anti-CD3ε induced a discrete B220(lo), but not a conventional B220(hi) subset, in the spleens of the allosensitized mice 14 days after anti-CD20 treatment. The splenic B220(lo) cells were refractory to anti-CD20 depletion. Flow cytometry revealed that the splenic B220(lo) cells were phenotypically similar to the B220(lo) AA4.1(+) CD23(-) sIgM(lo) sIgD(-) developing B cells (pre-B to immature B) normally presented in the bone marrow. Despite the presence of the splenic B220(lo) cells, mice treated with combined anti-CD3ε/CD20 produced limited alloantibodies in response to the primary skin allografts. Alloantibody production increased significantly in the mice following re-immunization by donor-specific splenocytes. We conclude that anti-CD3ε can induce an expansion of B220(lo) B cells in the spleens after B-cell depletion by anti-CD20. These B cells are not producing alloantibodies, but re-immunization of the mice with alloantigen leads to risk of alloantibody response.

  4. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    PubMed Central

    Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark D.; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Bäck, Tom A.; Fisher, Darrell R.; Press, Oliver W.

    2015-01-01

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in

  5. Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    DOE PAGES

    Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.; ...

    2015-03-18

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targetingmore » either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT

  6. Comparative efficacy of 177Lu and 90Y for anti-CD20 pretargeted radioimmunotherapy in murine lymphoma xenograft models.

    PubMed

    Frost, Sofia H L; Frayo, Shani L; Miller, Brian W; Orozco, Johnnie J; Booth, Garrett C; Hylarides, Mark D; Lin, Yukang; Green, Damian J; Gopal, Ajay K; Pagel, John M; Bäck, Tom A; Fisher, Darrell R; Press, Oliver W

    2015-01-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma xenograft

  7. Suppression of Rituximab-resistant B-cell lymphoma with a novel multi-component anti-CD20 mAb nanocluster

    PubMed Central

    Zhao, He; Sun, Yun; Zhao, Mengxin; Chen, Di; Zhu, Xiandi; Zhang, Li; Li, Bohua; Dai, Jianxin; Li, Wei

    2015-01-01

    Although the anti-CD20 antibody Rituximab has revolutionized the treatment of Non-Hodgkin Lymphoma (NHL), resistance to treatment still existed. Thus, strategies for suppressing Rituximab-resistant NHLs are urgently needed. Here, an anti-CD20 nanocluster (ACNC) is successfully constructed from its type I and type II mAb (Rituximab and 11B8). These distinct anti-CD20 mAbs are mass grafted to a short chain polymer (polyethylenimine). Compared with parental Rituximab and 11B8, the ACNC had a reduced “off-rate”. Importantly, ACNC efficiently inhibited Rituximab-resistant lymphomas in both disseminated and localized human NHL xenograft models. Further results revealed that ACNC is significantly potent in inducing caspase-dependent apoptosis and lysosome-mediated programmed cell death (PCD). This may help explain why ACNC is effective in suppressing rituximab-resistant lymphoma while Rituximab and 11B8 are not. Additionally, ACNC experienced low clearance from peripheral blood and high intratumor accumulation. This improved pharmacokinetics is attributed to the antibody-antigen reaction (active targeting) and enhanced permeability and retention (ERP) effect (passive targeting). This study suggested that ACNC might be a promising therapeutic agent for treatment of rituximab-resistant lymphomas. PMID:26284588

  8. New potential therapeutic approach for the treatment of B-Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.

    PubMed

    Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafò, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marín, Gustavo H; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Núñez, Luis; Macor, Paolo

    2013-01-01

    Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.

  9. New Potential Therapeutic Approach for the Treatment of B-Cell Malignancies Using Chlorambucil/Hydroxychloroquine-Loaded Anti-CD20 Nanoparticles

    PubMed Central

    Mezzaroba, Nelly; Zorzet, Sonia; Secco, Erika; Biffi, Stefania; Tripodo, Claudio; Calvaruso, Marco; Mendoza-Maldonado, Ramiro; Capolla, Sara; Granzotto, Marilena; Spretz, Ruben; Larsen, Gustavo; Noriega, Sandra; Lucafò, Marianna; Mansilla, Eduardo; Garrovo, Chiara; Marín, Gustavo H.; Baj, Gabriele; Gattei, Valter; Pozzato, Gabriele; Núñez, Luis; Macor, Paolo

    2013-01-01

    Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders. PMID:24098639

  10. Novel humanized anti-CD20 antibody BM-ca binds to a unique epitope and exerts stronger cellular activity than others.

    PubMed

    Kobayashi, Hideaki; Matsunaga, Yuka; Uchiyama, Yumiko; Nagura, Kenji; Komatsu, Yasuhiko

    2013-04-01

    Cellular activity of BM-ca, a novel humanized anti-CD20 antibody, was quantitatively compared with that of two other anti-CD20 antibodies used for clinical practice, rituximab and ofatumumab. The results of a complement-dependent cytotoxicity (CDC) assay revealed that the strongest antibody was ofatumumab, followed by BM-ca, with rituximab being the weakest. Ofatumumab and BM-ca were effective not only against rituximab-sensitive SU-DHL-4 cells but also against rituximab-resistant RC-K8 cells. In an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, although the effective concentrations against SU-DHL-4 cells were almost the same among these three antibodies, the maximum cytotoxic level was the highest for BM-ca. In an anti-cell proliferation assay using SU-DHL-4 cells, BM-ca was the most effective and ofatumumab, the weakest. Against RC-K8 cells, only BM-ca was effective. When combined with each of four cancer chemotherapeutics (prednisolone, vincristine, hydroxydaunorubicin, and cisplatin), BM-ca exerted the most effective combinatorial anti-cell proliferation activity. To assess the in vivo effect of BM-ca, we intravenously administered BM-ca into cynomolgus monkeys and found that the peripheral B-cell levels did not decrease in half of the animals. Sequencing of cDNA encoding CD20 of cynomolgus monkeys revealed that the responders and nonresponders had Leu/Pro (hetero) and Leu/Leu (homo) at amino acid (a.a.) position 160, respectively, suggesting that the epitope recognized by BM-ca was around this a.a. By analyzing reactivity to synthetic peptides, the epitope recognized by BM-ca was estimated to be a.a.'s 156-166, not shared with rituximab and ofatumumab. These results suggest BM-ca to be a promising anti-CD20 antibody having superior properties and recognizing a unique epitope.

  11. Novel humanized anti-CD20 antibody BM-ca binds to a unique epitope and exerts stronger cellular activity than others

    PubMed Central

    Kobayashi, Hideaki; Matsunaga, Yuka; Uchiyama, Yumiko; Nagura, Kenji; Komatsu, Yasuhiko

    2013-01-01

    Cellular activity of BM-ca, a novel humanized anti-CD20 antibody, was quantitatively compared with that of two other anti-CD20 antibodies used for clinical practice, rituximab and ofatumumab. The results of a complement-dependent cytotoxicity (CDC) assay revealed that the strongest antibody was ofatumumab, followed by BM-ca, with rituximab being the weakest. Ofatumumab and BM-ca were effective not only against rituximab-sensitive SU-DHL-4 cells but also against rituximab-resistant RC-K8 cells. In an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, although the effective concentrations against SU-DHL-4 cells were almost the same among these three antibodies, the maximum cytotoxic level was the highest for BM-ca. In an anti-cell proliferation assay using SU-DHL-4 cells, BM-ca was the most effective and ofatumumab, the weakest. Against RC-K8 cells, only BM-ca was effective. When combined with each of four cancer chemotherapeutics (prednisolone, vincristine, hydroxydaunorubicin, and cisplatin), BM-ca exerted the most effective combinatorial anti-cell proliferation activity. To assess the in vivo effect of BM-ca, we intravenously administered BM-ca into cynomolgus monkeys and found that the peripheral B-cell levels did not decrease in half of the animals. Sequencing of cDNA encoding CD20 of cynomolgus monkeys revealed that the responders and nonresponders had Leu/Pro (hetero) and Leu/Leu (homo) at amino acid (a.a.) position 160, respectively, suggesting that the epitope recognized by BM-ca was around this a.a. By analyzing reactivity to synthetic peptides, the epitope recognized by BM-ca was estimated to be a.a.'s 156–166, not shared with rituximab and ofatumumab. These results suggest BM-ca to be a promising anti-CD20 antibody having superior properties and recognizing a unique epitope. PMID:23634281

  12. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

    PubMed Central

    Shadman, Mazyar; Jones, Jon C.; Frayo, Shani L.; Kenoyer, Aimee L.; Hylarides, Mark D.; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sofia H. L.; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Theodore A.; Laird, Kelly L.; Till, Brian G.; Bäck, Tom; Sandmaier, Brenda M.; Pagel, John M.; Press, Oliver W.

    2015-01-01

    α-Emitting radionuclides deposit a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD). To evaluate this hypothesis, 211At-labeled 1F5 monoclonal antibody (mAb) (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At-labeled 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor-bearing animals treated with doses of up to 48 µCi of 211At-labeled anti-CD20 mAb ([211At]1F5-B10) experienced modest responses (0% cures but two- to threefold prolongation of survival compared with negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity was observed in the cured animals receiving 15 µCi of [211At]1F5-B10. These findings suggest that α-emitters are highly efficacious in MRD settings, where isolated cells and small tumor clusters prevail. PMID:25628467

  13. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model.

    PubMed

    Green, Damian J; Shadman, Mazyar; Jones, Jon C; Frayo, Shani L; Kenoyer, Aimee L; Hylarides, Mark D; Hamlin, Donald K; Wilbur, D Scott; Balkan, Ethan R; Lin, Yukang; Miller, Brian W; Frost, Sofia H L; Gopal, Ajay K; Orozco, Johnnie J; Gooley, Theodore A; Laird, Kelly L; Till, Brian G; Bäck, Tom; Sandmaier, Brenda M; Pagel, John M; Press, Oliver W

    2015-03-26

    α-Emitting radionuclides deposit a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD). To evaluate this hypothesis, (211)At-labeled 1F5 monoclonal antibody (mAb) (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to (211)At-labeled 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor-bearing animals treated with doses of up to 48 µCi of (211)At-labeled anti-CD20 mAb ([(211)At]1F5-B10) experienced modest responses (0% cures but two- to threefold prolongation of survival compared with negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with (211)At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity was observed in the cured animals receiving 15 µCi of [(211)At]1F5-B10. These findings suggest that α-emitters are highly efficacious in MRD settings, where isolated cells and small tumor clusters prevail.

  14. Specific Conjugation of the Hinge Region for Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-PEG-anti-CD20 Fab' Synthesis.

    PubMed

    Zhou, Zhan; Zhang, Jing; Zhang, Yan; Ma, Guanghui; Su, Zhiguo

    2016-01-20

    Conventional preparation strategies for antibody-drug conjugates (ADCs) result in heterogeneous products with various molecular sizes and species. In this study, we developed a homogeneous preparation strategy by site-specific conjugation of the anticancer drug with an antibody fragment. The model drug doxorubicin (DOX) was coupled to the Fab' fragment of anti-CD20 IgG at its permissive sites through a heterotelechelic PEG linker, generating an antibody fragment-drug conjugate (AFDC). Anti-CD20 IgG was digested and reduced specifically with β-mercaptoethylamine to generate the Fab' fragment with two free mercapto groups in its hinge region. Meanwhile, DOX was conjugated with α-succinimidylsuccinate ω-maleimide polyethylene glycol (NHS-PEG-MAL) to form MAL-PEG-DOX, which was subsequently linked to the free mercapto containing Fab' fragment to form a Fab'-PEG-DOX conjugate. The dual site-specific bioconjugation was achieved through the combination of highly selective reduction of IgG and introduction of heterotelechelic PEG linker. The resulting AFDC provides an utterly homogeneous product, with a definite ratio of one fragment to two drugs. Laser confocal microscopy and cell ELISA revealed that the AFDC could accumulate in the antigen-positive Daudi tumor cell. In addition, the Fab'-PEG-DOX retained appreciable targeting ability and improved antitumor activity, demonstrating an excellent therapeutic effect on the lymphoma mice model for better cure rate and significantly reduced side effects.

  15. Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model

    SciTech Connect

    Green, Damian J.; Shadman, Mazyar; Jones, Jon C.; Frayo, Shani; Kenoyer, Aimee L.; Hylarides, Mark; Hamlin, Donald K.; Wilbur, D. Scott; Balkan, Ethan R.; Lin, Yukang; Miller, Brian W.; Frost, Sophia; Gopal, Ajay K.; Orozco, Johnnie J.; Gooley, Ted; Laird, Kelley L.; Till, B. G.; Back, Tom; Sandmaier, B. M.; Pagel, John M.; Press, Oliver W.

    2015-03-26

    Alpha emitting radionuclides release a large amount of energy within a few cell diameters and may be particularly effective for radioimmunotherapy targeting minimal residual disease (MRD) conditions in which micrometastatic disease satellites are broadly distributed. To evaluate this hypothesis, 211At conjugated 1F5 mAb (anti-CD20) was studied in both bulky lymphoma tumor xenograft and MRD animal models. Superior treatment responses to 211At conjugated 1F5 mAb were evident in the MRD setting. Lymphoma xenograft tumor bearing animals treated with doses of up to 48µCi of anti-CD20 211At-decaborate [211At-B10-1F5] experienced modest responses (0% cures but 2-3-fold prolongation of survival compared to negative controls). In contrast, 70% of animals in the MRD lymphoma model demonstrated complete eradication of disease when treated with 211At-B10-1F5 at a radiation dose that was less than one-third (15 µCi) of the highest dose given to xenograft animals. Tumor progression among untreated control animals in both models was uniformly lethal. After 130 days, no significant renal or hepatic toxicity is observed in the cured animals receiving 15 µCi of 211At-B10-1F5. These findings suggest that in a MRD lymphoma model, where isolated cells and tumor microclusters prevail, α-emitters may be uniquely efficacious.

  16. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients.

    PubMed

    Salles, Gilles; Morschhauser, Franck; Lamy, Thierry; Milpied, Noel; Thieblemont, Catherine; Tilly, Hervé; Bieska, Gabi; Asikanius, Elina; Carlile, David; Birkett, Joe; Pisa, Pavel; Cartron, Guillaume

    2012-05-31

    Whereas the chimeric type I anti-CD20 Ab rituximab has improved outcomes for patients with B-cell malignancies significantly, many patients with non-Hodgkin lymphoma (NHL) remain incurable. Obinutuzumab (GA101) is a glycoengineered, humanized anti-CD20 type II Ab that has demonstrated superior activity against type I Abs in vitro and in preclinical studies. In the present study, we evaluated the safety, efficacy, and pharmacokinetics of GA101 in a phase 1 study of 21 patients with heavily pretreated, relapsed, or refractory CD20(+) indolent NHL. Patients received GA101 in a dose-escalating fashion (3 per cohort, range 50/100-1200/2000 mg) for 8 × 21-day cycles. The majority of adverse events (AEs) were grades 1 and 2 (114 of 132 total AEs). Seven patients reported a total of 18 grade 3 or 4 AEs. Infusion-related reactions were the most common AE, with most occurring during the first infusion and resolving with appropriate management. Three patients experienced grade 3 or 4 drug-related infusion-related reactions. The best overall response was 43%, with 5 complete responses and 4 partial responses. Data from this study suggest that GA101 was well tolerated and demonstrated encouraging activity in patients with previously treated NHL up to doses of 2000 mg. This trial is registered at www.clinicaltrials.gov as NCT00517530.

  17. A Review of Obinutuzumab (GA101), a Novel Type II Anti-CD20 Monoclonal Antibody, for the Treatment of Patients with B-Cell Malignancies.

    PubMed

    Tobinai, Kensei; Klein, Christian; Oya, Naoko; Fingerle-Rowson, Günter

    2017-02-01

    Obinutuzumab (GA101) is a novel, type II, glycoengineered, humanized anti-CD20 monoclonal antibody that has been developed to address the need for new therapeutics with improved efficacy in patients with lymphocytic leukemia and lymphoma of B-cell origin. Obinutuzumab has a distinct mode of action relative to type I anti-CD20 antibodies, such as rituximab, working primarily by inducing direct cell death and antibody-dependent cell-mediated cytotoxicity. Obinutuzumab is under investigation in a wide-ranging program of clinical trials in patients with B-cell malignancies. Efficacy as monotherapy has been reported in patients with relapsed/refractory indolent and aggressive non-Hodgkin lymphoma (NHL) and in chronic lymphocytic leukemia (CLL) of B-cell origin. Improved outcomes have also been noted when obinutuzumab is added to chemotherapy in patients with B-cell NHL, and superiority over rituximab has been reported with combination therapy in patients with CLL. Ongoing research is focusing on developing options for chemotherapy-free treatment and on new combinations of obinutuzumab with novel targeted agents.

  18. Peripheral blood T4 cell surface CCR5 density as a marker of activity in rheumatoid arthritis treated with anti-CD20 monoclonal antibody

    PubMed Central

    Portalès, Pierre; Fabre, Sylvie; Vincent, Thierry; Desmetz, Caroline; Réant, Brigitte; Noël, Danièle; Clot, Jacques; Jorgensen, Christian; Corbeau, Pierre

    2009-01-01

    The chemokine (C-C motif) receptor CCR5 and its ligand CCL5 play key roles in the intra-articular recruitment of peripheral blood mononuclear cells (PBMC) in rheumatoid arthritis (RA). Therefore, using quantitative cytofluorometry, we followed T4 cell surface CCR5 density in 27 subjects with RA before and after treatment with the anti-CD20 monoclonal antibody rituximab. We observed low T4 cell surface CCR5 densities before treatment, which correlated positively with disease activity, as determined using a disease activity score evaluated on 28 joints (DAS 28), and negatively with CCL5 mRNA concentrations in PBMC, contrasting with a high proportion of intracellular CCR5 molecules, a pattern compatible with ligand-induced CCR5 internalization. At 3 months post-treatment, CCL5 mRNA expression in PBMC declined, whereas T4 cell surface CCR5 densities increased proportionally to the decrease in DAS 28. Thus, peripheral blood T4 cell surface CCR5 density is a good surrogate marker of RA activity and of the efficiency of anti-CD20 therapy. PMID:19740335

  19. Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response.

    PubMed

    Singh, Vijay; Gupta, Damodar; Almasan, Alexandru

    2015-11-01

    Rituximab has been revolutionized and validated CD20 targeting monoclonal antibody. Although, it is widely used for lymphoma therapy and many patients have been benefited. However significant numbers of patients are refractory or developed resistance to current therapies due to low level of CD20 expression and/or availability on cells surface. Thus development of novel anti-CD20 mAbs with great cell killing ability and enhance CD20 levels on cell surface can potentially exploit lymphoma therapy. In this scenario, we are summarizing the recently developed mAbs against CD20 and compounds that have ability to induce CD20 expression at significant level. We also are providing information regarding combination strategy for use of radiation and anti-CD20 mAbs in vitro. However, it will need to be determined by rigorous at pre-clinical and clinic testing. We hope this review will be beneficial for current research in the area of immunotherapy or radio-immunotherapy.

  20. Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations

    PubMed Central

    Carpenet, Hélène; Cuvillier, Armelle; Monteil, Jacques; Quelven, Isabelle

    2015-01-01

    In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig) appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc), an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate—polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig’s immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT). Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%). 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C) and in serum (37°C), even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is “antibody safe” and

  1. Hexavalent bispecific antibodies represent a new class of anticancer therapeutics: 1. Properties of anti-CD20/CD22 antibodies in lymphoma

    PubMed Central

    Cardillo, Thomas M.; Stein, Rhona; Chang, Chien-Hsing

    2009-01-01

    The dock and lock (DNL) method is a new technology for generating multivalent antibodies. Here, we report in vitro and in vivo characterizations of 20-22 and 22-20, a pair of humanized hexavalent anti-CD20/22 bispecific antibodies (bsAbs) derived from veltuzumab (v-mab) and epratuzumab (e-mab). The 22-20 was made by site-specific conjugation of e-mab to 4 Fabs of v-mab; 20-22 is of the opposite configuration, composing v-mab and 4 Fabs of e-mab. Each bsAb translocates both CD22 and CD20 into lipid rafts, induces apoptosis and growth inhibition without second-antibody crosslinking, and is significantly more potent in killing lymphoma cells in vitro than their parental antibodies. Although both bsAbs triggered antibody-dependent cellular toxicity, neither displayed complement-dependent cytotoxicity. Intriguingly, 22-20 and 20-22 killed human lymphoma cells in preference to normal B cells ex vivo, whereas the parental v-mab depleted malignant and normal B cells equally. In vivo studies in Daudi tumors revealed 20-22, despite having a shorter serum half-life, had antitumor efficacy comparable with equimolar v-mab; 22-20 was less potent than 20-22 but more effective than e-mab and control bsAbs. These results indicate multiple advantages of hexavalent anti-CD20/22 bsAbs over the individual parental antibodies and suggest that these may represent a new class of cancer therapeutics. PMID:19372261

  2. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin's lymphoma.

    PubMed

    Negrea, George O; Elstrom, Rebecca; Allen, Steven L; Rai, Kanti R; Abbasi, Rashid M; Farber, Charles M; Teoh, Nick; Horne, Heather; Wegener, William A; Goldenberg, David M

    2011-04-01

    Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2(nd) generation anti-CD20 antibody veltuzumab in patients with CD20(+) indolent non-Hodgkin's lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin's lymphoma. (Clinicaltrials.gov identifier: NCT00546793).

  3. Subcutaneous injections of low-dose veltuzumab (humanized anti-CD20 antibody) are safe and active in patients with indolent non-Hodgkin’s lymphoma

    PubMed Central

    Negrea, George O.; Elstrom, Rebecca; Allen, Steven L.; Rai, Kanti R.; Abbasi, Rashid M.; Farber, Charles M.; Teoh, Nick; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2011-01-01

    Background Subcutaneous injections of anti-CD20 antibodies may offer benefits to both patients and the healthcare system for treatment of B-cell malignancies. Design and Methods A pilot study was undertaken to evaluate the potential for subcutaneous dosing with 2nd generation anti-CD20 antibody veltuzumab in patients with CD20+ indolent non-Hodgkin’s lymphoma. Patients with previously untreated or relapsed disease received 4 doses of 80, 160, or 320 mg veltuzumab injected subcutaneously every two weeks. Responses were assessed by computed tomography scans, with other evaluations including adverse events, safety laboratories, B-cell blood levels, serum veltuzumab levels, and human anti-veltuzumab antibody (HAHA) titers. Results Seventeen patients (14 follicular lymphoma; 13 stage III or IV disease; 5 treatment-naive) completed treatment with only occasional, mild-moderate, transient injection reactions and no other safety issues. Subcutaneous veltuzumab demonstrated a slow release pattern over several days, achieving a mean Cmax of 19, 25 and 63 μg/mL at 80, 160, and 320 mg doses for a total of 4 administrations, respectively. Depletion of circulating B cells occurred after the first injection. The objective response rate (partial responses plus complete responses plus complete responses unconfirmed) was 47% (8/17) with a complete response/complete response unconfirmed rate of 24% (4/17); 4 of 8 objective responses continued for 60 weeks or more. All serum samples evaluated for human anti-veltuzumab antibody were negative. Conclusions Subcutaneous injections of low-dose veltuzumab are convenient, well tolerated, and capable of achieving sustained serum levels, B-cell depletion, and durable objective responses in indolent non-Hodgkin’s lymphoma. (Clinicaltrials.gov identifier: NCT00546793) PMID:21173095

  4. The challenge of treating hepatitis C virus-associated cryoglobulinemic vasculitis in the era of anti-CD20 monoclonal antibodies and direct antiviral agents

    PubMed Central

    Rossi, Daniela; Solfietti, Laura; Fenoglio, Roberta; Menegatti, Elisa; Baldovino, Simone

    2017-01-01

    Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered. Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens. The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs. PMID:28454112

  5. B-cell depletion using an anti-CD20 antibody augments antitumor immune responses and immunotherapy in nonhematopoetic murine tumor models.

    PubMed

    Kim, Samuel; Fridlender, Zvi G; Dunn, Robert; Kehry, Marilyn R; Kapoor, Veena; Blouin, Aaron; Kaiser, Larry R; Albelda, Steven M

    2008-06-01

    The role played by B cells in cancer biology is complex and somewhat controversial. Previous studies using genetically engineered mice suggest that B cells may be immunosuppressive and inhibit tumor rejection. However, the effects of B-cell depletion employing an antibody in mice bearing solid tumors has not been tested owing to difficulties in making an effective antimouse CD20 antibody (similar to rituximab). Injection of a newly developed antimouse CD20 antibody was effective in depleting circulating B cells from blood and lymph nodes, although depletion was less complete in the spleen. B-cell depletion slowed the growth of new solid tumors (not expressing CD20) and retarded the growth of established tumors but did not induce tumor regression. However, when the antibody was combined with an active immunotherapy approach using an adenovirus vaccine expressing the human papilloma virus-E7 gene (Ad.E7) in mice bearing TC1 tumors (murine lung cancer cells expressing human papilloma virus-E7), we noted enhanced antitumor effects and increased numbers of tetramer+/CD8+ T cells within the spleens and activated CD8+ T cells within tumors. B-cell depletion using an anti-CD20 antibody was thus effective in retarding tumor growth in multiple solid tumor models and augmenting immunotherapy in a tumor vaccine model. These studies raise the possibility that B-cell depletion may be a useful adjunct in human immunotherapy trials.

  6. Combination anti-CD74 (milatuzumab) and anti-CD20 (rituximab) monoclonal antibody therapy has in vitro and in vivo activity in mantle cell lymphoma.

    PubMed

    Alinari, Lapo; Yu, Bo; Christian, Beth A; Yan, Fengting; Shin, Jungook; Lapalombella, Rosa; Hertlein, Erin; Lustberg, Mark E; Quinion, Carl; Zhang, Xiaoli; Lozanski, Gerard; Muthusamy, Natarajan; Prætorius-Ibba, Mette; O'Connor, Owen A; Goldenberg, David M; Byrd, John C; Blum, Kristie A; Baiocchi, Robert A

    2011-04-28

    Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a median survival of 3 years despite chemoimmunotherapy. Rituximab, a chimeric anti-CD20 monoclonal antibody (mAb), has shown only modest activity as single agent in MCL. The humanized mAb milatuzumab targets CD74, an integral membrane protein linked with promotion of B-cell growth and survival, and has shown preclinical activity against B-cell malignancies. Because rituximab and milatuzumab target distinct antigens and potentially signal through different pathways, we explored a preclinical combination strategy in MCL. Treatment of MCL cell lines and primary tumor cells with immobilized milatuzumab and rituximab resulted in rapid cell death, radical oxygen species generation, and loss of mitochondrial membrane potential. Cytoskeletal distrupting agents significantly reduced formation of CD20/CD74 aggregates, cell adhesion, and cell death, highlighting the importance of actin microfilaments in rituximab/milatuzumab-mediated cell death. Cell death was independent of caspase activation, Bcl-2 family proteins or modulation of autophagy. Maximal inhibition of p65 nuclear translocation was observed with combination treatment, indicating disruption of the NF-κB pathway. Significant in vivo therapeutic activity of combination rituximab and milatuzumab was demonstrated in a preclinical model of MCL. These data support clinical evaluation of combination milatuzumab and rituximab therapy in MCL.

  7. Subcutaneous immunoglobulins for the treatment of a patient with antisynthetase syndrome and secondary chronic immunodeficiency after anti-CD20 treatment: a case report.

    PubMed

    Cherin, Patrick; de Jaeger, Christophe; Crave, Jean-Charles; Delain, Jean-Christophe; Tadmouri, Abir; Amoura, Zahir

    2017-03-04

    Antisynthetase syndrome is a rare and debilitating multiorgan disease characterized by inflammatory myopathy, interstitial lung disease, cutaneous involvement, and frequent chronic inflammation of the joints. Standard treatments include corticosteroids and immunosuppressants. In some cases, treatment resistance may develop. Administration of immunoglobulins intravenously is recommended in patients with drug-resistant antisynthetase syndrome. Here, we describe the case of a 56-year-old woman of Algerian origin. She is the first case of a patient with multidrug-resistant antisynthetase syndrome featuring pulmonary involvement and arthropathy, and chronic secondary immune deficiency with recurrent infections, after anti-CD20 treatment, in which her primary antisynthetase syndrome-related symptoms and secondary immune deficiency were treated successfully with subcutaneous administration of immunoglobulin. The administration of immunoglobulin subcutaneously was introduced at a dose of 2 g/kg per month and was well tolerated. Clinical improvement was observed within 3 months of initiation of subcutaneous administration of immunoglobulin. After 22 months of treatment, she showed a significant improvement in terms of muscle strength, pulmonary involvement, arthralgia, and immunodeficiency. Her serum creatine phosphokinase and C-reactive protein levels remained normal. Finally, she was compliant and entirely satisfied with the treatment. Taken together, these observations suggest that administration of immunoglobulin subcutaneously may be a useful therapeutic approach to tackle steroid-refractory antisynthetase syndrome while ensuring minimal side effects and improved treatment compliance. This treatment also allowed, in our case, for the regression of the chronic immunodeficiency secondary to rituximab treatment.

  8. Target antigen density governs the efficacy of anti-CD20-CD28-CD3 ζ chimeric antigen receptor-modified effector CD8+ T cells.

    PubMed

    Watanabe, Keisuke; Terakura, Seitaro; Martens, Anton C; van Meerten, Tom; Uchiyama, Susumu; Imai, Misa; Sakemura, Reona; Goto, Tatsunori; Hanajiri, Ryo; Imahashi, Nobuhiko; Shimada, Kazuyuki; Tomita, Akihiro; Kiyoi, Hitoshi; Nishida, Tetsuya; Naoe, Tomoki; Murata, Makoto

    2015-02-01

    The effectiveness of chimeric Ag receptor (CAR)-transduced T (CAR-T) cells has been attributed to supraphysiological signaling through CARs. Second- and later-generation CARs simultaneously transmit costimulatory signals with CD3ζ signals upon ligation, but may lead to severe adverse effects owing to the recognition of minimal Ag expression outside the target tumor. Currently, the threshold target Ag density for CAR-T cell lysis and further activation, including cytokine production, has not yet been investigated in detail. Therefore, we determined the threshold target Ag density required to induce CAR-T cell responses using novel anti-CD20 CAR-T cells with a CD28 intracellular domain and a CD20-transduced CEM cell model. The newly developed CD20CAR-T cells demonstrated Ag-specific lysis and cytokine secretion, which was a reasonable level as a second-generation CAR. For lytic activity, the threshold Ag density was determined to be ∼200 molecules per target cell, whereas the Ag density required for cytokine production of CAR-T cells was ∼10-fold higher, at a few thousand per target cell. CD20CAR-T cells responded efficiently to CD20-downregulated lymphoma and leukemia targets, including rituximab- or ofatumumab-refractory primary chronic lymphocytic leukemia cells. Despite the potential influence of the structure, localization, and binding affinity of the CAR/Ag, the threshold determined may be used for target Ag selection. An Ag density below the threshold may not result in adverse effects, whereas that above the threshold may be sufficient for practical effectiveness. CD20CAR-T cells also demonstrated significant lytic activity against CD20-downregulated tumor cells and may exhibit effectiveness for CD20-positive lymphoid malignancies. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue

    SciTech Connect

    Liu, S Y.; Eary, Janet F.; Petersdorf, S H.; Martin, P J.; Maloney, D G.; Applebaum, F. R.; Matthews, D. C.; Bush, S A.; Durack, L. D.; Fisher, Darrell R. ); Gooley, T A.; Bernstein, I. D.; Press, O. W.

    1997-11-01

    Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS: Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty- nine patients received therapeutic infusions of single-agent (131)I- anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi[10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic do se-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti- B1 RIT is relatively well tolerated when given with autologous stem- cell support and often results in prolonged remission durations with few late toxicities.

  10. Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia

    PubMed Central

    Liebman, Howard A.; Saleh, Mansoor N.; Bussel, James B.; Negrea, O. George; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2016-01-01

    We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066 PMID:27515248

  11. Living donor kidney transplantation in patients with donor-specific HLA antibodies enabled by anti-CD20 therapy and peritransplant apheresis.

    PubMed

    Klein, Katrin; Süsal, Caner; Schäfer, Sebastian M; Becker, Luis Eduardo; Beimler, Jörg; Schwenger, Vedat; Zeier, Martin; Schemmer, Peter; Macher-Goeppinger, Stephan; Scherer, Sabine; Opelz, Gerhard; Morath, Christian

    2013-01-01

    Due to increasing waiting times for deceased donor kidneys, living donor kidney transplantation is increasingly performed in the presence of donor-specific antibodies (DSA). Twenty-three patients with Luminex-detected DSA were successfully desensitized by anti-CD20 therapy and immunoadsorption (N = 19) or plasmapheresis (N = 4) and received a kidney transplant from a living donor. Twelve of the 23 patients (52%) had a positive CDC and/or ELISA crossmatch result before desensitization. Six patients were negative in CDC as well as ELISA screening but positive in Luminex for DSA. The 23 patients received a median of 8 apheresis treatments before and 5 treatments after transplantation. Induction therapy was performed with either thymoglobulin (N = 11) or basiliximab (N = 12). The 2-year graft survival rate was 100%. At last follow up, a median of 12 months after transplantation, median serum creatinine was 1.42 mg/dL, median MDRD-GFR 59.5 mL/min/1.73 m(2), and median urinary protein-to-creatinine ratio 0.12. Ten out of fourteen patients (71%) who had completed the first year after transplantation by the time of analysis had no DSA by day 360. Acute T-cell mediated rejection was diagnosed in one patient (4%), and antibody-mediated changes were found in 5 patients (22%). Four out of these 5 patients showed evidence of persistent (N = 2) or reemerging plus/minus de novo DSA (N = 2) on day 360, and the 2 patients with persistent DSA lost their allograft subsequently on days 750 and 810, respectively. Infectious complications were infrequent. Our previously described treatment algorithm for desensitization of living donor kidney transplant recipients with DSA results in good graft outcomes with a low rate of side effects. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas

    SciTech Connect

    Press, O. W.; Eary, Janet F.; Gooley, T; Gopal, A K.; Liu, Stephen; Rajendran, Joseph G.; Maloney, David G.; Petersdorf, Stephen; Bush, Sharon A.; Durack, L. D.; Martin, P J.; Fisher, Darrell R. ); Wood, Brent; Borrow, James W.; Porter, Bruce; Smith, Justin P.; Matthews, D. C.; Appelbaum, F. R.; Bernstein, I. D.

    1999-11-01

    Relapsed B-cell lymphomas are incurable with conventional chemotherapy and radiation therapy, although a fraction of patients can be cured with high-dose chemoradiotherapy and autologous stem-cell transplantation (ASCT). We conducted a phase I/II trial to estimate the maximum tolerated dose (MTD) of iodine 131 (I-131)-tositumomab (anti-CD20 antibody) that could be combined with etoposide and cyclophosphamide followed by ASCT in patients with relapsed B-cell lymphomas. Fifty-two patients received a trace-labeled infusion of 1.7 mg/kg I-131-tositumomab (185-370 MBq) followed by serial quantitative gamma-camera imaging and estimation of absorbed doses of radiation to tumor sites and normal organs. Ten days later, patients received a therapeutic infusion of 1.7 mg/kg tositumomab labeled with an amount of I-131 calculated to deliver the target dose of radiation (20-27 Gy) to critical normal organs (liver, kidneys, and lungs). Patients were maintained in radiation isolation until their total -body radioactivity was less than 0.07 mSv/h at 1 m. They were then given etoposide and cyclophosphamide followed by ASCT. The MTD of I-131-tositumomab that could be safely combined with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide delivered 25 Gy to critical normal organs. The estimated overall survival (OS) and progression-free survival (PFS) of all treated patients at 2 years was 83% and 68%, respectively. These findings compare favorably with those in a nonrandomized control group of patients who underwent transplantation, external-beam total-body irradiation, and etoposide and cyclophosphamide therapy during the same period (OS of 53% and PFS of 36% at 2 years), even after adjustment for confounding variables in a multivariable analysis.

  13. Intraläsionale Therapie niedrig maligner primär kutaner B-Zell-Lymphome mit Anti-CD20-Antikörper: Nebenwirkungen korrelieren mit gutem klinischen Ansprechen.

    PubMed

    Eberle, Franziska C; Holstein, Julia; Scheu, Alexander; Fend, Falko; Yazdi, Amir S

    2017-03-01

    Die intraläsionale Gabe von Anti-CD20-Antikörpern (Rituximab) wurde als effektive Therapieoption für Patienten mit niedrig malignen primär kutanen B-Zell-Lymphomen beschrieben. Bis heute wurden allerdings keine Parameter identifiziert, welche reproduzierbar ein gutes klinisches Ansprechen dieser Therapie vorhersagen. Ziel dieser Studie ist, sowohl das klinische Ansprechen und die unerwünschten Nebenwirkungen als auch die Patientenwahrnehmung hinsichtlich intraläsionaler Injektionen von anti-CD20-Antikörpern zur Behandlung indolenter primär kutaner B-Zell-Lymphome im Vergleich mit anderen Therapien zu evaluieren. Elf Patienten mit einem primär kutanen B-Zell-Lymphom, namentlich primär kutanes Keimzentrumslymphom (n = 9) und primär kutanes Marginalzonenlymphom (n = 2), welche mittels intraläsionalem Anti-CD20-Antikörper behandelt wurden, wurden retrospektiv evaluiert hinsichtlich der Ansprechrate und unerwünschter Nebenwirkungen sowie in Bezug auf deren Selbsteinschätzung dieser und anderer Therapien des primär kutanen B-Zell-Lymphoms. Patienten, deren primär kutanes B-Zell-Lymphom mittels intraläsionaler Gabe von Anti-CD20-Antikörper behandelt wurde, zeigten ein komplettes oder partielles Ansprechen in 45 % beziehungsweise 27 % aller Patienten. Speziell Patienten mit grippeähnlichen Symptomen nach erfolgter Injektion zeigten ein gutes Ansprechen. Die Mehrheit der Patienten empfand die Therapie mit Rituximab als die beste Therapie im Vergleich zu anderen Therapien wie beispielsweise chirurgische Exzision oder Radiotherapie. Intraläsionales Rituximab ist eine effektive Therapie mit hoher Patientenzufriedenheit. Starke therapiebedingte Nebenwirkungen wie Fieber, Schüttelfrost und Kopfschmerzen nach Gabe von Rituximab könnten als Indikator für gute Wirksamkeit dienen. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  14. Construction of Anti-CD20 Single-Chain Antibody-CD28-CD137-TCRζ Recombinant Genetic Modified T Cells and its Treatment Effect on B Cell Lymphoma

    PubMed Central

    Chen, Fei; Fan, Chuming; Gu, Xuezhong; Zhang, Haixi; Liu, Qian; Gao, Xiaoli; Lu, Jie; He, Baoli; Lai, Xun

    2015-01-01

    Background Immunotherapy has been explored as a new therapy for B cell lymphoma, which is a non-Hodgkin’s lymphoma. Because CD20 is a B lymphocyte-specific marker, anti-CD20 single chain-tagged T lymphocytes have already begun to be experimentally used in B cell lymphoma treatment, but its use is still limited because of its unspecific targeting. T cells transfected with CD28 and CD137 can significantly improve the ability of cytokines secretion and anti-tumor effect, as well as extending T cell survival time and improving their proliferation ability. Material/Methods Genes containing anti-CD20-CD28-CD137-TCRζ were constructed. After cloning and sequencing, the plasmid was constructed and packaged by lentivirus. It was transfected to the peripheral blood T lymphocyte after identification transfection to induce the fusion protein expression. The cells were incubated with Raji cells and the LDH test was performed to detect the cytotoxic effect of CAR-T cells; the tumor volume and survival rate were measured to observe its inhibitory effect on B cell lymphoma in nude mice. Results Gene with anti-CD20-CD28-CD137-TCRζ was successfully constructed and transfected to the T cell surface. LDH assay revealed that CAR-T cells can kill the Raji cells with a killing rate of 32.89±6.26%. It can significantly inhibit B cell lymphoma growth in nude mice. Conclusions T lymphocytes transfected with anti-CD20-CD28-CD137-TCRζ fusion gene can kill B cell lymphoma, which could provide a new strategy for tumor treatment. PMID:26195067

  15. Comparative efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    SciTech Connect

    Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark D.; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Bäck, Tom A.; Fisher, Darrell R.; Press, Oliver W.; Afrin, Farhat

    2015-03-18

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0

  16. Regeneration of the immunoglobulin heavy-chain repertoire after transient B-cell depletion with an anti-CD20 antibody

    PubMed Central

    Rouzière, Anne-Sophie; Kneitz, Christian; Palanichamy, Arumugam; Dörner, Thomas; Tony, Hans-Peter

    2005-01-01

    B-cell depletive therapies have beneficial effects in patients suffering from rheumatoid arthritis. Nevertheless, the role of B cells in the pathogenesis of the disease is not clear. In particular, it is not known how the regeneration of the B-cell repertoire takes place. Two patients with active rheumatoid arthritis were treated with rituximab, and the rearranged immunoglobulin heavy-chain genes (Ig-VH) were analysed to follow the B-cell regeneration. Patient A was treated with two courses of rituximab, and B-cell regeneration was followed over 27 months by analysing more than 680 Ig-VH sequences. Peripheral B-cell depletion lasted 7 months and 10 months, respectively, and each time was accompanied by a clinical improvement. Patient B received one treatment course. B-cell depletion lasted 5 months and was accompanied by a good clinical response. B cells regenerated well in both patients, and the repopulated B-cell repertoire was characterised by a polyclonal and diverse use of Ig-VH genes, as expected in adult individuals. During the early phase of B-cell regeneration we observed the expansion and recirculation of a highly mutated B-cell population. These cells expressed very different Ig-VH genes. They were class-switched and could be detected for a short period only. Patient A was followed long term, whereby some characteristic changes in the VH2 family as well as in specific mini-genes like VH3–23, VH 4–34 or VH 1–69 were observed. In addition, rituximab therapy resulted in the loss of clonal B cells for the whole period. Our data show that therapeutic transient B-cell depletion by anti-CD20 antibodies results in the regeneration of a diverse and polyclonal heavy-chain repertoire. During the early phase of B-cell regeneration, highly mutated B cells recirculate for a short time period in both the patients analysed. The longitudinal observation of a single patient up to 27 months shows subtle intraindividual changes, which may indicate repertoire

  17. Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin's lymphoma

    PubMed Central

    Gui, Lin; Han, Xiaohong; He, Xiaohui; Song, Yuanyuan; Yao, Jiarui; Yang, Jianliang; Liu, Peng; Qin, Yan; Zhang, Shuxiang; Zhang, Weijing; Gai, Wenlin; Xie, Liangzhi

    2016-01-01

    Objective: This study was designed to determine the safety, pharmacokinetics and biologic effects of a human-mouse chimeric anti-CD20 monoclonal antibody (SCT400) in Chinese patients with CD20-positive B-cell non-Hodgkin's lymphoma (CD20+ B-cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods: Fifteen patients with CD20+ B-cell NHL received dose-escalating SCT400 infusions (250 mg/m2: n=3; 375 mg/m2: n=9; 500 mg/m2: n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses. Results: No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer (NK) cell count or immunoglobulin levels. No patient developed anti-SCT400 antibodies during the course of the study. SCT400 serum half-life (T1/2), maximum concentration (Cmax) and area under the curve (AUC) generally increased between the first and fourth infusions (P<0.05). At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0±75.0 h, respectively, and the Cmax was 200.6±20.2 g/mL vs. 339.1±71.0 g/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner (P<0.05). Patients with a high tumor burden had markedly lower serum SCT400 concentrations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions: SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20+ B-cell NHL. PMID:27199517

  18. Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study

    PubMed Central

    Fluge, Øystein; Bruland, Ove; Risa, Kristin; Storstein, Anette; Kristoffersen, Einar K.; Sapkota, Dipak; Næss, Halvor; Dahl, Olav; Nyland, Harald; Mella, Olav

    2011-01-01

    Background Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients. Methods and Findings In this double-blind, placebo-controlled phase II study (NCT00848692), 30 CFS patients were randomised to either Rituximab 500 mg/m2 or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV) was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67%) in the Rituximab group and in two out of 15 patients (13%) in the Placebo group (p = 0.003). Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8–44). Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed), with differences between the Rituximab and Placebo groups between 6–10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening. Conclusion The delayed responses starting from 2–7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical

  19. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

    PubMed

    Fluge, Øystein; Bruland, Ove; Risa, Kristin; Storstein, Anette; Kristoffersen, Einar K; Sapkota, Dipak; Næss, Halvor; Dahl, Olav; Nyland, Harald; Mella, Olav

    2011-01-01

    Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti-CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients. In this double-blind, placebo-controlled phase II study (NCT00848692), 30 CFS patients were randomised to either Rituximab 500 mg/m(2) or saline, given twice two weeks apart, with follow-up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV) was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67%) in the Rituximab group and in two out of 15 patients (13%) in the Placebo group (p = 0.003). Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44). Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed), with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening. The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact future

  20. Anti-CD20 IgA can protect mice against lymphoma development: evaluation of the direct impact of IgA and cytotoxic effector recruitment on CD20 target cells

    PubMed Central

    Pascal, Virginie; Laffleur, Brice; Debin, Arnaud; Cuvillier, Armelle; van Egmond, Marjolein; Drocourt, Daniel; Imbertie, Laurent; Pangault, Céline; Tarte, Karin; Tiraby, Gérard; Cogné, Michel

    2012-01-01

    Background While most antibody-based therapies use IgG because of their well-known biological properties, some functional limitations of these antibodies call for the development of derivatives with other therapeutic functions. Although less abundant than IgG in serum, IgA is the most abundantly produced Ig class in humans. Besides the specific targeting of its dimeric form to mucosal areas, IgA was shown to recruit polymorphonuclear neutrophils against certain targets more efficiently than does IgG1. Design and Methods In this study, we investigated the various pathways by which anti-tumor effects can be mediated by anti-CD20 IgA against lymphoma cells. Results We found that polymeric human IgA was significantly more effective than human IgG1 in mediating direct killing or growth inhibition of target cells in the absence of complement. We also demonstrated that this direct killing was able to indirectly induce the classical pathway of the complement cascade although to a lesser extent than direct recruitment of complement by IgG. Recruitment of the alternative complement pathway by specific IgA was also observed. In addition to activating complement for lysis of lymphoma cell lines or primary cells from patients with lymphoma, we showed that monomeric anti-CD20 IgA can effectively protect mice against tumor development in a passive immunization strategy and we demonstrated that this protective effect may be enhanced in mice expressing the human FcαRI receptor on their neutrophils. Conclusions We show that anti-CD20 IgA antibodies have original therapeutic properties against lymphoma cells, with strong direct effects, ability to recruit neutrophils for cell cytotoxicity and even recruitment of complement, although largely through an indirect way. PMID:22689689

  1. The different clinical effects of anti-BLyS, anti-APRIL and anti-CD20 antibodies point at a critical pathogenic role of γ-herpesvirus infected B cells in the marmoset EAE model.

    PubMed

    Anwar Jagessar, S; Fagrouch, Zahra; Heijmans, Nicole; Bauer, Jan; Laman, Jon D; Oh, Luke; Migone, Thi; Verschoor, Ernst J; 't Hart, Bert A

    2013-06-01

    The robust and rapid clinical effect of depleting anti-CD20 monoclonal antibodies (mAb) in multiple sclerosis (MS) demonstrates a critical pathogenic contribution of B cells. The clinical effect of anti-CD20 mAb has been replicated in a relevant preclinical MS model, experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys (Callithrix jacchus). By contrast, treatment with mAbs against two essential cytokines in B cell activation growth and survival, i.e. BlyS/BAFF and APRIL, was only partially effective. All three mAbs induced depletion of CD20+ B cells from the circulation, albeit with different kinetics and based on distinct mechanisms of action. In the current study we analyzed whether the different clinical effect of anti-CD20 mAb or the anti-BLyS and anti-APRIL mAbs is due to different depletion of B cells infected with the EBV of marmosets, CalHV3. Employing a novel PCR-based assay, half of the colony of group-housed marmosets was tested positive for CalHV3 DNA in secondary lymphoid organs. The same prevalence was observed in placebo-treated monkeys. In marmosets treated with anti-CD20 mAb the load of CalHV3 DNA in lymphoid organs was substantially reduced, while this was not observed in the monkeys treated with anti-BLyS or anti-APRIL mAbs. To examine the pathogenic role of virus-transformed B cells, we infused EBV-transformed B lymphoblastic cell (BLC) lines presenting the immunodominant MOG34-56 peptide. We observed in the recipients of MOG34-56 pulsed BLC, but not in their fraternal siblings infused with non-pulsed BLC, activation of anti-MOG34-56 T cells and meningeal inflammation. Collectively, the data show that among CD20+ B cells, the herpesvirus-transformed subset has a particularly important pathogenic role in the marmoset EAE model.

  2. High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation for Adults ≥ 60 Years Old with Relapsed or Refractory B-Cell Lymphoma

    SciTech Connect

    Gopal, Ajay K.; Rajendran, Joseph G.; Gooley, Ted; Pagel, John M.; Fisher, Darrell R.; Petersdorf, Stephen; Maloney, David G.; Eary, Janet F.; Appelbaum, Frederick R.; Press, Oliver W.

    2007-04-10

    Purpose: The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet they are often denied potentially curative high-dose therapy and autologous stem cell transplants (ASCT) due to the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Methods: Patients over age 60 with relapsed B-NHL received infusions of tositumomab anti-CD20 antibody labeled with 5-10mCi I-131 tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of I-131-tositumomab (median 525 mCi, range 328-1154 mCi) to deliver 25-27Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results: Twenty-four patients with a median age of 64 (range 60-76) who had received a median of four prior regimens (range 2-14) were treated. Thirteen (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survivals were 59% and 51%, respectively with a median follow-up of 2.9 years (range 1-6 years). All patients experienced expected myeloablation with engraftment of platelets (≥20K/µL) and neutrophils (≥500/µL) occurring a median of 9 and 15 days, respectively following ASCT. There were no treatment-related deaths, and only two patients experienced grade 4 non-hematologic toxicity. Conclusions: Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.

  3. Targeting CD20+ Aggressive B-cell Non-Hodgkin Lymphoma by Anti-CD20 CAR mRNA-Modified Expanded Natural Killer Cells In Vitro and in NSG Mice.

    PubMed

    Chu, Yaya; Hochberg, Jessica; Yahr, Ashlin; Ayello, Janet; van de Ven, Carmella; Barth, Matthew; Czuczman, Myron; Cairo, Mitchell S

    2015-04-01

    The prognosis is very dismal for patients with relapsed CD20(+) B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20(+) B-NHL. In this study, we investigated functional activities of anti-CD20 CAR-modified, expanded peripheral blood NK cells (exPBNK) following mRNA nucleofection against CD20(+) B-NHL in vitro and in vivo. CAR(+) exPBNK had significantly enhanced in vitro cytotoxicity, compared with CAR(-) exPBNK against CD20(+) Ramos (P < 0.05), Daudi, Raji, and two rituximab-resistant cell lines, Raji-2R and Raji-4RH (P < 0.001). As expected, there was no significant difference against CD20(-) RS4;11 and Jurkat cells. CD107a degranulation and intracellular IFNγ production were also enhanced in CAR(+) exPBNK in response to CD20(+) B-NHL -: specific stimulation. In Raji-Luc and Raji-2R-Luc xenografted NOD/SCID/γ-chain(-/-) (NSG) mice, the luciferase signals measured in the CAR(+) exPBNK-treated group were significantly reduced, compared with the signals measured in the untreated mice and in mice treated with the CAR(-) exPBNK. Furthermore, the CAR exPBNK-treated mice had significantly extended survival time (P < 0.001) and reduced tumor size, compared with those of the untreated and the CAR(-) exPBNK-treated mice (P < 0.05). These preclinical data suggest that ex vivo-exPBNK modified with anti-CD20 CAR may have therapeutic potential for treating patients with poor-risk CD20(+) hematologic malignancies. ©2014 American Association for Cancer Research.

  4. Efficacy and safety of an anti-CD20 monoclonal antibody (Reditux™) for the treatment of patients with moderate to severe rheumatoid arthritis following the failure of conventional synthetic disease-modifying anti-rheumatic drugs.

    PubMed

    Bhati, Manjeet; Bandyopadhyay, Syamasis

    2016-08-01

    Rituximab (anti-CD20 monoclonal antibody) has shown to improve symptoms in rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). An anti-CD20 monoclonal antibody (Reditux™) developed by Dr. Reddy's Laboratories, India, is currently approved for use both in rheumatology and oncology patients. This retrospective report evaluates the efficacy and safety data from the real-world use of Reditux™ over a 6-month period in Indian patients with RA. All consecutive moderate to severe RA patients who failed therapy with at least two DMARDs including methotrexate (MTX) for 6 months, TNFα inhibitor naive, and willing to take Reditux™ were included. They were prescribed two doses of 1 g Reditux™, at least 15 days apart, with continued stable doses of methotrexate. Efficacy and safety after 24 weeks relative to baseline was assessed using various health assessment variables. A total of 39 patients (mean age of 46 years; 67.5 % females) treated with Reditux™ were evaluated. Statistically significant differences were observed in mean changes of DAS28-CRP, DAS28-ESR, SDAI, HAQ and Patient Global Assessment scores from baseline to 24 weeks (p < 0.0001 for all). Average steroid use per week also significantly reduced at 24 weeks (p = 0.0002). There was no significant gender difference. Mean changes in SDAI, HAQ and Patient Global Assessment scores for patients on steroids were significantly different from those not on steroids (p < 0.05 for all). At 24 weeks, 97 % of patients achieved ACR20 response demonstrating the efficacy of Reditux™ treatment. The treatment was well tolerated by patients without any clinically relevant serious adverse events over 24 weeks. Though limited by number of patients and retrospective in nature, this analysis serves as a real-world evidence of efficacy and safety of Dr. Reddy's rituximab (Reditux™) in the treatment of cs

  5. Phase 1/2 study of ocaratuzumab, an Fc-engineered humanized anti-CD20 monoclonal antibody, in low-affinity FcγRIIIa patients with previously treated follicular lymphoma.

    PubMed

    Ganjoo, Kristen N; de Vos, Sven; Pohlman, Brad L; Flinn, Ian W; Forero-Torres, Andres; Enas, Nathan H; Cronier, Damien M; Dang, Nam H; Foon, Kenneth A; Carpenter, Susan P; Slapak, Christopher A; Link, Brian K; Smith, Mitchell R; Mapara, Markus Y; Wooldridge, James E

    2015-01-01

    This phase 2 study assessed the safety and efficacy of ocaratuzumab, a humanized anti-CD20 monoclonal antibody. Fifty patients with previously treated follicular lymphoma (FL) and a low-affinity genotype of FcγRIIIa received ocaratuzumab 375 mg/m(2) weekly for 4 weeks. Grade 3/4/5 adverse events (AEs) were reported in 11/1/1 patients, respectively. Serious AEs were reported by 11/50 patients, and three discontinued due to AEs. One patient died from aspiration pneumonia due to possibly drug-related nausea and vomiting. Investigator-assessed response rate was 30% (15/50), including four complete responses (CR), three CR unconfirmed (CRu) and eight partial responses (PR). Investigator-assessed median Progression-free survivial (PFS) was 38.3 weeks. Ocaratuzumab's pharmacokinetic profile was similar to that reported for rituximab. Lymphocyte subset analysis showed significant, selective reduction of B-cells during and after ocaratuzumab treatment. Ocaratuzumab at this dose and schedule is active and well tolerated in patients with previously treated FL with low affinity FcγRIIIa genotypes. ClinTrials registry number: NCT00354926.

  6. Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in (131)I-anti-CD20 rituximab radioimmunotherapy of non-Hodgkin's lymphoma.

    PubMed

    Boucek, Jan A; Turner, J Harvey

    2005-04-01

    Radioimmunotherapy (RIT) for relapsed non-Hodgkin's lymphoma is emerging as a promising treatment strategy. Myelosuppression is the dose-limiting toxicity and may be particularly problematic in patients heavily pretreated with chemotherapy. Reliable dosimetry is likely to minimise toxicity and improve treatment efficacy, and the aim of this study was to elucidate the complex problems of dosimetry of RIT by using an integrated SPECT/CT system. As a part of a clinical trial of (131)I-anti-CD20 rituximab RIT of non-Hodgkin's lymphoma, we employed a patient-specific prospective dosimetry method utilising the whole-body effective half-life of antibody and the patient's ideal weight to calculate the administered activity for RIT corresponding to a prescribed radiation absorbed dose of 0.75 Gy to the whole body. A novel technique of quantitation of bone marrow uptake with hybrid SPECT/CT imaging was developed to validate this methodology by using post-RIT extended imaging and data collection. A strong, statistically significant correlation (p=0.001) between whole-body effective half-life of antibody and effective marrow half-life was demonstrated. Furthermore, it was found that bone marrow activity concentration was proportional to administered activity per unit weight, height or body surface area (p<0.001). The results of this study show the proposed whole-body dosimetry method to be valid and clinically applicable for safe, effective RIT.

  7. Anti-CD20 Monoclonal Antibody Treatment of Human Herpesvirus 8-Associated, Body Cavity-Based Lymphoma with an Unusual Phenotype in a Human Immunodeficiency Virus-Negative Patient

    PubMed Central

    Pérez, Celeste L.; Rudoy, Silvia

    2001-01-01

    Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a gammaherpesvirus first detected in Kaposi's sarcoma tumor cells and subsequently in primary effusion lymphoma (PEL) tumor cells and peripheral blood mononuclear cells from PEL patients. PEL has been recognized as an individual nosologic entity based on its distinctive features and consistent association with HHV-8 infection. PEL is an unusual form of body cavity-based B-cell lymphoma (BCBL). It occurs predominantly in human immunodeficiency virus (HIV)-positive patients but occasionally also in elderly HIV-negative patients. We describe a case of PEL, with ascites, bilateral pleural effusions, and a small axillary lymphadenopathy, in a 72-year-old HIV-negative man. PCR performed on a lymph node specimen and in liquid effusion was positive for HHV-8 and negative for Epstein-Barr virus. The immunophenotype of the neoplastic cells was B CD19+ CD20+ CD22+ with coexpression of CD10 and CD23 and with clonal kappa light chain rearrangement. The patient was treated with Rituximab, a chimeric (human-mouse) anti-CD20 monoclonal antibody. Thirteen months later, the patient continued in clinical remission. This is the first report of an HHV-8-associated BCBL in an HIV-negative patient in Argentina. PMID:11527816

  8. Delivery of an miR155 inhibitor by anti-CD20 single-chain antibody into B cells reduces the acetylcholine receptor-specific autoantibodies and ameliorates experimental autoimmune myasthenia gravis.

    PubMed

    Wang, Y-Z; Tian, F-F; Yan, M; Zhang, J-M; Liu, Q; Lu, J-Y; Zhou, W-B; Yang, H; Li, J

    2014-05-01

    MicroRNA-155 (miR155) is required for antibody production after vaccination with attenuated Salmonella. miR155-deficient B cells generated reduced germinal centre responses and failed to produce high-affinity immunoglobulin (Ig)G1 antibodies. In this study, we observed up-regulation of miR155 in the peripheral blood mononuclear cells (PBMCs) of patients with myasthenia gravis (MG), and miR155 was also up-regulated in torpedo acetylcholine receptor (T-AChR)-stimulated B cells. We used an inhibitor of miR155 conjugated to anti-CD20 single-chain antibody to treat both the cultured B cells and the experimental autoimmune MG (EAMG) mice. Our results demonstrated that silencing of miR155 by its inhibitor impaired the B cell-activating factor (BAFF)-R-related signalling pathway and reduced the translocation of nuclear factor (NF)-κB into the nucleus. Additionally, AChR-specific autoantibodies were reduced, which may be related to the altered amounts of marginal zone B cells and memory B cells in the spleens of EAMG mice. Our study suggests that miR155 may be a promising target for the clinical therapy of MG. © 2014 British Society for Immunology.

  9. Delivery of an miR155 inhibitor by anti-CD20 single-chain antibody into B cells reduces the acetylcholine receptor-specific autoantibodies and ameliorates experimental autoimmune myasthenia gravis

    PubMed Central

    Wang, Y-Z; Tian, F-F; Yan, M; Zhang, J-M; Liu, Q; Lu, J-Y; Zhou, W-B; Yang, H; Li, J

    2014-01-01

    MicroRNA-155 (miR155) is required for antibody production after vaccination with attenuated Salmonella. miR155-deficient B cells generated reduced germinal centre responses and failed to produce high-affinity immunoglobulin (Ig)G1 antibodies. In this study, we observed up-regulation of miR155 in the peripheral blood mononuclear cells (PBMCs) of patients with myasthenia gravis (MG), and miR155 was also up-regulated in torpedo acetylcholine receptor (T-AChR)-stimulated B cells. We used an inhibitor of miR155 conjugated to anti-CD20 single-chain antibody to treat both the cultured B cells and the experimental autoimmune MG (EAMG) mice. Our results demonstrated that silencing of miR155 by its inhibitor impaired the B cell-activating factor (BAFF)-R-related signalling pathway and reduced the translocation of nuclear factor (NF)-κB into the nucleus. Additionally, AChR-specific autoantibodies were reduced, which may be related to the altered amounts of marginal zone B cells and memory B cells in the spleens of EAMG mice. Our study suggests that miR155 may be a promising target for the clinical therapy of MG. PMID:24387321

  10. Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial.

    PubMed

    Sharman, Jeff P; Farber, Charles M; Mahadevan, Daruka; Schreeder, Marshall T; Brooks, Heather D; Kolibaba, Kathryn S; Fanning, Suzanne; Klein, Leonard; Greenwald, Daniel R; Sportelli, Peter; Miskin, Hari P; Weiss, Michael S; Burke, John M

    2017-02-01

    Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty-one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high-risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long-term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).

  11. Expanded CD23(+)/CD21(hi) B cells in inflamed lymph nodes are associated with the onset of inflammatory-erosive arthritis in TNF-transgenic mice and are targets of anti-CD20 therapy.

    PubMed

    Li, Jie; Kuzin, Igor; Moshkani, Safiehkhatoon; Proulx, Steven T; Xing, Lianping; Skrombolas, Denise; Dunn, Robert; Sanz, Iñaki; Schwarz, Edward M; Bottaro, Andrea

    2010-06-01

    Anti-CD20 B cell depletion therapy (BCDT) is very effective for some patients with rheumatoid arthritis (RA); however the pathogenic role of B lymphocytes in RA and the primary targets of BCDT are unknown. The human TNF transgenic (hTNF-Tg) mouse model of RA displays a chronic, progressive disease that spreads from distal to proximal joints and is generally considered to be adaptive immune system independent. We have previously reported that knee arthritis in hTNF-Tg mice is accompanied by structural and functional changes of the adjoining popliteal lymph node (PLN), detectable by contrast-enhanced magnetic resonance imaging. To better understand these changes, in this paper we show that onset of knee synovitis and focal erosions are paralleled by PLN contraction and accumulation of large numbers of B cells in the lymphatic sinus spaces within the node. Flow cytometry from TNF-Tg mice 2, 4-5, and 8-12 mo old demonstrated that B cell accumulation in the PLN follows ankle arthritis, but commences before knee disease, and involves early expansion of CD21(hi), CD23(+), IgM(hi), CD1d(+), activation marker-negative, polyclonal B cells that are found to be specifically restricted to lymph nodes draining inflamed, arthritic joints. The same B cell population also accumulates in PLNs of K/BxN mice with autoantigen-dependent arthritis. Strikingly, we show that BCDT ameliorates hTNF-Tg disease and clears follicular and CD21(hi), CD23(+) B cells from the PLNs. On the basis of these findings, we propose a model whereby B cells contribute to arthritis in mice, and possibly RA, by directly affecting the structure, composition, and function of joint-draining lymph nodes.

  12. Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome

    PubMed Central

    Lunde, Sigrid; Kristoffersen, Einar K.; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein

    2016-01-01

    Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6–9.5 g/L, IgA 1.8–1.5 g/L, and IgM 0.97–0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B

  13. Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome.

    PubMed

    Lunde, Sigrid; Kristoffersen, Einar K; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein

    2016-01-01

    Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6-9.5 g/L, IgA 1.8-1.5 g/L, and IgM 0.97-0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B

  14. Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab.

    PubMed

    Yasuhiro, Tomoko; Sawada, Wako; Klein, Christian; Kozaki, Ryohei; Hotta, Shingo; Yoshizawa, Toshio

    2017-03-01

    The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101). ONO/GS-4059 combined with GA101 or RTX was significantly better than the respective monotherapy with tumor growth inhibition (TGI) of 90% for the GA101 combination and 86% for the RTX combination. In contrast, ibrutinib (PCI-32765) combined with RTX did not result in improved efficacy compared with respective monotherapy. Taken together these data indicate that the combination of ONO/GS-4059 with rituximab and particularly obinutuzumab may be an effective treatment for ABC-DLBCL.

  15. Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma

    SciTech Connect

    Lu, Chia-Yen; Chen, Gregory J.; Tai, Pei-Han; Yang, Yu-Chen; Hsu, Yu-Shen; Chang, Mingi; Hsu, Chuan-Lung

    2016-05-13

    Bispecific antibodies (bsAbs) are second generation antibodies for therapeutic application in immunotherapy. One of the major strategies of the bsAb platform is the recruitment of immune effector T cells by incorporating an anti-CD3 domain. A bispecific T-cell engager (BiTE), with one end having an affinity for CD3 and the other end with affinity for CD19, has been approved in the US and Europe for the treatment of acute lymphoblastic leukemia. However, due to their small size and lack of Fc region, these single-chain variable fragment (scFv) bsAbs have short half-lives in vivo. Additionally, poor solubility, structural instability, and low production yields have also become major challenges in the bulk production process. To overcome these challenges, we have engineered a tetravalent bsAb with bivalent binding specificity for the CD20 and CD3 antigen in an immunoglobulin G (IgG) format. The fusion of the anti-CD3 scFvs to the CD20 antibody via a linker-hinge domain (LHD) results in improved antibody stabilization and properties. Here we demonstrate this antibody's highly efficient cancer cell elimination in a dose-dependent manner in a CD20-expressing B lymphoblastoid cell line in vitro. Our data suggest the potential clinical application of this bsAb for the treatment of CD20-expressing B cell malignancies. - Highlights: • A bispecific antibody (bsAb) can increase immunotherapeutic efficacy. • A tetravalent bsAb with binding specificity for the CD20 and CD3 antigens is proposed. • A linker-hinge domain (LHD) within the bsAb results in improved antibody properties.

  16. Effective treatment of refractory pulmonary hemorrhage with monoclonal anti-CD20 antibody (rituximab).

    PubMed

    Pinto, Luis Fernando; Candia, Liliana; Garcia, Patricia; Marín, Juan Ignacio; Pachón, Ines; Espinoza, Luis R; Marquez, Javier

    2009-01-01

    We report a 19-year-old female with systemic lupus erythematosus and lupus nephritis who developed pulmonary hemorrhage (PH) refractory to conventional immunosuppressive treatment. She was initially treated with intravenous methylprednisolone and cyclophosphamide pulses. She required mechanical ventilation due to a lack of responsiveness and her disease was considered refractory to conventional treatment. Rituximab was administered and this was followed by clinical improvement in both PH and nephritis. Rituximab may be a useful therapeutic option for the treatment of refractory PH. Copyright 2008 S. Karger AG, Basel.

  17. Resolution of Q Fever–Associated Cryoglobulinemia With Anti-CD20 Monoclonal Antibody Treatment

    PubMed Central

    Hawkins, Kellie L.; Janoff, Edward N.; Janson, Robert W.

    2017-01-01

    Immunologic phenomena can complicate chronic infections with Coxiella burnetii (Q fever), including immune complex deposition causing vasculitis, neuropathy, and glomerulonephritis. We describe the case of a man with Q fever endocarditis, mixed cryoglobulinemia, and life-threatening vasculitis driven by immune complex deposition who was successfully treated with B cell depleting therapy (rituximab). PMID:28203574

  18. Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.

    PubMed

    Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

    2012-05-01

    Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.

  19. Mimotope vaccination for epitope-specific induction of anti-CD20 antibodies.

    PubMed

    Li, Meng; Yan, Zhen; Han, Wei; Zhang, Yingqi

    2006-02-01

    CD20 is expressed strictly by B-cells and is ubiquitously expressed at high surface densities of malignant human B-cells. This suggests that CD20 may be a tumor target for immunotherapy of B-cell lymphomas. Rituximab, a chimeric monoclonal antibody directed against CD20, has been demonstrated to be an effective treatment for non-Hodgkin's lymphoma (NHL) and some autoimmune diseases. In the current study, we used the phage display technique to generate mimotopes that complemented the screening Ab Rituximab. A total of seven candidate mimotopes were isolated from a 12-mer peptide library from which one mimotope was conjugated to keyhole limpet hemocyanin (KLH) or tetanus toxoid (TT). The immunogenicity of the two vaccines generated was examined in BALB/c mice. Sera from the vaccinated mice demonstrated high-titer specific antibodies to the mimotope conjugates. Antibody binding to native CD20 and Ab-mediated cytotoxicity (CDC, complement-dependent cytotoxicity) were also analyzed. Our data suggest that a Rituximab mimotope may be a useful tool for the construction of a functional vaccine to treat B-cell malignancy as well as some CD20 related autoimmune disorders.

  20. Design, expression and characterization of a single chain anti-CD20 antibody; a germline humanized antibody derived from Rituximab.

    PubMed

    Ahmadzadeh, Vahideh; Farajnia, Safar; Hosseinpour Feizi, Mohammad Ali; Khavarinejad, Ramazan Ali

    2014-10-01

    CD20 is a B cell lineage specific surface antigen involved in various B cell malignancies. So far, several murine and chimeric antibodies have been produced against this antigen among which Rituximab is a commercially approved antibody widely used in treatment of cancers associated with CD20 overexpression. The current study reports the production and characterization of a humanized single chain version of Rituximab through CDR grafting method. For either heavy or light chain variable domains, a human antibody with the highest sequence homology to Rituximab was selected from human germline sequences and used as framework donors. Vernier zone residues in framework regions were replaced with those of Rituximab to retain the antigen binding affinity of parental antibody. The reactivity of humanized single chain antibody with CD20 was examined by ELISA and dot blot assays. The ability of antibody to suppress the growth of CD20 overexpressing Raji cells was tested by MTT assay. Analysis of reactivity with CD20 antigen revealed that the humanized single chain antibody reacted to the target antigen with high affinity. Proliferation inhibition assay showed that humanized scFv could suppress the proliferation of Raji cells efficiently in a dose-dependent manner. This successful production of a humanized scFv with the ability to inhibit growth of CD20-expressing cancer cell may provide a promising alternative strategy for CD20 targeted therapy.

  1. Novel antisense therapeutics delivery systems: In vitro and in vivo studies of liposomes targeted with anti-CD20 antibody.

    PubMed

    Meissner, Justyna M; Toporkiewicz, Monika; Czogalla, Aleksander; Matusewicz, Lucyna; Kuliczkowski, Kazimierz; Sikorski, Aleksander F

    2015-12-28

    Antisense gene therapy using molecules such as antisense oligodeoxynucleotides, siRNA or miRNA is a very promising strategy for the treatment of neoplastic diseases. It can be combined with other treatment strategies to enhance therapeutic effect. In acute leukemias, overexpression of the antiapoptotic gene BCL2 is observed in more than 70% of cases. Therefore, reduction of the Bcl-2 protein level could, in itself, prevent the development of cancer or could possibly help sensitize cancer cells to apoptosis inducers. The main objective of our work is to develop therapeutic liposome formulations characterized by high transfection efficiency, stability in the presence of serum, as well as specificity and toxicity for target (leukemic) cells. Each of our liposomal formulations consists of a core composed of antisense oligonucleotides complexed by either cationic lipid, DOTAP, or a synthetic polycation, polyethyleneimine, encapsulated within liposomes modified with polyethylenoglycol. In addition, the liposomal shells are enriched with covalently-bound antibodies recognizing a well characterized bio-marker, CD20, exposed on the surface of leukemia cells. The resulting immunoliposomes selectively and effectively reduced the expression of BCL2 in target cells. Model animal experiments carried out on mice-engrafted tumors expressing the specific marker showed high efficiency of the liposome formulations against specific tumor development. In conclusion, we show that lipid formulations based on a polyplex or lipoplex backbone additionally equipped with antibodies are promising non-viral vectors for specific oligonucleotide transfer into human tumor cells.

  2. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    SciTech Connect

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  3. Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody.

    PubMed

    Wagner, Henry N; Wiseman, Gregory A; Marcus, Carol S; Nabi, Hani A; Nagle, Conrad E; Fink-Bennett, Darlene M; Lamonica, Dominick M; Conti, Peter S

    2002-02-01

    90Y-ibritumomab tiuxetan is a novel radioimmunotherapeutic agent recently approved for the treatment of relapsed or refractory low-grade, follicular, or CD20+ transformed non-Hodgkin's lymphoma (NHL). (90)Y-ibritumomab tiuxetan consists of a murine monoclonal antibody covalently attached to a metal chelator, which stably chelates (111)In for imaging and (90)Y for therapy. Both health care workers and patients receiving this therapy need to become familiar with how it differs from conventional chemotherapy and what, if any, safety precautions are necessary. Because (90)Y is a pure beta-emitter, the requisite safety precautions are not overly burdensome for health care workers or for patients and their families. (90)Y-ibritumomab tiuxetan is dosed on the basis of the patient's body weight and baseline platelet count; dosimetry is not required for determining the therapeutic dose in patients meeting eligibility criteria similar to those used in clinical trials, such as <25% lymphomatous involvement of the bone marrow. (111)In- and (90)Y-ibritumomab tiuxetan are labeled at commercial radiopharmacies and delivered for on-site dose preparation and administration. Plastic and acrylic materials are appropriate for shielding during dose preparation and administration; primary lead shielding should be avoided because of the potential exposure risk from bremsstrahlung. Because there are no penetrating gamma-emissions associated with the therapy, (90)Y-ibritumomab tiuxetan is routinely administered on an outpatient basis. Furthermore, the risk of radiation exposure to patients' family members has been shown to be in the range of background radiation, even without restrictions on contact. There is therefore no need to determine activity limits or dose rate limits before patients who have been treated with (90)Y radioimmunotherapy are released, as is necessary with patients who have been treated with radiopharmaceuticals that contain (131)I. Standard universal precautions for handling body fluids are recommended for health care workers and patients and their family members after (90)Y-ibritumomab tiuxetan administration. In summary, (90)Y-ibritumomab tiuxetan introduces (90)Y into clinical practice and expands the role nuclear medicine plays in the care of patients with cancer. Understanding the unique properties of this novel radioimmunoconjugate will facilitate its safe and effective use.

  4. Gamma camera scans and pretreatment tumor volumes as predictors of response and progression after Y-90 anti-CD20 radioimmunotherapy

    SciTech Connect

    Gokhale, Abhay S.; Mayadev, Jyoti; Pohlman, Brad . E-mail: macklir@ccf.org

    2005-09-01

    Purpose: To evaluate two potential approaches to predicting site-specific patterns of recurrence after yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) for CD20+ B-cell Non-Hodgkin's lymphoma. These predictive methods may be useful in evaluating the utility of local intensification of individual nodal or extranodal sites using external beam radiotherapy. Methods and Materials: Records and images were evaluated for 20 patients previously treated with yttrium-90 ibritumomab RIT. Intensity of isotope uptake on the pretreatment two-dimensional antibody scans and maximal extent of tumor deposits found on computed tomography images of each anatomic site were correlated with response and subsequent patterns of recurrence or progression. Results: Our data failed to suggest a significant correlation between the site-by-site two-dimensional image intensity on the pre-RIT scan and the likelihood of response at those sites. In contrast, an analysis of pretreatment target volumes did correlate significantly with progression. A collective analysis of disease sites from all 20 patients found that 83% (10/12) sites of 'bulky' (maximal diameter {>=}5 cm) disease displayed evidence of progression vs. 28% (26/93) of 'nonbulky' disease sites containing gross disease but no area measuring >5 cm (p < 0.001). All patients with at least one site of bulky disease had initial disease progression occur at a bulky site, with a bulky site being the sole first site of progression in approximately 50%. In patients with only nonbulky disease sites, approximately one third progressed initially at an entirely new site of disease. Conclusion: We conclude that we can use tumor bulk to establish a statistical hierarchy of likely tumor progression sites and use this pattern to direct the use of additional external beam radiotherapy to augment treatment.

  5. High-Dose 131I-Tositumomab (Anti-CD20) Radioimmunotherapy for Non-Hodgkin's Lymphoma: Adjusting Radiation Absorbed Dose to Actual Organ Volumes

    SciTech Connect

    Rajendran, Joseph G.; Fisher, Darrell R.; Gopal, A K.; Durack, L. D.; Press, O. W.; Eary, Janet F.

    2004-06-01

    Radioimmunotherapy (RIT) using 131I-tositumomab has been used successfully to treat relapsed or refractory B-cell non-Hodgin's lymphoma (NHL). Our approach to treatment planning has been to determine limits on radiation absorbed close to critical nonhematopoietic organs. This study demonstrates the feasibility of using CT to adjust for actual organ volumes in calculating organ-specific absorbed dose estimates. Methods: Records of 84 patients who underwent biodistribution studies after a trace-labeled infusion of 131I-tositumomab for RIT (January 1990 and April 2003) were reviewed. Serial planar -camera images and whole-body Nal probe counts were obtained to estimate 131I-antibody source-organ residence times as recommended by the MIRD Committee. The source-organ residence times for standard man or woman were adjusted by the ratio of the MIRD phantom organ mass to the CT-derived organ mass. Results: The mean radiation absorbed doses (in mGy/MBq) for our data using the MIRD model were lungs= 1.67; liver= 1.03; kidneys= 1.08; spleen= 2.67; and whole body= 0.3; and for CT volume-adjusted organ volumes (in mGy/MBq) were lungs= 1.30; liver= 0.92; kidneys= 0.76; spleen= 1.40; and whole body= 0.22. We determined the following correlation coefficients between the 2 methods for the various organs; lungs, 0.49; (P= 0.0001); liver, 0.64 (P= 0.004); kidneys, 0.45 (P= 0.0001), for the residence times. For therapy, patients received mean 131I administered activities of 19.2 GBq (520 mCi) after adjustment for CT-derived organ mass compared with 16.0 GBq (433 mCi) that would otherwise have been given had therapy been based only using standard MIRD organ volumes--a statistically significant difference (P= 0.0001). Conclusion: We observed large variations in organ masses among our patients. Our treatments were planned to deliver the maximally tolerated radiation dose to the dose-limiting normal organ. This work provides a simplified method for calculating patient-specific radiation doses by adjusting for the actual organ mass and shows the value of this approach in treatment planning for RIT.

  6. Combination anti-CD74 (milatuzumab) and anti-CD20 (rituximab) monoclonal antibody therapy has in vitro and in vivo activity in mantle cell lymphoma

    PubMed Central

    Alinari, Lapo; Yu, Bo; Christian, Beth A.; Yan, Fengting; Shin, Jungook; Lapalombella, Rosa; Hertlein, Erin; Lustberg, Mark E.; Quinion, Carl; Zhang, Xiaoli; Lozanski, Gerard; Muthusamy, Natarajan; Prætorius-Ibba, Mette; O'Connor, Owen A.; Goldenberg, David M.; Byrd, John C.; Blum, Kristie A.

    2011-01-01

    Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a median survival of 3 years despite chemoimmunotherapy. Rituximab, a chimeric anti–CD20 monoclonal antibody (mAb), has shown only modest activity as single agent in MCL. The humanized mAb milatuzumab targets CD74, an integral membrane protein linked with promotion of B-cell growth and survival, and has shown preclinical activity against B-cell malignancies. Because rituximab and milatuzumab target distinct antigens and potentially signal through different pathways, we explored a preclinical combination strategy in MCL. Treatment of MCL cell lines and primary tumor cells with immobilized milatuzumab and rituximab resulted in rapid cell death, radical oxygen species generation, and loss of mitochondrial membrane potential. Cytoskeletal distrupting agents significantly reduced formation of CD20/CD74 aggregates, cell adhesion, and cell death, highlighting the importance of actin microfilaments in rituximab/milatuzumab–mediated cell death. Cell death was independent of caspase activation, Bcl-2 family proteins or modulation of autophagy. Maximal inhibition of p65 nuclear translocation was observed with combination treatment, indicating disruption of the NF-κB pathway. Significant in vivo therapeutic activity of combination rituximab and milatuzumab was demonstrated in a preclinical model of MCL. These data support clinical evaluation of combination milatuzumab and rituximab therapy in MCL. PMID:21228331

  7. The impact of glucocorticoids and anti-cd20 therapy on cervical human papillomavirus infection risk in women with systemic lupus erythematosus

    PubMed Central

    Mendoza-Pinto, Claudia; Garcia-Carrasco, Mario; Vallejo-Ruiz, Veronica; Taboada-Cole, Alejandro; Muñoz-Guarneros, Margarita; Solis-Poblano, Juan Carlos; Pezzat-Said, Elias; Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis Felipe; de Lara, Luis Vazquez; Ramos-Alvarez, Gloria; Reyes-Leyva, Julio; Lopez-Colombo, Aurelio

    2013-01-01

    OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05), and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01) and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005) compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03). In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus. PMID:24473503

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

    ClinicalTrials.gov

    2017-09-27

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

  9. Desensitization with plasmapheresis and anti-Cd20 for ABO incompatible kidney transplantation from living donor: experience of a single center in Italy.

    PubMed

    Silvestre, C; Furian, L; Marson, P; Tison, T; Valente, M; Marchini, F; Rossi, B; Bonfante, L; Valerio, F; Cozzi, E; Rigotti, P

    2014-09-01

    Blood group incompatibility in kidney transplants from a living donor can be successfully overcome by using various desensitization protocols: intravenous immunoglobulin, plasmapheresis (PP), immunoadsorption, and double filtration PP. From July 2010 to October 2013, we performed 10 ABO incompatible kidney transplantation (KT) procedures from a living donor. The desensitization protocol was based on rituximab and PP+cytomegalovirus immune globulin. All patients received induction with basiliximab, except 1 case treated with Thymoglobuline® (ATG) for the simultaneous presence of donor-specific antibody. Tacrolimus and mycophenolate mofetil were initiated at the time of desensitization and continued after the transplant. After a mean follow-up of 11.6±10.4 months, all patients are alive with a functioning graft. The mean serum creatinine concentration at 1 month, 3 months, 6 months, and 1 year was 1.48±0.29, 1.47±0.18, 1.47±0.27, and 1.5±0.27 mg/dl. Three episodes of acute cellular rejection occurred in 2 patients. There was only 1 case of BK virus infection, treated with reduction of immunosuppressive therapy. The protocol biopsy specimens at 1, 3, and 6 months were C4d positive in the absence of acute rejection. Desensitization with rituximab, PP, and anti-cytomegalovirus immune globulin allowed us to perform transplants from living donors to ABO incompatible recipients with excellent results and reduced costs. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials

    PubMed Central

    Østergaard, Mikkel; Taylor, Peter C.; van Vollenhoven, Ronald F.; Chu, Myron; Mallett, Stephen; Perry, Hayley; Kurrasch, Regina

    2016-01-01

    Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development on subcutaneous delivery. Due to differences in study designs and populations, data are summarised separately for each study. Results 483 patients (243, 148 and 92 in OFA110635, OFA110634 and OFA111752 respectively) received up to 7 treatment courses of intravenous ofatumumab; cumulative duration of exposure was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17–47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70/92), serious adverse events for 18% (44/243), 20% (30/148) and 12% (11/92) and serious infections for 3% (8/243), 5% (7/148) and 1% (1/92) of patients in OFA110635, OFA110634 and OFA111752, respectively. The most common adverse events were infusion-related reactions during the first infusion of the first course (48–79%); serious infusion-related reactions were rare (<1% [1/243], 5% [8/148], and 1% [1/92] of patients). Two deaths occurred (fulminant hepatitis B virus infection and interstitial lung disease). Conclusions Ofatumumab was generally well tolerated with no evidence of increased safety risks with multiple retreatments. Serious infections were uncommon and did not increase over time. Trial Registration ClinicalTrials.gov 110635 ClinicalTrials.gov 110634 ClinicalTrials.gov 111752 PMID:27336685

  11. Anti-CD20 single chain variable antibody fragment-apolipoprotein A-I chimera containing nanodisks promote targeted bioactive agent delivery to CD20-positive lymphomas.

    PubMed

    Crosby, Natasha M; Ghosh, Mistuni; Su, Betty; Beckstead, Jennifer A; Kamei, Ayako; Simonsen, Jens B; Luo, Bing; Gordon, Leo I; Forte, Trudy M; Ryan, Robert O

    2015-08-01

    A fusion protein comprising an α-CD20 single chain variable fragment (scFv) antibody, a spacer peptide, and human apolipoprotein (apo) A-I was constructed and expressed in Escherichia coli. The lipid interaction properties intrinsic to apoA-I as well as the antigen recognition properties of the scFv were retained by the chimera. scFv•apoA-I was formulated into nanoscale reconstituted high-density lipoprotein particles (termed nanodisks; ND) and incubated with cultured cells. α-CD20 scFv•apoA-I ND bound to CD20-positive non-Hodgkins lymphoma (NHL) cells (Ramos and Granta) but not to CD20-negative T lymphocytes (i.e., Jurkat). Binding to NHL cells was partially inhibited by pre-incubation with rituximab, a monoclonal antibody directed against CD20. Confocal fluorescence microscopy analysis of Granta cells following incubation with α-CD20 scFv•apoA-I ND formulated with the intrinsically fluorescent hydrophobic polyphenol, curcumin, revealed α-CD20 scFv•apoA-I localizes to the cell surface, while curcumin off-loads and gains entry to the cell. Compared to control incubations, viability of cultured NHL cells was decreased upon incubation with α-CD20 scFv•apoA-I ND harboring curcumin. Thus, formulation of curcumin ND with α-CD20 scFv•apoA-I as the scaffold component confers cell targeting and enhanced bioactive agent delivery, providing a strategy to minimize toxicity associated with chemotherapeutic agents.

  12. Sobre la terapia génica para enfermedades de la retina.

    PubMed

    Fischer, M Dominik

    2017-07-11

    Las mutaciones en un gran número de genes provocan degeneración de la retina y ceguera sin que exista actualmente cura alguna. En las últimas décadas, la terapia génica para enfermedades de la retina ha evolucionado y se ha convertido en un nuevo y prometedor paradigma terapéutico para estas enfermedades poco comunes. Este artículo refleja las ideas y los conceptos que parten de la ciencia básica hacia la aplicabilidad de la terapia génica en el ámbito clínico. Se describen los avances y las reflexiones actuales sobre la eficacia de los ensayos clínicos en la actualidad y se discuten los posibles obstáculos y soluciones de cara al futuro de la terapia génica para enfermedades de la retina. © 2017 S. Karger AG, Basel.

  13. Successful treatment with a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) for a patient with relapsed mantle cell lymphoma who developed a human anti-chimeric antibody.

    PubMed

    Maeda, T; Yamada, Y; Tawara, M; Yamasaki, R; Yakata, Y; Tsutsumi, C; Onimaru, Y; Kamihira, S; Tomonaga, M

    2001-07-01

    Mantle cell lymphoma (MCL) has a poor prognosis without cure; the median overall survival ranges only from 3 to 4 years irrespective of conventional therapeutic regimens. IDEC-C2B8 (rituximab), a chimeric monoclonal antibody against the B-cell-specific antigen CD20, induces an evaluable clinical response in patients with MCL with mild toxicities. However, the single agent rituximab cannot cure MCL. Due to its low immunogenicity, an antibody against IDEC-C2B8 (human antichimeric antibody [HACA]) has rarely been produced in vivo. We report a patient with relapsed MCL who was successfully treated with IDEC-C2B8 for over a year although she developed HACA 6 months after the initial administration of IDEC-C2B8 in the phase II clinical trial conducted by Zenyaku Kogyo Co. Ltd. We followed the pharmacokinetics of IDEC-C2B8, the serum HACA titer, and the number of B lymphocytes in the peripheral blood in relation to clinical response. The HACA became undetectable soon after subsequent administrations of IDEC-C2B8. When the serum level of IDEC-C2B8 was kept elevated, clinical responses were apparently observed and HACA disappeared during this response period. There were no significant clinical toxicities related to the appearance of HACA. The present findings suggested that IDEC-C2B8 is effective and safe even in patients who have developed HACA.

  14. Effects and problems of adult ABO-incompatible living donor liver transplantation using protocol of plasma exchange, intra-arterial infusion therapy, and anti-CD20 monoclonal antibody without splenectomy: case reports of initial experiences and results in Korea.

    PubMed

    Kim, B-W; Park, Y-K; Kim, Y-B; Wang, H-J; Kim, M-W

    2008-12-01

    Adult ABO-incompatible liver transplantation is associated with a high risk of graft failure due to antibody-mediated humoral rejection (AMR). We evaluated the effects of a protocol using preoperative removal of isohemagglutinin, rituximab prophylaxis, and intrahepatic arterial infusion (HAI) therapy for ABO-incompatible adult living donor liver transplantation (LDLT). Between March 2005 and September 2007, we performed 94 adult LDLTs, including 3 ABO-incompatible cases. All ABO-incompatible LDLT patients underwent administration of 375 mg/m(2) rituximab on preoperative days 15 and 8 without splenectomy, as well as preoperative removal of isohemagglutinin using plasma exchange, and HAI therapy for postoperative 21 days. Postoperative anti-donor blood-type antibody titer and B-cell level were effectively suppressed by early rituximab prophylaxis in all patients. HAI therapy was effective to prevent AMR and even resolved mild AMR. However, all patients suffered bacterial infections, and 1 died of septicemia with good graft function. Another subject died of late-onset AMR that occurred after discontinuation of HAI therapy. An ABO-incompatible LDLT protocol using plasma exchange, rituximab prophylaxis, and intra-HAI therapy effectively suppressed anti-A/B antibody and prevented AMR. But this protocol should be further improved to reduce infectious complications and late onset of AMR.

  15. Testing Na+ in blood

    PubMed Central

    Lava, Sebastiano A.G.; Bianchetti, Mario G.; Milani, Gregorio P.

    2017-01-01

    Abstract Both direct potentiometry and indirect potentiometry are currently used for Na+ testing in blood. These measurement techniques show good agreement as long as protein and lipid concentrations in blood remain normal. In severely ill patients, indirect potentiometry commonly leads to relevant errors in Na+ estimation: 25% of specimens show a disagreement between direct and indirect potentiometry, which is ≥4 mmol/L (mostly spuriously elevated Na+ level due to low circulating albumin concentration). There is a need for increased awareness of the poor performance of indirect potentiometry in some clinical settings.

  16. Obinutuzumab in hematologic malignancies: lessons learned to date.

    PubMed

    Illidge, Tim; Klein, Christian; Sehn, Laurie H; Davies, Andrew; Salles, Gilles; Cartron, Guillaume

    2015-11-01

    The routine use of anti-CD20 monoclonal antibodies (mAbs) has improved patient outcomes in CD20-positive non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Despite the clinical success achieved with rituximab, relapses are still common with further improvements in anti-CD20 mAb efficacy required. Many novel anti-CD20 antibodies are in development, but obinutuzumab is currently the only type II glycoengineered anti-CD20 mAb in clinical testing. Obinutuzumab has increased antibody-dependent cell-mediated cytotoxicity, reduced complement-dependent cytotoxicity and enhanced direct non-apoptotic cell death. In preclinical models, obinutuzumab induced superior tumor remission compared with rituximab at the equivalent dose levels, and was active in rituximab-refractory tumors. Obinutuzumab exhibits encouraging efficacy as monotherapy in NHL, and combined with chemotherapy in relapsed/refractory NHL and treatment-naïve symptomatic CLL. In a recent randomized, phase III trial in patients with untreated comorbid CLL, overall response rate was significantly greater (78% vs. 65%, P<0.0001) and median progression-free survival was significantly prolonged (26.7 vs. 15.2months, P<0.0001) for obinutuzumab plus chlorambucil vs. rituximab plus chlorambucil. Obinutuzumab is a type II anti-CD20 antibody that utilizes distinct mechanisms of action relative to type I antibodies like rituximab and has led to significant clinical improvement over rituximab in a phase III trial in CLL. Further trials are ongoing to determine whether such improvements in outcome will be seen in CD20-positive B-cell malignancies.

  17. Na+ coordination at the Na2 site of the Na+/I- symporter.

    PubMed

    Ferrandino, Giuseppe; Nicola, Juan Pablo; Sánchez, Yuly E; Echeverria, Ignacia; Liu, Yunlong; Amzel, L Mario; Carrasco, Nancy

    2016-09-13

    The sodium/iodide symporter (NIS) mediates active I(-) transport in the thyroid-the first step in thyroid hormone biosynthesis-with a 2 Na(+): 1 I(-) stoichiometry. The two Na(+) binding sites (Na1 and Na2) and the I(-) binding site interact allosterically: when Na(+) binds to a Na(+) site, the affinity of NIS for the other Na(+) and for I(-) increases significantly. In all Na(+)-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na(+) ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues-S66, D191, Q194, and Q263-are also involved in Na(+) coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I(-) These residues are conserved throughout the entire SLC5 family, to which NIS belongs, suggesting that they serve a similar function in the other transporters. Our findings also suggest that the increase in affinity that each site displays when an ion binds to another site may result from changes in the dynamics of the transporter. These mechanistic insights deepen our understanding not only of NIS but also of other transporters, including many that, like NIS, are of great medical relevance.

  18. Na Cauda do Cometa

    NASA Astrophysics Data System (ADS)

    Voelzke, M. R.

    2009-01-01

    Quando viam um cometa, os antigos gregos imaginavam uma estrela com uma vasta cabeleira. Não à toa, a palavra deriva do termo koma, que significa cabelo. Constituídos por fragmentos de gelo e gases, os cometas possuem um núcleo sólido, que pode ter vários quilômetros de diâmetro, e uma cauda que sempre aponta na direção contrária ao Sol, devido aos ventos solares. Graças à aparência de pontos luminosos em movimento (ao contrário de outros astros, que parecem estáticos), esses corpos celestes foram interpretados por diferentes povos com muito misticismo, inspirando mitos tanto de boas-novas como de maus presságios. Conheça algumas dessas histórias:

  19. Na+ coordination at the Na2 site of the Na+/I− symporter

    PubMed Central

    Ferrandino, Giuseppe; Nicola, Juan Pablo; Sánchez, Yuly E.; Echeverria, Ignacia; Liu, Yunlong; Amzel, L. Mario; Carrasco, Nancy

    2016-01-01

    The sodium/iodide symporter (NIS) mediates active I− transport in the thyroid—the first step in thyroid hormone biosynthesis—with a 2 Na+: 1 I− stoichiometry. The two Na+ binding sites (Na1 and Na2) and the I− binding site interact allosterically: when Na+ binds to a Na+ site, the affinity of NIS for the other Na+ and for I− increases significantly. In all Na+-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na+ ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues—S66, D191, Q194, and Q263—are also involved in Na+ coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I−. These residues are conserved throughout the entire SLC5 family, to which NIS belongs, suggesting that they serve a similar function in the other transporters. Our findings also suggest that the increase in affinity that each site displays when an ion binds to another site may result from changes in the dynamics of the transporter. These mechanistic insights deepen our understanding not only of NIS but also of other transporters, including many that, like NIS, are of great medical relevance. PMID:27562170

  20. Solidification of NaCl-NaF eutectic in space

    NASA Technical Reports Server (NTRS)

    Yue, A. S.; Yu, J. G.

    1974-01-01

    Continuous and discontinuous NaF fibers, embedded in a NaCl matrix, have been produced in space and on earth, respectively. The production of continuous fibers in a eutectic mixture was attributed to the absence of convection current in the liquid during solidification in space. Image transmission and optical transmittance measurements of transverse sections of the space-grown and earth-grown ingots were made with a light microscope and a spectrometer. It was found that better optical properties were obtained from samples grown in space. This was attributed to a better alignment of NaF fibers along the ingot axis.

  1. Na+ recirculation and isosmotic transport.

    PubMed

    Larsen, E H; Møbjerg, N

    2006-01-01

    The Na(+) recirculation theory for solute-coupled fluid absorption is an expansion of the local osmosis concept introduced by Curran and analyzed by Diamond & Bossert. Based on studies on small intestine the theory assumes that the observed recirculation of Na(+) serves regulation of the osmolarity of the absorbate. Mathematical modeling reproducing bioelectric and hydrosmotic properties of small intestine and proximal tubule, respectively, predicts a significant range of observations such as isosmotic transport, hyposmotic transport, solvent drag, anomalous solvent drag, the residual hydraulic permeability in proximal tubule of AQP1 (-/-) mice, and the inverse relationship between hydraulic permeability and the concentration difference needed to reverse transepithelial water flow. The model reproduces the volume responses of cells and lateral intercellular space (lis) following replacement of luminal NaCl by sucrose as well as the linear dependence of volume absorption on luminal NaCl concentration. Analysis of solvent drag on Na(+) in tight junctions provides explanation for the surprisingly high metabolic efficiency of Na(+) reabsorption. The model predicts and explains low metabolic efficiency in diluted external baths. Hyperosmolarity of lis is governed by the hydraulic permeability of the apical plasma membrane and tight junction with 6-7 mOsm in small intestine and < or = 1 mOsm in proximal tubule. Truly isosmotic transport demands a Na(+) recirculation of 50-70% in small intestine but might be barely measurable in proximal tubule. The model fails to reproduce a certain type of observations: The reduced volume absorption at transepithelial osmotic equilibrium in AQP1 knockout mice, and the stimulated water absorption by gallbladder in diluted external solutions. Thus, it indicates cellular regulation of apical Na(+) uptake, which is not included in the mathematical treatment.

  2. Na Deposition on MnO(100)

    NASA Astrophysics Data System (ADS)

    Feng, Xu; Cox, David F.

    2016-03-01

    Na deposition on the MnO(100) surface was investigated by temperature programmed desorption (TPD), X-ray photoelectron spectroscopy (XPS) and low energy electron diffraction (LEED). Na TPD and XPS results indicate that adsorbed Na interacts strongly with the MnO substrate to form an irreversibly-adsorbed, oxidic Na compound on the surface for coverages up to 1 monolayer (ML). This strongly-bound Na diffuses into the MnO subsurface and bulk at elevated temperatures above 500 K. For Na coverages above 1 ML, metallic Na is present and desorbs from the surface below 500 K. The deposition of Na on MnO(100) follows a Stranski-Krastanov (SK) growth mode, with the formation of metallic Na islands following completion of the first Na monolayer. After Na deposition, the surface exhibits a diffuse (1 × 1) LEED pattern, suggesting the formation of disordered Na overlayers. After heating to 1000 K, the surface presents a (2 × 2) LEED pattern indicating that a surface reconstruction is induced by the diffusion of Na into the near surface region. CO2 can be used as a probe molecule in TPD to distinguish between metallic Na islands and oxidic Na in the first ML, and to indicate when Na that is still observable by XPS goes subsurface.

  3. Calmodulin limits pathogenic Na+ channel persistent current

    PubMed Central

    Yan, Haidun; Wang, Chaojian; Marx, Steven O.

    2017-01-01

    Increased “persistent” current, caused by delayed inactivation, through voltage-gated Na+ (NaV) channels leads to cardiac arrhythmias or epilepsy. The underlying molecular contributors to these inactivation defects are poorly understood. Here, we show that calmodulin (CaM) binding to multiple sites within NaV channel intracellular C-terminal domains (CTDs) limits persistent Na+ current and accelerates inactivation across the NaV family. Arrhythmia or epilepsy mutations located in NaV1.5 or NaV1.2 channel CTDs, respectively, reduce CaM binding either directly or by interfering with CTD–CTD interchannel interactions. Boosting the availability of CaM, thus shifting its binding equilibrium, restores wild-type (WT)–like inactivation in mutant NaV1.5 and NaV1.2 channels and likewise diminishes the comparatively large persistent Na+ current through WT NaV1.6, whose CTD displays relatively low CaM affinity. In cerebellar Purkinje neurons, in which NaV1.6 promotes a large physiological persistent Na+ current, increased CaM diminishes the persistent Na+ current, suggesting that the endogenous, comparatively weak affinity of NaV1.6 for apoCaM is important for physiological persistent current. PMID:28087622

  4. Astrocytes generate Na+-mediated metabolic waves.

    PubMed

    Bernardinelli, Yann; Magistretti, Pierre J; Chatton, Jean-Yves

    2004-10-12

    Glutamate-evoked Na+ increase in astrocytes has been identified as a signal coupling synaptic activity to glucose consumption. Astrocytes participate in multicellular signaling by transmitting intercellular Ca2+ waves. Here we show that intercellular Na+ waves are also evoked by activation of single cultured cortical mouse astrocytes in parallel with Ca2+ waves; however, there are spatial and temporal differences. Indeed, maneuvers that inhibit Ca2+ waves also inhibit Na+ waves; however, inhibition of the Na+/glutamate cotransporters or enzymatic degradation of extracellular glutamate selectively inhibit the Na+ wave. Thus, glutamate released by a Ca2+ wave-dependent mechanism is taken up by the Na+/glutamate cotransporters, resulting in a regenerative propagation of cytosolic Na+ increases. The Na+ wave gives rise to a spatially correlated increase in glucose uptake, which is prevented by glutamate transporter inhibition. Therefore, astrocytes appear to function as a network for concerted neurometabolic coupling through the generation of intercellular Na+ and metabolic waves.

  5. The NA62 trigger system

    NASA Astrophysics Data System (ADS)

    Krivda, M.; NA62 Collaboration

    2013-08-01

    The main aim of the NA62 experiment (NA62 Technical Design Report, na62.web.cern.ch/NA62/Documents/TD_Full_doc_v1.pdf> [1]) is to study ultra-rare Kaon decays. In order to select rare events over the overwhelming background, central systems with high-performance, high bandwidth, flexibility and configurability are necessary, that minimize dead time while maximizing data collection reliability. The NA62 experiment consists of 12 sub-detector systems and several trigger and control systems, for a total channel count of less than 100,000. The GigaTracKer (GTK) has the largest number of channels (54,000), and the Liquid Krypton (LKr) calorimeter shares with it the largest raw data rate (19 GB/s). The NA62 trigger system works with 3 trigger levels. The first trigger level is based on a hardware central trigger unit, so-called L0 Trigger Processor (L0TP), and Local Trigger Units (LTU), which are all located in the experimental cavern. Other two trigger levels are based on software, and done with a computer farm located on surface. The L0TP receives information from triggering sub-detectors asynchronously via Ethernet; it processes the information, and then transmits a final trigger decision synchronously to each sub-detector through the Trigger and Timing Control (TTC) system. The interface between L0TP and the TTC system, which is used for trigger and clock distribution, is provided by the Local Trigger Unit board (LTU). The LTU can work in two modes: global and stand-alone. In the global mode, the LTU provides an interface between L0TP and TTC system. In the stand-alone mode, the LTU can fully emulate L0TP and so provides an independent way for each sub-detector for testing or calibration purposes. In addition to the emulation functionality, a further functionality is implemented that allows to synchronize the clock of the LTU with the L0TP and the TTC system. For testing and debugging purposes, a Snap Shot Memory (SSM) interface is implemented, that can work

  6. Europlanet NA2 Science Networking

    NASA Astrophysics Data System (ADS)

    Harri, Ari-Matti; Szego, Karoly; Genzer, Maria; Schmidt, Walter; Krupp, Norbert; Lammer, Helmut; Kallio, Esa; Haukka, Harri

    2013-04-01

    Europlanet RI / NA2 Science Networking [1] focused on determining the major goals of current and future European planetary science, relating them to the Research Infrastructure that the Europlanet RI project [2] developed, and placing them in a more global context. NA2 also enhanced the ability of European planetary scientists to participate on the global scene with their own agenda-setting projects and ideas. The Networking Activity NA2 included five working groups, aimed at identifying key science issues and producing reference books on major science themes that will bridge the gap between the results of present and past missions and the scientific preparation of the future ones. Within the Europlanet RI project (2009-2012) the NA2 and NA2-WGs organized thematic workshops, an expert exchange program and training groups to improve the scientific impact of this Infrastructure. The principal tasks addressed by NA2 were: • Science activities in support to the optimal use of data from past and present space missions, involving the broad planetary science community beyond the "space club" • Science activities in support to the preparation of future planetary missions: Earth-based preparatory observations, laboratory studies, R&D on advanced instrumentation and exploration technologies for the future, theory and modeling etc. • Develop scientific activities, joint publications, dedicated meetings, tools and services, education activities, engaging the public and industries • Update science themes and addressing the two main scientific objectives • Prepare and support workshops of the International Space Science Institute (ISSI) in Bern and • Support Trans National Activities (TNAs), Joined Research Activities (JRAs) and the Integrated and Distributed Information Service (IDIS) of the Europlanet project These tasks were achieved by WG workshops organized by the NA2 working groups, by ISSI workshops and by an Expert Exchange Program. There were 17 official WG

  7. Sodium iron hexacyanoferrate with high Na content as a Na-rich cathode material for Na-ion batteries

    SciTech Connect

    You, Ya; Yu, Xi -Qian; Yin, Ya -Xia; Nam, Kyung -Wan; Guo, Yu -Guo

    2014-10-27

    Owing to the worldwide abundance and low-cost of Na, room-temperature Na-ion batteries are emerging as attractive energy storage systems for large-scale grids. Increasing the Na content in cathode material is one of the effective ways to achieve high energy density. Prussian blue and its analogues (PBAs) are promising Na-rich cathode materials since they can theoretically store two Na ions per formula. However, increasing the Na content in PBAs cathode materials is a big challenge in the current. Here we show that sodium iron hexacyanoferrate with high Na content could be obtained by simply controlling the reducing agent and reaction atmosphere during synthesis. The Na content can reach as high as 1.63 per formula, which is the highest value for sodium iron hexacyanoferrate. This Na-rich sodium iron hexacyanoferrate demonstrates a high specific capacity of 150 mA h g-1 and remarkable cycling performance with 90% capacity retention after 200 cycles. Furthermore, the Na intercalation/de-intercalation mechanism is systematically studied by in situ Raman, X-ray diffraction and X-ray absorption spectroscopy analysis for the first time. As a result, the Na-rich sodium iron hexacyanoferrate could function as a plenteous Na reservoir and has great potential as a cathode material toward practical Na-ion batteries.

  8. Sodium iron hexacyanoferrate with high Na content as a Na-rich cathode material for Na-ion batteries

    DOE PAGES

    You, Ya; Yu, Xi -Qian; Yin, Ya -Xia; ...

    2014-10-27

    Owing to the worldwide abundance and low-cost of Na, room-temperature Na-ion batteries are emerging as attractive energy storage systems for large-scale grids. Increasing the Na content in cathode material is one of the effective ways to achieve high energy density. Prussian blue and its analogues (PBAs) are promising Na-rich cathode materials since they can theoretically store two Na ions per formula. However, increasing the Na content in PBAs cathode materials is a big challenge in the current. Here we show that sodium iron hexacyanoferrate with high Na content could be obtained by simply controlling the reducing agent and reaction atmospheremore » during synthesis. The Na content can reach as high as 1.63 per formula, which is the highest value for sodium iron hexacyanoferrate. This Na-rich sodium iron hexacyanoferrate demonstrates a high specific capacity of 150 mA h g-1 and remarkable cycling performance with 90% capacity retention after 200 cycles. Furthermore, the Na intercalation/de-intercalation mechanism is systematically studied by in situ Raman, X-ray diffraction and X-ray absorption spectroscopy analysis for the first time. As a result, the Na-rich sodium iron hexacyanoferrate could function as a plenteous Na reservoir and has great potential as a cathode material toward practical Na-ion batteries.« less

  9. Ionic regulation of Na absorption in proximal colon: cation inhibition of electroneutral Na absorption

    SciTech Connect

    Sellin, J.H.; De Soignie, R.

    1987-01-01

    Active Na absorption (J/sub net//sup NA/) in rabbit proximal colon in vitro is paradoxically stimulated as (Na) in the bathing media is lowered with constant osmolarity. J/sub m..-->..s//sup Na/ increases almost linearly from 0 to 50 mM (Na)/sub 0/ but then plateaus and actually decreases from 50 to 140 mM (Na)/sub 0/, consistent with inhibition of an active transport process. Both lithium and Na are equally effective inhibitors of J/sub net//sup Na/, whereas choline and mannitol do not block the high rate of J/sub net//sup Na/ observed in decreased (Na)/sub 0/. Either gluconate or proprionate replacement of Cl inhibits J/sub net//sup Na/. J/sub net//sup Na/ at lowered (Na)/sub 0/ is electrically silent and is accompanied by increased Cl absorption; it is inhibited by 10/sup -3/ M amiloride and 10/sup -3/ theophylline but not by 10/sup -4/ M bumetanide. Epinephrine is equally effective at stimulating Na absorption at 50 and 140 mM (Na). Na gradient experiments are consistent with a predominantly serosal effect of the decreased (Na)/sub 0/. These results suggest that 1) Na absorption in rabbit proximal colon in vitro is stimulated by decreased (Na); 2) the effect is cation specific, both Na and Li blocking the stimulatory effect; 3) the transport is mediated by Na-H exchange and is Cl dependent but 4) is under different regulatory mechanisms than the epinephrine-sensitive Na-Cl cotransport previously described in proximal colon. Under the appropriate conditions, proximal colon absorbs Na extremely efficiently. Na-H exchange in this epithelium is cation inhibitable, either directly or by a secondary regulatory process.

  10. Deliquescence of NaCl-NaNO3 and KNO3-NaNO3 Salt Mixtures at 90C

    SciTech Connect

    Carroll, S; Craig, L; Wolery, T

    2003-12-29

    We conducted reversed deliquescence experiments in saturated NaCl-NaNO3-H2O and KNO{sub 3}-NaNO{sub 3}-H{sub 2}O systems at 90 C to determine relative humidity and solution composition. NaCl, NaNO{sub 3}, and KNO{sub 3} represent members of dust salt assemblages that are likely to deliquesce and form concentrated brines on high-level radioactive waste package surfaces in a repository environment at Yucca Mountain, NV, USA. Model predictions agree with experimental results for the NaCl-NaNO{sub 3}-H{sub 2}O system, but underestimate relative humidity by as much as 8% and solution composition by as much as 50% in the KNO{sub 3}-NaNO{sub 3}-H{sub 2}O system.

  11. Na+ Tolerance and Na+ Transport in Higher Plants

    PubMed Central

    TESTER, MARK; DAVENPORT, ROMOLA

    2003-01-01

    Tolerance to high soil [Na+] involves processes in many different parts of the plant, and is manifested in a wide range of specializations at disparate levels of organization, such as gross morphology, membrane transport, biochemistry and gene transcription. Multiple adaptations to high [Na+] operate concurrently within a particular plant, and mechanisms of tolerance show large taxonomic variation. These mechanisms can occur in all cells within the plant, or can occur in specific cell types, reflecting adaptations at two major levels of organization: those that confer tolerance to individual cells, and those that contribute to tolerance not of cells per se, but of the whole plant. Salt‐tolerant cells can contribute to salt tolerance of plants; but we suggest that equally important in a wide range of conditions are processes involving the management of Na+ movements within the plant. These require specific cell types in specific locations within the plant catalysing transport in a coordinated manner. For further understanding of whole plant tolerance, we require more knowledge of cell‐specific transport processes and the consequences of manipulation of transporters and signalling elements in specific cell types. PMID:12646496

  12. Compensatory regulation of Na+ absorption by Na+/H+ exchanger and Na+-Cl- cotransporter in zebrafish (Danio rerio)

    PubMed Central

    2013-01-01

    Introduction In mammals, internal Na+ homeostasis is maintained through Na+ reabsorption via a variety of Na+ transport proteins with mutually compensating functions, which are expressed in different segments of the nephrons. In zebrafish, Na+ homeostasis is achieved mainly through the skin/gill ionocytes, namely Na+/H+ exchanger (NHE3b)-expressing H+-ATPase rich (HR) cells and Na+-Cl- cotransporter (NCC)-expressing NCC cells, which are functionally homologous to mammalian proximal and distal convoluted tubular cells, respectively. The present study aimed to investigate whether or not the functions of HR and NCC ionocytes are differentially regulated to compensate for disruptions of internal Na+ homeostasis and if the cell differentiation of the ionocytes is involved in this regulation pathway. Results Translational knockdown of ncc caused an increase in HR cell number and a resulting augmentation of Na+ uptake in zebrafish larvae, while NHE3b loss-of-function caused an increase in NCC cell number with a concomitant recovery of Na+ absorption. Environmental acid stress suppressed nhe3b expression in HR cells and decreased Na+ content, which was followed by up-regulation of NCC cells accompanied by recovery of Na+ content. Moreover, knockdown of ncc resulted in a significant decrease of Na+ content in acid-acclimated zebrafish. Conclusions These results provide evidence that HR and NCC cells exhibit functional redundancy in Na+ absorption, similar to the regulatory mechanisms in mammalian kidney, and suggest this functional redundancy is a critical strategy used by zebrafish to survive in a harsh environment that disturbs body fluid Na+ homeostasis. PMID:23924428

  13. The hydrogen storage properties of Na decorated small boron cluster B6Na8

    NASA Astrophysics Data System (ADS)

    Tang, Chunmei; Wang, Zhiguo; Zhang, Xue; Wen, Ninghua

    2016-09-01

    The binding energy of the Na atoms to the hollow sites of the B6 cage is larger than the experimental cohesive energy of bulk Na, so the clustering of Na atoms can be avoided. The polarization interaction dominates the adsorption of H2 by the B6Na8 cluster. The Na-coated B6Na8sbnd B8sbnd B6Na8 complex with the dispersive Na atoms and four H2 molecules adsorbed per Na can serve as better building blocks of polymers than the (B6Na8)2 dimer. These findings suggest a new route to design cluster-assembled hydrogen storage materials based on sp2-terminated boron chains.

  14. Conversion and Distribution of Lead and Tin in NaOH-NaNO3 Fusion Process

    NASA Astrophysics Data System (ADS)

    Liu, Jingxin; Guo, Xueyi

    2016-12-01

    Oxidizing alkali fusion process has been studied to extract amphoteric metals. Transformation and distribution behaviors of typical amphoteric metals Pb and Sn in the NaOH-NaNO3 fusion process are systemically studied by theoretical analysis and experimental verification done in this work. Functions of NaOH and NaNO3 in the fusion process were also investigated. The results show the fused products, Na2PbO3 and Na2SnO3, are captured in the flux, and Na2PbO4 is speculated to reduce to Pb(II) in the following leaching process. By measuring solubility data of NaOH-Na2SnO3-PbO-H2O system, a strategy of crystallization is proposed to separate Sn with Pb in concentrated alkaline solution, and slice Na2Sn(OH)6 is obtained as a product.

  15. Conversion and Distribution of Lead and Tin in NaOH-NaNO3 Fusion Process

    NASA Astrophysics Data System (ADS)

    Liu, Jingxin; Guo, Xueyi

    2017-04-01

    Oxidizing alkali fusion process has been studied to extract amphoteric metals. Transformation and distribution behaviors of typical amphoteric metals Pb and Sn in the NaOH-NaNO3 fusion process are systemically studied by theoretical analysis and experimental verification done in this work. Functions of NaOH and NaNO3 in the fusion process were also investigated. The results show the fused products, Na2PbO3 and Na2SnO3, are captured in the flux, and Na2PbO4 is speculated to reduce to Pb(II) in the following leaching process. By measuring solubility data of NaOH-Na2SnO3-PbO-H2O system, a strategy of crystallization is proposed to separate Sn with Pb in concentrated alkaline solution, and slice Na2Sn(OH)6 is obtained as a product.

  16. A long-life Na-air battery based on a soluble NaI catalyst.

    PubMed

    Yin, Wen-Wen; Shadike, Zulipiya; Yang, Yin; Ding, Fei; Sang, Lin; Li, Hong; Fu, Zheng-Wen

    2015-02-11

    A Na-air battery with NaI dissolved in a typical organic electrolyte could run up to 150 cycles with a capacity limit of 1000 mA h g(-1). The low charge voltage plateau of 3.2 V vs. Na(+)/Na in a Na-air battery should mainly be attributed to the oxidation reaction of active iodine anions.

  17. Silicene for Na-ion battery applications

    NASA Astrophysics Data System (ADS)

    Zhu, Jiajie; Schwingenschlögl, Udo

    2016-09-01

    Na-ion batteries are promising candidates to replace Li-ion batteries in large scale applications because of the advantages in natural abundance and cost of Na. Silicene has potential as the anode in Li-ion batteries but so far has not received attention with respect to Na-ion batteries. In this context, freestanding silicene, a graphene-silicene-graphene heterostructure, and a graphene-silicene superlattice are investigated for possible application in Na-ion batteries, using first-principles calculations. The calculated Na capacities of 954 mAh/g for freestanding silicene and 730 mAh/g for the graphene-silicene superlattice (10% biaxial tensile strain) are highly competitive and potentials of \\gt 0.3 {{V}} against the Na{}+/Na potential exceed the corresponding value of graphite. In addition, the diffusion barriers are predicted to be \\lt 0.3 {eV}.

  18. Kinetic Analysis of H(+)-Na(+) Selectivity in a Light-Driven Na(+)-Pumping Rhodopsin.

    PubMed

    Kato, Yoshitaka; Inoue, Keiichi; Kandori, Hideki

    2015-12-17

    Krokinobacter eikastus rhodopsin 2 (KR2) is a recently identified light-driven Na(+) pump from a marine bacterium. KR2 pumps Na(+) in NaCl solution but pumps H(+) in the absence of Na(+) and Li(+). The Na(+) transport mechanism in KR2 has been extensively studied, whereas understanding of the H(+) transport mechanism is very limited. Here we studied ion uptake mechanisms and H(+)-Na(+) selectivity using flash photolysis. The results show that decay of the blue-shifted M intermediate is dependent on both [Na(+)] and [H(+)], indicating that KR2 competitively uptakes Na(+) or H(+) upon M decay. Comprehensive concentration dependence of Na(+) and H(+) revealed that the rate constant of H(+) uptake (kH) was much larger than that of Na(+) uptake (kNa) with a ratio (kH/kNa) of >10(3). Therefore, KR2 pumps only H(+) when Na(+) and H(+) concentrations are similar. On the contrary, KR2 pumps Na(+) exclusively under physiological conditions in which [Na(+)] is much greater than [H(+)].

  19. Structural effects of 34Na in the 33Na(n ,γ )34Na radiative capture reaction

    NASA Astrophysics Data System (ADS)

    Singh, G.; Shubhchintak, Chatterjee, R.

    2017-06-01

    Background: The path towards the production of r -process seed nuclei follows a course where the neutron rich light and medium mass nuclei play a crucial role. The neutron capture rates for these exotic nuclei could dominate over their α -capture rates, thereby enhancing their abundances at or near the drip line. Sodium isotopes especially should have a strong neutron capture flow to gain abundance at the drip line. In this context, study of 33Na(n ,γ )34Na and 33Na(α ,n )36Al reactions becomes indispensable. Purpose: In this paper, we calculate the radiative neutron capture cross section for the 33Na(n ,γ )34Na reaction involving deformation effects. Subsequently, the rate for this reaction is found and compared with that of the α -capture for the 33Na(α ,n )36Al reaction to determine the possible path flow for the abundances of sodium isotopes. Method: We use the entirely quantum mechanical theory of finite-range distorted-wave Born approximation upgraded to incorporate deformation effects, and calculate the Coulomb dissociation of 34Na as it undergoes elastic breakup on 208Pb when directed at a beam energy of 100 MeV/u. Using the principle of detailed balance to study the reverse photodisintegration reaction, we find the radiative neutron capture cross section with variation in one-neutron binding energy and quadrupole deformation of 34Na. The rate of this 33Na(n ,γ )34Na reaction is then compared with that of the α -capture by 33Na deduced from the Hauser-Feshbach theory. Results: The nonresonant one-neutron radiative capture cross section for 33Na(n ,γ )34Na is calculated and is found to increase with increasing deformation of 34Na. An analytic scrutiny of the capture cross section with neutron separation energy as a parameter is also done at different energy ranges. The calculated reaction rate is compared with the rate of the 33Na(α ,n )36Al reaction, and is found to be significantly higher below a temperature of T9=2 . Conclusion: At the

  20. Revisiting the hydration structure of aqueous Na+

    NASA Astrophysics Data System (ADS)

    Galib, M.; Baer, M. D.; Skinner, L. B.; Mundy, C. J.; Huthwelker, T.; Schenter, G. K.; Benmore, C. J.; Govind, N.; Fulton, J. L.

    2017-02-01

    A combination of theory, X-ray diffraction (XRD) and extended x-ray absorption fine structure (EXAFS) are used to probe the hydration structure of aqueous Na+. The high spatial resolution of the XRD measurements corresponds to Qmax = 24 Å-1 while the first-reported Na K-edge EXAFS measurements have a spatial resolution corresponding to 2k = Qmax = 16 Å-1. Both provide an accurate measure of the shape and position of the first peak in the Na-O pair distribution function, gNaO(r). The measured Na-O distances of 2.384 ± 0.003 Å (XRD) and 2.37 ± 0.024 Å (EXAFS) are in excellent agreement. These measurements show a much shorter Na-O distance than generally reported in the experimental literature (Na-Oavg ˜ 2.44 Å) although the current measurements are in agreement with recent neutron diffraction measurements. The measured Na-O coordination number from XRD is 5.5 ± 0.3. The measured structure is compared with both classical and first-principles density functional theory (DFT) simulations. Both of the DFT-based methods, revPBE and BLYP, predict a Na-O distance that is too long by about 0.05 Å with respect to the experimental data (EXAFS and XRD). The inclusion of dispersion interactions (-D3 and -D2) significantly worsens the agreement with experiment by further increasing the Na-O distance by 0.07 Å. In contrast, the use of a classical Na-O Lennard-Jones potential with SPC/E water accurately predicts the Na-O distance as 2.39 Å although the Na-O peak is over-structured with respect to experiment.

  1. Revisiting the hydration structure of aqueous Na().

    PubMed

    Galib, M; Baer, M D; Skinner, L B; Mundy, C J; Huthwelker, T; Schenter, G K; Benmore, C J; Govind, N; Fulton, J L

    2017-02-28

    A combination of theory, X-ray diffraction (XRD) and extended x-ray absorption fine structure (EXAFS) are used to probe the hydration structure of aqueous Na(+). The high spatial resolution of the XRD measurements corresponds to Qmax = 24 Å(-1) while the first-reported Na K-edge EXAFS measurements have a spatial resolution corresponding to 2k = Qmax = 16 Å(-1). Both provide an accurate measure of the shape and position of the first peak in the Na-O pair distribution function, gNaO(r). The measured Na-O distances of 2.384 ± 0.003 Å (XRD) and 2.37 ± 0.024 Å (EXAFS) are in excellent agreement. These measurements show a much shorter Na-O distance than generally reported in the experimental literature (Na-Oavg ∼ 2.44 Å) although the current measurements are in agreement with recent neutron diffraction measurements. The measured Na-O coordination number from XRD is 5.5 ± 0.3. The measured structure is compared with both classical and first-principles density functional theory (DFT) simulations. Both of the DFT-based methods, revPBE and BLYP, predict a Na-O distance that is too long by about 0.05 Å with respect to the experimental data (EXAFS and XRD). The inclusion of dispersion interactions (-D3 and -D2) significantly worsens the agreement with experiment by further increasing the Na-O distance by 0.07 Å. In contrast, the use of a classical Na-O Lennard-Jones potential with SPC/E water accurately predicts the Na-O distance as 2.39 Å although the Na-O peak is over-structured with respect to experiment.

  2. The effect of Na vapor on the Na content of chondrules

    NASA Technical Reports Server (NTRS)

    Lewis, R. Dean; Lofgren, Gary E.; Franzen, Hugo F.; Windom, Kenneth E.

    1993-01-01

    Chondrules contain higher concentrations of volatiles (Na) than expected for melt droplets in the solar nebula. Recent studies have proposed that chondrules may have formed under non-canonical nebular conditions such as in particle/gas-rich clumps. Such chondrule formation areas may have contained significant Na vapor. To test the hypothesis of whether a Na-rich vapor would minimize Na volatilization reaction rates in a chondrule analog and maintain the Na value of the melt, experiments were designed where a Na-rich vapor could be maintained around the sample. A starting material with a melting point lower that typical chondrules was required to keep the logistics of working with Na volatilization from NaCl within the realm of feasibility. The Knippa basalt, a MgO-rich alkali olivine basalt with a melting temperature of 1325 +/- 5 C and a Na2O content of 3.05 wt%, was used as the chondrule analog. Experiments were conducted in a 1 atm, gas-mixing furnace with the fO2 controlled by a CO/CO2 gas mixture and fixed at the I-W buffer curve. To determine the extent of Na loss from the sample, initial experiments were conducted at high temperatures (1300 C - 1350 C) for duration of up to 72 h without a Na-rich vapor present. Almost all (up to 98%) Na was volatilized in runs of 72 h. Subsequent trials were conducted at 1330 C for 16 h in the presence of a Na-rich vapor, supplied by a NaCl-filled crucible placed in the bottom of the furnace. Succeeding Knudsen cell weight-loss mass-spectrometry analysis of NaCl determined the P(sub Na) for these experimental conditions to be in the 10(exp -6) atm range. This value is considered high for nebula conditions but is still plausible for non-canonical environments. In these trials the Na2O content of the glass was maintained or in some cases increased; Na2O values ranged from 2.62% wt to 4.37% wt. The Na content of chondrules may be controlled by the Na vapor pressure in the chondrule formation region. Most heating events capable

  3. Extracellular Na+ inhibits Na+/H+ exchange: cell shrinkage reduces the inhibition.

    PubMed

    Dunham, Philip B; Kelley, Scott J; Logue, Paul J

    2004-08-01

    Na+/H+ exchangers (NHE) are ubiquitous transporters participating in regulation of cell volume and pH. Cell shrinkage, acidification, and growth factors activate NHE by increasing its sensitivity to intracellular H+ concentration. In this study, the kinetics were studied in dog red blood cells of Na+ influx through NHE as a function of external Na+ concentration ([Na+](o)). In cells in isotonic media, [Na+](o) inhibited Na+ influx >40 mM. Osmotic shrinkage activated NHE by reducing this inhibition. In cells in isotonic media + 120 mM sucrose, there was no inhibition, and influx was a hyperbolic function of [Na+](o). The kinetics of Na+-inhibited Na+ influx were analyzed at various extents of osmotic shrinkage. The curves for inhibited Na+ fluxes were sigmoid, indicating more than one Na+ inhibitory site associated with each transporter. Shrinkage significantly increased the Na+ concentration at half-maximal velocity of Na+-inhibited Na+ influx, the mechanism by which shrinkage activates NHE.

  4. Mechanism of epithelial lithium transport. Evidence for basolateral Na:Na and Na:Li exchange

    PubMed Central

    1983-01-01

    Measurement of transmural sodium fluxes across isolated, ouabain- inhibited turtle colon in the presence of a serosal-to-mucosal sodium gradient shows that in the absence of active transport the amiloride- sensitive cellular path contains at least two routes for the transmural movement of sodium and lithium, one a conductive path and the other a nonconductive, cation-exchange mechanism. The latter transport element can exchange lithium for sodium, and the countertransport of these two cations provides a mechanistic basis for the ability of tight epithelia to actively absorb lithium despite the low affinity of the basolateral Na/K-ATPase for this cation. PMID:6644269

  5. Growth of binary organic NLO crystals: m.NA-p.NA and m.NA-CNA system

    NASA Technical Reports Server (NTRS)

    Singh, N. B.; Henningsen, T.; Hopkins, R. H.; Mazelsky, R.

    1993-01-01

    Experiments were carried out to grow 3.Nitroaniline (m.NA) crystals doped with 4.Nitroaniline (p.NA) and 2.chloro 4.Nitroaniline (CNA). The measured undercooling for m.NA, p.NA, and CNA were 0.21 tm K, 0.23 tm K, and 0.35 tm K respectively, where tm represents the melting temperature of the pure component. Because of the crystals' large heat of fusion and large undercooling, it was not possible to grow good quality crystals with low thermal gradients. In the conventional two-zone Bridgman furnace we had to raise the temperature of the hot zone above the decomposition temperature of CNA, p.NA, and m.NA to achieve the desired thermal gradient. To avoid decomposition, we used an unconventional Bridgman furnace. Two immiscible liquids, silicone oil and ethylene glycol, were used to build a special two-zone Bridgman furnace. A temperature gradient of 18 K/cm was achieved without exceeding the decomposition temperature of the crystal. The binary crystals, m.NA-p.NA and m.NA-CNA, were grown in centimeter size in this furnace. X-ray and optical characterization showed good optical quality.

  6. 13C and 23Na NMR studies of Na2C60 and Na6C60 fullerides

    NASA Astrophysics Data System (ADS)

    Rachdi, F.; Hajji, L.; Galtier, M.; Yildirim, T.; Fischer, J. E.; Goze, C.; Mehring, M.

    1997-10-01

    We report on 13C and 23Na NMR measurements on Na2C60 and Na6C60 compounds. The room-temperature 13C NMR spectra of Na2C60 and Na6C60 samples present a narrow isotropic line at 172 and 176 ppm, respectively. The Na6C60 resonance is shifted 20 ppm more down field than the resonances of A6C60 compounds with heavier alkalis, indicating a partial charge transfer to the threefold degenerate t1u level which is totally filled in the latter compounds. The 23Na NMR spectrum of A2C60 shows one line at 73 ppm and the one of A6C60 presents two lines at 73 and 147 ppm. The intensity ratio of the latter lines is about 2:1. According to previously reported x-ray data we attribute the line at 147 ppm to the Na tetramers in the octahedral sites and the line at 73 ppm to the Na cations in the tetrahedral ones which are singly occupied.

  7. Maintaining the Na atmosphere of Mercury

    NASA Technical Reports Server (NTRS)

    Killen, Rosemary M.; Morgan, Thomas H.

    1993-01-01

    The possible sources of the Na atmosphere of Mercury are calculatively studied. The likely structure, composition, and temperature of the planet's upper crust is examined along with the probable flux of Na from depth by grain boundary diffusion and by Knudsen flow. The creation of fresh regolith is considered along with mechanisms for supplying Na from the surface to the exosphere. The implications of the calculations for the probable abundances in the regolith are discussed.

  8. Maintaining the NA atmosphere of Mercury

    NASA Astrophysics Data System (ADS)

    Killen, R. M.; Morgan, T. H.

    1993-02-01

    The possible sources of the Na atmosphere of Mercury are calculatively studied. The likely structure, composition, and temperature of the planet's upper crust is examined along with the probable flux of Na from depth by grain boundary diffusion and by Knudsen flow. The creation of fresh regolith is considered along with mechanisms for supplying Na from the surface to the exosphere. The implications of the calculations for the probable abundances in the regolith are discussed.

  9. Simulation study of Na-majorite

    NASA Astrophysics Data System (ADS)

    Dymshits, A.; Vinograd, V.; Paulsen, N.; Winkler, B.; Perchuk, L.; Bobrov, A.

    2009-04-01

    Garnets, which are found as inclusions in diamonds, often have the excess of Na2O and SiO2 [Stachel, 2001]. Experimental studies suggest that Na is incorporated in pyrope-rich garnet via the coupled substitution Mg+Al=Na+Si [Bobrov et al., 2008]. This study is concerned with the determination of the structure and the thermodynamic properties of NaGrt (Na2MgSi5O12), which is assumed to be the end-member of pyrope-rich garnets with the excess of Na2O and SiO2. Static lattice energy calculations were performed with the program GULP [Gale & Rohl, 2003] using the force-field model [Vinograd et al., 2007] for 200 structures of Na2MgSi5O12 composition. These structures were prepared from Ia3-d pyrope Mg3Al2Si3O12 by replacing all octahedral Al atoms with Si and 2/3 of Mg atoms with Na. The distribution of Mg and Na was varied randomly. The static energies of these structures were cluster expanded using 8 pairwise effective cluster interactions (ECI). The ECIs were used to constrain Monte Carlo simulations within a 4×4×4 supercell (NNN exchangeable sites). The annealing experiments have shown that the lowest energy structure has the space group I4

  10. Painful Na-channelopathies: an expanding universe.

    PubMed

    Waxman, Stephen G

    2013-07-01

    The universe of painful Na-channelopathies--human disorders caused by mutations in voltage-gated sodium channels--has recently expanded in three dimensions. We now know that mutations of sodium channels cause not only rare genetic 'model disorders' such as inherited erythromelalgia and channelopathy-associated insensitivity to pain but also common painful neuropathies. We have learned that mutations of NaV1.8, as well as mutations of NaV1.7, can cause painful Na-channelopathies. Moreover, recent studies combining atomic level structural models and pharmacogenomics suggest that the goal of genomically guided pain therapy may not be unrealistic.

  11. NA-NET numerical analysis net

    SciTech Connect

    Dongarra, J. . Dept. of Computer Science Oak Ridge National Lab., TN ); Rosener, B. . Dept. of Computer Science)

    1991-12-01

    This report describes a facility called NA-NET created to allow numerical analysts (na) an easy method of communicating with one another. The main advantage of the NA-NET is uniformity of addressing. All mail is addressed to the Internet host na-net.ornl.gov'' at Oak Ridge National Laboratory. Hence, members of the NA-NET do not need to remember complicated addresses or even where a member is currently located. As long as moving members change their e-mail address in the NA-NET everything works smoothly. The NA-NET system is currently located at Oak Ridge National Laboratory. It is running on the same machine that serves netlib. Netlib is a separate facility that distributes mathematical software via electronic mail. For more information on netlib consult, or send the one-line message send index'' to netlib{at}ornl.gov. The following report describes the current NA-NET system from both a user's perspective and from an implementation perspective. Currently, there are over 2100 members in the NA-NET. An average of 110 mail messages pass through this facility daily.

  12. NA-NET numerical analysis net

    SciTech Connect

    Dongarra, J. |; Rosener, B.

    1991-12-01

    This report describes a facility called NA-NET created to allow numerical analysts (na) an easy method of communicating with one another. The main advantage of the NA-NET is uniformity of addressing. All mail is addressed to the Internet host ``na-net.ornl.gov`` at Oak Ridge National Laboratory. Hence, members of the NA-NET do not need to remember complicated addresses or even where a member is currently located. As long as moving members change their e-mail address in the NA-NET everything works smoothly. The NA-NET system is currently located at Oak Ridge National Laboratory. It is running on the same machine that serves netlib. Netlib is a separate facility that distributes mathematical software via electronic mail. For more information on netlib consult, or send the one-line message ``send index`` to netlib{at}ornl.gov. The following report describes the current NA-NET system from both a user`s perspective and from an implementation perspective. Currently, there are over 2100 members in the NA-NET. An average of 110 mail messages pass through this facility daily.

  13. First mesopause Na retrievals from satellite Na D-line nightglow observations

    NASA Astrophysics Data System (ADS)

    Savigny, C.; Langowski, M. P.; Zilker, B.; Burrows, J. P.; Fussen, D.; Sofieva, V. F.

    2016-12-01

    We report the retrieval of Na concentration profiles in the mesopause region from satellite observations of the Na D-line nightglow emission near 589 nm made by the Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY) on the Envisat spacecraft. The retrieval assumes the Na D-line excitation mechanism originally proposed by Chapman in 1939. The retrieval approach, including treatment of self-absorption by Na, a retrieval uncertainty budget, and first retrieval results, is presented. The retrieved Na profiles are compared to independent satellite measurements. Good agreement in terms of peak altitude, peak concentration, and vertical column density is found. The retrievals constitute the first Na profile retrievals from satellite observations of the Na D-line nightglow emission profile. They enable our understanding of the Na nightglow excitation mechanism to be tested.

  14. Na+/Ca2+ exchange and Na+/K+-ATPase in the heart

    PubMed Central

    Shattock, Michael J; Ottolia, Michela; Bers, Donald M; Blaustein, Mordecai P; Boguslavskyi, Andrii; Bossuyt, Julie; Bridge, John H B; Chen-Izu, Ye; Clancy, Colleen E; Edwards, Andrew; Goldhaber, Joshua; Kaplan, Jack; Lingrel, Jerry B; Pavlovic, Davor; Philipson, Kenneth; Sipido, Karin R; Xie, Zi-Jian

    2015-01-01

    This paper is the third in a series of reviews published in this issue resulting from the University of California Davis Cardiovascular Symposium 2014: Systems approach to understanding cardiac excitation–contraction coupling and arrhythmias: Na+ channel and Na+ transport. The goal of the symposium was to bring together experts in the field to discuss points of consensus and controversy on the topic of sodium in the heart. The present review focuses on cardiac Na+/Ca2+ exchange (NCX) and Na+/K+-ATPase (NKA). While the relevance of Ca2+ homeostasis in cardiac function has been extensively investigated, the role of Na+ regulation in shaping heart function is often overlooked. Small changes in the cytoplasmic Na+ content have multiple effects on the heart by influencing intracellular Ca2+ and pH levels thereby modulating heart contractility. Therefore it is essential for heart cells to maintain Na+ homeostasis. Among the proteins that accomplish this task are the Na+/Ca2+ exchanger (NCX) and the Na+/K+ pump (NKA). By transporting three Na+ ions into the cytoplasm in exchange for one Ca2+ moved out, NCX is one of the main Na+ influx mechanisms in cardiomyocytes. Acting in the opposite direction, NKA moves Na+ ions from the cytoplasm to the extracellular space against their gradient by utilizing the energy released from ATP hydrolysis. A fine balance between these two processes controls the net amount of intracellular Na+ and aberrations in either of these two systems can have a large impact on cardiac contractility. Due to the relevant role of these two proteins in Na+ homeostasis, the emphasis of this review is on recent developments regarding the cardiac Na+/Ca2+ exchanger (NCX1) and Na+/K+ pump and the controversies that still persist in the field. PMID:25772291

  15. Exploration of NaVOPO4 as a cathode for a Na-ion battery.

    PubMed

    Song, Jie; Xu, Maowen; Wang, Long; Goodenough, John B

    2013-06-11

    Monoclinic NaVOPO4 is explored as a cathode material for a sodium ion battery. It exhibits electrochemical activity operating at an average potential of 3.6 V (vs. Na(+)/Na) and delivers a reversible capacity of 90 mA h g(-1) at 1/15 C.

  16. Kinetin Reversal of NaCl Effects

    PubMed Central

    Katz, Adriana; Dehan, Klara; Itai, Chanan

    1978-01-01

    Leaf discs of Nicotiana rustica L. were floated on NaCl in the presence of kinetin or abscisic acid. On the 5th day 14CO2 fixation, [3H]leucine incorporation, stomatal conductance, and chlorophyll content were determined. Kinetin either partially or completely reversed the inhibitory effects of NaCl while ABA had no effect. PMID:16660618

  17. High NA Nicrostepper Final Optical Design Report

    SciTech Connect

    Hudyma, R

    1999-09-24

    The development of a new EUV high NA small-field exposure tool has been proposed for obtaining mask defect printability data in a timeframe several years before beta-tools are available. The imaging system for this new Micro-Exposure Tool (MET), would have a numerical aperture (NA) of about 0.3, similar to the NA for a beta-tool, but substantially larger than the 0.10 NA for the Engineering Test Stand (ETS) and 0.088 NA for the existing 10x Microstepper. This memorandum discusses the development and summarizes the performance of the camera for the MET and includes a listing of the design prescription, detailed analysis of the distortion, and analysis demonstrating the capability to resolution 30 nm features under the conditions of partially coherent illumination.

  18. Negative electrodes for Na-ion batteries.

    PubMed

    Dahbi, Mouad; Yabuuchi, Naoaki; Kubota, Kei; Tokiwa, Kazuyasu; Komaba, Shinichi

    2014-08-07

    Research interest in Na-ion batteries has increased rapidly because of the environmental friendliness of sodium compared to lithium. Throughout this Perspective paper, we report and review recent scientific advances in the field of negative electrode materials used for Na-ion batteries. This paper sheds light on negative electrode materials for Na-ion batteries: carbonaceous materials, oxides/phosphates (as sodium insertion materials), sodium alloy/compounds and so on. These electrode materials have different reaction mechanisms for electrochemical sodiation/desodiation processes. Moreover, not only sodiation-active materials but also binders, current collectors, electrolytes and electrode/electrolyte interphase and its stabilization are essential for long cycle life Na-ion batteries. This paper also addresses the prospect of Na-ion batteries as low-cost and long-life batteries with relatively high-energy density as their potential competitive edge over the commercialized Li-ion batteries.

  19. Na+ binding to the Na(+)-glucose cotransporter is potential dependent.

    PubMed

    Bennett, E; Kimmich, G A

    1992-02-01

    Activity of the Na(+)-glucose cotransporter in LLC-PK1 epithelial cells was assayed by measuring sugar-induced currents (IAMG) using whole cell recording techniques. IAMG was compared among cells by standardizing the measured currents to cell size using cell capacitance measurements. IAMG at a given membrane potential was measured as a function of alpha-methylglucoside (AMG) concentration and can be fit to Michaelis-Menten kinetics. IAMG at varying Na+ concentrations can be described by the Hill equation with a Hill coefficient of 1.6 at all tested potentials. At high external Na+ levels (155 mM), Na+ is at least 90% saturating at all tested potentials. Maximal currents at a given membrane potential (Im) are calculated from the Michaelis-Menten equation fit to data measuring IAMG vs. AMG concentration at a constant Na+ concentration. Im showed potential dependence under all conditions. Potential-dependent Na+ binding rate(s) cannot alone explain the observed potential dependence of Im under saturating Na+ conditions. Therefore, because Im is potential dependent, at least one step of the transport cycle other than external Na+ binding must be potential dependent. Im was also calculated from data taken at 40 mM external Na+. At all potentials studied, Im at 155 mM Na+ is greater than Im calculated at 40 mM Na+. This implies that the rate of external Na+ binding to the transporter at 40 mM also affects the maximal transport rate. Furthermore, Im at 40 mM external Na+ increases with hyperpolarization faster than Im at 155 mM Na+. Together, these facts indicate that the rate at which Na+ binds to the transporter is also potential dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Na-doped optical Germanium bulk crystals

    NASA Astrophysics Data System (ADS)

    Pekar, G. S.; Singaevsky, A. F.

    2012-09-01

    In an effort to develop a material for infrared (IR) optics with improved parameters, bulk crystals of optical germanium doped with Na have been first grown and studied. Single-crystalline and coarse-crystalline Ge:Na boules of different shapes and dimensions, up to 10 kg by weight, have been grown. Sodium was incorporated into the Ge crystal during the crystal growing from the melt. Despite the fact that Na contamination in the source material was not strictly controlled, the density of Na in the grown crystals determined by the neutron activation analysis as well as by the glow discharge mass spectrometry did not exceed 1015 cm-3. Just this value may be supposed to be close to the solubility limit of Na incorporated in Ge in the course of bulk crystal growth. A first demonstration of donor behavior of Na in bulk Ge crystals is made by means of a thermoelectric type of testing. An interstitial location of Na impurity has been verified by experiments on donor drift in the dc electric field. The crystals are grown with free electron density in the range from 5ṡ1013 to 4ṡ1014 cm-3 which is optimal for using Ge crystals as an optical material for fabricating passive elements of the IR technique. A comparison between the properties of Ge:Na crystals and Ge crystals doped with Sb, a conventional impurity in optical germanium, grown under the same technological conditions and from the same intrinsic Ge as a source material, revealed a number of advantages of Ge:Na crystals; among them, the higher transparency in the IR region, smaller radiation scattering and higher regular optical transmission, lower dislocation density, more uniform distribution of electrical and optical characteristics over the crystal volume, the identity of optical parameters in the single-crystalline, and coarse-crystalline boules. No degradation of optical elements fabricated from Ge:Na crystals was detected in the course of their commercial application, starting from 1998.

  1. Pharmacological modulation of human cardiac Na+ channels.

    PubMed

    Krafte, D S; Davison, K; Dugrenier, N; Estep, K; Josef, K; Barchi, R L; Kallen, R G; Silver, P J; Ezrin, A M

    1994-02-15

    Pharmacological modulation of human sodium current was examined in Xenopus oocytes expressing human heart Na+ channels. Na+ currents activated near -50 mV with maximum current amplitudes observed at -20 mV. Steady-state inactivation was characterized by a V1/2 value of -57 +/- 0.5 mV and a slope factor (k) of 7.3 +/- 0.3 mV. Sodium currents were blocked by tetrodotoxin with an IC50 value of 1.8 microM. These properties are consistent with those of Na+ channels expressed in mammalian myocardial cells. We have investigated the effects of several pharmacological agents which, with the exception of lidocaine, have not been characterized against cRNA-derived Na+ channels expressed in Xenopus oocytes. Lidocaine, quinidine and flecainide blocked resting Na+ channels with IC50 values of 521 microM, 198 microM, and 41 microM, respectively. Use-dependent block was also observed for all three agents, but concentrations necessary to induce block were higher than expected for quinidine and flecainide. This may reflect differences arising due to expression in the Xenopus oocyte system or could be a true difference in the interaction between human cardiac Na+ channels and these drugs compared to other mammalian Na+ channels. Importantly, however, this result would not have been predicted based upon previous studies of mammalian cardiac Na+ channels. The effects of DPI 201-106, RWJ 24517, and BDF 9148 were also tested and all three agents slowed and/or removed Na+ current inactivation, reduced peak current amplitudes, and induced use-dependent block. These data suggest that the alpha-subunit is the site of interaction between cardiac Na+ channels and Class I antiarrhythmic drugs as well as inactivation modifiers such as DPI 201-106.

  2. Long range intermolecular interactions between the alkali diatomics Na2, K2, and NaK

    NASA Astrophysics Data System (ADS)

    Zemke, Warren T.; Byrd, Jason N.; Michels, H. Harvey; Montgomery, John A.; Stwalley, William C.

    2010-06-01

    Long range interactions between the ground state alkali diatomics Na2-Na2, K2-K2, Na2-K2, and NaK-NaK are examined. Interaction energies are first determined from ab initio calculations at the coupled-cluster with singles, doubles, and perturbative triples [CCSD(T)] level of theory, including counterpoise corrections. Long range energies calculated from diatomic molecular properties (polarizabilities and dipole and quadrupole moments) are then compared with the ab initio energies. A simple asymptotic model potential ELR=Eelec+Edisp+Eind is shown to accurately represent the intermolecular interactions for these systems at long range.

  3. Long range intermolecular interactions between the alkali diatomics Na(2), K(2), and NaK.

    PubMed

    Zemke, Warren T; Byrd, Jason N; Michels, H Harvey; Montgomery, John A; Stwalley, William C

    2010-06-28

    Long range interactions between the ground state alkali diatomics Na(2)-Na(2), K(2)-K(2), Na(2)-K(2), and NaK-NaK are examined. Interaction energies are first determined from ab initio calculations at the coupled-cluster with singles, doubles, and perturbative triples [CCSD(T)] level of theory, including counterpoise corrections. Long range energies calculated from diatomic molecular properties (polarizabilities and dipole and quadrupole moments) are then compared with the ab initio energies. A simple asymptotic model potential E(LR)=E(elec)+E(disp)+E(ind) is shown to accurately represent the intermolecular interactions for these systems at long range.

  4. Cytosolic Na+ controls and epithelial Na+ channel via the Go guanine nucleotide-binding regulatory protein.

    PubMed Central

    Komwatana, P; Dinudom, A; Young, J A; Cook, D I

    1996-01-01

    In tight Na+-absorbing epithelial cells, the fate of Na+ entry through amiloride-sensitive apical membrane Na+ channels is matched to basolateral Na+ extrusion so that cell Na+ concentration and volume remain steady. Control of this process by regulation of apical Na+ channels has been attributed to changes in cytosolic Ca2+ concentration or pH, secondary to changes in cytosolic Na+ concentration, although cytosolic Cl- seems also to be involved. Using mouse mandibular gland duct cells, we now demonstrate that increasing cytosolic Na+ concentration inhibits apical Na+ channels independent of changes in cytosolic Ca2+, pH, or Cl-, and the effect is blocked by GDP-beta-S, pertussis toxin, and antibodies against the alpha-subunits of guanine nucleotide-binding regulatory proteins (Go). In contrast, the inhibitory effect of cytosolic anions is blocked by antibodies to inhibitory guanine nucleotide-binding regulatory proteins (Gi1/Gi2. It thus appears that apical Na+ channels are regulated by Go and Gi proteins, the activities of which are controlled, respectively, by cytosolic Na+ and Cl-. Images Fig. 4 PMID:8755611

  5. Cytosolic Na+ Controls an Epithelial Na+ Channel Via the Go Guanine Nucleotide-Binding Regulatory Protein

    NASA Astrophysics Data System (ADS)

    Komwatana, P.; Dinudom, A.; Young, J. A.; Cook, D. I.

    1996-07-01

    In tight Na+-absorbing epithelial cells, the rate of Na+ entry through amiloride-sensitive apical membrane Na+ channels is matched to basolateral Na+ extrusion so that cell Na+ concentration and volume remain steady. Control of this process by regulation of apical Na+ channels has been attributed to changes in cytosolic Ca2+ concentration or pH, secondary to changes in cytosolic Na+ concentration, although cytosolic Cl- seems also to be involved. Using mouse mandibular gland duct cells, we now demonstrate that increasing cytosolic Na+ concentration inhibits apical Na+ channels independent of changes in cytosolic Ca2+, pH, or Cl-, and the effect is blocked by GDP-β -S, pertussis toxin, and antibodies against the α -subunits of guanine nucleotide-binding regulatory proteins (Go). In contrast, the inhibitory effect of cytosolic anions is blocked by antibodies to inhibitory guanine nucleotide-binding regulatory proteins (Gi1/Gi2. It thus appears that apical Na+ channels are regulated by Go and Gi proteins, the activities of which are controlled, respectively, by cytosolic Na+ and Cl-.

  6. Anomalously high Na(+) and low Li(+) mobility in intercalated Na2Ti6O13.

    PubMed

    Ling, Chen; Zhang, Ruigang

    2017-04-12

    We report an anomalous diffusion behavior in intercalated Na2Ti6O13. Using first-principles calculations, the direct migration of inserted Na(+) along the tunnel direction is predicted to have a barrier of 0.24-0.44 eV, while the migration of inserted Li(+) along the tunnel direction has a barrier of 0.86-1.15 eV. Although Li(+) can also diffuse along a zig-zag path in the tunnel, the barrier of 0.86-0.99 eV is still much higher than that for Na(+). Our results surprisingly lead to the conclusion that the diffusion of larger Na(+) is 4-8 orders of magnitude faster than Li(+) in the same host lattice, and explain the experimentally observed exceptional rate capability of Na2Ti6O13 as the Na-ion battery anode. The anomalous diffusion behavior is attributed to the geometric features of Na2Ti6O13. For migration of Li(+) it is necessary to weaken Li-O bonds and to overcome the repulsion between Li and host Na ions simultaneously, while for Na(+) diffusion the improved Na-O bonding at the transition state partially compensates for the energy penalty from the repulsion of host Na ions.

  7. Extracellular Na+ levels regulate formation and activity of the NaX/alpha1-Na+/K+-ATPase complex in neuronal cells

    PubMed Central

    Berret, Emmanuelle; Smith, Pascal Y.; Henry, Mélaine; Soulet, Denis; Hébert, Sébastien S.; Toth, Katalin; Mouginot, Didier; Drolet, Guy

    2014-01-01

    MnPO neurons play a critical role in hydromineral homeostasis regulation by acting as sensors of extracellular sodium concentration ([Na+]out). The mechanism underlying Na+-sensing involves Na+-flow through the NaX channel, directly regulated by the Na+/K+-ATPase α1-isoform which controls Na+-influx by modulating channel permeability. Together, these two partners form a complex involved in the regulation of intracellular sodium ([Na+]in). Here we aim to determine whether environmental changes in Na+ could actively modulate the NaX/Na+/K+-ATPase complex activity. We investigated the complex activity using patch-clamp recordings from rat MnPO neurons and Neuro2a cells. When the rats were fed with a high-salt-diet, or the [Na+] in the culture medium was increased, the activity of the complex was up-regulated. In contrast, drop in environmental [Na+] decreased the activity of the complex. Interestingly under hypernatremic condition, the colocalization rate and protein level of both partners were up-regulated. Under hyponatremic condition, only NaX protein expression was increased and the level of NaX/Na+/K+-ATPase remained unaltered. This unbalance between NaX and Na+/K+-ATPase pump proportion would induce a bigger portion of Na+/K+-ATPase-control-free NaX channel. Thus, we suggest that hypernatremic environment increases NaX/Na+/K+-ATPase α1-isoform activity by increasing the number of both partners and their colocalization rate, whereas hyponatremic environment down-regulates complex activity via a decrease in the relative number of NaX channels controlled by the pump. PMID:25538563

  8. Laser-induced ionization of Na vapor

    SciTech Connect

    Wu, R.C.Y.; Judge, D.L.; Roussel, F.; Carre, B.; Breger, P.; Spiess, G.

    1982-01-01

    The production of Na/sub 2//sup +/ ions by off-resonant laser excitation in the 5800-6200A region mainly results from two-photon absorption by the Na/sub 2/ molecule to highly excited gerade states followed by (a) direct ionization by absorbing a third photon or (b) coupling to the molecular Na/sub 2/ D/sup 1/PI..mu.. Rydberg state which is subsequently ionized by absorbing a third photon. This mechanism, i.e., a two-photon resonance three photon ionization process, explains a recent experimental observation of Roussel et al. It is suggested that the very same mechanism is also responsible for a similar observation reported by Polak-Dingels et al in their work using two crossed Na beams. In the latter two studies the laser-induced associative ionization processes were reported to be responsible for producing the Na/sub 2//sup +/ ion. From the ratio of molecular to atomic concentration in the crossed beam experiment of Polak-Dingels et al we estimate that the cross section for producing Na/sub 2//sup +/ through laser-induced associative ionization is at least four orders of magnitude smaller than ionization through the two-photon resonance three photon ionization process in Na/sub 2/ molecules.

  9. Laser-induced ionization of Na vapor

    NASA Astrophysics Data System (ADS)

    Wu, C. Y. Robert; Judge, D. L.; Roussel, F.; Carré, B.; Breger, P.; Spiess, G.

    1982-09-01

    The production of Na2+ ions by off-resonant laser excitation in the 5800-6200Å region mainly results from two-photon absorption by the Na2 molecule to highly excited gerade states followed by (a) direct ionization by absorbing a third photon or (b) coupling to the molecular Na2 D1Πu Rydberg state which is subsequently ionized by absorbing a third photon. This mechanism, i.e., a two-photon resonance three photon ionization process, explains a recent experimental observation of Roussel et al. It is suggested that the very same mechanism is also responsible for a similar observation reported by Polak-Dingels et al in their work using two crossed Na beams. In the latter two studies the laser-induced associative ionization processes were reported to be responsible for producing the Na2+ ion. From the ratio of molecular to atomic concentration in the crossed beam experiment of Polak-Dingels et al. we estimate that the cross section for producing Na2+ through laser-induced associative ionization is at least four orders of magnitude smaller than ionization through the two-photon resonance three photon ionization process in Na2 molecules.

  10. NMR studies on Na+ transport in Synechococcus PCC 6311

    NASA Technical Reports Server (NTRS)

    Nitschmann, W. H.; Packer, L.

    1992-01-01

    The freshwater cyanobacterium Synechococcus PCC 6311 is able to adapt to grow after sudden exposure to salt (NaCl) stress. We have investigated the mechanism of Na+ transport in these cells during adaptation to high salinity. Na+ influx under dark aerobic conditions occurred independently of delta pH or delta psi across the cytoplasmic membrane, ATPase activity, and respiratory electron transport. These findings are consistent with the existence of Na+/monovalent anion cotransport or simultaneous Na+/H+ +anion/OH- exchange. Na+ influx was dependent on Cl-, Br-, NO3-, or NO2-. No Na+ uptake occurred after addition of NaI, NaHCO3, or Na2SO4. Na+ extrusion was absolutely dependent on delta pH and on an ATPase activity and/or on respiratory electron transport. This indicates that Na+ extrusion via Na+/H+ exchange is driven by primary H+ pumps in the cytoplasmic membrane. Cells grown for 4 days in 0.5 m NaCl medium, "salt-grown cells," differ from control cells by a lower maximum velocity of Na+ influx and by lower steady-state ratios of [Na+]in/[Na+]out. These results indicate that cells grown in high-salt medium increase their capacity to extrude Na+. During salt adaptation Na+ extrusion driven by respiratory electron transport increased from about 15 to 50%.

  11. Myocardial Na,K-ATPase: Clinical aspects

    PubMed Central

    Kjeldsen, Keld

    2003-01-01

    The specific binding of digitalis glycosides to Na,K-ATPase is used as a tool for Na,K-ATPase quantification with high accuracy and precision. In myocardial biopsies from patients with heart failure, total Na,K-ATPase concentration is decreased by around 40%; a correlation exists between a decrease in heart function and a decrease in Na,K-ATPase concentration. During digitalization, around 30% of remaining pumps are occupied by digoxin. Myocardial Na,K-ATPase is also influenced by other drugs used for the treatment of heart failure. Thus, potassium loss during diuretic therapy has been found to reduce myocardial Na,K-ATPase, whereas angiotensin-converting enzyme inhibitors may stimulate Na,K pump activity. Furthermore, hyperaldosteronism induced by heart failure has been found to decrease Na,K-ATPase activity. Accordingly, treatment with the aldosterone antagonist, spironolactone, may also influence Na,K-ATPase activity. The importance of Na,K pump modulation with heart disease, inhibition in digitalization and other effects of medication should be considered in the context of sodium, potassium and calcium regulation. It is recommended that digoxin be administered to heart failure patients who, after institution of mortality-reducing therapy, still have heart failure symptoms, and that the therapy be continued if symptoms are revealed or reduced. Digitalis glycosides are the only safe inotropic drugs for oral use that improve hemodynamics in heart failure. An important aspect of myocardial Na,K pump affection in heart disease is its influence on extracellular potassium (Ke) homeostasis. Two important aspects should be considered: potassium handling among myocytes, and effects of potassium entering the extracellular space of the heart via the bloodstream. It should be noted that both of these aspects of Ke homeostasis are affected by regulatory aspects, eg, regulation of the Na,K pump by physiological and pathophysiological conditions, as well as by medical

  12. Characteristics and pharmacological regulation of epithelial Na+ channel (ENaC) and epithelial Na+ transport.

    PubMed

    Marunaka, Yoshinori

    2014-01-01

    Epithelial Na(+) transport participates in control of various body functions and conditions: e.g., homeostasis of body fluid content influencing blood pressure, control of amounts of fluids covering the apical surface of alveolar epithelial cells at appropriate levels for normal gas exchange, and prevention of bacterial/viral infection. Epithelial Na(+) transport via the transcellular pathway is mediated by the entry step of Na(+) across the apical membrane via Epithelial Na(+) Channel (ENaC) located at the apical membrane, and the extrusion step of Na(+) across the basolateral membrane via the Na(+),K(+)-ATPase located at the basolateral membrane. The rate-limiting step of the epithelial Na(+) transport via the transcellular pathway is generally recognized to be the entry step of Na(+) across the apical membrane via ENaC. Thus, up-/down-regulation of ENaC essentially participates in regulatory systems of blood pressure and normal gas exchange. Amount of ENaC-mediated Na(+) transport is determined by the number of ENaCs located at the apical membrane, activity (open probability) of individual ENaC located at the apical membrane, single channel conductance of ENaC located at the apical membrane, and driving force for the Na(+) entry via ENaCs across the apical membrane. In the present review article, I discuss the characteristics of ENaC and how these factors are regulated.

  13. Computational and Experimental Investigations of Na-Ion Conduction in Cubic Na3PSe4

    DOE PAGES

    Bo, Shou -Hang; Wang, Yan; Kim, Jae Chul; ...

    2015-11-17

    All-solid-state Na-ion batteries that operate at or close to room temperature are a promising next-generation battery technology with enhanced safety and reduced manufacturing cost. An indispensable component of this technology is the solid-state electrolyte that allows rapid shuttling of the mobile cation (i.e., Na+) between the cathode and anode. However, there are very few fast Na-ion conductors with ionic conductivity approaching that of the liquid counterparts (i.e., 1 mS cm–1). In this work, we present the synthesis and characterization of a fast Na-ion conductor, cubic Na3PSe4. This material possesses a room-temperature ionic conductivity exceeding 0.1 mS cm–1 and does notmore » require high-temperature sintering to minimize grain boundary resistance, making it a promising solid-state electrolyte candidate for all-solid-state Na-ion battery applications. On the basis of density functional theory, nudged elastic band, and molecular dynamics investigations, we demonstrate that the framework of cubic Na3PSe4 only permits rapid Na+ diffusion with the presence of defects, and that the formation of the Na vacancy (charge-balanced by slight Se2– oxidation) is more energetically favorable among the various defects considered. This finding provides important guidelines to further improve Na-ion conductivity in this class of materials.« less

  14. Glutathionylation-Dependence of Na(+)-K(+)-Pump Currents Can Mimic Reduced Subsarcolemmal Na(+) Diffusion.

    PubMed

    Garcia, Alvaro; Liu, Chia-Chi; Cornelius, Flemming; Clarke, Ronald J; Rasmussen, Helge H

    2016-03-08

    The existence of a subsarcolemmal space with restricted diffusion for Na(+) in cardiac myocytes has been inferred from a transient peak electrogenic Na(+)-K(+) pump current beyond steady state on reexposure of myocytes to K(+) after a period of exposure to K(+)-free extracellular solution. The transient peak current is attributed to enhanced electrogenic pumping of Na(+) that accumulated in the diffusion-restricted space during pump inhibition in K(+)-free extracellular solution. However, there are no known physical barriers that account for such restricted Na(+) diffusion, and we examined if changes of activity of the Na(+)-K(+) pump itself cause the transient peak current. Reexposure to K(+) reproduced a transient current beyond steady state in voltage-clamped ventricular myocytes as reported by others. Persistence of it when the Na(+) concentration in patch pipette solutions perfusing the intracellular compartment was high and elimination of it with K(+)-free pipette solution could not be reconciled with restricted subsarcolemmal Na(+) diffusion. The pattern of the transient current early after pump activation was dependent on transmembrane Na(+)- and K(+) concentration gradients suggesting the currents were related to the conformational poise imposed on the pump. We examined if the currents might be accounted for by changes in glutathionylation of the β1 Na(+)-K(+) pump subunit, a reversible oxidative modification that inhibits the pump. Susceptibility of the β1 subunit to glutathionylation depends on the conformational poise of the Na(+)-K(+) pump, and glutathionylation with the pump stabilized in conformations equivalent to those expected to be imposed on voltage-clamped myocytes supported this hypothesis. So did elimination of the transient K(+)-induced peak Na(+)-K(+) pump current when we included glutaredoxin 1 in patch pipette solutions to reverse glutathionylation. We conclude that transient K(+)-induced peak Na(+)-K(+) pump current reflects the effect

  15. Catalysis of Na+ permeation in the bacterial sodium channel NaVAb

    PubMed Central

    Chakrabarti, Nilmadhab; Ing, Christopher; Payandeh, Jian; Zheng, Ning; Catterall, William A.; Pomès, Régis

    2013-01-01

    Determination of a high-resolution 3D structure of voltage-gated sodium channel NaVAb opens the way to elucidating the mechanism of ion conductance and selectivity. To examine permeation of Na+ through the selectivity filter of the channel, we performed large-scale molecular dynamics simulations of NaVAb in an explicit, hydrated lipid bilayer at 0 mV in 150 mM NaCl, for a total simulation time of 21.6 μs. Although the cytoplasmic end of the pore is closed, reversible influx and efflux of Na+ through the selectivity filter occurred spontaneously during simulations, leading to equilibrium movement of Na+ between the extracellular medium and the central cavity of the channel. Analysis of Na+ dynamics reveals a knock-on mechanism of ion permeation characterized by alternating occupancy of the channel by 2 and 3 Na+ ions, with a computed rate of translocation of (6 ± 1) × 106 ions⋅s−1 that is consistent with expectations from electrophysiological studies. The binding of Na+ is intimately coupled to conformational isomerization of the four E177 side chains lining the extracellular end of the selectivity filter. The reciprocal coordination of variable numbers of Na+ ions and carboxylate groups leads to their condensation into ionic clusters of variable charge and spatial arrangement. Structural fluctuations of these ionic clusters result in a myriad of ion binding modes and foster a highly degenerate, liquid-like energy landscape propitious to Na+ diffusion. By stabilizing multiple ionic occupancy states while helping Na+ ions diffuse within the selectivity filter, the conformational flexibility of E177 side chains underpins the knock-on mechanism of Na+ permeation. PMID:23803856

  16. Interaction between Na+ and H+ ions on Na-H exchange in sheep cardiac Purkinje fibers.

    PubMed

    Wu, M L; Vaughan-Jones, R D

    1997-04-01

    The interaction between Na+ and H+ ions upon Na-H exchange (NHE) was examined in sheep cardiac Purkinje fibers. Acid equivalent fluxes through NHE were examined using recordings of intracellular pH and Na+ in isolated preparations measured with ion selective microelectrodes. The extent of acid-extrusion by NHE was estimated from pH(i) recovery-rate, multiplied by beta(i) (intracellular buffering power) in response to an internal acid load induced by 20 mm NH4Cl removal (nominally HCO3- free media). A mixed inhibitory effect was found of extracellular H+ on external Na+-activation of NHE (i.e. an increase, at low pH(o), in the apparent Michaelis constant for external Na+ ions [K(Nao)(0.5)] and a decrease in the maximum transport rate [V(Nao)(max)]). In addition, we confirmed that the stoichiometry of Na(o) binding is unaffected by the pH(o) (between 7.5 and 6.5), showing a Hill coefficient close to one. The interaction between Na+ and H+ ions at the internal face of the cardiac NHE was also studied. Our evidence suggests that an increase in the intracellular Na+ ion concentration ([Na+]i) inhibits acid efflux and that this inhibition can be approximated by the decrease in thermodynamic driving force caused by reducing the transmembrane Na+ gradient. It appears, however, that small variations in [Na+]i from the normal resting level (intracellular sodium activity, a(i)Na = 7 to 13 mm) have little or no effect on acid efflux, suggesting that variation of a(i)Na is not a physiologically important controller of NHE activity in heart.

  17. Glutathionylation-Dependence of Na+-K+-Pump Currents Can Mimic Reduced Subsarcolemmal Na+ Diffusion

    PubMed Central

    Garcia, Alvaro; Liu, Chia-Chi; Cornelius, Flemming; Clarke, Ronald J.; Rasmussen, Helge H.

    2016-01-01

    The existence of a subsarcolemmal space with restricted diffusion for Na+ in cardiac myocytes has been inferred from a transient peak electrogenic Na+-K+ pump current beyond steady state on reexposure of myocytes to K+ after a period of exposure to K+-free extracellular solution. The transient peak current is attributed to enhanced electrogenic pumping of Na+ that accumulated in the diffusion-restricted space during pump inhibition in K+-free extracellular solution. However, there are no known physical barriers that account for such restricted Na+ diffusion, and we examined if changes of activity of the Na+-K+ pump itself cause the transient peak current. Reexposure to K+ reproduced a transient current beyond steady state in voltage-clamped ventricular myocytes as reported by others. Persistence of it when the Na+ concentration in patch pipette solutions perfusing the intracellular compartment was high and elimination of it with K+-free pipette solution could not be reconciled with restricted subsarcolemmal Na+ diffusion. The pattern of the transient current early after pump activation was dependent on transmembrane Na+- and K+ concentration gradients suggesting the currents were related to the conformational poise imposed on the pump. We examined if the currents might be accounted for by changes in glutathionylation of the β1 Na+-K+ pump subunit, a reversible oxidative modification that inhibits the pump. Susceptibility of the β1 subunit to glutathionylation depends on the conformational poise of the Na+-K+ pump, and glutathionylation with the pump stabilized in conformations equivalent to those expected to be imposed on voltage-clamped myocytes supported this hypothesis. So did elimination of the transient K+-induced peak Na+-K+ pump current when we included glutaredoxin 1 in patch pipette solutions to reverse glutathionylation. We conclude that transient K+-induced peak Na+-K+ pump current reflects the effect of conformation-dependent β1 pump subunit

  18. Thermodynamic Model for the Solubility of Cr(OH)(3)(am) in Concentrated NaOH and NaOH-NaNO3 Solutions

    SciTech Connect

    Rai, Dhanpat ); Hess, Nancy J. ); Rao, Linfeng; Zhang, Zhicheng; Felmy, Andrew R. ); Moore, Dean A. ); Clark, Sue B.; Lumetta, Gregg J. )

    2001-12-01

    The objectives of this study were to develop a reliable thermodynamic model for predicting Cr(III) behavior in concentrated NaOH and in mixed NaOH-NaNO3 solutions for application to effective caustic leaching strategies for high-level tank sludges. To meet these objectives, the solubility of Cr(OH)3(am) was measured in 0.003 to 10.5 m NaOH, 3.0 m es in NaOH concentration...

  19. Erythrocyte 22Na+ influx in hypertension

    SciTech Connect

    Shalev, O.; Eaton, J.W.; Ben-Ishay, D.

    1984-01-01

    We assessed 22Na+ uptake by erythrocytes (RBC) from 38 individuals with essential hypertension and 37 healthy controls. All subjects were male, white, non-obese and with normal renal function, obviating sex, race, hormonal, ponderal and renal factors known to influence RBC Na+ handling. The mean +/- sem 22Na+ uptake of the patients was 284 +/- 16 mumole/liter RBC/hour while that of normal controls was 249 +/- 11 mumole/liter RBC/hour; although the difference reached borderline significance, individual values showed considerable overlap. Consequently, in our population, RBC 22Na+ uptake is not a reliable marker for essential hypertension. We believe that previous studies should be reassessed with regard to patients' characteristics and future studies employ rigorous criteria in selection of subjects.

  20. Hydrogen-fluorine exchange in NaBH4-NaBF4.

    PubMed

    Rude, L H; Filsø, U; D'Anna, V; Spyratou, A; Richter, B; Hino, S; Zavorotynska, O; Baricco, M; Sørby, M H; Hauback, B C; Hagemann, H; Besenbacher, F; Skibsted, J; Jensen, T R

    2013-11-07

    Hydrogen-fluorine exchange in the NaBH4-NaBF4 system is investigated using a range of experimental methods combined with DFT calculations and a possible mechanism for the reactions is proposed. Fluorine substitution is observed using in situ synchrotron radiation powder X-ray diffraction (SR-PXD) as a new Rock salt type compound with idealized composition NaBF2H2 in the temperature range T = 200 to 215 °C. Combined use of solid-state (19)F MAS NMR, FT-IR and DFT calculations supports the formation of a BF2H2(-) complex ion, reproducing the observation of a (19)F chemical shift at -144.2 ppm, which is different from that of NaBF4 at -159.2 ppm, along with the new absorption bands observed in the IR spectra. After further heating, the fluorine substituted compound becomes X-ray amorphous and decomposes to NaF at ~310 °C. This work shows that fluorine-substituted borohydrides tend to decompose to more stable compounds, e.g. NaF and BF3 or amorphous products such as closo-boranes, e.g. Na2B12H12. The NaBH4-NaBF4 composite decomposes at lower temperatures (300 °C) compared to NaBH4 (476 °C), as observed by thermogravimetric analysis. NaBH4-NaBF4 (1:0.5) preserves 30% of the hydrogen storage capacity after three hydrogen release and uptake cycles compared to 8% for NaBH4 as measured using Sievert's method under identical conditions, but more than 50% using prolonged hydrogen absorption time. The reversible hydrogen storage capacity tends to decrease possibly due to the formation of NaF and Na2B12H12. On the other hand, the additive sodium fluoride appears to facilitate hydrogen uptake, prevent foaming, phase segregation and loss of material from the sample container for samples of NaBH4-NaF.

  1. Deliquescence of NaCl-NaNO3, KNO3-NaNO3, and NaCl-KNO3 Salt Mixtures From 90 to 120?C

    SciTech Connect

    Carroll, S A; Craig, L; Wolery, T J

    2004-10-20

    We conducted reversed deliquescence experiments in saturated NaCl-NaNO{sub 3}-H{sub 2}O, KNO{sub 3}-NaNO{sub 3}-H{sub 2}O, and NaCl-KNO{sub 3}-H{sub 2}O systems from 90 to 120 C as a function of relative humidity and solution composition. NaCl, NaNO{sub 3}, and KNO{sub 3} represent members of dust salt assemblages that are likely to deliquesce and form concentrated brines on high-level radioactive waste package surfaces in a repository environment at Yucca Mountain, NV, USA. Discrepancy between model prediction and experimental code can be as high as 8% for relative humidity and 50% for dissolved ion concentration. The discrepancy is attributed primarily to the use of 25 C models for Cl-NO{sub 3} and K-NO{sub 3} ion interactions in the current Yucca Mountain Project high-temperature Pitzer model to describe the non-ideal behavior of these highly concentrated solutions.

  2. Theoretical study of Na-atom emission from NaCl (100) surfaces

    NASA Astrophysics Data System (ADS)

    Puchin, Vladimir; Shluger, Alexander; Nakai, Yasuo; Itoh, Noriaki

    1994-04-01

    Several models for the elementary processes causing the emission of alkali atoms by electronic excitation of NaCl (100) surfaces have been investigated theoretically. First, the desorption of a Na atom neighboring an electronically excited F center on the surface is simulated using a quantum-mechanical embedded-cluster technique. It is shown that emission of a Na atom is energetically favorable. The kinetics of this process is shown to be controlled by the probability of a nonradiative transition between the two states: the excited state of the F center and that corresponding to a Na atom desorbing from the surface. The potential barrier for desorption of an excited Na atom from the excited F-center state is found to be 2.1 eV. It is also found that the energy for emission of a Na atom from a cluster of F centers (the F3 center) is considerably reduced (for a certain configuration of the defect) with respect to the similar energy for a single F center. The energy barrier for emission of a Na atom neighboring an F' center on the surface is calculated to be 1 eV. It is shown that the electronic excitation of kinklike sites, with a Na atom at the edge, can lead to a barrierless emission of a Na atom, leaving a Vk-type defect behind. The results of calculations are discussed critically on the basis of existing experimental data.

  3. Glutamate Water Gates in the Ion Binding Pocket of Na(+) Bound Na(+), K(+)-ATPase.

    PubMed

    Han, Minwoo; Kopec, Wojciech; Solov'yov, Ilia A; Khandelia, Himanshu

    2017-01-13

    The dynamically changing protonation states of the six acidic amino acid residues in the ion binding pocket of the Na(+), K(+) -ATPase (NKA) during the ion transport cycle are proposed to drive ion binding, release and possibly determine Na(+) or K(+) selectivity. We use molecular dynamics (MD) and density functional theory (DFT) simulations to determine the protonation scheme of the Na(+) bound conformation of NKA. MD simulations of all possible protonation schemes show that the bound Na(+) ions are most stably bound when three or four protons reside in the binding sites, and that Glu954 in site III is always protonated. Glutamic acid residues in the three binding sites act as water gates, and their deprotonation triggers water entry to the binding sites. From DFT calculations of Na(+) binding energies, we conclude that three protons in the binding site are needed to effectively bind Na(+) from water and four are needed to release them in the next step. Protonation of Asp926 in site III will induce Na(+) release, and Glu327, Glu954 and Glu779 are all likely to be protonated in the Na(+) bound occluded conformation. Our data provides key insights into the role of protons in the Na(+) binding and release mechanism of NKA.

  4. Anion-coupled Na efflux mediated by the human red blood cell Na/K pump

    PubMed Central

    1990-01-01

    The red cell Na/K pump is known to continue to extrude Na when both Na and K are removed from the external medium. Because this ouabain- sensitive flux occurs in the absence of an exchangeable cation, it is referred to as uncoupled Na efflux. This flux is also known to be inhibited by 5 mM Nao but to a lesser extent than that inhibitable by ouabain. Uncoupled Na efflux via the Na/K pump therefore can be divided into a Nao-sensitive and Nao-insensitive component. We used DIDS- treated, SO4-equilibrated human red blood cells suspended in HEPES- buffered (pHo 7.4) MgSO4 or (Tris)2SO4, in which we measured 22Na efflux, 35SO4 efflux, and changes in the membrane potential with the fluorescent dye, diS-C3 (5). A principal finding is that uncoupled Na efflux occurs electroneurally, in contrast to the pump's normal electrogenic operation when exchanging Nai for Ko. This electroneutral uncoupled efflux of Na was found to be balanced by an efflux of cellular anions. (We were unable to detect any ouabain-sensitive uptake of protons, measured in an unbuffered medium at pH 7.4 with a Radiometer pH-STAT.) The Nao-sensitive efflux of Nai was found to be 1.95 +/- 0.10 times the Nao-sensitive efflux of (SO4)i, indicating that the stoichiometry of this cotransport is two Na+ per SO4=, accounting for 60-80% of the electroneutral Na efflux. The remainder portion, that is, the ouabain-sensitive Nao-insensitive component, has been identified as PO4-coupled Na transport and is the subject of a separate paper. That uncoupled Na efflux occurs as a cotransport with anions is supported by the result, obtained with resealed ghosts, that when internal and external SO4 was substituted by the impermeant anion, tartrate i,o, the efflux of Na was inhibited 60-80%. This inhibition could be relieved by the inclusion, before DIDS treatment, of 5 mM Cli,o. Addition of 10 mM Ko to tartrate i,o ghosts, with or without Cli,o, resulted in full activation of Na/K exchange and the pump's electrogenicity

  5. Glutamate Water Gates in the Ion Binding Pocket of Na+ Bound Na+, K+-ATPase

    PubMed Central

    Han, Minwoo; Kopec, Wojciech; Solov’yov, Ilia A.; Khandelia, Himanshu

    2017-01-01

    The dynamically changing protonation states of the six acidic amino acid residues in the ion binding pocket of the Na+, K+ -ATPase (NKA) during the ion transport cycle are proposed to drive ion binding, release and possibly determine Na+ or K+ selectivity. We use molecular dynamics (MD) and density functional theory (DFT) simulations to determine the protonation scheme of the Na+ bound conformation of NKA. MD simulations of all possible protonation schemes show that the bound Na+ ions are most stably bound when three or four protons reside in the binding sites, and that Glu954 in site III is always protonated. Glutamic acid residues in the three binding sites act as water gates, and their deprotonation triggers water entry to the binding sites. From DFT calculations of Na+ binding energies, we conclude that three protons in the binding site are needed to effectively bind Na+ from water and four are needed to release them in the next step. Protonation of Asp926 in site III will induce Na+ release, and Glu327, Glu954 and Glu779 are all likely to be protonated in the Na+ bound occluded conformation. Our data provides key insights into the role of protons in the Na+ binding and release mechanism of NKA. PMID:28084301

  6. Stoichiometry and Na+ binding cooperativity of rat and flounder renal type II Na+-Pi cotransporters.

    PubMed

    Forster, I C; Loo, D D; Eskandari, S

    1999-04-01

    The stoichiometry of the rat and flounder isoforms of the renal type II sodium-phosphate (Na+-Pi) cotransporter was determined directly by simultaneous measurements of phosphate (Pi)-induced inward current and uptake of radiolabeled Pi and Na+ in Xenopus laevis oocytes expressing the cotransporters. There was a direct correlation between the Pi-induced inward charge and Pi uptake into the oocytes; the slope indicated that one net inward charge was transported per Pi. There was also a direct correlation between the Pi-induced inward charge and Na+ influx; the slope indicated that the influx of three Na+ ions resulted in one net inward charge. This behavior was similar for both isoforms. We conclude that for both Na+-Pi cotransporter isoforms the Na+:Pi stoichiometry is 3:1 and that divalent Pi is the transported substrate. Steady-state activation of the currents showed that the Hill coefficients for Pi were unity for both isoforms, whereas for Na+, they were 1.8 (flounder) and 2.5 (rat). Therefore, despite significant differences in the apparent Na+ binding cooperativity, the estimated Na+:Pi stoichiometry was the same for both isoforms.

  7. Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na(+) and restricted dietary Na().

    PubMed

    Alshahrani, Saeed; Rapoport, Robert M; Soleimani, Manoocher

    2017-03-01

    Reduced renal Na(+) reabsorption along with restricted dietary Na(+) depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na(+) reabsorption and restricted dietary Na(+) associated with considerable hypotension and renin-angiotensin system activation: (1) the Na(+)-Cl(-)-Co-transporter (NCC) knockout (KO) with Na(+) restricted diet (0.1%, 2 weeks) and (2) the relatively more severe pendrin (apical chloride/bicarbonate exchanger) and NCC double KO. Contractile sensitivity to KCl, phenylephrine, and/or U46619 remained unaltered in aorta from both models. Maximal KCl and phenylephrine contraction expressed as force/aorta length from NCC KO with Na(+)-restricted diet remained unaltered, while in pendrin/NCC double KO were reduced to 49 and 64%, respectively. Wet weight of aorta from NCC KO with Na(+)-restricted diet remained unaltered, while pendrin/NCC double KO was reduced to 67%, consistent with decreased medial width determined with Verhoeff-Van Gieson stain. These findings suggest that hypotension associated with severe intravascular volume depletion, as the result of decreased renal Na(+) reabsorption, may in part be due to decreased contractile reactivity as a consequence of reduced vascular hypertrophy.

  8. Influence of sodium halides (NaF, NaCl, NaBr, NaI) on the photocatalytic performance of hydrothermally synthesized hematite photoanodes.

    PubMed

    Wang, Tsinghai; Huang, Mao-Chia; Hsieh, Yi-Kong; Chang, Wen-Sheng; Lin, Jing-Chie; Lee, Chih-Hao; Wang, Chu-Fang

    2013-08-28

    It has been suggested that a high concentration of Fe(3+) in solution, a low pH, and noncomplexing ions of high ionic strength are all essential for developing a high-quality hematite array. Our curiosity was piqued regarding the role of the electrolyte ions in the hydrothermal synthesis of hematite photoanodes. In this study, we prepared hematite photoanodes hydrothermally from precursor solutions of 0.1 M FeCl3 at pH 1.55 with a background electrolyte of 1.0 M sodium halide (NaF, NaCl, NaBr, or NaI). We compared the structures and properties of the as-obtained hematite photoanodes with those of the material prepared in 1.0 M NaNO3, the most widely adopted electrolyte in previous studies. Among our studied systems, we found that the hematite photoanode prepared in NaCl solution was the only one possessing properties similar to those of the sample obtained from the NaNO3 solution-most importantly in terms of photoelectrochemical performance (ca. 0.2 mA/cm(2) with +0.4 V vs SCE). The hematites obtained from the NaF, NaBr, and NaI solutions exhibited much lower (by approximately 2 orders of magnitude) photocurrent densities under the same conditions, possibly because of their relatively less ordered crystallinity and the absence of rodlike morphologies. Because the synthetic protocol was identical in each case, we believe that these two distinct features reflect the environments in which these hematite photoanodes were formed. Consistent with the latest studies reported in the literature of the X-ray photoelectron spectra of fast-frozen hematite colloids in aqueous solutions, it appears that the degree of surface ion loading at the electrolyte-hematite interface (Stern layer) is critical during the development of hematite photoanodes. We suspect that a lower ion surface loading benefits the hematite developing relatively higher-order and a rodlike texture, thereby improving the photoelectrochemical activity.

  9. Elastic Coulomb breakup of 34Na

    NASA Astrophysics Data System (ADS)

    Singh, G.; Shubhchintak, Chatterjee, R.

    2016-08-01

    Background: 34Na is conjectured to play an important role in the production of seed nuclei in the alternate r -process paths involving light neutron rich nuclei very near the β -stability line, and as such, it is important to know its ground state properties and structure to calculate rates of the reactions it might be involved in, in the stellar plasma. Found in the region of `island of inversion', its ground state might not be in agreement with normal shell model predictions. Purpose: The aim of this paper is to study the elastic Coulomb breakup of 34Na on 208Pb to give us a core of 33Na with a neutron and in the process we try and investigate the one neutron separation energy and the ground state configuration of 34Na. Method: A fully quantum mechanical Coulomb breakup theory within the architecture of post-form finite range distorted wave Born approximation extended to include the effects of deformation is used to research the elastic Coulomb breakup of 34Na on 208Pb at 100 MeV/u. The triple differential cross section calculated for the breakup is integrated over the desired components to find the total cross-section, momentum, and angular distributions as well as the average momenta, along with the energy-angular distributions. Results: The total one neutron removal cross section is calculated to test the possible ground state configurations of 34Na. The average momentum results along with energy-angular calculations indicate 34Na to have a halo structure. The parallel momentum distributions with narrow full widths at half-maxima signify the same. Conclusion: We have attempted to analyze the possible ground state configurations of 34Na and in congruity with the patterns in the `island of inversion' conclude that even without deformation, 34Na should be a neutron halo with a predominant contribution to its ground state most probably coming from 33Na(3 /2+)⊗ 2 p3 /2ν configuration. We also surmise that it would certainly be useful and rewarding to test our

  10. Quasi–solid state rechargeable Na-CO2 batteries with reduced graphene oxide Na anodes

    PubMed Central

    Hu, Xiaofei; Li, Zifan; Zhao, Yaran; Sun, Jianchao; Zhao, Qing; Wang, Jianbin; Tao, Zhanliang; Chen, Jun

    2017-01-01

    Na-CO2 batteries using earth-abundant Na and greenhouse gas CO2 are promising tools for mobile and stationary energy storage, but they still pose safety risks from leakage of liquid electrolyte and instability of the Na metal anode. These issues result in extremely harsh operating conditions of Na-CO2 batteries and increase the difficulty of scaling up this technology. We report the development of quasi–solid state Na-CO2 batteries with high safety using composite polymer electrolyte (CPE) and reduced graphene oxide (rGO) Na anodes. The CPE of PVDF-HFP [poly(vinylidene fluoride-co-hexafluoropropylene)]–4% SiO2/NaClO4–TEGDME (tetraethylene glycol dimethyl ether) has high ion conductivity (1.0 mS cm−1), robust toughness, a nonflammable matrix, and strong electrolyte-locking ability. In addition, the rGO-Na anode presents fast and nondendritic Na+ plating/stripping (5.7 to 16.5 mA cm−2). The improved kinetics and safety enable the constructed rGO-Na/CPE/CO2 batteries to successfully cycle in wide CO2 partial pressure window (5 to 100%, simulated car exhaust) and especially to run for 400 cycles at 500 mA g−1 with a fixed capacity of 1000 mA·hour g−1 in pure CO2. Furthermore, we scaled up the reversible capacity to 1.1 A·hour in pouch-type batteries (20 × 20 cm, 10 g, 232 Wh kg−1). This study makes quasi–solid state Na-CO2 batteries an attractive prospect. PMID:28164158

  11. Quasi-solid state rechargeable Na-CO2 batteries with reduced graphene oxide Na anodes.

    PubMed

    Hu, Xiaofei; Li, Zifan; Zhao, Yaran; Sun, Jianchao; Zhao, Qing; Wang, Jianbin; Tao, Zhanliang; Chen, Jun

    2017-02-01

    Na-CO2 batteries using earth-abundant Na and greenhouse gas CO2 are promising tools for mobile and stationary energy storage, but they still pose safety risks from leakage of liquid electrolyte and instability of the Na metal anode. These issues result in extremely harsh operating conditions of Na-CO2 batteries and increase the difficulty of scaling up this technology. We report the development of quasi-solid state Na-CO2 batteries with high safety using composite polymer electrolyte (CPE) and reduced graphene oxide (rGO) Na anodes. The CPE of PVDF-HFP [poly(vinylidene fluoride-co-hexafluoropropylene)]-4% SiO2/NaClO4-TEGDME (tetraethylene glycol dimethyl ether) has high ion conductivity (1.0 mS cm(-1)), robust toughness, a nonflammable matrix, and strong electrolyte-locking ability. In addition, the rGO-Na anode presents fast and nondendritic Na(+) plating/stripping (5.7 to 16.5 mA cm(-2)). The improved kinetics and safety enable the constructed rGO-Na/CPE/CO2 batteries to successfully cycle in wide CO2 partial pressure window (5 to 100%, simulated car exhaust) and especially to run for 400 cycles at 500 mA g(-1) with a fixed capacity of 1000 mA·hour g(-1) in pure CO2. Furthermore, we scaled up the reversible capacity to 1.1 A·hour in pouch-type batteries (20 × 20 cm, 10 g, 232 Wh kg(-1)). This study makes quasi-solid state Na-CO2 batteries an attractive prospect.

  12. Electrophysiological Determination of Submembrane Na(+) Concentration in Cardiac Myocytes.

    PubMed

    Hegyi, Bence; Bányász, Tamás; Shannon, Thomas R; Chen-Izu, Ye; Izu, Leighton T

    2016-09-20

    In the heart, Na(+) is a key modulator of the action potential, Ca(2+) homeostasis, energetics, and contractility. Because Na(+) currents and cotransport fluxes depend on the Na(+) concentration in the submembrane region, it is necessary to accurately estimate the submembrane Na(+) concentration ([Na(+)]sm). Current methods using Na(+)-sensitive fluorescent indicators or Na(+) -sensitive electrodes cannot measure [Na(+)]sm. However, electrophysiology methods are ideal for measuring [Na(+)]sm. In this article, we develop patch-clamp protocols and experimental conditions to determine the upper bound of [Na(+)]sm at the peak of action potential and its lower bound at the resting state. During the cardiac cycle, the value of [Na(+)]sm is constrained within these bounds. We conducted experiments in rabbit ventricular myocytes at body temperature and found that 1) at a low pacing frequency of 0.5 Hz, the upper and lower bounds converge at 9 mM, constraining the [Na(+)]sm value to ∼9 mM; 2) at 2 Hz pacing frequency, [Na(+)]sm is bounded between 9 mM at resting state and 11.5 mM; and 3) the cells can maintain [Na(+)]sm to the above values, despite changes in the pipette Na(+) concentration, showing autoregulation of Na(+) in beating cardiomyocytes.

  13. Interaction of NaCl(g) and HCl(g) with condensed NA2SO4

    NASA Technical Reports Server (NTRS)

    Stearns, C. A.; Kohl, F. J.; Fryburg, G. C.; Miller, R. A.

    1977-01-01

    The interaction of Na2SO4(l) with NaCl(g), HCl(g) and H2O(g) was studied in atmospheric pressure flowing air and oxygen at Na2SO4(l) temperatures of 900 and 1000 C. Thermomicrogravimetric and high pressure mass spectrometric sampling techniques were used. Experimental results establish that previously reported enhanced rates of weight loss of Na2SO4(l) in the presence of NaCl(g) are due to the reaction: Na2SO4(c) + 2HCl(g) = 2NaCl(g) + SO2(g) + H2O(g) + 1/2O2(g) being driven to the right in flowing gas systems. The HCl(g) is the product of hydrolysis of NaCl caused by small but significant amounts of H2O(g) present in the system. Thermochemical calculations are used to show that even with sub-ppm levels of H2O(g) present, significant quantities of HCl(g) are produced.

  14. Dynamics of Na + in a single crystal of Naβ″Al 2O 3

    NASA Astrophysics Data System (ADS)

    Fanjat, N.; Lucazeau, G.; Bates, J.; Dianoux, A. J.

    1989-01-01

    A single crystal of Naβ″ Al 2O 3 has been used to measure quasi-elastic neutron scattering spectra at 227 and 377°C. Fitted data are presented with a new model and the results are compared to those obtained with NaβAl 2O 3.

  15. Voltage dependence of Na translocation by the Na/K pump.

    PubMed

    Nakao, M; Gadsby, D C

    During each complete reaction cycle, the Na/K pump transports three Na ions out across the cell membrane and two K ions in. The resulting net extrusion of positive charge generates outward membrane current but, until now, it was unclear how that net charge movement occurs. Reasonable possibilities included a single positive charge moving outwards during Na translocation; or a single negative charge moving inwards during K translocation; or either positive or negative charges moving during both translocation steps, but in unequal quantities. Any step that involves net charge movement through the membrane must have voltage-dependent transition rates. Here we report measurements of transient, voltage-dependent, displacement currents generated by the pump when its normal Na/K transport cycle has been interrupted by removal of external K and it is thus constrained to carry out Na/Na exchange. The quantity and voltage sensitivity of the charge moved during these transient currents suggests that Na translocation includes a voltage-dependent transition involving movement of one positive charge across the membrane. This single step can thus fully account for the electrogenic nature of Na/K exchange. The result provides important new insight into the molecular mechanism of active cation transport.

  16. Dynamics of Na(+)(Benzene) + Benzene Association and Ensuing Na(+)(Benzene)2* Dissociation.

    PubMed

    Paul, Amit K; Kolakkandy, Sujitha; Hase, William L

    2015-07-16

    Chemical dynamics simulations were used to study Bz + Na(+)(Bz) → Na(+)(Bz)2* association and the ensuing dissociation of the Na(+)(Bz)2* cluster (Bz = benzene). An interesting and unexpected reaction found from the simulations is direct displacement, for which the colliding Bz molecule displaces the Bz molecule attached to Na(+), forming Na(+)(Bz). The rate constant for Bz + Na(+)(Bz) association was calculated at 750 and 1000 K, and found to decrease with increase in temperature. By contrast, the direct displacement rate constant increases with temperature. The cross section and rate constant for direct displacement are approximately an order of magnitude lower than those for association. The Na(+)(Bz)2* cluster, formed by association, dissociates with a biexponential probability, with the rate constant for the short-time component approximately an order of magnitude larger than that for the longer time component. The latter rate constant agrees with that of Rice-Ramsperger-Kassel-Marcus (RRKM) theory, consistent with rapid intramolecular vibrational energy redistribution (IVR) and intrinsic RRKM dynamics for the Na(+)(Bz)2* cluster. A coupled phase space model was used to analyze the biexponential dissociation probability.

  17. Low-affinity Na+ uptake in the halophyte Suaeda maritima.

    PubMed

    Wang, Suo-Min; Zhang, Jin-Lin; Flowers, Timothy J

    2007-10-01

    Na(+) uptake by plant roots has largely been explored using species that accumulate little Na(+) into their shoots. By way of contrast, the halophyte Suaeda maritima accumulates, without injury, concentrations of the order of 400 mM NaCl in its leaves. Here we report that cAMP and Ca(2+) (blockers of nonselective cation channels) and Li(+) (a competitive inhibitor of Na(+) uptake) did not have any significant effect on the uptake of Na(+) by the halophyte S. maritima when plants were in 25 or 150 mM NaCl (150 mM NaCl is near optimal for growth). However, the inhibitors of K(+) channels, TEA(+) (10 mM), Cs(+) (3 mM), and Ba(2+) (5 mM), significantly reduced the net uptake of Na(+) from 150 mM NaCl over 48 h, by 54%, 24%, and 29%, respectively. TEA(+) (10 mM), Cs(+) (3 mM), and Ba(2+) (1 mm) also significantly reduced (22)Na(+) influx (measured over 2 min in 150 mM external NaCl) by 47%, 30%, and 31%, respectively. In contrast to the situation in 150 mm NaCl, neither TEA(+) (1-10 mM) nor Cs(+) (0.5-10 mM) significantly reduced net Na(+) uptake or (22)Na(+) influx in 25 mM NaCl. Ba(2+) (at 5 mm) did significantly decrease net Na(+) uptake (by 47%) and (22)Na(+) influx (by 36% with 1 mM Ba(2+)) in 25 mM NaCl. K(+) (10 or 50 mM) had no effect on (22)Na(+) influx at concentrations below 75 mM NaCl, but the influx of (22)Na(+) was inhibited by 50 mM K(+) when the external concentration of NaCl was above 75 mM. The data suggest that neither nonselective cation channels nor a low-affinity cation transporter are major pathways for Na(+) entry into root cells. We propose that two distinct low-affinity Na(+) uptake pathways exist in S. maritima: Pathway 1 is insensitive to TEA(+) or Cs(+), but sensitive to Ba(2+) and mediates Na(+) uptake under low salinities (25 mM NaCl); pathway 2 is sensitive to TEA(+), Cs(+), and Ba(2+) and mediates Na(+) uptake under higher external salt concentrations (150 mM NaCl). Pathway 1 might be mediated by a high-affinity K transporter

  18. Anion-coupled Na efflux mediated by the human red blood cell Na/K pump

    SciTech Connect

    Dissing, S.; Hoffman, J.F. )

    1990-07-01

    The red cell Na/K pump is known to continue to extrude Na when both Na and K are removed from the external medium. Because this ouabain-sensitive flux occurs in the absence of an exchangeable cation, it is referred to as uncoupled Na efflux. This flux is also known to be inhibited by 5 mM Nao but to a lesser extent than that inhibitable by ouabain. Uncoupled Na efflux via the Na/K pump therefore can be divided into a Nao-sensitive and Nao-insensitive component. We used DIDS-treated, SO4-equilibrated human red blood cells suspended in HEPES-buffered (pHo 7.4) MgSO4 or (Tris)2SO4, in which we measured 22Na efflux, 35SO4 efflux, and changes in the membrane potential with the fluorescent dye, diS-C3 (5). A principal finding is that uncoupled Na efflux occurs electroneurally, in contrast to the pump's normal electrogenic operation when exchanging Nai for Ko. This electroneutral uncoupled efflux of Na was found to be balanced by an efflux of cellular anions. (We were unable to detect any ouabain-sensitive uptake of protons, measured in an unbuffered medium at pH 7.4 with a Radiometer pH-STAT.) The Nao-sensitive efflux of Nai was found to be 1.95 +/- 0.10 times the Nao-sensitive efflux of (SO4)i, indicating that the stoichiometry of this cotransport is two Na+ per SO4=, accounting for 60-80% of the electroneutral Na efflux. The remainder portion, that is, the ouabain-sensitive Nao-insensitive component, has been identified as PO4-coupled Na transport and is the subject of a separate paper. That uncoupled Na efflux occurs as a cotransport with anions is supported by the result, obtained with resealed ghosts, that when internal and external SO4 was substituted by the impermeant anion, tartrate i,o, the efflux of Na was inhibited 60-80%. This inhibition could be relieved by the inclusion, before DIDS treatment, of 5 mM Cli,o.

  19. A thermochemical explanation for the stability of NaCl3 and NaCl7

    NASA Astrophysics Data System (ADS)

    Fernandes de Farias, Robson

    2017-03-01

    Thermodynamically stable cubic and orthorhombic NaCl3 as well as NaCl7 have been synthesized (Zhang et al., 2013). In the present work, a thermochemical explanation for the stability of such unusual sodium chlorides is provided, based on lattice energy values. Using the Glasser-Jenkins generalized equation (Glasser and Jenkins, 2000) lattice energies (kJ mol-1) of -162.5, -168.9 and -113.1 are calculated for Pm3n NaCl3, Pnma NaCl3 and NaCl7, respectively. It is postulated that any NaxCly compound could be synthesized, if the ionic character of the Nasbnd Cl bond in the prepared compound remains around 80%, and the sodium charge below unit.

  20. Na-ion dynamics in Quasi-1D compound NaV2O4

    NASA Astrophysics Data System (ADS)

    Månsson, M.; Umegaki, I.; Nozaki, H.; Higuchi, Y.; Kawasaki, I.; Watanabe, I.; Sakurai, H.; Sugiyama, J.

    2014-12-01

    We have used the pulsed muon source at ISIS to study high-temperature Na-ion dynamics in the quasi-one-dimensional (Q1D) metallic antiferromagnet NaV2O4. By performing systematic zero-field and longitudinal-field measurements as a function of temperature we clearly distinguish that the hopping rate increases exponentially above Tdiff ≈ 250 K. The data is well fitted to an Arrhenius type equation typical for a diffusion process, showing that the Na-ions starts to be mobile above Tdiff. Such results make this compound very interesting for the tuning of Q1D magnetism using atomic-scale ion-texturing through the periodic potential from ordered Na-vacancies. Further, it also opens the door to possible use of NaV2O4 and related compounds in energy related applications.

  1. Na/K pump inactivation, subsarcolemmal Na measurements, and cytoplasmic ion turnover kinetics contradict restricted Na spaces in murine cardiac myocytes.

    PubMed

    Lu, Fang-Min; Hilgemann, Donald W

    2017-07-03

    Decades ago, it was proposed that Na transport in cardiac myocytes is modulated by large changes in cytoplasmic Na concentration within restricted subsarcolemmal spaces. Here, we probe this hypothesis for Na/K pumps by generating constitutive transsarcolemmal Na flux with the Na channel opener veratridine in whole-cell patch-clamp recordings. Using 25 mM Na in the patch pipette, pump currents decay strongly during continuous activation by extracellular K (τ, ∼2 s). In contradiction to depletion hypotheses, the decay becomes stronger when pump currents are decreased by hyperpolarization. Na channel currents are nearly unchanged by pump activity in these conditions, and conversely, continuous Na currents up to 0.5 nA in magnitude have negligible effects on pump currents. These outcomes are even more pronounced using 50 mM Li as a cytoplasmic Na congener. Thus, the Na/K pump current decay reflects mostly an inactivation mechanism that immobilizes Na/K pump charge movements, not cytoplasmic Na depletion. When channel currents are increased beyond 1 nA, models with unrestricted subsarcolemmal diffusion accurately predict current decay (τ ∼15 s) and reversal potential shifts observed for Na, Li, and K currents through Na channels opened by veratridine, as well as for Na, K, Cs, Li, and Cl currents recorded in nystatin-permeabilized myocytes. Ion concentrations in the pipette tip (i.e., access conductance) track without appreciable delay the current changes caused by sarcolemmal ion flux. Importantly, cytoplasmic mixing volumes, calculated from current decay kinetics, increase and decrease as expected with osmolarity changes (τ >30 s). Na/K pump current run-down over 20 min reflects a failure of pumps to recover from inactivation. Simulations reveal that pump inactivation coupled with Na-activated recovery enhances the rapidity and effectivity of Na homeostasis in cardiac myocytes. In conclusion, an autoregulatory mechanism enhances cardiac Na/K pump activity when

  2. Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na+ replete mice.

    PubMed

    Vitzthum, Helga; Seniuk, Anika; Schulte, Laura Helene; Müller, Maxie Luise; Hetz, Hannah; Ehmke, Heimo

    2014-03-01

    A network of kinases, including WNKs, SPAK and Sgk1, is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as a key hormone in orchestrating these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load. We therefore investigated the integrated blood pressure, renal, hormonal and gene and protein expression responses to large changes of K+ intake in Na+ replete mice. Both low and high K+ intake increased blood pressure and caused Na+ retention. Low K+ intake was accompanied by an upregulation of the sodium-chloride cotransporter (NCC) and its activating kinase SPAK, and inhibition of NCC normalized blood pressure. Renal responses were unaffected by angiotensin AT1 receptor antagonism, indicating that low K+ intake activates the distal nephron by an angiotensin-independent mode of action. High K+ intake was associated with elevated plasma aldosterone concentrations and an upregulation of the epithelial sodium channel (ENaC) and its activating kinase Sgk1. Surprisingly, high K+ intake increased blood pressure even during ENaC or mineralocorticoid receptor antagonism, suggesting the contribution of aldosterone-independent mechanisms. These findings show that in a Na+ replete state, changes in K+ intake induce specific molecular and functional adaptations in the distal nephron that cause a functional coupling of renal K+ and Na+ handling, resulting in Na+ retention and high blood pressure when K+ intake is either restricted or excessively increased.

  3. Changes in Intracellular Na+ following Enhancement of Late Na+ Current in Virtual Human Ventricular Myocytes

    PubMed Central

    Giles, Wayne R.

    2016-01-01

    The slowly inactivating or late Na+ current, INa-L, can contribute to the initiation of both atrial and ventricular rhythm disturbances in the human heart. However, the cellular and molecular mechanisms that underlie these pro-arrhythmic influences are not fully understood. At present, the major working hypothesis is that the Na+ influx corresponding to INa-L significantly increases intracellular Na+, [Na+]i; and the resulting reduction in the electrochemical driving force for Na+ reduces and (may reverse) Na+/Ca2+ exchange. These changes increase intracellular Ca2+, [Ca2+]i; which may further enhance INa-L due to calmodulin-dependent phosphorylation of the Na+ channels. This paper is based on mathematical simulations using the O’Hara et al (2011) model of baseline or healthy human ventricular action potential waveforms(s) and its [Ca2+]i homeostasis mechanisms. Somewhat surprisingly, our results reveal only very small changes (≤ 1.5 mM) in [Na+]i even when INa-L is increased 5-fold and steady-state stimulation rate is approximately 2 times the normal human heart rate (i.e. 2 Hz). Previous work done using well-established models of the rabbit and human ventricular action potential in heart failure settings also reported little or no change in [Na+]i when INa-L was increased. Based on our simulations, the major short-term effect of markedly augmenting INa-L is a significant prolongation of the action potential and an associated increase in the likelihood of reactivation of the L-type Ca2+ current, ICa-L. Furthermore, this action potential prolongation does not contribute to [Na+]i increase. PMID:27875582

  4. Changes in Intracellular Na+ following Enhancement of Late Na+ Current in Virtual Human Ventricular Myocytes.

    PubMed

    Cardona, Karen; Trenor, Beatriz; Giles, Wayne R

    2016-01-01

    The slowly inactivating or late Na+ current, INa-L, can contribute to the initiation of both atrial and ventricular rhythm disturbances in the human heart. However, the cellular and molecular mechanisms that underlie these pro-arrhythmic influences are not fully understood. At present, the major working hypothesis is that the Na+ influx corresponding to INa-L significantly increases intracellular Na+, [Na+]i; and the resulting reduction in the electrochemical driving force for Na+ reduces and (may reverse) Na+/Ca2+ exchange. These changes increase intracellular Ca2+, [Ca2+]i; which may further enhance INa-L due to calmodulin-dependent phosphorylation of the Na+ channels. This paper is based on mathematical simulations using the O'Hara et al (2011) model of baseline or healthy human ventricular action potential waveforms(s) and its [Ca2+]i homeostasis mechanisms. Somewhat surprisingly, our results reveal only very small changes (≤ 1.5 mM) in [Na+]i even when INa-L is increased 5-fold and steady-state stimulation rate is approximately 2 times the normal human heart rate (i.e. 2 Hz). Previous work done using well-established models of the rabbit and human ventricular action potential in heart failure settings also reported little or no change in [Na+]i when INa-L was increased. Based on our simulations, the major short-term effect of markedly augmenting INa-L is a significant prolongation of the action potential and an associated increase in the likelihood of reactivation of the L-type Ca2+ current, ICa-L. Furthermore, this action potential prolongation does not contribute to [Na+]i increase.

  5. Recent results from MoNA-LISA

    NASA Astrophysics Data System (ADS)

    Spyrou, Artemisia

    2012-03-01

    Studies of the nuclear properties of nuclei close and even beyond the limits of stability have revealed exotic modes of decay and new structural characteristics. The MoNA-LISA array is used at the National Superconducting Cyclotron Laboratory at Michigan State University to study nuclei along the neutron dripline. In a typical experiment, a radioactive beam is employed to produce the neutron-unbound state of interest. This state/resonance immediately decay into a neutron, which is detected by MoNA-LISA and a remaining charged nucleus detected by the sweeper magnet detector suite. In this talk, new exciting findings from recent MoNA-LISA experiments will be presented. These include the first observation of a dineutron decay from ^16Be, the exploration of the ``south shore'' of the Island of Inversion and the first evidence of the decay of the troubling nucleus ^26O.

  6. Photoionization studies of Na/sub 2/Cl and Na/sub 2/O and reactions of metal clusters

    SciTech Connect

    Peterson, K.I.; Dao, P.D.; Castleman, A.W. Jr.

    1983-07-15

    Reaction between metal clusters and various reactant gases in a coexpanding nozzle led to the formation of Na/sub 2/Cl and Na/sub 2/O. These species were subjected to photoionization using a UV light source, monochromator, and mass spectrometer detection system. Appearance potentials of 95.7 and 116.7 kcal/mol were obtained for Na/sub 2/Cl and Na/sub 2/O, respectively. The appearance potential of the Na/sub 2/Cl lies between the ionization potential of the metal and the electron affinity of chlorine, while that of Na/sub 2/O is close to the ionization potential of the metal. Using these values and other literature data, energies were derived for the following bonds: Na--NaCl (19.7 kcal/mol), Na/sup +//sub 2/xCl (115.5), Na/sub 2/xCl (98.9), and Na/sup +//sub 2/xCl/sup -/ (127.8); Na/sup +/xNaO (56.8), Na/sup +//sub 2/xO (94.2), Na/sub 2/xO (98.6), and Na/sup +//sub 2/xO/sup -/ (177.2).

  7. Targeting voltage gated sodium channels NaV1.7, Na V1.8, and Na V1.9 for treatment of pathological cough.

    PubMed

    Muroi, Yukiko; Undem, Bradley J

    2014-02-01

    Recent advances in our understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that drugs capable of selective blockade of NaV subtypes may be a safe and effective strategy for the treatment of unwanted cough. Among the nine NaV subtypes (NaV1.1-NaV1.9), the afferent nerves involved in initiating cough, in common with nociceptive neurons in the somatosensory system, express mainly NaV1.7, NaV1.8, and NaV1.9. Although knowledge about the effect of selectively blocking these channels on the cough reflex is limited, their biophysical properties indicate that each may contribute to the hypertussive and allotussive state that typifies subacute and chronic nonproductive cough.

  8. Intracellular [Na+], Na+ pathways, and fluid transport in cultured bovine corneal endothelial cells.

    PubMed

    Kuang, Kunyan; Li, Yansui; Yiming, Maimaiti; Sánchez, José M; Iserovich, Pavel; Cragoe, E J; Diecke, Friedrich P J; Fischbarg, Jorge

    2004-07-01

    The mechanism of fluid transport across corneal endothelium remains unclear. We examine here the relative contributions of cellular mechanisms of Na+ transport and the homeostasis of intracellular [Na+] in cultured bovine corneal endothelial cells, and the influence of ambient Na+ and HCO3- on the deturgescence of rabbit cornea. Bovine corneal endothelial cells plated on glass coverslips were incubated for 60 min with 10 microm of the fluorescent Na+ indicator SBFI precursor in HCO3- HEPES (BH) Ringer's solution. After loading, cells were placed in a perfusion chamber. Indicator fluorescence (490 nm) was determined with a Chance-Legallais time-sharing fluorometer. Its voltage output was the ratio of the emissions excited at 340 and 380 nm. For calibration, cells were treated with gramicidin D. For fluid transport measurements, rabbit corneas were mounted in a Dikstein-Maurice chamber, and stromal thickness was measured with a specular microscope. The steady-state [Na+]i in BH was 14.36+/-0.38 mM (n = mean+/-s.e.). Upon exposure to Na+ -free BH solution (choline substituted), [Na+]i decreased to 1.81+/-0.20mM (n = 19). When going from Na+ -free plus 100 microm ouabain to BH plus ouabain, [Na+]i increased to 46.17+/-2.50 (n = 6) with a half time of 1.26+/-0.04 min; if 0.1 microm phenamil plus ouabain were present, it reached only 21.78+/-1.50mm. The exponential time constants (min-1) were: 0.56+/-0.04 for the Na+ pump; 0.39+/-0.01 for the phenamil sensitive Na+ channel; and 0.17+/-0.02 for the ouabain-phenamil-insensitive pathways. In HCO3- free medium (gluconate substituted), [Na+]i was 14.03+/-0.11mM; upon changing to BH medium, it increased to 30.77+/-0.74 mm. This last [Na+]i increase was inhibited 66% by 100 microm DIDS. Using BH medium, corneal thickness remained nearly constant, increasing at a rate of only 2.9+/-0.9 microm hr-1 during 3 hr. However, stromal thickness increased drastically (swelling rate 36.1+/-2.6 microm hr-1) in corneas superfused with BH

  9. Concentration dependence of Li+/Na+ diffusion in manganese hexacyanoferrates

    NASA Astrophysics Data System (ADS)

    Takachi, Masamitsu; Fukuzumi, Yuya; Moritomo, Yutaka

    2016-06-01

    Manganese hexacyanoferrates (Mn-HCFs) with a jungle-gym-type structure are promising cathode materials for Li+/Na+ secondary batteries (LIBs/SIBs). Here, we investigated the diffusion constants D Li/D Na of Li+/Na+ against the Li+/Na+ concentration x Na/x Li and temperature (T) of A 1.32Mn[Fe(CN)6]0.833.6H2O (A = Li and Na). We evaluated the activation energy E\\text{a}\\text{Li}/E\\text{a}\\text{Na} of D Li/D Na against x Na/x Li. We found that E\\text{a}\\text{Na} steeply increases with x Na from 0.41 eV at x Na = 0.69 to 0.7 eV at 1.1. The increase in E\\text{a}\\text{Na} is ascribed to the occupancy effect of the Na+ site. The increase in E\\text{a}\\text{Li} is suppressed, probably because the number of Li+ sites is three times that of Na+ sites.

  10. Na+/K+-ATPase: Activity and inhibition

    NASA Astrophysics Data System (ADS)

    Čolović, M.; Krstić, D.; Krinulović, K.; Momić, T.; Savić, J.; Vujačić, A.; Vasić, V.

    2009-09-01

    The aim of the study was to give an overview of the mechanism of inhibition of Na+/K+-ATPase activity induced by some specific and non specific inhibitors. For this purpose, the effects of some ouabain like compounds (digoxin, gitoxin), noble metals complexes ([PtCl2DMSO2], [AuCl4]-, [PdCl4]2-, [PdCl(dien)]+, [PdCl(Me4dien)]+), transition metal ions (Cu2+, Zn2+, Fe2+, Co2+), and heavy metal ions (Hg2+, Pb2+, Cd2+) on the activity of Na+/K+-ATPase from rat synaptic plasma membranes (SPM), porcine cerebral cortex and human erythrocytes were discussed.

  11. Compact clinical high-NA multiphoton endoscopy

    NASA Astrophysics Data System (ADS)

    Weinigel, Martin; Breunig, Hans Georg; Fischer, Peter; Kellner-Höfer, Marcel; Bückle, Rainer; König, Karsten

    2012-02-01

    Multiphoton imaging methods are excellent for non-invasive imaging of living tissue without any need of additional contrast agents. The increasing demand for endoscopic techniques has forced the development of multiphoton endoscopes for imaging of areas with reduced accessibility like chronic wounds. Gradient index (GRIN) lenses can miniaturize the bulky distal focusing optics of conventional tomographs to a diameter of less than 1.4 mm and a numerical aperture (NA) of 0.8. We combined a high NA clinical multiphoton endoscope with existing multiphoton tomographs like the DermaInspect® and the MPTflex® to enable the examination of wound healing processes.

  12. CAPE-2 Cubesat - ELaNa IV

    NASA Image and Video Library

    2016-07-25

    CAPE-2: Cajun Advanced Picosatellite Experiment – ELaNa IV CAPE-2 was developed by students from the University of Louisiana Lafayette to engage, inspire and educate K-12 students to encourage them to pursue STEM careers. The secondary focus is the technology demonstration of deployed solar panels to support the following payloads: text to speech, voice repeater, tweeting, email, file transfer and data collection from buoys. Launched by NASA’s CubeSat Launch Initiative on the ELaNa IV mission as an auxiliary payload aboard the U.S. Air Force-led Operationally Responsive Space (ORS-3) Mission on November 19, 2013.

  13. Sodium-difluoro(oxalato)borate (NaDFOB): a new electrolyte salt for Na-ion batteries.

    PubMed

    Chen, Juner; Huang, Zhenguo; Wang, Caiyun; Porter, Spencer; Wang, Baofeng; Lie, Wilford; Liu, Hua Kun

    2015-06-18

    A new electrolyte salt, sodium-difluoro(oxalato)borate (NaDFOB), was synthesized and studied, which enables excellent reversible capacity and high rate capability when used in Na/Na0.44MnO2 half cells. NaDFOB has excellent compatibility with various common solvents used in Na-ion batteries, in strong contrast to the solvent dependent performances of NaClO4 and NaPF6. In addition, NaDFOB possesses good stability and generates no toxic or dangerous products when exposed to air and water. All these properties demonstrate that NaDFOB could be used to prepare high performance electrolytes for emerging Na-ion batteries.

  14. Response of saliva Na/K ratio to changing Na supply of lactating cows under tropical conditions.

    PubMed

    Thiangtum, Wandee; Schonewille, J Thomas; Verstegen, Martin Wa; Arsawakulsudhi, Supot; Rukkwamsuk, Theera; Hendriks, Wouter H

    2017-06-01

    Factorial determination of the sodium (Na) requirement of heat-stressed lactating cows is hindered by accurate estimates of the Na losses through sweat. Direct studies, therefore, may be needed requiring information on the time course of healthy animals to become Na depleted and the subsequent rate of repletion. The rate of Na depletion and subsequent rate of Na repletion with two levels of dietary Na to lactating dairy cows housed under tropical conditions were investigated using the salivary Na/K. The 12 lactating cows (salivary Na/K ratio 14.6) rapidly developed clinical signs of Na deficiency, including pica, polyuria and polydipsia, reduced body weight and reduced milk yield when fed a low-Na ration (0.33 g kg(-1) dry matter (DM)) for 3 weeks. Deficiency symptoms were associated with a rapid decrease in salivary Na/K ratio to <4.3 from 7 to 21 days. Subsequent repletion of the cows with NaCl to a ration concentration of 1.1 or 1.6 g Na kg(-1) DM for 5 weeks did not restore salivary Na/K ratio to values of >6. A daily Na intake of heat-stressed lactating cows to a ration intake of 1.6 g Na kg(-1) DM was insufficient to restore Na deficiency. One week was sufficient to deplete heat-stressed lactating cows of Na, allowing for rapid dose-response studies utilizing the salivary Na/K ratio as a parameter for Na status of cows under tropical conditions. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  15. Retirada do leito após a descontinuação da ventilação mecânica: há repercussão na mortalidade e no tempo de permanência na unidade de terapia intensiva?

    PubMed

    Soares, Thiago Rios; Avena, Kátia de Miranda; Olivieri, Flávia Milholo; Feijó, Luciana Ferreira; Mendes, Kristine Menezes Barberino; Souza Filho, Sydney Agareno de; Gomes, André Mansur de Carvalho Guanaes

    2010-03-01

    To describe the withdrawal of the bed frequency in mechanic ventilation patients and its impact on mortality and length of stay in the intensive care unit. This was a retrospective cohort study in mechanical ventilation patients. Clinical and epidemiological variables, withdrawal of bed related motor therapy, intensive care unit length of stay and mortality were evaluated. We studied 91 patients, mean age of 62.5± 18.8 years, predominantly female (52%) and mean intensive care unit length of stay of 07 days (95% CI, 8-13 days). Considering the withdrawal of the bed or not, no difference was observed between groups regarding length of stay in intensive care unit. Patients who were withdrawn of bed had a lower clinical severity. Their mortality rate was 29.7%. The not withdrawn of bed group had higher both actual and expected mortality. Patients withdrawn of bed following mechanical ventilation discontinuation showed lower mortality. It is suggested that early intensive care unit mobilization and withdrawal of bed should be stimulated.

  16. Semisynthesis of NaK; a Na+ and K+ conducting ion channel

    PubMed Central

    Linn, Kellie M.; Derebe, Mehebaw G.; Jiang, Youxing; Valiyaveetil, Francis I.

    2010-01-01

    In this contribution, we describe the semisynthesis of NaK, a bacterial non-selective cation channel. In the semisynthesis, the NaK polypeptide is assembled from a recombinantly expressed thioester peptide and a chemically synthesized peptide using the native chemical ligation reaction. We describe a temporary tagging strategy for the purification of the hydrophobic synthetic peptide and demonstrate the efficient ligation of the synthetic peptide with the recombinant peptide thioester to form the semisynthetic NaK polypeptide. Following assembly, the NaK polypeptide is folded in vitro to the native state using lipid vesicles. Functional characterization of the folded semisynthetic NaK channels indicates that it is functionally similar to the wild type protein. We used semisynthesis to substitute aspartate 66 in the selectivity filter region of the NaK channel with the unnatural amino acids, homoserine and cysteine sulfonic acid. Functional analysis of these mutants suggests that the presence of a negatively charged residue in the vicinity of the ion binding sites is necessary for optimal flux of ions through the NaK channel. PMID:20415433

  17. Semisynthesis of NaK, a Na(+) and K(+) conducting ion channel.

    PubMed

    Linn, Kellie M; Derebe, Mehabaw G; Jiang, Youxing; Valiyaveetil, Francis I

    2010-06-01

    In this contribution, we describe the semisynthesis of NaK, a bacterial nonselective cation channel. In the semisynthesis, the NaK polypeptide is assembled from a recombinantly expressed thioester peptide and a chemically synthesized peptide using the native chemical ligation reaction. We describe a temporary tagging strategy for the purification of the hydrophobic synthetic peptide and demonstrate the efficient ligation of the synthetic peptide with the recombinant peptide thioester to form the semisynthetic NaK polypeptide. Following assembly, the NaK polypeptide is folded in vitro to the native state using lipid vesicles. Functional characterization of the folded semisynthetic NaK channels indicates that it is functionally similar to the wild-type protein. We used semisynthesis to substitute aspartate 66 in the selectivity filter region of the NaK channel with the unnatural amino acids homoserine and cysteine sulfonic acid. Functional analysis of these mutants suggests that the presence of a negatively charged residue in the vicinity of the ion binding sites is necessary for optimal flux of ions through the NaK channel.

  18. Study on Na layer response to geomagnetic activities based on Odin/OSIRIS Na density data

    NASA Astrophysics Data System (ADS)

    Tsuda, Takuo; Nakamura, Takuji; Hedin, Jonas; Gumbel, Jorg; Hosokawa, Keisuke; Ejiri, Mitsumu K.; Nishiyama, Takanori; Takahashi, Toru

    2016-07-01

    The Na layer is normally distributed from 80 to 110 km, and the height range is corresponding to the ionospheric D and E region. In the polar region, the energetic particles precipitating from the magnetosphere can often penetrate into the E region and even into the D region. Thus, the influence of the energetic particles to the Na layer is one of interests in the aspect of the atmospheric composition change accompanied with the auroral activity. There are several previous studies in this issue. For example, recently, we have reported an initial result on a clear relationship between the electron density increase (due to the energetic particles) and the Na density decrease from observational data sets obtained by Na lidar, EISCAT VHF radar, and optical instruments at Tromsoe, Norway on 24-25 January 2012. However, all of the previous studies had been carried out based on case studies by ground-based lidar observations. In this study, we have performed, for the first time, statistical analysis using Na density data from 2004 to 2009 obtained with the Optical Spectrograph and InfraRed Imager System (OSIRIS) onboard Odin satellite. In the presentation, we will show relationship between the Na density and geomagnetic activities, and its latitudinal variation. Based on these results, the Na layer response to the energetic particles will be discussed.

  19. Role of the Na(+)-translocating NADH:quinone oxidoreductase in voltage generation and Na(+) extrusion in Vibrio cholerae.

    PubMed

    Vorburger, Thomas; Nedielkov, Ruslan; Brosig, Alexander; Bok, Eva; Schunke, Emina; Steffen, Wojtek; Mayer, Sonja; Götz, Friedrich; Möller, Heiko M; Steuber, Julia

    2016-04-01

    For Vibrio cholerae, the coordinated import and export of Na(+) is crucial for adaptation to habitats with different osmolarities. We investigated the Na(+)-extruding branch of the sodium cycle in this human pathogen by in vivo (23)Na-NMR spectroscopy. The Na(+) extrusion activity of cells was monitored after adding glucose which stimulated respiration via the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR). In a V. cholerae deletion mutant devoid of the Na(+)-NQR encoding genes (nqrA-F), rates of respiratory Na(+) extrusion were decreased by a factor of four, but the cytoplasmic Na(+) concentration was essentially unchanged. Furthermore, the mutant was impaired in formation of transmembrane voltage (ΔΨ, inside negative) and did not grow under hypoosmotic conditions at pH8.2 or above. This growth defect could be complemented by transformation with the plasmid encoded nqr operon. In an alkaline environment, Na(+)/H(+) antiporters acidify the cytoplasm at the expense of the transmembrane voltage. It is proposed that, at alkaline pH and limiting Na(+) concentrations, the Na(+)-NQR is crucial for generation of a transmembrane voltage to drive the import of H(+) by electrogenic Na(+)/H(+) antiporters. Our study provides the basis to understand the role of the Na(+)-NQR in pathogenicity of V. cholerae and other pathogens relying on this primary Na(+) pump for respiration. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Na(+) dependence of K(+) -induced natriuresis, kaliuresis and Na(+) /Cl(-) cotransporter dephosphorylation.

    PubMed

    Jensen, I S; Larsen, C K; Leipziger, J; Sørensen, M V

    2016-09-01

    High dietary K(+) intake is associated with protection against hypertension. In mammals, acute K(+) intake induces natriuresis and kaliuresis, associated with a marked dephosphorylation of the renal Na(+) /Cl(-) cotransporter (NCC). It has been suggested that reduced activity of NCC increases the driving force for more distal tubular epithelial Na(+) channel (ENaC)-dependent K(+) secretion. This study investigated the ENaC dependence of urinary K(+) and Na(+) excretion following acute K(+) loading. Mice were fed low (0.03%), control (0.2%) or high (2%) Na(+) diets for 25 days to preserve or promote Na(+) loss and thus ENaC activity. Once a week, the mice received either K(+) -containing gavage or a control gavage. Following the gavage treatment, the mice were placed in metabolic cages and urine was collected in real time. ENaC dependence of kaliuresis was assessed by benzamil injections prior to gavage. We confirmed that dietary Na(+) content is inversely related to plasma aldosterone, NCC phosphorylation and ENaC cleavage products. The novel findings were as follows: (i) acute K(+) feeding caused NCC dephosphorylation in all dietary groups; (ii) under all dietary conditions, K(+) loading induced natriuresis; (iii) high Na(+) diet markedly reduced the K(+) excretion following K(+) gavage; (iv) benzamil injection prior to K(+) loading increased natriuresis, decreased kaliuresis and eliminated the differences between the dietary groups. These data indicate that acute K(+) -induced kaliuresis is ENaC dependent. Maximal K(+) excretion rates are attenuated when ENaC is physiologically down-regulated or pharmacologically blocked. NCC is dephosphorylated following acute K(+) loading under all dietary Na(+) regimens. This leads to natriuresis, even in severely Na(+) -restricted animals. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  1. Electronic Polarisability of NaNO2-NaNO3 and NaOH-NaNO3 Ionic Melts and Effective Ionic Radius of OH-

    NASA Astrophysics Data System (ADS)

    Iwadate, Yasuhiko; Ohnishi, Ryosuke; Ohkubo, Takahiro

    2017-01-01

    Molar volumes and refractive indexes of molten NaNO2-NaNO3 and NaOH-NaNO3 systems were measured by dilatometry and goniometry, respectively. The molar volumes of both systems increased with increasing temperature. Refractive indexes decreased with a rise of temperature or with increasing wavelength of the incident visible light. Assuming that the electronic polarisability is inherent in an ion, the electronic polarisability of a OH- ion in the melt was estimated from the Lorentz-Lorenz equation to be 1.26×10-30 m3, being comparable with that in the crystal. The effective ionic radius of a OH- ion was evaluated from the obtained electronic polarisability to be 1.34×10-10 m, using the correlation between the third power of the ionic radius and the electronic polarisability of an ion so far reported. The effective ionic radius obtained in this work was in good agreement with that assigned by Shannon.

  2. Light-induced drift of Na atoms

    NASA Astrophysics Data System (ADS)

    Werij, H. G. C.; Woerdman, J. P.

    1988-10-01

    Light can induce a flux of optically absorbing particles immersed in a buffer gas, when these particles have a different mobility in the ground and excited state. This paper presents a study of light-induced drift (LID) of Na atoms in noble gases, which can be regarded as the “canonical” system for experiments in this field. We have experimentally studied the LID effect in the optically thin and the optically thick regimes. Parameters which have been varied are laser frequency, laser intensity, buffer gas pressure and buffer gas species. This work gives the first critical comparison of LID experiments with realistic theory in which the multilevel complications of the Na atom have been incorporated. In the optically thick case (“optical piston”) one can distinguish the open cell and the closed cell regimes. Effects of adsorption and desorption of Na atoms at the surface of the cell wall have been incorporated into the theory. The experimental data are in excellent agreement with the results of a four-level rate-equation model for LID which incorporates the fine and hyperfine structure of the level scheme of the Na absorbers.

  3. Mechanisms contributing to the cardiac inotropic effect of Na pump inhibition and reduction of extracellular Na

    PubMed Central

    1987-01-01

    Reduction of the transsarcolemmal [Na] gradient in rabbit cardiac muscle leads to an increase in the force of contraction. This has frequently been attributed to alteration of Ca movements via the sarcolemmal Na/Ca exchange system. However, the specific mechanisms that mediate the increased force at individual contractions have not been clearly established. In the present study, the [Na] gradient was decreased by reduction of extracellular [Na] or inhibition of the Na pump by either the cardioactive steroid acetylstrophanthidin or by reduction of extracellular [K]. Contractile performance and changes in extracellular Ca (sensed by double-barreled Ca-selective microelectrodes) were studied in order to elucidate the underlying basis for the increase in force. In the presence of agents that inhibit sarcoplasmic reticulum (SR) function (10 mM caffeine, 100-500 nM ryanodine), reduction of the [Na] gradient produced increases in contractile force similar to that observed in the absence of caffeine or ryanodine. It is concluded that an intact, functioning SR is not required for the inotropic effect of [Na] gradient reduction (at least in rabbit ventricle). However, this does not exclude a possible contribution of enhanced SR Ca release in the inotropic response to [Na] gradient reduction in the absence of caffeine or ryanodine. Acetylstrophanthidin (3-5 microM) usually leads to an increase in the magnitude of extracellular Ca depletions associated with individual contractions. However, acetylstrophanthidin can also increase extracellular Ca accumulation during the contraction, especially at potentiated contractions. This extracellular Ca accumulation can be suppressed by ryanodine and it is suggested that this apparent enhancement of Ca efflux is secondary to an enhanced release of Ca from the SR. Under conditions where Ca efflux during contractions is minimized (after a rest interval in the presence of ryanodine), acetylstrophanthidin increased both the rate and the

  4. Intracellular Na(+) and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons.

    PubMed

    Wang, Yi-Chi; Yang, Jyh-Jeen; Huang, Rong-Chi

    2012-10-01

    Na/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na(+) and energy metabolism in regulating Na/K pump activity and neuronal excitability. Removal of extracellular K(+) to block the Na/K pump excited SCN neurons to fire at higher rates and return to normal K(+) to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K(+)-induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na(+) imaging with a Na(+)-sensitive fluorescent dye indicated saturating accumulation of intracellular Na(+) in response to pump blockade with zero K(+). The Na(+) ionophore monensin also induced Na(+) loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na(+) or by pump blockade. Conversely, Na(+) depletion with Na(+)-free pipette solution depolarized membrane potential but retained residual Na/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na(+) levels in all cells. Nonetheless, the Na/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na/K pump. Together, the results indicate the importance of intracellular Na(+) and energy metabolism in regulating Na/K pump activity as well as neuronal excitability in the SCN neurons.

  5. Laser trapping of {sup 21}Na atoms

    SciTech Connect

    Lu, Zheng-Tian

    1994-09-01

    This thesis describes an experiment in which about four thousand radioactive {sup 21}Na (t{sub l/2} = 22 sec) atoms were trapped in a magneto-optical trap with laser beams. Trapped {sup 21}Na atoms can be used as a beta source in a precision measurement of the beta-asymmetry parameter of the decay of {sup 21}Na {yields} {sup 21}Ne + {Beta}{sup +} + v{sub e}, which is a promising way to search for an anomalous right-handed current coupling in charged weak interactions. Although the number o trapped atoms that we have achieved is still about two orders of magnitude lower than what is needed to conduct a measurement of the beta-asymmetry parameter at 1% of precision level, the result of this experiment proved the feasibility of trapping short-lived radioactive atoms. In this experiment, {sup 21}Na atoms were produced by bombarding {sup 24}Mg with protons of 25 MeV at the 88 in. Cyclotron of Lawrence Berkeley Laboratory. A few recently developed techniques of laser manipulation of neutral atoms were applied in this experiment. The {sup 21}Na atoms emerging from a heated oven were first transversely cooled. As a result, the on-axis atomic beam intensity was increased by a factor of 16. The atoms in the beam were then slowed down from thermal speed by applying Zeeman-tuned slowing technique, and subsequently loaded into a magneto-optical trap at the end of the slowing path. The last two chapters of this thesis present two studies on the magneto-optical trap of sodium atoms. In particular, the mechanisms of magneto-optical traps at various laser frequencies and the collisional loss mechanisms of these traps were examined.

  6. [Regulation of the Na/Ca exchanger].

    PubMed

    DiPolo, R; Rojas, H; Beaugé, L

    1993-01-01

    The introduction of the squid giant axon preparation to studies on Ca homeostasis has proven very useful in laying the foundations in the study of Ca regulation. In particular the Na/Ca exchange mechanism has been characterized in terms of its regulatory processes using the well define technique of intracellular dialysis and membrane potential control. The Na/Ca exchange countertransport system plays a critical role in physiological processes including cardiac contractility and photoreception. It has also been implicate in the etiology of essential hypertension, cardiac arrhythmias and cell death. The ability of the Na/Ca exchanger to regulate the intracellular ionized Ca concentration ([Ca2+i]) under physiological conditions, is determined by the direction (net Ca efflux or Ca influx), and magnitude of transport. The direction of Ca transport is decided by the chemical gradient of sodium and calcium. The magnitude of the exchange is regulated by kinetic factors. This kinetic factors are critical since they decide whether the exchanger will mediate a net Ca movement under certain conditions. Recently, a large effort has been put together to characterize the secondary modulation of the Na/Ca exchanger. In particular modulation by MgATP and intracellular Ca2+. In nerve cells we have discover that MgATP regulates the exchanger through as phosphorylation-dephosphorylation processes most probably relate to the action of a kinase-phosphatase system. The other important ligand that regulates the exchange activity is the level of [Ca2+i]. We have found the presence of a regulatory site in the cytoplasmic face of the exchanger different from the transport site and probably responsible for turning the carrier "on" or "off". In this article we will depict some of the processes involved in the metabolic and ionic regulation of the Na/Ca exchanger.

  7. The Na4(+3) Clusters in Sodium Sodalite

    DTIC Science & Technology

    1992-05-15

    ATES COVOIN0i-15-92 Technical 06-01-91 to 05-31-92 4. TITLE ANA SUGTITLE S. RNORNG NUMBER The Na4+ 3 Clusters in Sodium Sodalite NN l14-e0-J-se59a 𔄀...3 [AlSiO 4]3 sodalite prepared by high vacuum deposition of sodium atoms. The samples with a Na 43 +:Na33+ cluster ratio up to 1:10 show a single...absorption feature with -m. = 628 nm (1.99 eV). The absorption originates from the individual sodalite cages containing Na 43+ cluster. For the Na 43+:Na

  8. Furosemide-sensitive Na and K fluxes in human red cells. Net uphill Na extrusion and equilibrium properties

    PubMed Central

    1986-01-01

    This paper reports experiments designed to find the concentrations of internal and external Na and K at which inward and outward furosemide- sensitive (FS) Na and K fluxes are equal, so that there is no net FS movement of Na and K. The red cell cation content was modified by using the ionophore nystatin, varying cell Na (Nai) from 0 to 34 mM (K substitution, high-K cells) and cell K (Ki) from 0 to 30 mM (Na substitution, high-Na cells). All incubation media contained NaCl (Nao = 130 or 120 nM), and KCl (Ko = 0-30 mM). In high-K cells, incubated in the absence of Ko, there was net extrusion of Na through the FS pathway. The net FS Na extrusion increased when Nai was increased. Low concentrations of Ko (0-6 mM) slightly stimulated, whereas higher concentrations of Ko inhibited, FS Na efflux. Increasing Ko stimulated the FS Na influx (K0.5 = 4 mM). Under conditions similar to those that occur in vivo (Nai = 10, Ki = 130, Nao = 130, Ko = 4 mM, Cli/Clo = 0.7), net extrusion of Na occurs through the FS pathway (180-250 mumol/liter cell X h). The concentration of Ko at which the FS Na influx and efflux and the FS K influx and efflux become equal increased when Nai increased in high-K cells and when Ki was increased in high-Na cells. The net FS Na and K fluxes both approached zero at similar internal and external Na and K concentrations. In high-K cells, under conditions when net Na and K fluxes were near zero, the ratio of FS Na to FS K unidirectional flux was found to be 2:3. In high-K cells, the empirical expression (Nai/Nao)2(Ki/Ko)3 remained at constant value (apparent equilibrium constant, Kappeq +/- SEM = 22 +/- 2) for each set of internal and external cation concentrations at which there was no net Na flux. These results indicate that in the physiological region of concentrations of internal and external Na, K, and Cl, the stoichiometry of the FS Na and K fluxes is 2 Na:3 K. In high-Na cells under conditions when net FS Na and K fluxes were near zero, the ratio of

  9. The solubility of Cr(OH){sub 3}(am) in concentrated NaOH and NaOH-NaNO{sub 3} solutions

    SciTech Connect

    Felmy, A.R.; Rai, D.; Fulton, R.W.

    1994-08-01

    Chromium is a major component of the Hanford waste tank sludges, and the presence of Cr in the sludges is a significant concern in the disposal of these sludges because Cr can interfere with the formation of waste glasses. One of the current pretreatment strategies for removing constituents that can interfere with glass formation, such as P and Cr, is to wash/dissolve the sludges in basic NaOH solutions. The solubility of Cr(OH){sub 3}(am) was measured in concentrated NaOH ranging in concentration from 0.1M to 6.0M and in NaOH-NaNO{sub 3} solutions with fixed NaOH concentration and variable NaNO{sub 3} concentration at room temperature (22--23 C). Equilibrium between solids and solutions was approached relatively slowly and required approximately 60--70 days before steady-state concentrations were reached. A thermodynamic model, based upon the Pitzer equations, was developed from the solubility data in NaOH, which includes only two aqueous Cr species (Cr(OH){sub 4}{sup {minus}} and NaCr(OH){sub 4}(aq)) and ion-interaction parameters for Na{sup +} with Cr(OH){sub 4}{sup {minus}}. This model was then tested in the mixed NaOH-NaNO{sub 3} solutions and found to be reliable.

  10. Effects of non-uniform root zone salinity on water use, Na+ recirculation, and Na+ and H+ flux in cotton.

    PubMed

    Kong, Xiangqiang; Luo, Zhen; Dong, Hezhong; Eneji, A Egrinya; Li, Weijiang

    2012-03-01

    A new split-root system was established through grafting to study cotton response to non-uniform salinity. Each root half was treated with either uniform (100/100 mM) or non-uniform NaCl concentrations (0/200 and 50/150 mM). In contrast to uniform control, non-uniform salinity treatment improved plant growth and water use, with more water absorbed from the non- and low salinity side. Non-uniform treatments decreased Na(+) concentrations in leaves. The [Na(+)] in the '0' side roots of the 0/200 treatment was significantly higher than that in either side of the 0/0 control, but greatly decreased when the '0' side phloem was girdled, suggesting that the increased [Na(+)] in the '0' side roots was possibly due to transportation of foliar Na(+) to roots through phloem. Plants under non-uniform salinity extruded more Na(+) from the root than those under uniform salinity. Root Na(+) efflux in the low salinity side was greatly enhanced by the higher salinity side. NaCl-induced Na(+) efflux and H(+) influx were inhibited by amiloride and sodium orthovanadate, suggesting that root Na(+) extrusion was probably due to active Na(+)/H(+) antiport across the plasma membrane. Improved plant growth under non-uniform salinity was thus attributed to increased water use, reduced leaf Na(+) concentration, transport of excessive foliar Na(+) to the low salinity side, and enhanced Na(+) efflux from the low salinity root.

  11. Synthesis of Na-A and/or Na-X zeolite/porous carbon composites from carbonized rice husk

    NASA Astrophysics Data System (ADS)

    Katsuki, Hiroaki; Komarneni, Sridhar

    2009-07-01

    Na-A and/or Na-X zeolite/porous carbon composites were prepared under hydrothermal conditions by NaOH dissolution of silica first from carbonized rice husk followed by addition of NaAlO 2 and in situ crystallization of zeolites i.e., using a two-step process. When a one-step process was used, both Na-A and Na-X zeolites crystallized on the surface of carbon. Na-A or Na-X zeolite crystals were prepared on the porous carbonized rice husk at 90 °C for 2-6 h by changing the SiO 2/Al 2O 3, H 2O/Na 2O and Na 2O/SiO 2 molar ratios of precursors in the two-step process. The surface area and NH 4+-cation exchange capacity (CEC) of Na-A zeolite/porous carbon were found to be 171 m 2/g and 506 meq/100 g, respectively, while those of Na-X zeolite/porous carbon composites were 676 m 2/g and 317 meq/100 g, respectively. Na-A and Na-X zeolites are well-known microporous and hydrophilic materials while carbonized rice husk was found to be mesoporous (pores of ˜3.9 nm) and hydrophobic. These hybrid microporous-mesoporous and hydrophilic-hydrophobic composites are expected to be useful for decontamination of metal cations as well as organic contaminants simultaneously.

  12. Regulation of cardiac myocyte contractility by phospholemman: Na+/Ca2+ exchange versus Na+ -K+ -ATPase.

    PubMed

    Song, Jianliang; Zhang, Xue-Qian; Wang, JuFang; Cheskis, Ellina; Chan, Tung O; Feldman, Arthur M; Tucker, Amy L; Cheung, Joseph Y

    2008-10-01

    Phospholemman (PLM) regulates cardiac Na(+)/Ca(2+) exchanger (NCX1) and Na(+)-K(+)-ATPase in cardiac myocytes. PLM, when phosphorylated at Ser(68), disinhibits Na(+)-K(+)-ATPase but inhibits NCX1. PLM regulates cardiac contractility by modulating Na(+)-K(+)-ATPase and/or NCX1. In this study, we first demonstrated that adult mouse cardiac myocytes cultured for 48 h had normal surface membrane areas, t-tubules, and NCX1 and sarco(endo)plasmic reticulum Ca(2+)-ATPase levels, and retained near normal contractility, but alpha(1)-subunit of Na(+)-K(+)-ATPase was slightly decreased. Differences in contractility between myocytes isolated from wild-type (WT) and PLM knockout (KO) hearts were preserved after 48 h of culture. Infection with adenovirus expressing green fluorescent protein (GFP) did not affect contractility at 48 h. When WT PLM was overexpressed in PLM KO myocytes, contractility and cytosolic Ca(2+) concentration ([Ca(2+)](i)) transients reverted back to those observed in cultured WT myocytes. Both Na(+)-K(+)-ATPase current (I(pump)) and Na(+)/Ca(2+) exchange current (I(NaCa)) in PLM KO myocytes rescued with WT PLM were depressed compared with PLM KO myocytes. Overexpressing the PLMS68E mutant (phosphomimetic) in PLM KO myocytes resulted in the suppression of I(NaCa) but had no effect on I(pump). Contractility, [Ca(2+)](i) transient amplitudes, and sarcoplasmic reticulum Ca(2+) contents in PLM KO myocytes overexpressing the PLMS68E mutant were depressed compared with PLM KO myocytes overexpressing GFP. Overexpressing the PLMS68A mutant (mimicking unphosphorylated PLM) in PLM KO myocytes had no effect on I(NaCa) but decreased I(pump). Contractility, [Ca(2+)](i) transient amplitudes, and sarcoplasmic reticulum Ca(2+) contents in PLM KO myocytes overexpressing the S68A mutant were similar to PLM KO myocytes overexpressing GFP. We conclude that at the single-myocyte level, PLM affects cardiac contractility and [Ca(2+)](i) homeostasis primarily by its direct

  13. Hypo-osmotic stimulation of active Na+ transport in frog muscle: apparent upregulation of Na+ pumps.

    PubMed

    Venosa, R A

    1991-03-01

    The purpose of this work was to determine if hypotonicity, in addition to the stimulation of active Na+ transport (Venosa, R.A., 1978, Biochim. Biophys. Acta 510:378-383), promoted changes in (i) active K+ influx, (ii) passive Na+ and K+ fluxes, and (iii) the number of 3H-ouabain binding sites. The results indicate that a reduction of external osmotic pressure (pi) to one-half of its normal value (pi = 0.5) produced the following effects: (i) an increase in active K+ influx on the order of 160%, (ii) a 20% reduction in Na+ influx and K+ permeability (PK), and (iii) a 40% increase in the apparent density of ouabain binding sites. These data suggest that the hypotonic stimulation of the Na+ pump is not caused by an increased leak of either Na+ (inward) or K+ (outward). It is unlikely that the stimulation of active Na+ extrusion and the rise in the apparent number of pump sites produced by hypotonicity were due to a reduction of the intracellular ionic strength. It appears that, at least in part, the stimulation of active Na+ transport takes place whenever muscles are transferred from one medium to another of lower tonicity even if neither one was hypotonic (for instance pi = 2 to pi = 1 transfer). Comparison of the present results with those previously reported indicate that in addition to the number of pump sites, the cycling rate of the pump is increased by hypotonicity. Active Na+ and K+ fluxes were not significantly altered by hypertonicity (pi = 2).

  14. Studies of Inelastic Collisions of NaK and NaCs Molecules with Atomic Perturbers

    NASA Astrophysics Data System (ADS)

    Jones, Joshua A.

    We have investigated collisions of NaK molecules in the first excited state [2(A)1Sigma+], with Ar and He collision partners using laser-induced fluorescence spectroscopy (LIF) and polarization-labeling (PL) spectroscopy in a two-step excitation scheme. Additionally, we have investigated collisions of NaCs molecules in the first excited state [2(A)1Sigma +] with Ar and He perturbers using the LIF technique. We use a pump-probe, two-step excitation process. The pump laser prepares the molecule in a particular ro-vibrational (v, J) level in the A state. The probe laser frequency is scanned over transitions to the 31Π in NaK or to the 53Π in NaCs. In addition to observing strong direct lines, we also see weak collisional satellite lines that arise from collisions in the intermediate state that take the molecule from the prepared level (v, J) to level (v, J + Delta J). The ratio of the intensity of the collisional line to the intensity of the direct line in LIF and PL yield information about population and orientation transfer. Our results show a propensity for DeltaJ=even collisions of NaK with Ar and an even stronger propensity for collisions with He. Collisions of NaCs with Ar do not show any such J=even propensity. Preliminary investigations of collisions of NaCs with He seem to indicate a slight J=even propensity. In addition, we observe that rotationally inelastic collisions of excited NaK molecules with potassium atoms destroy almost all of the orientation, while collisions with argon destroy about one third to two thirds and collisions with helium destroy only about zero to one third of the initial orientation.

  15. K+ Congeners That Do Not Compromise Na+ Activation of the Na+,K+-ATPase

    PubMed Central

    Mahmmoud, Yasser A.; Kopec, Wojciech; Khandelia, Himanshu

    2015-01-01

    The Na+,K+-ATPase is essential for ionic homeostasis in animal cells. The dephosphoenzyme contains Na+ selective inward facing sites, whereas the phosphoenzyme contains K+ selective outward facing sites. Under normal physiological conditions, K+ inhibits cytoplasmic Na+ activation of the enzyme. Acetamidinium (Acet+) and formamidinium (Form+) have been shown to permeate the pump through the outward facing sites. Here, we show that these cations, unlike K+, are unable to enter the inward facing sites in the dephosphorylated enzyme. Consistently, the organic cations exhibited little to no antagonism to cytoplasmic Na+ activation. Na+,K+-ATPase structures revealed a previously undescribed rotamer transition of the hydroxymethyl side chain of the absolutely conserved Thr772 of the α-subunit. The side chain contributes its hydroxyl to Na+ in site I in the E1 form and rotates to contribute its methyl group toward K+ in the E2 form. Molecular dynamics simulations to the E1·AlF4−·ADP·3Na+ structure indicated that 1) bound organic cations differentially distorted the ion binding sites, 2) the hydroxymethyl of Thr772 rotates to stabilize bound Form+ through water molecules, and 3) the rotamer transition is mediated by water traffic into the ion binding cavity. Accordingly, dehydration induced by osmotic stress enhanced the interaction of the congeners with the outward facing sites and profoundly modified the organization of membrane domains of the α-subunit. These results assign a catalytic role for water in pump function, and shed light on a backbone-independent but a conformation-dependent switch between H-bond and dispersion contact as part of the catalytic mechanism of the Na+,K+-ATPase. PMID:25533461

  16. Na Partitioning During Thermomechanical Processing of an Mg-Sn-Zn-Na Alloy

    NASA Astrophysics Data System (ADS)

    TerBush, Jessica R.; Stanford, Nicole; Nie, Jian-Feng; Barnett, Matthew R.

    2013-11-01

    Microstructural characterization was used to examine the changes that occur in an Mg-6Sn-5Zn-0.3Na alloy from casting to extrusion at either 623 K or 723 K (350 °C or 450 °C) followed by artificial aging at 473 K (200 °C). In particular, the partitioning of Na was examined at each step using STEM-EDS mapping. Na atoms were found to preferentially partition to the Mg-Zn phase when present. After extrusion, when no Mg-Zn was observed, the spherical Mg2Sn particles were found to be enriched in Na, particularly at the higher extrusion temperature. Artificial aging following extrusion resulted in a change in Na partitioning, and a coarse distribution of Mg-Zn precipitate rods. Na microadditions led to a high as-extruded hardness, but a significant tension-compression yield asymmetry was still observed at room temperature. The compressive yield strength was found to decrease significantly after 1000 hours of aging.

  17. Conduction of Na+ and K+ through the NaK Channel: Molecular and Brownian Dynamics Studies

    PubMed Central

    Vora, Taira; Bisset, David; Chung, Shin-Ho

    2008-01-01

    Conduction of ions through the NaK channel, with M0 helix removed, was studied using both Brownian dynamics and molecular dynamics. Brownian dynamics simulations predict that the truncated NaK has approximately a third of the conductance of the related KcsA K+ channel, is outwardly rectifying, and has a Michaelis-Menten current-concentration relationship. Current magnitude increases when the glutamine residue located near the intracellular gate is replaced with a glutamate residue. The channel is blocked by extracellular Ca2+. Molecular dynamics simulations show that, under the influence of a strong applied potential, both Na+ and K+ move across the selectivity filter, although conduction rates for Na+ ions are somewhat lower. The mechanism of conduction of Na+ differs significantly from that of K+ in that Na+ is preferentially coordinated by single planes of pore-lining carbonyl oxygens, instead of two planes as in the usual K+ binding sites. The water-containing filter pocket resulting from a single change in the selectivity filter sequence (compared to potassium channels) disrupts several of the planes of carbonyl oxygens, and thus reduces the filter's ability to discriminate against sodium. PMID:18456826

  18. Conduction of Na+ and K+ through the NaK channel: molecular and Brownian dynamics studies.

    PubMed

    Vora, Taira; Bisset, David; Chung, Shin-Ho

    2008-08-01

    Conduction of ions through the NaK channel, with M0 helix removed, was studied using both Brownian dynamics and molecular dynamics. Brownian dynamics simulations predict that the truncated NaK has approximately a third of the conductance of the related KcsA K+ channel, is outwardly rectifying, and has a Michaelis-Menten current-concentration relationship. Current magnitude increases when the glutamine residue located near the intracellular gate is replaced with a glutamate residue. The channel is blocked by extracellular Ca2+. Molecular dynamics simulations show that, under the influence of a strong applied potential, both Na+ and K+ move across the selectivity filter, although conduction rates for Na+ ions are somewhat lower. The mechanism of conduction of Na+ differs significantly from that of K+ in that Na+ is preferentially coordinated by single planes of pore-lining carbonyl oxygens, instead of two planes as in the usual K+ binding sites. The water-containing filter pocket resulting from a single change in the selectivity filter sequence (compared to potassium channels) disrupts several of the planes of carbonyl oxygens, and thus reduces the filter's ability to discriminate against sodium.

  19. Na/beta-alumina/NaAlCl4, Cl2/C circulating cell

    NASA Astrophysics Data System (ADS)

    Cherng, Jing-Yih; Bennion, Douglas N.

    1987-09-01

    A study was made of a high specific energy battery based on a sodium negative electrode and a chlorine positive electrode with molten AlCl3-NaCl electrolyte and a solid beta alumina separator. The basic performance of a Na beta-alumina NaAlCl4, Cl2/C circulating cell at 200 C was demonstrated. This cell can be started at 150 C. The use of melting sodium chloroaluminate electrolyte overcomes some of the material problems associated with the high working temperatures of present molten salt systems, such as Na/S and LiAl/FeS, and retains the advantages of high energy density and relatively efficient electrode processes. Preliminary investigations were conducted on a sodium-chlorine static cell, material compability, electrode design, wetting, and theoretical calculations to assure a better chance of success before assembling a Na/Cl2 circulating cell. Mathematical models provide a theoretical explanation for the performance of the NaCl2 battery. The results of mathematical models match the experimental results very well. According to the result of the mathematical modeling, an output at 180 mA/sq cm and 3.2 V can be obtained with optimized cell design.

  20. Na+-NQR (Na+-translocating NADH:ubiquinone oxidoreductase) as a novel target for antibiotics.

    PubMed

    Dibrov, Pavel; Dibrov, Elena; Pierce, Grant N

    2017-09-01

    The recent breakthrough in structural studies on Na+-translocating NADH:ubiquinone oxidoreductase (Na+-NQR) from the human pathogen Vibrio cholerae creates a perspective for the systematic design of inhibitors for this unique enzyme, which is the major Na+ pump in aerobic pathogens. Widespread distribution of Na+-NQR among pathogenic species, its key role in energy metabolism, its relation to virulence in different species as well as its absence in eukaryotic cells makes this enzyme especially attractive as a target for prospective antibiotics. In this review, the major biochemical, physiological and, especially, the pharmacological aspects of Na+-NQR are discussed to assess its 'target potential' for drug development. A comparison to other primary bacterial Na+ pumps supports the contention that NQR is a first rate prospective target for a new generation of antimicrobials. A new, narrowly targeted furanone inhibitor of NQR designed in our group is presented as a molecular platform for the development of anti-NQR remedies. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Final-state symmetry of Na 1s core-shell excitons in NaCl and NaF

    SciTech Connect

    Nagle, K.P.; Seidler, G.T.; Shirley, E.L.; Fister, T.T.; Bradley, J.A.; Brown, F.C.

    2009-08-13

    We report measurements of the Na 1s contribution to the nonresonant inelastic x-ray scattering (NRIXS) from NaCl and NaF. Prior x-ray absorption studies have observed two pre-edge excitons in both materials. The momentum-transfer dependence (q dependence) of the measured NRIXS cross section and of real-space full multiple scattering and Bethe-Salpeter calculations determine that the higher-energy core excitons are s type for each material. The lower-energy core excitons contribute at most weakly to the NRIXS signal and we propose that these may be surface core excitons, as have been observed in several other alkali halides. The analysis of the orbital angular momentum of these features leads to a discussion of the limited sensitivity of NRIXS measurements to d-type final states when investigating 1s initial states. In this case the s- and p-type final density of states can be characterized by measurements at a small number of momentum transfers. This is in contrast to the case of more complex initial states for which measurements at a large number of momentum transfers are needed to separate the rich admixture of accessible and contributing final-state symmetries.

  2. Computational interpretation of 23Na MQMAS NMR spectra: A comprehensive investigation of the Na environment in silicate glasses

    NASA Astrophysics Data System (ADS)

    Gambuzzi, Elisa; Charpentier, Thibault; Menziani, Maria Cristina; Pedone, Alfonso

    2014-09-01

    Molecular dynamics, density functional theory calculations and 23Na NMR experiments have been used to inspect the chemical and structural characteristics of the Na environment in soda-lime silicate (CSN) and aluminosilicate (CASN) glasses. The use of an improved 3QMAS pulse sequence has allowed a clear identification of different Na sites. Average coordination numbers have been extracted by fitting the 23Na 3QMAS spectra with the computed NMR parameters. The results show that the 23Na δiso values correlate with the average <Na-O> distances only when the different coordination numbers are explicitly taken into account.

  3. An enhancement to the NA4 gear vibration diagnostic parameter

    NASA Technical Reports Server (NTRS)

    Decker, Harry J.; Handschuh, Robert F.; Zakrajsek, James J.

    1994-01-01

    A new vibration diagnostic parameter for health monitoring of gears, NA4*, is proposed and tested. A recently developed gear vibration diagnostic parameter NA4 outperformed other fault detection methods at indicating the start and initial progression of damage. However, in some cases, as the damage progressed, the sensitivity of the NA4 and FM4 parameters tended to decrease and no longer indicated damage. A new parameter, NA4* was developed by enhancing NA4 to improve the trending of the parameter. This allows for the indication of damage both at initiation and also as the damage progresses. The NA4* parameter was verified and compared to the NA4 and FM4 parameters using experimental data from single mesh spur and spiral bevel gear fatigue rigs. The primary failure mode for the test cases was naturally occurring tooth surface pitting. The NA4* parameter is shown to be a more robust indicator of damage.

  4. Mechanisms and regulation of Na(+) uptake by freshwater fish.

    PubMed

    Kumai, Yusuke; Perry, Steve F

    2012-12-01

    Mechanisms of ion uptake by freshwater (FW) fish have received considerable attention over the past 80 years. Through an assortment of techniques incorporating whole animal physiology, electrophysiology and molecular biological approaches, three models have been proposed to account for Na(+) uptake. (1) Direct exchange of Na(+) and H(+) via one or more types of Na(+)/H(+) exchanger (slc9), (2) uptake of Na(+) through epithelial Na(+) channels energized by an electrical gradient created by H(+)-ATPase and (3) Na(+)/Cl(-) co-transport (slc12). While each mechanism is supported at least in part by theoretical or experimental data, there are several outstanding questions that have not yet been fully resolved. Furthermore, there are few details concerning how these Na(+) uptake mechanisms are fine tuned in response to the fluctuating FW environments. In this review, we summarize the current understanding of these three Na(+) uptake mechanisms and discuss their regulation by endocrine (cortisol and prolactin) and neurohumoral (catecholamines) factors.

  5. U. S. EPA’S NA APPROACH FOR PETROLEUM HYDROCARBONS

    EPA Science Inventory

    Most evaluations of NA of petroleum hydrocarbons use geochemical data to document the NA through biodegradation. The expected trends during biodegradation (plume interior vs. background concentrations) are Dissolved oxygen concentrations below background, Nitrate concentrations ...

  6. U. S. EPA’S NA APPROACH FOR PETROLEUM HYDROCARBONS

    EPA Science Inventory

    Most evaluations of NA of petroleum hydrocarbons use geochemical data to document the NA through biodegradation. The expected trends during biodegradation (plume interior vs. background concentrations) are Dissolved oxygen concentrations below background, Nitrate concentrations ...

  7. Inelastic and reactive collisions with polarized excited Na atoms

    SciTech Connect

    Schmidt, H.; Hertel, I.V.; Lee, Y.T.

    1985-07-01

    Polarization effects in inelastic collisions of laser state-prepared Na(3/sup 2/P, M/sub J/) with Na/sup +/ leading to Na(3/sup 2/D) or Na(3/sup 2/S) are discussed for the energy range E/sub cm/ = 5-47.5eV. Studies with linearly polarized light can be explained with a simple ''locking'' model of the Na(P)-orbital. The investigations employing circularly polarized light are a very sensitive test of the models describing the nonadiabatic angular momentum coupling between electronic and nuclear motion. The dynamical effects of the electronic spin on the angular momentum transfer are discussed. Recent crossed-beam experiments on the Na + O/sub 2/ -> NaO = O reaction in the energy range E/sub cm/ = 0/3-0.8eV show a pronounced dependence on the electric electronic symmetry of Na. 17 refs., 11 figs.

  8. Elementary immunology: Na(+) as a regulator of immunity.

    PubMed

    Schatz, Valentin; Neubert, Patrick; Schröder, Agnes; Binger, Katrina; Gebhard, Matthias; Müller, Dominik N; Luft, Friedrich C; Titze, Jens; Jantsch, Jonathan

    2017-02-01

    The skin can serve as an interstitial Na(+) reservoir. Local tissue Na(+) accumulation increases with age, inflammation and infection. This increased local Na(+) availability favors pro-inflammatory immune cell function and dampens their anti-inflammatory capacity. In this review, we summarize available data on how NaCl affects various immune cells. We particularly focus on how salt promotes pro-inflammatory macrophage and T cell function and simultaneously curtails their regulatory and anti-inflammatory potential. Overall, these findings demonstrate that local Na(+) availability is a promising novel regulator of immunity. Hence, the modulation of tissue Na(+) levels bears broad therapeutic potential: increasing local Na(+) availability may help in treating infections, while lowering tissue Na(+) levels may be used to treat, for example, autoimmune and cardiovascular diseases.

  9. Ofatumumab plus chlorambucil as a first-line therapy in less fit patients with chronic lymphocytic leukemia: analysis of COMPLEMENT1 and other monoclonal antibodies association data

    PubMed Central

    Frustaci, Anna Maria; Tedeschi, Alessandra; Picardi, Paola; Mazzucchelli, Maddalena; Cairoli, Roberto; Montillo, Marco

    2016-01-01

    The management of patients with chronic lymphocytic leukemia (CLL) has radically improved over the last few years with the addition of anti-CD20 monoclonal antibodies (MoAbs) to chemotherapy. Chlorambucil has been considered for decades as a suitable therapeutic option for frail patients. Taking into account the advantage offered by the addition of MoAbs to chemotherapy, different studies up to now have explored the feasibility of chlorambucil-based chemoimmunotherapies in treatment-naïve CLL. COMPLEMENT1 is a prospective, randomized, open-label trial evaluating the efficacy and safety of ofatumumab added to chlorambucil, compared with chlorambucil in monotherapy, in the setting of untreated patients with CLL considered unsuitable for a fludarabine-based approach. Progression-free survival was significantly longer in the chemoimmunotherapy arm when compared with the single-agent chlorambucil (22.4 months versus 13.1 months). Response rate and quality were also improved in the combination arm. Furthermore, the addition of ofatumumab did not lead to an unmanageable toxicity. While the employment of anti-CD20 antibodies represents an advantage in the treatment of the CLL symptomatic population, at present different patient selection and treatment schedules do not allow a reliable comparison between chlorambucil-based regimens. The addition of ofatumumab to chlorambucil represents a further therapeutic gain in CLL. Longer follow up and direct comparison with other MoAbs are warranted to establish the preferred first-line treatment in elderly and unfit patients. PMID:27493712

  10. Design of Na(+) -Selective Fluorescent Probes: A Systematic Study of the Na(+) -Complex Stability and the Na(+) /K(+) Selectivity in Acetonitrile and Water.

    PubMed

    Schwarze, Thomas; Müller, Holger; Schmidt, Darya; Riemer, Janine; Holdt, Hans-Jürgen

    2017-05-29

    There is a tremendous demand for highly Na(+) -selective fluoroionophores to monitor the top analyte Na(+) in life science. Here, we report a systematic route to develop highly Na(+) /K(+) selective fluorescent probes. Thus, we synthesized a set of fluoroionophores 1, 3, 4, 5, 8 and 9 (see Scheme ) to investigate the Na(+) /K(+) selectivity and Na(+) - complex stability in CH3 CN and H2 O. These Na(+) -probes bear different 15-crown-5 moieties to bind Na(+) stronger than K(+) . In the set of the diethylaminocoumarin-substituted fluoroionophores 1-5, the following trend of fluorescence quenching 1>3>2>4>5 in CH3 CN was observed. Therefore, the flexibility of the aza-15-crown-5 moieties in 1-4 determines the conjugation of the nitrogen lone pair with the aromatic ring. As a consequence, 1 showed in CH3 CN the highest Na(+) -induced fluorescence enhancement (FE) by a factor of 46.5 and a weaker K(+) induced FE of 3.7. The Na(+) -complex stability of 1-4 in CH3 CN is enhanced in the following order of 2>4>3>1, assuming that the O-atom of the methoxy group in the ortho-position, as shown in 2, strengthened the Na(+) -complex formation. Furthermore, we found for the N-(o-methoxyphenyl)aza-15-crown-5 substituted fluoroionophores 2, 8 and 9 in H2 O, an enhanced Na(+) -complex stability in the following order 8>2>9 and an increased Na(+) /K(+) selectivity in the reverse order 9>2>8. Notably, the Na(+) -induced FE of 8 (FEF=10.9), 2 (FEF=5.0) and 9 (FEF=2.0) showed a similar trend associated with a decreased K(+) -induced FE [8 (FEF=2.7)>2 (FEF=1.5)>9 (FEF=1.1)]. Here, the Na(+) -complex stability and Na(+) /K(+) selectivity is also influenced by the fluorophore moiety. Thus, fluorescent probe 8 (Kd =48 mm) allows high-contrast, sensitive, and selective Na(+) measurements over extracellular K(+) levels. A higher Na(+) /K(+) selectivity showed fluorescent probe 9, but also a higher Kd value of 223 mm. Therefore, 9 is a suitable tool to measure Na(+) concentrations up to

  11. Na+ deposition in the fibrotic skin of systemic sclerosis patients detected by 23Na-magnetic resonance imaging.

    PubMed

    Kopp, Christoph; Beyer, Christian; Linz, Peter; Dahlmann, Anke; Hammon, Matthias; Jantsch, Jonathan; Neubert, Patrick; Rosenhauer, Daniela; Müller, Dominik N; Cavallaro, Alexander; Eckardt, Kai-Uwe; Schett, Georg; Luft, Friedrich C; Uder, Michael; Distler, Jörg H W; Titze, Jens

    2017-04-01

    Skin fibrosis is the predominant feature of SSc and arises from excessive extracellular matrix deposition. Glycosaminoglycans are macromolecules of the extracellular matrix, which facilitate Na + accumulation in the skin. We used 23 Na-MRI to quantify Na + in skin. We hypothesized that skin Na + might accumulate in SSc and might be a biomarker for skin fibrosis. In this observational case-control study, skin Na + was determined by 23 Na-MRI using a Na + volume coil in 12 patients with diffuse cutaneous SSc and in 21 control subjects. We assessed skin fibrosis by the modified Rodnan skin score prior to 23 Na-MRI and on follow-up 12 months later. 23 Na-MRI demonstrated increased Na + in the fibrotic skin of SSc patients compared with skin from controls [mean ( s . d .): 27.2 (5.6) vs 21.4 (5.3) mmol/l, P < 0.01]. Na + content was higher in fibrotic than in non-fibrotic SSc skin [26.2 (4.8) vs 19.2 (3.4) mmol/l, P < 0.01]. Furthermore, skin Na + amount was correlated with changes in follow-up modified Rodnan skin score (R 2 = 0.68). 23 Na-MRI detected increased Na + in the fibrotic SSc skin; high Na + content was associated with progressive skin disease. Our findings provide the first evidence that 23 Na-MRI might be a promising tool to assess skin Na + and thereby predict progression of skin fibrosis in SSc.

  12. Na+-driven bacterial flagellar motors.

    PubMed

    Imae, Y; Atsumi, T

    1989-12-01

    Bacterial flagellar motors are the reversible rotary engine which propels the cell by rotating a helical flagellar filament as a screw propeller. The motors are embedded in the cytoplasmic membrane, and the energy for rotation is supplied by the electrochemical potential of specific ions across the membrane. Thus, the analysis of motor rotation at the molecular level is linked to an understanding of how the living system converts chemical energy into mechanical work. Based on the coupling ions, the motors are divided into two types; one is the H+-driven type found in neutrophiles such as Bacillus subtilis and Escherichia coli and the other is the Na+-driven type found in alkalophilic Bacillus and marine Vibrio. In this review, we summarize the current status of research on the rotation mechanism of the Na+-driven flagellar motors, which introduces several new aspects in the analysis.

  13. {beta} decay of {sup 32}Na

    SciTech Connect

    Mattoon, C. M.; Sarazin, F.; Hackman, G.; Ball, G. C.; Chakrawarthy, R. S.; Scraggs, H. C.; Smith, M. B.; Cunningham, E. S.; Walker, P. M.; Austin, R. A. E.; Finlay, P.; Grinyer, G. F.; Hyland, B.; Phillips, A. A.; Schumaker, M. A.; Svensson, C. E.; Garrett, P. E.; Koopmans, K. A.; Waddington, J. C.; Washbrook, B.

    2007-01-15

    The {beta}-decay of {sup 32}Na has been studied using {beta}-{gamma} coincidences. New transitions and levels are tentatively placed in the level scheme of {sup 32}Mg from an analysis of {gamma}-{gamma} and {beta}-{gamma}-{gamma} coincidences. The observation of the indirect feeding of the 2321 keV state in {sup 32}Mg removes some restrictions previously placed on the spin assignment for this state. No evidence of a state at 2117 keV in {sup 32}Mg is found. Previously unobserved weak transitions up to 5.4 MeV were recorded but could not be placed in the decay scheme of {sup 32}Na.

  14. [Tui-Na, an oriental massage].

    PubMed

    Esteve Torres, Andreu

    2005-05-01

    Tui-Na is an oriental massage whose principles are based on traditional Chinese medicine. This medicine conceives a person as one entire entity giving as much importance to emotional and physical aspects as to everything that surrounds a person, including climate, social relationships, diet. This philosophy believes that an individual will achieve his/her ideal health state when he/she has found interior harmony and is in balance with all his/her environment. From this viewpoint, this philosophy understands pathology as an unbalance or a lack of harmony in an organism. Tui-Na massage is one of the techniques which make use of traditional Chinese medicine to maintain, or to recuperate, an organism's balance.

  15. Dielectronic recombination resonances in Na8+

    NASA Astrophysics Data System (ADS)

    Nikolić, D.; Lindroth, E.; Kieslich, S.; Brandau, C.; Schippers, S.; Shi, W.; Müller, A.; Gwinner, G.; Schnell, M.; Wolf, A.

    2004-12-01

    The electron-ion recombination spectrum of the Li-like Na8+ ion in the energy range 0.0-0.5eV is presented. Experimental results obtained by storage-ring techniques are compared with a calculated spectrum, based on a combination of relativistic many-body methods and complex rotation, and the agreement is found to be very good. The deviations between measured and calculated dielectronic recombination resonance energies are usually below about 2meV with a maximum difference at 5.5meV , while the theoretical cross sections deviate by at most 20% from the experiment. The recombination spectrum in the investigated energy region is determined by the 2pj7ℓj' Rydberg manifold of dielectronic recombination resonances, comprising 61 states within half an eV above the ground state of Na8+ . The theoretical resonance parameters of all contributing states are provided.

  16. The two C-terminal tyrosines stabilize occluded Na/K pump conformations containing Na or K ions.

    PubMed

    Vedovato, Natascia; Gadsby, David C

    2010-07-01

    Interactions of the three transported Na ions with the Na/K pump remain incompletely understood. Na/K pump crystal structures show that the extended C terminus of the Na,K-adenosine triphosphatase (ATPase) alpha subunit directly contacts transmembrane helices. Deletion of the last five residues (KETYY in almost all Na/K pumps) markedly lowered the apparent affinity for Na activation of pump phosphorylation from ATP, a reflection of cytoplasmic Na affinity for forming the occluded E1P(Na3) conformation. ATPase assays further suggested that C-terminal truncations also interfere with low affinity Na interactions, which are attributable to extracellular effects. Because extracellular Na ions traverse part of the membrane's electric field to reach their binding sites in the Na/K pump, their movements generate currents that can be monitored with high resolution. We report here electrical measurements to examine how Na/K pump interactions with extracellular Na ions are influenced by C-terminal truncations. We deleted the last two (YY) or five (KESYY) residues in Xenopus laevis alpha1 Na/K pumps made ouabain resistant by either of two kinds of point mutations and measured their currents as 10-mM ouabain-sensitive currents in Xenopus oocytes after silencing endogenous Xenopus Na/K pumps with 1 microM ouabain. We found the low affinity inhibitory influence of extracellular Na on outward Na/K pump current at negative voltages to be impaired in all of the C-terminally truncated pumps. Correspondingly, voltage jump-induced transient charge movements that reflect pump interactions with extracellular Na ions were strongly shifted to more negative potentials; this signals a several-fold reduction of the apparent affinity for extracellular Na in the truncated pumps. Parallel lowering of Na affinity on both sides of the membrane argues that the C-terminal contacts provide important stabilization of the occluded E1P(Na3) conformation, regardless of the route of Na ion entry into the

  17. The two C-terminal tyrosines stabilize occluded Na/K pump conformations containing Na or K ions

    PubMed Central

    Vedovato, Natascia

    2010-01-01

    Interactions of the three transported Na ions with the Na/K pump remain incompletely understood. Na/K pump crystal structures show that the extended C terminus of the Na,K–adenosine triphosphatase (ATPase) α subunit directly contacts transmembrane helices. Deletion of the last five residues (KETYY in almost all Na/K pumps) markedly lowered the apparent affinity for Na activation of pump phosphorylation from ATP, a reflection of cytoplasmic Na affinity for forming the occluded E1P(Na3) conformation. ATPase assays further suggested that C-terminal truncations also interfere with low affinity Na interactions, which are attributable to extracellular effects. Because extracellular Na ions traverse part of the membrane’s electric field to reach their binding sites in the Na/K pump, their movements generate currents that can be monitored with high resolution. We report here electrical measurements to examine how Na/K pump interactions with extracellular Na ions are influenced by C-terminal truncations. We deleted the last two (YY) or five (KESYY) residues in Xenopus laevis α1 Na/K pumps made ouabain resistant by either of two kinds of point mutations and measured their currents as 10-mM ouabain–sensitive currents in Xenopus oocytes after silencing endogenous Xenopus Na/K pumps with 1 µM ouabain. We found the low affinity inhibitory influence of extracellular Na on outward Na/K pump current at negative voltages to be impaired in all of the C-terminally truncated pumps. Correspondingly, voltage jump–induced transient charge movements that reflect pump interactions with extracellular Na ions were strongly shifted to more negative potentials; this signals a several-fold reduction of the apparent affinity for extracellular Na in the truncated pumps. Parallel lowering of Na affinity on both sides of the membrane argues that the C-terminal contacts provide important stabilization of the occluded E1P(Na3) conformation, regardless of the route of Na ion entry into the

  18. The temperature dependence of the cross section for the energy pooling process Na(3P)+Na(3P) to Na(4D)+Na(3S)

    NASA Astrophysics Data System (ADS)

    Horvatic, V.; Movre, M.; Vadla, C.

    1999-10-01

    We report the measurements of the temperature dependence of the cross section σ4D for the energy pooling process Na(3P)+Na(3P) to Na(4D)+Na(3S). The latest two, as yet undisputed, results for σ4D obtained by different authors at T = 597 K and T = 483 K suggest that this cross section decreases with increasing T, which contradicts the theory and other experiments on similar processes. To resolve this controversy and to examine the temperature trend of the cross section, we have measured the σ4D in the temperature range 567-705 K, covering the high-temperature region that has not yet been investigated experimentally. To determine σ4D we have excited sodium atoms in the quasistatic wing of the D1 line using a cw dye laser and measured the fluorescence intensity for the 4D to 3P3/2 transition, relative to the intensity of the optically thin quasistatic wing of the D2 line. The spatial distribution of the number density of the sodium atoms in the 3P3/2 state and the sodium ground-state number density were measured too. The method used for the determination of the cross section is advantageous since it entirely circumvents the need to account for the radiation trapping of 3P level radiation, which was substantial under experimental conditions of the ground-state densities being 1014-1016 cm-3. The measurements of the cross section σ4D in the investigated temperature range have shown that it increases as ~exp(-Δ E/kT). From the experiment we obtained Δ E = (608±95) cm-1, which is in excellent agreement with the energy defect (613 cm-1) for the considered process, and in fair agreement with the values which follow from recent theoretical calculations.

  19. The complex lightcurve of 1992 NA

    NASA Astrophysics Data System (ADS)

    Wisniewski, Wieslaw Z.; Harris, A. W.

    1994-04-01

    Amor asteroid 1992 NA was monitored during three nights at a large phase angle of -65 deg. The lightcurves obtained did not reveal a repeatable curve with two maxima and two minima. However, some features suggested a periodicity with three maxima and three minima. A satisfactory composite lightcurve of this form was obtained by means of an 'eyeball' fit and by Fourier analysis. Individual and composite lightcurves are presented. The observed colors are consistent with the C class.

  20. The NA62 experiment at CERN

    NASA Astrophysics Data System (ADS)

    Venditti, Stefano

    2016-12-01

    The goal of the NA62 experiment at CERN is to collect O(100) events of the ultrarare K+→ π +ν bar {ν } decay in two years. After a long R&D phase and a successful pilot run in 2014, the first data-taking phase took place in 2015. In this paper the importance of the experiment's physics goal, as well as the experimental solutions adopted in order to attain it, will be reviewed.

  1. The complex lightcurve of 1992 NA

    NASA Technical Reports Server (NTRS)

    Wisniewski, Wieslaw Z.; Harris, A. W.

    1994-01-01

    Amor asteroid 1992 NA was monitored during three nights at a large phase angle of -65 deg. The lightcurves obtained did not reveal a repeatable curve with two maxima and two minima. However, some features suggested a periodicity with three maxima and three minima. A satisfactory composite lightcurve of this form was obtained by means of an 'eyeball' fit and by Fourier analysis. Individual and composite lightcurves are presented. The observed colors are consistent with the C class.

  2. Conformational changes couple Na+ and glucose transport

    PubMed Central

    Loo, Donald D. F.; Hirayama, Bruce A.; Gallardo, Elsa M.; Lam, Jason T.; Turk, Eric; Wright, Ernest M.

    1998-01-01

    The mechanism by which cotransport proteins couple their substrates across cell membranes is not known. A commonly proposed model is that cotransport results from ligand-induced conformational transitions that change the accessibility of ligand-binding sites from one side of the membrane to the other. To test this model, we have measured the accessibility of covalent probes to a cysteine residue (Q457C) placed in the putative sugar-translocation domain of the Na+/glucose cotransporter (SGLT1). The mutant protein Q457C was able to transport sugar, but transport was abolished after alkylation by methanethiosulfonate reagents. Alkylation blocked sugar translocation but not sugar binding. Accessibility of Q457C to alkylating reagents required external Na+ and was blocked by external sugar and phlorizin. The voltage dependence of accessibility was directly correlated with the presteady–state charge movement of SGLT1. Voltage-jump experiments with rhodamine-6-maleimide-labeled Q457C showed that the time course and level of changes in fluorescence closely followed the presteady–state charge movement. We conclude that conformational changes are responsible for the coupling of Na+ and sugar transport and that Q457 plays a critical role in sugar translocation by SGLT1. PMID:9636229

  3. Glial Na(+) -dependent ion transporters in pathophysiological conditions.

    PubMed

    Boscia, Francesca; Begum, Gulnaz; Pignataro, Giuseppe; Sirabella, Rossana; Cuomo, Ornella; Casamassa, Antonella; Sun, Dandan; Annunziato, Lucio

    2016-10-01

    Sodium dynamics are essential for regulating functional processes in glial cells. Indeed, glial Na(+) signaling influences and regulates important glial activities, and plays a role in neuron-glia interaction under physiological conditions or in response to injury of the central nervous system (CNS). Emerging studies indicate that Na(+) pumps and Na(+) -dependent ion transporters in astrocytes, microglia, and oligodendrocytes regulate Na(+) homeostasis and play a fundamental role in modulating glial activities in neurological diseases. In this review, we first briefly introduced the emerging roles of each glial cell type in the pathophysiology of cerebral ischemia, Alzheimer's disease, epilepsy, Parkinson's disease, Amyotrophic Lateral Sclerosis, and myelin diseases. Then, we discussed the current knowledge on the main roles played by the different glial Na(+) -dependent ion transporters, including Na(+) /K(+) ATPase, Na(+) /Ca(2+) exchangers, Na(+) /H(+) exchangers, Na(+) -K(+) -Cl(-) cotransporters, and Na(+) - HCO3- cotransporter in the pathophysiology of the diverse CNS diseases. We highlighted their contributions in cell survival, synaptic pathology, gliotransmission, pH homeostasis, and their role in glial activation, migration, gliosis, inflammation, and tissue repair processes. Therefore, this review summarizes the foundation work for targeting Na(+) -dependent ion transporters in glia as a novel strategy to control important glial activities associated with Na(+) dynamics in different neurological disorders. GLIA 2016;64:1677-1697. © 2016 Wiley Periodicals, Inc.

  4. 33 CFR 147.833 - Na Kika FDS safety zone.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Na Kika FDS safety zone. 147.833 Section 147.833 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.833 Na Kika FDS safety zone. (a) Description. Na...

  5. 33 CFR 147.833 - Na Kika FDS safety zone.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Na Kika FDS safety zone. 147.833 Section 147.833 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.833 Na Kika FDS safety zone. (a) Description. Na...

  6. 33 CFR 147.833 - Na Kika FDS safety zone.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Na Kika FDS safety zone. 147.833 Section 147.833 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.833 Na Kika FDS safety zone. (a) Description. Na...

  7. 33 CFR 147.833 - Na Kika FDS safety zone.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Na Kika FDS safety zone. 147.833 Section 147.833 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.833 Na Kika FDS safety zone. (a) Description. Na...

  8. 33 CFR 147.833 - Na Kika FDS safety zone.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Na Kika FDS safety zone. 147.833 Section 147.833 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.833 Na Kika FDS safety zone. (a) Description. Na...

  9. Spontaneous NA+ transients in individual mitochondria of intact astrocytes.

    PubMed

    Azarias, Guillaume; Van de Ville, Dimitri; Unser, Michael; Chatton, Jean-Yves

    2008-02-01

    Mitochondria in intact cells maintain low Na(+) levels despite the large electrochemical gradient favoring cation influx into the matrix. In addition, they display individual spontaneous transient depolarizations. The authors report here that individual mitochondria in living astrocytes exhibit spontaneous increases in their Na(+) concentration (Na(mit)(+) spiking), as measured using the mitochondrial probe CoroNa Red. In a field of view with approximately 30 astrocytes, up to 1,400 transients per minute were typically detected under resting conditions. Na(mit)(+) spiking was also observed in neurons, but was scarce in two nonneural cell types tested. Astrocytic Na(mit)(+) spikes averaged 12.2 +/- 0.8 s in duration and 35.5 +/- 3.2 mM in amplitude and coincided with brief mitochondrial depolarizations; they were impaired by mitochondrial depolarization and ruthenium red pointing to the involvement of a cation uniporter. Na(mit)(+) spiking activity was significantly inhibited by mitochondrial Na(+)/H(+) exchanger inhibition and sensitive to cellular pH and Na(+) concentration. Ca(2+) played a permissive role on Na(mit)(+) spiking activity. Finally, the authors present evidence suggesting that Na(mit)(+) spiking frequency was correlated with cellular ATP levels. This study shows that, under physiological conditions, individual mitochondria in living astrocytes exhibit fast Na(+) exchange across their inner membrane, which reveals a new form of highly dynamic and localized functional regulation.

  10. Na/K-ATPase Mimetic pNaKtide Peptide Inhibits the Growth of Human Cancer Cells*

    PubMed Central

    Li, Zhichuan; Zhang, Zhongbing; Xie, Joe X.; Li, Xin; Tian, Jiang; Cai, Ting; Cui, Hongjuan; Ding, Hanfei; Shapiro, Joseph I.; Xie, Zijian

    2011-01-01

    Cells contain a large pool of nonpumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. A supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces the activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness of pNaKtide and suggest that the defect in Na/K-ATPase-mediated signal transduction may be targeted for developing new anticancer therapeutics. PMID:21784855

  11. Reflectivity of NaK Droplets

    NASA Astrophysics Data System (ADS)

    Wiedemann, C.; Oswald, M.; Stabroth, S.; Klinkrad, H.; Vörsmann, P.

    An important contribution to the space debris population near 900 km orbital altitude are the NaK droplets. Sixteen nuclear powered satellites of the type RORSAT launched between 1980 and 1988 activated a reactor core ejection system close to this altitude. The core ejection causes an opening of the primary coolant circuit. The liquid coolant has been released into space during these core ejections, forming droplets up to a diameter of 5.5 cm. These droplets consist of an alloy of two alkali metals, sodium and potassium (NaK). In this paper the monochromatic and the total reflectivity of NaK is calculated using theoretical models. The reflectivity depends on the alloy composition and temperature of a droplet. The alloy composition may change due to evaporation, resulting in an enrichment of sodium especially at the droplet surface. According to the literature, there is only a limited number of available measurement data concerning the optical properties of NaK alloys. Furthermore the published data for pure sodium and potassium are controversial. Thus it is necessary to investigate the optical properties of alkali metals and their alloys. Mainly two types of optical absorption, the intraband and the interband absorption, are considered. The intraband absorption is calculated using the Drude-model which uses electrical properties to derive the optical constants of pure metals or alloys. Drude assumes that the valence electrons can be treated as free electrons. The electrons behave like an ideal gas of uncharged particles. The theory of free electrons is a very simple model for the description of the valence electrons in metals. This assumption is sufficient for alkali metals, because they show a nearly free electron behavior. For the interband absorption the classical Butcher-model is used. Furthermore an absorption anomaly which has been observed in some alkali metals is discussed. Especially for potassium, some measurements revealed an unexpected absorption in the

  12. Route, mechanism, and implications of proton import during Na+/K+ exchange by native Na+/K+-ATPase pumps.

    PubMed

    Vedovato, Natascia; Gadsby, David C

    2014-04-01

    A single Na(+)/K(+)-ATPase pumps three Na(+) outwards and two K(+) inwards by alternately exposing ion-binding sites to opposite sides of the membrane in a conformational sequence coupled to pump autophosphorylation from ATP and auto-dephosphorylation. The larger flow of Na(+) than K(+) generates outward current across the cell membrane. Less well understood is the ability of Na(+)/K(+) pumps to generate an inward current of protons. Originally noted in pumps deprived of external K(+) and Na(+) ions, as inward current at negative membrane potentials that becomes amplified when external pH is lowered, this proton current is generally viewed as an artifact of those unnatural conditions. We demonstrate here that this inward current also flows at physiological K(+) and Na(+) concentrations. We show that protons exploit ready reversibility of conformational changes associated with extracellular Na(+) release from phosphorylated Na(+)/K(+) pumps. Reversal of a subset of these transitions allows an extracellular proton to bind an acidic side chain and to be subsequently released to the cytoplasm. This back-step of phosphorylated Na(+)/K(+) pumps that enables proton import is not required for completion of the 3 Na(+)/2 K(+) transport cycle. However, the back-step occurs readily during Na(+)/K(+) transport when external K(+) ion binding and occlusion are delayed, and it occurs more frequently when lowered extracellular pH raises the probability of protonation of the externally accessible carboxylate side chain. The proton route passes through the Na(+)-selective binding site III and is distinct from the principal pathway traversed by the majority of transported Na(+) and K(+) ions that passes through binding site II. The inferred occurrence of Na(+)/K(+) exchange and H(+) import during the same conformational cycle of a single molecule identifies the Na(+)/K(+) pump as a hybrid transporter. Whether Na(+)/K(+) pump-mediated proton inflow may have any physiological or

  13. DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex

    PubMed Central

    Chao, Dongman; He, Xiaozhou; Yang, Yilin; Bazzy-Asaad, Alia; Lazarus, Lawrence H.; Balboni, Gianfranco; Kim, Dong H.; Xia, Ying

    2012-01-01

    Activation of delta-opioid receptors (DOR) is neuroprotective against hypoxic/ischemic injury in the cortex, which is at least partially related to its action against hypoxic/ischemic disruption of ionic homeostasis that triggers neuronal injury. Na+ influx through TTX-sensitive voltage-gated Na+ channels may be a main mechanism for hypoxia-induced disruption of K+ homeostasis, with DOR activation attenuating the disruption of ionic homeostasis by targeting voltage-gated Na+ channels. In the present study we examined the role of DOR in the regulation of Na+ influx in anoxia and simulated ischemia (oxygen-glucose deprivation) as well as the effect of DOR activation on the Na+ influx induced by a Na+ channel opener without anoxic/ischemic stress and explored a potential PKC mechanism underlying the DOR action. We directly measured extracellular Na+ activity in mouse cortical slices with Na+ selective electrodes and found that (1) anoxia-induced Na+ influx occurred mainly through TTX-sensitive Na+ channels; (2) DOR activation inhibited the anoxia/ischemia-induced Na+ influx; (3) veratridine, a Na+ channel opener, enhanced the anoxia-induced Na+ influx; this could be attenuated by DOR activation; (4) DOR activation did not reduce the anoxia-induced Na+ influx in the presence of chelerythrine, a broad-spectrum PKC blocker; and (5) DOR effects were blocked by PKCβII peptide inhibitor, and PKCθ pseudosubstrate inhibitor, respectively. We conclude that DOR activation inhibits anoxia-induced Na+ influx through Na+ channels via PKC (especially PKCβII and PKCθ isoforms) dependent mechanisms in the cortex. PMID:22609332

  14. A computational study of Na behavior on graphene

    NASA Astrophysics Data System (ADS)

    Malyi, Oleksandr I.; Sopiha, Kostiantyn; Kulish, Vadym V.; Tan, Teck L.; Manzhos, Sergei; Persson, Clas

    2015-04-01

    We present the first ab initio and molecular dynamics study of Na adsorption and diffusion on ideal graphene that considers Na-Na interaction and dispersion forces. From density functional theory (DFT) calculations using the generalized gradient approximation (GGA), the binding energy (vs. the vacuum reference state) of -0.75 eV is higher than the cohesive energy of Na metal (ENa metal cohesive energy (EcohDFT - D = - 1.21 eV) when dispersion correction is included (DFT-D), with Eb = -1.14 eV. Both DFT and DFT-D predict that the increase of Na concentration on graphene results in formation of Na complexes. This is evidenced by smaller Bader charge on Na atoms of Na dimer, 0.55e (0.48e for DFT) compared to 0.86e (for both DFT and DFT-D) for the single atom adsorption as well as by the formation of a Nasbnd Na bond identified by analysis of the electron density. These results suggest that ideal graphene is not a promising anode material for Na-ion batteries. Analysis of diffusion pathways for a Na dimer shows that the dimer remains stable during the diffusion, and computed migration barriers are significantly lower for the dimer than that for the single atom diffusion. This indicates that Na-Na interaction should be taken into account during the analysis of Na transport on graphene. Finally, we show that the typical defects (vacancy and divacancy) induce significant strengthening of the Nasbnd C interaction. In particular, the largest change to the interaction is computed for vacancy-defected graphene, where the found lowest binding energy (vs. the metal reference state) is about 1.15 eV (1.21 eV for DFT) lower than that for ideal graphene.

  15. pNaKtide inhibits Na/K-ATPase reactive oxygen species amplification and attenuates adipogenesis

    PubMed Central

    Sodhi, Komal; Maxwell, Kyle; Yan, Yanling; Liu, Jiang; Chaudhry, Muhammad A.; Getty, Morghan; Xie, Zijian; Abraham, Nader G.; Shapiro, Joseph I.

    2015-01-01

    Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed a high-fat diet corroborated our in vitro observations. Administration of pNaKtide in these mice reduced body weight gain, restored systemic redox and inflammatory milieu, and, crucially, improved insulin sensitivity. Thus, we propose that inhibition of Na/K-ATPase amplification of oxidative stress may ultimately be a novel way to combat obesity, insulin resistance, and metabolic syndrome. PMID:26601314

  16. Zero-gravity growth of NaF-NaCl eutectics in the NASA Skylab program

    NASA Technical Reports Server (NTRS)

    Yue, A. S.; Allen, F. G.; Yu, J. G.

    1976-01-01

    Continuous and discontinuous NaF fibers, embedded in a NaCl matrix, were produced in space and on earth. The production of continuous fibers in a eutectic mixture is attributed to the absence of convection current in the liquid during solidification in space. Image transmission and optical transmittance measurements of transverse sections of the space-grown and earth-grown ingots were made with a light microscope and a spectrometer. It is shown that better optical properties were obtained from samples grown in space. This was attributed to a better alignment of NaF fibers along the ingot axis. A new concept is advanced to explain the phenomenon of transmittance versus far infrared wavelength of the directionally solidified NaCl-NaF eutectic in terms of the two-dimensional Bragg Scattering and the polarization effect of Rayleigh scattering. This concept can be applied to other eutectic systems as long as the index of refraction of the matrix over a range of wavelengths is known. Experimental data are in agreement with the theoretical prediction.

  17. Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi

    PubMed Central

    Dracatos, Peter M.; Payne, Jennifer; Di Pietro, Antonio; Anderson, Marilyn A.; Plummer, Kim M.

    2016-01-01

    Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. Some plant defensins interact with fungal cell wall O-glycosylated proteins. Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2. PMID:27598152

  18. Shoot Na+ exclusion and increased salinity tolerance engineered by cell type-specific alteration of Na+ transport in Arabidopsis.

    PubMed

    Møller, Inge S; Gilliham, Matthew; Jha, Deepa; Mayo, Gwenda M; Roy, Stuart J; Coates, Juliet C; Haseloff, Jim; Tester, Mark

    2009-07-01

    Soil salinity affects large areas of cultivated land, causing significant reductions in crop yield globally. The Na+ toxicity of many crop plants is correlated with overaccumulation of Na+ in the shoot. We have previously suggested that the engineering of Na+ exclusion from the shoot could be achieved through an alteration of plasma membrane Na+ transport processes in the root, if these alterations were cell type specific. Here, it is shown that expression of the Na+ transporter HKT1;1 in the mature root stele of Arabidopsis thaliana decreases Na+ accumulation in the shoot by 37 to 64%. The expression of HKT1;1 specifically in the mature root stele is achieved using an enhancer trap expression system for specific and strong overexpression. The effect in the shoot is caused by the increased influx, mediated by HKT1;1, of Na+ into stelar root cells, which is demonstrated in planta and leads to a reduction of root-to-shoot transfer of Na+. Plants with reduced shoot Na+ also have increased salinity tolerance. By contrast, plants constitutively expressing HKT1;1 driven by the cauliflower mosaic virus 35S promoter accumulated high shoot Na+ and grew poorly. Our results demonstrate that the modification of a specific Na+ transport process in specific cell types can reduce shoot Na+ accumulation, an important component of salinity tolerance of many higher plants.

  19. Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi.

    PubMed

    Dracatos, Peter M; Payne, Jennifer; Di Pietro, Antonio; Anderson, Marilyn A; Plummer, Kim M

    2016-09-03

    Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. Some plant defensins interact with fungal cell wall O-glycosylated proteins. Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2.

  20. Na+ channel function, regulation, structure, trafficking and sequestration

    PubMed Central

    Chen-Izu, Ye; Shaw, Robin M; Pitt, Geoffrey S; Yarov-Yarovoy, Vladimir; Sack, Jon T; Abriel, Hugues; Aldrich, Richard W; Belardinelli, Luiz; Cannell, Mark B; Catterall, William A; Chazin, Walter J; Chiamvimonvat, Nipavan; Deschenes, Isabelle; Grandi, Eleonora; Hund, Thomas J; Izu, Leighton T; Maier, Lars S; Maltsev, Victor A; Marionneau, Celine; Mohler, Peter J; Rajamani, Sridharan; Rasmusson, Randall L; Sobie, Eric A; Clancy, Colleen E; Bers, Donald M

    2015-01-01

    This paper is the second of a series of three reviews published in this issue resulting from the University of California Davis Cardiovascular Symposium 2014: Systems approach to understanding cardiac excitation–contraction coupling and arrhythmias: Na+ channel and Na+ transport. The goal of the symposium was to bring together experts in the field to discuss points of consensus and controversy on the topic of sodium in the heart. The present review focuses on Na+ channel function and regulation, Na+ channel structure and function, and Na+ channel trafficking, sequestration and complexing. PMID:25772290

  1. Effect of Na+ on surface fractal dimension of compacted bentonite

    NASA Astrophysics Data System (ADS)

    Xiang, G. S.; Xu, Y. F.; Jiang, H.

    2015-05-01

    Compacted Tsukinuno bentonite was immersed into NaCl solutions of different concentrations in oedometers, and the surface fractal dimension of bentonite-saline association was measured by nitrogen adsorption isotherms. The application of the Frenkel-Halsey-Hill equation and the Neimark thermodynamic method to nitrogen adsorption isotherms indicated that the surface roughness was greater for the bentonite-saline association. The surface fractal dimension of bentonite increased in the NaCl solution with low Na+ concentration, but decreased at high Na+ concentration. This process was accompanied by the same tendency in specific surface area and microporosity with the presence of Na+ coating in the clay particles.

  2. Na+-K+ pump regulation and skeletal muscle contractility.

    PubMed

    Clausen, Torben

    2003-10-01

    In skeletal muscle, excitation may cause loss of K+, increased extracellular K+ ([K+]o), intracellular Na+ ([Na+]i), and depolarization. Since these events interfere with excitability, the processes of excitation can be self-limiting. During work, therefore, the impending loss of excitability has to be counterbalanced by prompt restoration of Na+-K+ gradients. Since this is the major function of the Na+-K+ pumps, it is crucial that their activity and capacity are adequate. This is achieved in two ways: 1) by acute activation of the Na+-K+ pumps and 2) by long-term regulation of Na+-K+ pump content or capacity. 1) Depending on frequency of stimulation, excitation may activate up to all of the Na+-K+ pumps available within 10 s, causing up to 22-fold increase in Na+ efflux. Activation of the Na+-K+ pumps by hormones is slower and less pronounced. When muscles are inhibited by high [K+]o or low [Na+]o, acute hormone- or excitation-induced activation of the Na+-K+ pumps can restore excitability and contractile force in 10-20 min. Conversely, inhibition of the Na+-K+ pumps by ouabain leads to progressive loss of contractility and endurance. 2) Na+-K+ pump content is upregulated by training, thyroid hormones, insulin, glucocorticoids, and K+ overload. Downregulation is seen during immobilization, K+ deficiency, hypoxia, heart failure, hypothyroidism, starvation, diabetes, alcoholism, myotonic dystrophy, and McArdle disease. Reduced Na+-K+ pump content leads to loss of contractility and endurance, possibly contributing to the fatigue associated with several of these conditions. Increasing excitation-induced Na+ influx by augmenting the open-time or the content of Na+ channels reduces contractile endurance. Excitability and contractility depend on the ratio between passive Na+-K+ leaks and Na+-K+ pump activity, the passive leaks often playing a dominant role. The Na+-K+ pump is a central target for regulation of Na+-K+ distribution and excitability, essential for second

  3. Acidosis Differentially Modulates Inactivation in NaV1.2, NaV1.4, and NaV1.5 Channels

    PubMed Central

    Vilin, Yury Y.; Peters, Colin H.; Ruben, Peter C.

    2012-01-01

    NaV channels play a crucial role in neuronal and muscle excitability. Using whole-cell recordings we studied effects of low extracellular pH on the biophysical properties of NaV1.2, NaV1.4, and NaV1.5, expressed in cultured mammalian cells. Low pH produced different effects on different channel subtypes. Whereas NaV1.4 exhibited very low sensitivity to acidosis, primarily limited to partial block of macroscopic currents, the effects of low pH on gating in NaV1.2 and NaV1.5 were profound. In NaV1.2 low pH reduced apparent valence of steady-state fast inactivation, shifted the τ(V) to depolarizing potentials and decreased channels availability during onset to slow and use-dependent inactivation (UDI). In contrast, low pH delayed open-state inactivation in NaV1.5, right-shifted the voltage-dependence of window current, and increased channel availability during onset to slow and UDI. These results suggest that protons affect channel availability in an isoform-specific manner. A computer model incorporating these results demonstrates their effects on membrane excitability. PMID:22701426

  4. Shank2 redistributes with NaPilla during regulated endocytosis

    PubMed Central

    Dobrinskikh, Evgenia; Giral, Hector; Caldas, Yupanqui A.; Levi, Moshe

    2010-01-01

    Serum phosphate levels are acutely impacted by the abundance of sodium-phosphate cotransporter IIa (NaPiIIa) in the apical membrane of renal proximal tubule cells. PSD-95/Disks Large/Zonula Occludens (PDZ) domain-containing proteins bind NaPiIIa and likely contribute to the delivery, retention, recovery, and trafficking of NaPiIIa. Shank2 is a distinctive PDZ domain protein that binds NaPiIIa. Its role in regulating NaPiIIa activity, distribution, and abundance is unknown. In the present in vivo study, rats were maintained on a low-phosphate diet, and then plasma phosphate levels were acutely elevated by high-phosphate feeding to induce the recovery, endocytosis, and degradation of NaPiIIa. Western blot analysis of renal cortical tissue from rats given high-phosphate feed showed NaPiIIa and Shank2 underwent degradation. Quantitative immunofluorescence analyses, including microvillar versus intracellular intensity ratios and intensity correlation quotients, showed that Shank2 redistributed with NaPiIIa during the time course of NaPiIIa endocytosis. Furthermore, NaPiIIa and Shank2 trafficked through distinct endosomal compartments (clathrin, early endosomes, lysosomes) with the same temporal pattern. These in vivo findings indicate that Shank2 is positioned to coordinate the regulated endocytic retrieval and downregulation of NaPiIIa in rat renal proximal tubule cells. PMID:20810910

  5. Jahn–Teller Assisted Na Diffusion for High Performance Na Ion Batteries

    SciTech Connect

    Li, Xin; Wang, Yan; Wu, Di; Liu, Lei; Bo, Shou-Hang; Ceder, Gerbrand

    2016-08-30

    Na energy storage technology is strategically attractive for large scale applications such as grid energy storage. Here, we show in this paper that there is a clear relation between the Jahn$-$Teller activity of a transition metal ion at the end of charge and the mobility of Na in a cathode material. This is particularly important as mobility at the end of charge limits the capacity of current materials. Consequently, by using this classical piece of physics in the battery world, it is possible to create higher capacity Na-cathode materials. Even more exciting is that the ideal element to impart this effect on cathodes is Fe, which is the least expensive of the transition metal oxides and can therefore enable low cost cathode materials.

  6. Synthesis of Na-A and/or Na-X zeolite/porous carbon composites from carbonized rice husk

    SciTech Connect

    Katsuki, Hiroaki; Komarneni, Sridhar

    2009-07-15

    Na-A and/or Na-X zeolite/porous carbon composites were prepared under hydrothermal conditions by NaOH dissolution of silica first from carbonized rice husk followed by addition of NaAlO{sub 2} and in situ crystallization of zeolites i.e., using a two-step process. When a one-step process was used, both Na-A and Na-X zeolites crystallized on the surface of carbon. Na-A or Na-X zeolite crystals were prepared on the porous carbonized rice husk at 90 deg. C for 2-6 h by changing the SiO{sub 2}/Al{sub 2}O{sub 3}, H{sub 2}O/Na{sub 2}O and Na{sub 2}O/SiO{sub 2} molar ratios of precursors in the two-step process. The surface area and NH{sub 4}{sup +}-cation exchange capacity (CEC) of Na-A zeolite/porous carbon were found to be 171 m{sup 2}/g and 506 meq/100 g, respectively, while those of Na-X zeolite/porous carbon composites were 676 m{sup 2}/g and 317 meq/100 g, respectively. Na-A and Na-X zeolites are well-known microporous and hydrophilic materials while carbonized rice husk was found to be mesoporous (pores of {approx}3.9 nm) and hydrophobic. These hybrid microporous-mesoporous and hydrophilic-hydrophobic composites are expected to be useful for decontamination of metal cations as well as organic contaminants simultaneously. - Graphical Abstract: Novel Na-X zeolite/porous carbon composite.

  7. Specific oxidation pattern of soluble starch with TEMPO-NaBr-NaClO system.

    PubMed

    Hao, Jie; Lu, Jiaojiao; Xu, Naiyu; Linhardt, Robert J; Zhang, Zhenqing

    2016-08-01

    Oxidized starch, one of the most important starch derivatives, has many different properties and applications. Currently, there are two ways to produce oxidized starch, through specific and nonspecific oxidation. Specific oxidation using the stable nitroxyl radical, 2,2,6,6-tetramethyl preparidinloxy (TEMPO), with NaBr and NaClO can produce oxidized starches with different properties under good quality control. In the current study, we examine the products of specifically oxidized starch. As the amount of oxidant and the temperature, two critical factors impacting the oxidation of starch were thoroughly investigated. Analysis of the molecular weight (MW), degree of oxidization (DO) and the detailed structures of corresponding products was accomplished using gel permeation chromatography with multi-angle laser light scattering (GPC-MALLS), infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and quadrapole time-of-flight mass spectrometry (Q/TOF-MS). According to the analytical results, the oxidation patterns of starch treated with specific oxidant TEMPO-NaBr-NaClO were established. When high amounts of oxidant was applied, more glucose residues within starch were oxidized to glucuronic acids (higher DO) and substantial degradation to starch oligosaccharides was observed. By selecting a reaction temperature of 25°C a high DO could be obtained for a given amount of oxidant. The reducing end sugar residue within oxidized starch was itself oxidized and ring opened in all TEMPO-NaBr-NaClO reactions. Furthermore, extra oxidant generated additional novel structures in the reducing end residues of some products, particularly in low temperature reactions.

  8. Design and implementation of the NaI(Tl)/CsI(Na) detectors output signal generator

    NASA Astrophysics Data System (ADS)

    Zhou, Xu; Liu, Cong-Zhan; Zhao, Jian-Ling; Zhang, Fei; Zhang, Yi-Fei; Li, Zheng-Wei; Zhang, Shuo; Li, Xu-Fang; Lu, Xue-Feng; Xu, Zhen-Ling; Lu, Fang-Jun

    2014-02-01

    We designed and implemented a signal generator that can simulate the output of the NaI(Tl)/CsI(Na) detectors' pre-amplifier onboard the Hard X-ray Modulation Telescope (HXMT). Using the development of the FPGA (Field Programmable Gate Array) with VHDL language and adding a random constituent, we have finally produced the double exponential random pulse signal generator. The statistical distribution of the signal amplitude is programmable. The occurrence time intervals of the adjacent signals contain negative exponential distribution statistically.

  9. Neutron spectroscopy of water dynamics in NaX and NaA zeolites

    NASA Astrophysics Data System (ADS)

    Kamitakahara, William A.; Wada, Noboru

    2008-04-01

    We have investigated the dynamics of water molecules in zeolites NaA and NaX by high-resolution quasielastic neutron scattering methods. Between 260 and 310 K, the local translational diffusive motion of water in the zeolites is one to two orders of magnitude slower than in bulk water. The Q dependence of the scattering shows effects of confinement and the presence of both relatively mobile and immobile molecules. The speed of the diffusive motion depends strongly on hydration level. Comparison with other hydrated siliceous materials indicates that the host charge per water molecule is a major factor in determining the time scale of diffusion.

  10. Direct Reactions with MoNA-LISA

    NASA Astrophysics Data System (ADS)

    Kuchera, Anthony

    2016-03-01

    Nuclear reactions can be used to probe the structure of nuclei. Direct reactions, which take place on short time scales, are well-suited for experiments with beams of short-lived nuclei. One such reaction is nucleon knockout where a proton or neutron is removed from the incoming beam from the interaction with a target. Single nucleon knockout reactions have been used to study the single-particle nature of nuclear wave functions. A recent experiment at the National Superconducting Cyclotron Laboratory was performed to measure cross sections from single nucleon knockout reactions for several p-shell nuclei. Detection of the residual nucleus in coincidence with any gamma rays emitted from the target allowed cross sections to ground and excited states to be measured. Together with input from reaction theory, ab initio structure theories can be tested. Simultaneously the accuracy of knockout reaction models can be validated by detecting the knocked out neutron with the Modular Neutron Array and Large multi-Institutional Scintillator Array (MoNA-LISA). Preliminary results from this experiment will be shown. Knockout reactions can also be used to populate nuclei which are neutron unbound, thus emit neutrons nearly instantaneously. The structure of these nuclei, therefore, cannot be probed with gamma ray spectroscopy. However, with large neutron detectors like MoNA-LISA the properties of these short-lived nuclei are able to be measured. Recent results using MoNA-LISA to study the structure of neutron-rich nuclei will be presented. The author would like to acknowledge support from the NNSA and NSF.

  11. Revisiting the hydration structure of aqueous Na+

    DOE PAGES

    Galib, M.; Baer, M. D.; Skinner, L. B.; ...

    2017-02-27

    In this paper, a combination of theory, X-ray diffraction (XRD) and extended x-ray absorption fine structure (EXAFS) are used to probe the hydration structure of aqueous Na+. The high spatial resolution of the XRD measurements corresponds to Qmax = 24 Å–1 while the first-reported Na K-edge EXAFS measurements have a spatial resolution corresponding to 2k = Qmax = 16 Å–1. Both provide an accurate measure of the shape and position of the first peak in the Na–O pair distribution function, gNaO(r). The measured Na–O distances of 2.384 ± 0.003 Å (XRD) and 2.37 ± 0.024 Å (EXAFS) are in excellentmore » agreement. These measurements show a much shorter Na–O distance than generally reported in the experimental literature (Na–Oavg ~ 2.44 Å) although the current measurements are in agreement with recent neutron diffraction measurements. The measured Na–O coordination number from XRD is 5.5 ± 0.3. The measured structure is compared with both classical and first-principles density functional theory (DFT) simulations. Both of the DFT-based methods, revPBE and BLYP, predict a Na–O distance that is too long by about 0.05 Å with respect to the experimental data (EXAFS and XRD). The inclusion of dispersion interactions (–D3 and –D2) significantly worsens the agreement with experiment by further increasing the Na–O distance by 0.07 Å. In contrast, the use of a classical Na–O Lennard-Jones potential with SPC/E water accurately predicts the Na–O distance as 2.39 Å although the Na–O peak is over-structured with respect to experiment.« less

  12. FT-IR and XRD analysis of natural Na-bentonite and Cu(II)-loaded Na-bentonite

    NASA Astrophysics Data System (ADS)

    Zhirong, Liu; Azhar Uddin, Md.; Zhanxue, Sun

    2011-09-01

    Na-bentonite has been studied extensively because of its strong adsorption capacity and complexation ability. In this work, surface area, total pore volume, mean pore diameter, TG, DTA, FT-IR and XRD were carried out in order to reveal the characteristics of natural Na-bentonite. XRD and FT-IR of natural Na-bentonite (China) and Cu-loaded Na-bentonite as a function of Na-bentonite dosage and temperature using batch technique were characterized in detail, respectively.

  13. FT-IR and XRD analysis of natural Na-bentonite and Cu(II)-loaded Na-bentonite.

    PubMed

    Zhirong, Liu; Azhar Uddin, Md; Zhanxue, Sun

    2011-09-01

    Na-bentonite has been studied extensively because of its strong adsorption capacity and complexation ability. In this work, surface area, total pore volume, mean pore diameter, TG, DTA, FT-IR and XRD were carried out in order to reveal the characteristics of natural Na-bentonite. XRD and FT-IR of natural Na-bentonite (China) and Cu-loaded Na-bentonite as a function of Na-bentonite dosage and temperature using batch technique were characterized in detail, respectively.

  14. COPPER Students - ELaNa IV

    NASA Image and Video Library

    2013-07-11

    The Close Orbiting Propellant Plume Elemental Recognition (COPPER) was developed by students from St. Louis University as a technology demonstration mission whose objective is to test the suitability of a commercially-available compact uncooled microbolometer (tiny infrared camera) array for scientific imagery of Earth in the long-wave infrared range (LWIR, 7-13 microns). Launched by NASA’s CubeSat Launch Initiative on the ELaNa IV mission as an auxiliary payload aboard the U.S. Air Force-led Operationally Responsive Space (ORS-3) Mission on November 19, 2013.

  15. CONCEPTUAL BASIS FOR NATURAL ATTENUATION (NA) ...

    EPA Pesticide Factsheets

    As used in enforcement actions at hazardous waste sites by U.S. EPA, monitored natural attenuation is a remedy fully equivalent to any other remedy. The acceptance of MNA is based on three lines of evidence: historical ground water and/or soil chemistry data that demonstrates a trend of declining contaminant concentration, 2. hydrogeologic and geochemical data that demonstrate NA processes and rates, and 3. Field or microcosm studies. MNA is appropriate as remedial approach only where it can be demonstrated to achieve remedial objectives within reasonable time frame, and meets the applicable remedy selection criteria for the particular regulatory program. To inform the public.

  16. The NA62 experiment at CERN

    NASA Astrophysics Data System (ADS)

    Piccini, Mauro

    2016-11-01

    The rare decays K → πvv¯ are excellent processes to make tests of new physics at the highest scale complementary to LHC thanks to their theoretically cleanness. The NA62 experiment at CERN SPS aims to collect of the order of 100 events in two years of data taking for the decay K+ → π+vv¯, keeping the background at the level of 10%. Part of the experimental apparatus has been commissioned during a technical run in 2012. The diverse and innovative experimental techniques will be explained and some preliminary results obtained during the 2014 pilot run will be reviewed.

  17. Status of the NA62 Experiment

    NASA Astrophysics Data System (ADS)

    Palladino, Vito

    2016-04-01

    The rare decays {{{K}}^ + } to {π ^ + }{{ν bar ν }} are excellent processes to make tests of new physics at the highest scale complementary to LHC thanks to their theoretically cleaness. The NA62 experiment at CERN SPS aims to collect of the order of 100 events in two years of data taking, keeping the background at the level of 10%. Part of the experimental apparatus has been commissioned during a technical run in 2012. The physics prospects and the status of the experiment will be reviewed after the commissioning run of 2014 and the data taking in 2015.

  18. The NA62 Gigatracker pixel detector system

    NASA Astrophysics Data System (ADS)

    Mazza, G.; Ceccucci, A.; Cortina, E.; Cotta Ramusino, A.; Dellacasa, G.; Fiorini, M.; Garbolino, S.; Jarron, P.; Kaplon, J.; Kluge, A.; Marchetto, F.; Martin, E.; Martoiu, S.; Noy, M.; Petrucci, F.; Riedler, P.; Rivetti, A.; Tiuraniemi, S.

    2010-05-01

    The silicon tracker for the NA62 experiment has to provide both a time resolution of 150 ps rms and a space resolution of about 100 μm rms. These challenging specifications require the development of a new readout electronics in order to address the problem of measuring the tracks arrival time with such a high channel density. Moreover, the high particle density (up to 1.5 MHz/mm2 in the center and 0.8-1 GHz in total) requires a high speed measurement and data transmission in order to keep the dead time below 1%.

  19. Subnitride chemistry: A first-principles study of the NaBa 3N, Na 5Ba 3N, and Na 16Ba 6N phases

    NASA Astrophysics Data System (ADS)

    Oliva, Josep M.

    2005-04-01

    An ab initio study on the electronic structure of the subnitrides NaBa 3N, Na 5Ba 3N, and Na 16Ba 6N is performed for the first time. The NaBa 3N and Na 5Ba 3N phases consist of infinite 1∞[NBa 6/2] strands composed of face-sharing NBa 6 octahedra surrounded by a "sea" of sodium atoms. The Na 16Ba 6N phase consist of discrete [NBa 6] octahedra arranged in a body-cubic fashion, surrounded by a "sea" of sodium atoms. Our calculations suggest that the title subnitrides are metals. Analysis of the electronic structure shows partial interaction of N(2s) with Ba(5 p) electrons in the lower energy region for NaBa 3N and Na 5Ba 3N. However, no dispersion is observed for the N(2s) and Ba(5 p) bands in the cubic phase Na 16Ba 6N. The metallic band below the Fermi level shows a strong mixing of N(2p), Ba(6 s), Ba(5 d), Ba(6 p), Na(3 s) and Na(3 p) orbitals. The metallic character in these nitrides stems from delocalized electrons corresponding to hybridized 5dl6sm6pn barium orbitals which interact with hybridized 3sn3pm sodium orbitals. Analysis of the electron density and electronic structure in these nitrides shows two different regions: a metallic matrix corresponding to the sodium atoms and the regions around them and heteropolar bonding between nitrogen and barium within the infinite 1∞[NBa 6/2] strands of the NaBa 3N and Na 5Ba 3N phases, and within the isolated [NBa 6] octahedra of the Na 16Ba 6N phase. The nitrogen atoms inside the strands and octahedra are negatively charged, the anionic character of nitrogens being larger in the isolated octahedra of the cubic phase Na 16Ba 6N, due to the lack of electron delocalization along one direction as opposed to the other phases. The sodium and barium atoms appear to be slightly negatively and positively charged, the latter to a larger extent. From the computed Ba-N overlap populations as well as the analysis of the contour maps of differences between total density and superposition of atomic densities, we suggest

  20. Interactions between Na+ channels and Na+-HCO3- cotransporters in the freshwater fish gill MR cell: a model for transepithelial Na+ uptake.

    PubMed

    Parks, Scott K; Tresguerres, Martin; Goss, Greg G

    2007-02-01

    Isolated mitochondria-rich (MR) cells from the rainbow trout gill epithelium were subjected to intracellular pH (pH(i)) imaging with the pH-sensitive dye BCECF-AM. MR cells were categorized into two distinct functional subtypes based on their ability to recover pH(i) from an NH(4)Cl-induced acidification in the absence of Na(+). An apparent link between resting pH(i) and Na(+)-independent pH(i) recovery was made. We observed a unique pH(i) acidification event that was induced by extracellular Na(+) addition. This further classified the mixed MR cell population into two functional subtypes: the majority of cells (77%) demonstrated the Na(+)-induced pH(i) acidification, whereas the minority (23%) demonstrated an alkalinization of pH(i) under the same circumstances. The focus of this study was placed on the Na(+)-induced acidification and pharmacological analysis via the use of amiloride and phenamil, which revealed that Na(+) uptake was responsible for the intracellular acidification. Further experiments revealed that pH(i) acidification could be abolished when Na(+) was allowed entry into the cell, but the activity of an electrogenic Na(+)-HCO(3)(-) cotransporter (NBC) was inhibited by DIDS. The electrogenic NBC activity was supported by a DIDS-sensitive, Na(+)-induced membrane potential depolarization as observed via imaging of the voltage-sensitive dye bis-oxonol. We also demonstrated NBC immunoreactivity via Western blotting and immunohistochemistry in gill tissue. We propose a model for transepithelial Na(+) uptake occurring via an apical Na(+) channel linked to a basolateral, electrogenic NBC in one subpopulation of MR cells.

  1. On the regulation of Na+/H+ and K+/H+ antiport in yeast mitochondria: evidence for the absence of an Na(+)-selective Na+/H+ antiporter.

    PubMed

    Welihinda, A A; Trumbly, R J; Garlid, K D; Beavis, A D

    1993-10-04

    Unlike mammalian mitochondria, yeast mitochondria swell spontaneously in both NaOAc and KOAc. This swelling reflects the activity of an electroneutral cation/H+ antiport pathway. Transport of neither salt is stimulated by depletion of endogenous divalent cations; however, it can be inhibited by addition of exogenous divalent cations (Mg2+ IC50 = 2.08 mM, Ca2+ IC50 = 0.82 mM). Transport of both Na+ and K+ can be completely inhibited by the amphiphilic amines propranolol (IC50 = 71 microM) and quinine (IC50 = 199 microM) with indistinguishable IC50 values. Dicyclohexylcarbodiimide inhibits with a second-order rate constant of 1.6 x 10(-4) (nmol DCCD/mg)-1 min-1 at 0 degrees C; however, with both Na+ and K+ inhibition reaches a maximum of about 46%. The remaining transport can still be inhibited by propranolol. Transport of both cations is sensitive to pH; yielding linear Hill plots and Dixon plots with a pIC50 value of 7.7 for both Na+ and K+. These properties are qualitatively the same as those of the non-selective K+/H+ antiporter of mammalian mitochondria. However, the remarkable similarity between the data obtained in Na+ and K+ media suggests that an antiporter akin to the Na(+)-selective Na+/H+ antiporter of mammalian mitochondria, which is inhibited by none of these agents, is absent in yeast. In an attempt to reveal the activity of a propranolol-insensitive Na(+)-selective antiporter, we compared the rates of Na+/H+ and K+/H+ antiport in the presence of sufficient propranolol to block the K+/H+ antiporter. Between pH 4.6 and 8.8 no difference could be detected. Consequently, we conclude that yeast mitochondria lack the typical Na(+)-selective Na+/H+ antiporter of mammalian mitochondria.

  2. Novel regulation of cell [Na(+)] in macula densa cells: apical Na(+) recycling by H-K-ATPase.

    PubMed

    Peti-Peterdi, János; Bebok, Zsuzsa; Lapointe, Jean-Yves; Bell, P Darwin

    2002-02-01

    Na-K-ATPase is the nearly ubiquitous enzyme that maintains low-Na(+), high-K(+) concentrations in cells by actively extruding Na(+) in exchange for K(+). The prevailing paradigm in polarized absorbing epithelial cells, including renal nephron segments and intestine, has been that Na-K-ATPase is restricted to the basolateral membrane domain, where it plays a prominent role in Na(+) absorption. We have found, however, that macula densa (MD) cells lack functionally and immunologically detectable amounts of Na-K-ATPase protein. In fact, these cells appear to regulate their cytosolic [Na(+)] via another member of the P-type ATPase family, the colonic form of H-K-ATPase, which is located at the apical membrane in these cells. We now report that this constitutively expressed apical MD colonic H-K-ATPase can function as a Na(H)-K-ATPase and regulate cytosolic [Na(+)] in a novel manner. This apical Na(+)-recycling mechanism may be important as part of the sensor function of MD cells and represents a new paradigm in cell [Na(+)] regulation.

  3. Penning and associative ionization in crossed-beam Na/Na collisions assisted by strong resonant laser fields

    SciTech Connect

    Weiner, J.; Polak-Dingels, P.

    1981-01-01

    We observe the production of Na/sub 2//sup +/ and Na/sup +/ arising from single collisions between crossed beams of sodium atoms when a laser field is tuned near the Na(3p /sup 2/P/sub 3/2/) and Na(3p /sup 2/P/sub 1/2/) transitions. Measurements of ion intensity vs laser intensity show that at moderately high power true laser-induced processes dominate over purely collisional effects. Relative intensity of mass-selected ions produced at either member of the Na resonance doublet shows conclusively that Na/sup +/ does not arise simply from photodissociation of Na/sub 2//sup +/ but must result from a direct, laser-induced collisional ionization.

  4. Vanadate sensitivity of Na+, K+-ATPase from Schistosoma mansoni and its modulation by Na+, K+ and Mg2+.

    PubMed

    Noel, F; Pardon, R S

    1989-01-01

    Vanadate inhibitory effects on Na+, K+-ATPases from carcass of Schistosoma mansoni and from lamb kidney outer medulla were compared in the presence of various concentrations of Na+, K+ and Mg2+. Depending on the ionic conditions, the schistosomal Na+, K+-ATPase was 2.4- to 175-fold less sensitive to vanadate than the lamb kidney enzyme. In 100 mM Na+, 3 mM K+ and 3 mM Mg2+, schistosomal Na+, K+-ATPase was surprisingly resistant to vanadate (I50 = 944 microM). The difference in vanadate sensitivity between schistosomal and lamb Na+, K+-ATPases may be due to a species difference in the efficacy of Na+, K+ and Mg2+ in promoting conformational changes between E1 and E2 forms of the enzyme.

  5. Effects of non-uniform root zone salinity on water use, Na+ recirculation, and Na+ and H+ flux in cotton

    PubMed Central

    Kong, Xiangqiang; Luo, Zhen; Dong, Hezhong; Eneji, A. Egrinya

    2012-01-01

    A new split-root system was established through grafting to study cotton response to non-uniform salinity. Each root half was treated with either uniform (100/100 mM) or non-uniform NaCl concentrations (0/200 and 50/150 mM). In contrast to uniform control, non-uniform salinity treatment improved plant growth and water use, with more water absorbed from the non- and low salinity side. Non-uniform treatments decreased Na+ concentrations in leaves. The [Na+] in the ‘0’ side roots of the 0/200 treatment was significantly higher than that in either side of the 0/0 control, but greatly decreased when the ‘0’ side phloem was girdled, suggesting that the increased [Na+] in the ‘0’ side roots was possibly due to transportation of foliar Na+ to roots through phloem. Plants under non-uniform salinity extruded more Na+ from the root than those under uniform salinity. Root Na+ efflux in the low salinity side was greatly enhanced by the higher salinity side. NaCl-induced Na+ efflux and H+ influx were inhibited by amiloride and sodium orthovanadate, suggesting that root Na+ extrusion was probably due to active Na+/H+ antiport across the plasma membrane. Improved plant growth under non-uniform salinity was thus attributed to increased water use, reduced leaf Na+ concentration, transport of excessive foliar Na+ to the low salinity side, and enhanced Na+ efflux from the low salinity root. PMID:22200663

  6. Synthesis of NaYF4, NaLuF4 and NaGdF4-based upconversion nanocrystals with hydro (solvo) thermal methods.

    PubMed

    Yin, Dongguang; Song, Kailin; Ou, Yangjuan; Wang, Chengcheng; Liu, Bing; Wu, Minghong

    2013-06-01

    Serials of NaYF4, NaLuF4 and NaGdF4-based nanocrystals have been synthesized successfully by solvothermal and hydrothermal, respectively. The properties of the products were characterized and compared. The nanocrystals prepared by hydrothermal method exhibited uniform hexagonal phase and large size, while the nanocrystals prepared by solvothermal method displayed high upconversion luminescence (UCL) and small size. The UCL intensities of the nanocrystals prepared by solvothermal method were higher than that of nanocrystals from hydrothermal method. Whether using solvothermal or hydrothermal method, the UCL intensities of the nanocrystals were in the sequence (from strong to weak) of NaLuF4:Gd/Yb/Tm, NaLuF4:Yb/Tm, NaGdF4:Yb/Tm, NaYF4:Gd/Yb/Tm and NaYF4:Yb/Tm, respectively. This is the first time to systematically compare three kinds of host-based nanocrystals, which are prepared by two different approaches with various lanthanide ions doped. This work could provide new insight into fabrication of upconversion nanocrystals with intense UCL and controllable morphology and size via using suitable doping ions, host materials and efficient approaches.

  7. NaSrMn2F7, NaCaFe2F7, and NaSrFe2F7: novel single crystal pyrochlore antiferromagnets

    NASA Astrophysics Data System (ADS)

    Sanders, M. B.; Krizan, J. W.; Plumb, K. W.; McQueen, T. M.; Cava, R. J.

    2017-02-01

    The crystal structures and magnetic properties of three previously unreported A2B2F7 pyrochlore materials, NaSrMn2F7, NaCaFe2F7, and NaSrFe2F7 are presented. In these compounds, either S  =  2Fe2+ or S  =  5/2Mn2+ is on the B site, while nonmagnetic Na and Ca (Na and Sr) are disordered on the A site. The materials, which were grown as crystals via the floating zone method, display high effective magnetic moments and large Curie-Weiss thetas. Despite these characteristics, no ordering transition is detected. However, freezing of the magnetic spins, characterized by peaks in the susceptibility or specific heat, is observed at very low temperatures. The empirical frustration index, f  =  -θ CW/T f, for the materials are 36 (NaSrMn2F7), 27 (NaSrFe2F7), and 19 (NaCaFe2F7). AC susceptibility, DC susceptibility, and heat capacity measurements are used to characterize the observed spin glass behavior. The results suggest that the compounds are frustrated pyrochlore antiferromagnets with weak bond disorder. The magnetic phenomena that these fluoride pyrochlores exhibit, in addition to their availability as relatively large single crystals, make them promising candidates for the study of geometric magnetic frustration.

  8. NA-CORDEX: Overview and Sample Results

    NASA Astrophysics Data System (ADS)

    Bukovsky, Melissa; Mearns, Linda; Arritt, Raymond; Castro, Christopher; Chang, Hsin-I.; Christensen, Jens; Christensen, Ole; Frigon, Anne; Gutowski, William; Kjellström, Erik; Laprise, René; McGinnis, Seth; Nikulin, Grigory; Scinocca, John; Sushama, Laxmi; Winger, Katje

    2017-04-01

    The North American CORDEX program (NA-CORDEX) has produced a good number of projections of climate according to the first phase of the CORDEX program. These simulations are based on a wide range of regional and global climate models, and some matrices of combinations have resulted. The RCMs involved include: WRF, CanRCM4, CRCM5, RegCM4, RCA4, and HirHam5. Driving GCMs include: EC-EARTH, CanESM2, HadGEM2-ES, GFDL-ESM2M, MPI-ESM-LR. These GCMs nicely span the equilibrium climate sensitivity of the GCMs making up the CMIP5 suite of models. Simulations have been performed both at .44 and .22 spatial resolutions and often for both RCP8.5 and 4.5. We will present an update of the status of NA-CORDEX, an overview of the simulations, and some of the results for North America, focusing on the quality of the baseline climate simulations and the projections of precipitation and temperature.

  9. The NA62 GigaTracker

    NASA Astrophysics Data System (ADS)

    Aglieri Rinella, G.; Feito, D. Alvarez; Arcidiacono, R.; Biino, C.; Bonacini, S.; Ceccucci, A.; Chiozzi, S.; Gil, E. Cortina; Ramusino, A. Cotta; Degrange, J.; Fiorini, M.; Gamberini, E.; Gianoli, A.; Kaplon, J.; Kluge, A.; Mapelli, A.; Marchetto, F.; Minucci, E.; Morel, M.; Noël, J.; Noy, M.; Perktold, L.; Perrin-Terrin, M.; Petagna, P.; Petrucci, F.; Poltorak, K.; Romagnoli, G.; Ruggiero, G.; Velghe, B.; Wahl, H.

    2017-02-01

    The GigaTracker is a hybrid silicon pixel detector built for the NA62 experiment aiming at measuring the branching fraction of the ultra-rare kaon decay K+ →π+ ν ν bar at the CERN SPS. The detector has to track particles in a beam with a flux reaching 1.3 MHz/mm2 and provide single-hit timing with 200 ps RMS resolution for a total material budget of less than 0.5% X0 per station. The tracker comprises three 60.8 mm×27 mm stations installed in vacuum (∼10-6 mbar) and cooled with liquid C6F14 circulating through micro-channels etched inside a few hundred micron thick silicon plates. Each station is composed of a 200 μm thick silicon sensor read out by 2×5 custom 100 μm thick ASICs, called TDCPix. Each chip contains 40×45 asynchronous pixels, 300 μm×300 μm each and is instrumented with 100 ps bin time-to-digital converters. In order to cope with the high rate, the TDCPix is equipped with four 3.2 Gb/s serialisers sending out the data. We will describe the detector and the results from the 2014 and 2015 NA62 runs.

  10. Minimizing Load Effects on NA4 Gear Vibration Diagnostic Parameter

    NASA Technical Reports Server (NTRS)

    Dempsey, Paula J.; Zakrajsek, James J.

    2001-01-01

    NA4 is a vibration diagnostic parameter, developed by researchers at NASA Glenn Research Center, for health monitoring of gears in helicopter transmissions. The NA4 reacts to the onset of gear pitting damage and continues to react to the damage as it spreads. This research also indicates NA4 reacts similarly to load variations. The sensitivity of NA4 to load changes will substantially affect its performance on a helicopter gearbox that experiences continuously changing load throughout its flight regimes. The parameter NA4 has been used to monitor gear fatigue tests at constant load. At constant load, NA4 effectively detects the onset of pitting damage and tracks damage severity. Previous research also shows that NA4 reacts to changes in load applied to the gears in the same way it reacts to the onset of pitting damage. The method used to calculate NA4 was modified to minimize these load effects. The modified NA4 parameter was applied to four sets of experimental data. Results indicate the modified NA4 is no longer sensitive to load changes, but remains sensitive to pitting damage.

  11. Adsorbed or intercalated: Na on graphene/Ir(111)

    NASA Astrophysics Data System (ADS)

    Pervan, Petar; Lazić, Predrag

    2017-09-01

    Interaction of sodium with graphene (Gr) on Ir(111) was studied with the aim to resolve the issue of Na adsorption/intercalation kinetics. The system Na/Gr/Ir(111) was studied by means of angle-resolved photoemission spectroscopy, low-energy electron diffraction, and ab initio density functional theory (DFT) calculation. It has been found that at room temperature (RT) and low concentrations Na is dominantly adsorbed on graphene. At higher concentrations, an intercalation process sets in so that it is possible to observe the coexistence of these two states. Eventually, all Na atoms are found in the intercalated state as determined by exposure to oxygen. While adsorption of Na on graphene already intercalated by Na [Na/Gr/Na/Ir(111) system] at RT was not possible, we could observe Li adsorption through the increase of Dirac point binding energy. Li coadsorption strongly affects the binding energy of the iridium surface state as well. This finding was supported by DFT calculations of adsorption energy of Na and Li on bare and fully Na intercalated graphene.

  12. Elevated intracellular Na(+) concentrations in developing spinal neurons.

    PubMed

    Lindsly, Casie; Gonzalez-Islas, Carlos; Wenner, Peter

    2017-03-01

    Over 25 years ago it was first reported that intracellular chloride levels (Cl(-)in ) were higher in developing neurons than in maturity. This finding has had significant implications for understanding the excitability of developing networks and recognizing the underlying causes of hyperexcitability associated with disease and neural injury. While there is some evidence that intracellular sodium levels (Na(+)in ) change during the development of non-neural cells, it has largely been assumed that Na(+)in is the same in developing and mature neurons. Here, using the sodium indicator SBFI, we test this idea and find that Na(+)in is significantly higher in embryonic spinal motoneurons and interneurons than in maturity. We find that Na(+)in reaches ~ 60 mM in mid-embryonic development and is then reduced to ~ 30 mM in late embryonic development. By retrogradely labeling motoneurons with SBFI we can reliably follow Na(+)in levels in vitro for hours. Bursts of spiking activity, and blocking voltage-gated sodium channels did not influence observed motoneuron sodium levels. On the other hand, Na(+)in was reduced by blocking the Na(+) -K(+) -2Cl(-) cotransporter NKCC1, and was highly sensitive to changes in external Na(+) and a blocker of the Na(+) /K(+) ATPase. Our findings suggest that the Na(+) gradient is weaker in embryonic neuronal development and strengthens in maturity in a manner similar to that of Cl(-) .

  13. Hydrogen Sulfide Induced Disruption of Na+ Homeostasis in the Cortex

    PubMed Central

    Chao, Dongman; He, Xiaozhou; Yang, Yilin; Balboni, Gianfranco; Salvadori, Severo; Kim, Dong H.; Xia, Ying

    2012-01-01

    Maintenance of ionic balance is essential for neuronal functioning. Hydrogen sulfide (H2S), a known toxic environmental gaseous pollutant, has been recently recognized as a gasotransmitter involved in numerous biological processes and is believed to play an important role in the neural activities under both physiological and pathological conditions. However, it is unclear if it plays any role in maintenance of ionic homeostasis in the brain under physiological/pathophysiological conditions. Here, we report by directly measuring Na+ activity using Na+ selective electrodes in mouse cortical slices that H2S donor sodium hydrosulfide (NaHS) increased Na+ influx in a concentration-dependent manner. This effect could be partially blocked by either Na+ channel blocker or N-methyl-D-aspartate receptor (NMDAR) blocker alone or almost completely abolished by coapplication of both blockers but not by non-NMDAR blocker. These data suggest that increased H2S in pathophysiological conditions, e.g., hypoxia/ischemia, potentially causes a disruption of ionic homeostasis by massive Na+ influx through Na+ channels and NMDARs, thus injuring neural functions. Activation of delta-opioid receptors (DOR), which reduces Na+ currents/influx in normoxia, had no effect on H2S-induced Na+ influx, suggesting that H2S-induced disruption of Na+ homeostasis is resistant to DOR regulation and may play a major role in neuronal injury in pathophysiological conditions, e.g., hypoxia/ischemia. PMID:22474073

  14. Rydberg States of Na-doped Helium Nanodroplets

    NASA Astrophysics Data System (ADS)

    Drabbels, Marcel

    2008-03-01

    The dynamics of excited states of Na atoms deposited on the surface of helium nanodroplets has been investigated with velocity map ion imaging, photoelectron spectroscopy and time-of-flight mass-spectroscopy. For the first time, the excitation spectra of Na-doped helium nanodroplets corresponding to Rydberg states of Na atoms have been measured from the lowest excited 3p state up to the ionization threshold. All lines in the excitation spectra are shifted and broadened with respect to the corresponding atomic lines. In addition to bare Na* atoms also Na*HeN (N = 1-6) exciplexes are detected upon excitation. Photoelectron spectroscopy reveals the desorption of Na* not only in the initially excited states but also in lower lying states, indicating that relaxation plays an important role. The recorded velocity distributions show interesting characteristics: for the lowest states the mean kinetic energy of Na* increases linearly with excitation energy. The velocity distributions of Na*HeN exciplexes do not manifest such remarkable properties. The observations can be largely explained by assuming that the interaction of Na* with the helium nanodroplet can be described by the sum of Na*-He pair potentials.

  15. Direct interaction of Na-azide with the KATP channel.

    PubMed

    Trapp, S; Ashcroft, F M

    2000-11-01

    1. The effects of the metabolic inhibitor sodium azide were tested on excised macropatches from Xenopus oocytes expressing cloned ATP-sensitive potassium (KATP) channels of the Kir6.2/SUR1 type. 2. In inside-out patches from oocytes expressing Kir6.2 delta C36 (a truncated form of Kir6.2 that expresses in the absence of SUR), intracellular Na-azide inhibited macroscopic currents with an IC50 of 11 mM. The inhibitory effect of Na-azide was mimicked by the same concentration of NaCl, but not by sucrose. 3. Na-azide and NaCl blocked Kir6.2/SUR1 currents with IC50 of 36 mM and 19 mM, respectively. Inhibition was abolished in the absence of intracellular Mg2+. In contrast, Kir6.2 delta C36 currents were inhibited by Na-azide both in the presence or absence of intracellular Mg2+. 4. Kir6.2/SUR1 currents were less sensitive to 3 mM Na-azide in the presence of MgATP. This apparent reduction in sensitivity is caused by a small activatory effect of Na-azide conferred by SUR. 5. We conclude that, in addition to its well-established inhibitory effect on cellular metabolism, which leads to activation of KATP channels in intact cells, intracellular Na-azide has direct effects on the KATP channel. Inhibition is intrinsic to Kir6.2, is mediated by Na+, and is modulated by SUR. There is also a small, ATP-dependent, stimulatory effect of Na-azide mediated by the SUR subunit. The direct effects of 3 mM Na-azide on KATP channels are negligible in comparison to the metabolic activation produced by the same Na-azide concentration.

  16. Theoretical calculation of low-lying states of NaAr and NaXe

    NASA Technical Reports Server (NTRS)

    Laskowski, B. C.; Langhoff, S. R.; Stallcop, J. R.

    1981-01-01

    Potential curves as well as dipole moments and linking transition moments are calculated for the ground X 2 Sigma + and low lying excited A 2 Pi, B 2 Sigma +, C 2 Sigma +, (4) 2 Sigma +, (2) 2 Pi and (1) 2 Delta states of NaAr and NaXe. Calculations are performed using a self-consistent field plus configuration-interaction procedure with the core electrons replaced by an ab initio effective core potential. The potential curves obtained are found to be considerably less repulsive than the semiempirical curves of Pascale and Vandeplanque (1974) and to agree well with existing experimental data, although the binding energies of those states having potential minima due to van der Waals interactions are underestimated. Emission bands are also calculated for the X 2 Sigma + - C 2 Sigma + excimer transitions of NaAr and NaXe using the calculated transition moments and potential curves, and shown to agree well with experiment on the short-wavelength side of the maximum.

  17. Decomposition Kinetics of Titania Slag in Eutectic NaOH-NaNO3 System

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Wang, Zhi; Qi, Tao; Wang, Lina; Xue, Tianyan

    2016-02-01

    The decomposition kinetics and mechanism of titania slag in eutectic NaOH-NaNO3 system were studied in the temperature range 623 K to 723 K (350 °C to 450 °C). Decomposed products were examined using X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray spectroscopy. It has been identified that the main product is Na2TiO3 and the decomposition kinetics of titania slag followed a shrinking unreacted core model. It is proposed that the chemical reaction process was the rate determining step with apparent activation energy of 62.4 kJ/mol. NaNO3 was mainly acted as oxygen carrier and mass transport agent to lower the viscosity of the system. The purity of TiO2 obtained in the product was up to 99.3 pct. A flow diagram to produce TiO2 and to recycle the media was proposed.

  18. 24Mg(p, α)21Na reaction study for spectroscopy of 21Na

    DOE PAGES

    Cha, S. M.; Chae, K. Y.; Kim, A.; ...

    2015-11-03

    The Mg-24(p, alpha)Na-21 reaction was measured at the Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory in order to better constrain the spins and parities of the energy levels in Na-21 for the astrophysically important F-17(alpha, p)Ne-20 reaction rate calculation. 31-MeV proton beams from the 25-MV tandem accelerator and enriched Mg-24 solid targets were used. When recoiling He-4 particles from the Mg-24(p, alpha)Na-21 reaction we used a highly segmented silicon detector array to detect them; it measured the yields of He-4 particles over a range of angles simultaneously. A observed a new level at 6661 ± 5 keVmore » in the present work. The extracted angular distributions for the first four levels of Na-21 and the results from distorted wave Born approximation (DWBA) calculations were compared to verify and extract the angular momentum transfer.« less

  19. Regulation of persistent Na current by interactions between beta subunits of voltage-gated Na channels.

    PubMed

    Aman, Teresa K; Grieco-Calub, Tina M; Chen, Chunling; Rusconi, Raffaella; Slat, Emily A; Isom, Lori L; Raman, Indira M

    2009-02-18

    The beta subunits of voltage-gated Na channels (Scnxb) regulate the gating of pore-forming alpha subunits, as well as their trafficking and localization. In heterologous expression systems, beta1, beta2, and beta3 subunits influence inactivation and persistent current in different ways. To test how the beta4 protein regulates Na channel gating, we transfected beta4 into HEK (human embryonic kidney) cells stably expressing Na(V)1.1. Unlike a free peptide with a sequence from the beta4 cytoplasmic domain, the full-length beta4 protein did not block open channels. Instead, beta4 expression favored open states by shifting activation curves negative, decreasing the slope of the inactivation curve, and increasing the percentage of noninactivating current. Consequently, persistent current tripled in amplitude. Expression of beta1 or chimeric subunits including the beta1 extracellular domain, however, favored inactivation. Coexpressing Na(V)1.1 and beta4 with beta1 produced tiny persistent currents, indicating that beta1 overcomes the effects of beta4 in heterotrimeric channels. In contrast, beta1(C121W), which contains an extracellular epilepsy-associated mutation, did not counteract the destabilization of inactivation by beta4 and also required unusually large depolarizations for channel opening. In cultured hippocampal neurons transfected with beta4, persistent current was slightly but significantly increased. Moreover, in beta4-expressing neurons from Scn1b and Scn1b/Scn2b null mice, entry into inactivated states was slowed. These data suggest that beta1 and beta4 have antagonistic roles, the former favoring inactivation, and the latter favoring activation. Because increased Na channel availability may facilitate action potential firing, these results suggest a mechanism for seizure susceptibility of both mice and humans with disrupted beta1 subunits.

  20. [Na] and [K] dependence of the Na/K pump current-voltage relationship in guinea pig ventricular myocytes

    PubMed Central

    1989-01-01

    Na/K pump current was determined between -140 and +60 mV as steady- state, strophanthidin-sensitive, whole-cell current in guinea pig ventricular myocytes, voltage-clamped and internally dialyzed via wide- tipped pipettes. Solutions were designed to minimize all other components of membrane current. A device for exchanging the solution inside the pipette permitted investigation of Na/K pump current-voltage (I-V) relationships at several levels of pipette [Na] [( Na]pip) in a single cell; the effects of changes in external [Na] [( Na]o) or external [K] [( K]o) were also studied. At 50 mM [Na]pip, 5.4 mM [K]o, and approximately 150 mM [Na]o, Na/K pump current was steeply voltage dependent at negative potentials but was approximately constant at positive potentials. Under those conditions, reduction of [Na]o enhanced pump current at negative potentials but had little effect at positive potentials: at zero [Na]o, pump current was only weakly voltage dependent. At 5.4 mM [K]o and approximately 150 mM [Na]o, reduction of [Na]pip from 50 mM scaled down the sigmoid pump I-V relationship and shifted it slightly to the right (toward more positive potentials). Pump current at 0 mV was activated by [Na]pip according to the Hill equation with best-fit K0.5 approximately equal to 11 mM and Hill coefficient nH approximately equal to 1.4. At zero [Na]o, reduction of [Na]pip seemed to simply scale down the relatively flat pump I-V relationship: Hill fit parameters for pump activation by [Na]pip at 0 mV were K0.5 approximately equal to 10 mM, nH approximately equal to 1.4. At 50 mM [Na]pip and high [Na]o, reduction of [K]o from 5.4 mM scaled down the sigmoid I-V relationship and shifted it slightly to the right: at 0 mV, K0.5 approximately equal to 1.5 mM and nH approximately equal to 1.0. At zero [Na]o, lowering [K]o simply scaled down the flat pump I-V relationships yielding, at 0 mV, K0.5 approximately equal to 0.2 mM, nH approximately equal to 1.1. The voltage

  1. Catecholamine-induced transport systems in trout erythrocyte. Na+/H+ countertransport or NaCl cotransport?

    PubMed Central

    1986-01-01

    It has previously been shown (Baroin, A., F. Garcia-Romeu, T. Lamarre, and R. Motais. 1984a, b. Journal of Physiology. 350:137, 356:21; Mahe, Y., F. Garcia-Romeu, and R. Motais. 1985. European Journal of Pharmacology. 116:199) that the addition of catecholamines to an isotonic suspension of nucleated red blood cells of the rainbow trout first stimulates a cAMP-dependent, amiloride-sensitive Na+/H+ exchange. This stimulation seems to be transient. It is followed by a more permanent activation of a coupled entry of Na+ and Cl-, which is inhibited by amiloride but also by inhibitors of band 3 protein (DIDS, furosemide, niflumic acid). The coupled entry of Na+ and Cl- could therefore result from the parallel and simultaneous exchange of Na+out for H+in (via the cAMP-dependent Na+/H+ antiporter) and Cl- out for HCO3- in (via the anion exchange system located in band 3 protein). However, in view of the following arguments, it had been proposed that NaCl uptake does not proceed by the double-exchanger system but via an NaCl cotransport: (a) Na+ entry requires Cl- as anion (in NO3- medium, the Na uptake is strongly inhibited, whereas NO3- is an extremely effective substitute for Cl- in the anion exchange system); (b) Na uptake is not significantly affected by the presence of HCO3- in the suspension medium despite the fact that in red cells, Cl-/HCO3- exchange occurs more readily than the exchanges of Cl- for basic equivalents in a theoretically CO2-free medium (the so-called Cl-/OH- exchanges). The purpose of the present paper was a reassessment of the two models by using monensin, an ionophore allowing Na+/H+ exchange. From this study, it appears that NaCl entry results from the simultaneous functioning of the Na+/H+ antiporter and the anion exchange system. The apparent Cl dependence is explained by the fact that, in these erythrocytes, NO3- clearly inhibits the turnover rate of the Na+/H+ antiporter. As Na+/H+ exchange is the driving component in the salt uptake process

  2. Coordinated regulation of cardiac Na(+)/Ca (2+) exchanger and Na (+)-K (+)-ATPase by phospholemman (FXYD1).

    PubMed

    Cheung, Joseph Y; Zhang, Xue-Qian; Song, Jianliang; Gao, Erhe; Chan, Tung O; Rabinowitz, Joseph E; Koch, Walter J; Feldman, Arthur M; Wang, JuFang

    2013-01-01

    Phospholemman (PLM) is the founding member of the FXYD family of regulators of ion transport. PLM is a 72-amino acid protein consisting of the signature PFXYD motif in the extracellular N terminus, a single transmembrane (TM) domain, and a C-terminal cytoplasmic tail containing three phosphorylation sites. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. The TM domain of PLM interacts with TM9 of the α-subunit of Na(+)-K(+)-ATPase, while its cytoplasmic tail interacts with two small regions (spanning residues 248-252 and 300-304) of the proximal intracellular loop of Na(+)/Ca(2+) exchanger. Under stress, catecholamine stimulation phosphorylates PLM at serine(68), resulting in relief of inhibition of Na(+)-K(+)-ATPase by decreasing K(m) for Na(+) and increasing V(max), and simultaneous inhibition of Na(+)/Ca(2+) exchanger. Enhanced Na(+)-K(+)-ATPase activity lowers intracellular Na(+), thereby minimizing Ca(2+) overload and risks of arrhythmias. Inhibition of Na(+)/Ca(2+) exchanger reduces Ca(2+) efflux, thereby preserving contractility. Thus, the coordinated actions of PLM during stress serve to minimize arrhythmogenesis and maintain inotropy. In acute cardiac ischemia and chronic heart failure, either expression or phosphorylation of PLM or both are altered. PLM regulates important ion transporters in the heart and offers a tempting target for development of drugs to treat heart failure.

  3. Na emission and bubble instability in single-bubble sonoluminescence.

    PubMed

    Choi, Pak-Kon; Takumori, Keisuke; Lee, Hyang-Bok

    2017-09-01

    Na emission in single-bubble sonoluminescence (SBSL) was observed from 0.1mM sodium dodecyl sulfate (SDS) solution containing a dissolved noble gas at a low acoustic pressure, at which a continuous spectral component was negligible. High-speed shadowgraph movies were captured at a frame rate of 30,000fps, which indicated that bubble dancing is responsible for the Na emission. The measured bubble path length was well correlated with the Na intensity. The disintegration of a daughter bubble followed by immediate coalescence was frequently observed, which may have been the cause of the bubble dancing. A comparison of the Na spectra obtained in SBSL and multibubble SL showed that the conditions under which Na emission is generated are twofold. A narrow component was observed in the Na spectrum in SBSL, while narrow and broad components were observed in MBSL. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The paranodal cytoskeleton clusters Na(+) channels at nodes of Ranvier.

    PubMed

    Amor, Veronique; Zhang, Chuansheng; Vainshtein, Anna; Zhang, Ao; Zollinger, Daniel R; Eshed-Eisenbach, Yael; Brophy, Peter J; Rasband, Matthew N; Peles, Elior

    2017-01-30

    A high density of Na(+) channels at nodes of Ranvier is necessary for rapid and efficient action potential propagation in myelinated axons. Na+ channel clustering is thought to depend on two axonal cell adhesion molecules that mediate interactions between the axon and myelinating glia at the nodal gap (i.e., NF186) and the paranodal junction (i.e., Caspr). Here we show that while Na(+) channels cluster at nodes in the absence of NF186, they fail to do so in double conditional knockout mice lacking both NF186 and the paranodal cell adhesion molecule Caspr, demonstrating that a paranodal junction-dependent mechanism can cluster Na(+) channels at nodes. Furthermore, we show that paranode-dependent clustering of nodal Na(+) channels requires axonal βII spectrin which is concentrated at paranodes. Our results reveal that the paranodal junction-dependent mechanism of Na(+)channel clustering is mediated by the spectrin-based paranodal axonal cytoskeleton.

  5. Pyrophosphate-Fueled Na+ and H+ Transport in Prokaryotes

    PubMed Central

    Malinen, Anssi M.; Luoto, Heidi H.

    2013-01-01

    SUMMARY In its early history, life appeared to depend on pyrophosphate rather than ATP as the source of energy. Ancient membrane pyrophosphatases that couple pyrophosphate hydrolysis to active H+ transport across biological membranes (H+-pyrophosphatases) have long been known in prokaryotes, plants, and protists. Recent studies have identified two evolutionarily related and widespread prokaryotic relics that can pump Na+ (Na+-pyrophosphatase) or both Na+ and H+ (Na+,H+-pyrophosphatase). Both these transporters require Na+ for pyrophosphate hydrolysis and are further activated by K+. The determination of the three-dimensional structures of H+- and Na+-pyrophosphatases has been another recent breakthrough in the studies of these cation pumps. Structural and functional studies have highlighted the major determinants of the cation specificities of membrane pyrophosphatases and their potential use in constructing transgenic stress-resistant organisms. PMID:23699258

  6. Simulation of Na D emission near Europa during eclipse

    USGS Publications Warehouse

    Cassidy, T.A.; Johnson, R.E.; Geissler, P.E.; Leblanc, F.

    2008-01-01

    The Cassini imaging science subsystem observed Europa in eclipse during Cassini's Jupiter flyby. The disk-resolved observations revealed a spatially nonuniform emission in the wavelength range of 200-1050 nm (clear filters). By building on observations and simulations of Europa's Na atmosphere and torus we find that electron-excited Na in Europa's tenuous atmosphere can account for the observed emission if the Na is ejected preferentially from Europa's dark terrain. Copyright 2008 by the American Geophysical Union.

  7. Recent results and prospects for NA62 experiment

    NASA Astrophysics Data System (ADS)

    Martellotti, Silvia; Aglieri Rinella, G.; Aliberti, R.; Ambrosino, F.; Ammendola, R.; Angelucci, B.; Antonelli, A.; Anzivino, G.; Arcidiacono, R.; Azhinenko, I.; Balev, S.; Barbanera, M.; Bendotti, J.; Biagioni, A.; Bician, L.; Biino, C.; Bizzeti, A.; Blazek, T.; Blik, A.; Bloch-Devaux, B.; Bolotov, V.; Bonaiuto, V.; Boretto, M.; Bragadireanu, M.; Britton, D.; Britvich, G.; Brunetti, M. B.; Bryman, D.; Bucci, F.; Butin, F.; Capitolo, E.; Capoccia, C.; Capussela, T.; Cassese, A.; Catinaccio, A.; Cecchetti, A.; Ceccucci, A.; Cenci, P.; Cerny, V.; Cerri, C.; Checcucci, B.; Chikilev, O.; Chiozzi, S.; Ciaranfi, R.; Collazuol, G.; Conovaloff, A.; Cooke, P.; Cooper, P.; Corradi, G.; Cortina Gil, E.; Costantini, F.; Cotorobai, F.; Cotta Ramusino, A.; Coward, D.; D'Agostini, G.; Dainton, J.; Dalpiaz, P.; Danielsson, H.; Degrange, J.; De Simone, N.; Di Filippo, D.; Di Lella, L.; Di Lorenzo, S.; Dixon, N.; Doble, N.; Dobrich, B.; Duk, V.; Elsha, V.; Engelfried, J.; Enik, T.; Estrada, N.; Falaleev, V.; Fantechi, R.; Fascianelli, V.; Federici, L.; Fedotov, S.; Fiorini, M.; Fry, J.; Fu, J.; Fucci, A.; Fulton, L.; Gallorini, S.; Galeotti, S.; Gamberini, E.; Gatignon, L.; Georgiev, G.; Gianoli, A.; Giorgi, M.; Giudici, S.; Glonti, L.; Goncalves Martins, A.; Gonnella, F.; Goudzovski, E.; Guida, R.; Gushchin, E.; Hahn, F.; Hallgren, B.; Heath, H.; Herman, F.; Husek, T.; Hutanu, O.; Hutchcroft, D.; Iacobuzio, L.; Iacopini, E.; Imbergamo, E.; Jamet, O.; Jarron, P.; Jones, E.; Kampf, K.; Kaplon, J.; Kekelidze, V.; Kholodenko, S.; Khoriauli, G.; Khotyantsev, A.; Khudyakov, A.; Kiryushin, Yu.; Kleimenova, A.; Kleinknecht, K.; Kluge, A.; Koval, M.; Kozhuharov, V.; Krivda, M.; Kucerova, Z.; Kudenko, Y.; Kunze, J.; Lamanna, G.; Latino, G.; Lazzeroni, C.; Lehmann-Miotto, G.; Lenci, R.; Lenti, M.; Leonardi, E.; Lichard, P.; Lietava, R.; Litov, L.; Lollini, R.; Lomidze, D.; Lonardo, A.; Lupi, M.; Lurkin, N.; McCormick, K.; Madigozhin, D.; Maire, G.; Mandeiro, C.; Mannelli, I.; Mannocchi, G.; Mapelli, A.; Marchetto, F.; Marchevski, R.; Martellotti, S.; Massarotti, P.; Massri, K.; Matak, P.; Maurice, E.; Mefodev, A.; Menichetti, E.; Minucci, E.; Mirra, M.; Misheva, M.; Molokanova, N.; Morant, J.; Morel, M.; Moulson, M.; Movchan, S.; Munday, D.; Napolitano, M.; Neri, I.; Newson, F.; Norton, A.; Noy, M.; Nuessle, G.; Numao, T.; Obraztsov, V.; Ostankov, A.; Padolski, S.; Page, R.; Palladino, V.; Paoluzzi, G.; Parkinson, C.; Pedreschi, E.; Pepe, M.; Perez Gomez, F.; Perrin-Terrin, M.; Peruzzo, L.; Petrov, P.; Petrucci, F.; Piandani, R.; Piccini, M.; Pietreanu, D.; Pinzino, J.; Polenkevich, I.; Pontisso, L.; Potrebenikov, Yu.; Protopopescu, D.; Raffaelli, F.; Raggi, M.; Riedler, P.; Romano, A.; Rubin, P.; Ruggiero, G.; Russo, V.; Ryjov, V.; Salamon, A.; Salina, G.; Samsonov, V.; Santoni, C.; Saracino, G.; Sargeni, F.; Semenov, V.; Sergi, A.; Serra, M.; Shaikhiev, A.; Shkarovskiy, S.; Skillicorn, I.; Soldi, D.; Sotnikov, A.; Sougonyaev, V.; Sozzi, M.; Spadaro, T.; Spinella, F.; Staley, R.; Sturgess, A.; Sutcliffe, P.; Szilasi, N.; Tagnani, D.; Trilov, S.; Valdata-Nappi, M.; Valente, P.; Vasile, M.; Vassilieva, T.; Velghe, B.; Veltri, M.; Venditti, S.; Vicini, P.; Volpe, R.; Vormstein, M.; Wahl, H.; Wanke, R.; Wertelaers, P.; Winhart, A.; Winston, R.; Wrona, B.; Yushchenko, O.; Zamkovsky, M.; Zinchenko, A.; NA62 Collaboration

    2017-04-01

    The K+ →π+ ν ν ‾ decay is theoretically one of the cleanest meson decays and so a good place to look for indirect effects of new physics complementary to LHC searches. The NA62 experiment at CERN is designed to measure the branching ratio of this decay with 10% precision. NA62 was commissioned in October 2014, took data in pilot runs in 2014 and 2015. The NA62 experimental setup is illustrated and data quality is reported.

  8. Neutron diffraction studies of the Na-ion battery electrode materials NaCoCr2(PO4)3, NaNiCr2(PO4)3, and Na2Ni2Cr(PO4)3

    NASA Astrophysics Data System (ADS)

    Yahia, H. Ben; Essehli, R.; Avdeev, M.; Park, J.-B.; Sun, Y.-K.; Al-Maadeed, M. A.; Belharouak, I.

    2016-06-01

    The new compounds NaCoCr2(PO4)3, NaNiCr2(PO4)3, and Na2Ni2Cr(PO4)3 were synthesized by sol-gel method and their crystal structures were determined by using neutron powder diffraction data. These compounds were characterized by galvanometric cycling and cyclic voltammetry. NaCoCr2(PO4)3, NaNiCr2(PO4)3, and Na2Ni2Cr(PO4)3 crystallize with a stuffed α-CrPO4-type structure. The structure consists of a 3D-framework made of octahedra and tetrahedra that are sharing corners and/or edges generating channels along [100] and [010], in which the sodium atoms are located. Of significance, in the structures of NaNiCr2(PO4)3, and Na2Ni2Cr(PO4)3 a statistical disorder Ni2+/Cr3+ was observed on both the 8g and 4a atomic positions, whereas in NaCoCr2(PO4)3 the statistical disorder Co2+/Cr3+ was only observed on the 8g atomic position. When tested as negative electrode materials, NaCoCr2(PO4)3, NaNiCr2(PO4)3, and Na2Ni2Cr(PO4)3 delivered specific capacities of 352, 385, and 368 mA h g-1, respectively, which attests to the electrochemical activity of sodium in these compounds.

  9. Magnesium correction to the NaKCa chemical geothermometer

    USGS Publications Warehouse

    Fournier, R.O.; Potter, R.W.

    1979-01-01

    Equations and graphs have been devised to correct for the adverse effects of magnesium upon the Na-K-Ca chemical geothermometer. Either the equations or graphs can be used to determine appropriate temperature corrections for given waters with calculated NaKCa temperatures > 70??C and R 50 are probably derived from relatively cool aquifers with temperatures approximately equal to the measured spring temperature, irrespective of much higher calculated Na-K-Ca temperatures. ?? 1979.

  10. Sodium superionic conduction in Na2B12H12.

    PubMed

    Udovic, Terrence J; Matsuo, Motoaki; Unemoto, Atsushi; Verdal, Nina; Stavila, Vitalie; Skripov, Alexander V; Rush, John J; Takamura, Hitoshi; Orimo, Shin-ichi

    2014-04-11

    Impedance measurements indicate that Na2B12H12 exhibits dramatic Na(+) conductivity (on the order of 0.1 S cm(-1)) above its order-disorder phase-transition at ≈529 K, rivaling that of current, solid-state, ceramic-based, Na-battery electrolytes. Superionicity may be aided by the large size, quasispherical shape, and high rotational mobility of the B12H12(2-) anions.

  11. Kinetic properties and Na+ dependence of rheogenic Na(+)-HCO3- co-transport in frog retinal pigment epithelium.

    PubMed Central

    la Cour, M

    1991-01-01

    1. Na(+)-HCO3- co-transport across the retinal membrane of the frog retinal pigment epithelium was studied by means of double-barrelled pH-selective microelectrodes. Transient changes in the intracellular pH were monitored in response to abrupt changes in the Na+ concentration on the retinal side of the epithelium. 2. The experiments were performed as follows. The Na(+)-HCO3- co-transport was inhibited by perfusing the retinal side of the epithelium with a Na(+)-free solution. The co-transport was then stimulated by changing the perfusate from the Na(+)-free solution to a solution which contained from 5 to 110 mM-Na+. The resulting inward Na(+)-HCO3- co-transport produced an intracellular alkalinization, the initial rate of which was used to calculate the initial rate of Na(+)-HCO3- co-transport, JHCO3-. 3. The Na+ dependence of the Na(+)-HCO3- co-transport was studied at two different values of extracellular pH (7.40 and 7.10), at constant extracellular HCO3- concentration (27.5 mM) and at two different extracellular HCO3- concentrations (27.5 mM and 55 mM) at constant extracellular pH (7.40). In these experiments, the calculated values of JHCO3- followed single Michaelis-Menten kinetics with respect to the extracellular Na+ concentration. 4. The data are consistent with a model in which the co-transporter has a single binding site for the Na+ ion with an apparent affinity constant (apparent Km) of 37 mM. The apparent affinity constant for Na+ was independent of the extracellular concentration of CO3(2-) in the range of 16-65 microM, and of the extracellular HCO3- concentration in the range 27.5-55 mM. 5. The NaCO3- ion-pair hypothesis, in which sodium binds to the co-transporter and is translocated across the cell membrane as the NaCO3- ion pair, was analysed. For stoichiometries 1:2 and 1:3 of the Na(+)-HCO3- co-transport, the NaCO3- ion-pair hypothesis was found incompatible with the data. 6. The intracellular buffer capacity as measured by the CO2 method was

  12. Symbiodinium isolation by NaOH treatment.

    PubMed

    Zamoum, Thamilla; Furla, Paola

    2012-11-15

    The presence of photosynthetic zooxanthellae (dinoflagellates) in the tissue of many cnidarians is the main reason for their ecological success (i.e. coral reefs). It could also be the main cause of their demise, as the worldwide bleaching of reef-building coral is nothing less than the breakdown of this symbiotic association. The stability of this relationship is the principal marker for the biomonitoring of cnidarian health. We have therefore developed a new, simple method to isolate zooxanthellae in a few steps using NaOH solution. The protocol was validated in three symbiotic cnidarian species: a sea anemone, a gorgonian and a coral. Our method allows the isolation of intact and viable zooxanthellae with better yields than classic methods, especially for species with a calcareous skeleton. Moreover, the isolated zooxanthellae were free of host nucleic contaminants, facilitating subsequent specific molecular analyses.

  13. The NA49 large acceptance hadron detector

    NASA Astrophysics Data System (ADS)

    Afanasiev, S.; Alber, T.; Appelshäuser, H.; Bächler, J.; Barna, D.; Barnby, L. S.; Bartke, J.; Barton, R. A.; Betev, L.; Bialkowska, H.; Bieser, F.; Billmeier, A.; Blyth, C. O.; Bock, R.; Bormann, C.; Bracinik, J.; Brady, F. P.; Brockmann, R.; Brun, R.; Buncic, P.; Caines, H. L.; Cebra, D.; Cooper, G. E.; Cramer, J. G.; Csato, P.; Cyprian, M.; Dunn, J.; Eckardt, V.; Eckhardt, F.; Empl, T.; Eschke, J.; Ferguson, M. I.; Fessler, H.; Fischer, H. G.; Flierl, D.; Fodor, Z.; Frankenfeld, U.; Foka, P.; Freund, P.; Friese, V.; Ftacnik, J.; Fuchs, M.; Gabler, F.; Gal, J.; Ganz, R.; Gaździcki, M.; Gładysz, E.; Grebieszkow, J.; Günther, J.; Harris, J. W.; Hegyi, S.; Henkel, T.; Hill, L. A.; Hlinka, V.; Huang, I.; Hümmler, H.; Igo, G.; Irmscher, D.; Ivanov, M.; Janik, R.; Jacobs, P.; Jones, P. G.; Kadija, K.; Kolesnikov, V. I.; Kowalski, M.; Lasiuk, B.; Lévai, P.; Liebicher, K.; Lynen, U.; Malakhov, A. I.; Margetis, S.; Markert, C.; Marks, C.; Mayes, B.; Melkumov, G. L.; Mock, A.; Molnár, J.; Nelson, J. M.; Oldenburg, M.; Odyniec, G.; Palla, G.; Panagiotou, A. D.; Pestov, Y.; Petridis, A.; Pikna, M.; Pimpl, W.; Pinsky, L.; Piper, A.; Porter, R. J.; Poskanzer, A. M.; Poziombka, S.; Prindle, D. J.; Pühlhofer, F.; Rauch, W.; Reid, J. G.; Renfordt, R.; Retyk, W.; Ritter, H. G.; Röhrich, D.; Roland, C.; Roland, G.; Rudolph, H.; Rybicki, A.; Sammer, T.; Sandoval, A.; Sann, H.; Schäfer, E.; Schmidt, R.; Schmischke, D.; Schmitz, N.; Schönfelder, S.; Semenov, A. Yu.; Seyboth, J.; Seyboth, P.; Seyerlein, J.; Sikler, F.; Sitar, B.; Skrzypczak, E.; Squier, G. T. A.; Stelzer, H.; Stock, R.; Strmen, P.; Ströbele, H.; Struck, C.; Susa, T.; Szarka, I.; Szentpetery, I.; Szymański, P.; Sziklai, J.; Toy, M.; Trainor, T. A.; Trentalange, S.; Ullrich, T.; Vassiliou, M.; Veres, G.; Vesztergombi, G.; Vranic, D.; Wang, F. Q.; Weerasundara, D. D.; Wenig, S.; Whitten, C.; Wieman, H.; Wienold, T.; Wood, L.; Yates, T. A.; Zimanyi, J.; Zhu, X.-Z.; Zybert, R.

    1999-07-01

    The NA49 detector is a wide acceptance spectrometer for the study of hadron production in p+p, p+A, and A+A collisions at the CERN SPS. The main components are 4 large-volume TPCs for tracking and particle identification via d E/d x. TOF scintillator arrays complement particle identification. Calorimeters for transverse energy determination and triggering, a detector for centrality selection in p+A collisions, and beam definition detectors complete the set-up. A description of all detector components is given with emphasis on new technical realizations. Performance and operational experience are discussed in particular with respect to the high track density environment of central Pb+Pb collisions.

  14. Na-Zn liquid metal battery

    NASA Astrophysics Data System (ADS)

    Xu, Junli; Kjos, Ole Sigmund; Osen, Karen Sende; Martinez, Ana Maria; Kongstein, Ole Edvard; Haarberg, Geir Martin

    2016-11-01

    A new kind of membrane free liquid metal battery was developed. The battery employs liquid sodium and zinc as electrodes both in liquid state, and NaCl-CaCl2 molten salts as electrolyte. The discharge flat voltage is in the range of about 1.4 V-1.8 V, and the cycle efficiency achieved is about 90% at low discharge current densities (below 40 mA cm-2). Moreover, this battery can also be charged and discharged at high current density with good performance. The discharge flat voltage is above 1.1 V when it is discharged at 100 mA cm-2, while it is about 0.8 V with 100% cycle efficiency when it is discharged at 200 mA cm-2. Compared to other reported liquid metal battery, this battery has lower cost, which suggests broad application prospect in energy storage systems for power grid.

  15. Pion and kaon freezeout in NA44

    SciTech Connect

    NA44 Collaboration

    1994-12-01

    The NA44 spectrometer is optimized for the study of single and two-particle particle spectra near mid-rapidity for transverse momenta below {approx} 1 GeV/c. A large fraction of all pairs in the spectrometer`s acceptance are at low relative momenta, resulting in small statistical uncertainties on the extracted size parameters. In addition, the spectrometer`s clean particle identification allows the authors to measure correlation functions for pions, kaons, and protons. This contribution will concentrate on the source size parameters determined from pion and kaon correlation functions. These size parameters will be compared to calculations from the RQMD event generator and also interpreted in the context of a hydrodynamic model. Finally, the measured single particle spectra will be examined from the viewpoint of hydrodynamics.

  16. Study of OSL in NaF: Ca,Cu

    NASA Astrophysics Data System (ADS)

    More, Y. K.; Wankhede, S. P.; Moharil, S. V.

    2013-06-01

    Sodium Fluoride containing Cu+ ions was prepared by R.A.P. followed by melt-quenching technique. Results on photo, thermo and optically stimulated luminescence in NaF:Ca,Cu are reported. OSL sensitivity of NaF:Ca,Cu is approximately 2 times than that of standard phosphor LMP. The rate of OSL depletion for 90% decay for NaF:Ca,Cu is 0.3 times as that of OSL phosphor LMP. NaF:Ca,Cu thus deserves much more attention than it has received up till now.

  17. Influenza virus neuraminidase (NA): a target for antivirals and vaccines.

    PubMed

    Jagadesh, Anitha; Salam, Abdul Ajees Abdul; Mudgal, Piya Paul; Arunkumar, Govindakarnavar

    2016-08-01

    Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. However, antigenic shifts and drifts are major concerns with influenza virus, requiring effective global monitoring and updating of vaccines. Current vaccines are standardized primarily based on the amount of hemagglutinin, a major surface antigen, which chiefly constitutes these preparations along with the varying amounts of neuraminidase (NA). Anti-influenza drugs targeting the active site of NA have been in use for more than a decade now. However, NA has not been approved as an effective antigenic component of the influenza vaccine because of standardization issues. Although some studies have suggested that NA antibodies are able to reduce the severity of the disease and induce a long-term and cross-protective immunity, a few major scientific issues need to be addressed prior to launching NA-based vaccines. Interestingly, an increasing number of studies have shown NA to be a promising target for future influenza vaccines. This review is an attempt to consolidate studies that reflect the strength of NA as a suitable vaccine target. The studies discussed in this article highlight NA as a potential influenza vaccine candidate and support taking the process of developing NA vaccines to the next stage.

  18. The Physiological Relevance of Na+-Coupled K+-Transport.

    PubMed Central

    Maathuis, FJM.; Verlin, D.; Smith, F. A.; Sanders, D.; Fernandez, J. A.; Walker, N. A.

    1996-01-01

    Plant roots utilize at least two distinct pathways with high and low affinities to accumulate K+. The system for high-affinity K+ uptake, which takes place against the electrochemical K+ gradient, requires direct energization. Energization of K+ uptake via Na+ coupling has been observed in algae and was recently proposed as a mechanism for K+ uptake in wheat (Triticum aestivum L.). To investigate whether Na+ coupling has general physiological relevance in energizing K+ transport, we screened a number of species, including Arabidopsis thaliana L. Heynh. ecotype Columbia, wheat, and barley (Hordeum vulgare L.), for the presence of Na+-coupled K+ uptake. Rb+-flux analysis and electrophysiological K+-transport assays were performed in the presence and absence of Na+ and provided evidence for a coupling between K+ and Na+ transport in several aquatic species. However, all investigated terrestrial species were able to sustain growth and K+ uptake in the absence of Na+. Furthermore, the addition of Na+ was either without effect or inhibited K+ absorption. The latter characteristic was independent of growth conditions with respect to Na+ status and pH. Our results suggest that in terrestrial species Na+-coupled K+ transport has no or limited physiological relevance, whereas in certain aquatic angiosperms and algae this type of secondary transport energization plays a significant role. PMID:12226467

  19. New solid conductors of Na/+/ and K/+/ ions

    NASA Technical Reports Server (NTRS)

    Singer, J.; Fielder, W. L.; Kautz, H. E.; Fordyce, J. S.

    1976-01-01

    About 40 structure types for solid conductors of Na(+) and K(+) ions are surveyed. Five compounds in three structure types are discovered to be good solid conductors of alkali metal ions, capable of ion transport with conductivities in the vicinity of 0.00001/ohm-cm at 25 C. These compounds are a bcc form of NaSbO3, an orthorhombic layer structure of the composition 2M2O.3Nb2O5 with M equal to Na or K, and the Na pyrochlores NaTa2O5F and NaTaWO6. Ion exchange is required to produce each of these Na compounds. Only the 2K2O.3Nb2O5 can so far be synthesized directly from the oxides and thus is the only one which can be sintered readily. The niobate is about as good a conductor of K(+) ion as is K-beta alumina. The NaSbO3 compares well with Na beta at 280 C. A number of phase diagrams are developed.

  20. New solid conductors of Na/+/ and K/+/ ions

    NASA Technical Reports Server (NTRS)

    Singer, J.; Fielder, W. L.; Kautz, H. E.; Fordyce, J. S.

    1976-01-01

    About 40 structure types for solid conductors of Na(+) and K(+) ions are surveyed. Five compounds in three structure types are discovered to be good solid conductors of alkali metal ions, capable of ion transport with conductivities in the vicinity of 0.00001/ohm-cm at 25 C. These compounds are a bcc form of NaSbO3, an orthorhombic layer structure of the composition 2M2O.3Nb2O5 with M equal to Na or K, and the Na pyrochlores NaTa2O5F and NaTaWO6. Ion exchange is required to produce each of these Na compounds. Only the 2K2O.3Nb2O5 can so far be synthesized directly from the oxides and thus is the only one which can be sintered readily. The niobate is about as good a conductor of K(+) ion as is K-beta alumina. The NaSbO3 compares well with Na beta at 280 C. A number of phase diagrams are developed.

  1. Kaolin-based geopolymers with various NaOH concentrations

    NASA Astrophysics Data System (ADS)

    Heah, C. Y.; Kamarudin, H.; Mustafa Al Bakri, A. M.; Bnhussain, M.; Luqman, M.; Khairul Nizar, I.; Ruzaidi, C. M.; Liew, Y. M.

    2013-03-01

    Kaolin geopolymers were produced by the alkali-activation of kaolin with an activator solution (a mixture of NaOH and sodium silicate solutions). The NaOH solution was prepared at a concentration of 6-14 mol/L and was mixed with the sodium silicate solution at a Na2SiO3/NaOH mass ratio of 0.24 to prepare an activator solution. The kaolin-to-activator solution mass ratio used was 0.80. This paper aimed to analyze the effect of NaOH concentration on the compressive strength of kaolin geopolymers at 80°C for 1, 2, and 3 d. Kaolin geopolymers were stable in water, and strength results showed that the kaolin binder had adequate compressive strength with 12 mol/L of NaOH concentration. When the NaOH concentration increased, the SiO2/Na2O decreased. The increased Na2O content enhanced the dissolution of kaolin as shown in X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analyses. However, excess in this content was not beneficial for the strength development of kaolin geopolymers. In addition, there was the formation of more geopolymeric gel in 12 mol/L samples. The XRD pattern of the samples showed a higher amorphous content and a more geopolymer bonding existed as proved by FTIR analysis.

  2. Characterization of ZnAl cast alloys with Na addition

    SciTech Connect

    Gancarz, Tomasz; Cempura, Grzegorz; Skuza, Wojciech

    2016-01-15

    This study was aimed at evaluating the microstructural change and thermal, electrical and mechanical properties with the addition of Na to eutectic ZnAl alloys. Solders based on eutectic ZnAl containing 0.2 to 3.0 (wt.%) of Na were developed for high temperature solder. Differential scanning calorimetry (DSC) measurements were performed to determine the melting temperatures of the alloys. Thermal linear expansion and electrical resistivity measurements were performed over − 50 °C to 300 °C and 30 °C to 300 °C temperature ranges, respectively. The microstructure of the specimens was analyzed using scanning (SEM) and transmission electron microscopy (TEM) techniques. Chemical microanalysis was performed by energy-dispersive X-ray spectroscopy (EDS) on SEM and TEM. The precipitates of NaZn{sub 13} were confirmed by X-ray diffraction (XRD) measurements and selected area electron diffraction (SAED) techniques. The addition of Na to eutectic ZnAl alloy increased the electrical resistivity and reduced the coefficient of thermal expansion; however, the melting point did not change. The mechanical properties, strain and microhardness increased with Na content in alloys. - Highlights: • High temperature soldering materials of ZnAl with Na were designed and characterized. • Precipitates of NaZn{sub 13}were observed and confirmed using TEM and XRD. • Addition of Na to eutectic ZnAl cussed increased mechanical properties. • NaZn{sub 13} caused increased electrical resistivity and microhardness, and reduced the CTE.

  3. Tuning NaYF4 Nanoparticles through Alkaline Earth Doping

    PubMed Central

    Chen, Xian; Peng, Dengfeng; Wang, Feng

    2013-01-01

    Phase and size of lanthanide-doped nanoparticles are the most important characteristics that dictate optical properties of these nanoparticles and affect their technological applications. Herein, we present a systematic study to examine the effect of alkaline earth doping on the formation of NaYF4 upconversion nanoparticles. We show that alkaline earth doping has a dual function of tuning particle size of hexagonal phase NaYF4 nanoparticles and stabilizing cubic phase NaYF4 nanoparticles depending on composition and concentration of the dopant ions. The study described here represents a facile and general strategy to tuning the properties of NaYF4 upconversion nanoparticles. PMID:28348353

  4. Transcriptional regulators of Na,K-ATPase subunits

    PubMed Central

    Li, Zhiqin; Langhans, Sigrid A.

    2015-01-01

    The Na,K-ATPase classically serves as an ion pump creating an electrochemical gradient across the plasma membrane that is essential for transepithelial transport, nutrient uptake and membrane potential. In addition, Na,K-ATPase also functions as a receptor, a signal transducer and a cell adhesion molecule. With such diverse roles, it is understandable that the Na,K-ATPase subunits, the catalytic α-subunit, the β-subunit and the FXYD proteins, are controlled extensively during development and to accommodate physiological needs. The spatial and temporal expression of Na,K-ATPase is partially regulated at the transcriptional level. Numerous transcription factors, hormones, growth factors, lipids, and extracellular stimuli modulate the transcription of the Na,K-ATPase subunits. Moreover, epigenetic mechanisms also contribute to the regulation of Na,K-ATPase expression. With the ever growing knowledge about diseases associated with the malfunction of Na,K-ATPase, this review aims at summarizing the best-characterized transcription regulators that modulate Na,K-ATPase subunit levels. As abnormal expression of Na,K-ATPase subunits has been observed in many carcinoma, we will also discuss transcription factors that are associated with epithelial-mesenchymal transition, a crucial step in the progression of many tumors to malignant disease. PMID:26579519

  5. Mercury's Na Exosphere from MESSENGER Data

    NASA Technical Reports Server (NTRS)

    Killen, Rosemary M.; Burger, M. H.; Cassidy, T. A.; Sarantos, M.; Vervack, R. J.; McClintock, W. El; Merkel, A. W.; Sprague, A. L.; Solomon, S. C.

    2012-01-01

    MESSENGER entered orbit about Mercury on March 18, 2011. Since then, the Ultraviolet and Visible Spectrometer (UWS) channel of MESSENGER's Mercury Atmospheric and Surface Composition Spectrometer (MASCS) has been observing Mercury's exosphere nearly continuously. Daily measurements of Na brightness were fitted with non-uniform exospheric models. With Monte Carlo sampling we traced the trajectories of a representative number of test particles, generally one million per run per source process, until photoionization, escape from the gravitational well, or permanent sticking at the surface removed the atom from the simulation. Atoms were assumed to partially thermally accommodate on each encounter with the surface with accommodation coefficient 0.25. Runs for different assumed source processes are run separately, scaled and co-added. Once these model results were saved onto a 3D grid, we ran lines of sight from the MESSENGER spacecraft :0 infinity using the SPICE kernels and we computed brightness integrals. Note that only particles that contribute to the measurement can be constrained with our method. Atoms and molecules produced on the nightside must escape the shadow in order to scatter light if the excitation process is resonant-light scattering, as assumed here. The aggregate distribution of Na atoms fits a 1200 K gas, with a PSD distribution, along with a hotter component. Our models constrain the hot component, assumed to be impact vaporization, to be emitted with a 2500 K Maxwellian. Most orbits show a dawnside enhancement in the hot component broadly spread over the leading hemisphere. However, on some dates there is no dawn/dusk asymmetry. The portion of the hot/cold source appears to be highly variable.

  6. Mercury's Na Exosphere from MESSENGER Data

    NASA Technical Reports Server (NTRS)

    Killen, Rosemary M.; Burger, M. H.; Cassidy, T. A.; Sarantos, M.; Vervack, R. J.; McClintock, W. El; Merkel, A. W.; Sprague, A. L.; Solomon, S. C.

    2012-01-01

    MESSENGER entered orbit about Mercury on March 18, 2011. Since then, the Ultraviolet and Visible Spectrometer (UWS) channel of MESSENGER's Mercury Atmospheric and Surface Composition Spectrometer (MASCS) has been observing Mercury's exosphere nearly continuously. Daily measurements of Na brightness were fitted with non-uniform exospheric models. With Monte Carlo sampling we traced the trajectories of a representative number of test particles, generally one million per run per source process, until photoionization, escape from the gravitational well, or permanent sticking at the surface removed the atom from the simulation. Atoms were assumed to partially thermally accommodate on each encounter with the surface with accommodation coefficient 0.25. Runs for different assumed source processes are run separately, scaled and co-added. Once these model results were saved onto a 3D grid, we ran lines of sight from the MESSENGER spacecraft :0 infinity using the SPICE kernels and we computed brightness integrals. Note that only particles that contribute to the measurement can be constrained with our method. Atoms and molecules produced on the nightside must escape the shadow in order to scatter light if the excitation process is resonant-light scattering, as assumed here. The aggregate distribution of Na atoms fits a 1200 K gas, with a PSD distribution, along with a hotter component. Our models constrain the hot component, assumed to be impact vaporization, to be emitted with a 2500 K Maxwellian. Most orbits show a dawnside enhancement in the hot component broadly spread over the leading hemisphere. However, on some dates there is no dawn/dusk asymmetry. The portion of the hot/cold source appears to be highly variable.

  7. Mercury's Na Exosphere from MESSENGER data

    NASA Astrophysics Data System (ADS)

    Killen, Rosemary M.; Burger, M. H.; Cassidy, T. A.; Sarantos, M.; Vervack, R. J.; McClintock, W. E.; Merkel, A. W.; Sprague, A. L.; Solomon, S. C.

    2012-10-01

    MESSENGER entered orbit about Mercury on March 18, 2011. Since then, the Ultraviolet and Visible Spectrometer (UVVS) channel of MESSENGER's Mercury Atmospheric and Surface Composition Spectrometer (MASCS) has been observing Mercury's exosphere nearly continuously. Daily measurements of Na brightness were fitted with non-uniform exospheric models. With Monte Carlo sampling we traced the trajectories of a representative number of test particles, generally one million per run per source process, until photoionization, escape from the gravitational well, or permanent sticking at the surface removed the atom from the simulation. Atoms were assumed to partially thermally accommodate on each encounter with the surface with accommodation coefficient 0.25. Runs for different assumed source processes are run separately, scaled and co-added. Once these model results were saved onto a 3D grid, we ran lines of sight from the MESSENGER spacecraft to infinity using the SPICE kernels and we computed brightness integrals. Note that only particles that contribute to the measurement can be constrained with our method. Atoms and molecules produced on the nightside must escape the shadow in order to scatter light if the excitation process is resonant-light scattering, as assumed here. The aggregate distribution of Na atoms fits a 1200 K gas, with a PSD distribution, along with a hotter component. Our models constrain the hot component, assumed to be impact vaporization, to be emitted with a 2500 K Maxwellian. Most orbits show a dawnside enhancement in the hot component broadly spread over the leading hemisphere. However, on some dates there is no dawn/dusk asymmetry. The hot portion of the source appears to be highly variable. The authors acknowledge support from NASA through the MESSENGER Participating Scientist Program and Planetary Atmospheres research grants.

  8. Scintillation efficiency measurement of Na recoils in NaI(Tl) below the DAMA/LIBRA energy threshold

    NASA Astrophysics Data System (ADS)

    Xu, Jingke; Shields, Emily; Calaprice, Frank; Westerdale, Shawn; Froborg, Francis; Suerfu, Burkhant; Alexander, Thomas; Aprahamian, Ani; Back, Henning O.; Casarella, Clark; Fang, Xiao; Gupta, Yogesh K.; Ianni, Aldo; Lamere, Edward; Lippincott, W. Hugh; Liu, Qian; Lyons, Stephanie; Siegl, Kevin; Smith, Mallory; Tan, Wanpeng; Kolk, Bryant Vande

    2015-07-01

    The dark matter interpretation of the DAMA modulation signal depends on the NaI(Tl) scintillation efficiency of nuclear recoils. Previous measurements for Na recoils have large discrepancies, especially in the DAMA/LIBRA modulation energy region. We report a quenching effect measurement of Na recoils in NaI(Tl) from 3 to 52 keVnr, covering the whole DAMA/LIBRA energy region for dark matter-Na scattering interpretations. By using a low-energy, pulsed neutron beam, a double time-of-flight technique, and pulse-shape discrimination methods, we obtained the most accurate measurement of this kind for NaI(Tl) to date. The results differ significantly from the DAMA reported values at low energies but fall between the other previous measurements. We present the implications of the new quenching results for the dark matter interpretation of the DAMA modulation signal.

  9. Attenuation of Na/K-ATPase Mediated Oxidant Amplification with pNaKtide Ameliorates Experimental Uremic Cardiomyopathy

    PubMed Central

    Liu, Jiang; Tian, Jiang; Chaudhry, Muhammad; Maxwell, Kyle; Yan, Yanling; Wang, Xiaoliang; Shah, Preeya T.; Khawaja, Asad A.; Martin, Rebecca; Robinette, Tylor J.; El-Hamdani, Adee; Dodrill, Michael W.; Sodhi, Komal; Drummond, Christopher A.; Haller, Steven T.; Kennedy, David J.; Abraham, Nader G.; Xie, Zijian; Shapiro, Joseph I.

    2016-01-01

    We have previously reported that the sodium potassium adenosine triphosphatase (Na/K-ATPase) can effect the amplification of reactive oxygen species. In this study, we examined whether attenuation of oxidant stress by antagonism of Na/K-ATPase oxidant amplification might ameliorate experimental uremic cardiomyopathy induced by partial nephrectomy (PNx). PNx induced the development of cardiac morphological and biochemical changes consistent with human uremic cardiomyopathy. Both inhibition of Na/K-ATPase oxidant amplification with pNaKtide and induction of heme oxygenase-1 (HO-1) with cobalt protoporphyrin (CoPP) markedly attenuated the development of phenotypical features of uremic cardiomyopathy. In a reversal study, administration of pNaKtide after the induction of uremic cardiomyopathy reversed many of the phenotypical features. Attenuation of Na/K-ATPase oxidant amplification may be a potential strategy for clinical therapy of this disorder. PMID:27698370

  10. Scintillation Efficiency Measurement of Na Recoils in NaI(Tl) Below the DAMA/LIBRA Energy Threshold

    SciTech Connect

    Xu, Jingke; Shields, Emily; Calaprice, Frank; Westerdale, Shawn; Froborg, Francis; Suerfu, Burkhant; Alexander, Thomas; Aprahamian, Ani; Back, Henning O.; Casarella, Clark; Fang, Xiao; Gupta, Yogesh K.; Ianni, Aldo; Lamere, Edward; Lippincott, W. Hugh; Liu, Qian; Lyons, Stephanie; Siegl, Kevin; Smith, Mallory; Tan, Wanpeng; Kolk, Bryant Vande

    2015-07-30

    The dark matter interpretation of the DAMA modulation signal depends on the NaI(Tl) scintillation efficiency of nuclear recoils. Previous measurements for Na recoils have large discrepancies, especially in the DAMA/LIBRA modulation energy region. We report a quenching effect measurement of Na recoils in NaI(Tl) from 3 to 52 keVnr, covering the whole DAMA/LIBRA energy region for dark matter-Na scattering interpretations. By using a low-energy, pulsed neutron beam, a double time-of-flight technique, and pulse-shape discrimination methods, we obtained the most accurate measurement of this kind for NaI(Tl) to date. The results differ significantly from the DAMA reported values at low energies but fall between the other previous measurements. We present the implications of the new quenching results for the dark matter interpretation of the DAMA modulation signal.

  11. Na/K Pump and Beyond: Na/K-ATPase as a Modulator of Apoptosis and Autophagy.

    PubMed

    Felippe Gonçalves-de-Albuquerque, Cassiano; Ribeiro Silva, Adriana; Ignácio da Silva, Camila; Caire Castro-Faria-Neto, Hugo; Burth, Patrícia

    2017-04-21

    Lung cancer is a leading cause of global cancer deaths. Na/K-ATPase has been studied as a target for cancer treatment. Cardiotonic steroids (CS) trigger intracellular signalling upon binding to Na/K-ATPase. Normal lung and tumour cells frequently express different pump isoforms. Thus, Na/K-ATPase is a powerful target for lung cancer treatment. Drugs targeting Na/K-ATPase may induce apoptosis and autophagy in transformed cells. We argue that Na/K-ATPase has a role as a potential target in chemotherapy in lung cancer treatment. We discuss the effects of Na/K-ATPase ligands and molecular pathways inducing deleterious effects on lung cancer cells, especially those leading to apoptosis and autophagy.

  12. Decomposition reactions for NaAl H4 , Na3 Al H6 , and NaH: First-principles study

    NASA Astrophysics Data System (ADS)

    Ke, Xuezhi; Tanaka, Isao

    2005-01-01

    The electronic properties and lattice dynamics of the sodium alanate phases have been studied by the density functional calculations. The phases include NaAlH4 (space group, I41/a ), Na3AlH6 (space group, P21/n ), and NaH (space group, Fm-3m ). The electronic properties are discussed on the basis of the electronic band structures, the atomic charges, the bond overlap population analysis, and the Born effective charges. The phonon dispersion relations and phonon density of states (DOS) of the phases are calculated by a direct force-constant method. Within the quasiharmonic approximation, the calculated thermodynamic functions including the heat capacity, the vibrational enthalpy, and the vibrational entropy are in good agreement with experimental values. Three decomposition reactions are studied based on the thermodynamic functions. The reactions are (1) NaAlH4→(1)/(3)Na3AlH6+(2)/(3)Al+H2 , (2) (1)/(3)Na3AlH6→NaH+(1)/(3)Al+(1)/(2)H2 , and (3) NaH→Na+(1)/(2)H2 . The reactions (1), (2), and (3) are predicted to take place at 285, 390, and 726K , respectively, which are in good agreement with the experiment (353, 423, and 698K , respectively). The individual contributions to the reactions including the enthalpy and entropy are investigated. We found that the enthalpy for the reaction is almost constant, and the net entropy contribution ( TΔS ) to the reaction is approximately equal to the entropy contribution of the H2 gas molecule (produced in that reaction).

  13. RNA adducts with Na 2SeO 4 and Na 2SeO 3 - Stability and structural features

    NASA Astrophysics Data System (ADS)

    Nafisi, Shohreh; Manouchehri, Firouzeh; Montazeri, Maryam

    2011-12-01

    Selenium compounds are widely available in dietary supplements and have been extensively studied for their antioxidant and anticancer properties. Low blood Se levels were found to be associated with an increased incidence and mortality from various types of cancers. Although many in vivo and clinical trials have been conducted using these compounds, their biochemical and chemical mechanisms of efficacy are the focus of much current research. This study was designed to examine the interaction of Na 2SeO 4 and Na 2SeO 3 with RNA in aqueous solution at physiological conditions, using a constant RNA concentration (6.25 mM) and various sodium selenate and sodium selenite/polynucleotide (phosphate) ratios of 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. Fourier transform infrared, UV-Visible spectroscopic methods were used to determine the drug binding modes, the binding constants, and the stability of Na 2SeO 4 and Na 2SeO 3-RNA complexes in aqueous solution. Spectroscopic evidence showed that Na 2SeO 4 and Na 2SeO 3 bind to the major and minor grooves of RNA ( via G, A and U bases) with some degree of the Se-phosphate (PO 2) interaction for both compounds with overall binding constants of K(Na 2SeO 4-RNA) = 8.34 × 10 3 and K(Na 2SeO 3-RNA) = 4.57 × 10 3 M -1. The order of selenium salts-biopolymer stability was Na 2SeO 4-RNA > Na 2SeO 3-RNA. RNA aggregations occurred at higher selenium concentrations. No biopolymer conformational changes were observed upon Na 2SeO 4 and Na 2SeO 3 interactions, while RNA remains in the A-family structure.

  14. Mechanism of μ-conotoxin PIIIA binding to the voltage-gated Na+ channel NaV1.4.

    PubMed

    Chen, Rong; Robinson, Anna; Chung, Shin-Ho

    2014-01-01

    Several subtypes of voltage-gated Na+ (NaV) channels are important targets for pain management. μ-Conotoxins isolated from venoms of cone snails are potent and specific blockers of different NaV channel isoforms. The inhibitory effect of μ-conotoxins on NaV channels has been examined extensively, but the mechanism of toxin specificity has not been understood in detail. Here the known structure of μ-conotoxin PIIIA and a model of the skeletal muscle channel NaV1.4 are used to elucidate elements that contribute to the structural basis of μ-conotoxin binding and specificity. The model of NaV1.4 is constructed based on the crystal structure of the bacterial NaV channel, NaVAb. Six different binding modes, in which the side chain of each of the basic residues carried by the toxin protrudes into the selectivity filter of NaV1.4, are examined in atomic detail using molecular dynamics simulations with explicit solvent. The dissociation constants (Kd) computed for two selected binding modes in which Lys9 or Arg14 from the toxin protrudes into the filter of the channel are within 2 fold; both values in close proximity to those determined from dose response data for the block of NaV currents. To explore the mechanism of PIIIA specificity, a double mutant of NaV1.4 mimicking NaV channels resistant to μ-conotoxins and tetrodotoxin is constructed and the binding of PIIIA to this mutant channel examined. The double mutation causes the affinity of PIIIA to reduce by two orders of magnitude.

  15. A 23Na magic angle spinning nuclear magnetic resonance, XANES, and high-temperature X-ray diffraction study of NaUO3, Na4UO5, and Na2U2O7.

    PubMed

    Smith, A L; Raison, P E; Martel, L; Charpentier, T; Farnan, I; Prieur, D; Hennig, C; Scheinost, A C; Konings, R J M; Cheetham, A K

    2014-01-06

    The valence state of uranium has been confirmed for the three sodium uranates NaU(V)O3/[Rn](5f(1)), Na4U(VI)O5/[Rn](5f(0)), and Na2U(VI)2O7/[Rn](5f(0)), using X-ray absorption near-edge structure (XANES) spectroscopy. Solid-state (23)Na magic angle spinning nuclear magnetic resonance (MAS NMR) measurements have been performed for the first time, yielding chemical shifts at -29.1 (NaUO3), 15.1 (Na4UO5), and -14.1 and -19 ppm (Na1 8-fold coordinated and Na2 7-fold coordinated in Na2U2O7), respectively. The [Rn]5f(1) electronic structure of uranium in NaUO3 causes a paramagnetic shift in comparison to Na4UO5 and Na2U2O7, where the electronic structure is [Rn]5f(0). A (23)Na multi quantum magic angle spinning (MQMAS) study on Na2U2O7 has confirmed a monoclinic rather than rhombohedral structure with evidence for two distinct Na sites. DFT calculations of the NMR parameters on the nonmagnetic compounds Na4UO5 and Na2U2O7 have permitted the differentiation between the two Na sites of the Na2U2O7 structure. The linear thermal expansion coefficients of all three compounds have been determined using high-temperature X-ray diffraction: αa = 22.7 × 10(-6) K(-1), αb = 12.9 × 10(-6) K(-1), αc = 16.2 × 10(-6) K(-1), and αvol = 52.8 × 10(-6) K(-1) for NaUO3 in the range 298-1273 K; αa = 37.1 × 10(-6) K(-1), αc = 6.2 × 10(-6) K(-1), and αvol = 81.8 × 10(-6) K(-1) for Na4UO5 in the range 298-1073 K; αa = 6.7 × 10(-6) K(-1), αb = 14.4 × 10(-6) K(-1), αc = 26.8 × 10(-6) K(-1), αβ = -7.8 × 10(-6) K(-1), and αvol = -217.6 × 10(-6) K(-1) for Na2U2O7 in the range 298-573 K. The α to β phase transition reported for the last compound above about 600 K was not observed in the present studies, either by high-temperature X-ray diffraction or by differential scanning calorimetry.

  16. Path integral study of the correlated electronic states of Na4-Na6

    NASA Astrophysics Data System (ADS)

    Hall, Randall W.

    1990-12-01

    Feynman's path integral formulation of quantum mechanics is used to study the correlated electronic states of Na4-Na6. Two types of simulations are performed: in the first, the nuclei are allowed to move at finite temperature in order to find the most stable geometries. In agreement with previous calculations, we find that planar structures are the most stable and that there is significant vibrational amplitude at finite temperatures, indicating that the Born-Oppenheimer surface is relatively flat. In the second type of simulation, the nuclei are held fixed at symmetric and asymmetric geometries and the correlated electron density is found. Our results show that the electrons are localized, rather than delocalized as previous workers have concluded from examination of the single-particle orbitals. We find that the best picture of these clusters is that they contain three-center, two-electron bonds.

  17. Towards environmentally friendly Na-ion batteries: Moisture and water stability of Na2Ti3O7

    NASA Astrophysics Data System (ADS)

    Zarrabeitia, M.; Castillo-Martínez, E.; López Del Amo, J. M.; Eguía-Barrio, A.; Muñoz-Márquez, M. A.; Rojo, T.; Casas-Cabanas, M.

    2016-08-01

    We report here on the moisture and water stability of the promising Na-ion anode material Na2Ti3O7. Spontaneous Na+/H+ exchange is detected by PXRD after air exposure, forming solid solution compounds of the form Na2-xHxTi3O7 (0 < x < 2). By controlled ion exchange in aqueous solution two mixed compositions are prepared and their composition and structure are characterized with a panel of techniques. Both mixed compositions crystallize in C2/m space group like H2Ti3O7, and therefore Na+/H+ exchange is found to involve a structural transition from AA stacking of [TiO6] layers to AB stacking sequence. The electrochemical behaviour of the mixed compositions vs. Na+/Na is studied as well as that of an electrode of pure Na2Ti3O7 prepared in water media. The water-processed electrode is shown to exhibit a superior cycling stability and therefore the results obtained highlight the potential of Na2Ti3O7 as a green, low cost anode material for NIBs.

  18. Structural and Na-ion conduction characteristics of Na3PSxSe4–x

    DOE PAGES

    Bo, Shou -Hang; Wang, Yan; Ceder, Gerbrand

    2016-05-19

    The recent discovery of the isostructrual cubic Na3PS4 and Na3PSe4 as fast Na-ion conductors provided a general structural framework for the exploration of new sodium superionic conductors. In this work, we systematically investigated the structures and ionic conduction characteristics of a series of compounds with the general chemical formula of Na3PSxSe4–x. Synthesis of Na3PS4 under different conditions (e.g., temperature, reaction vessel, mass of the precursors) reveals the reactivity of the precursors with the reaction tubes, producing different polymorphs. X-ray diffraction studies on the solid solution phases Na3PSxSe4–x identified a tetragonal-to-cubic phase transition with increasing Se concentration. This observation is consistentmore » with the computed stability of the tetragonal and cubic polymorphs, where the energy difference between the two polymorphs becomes very close to zero in Se-rich compositions. Furthermore, ab initio molecular dynamic simulations suggest that the fast Na-ion conduction in Na3PSxSe4–x may not be causally related with the symmetry or the composition of these phases. The formation of defects, instead, enables fast Na-ion conduction in this class of materials.« less

  19. Na+ and K+ levels in living cells: do they depend on the rate of outward transport of Na+?

    PubMed

    Ling, G N; Ochsenfeld, M M

    1976-01-01

    At 25 degrees C, frog sartorius muslces rapidly gained Na+ and lost K+ in iodoacetamide and pure nitrogen. Beginning at normal levels, the concentrations of these ions in the cells reached those in the surrounding Ringer solution in 140 min. Yet during that time the Na+ efflux rate showed no sign of the slowing down demanded by Na-pump theory. The data support the view that maintenance and alterations of N1+ levels in frog muslce cells reflect adsorption on protein sites and the solubility property of bulk phase water and are independent of the rate at which Na+ leaves the cell surface.

  20. Estimating the hydrogen ion concentration in concentrated NaCl and Na{sub 2}SO{sub 4} electrolytes

    SciTech Connect

    Rai, D.; Felmy, A.R.; Juracich, S.P.; Rao, F.

    1995-06-01

    Combination glass electrodes were tested for determining H{sup +} concentrations in concentrated pure and mixed NaCl and Na{sub 2}SO{sub 4} solutions, as well as natural brine systems. NaCl, Na{sub 2}SO{sub 4}, and mixtures of NaCl and Na{sub 2}SO{sub 4} solutions were analyzed. Correction factors for estimating pC{sub H}{sup +} (negative logarithm of H{sup +} concentration) were determined from measured/observed pH values. Required Gran-type titrations were done with HCl and/or NaOH. The titration method is described and a step-by-step procedure provided; it has been used previously for determining pC{sub H}{sup +} values of synthetic chloride-dominated brines. Precautions are required to determine correction factors for electrolytes that react with H{sup +} or OH{sup {minus}} [sulfate brines for titration with acid; magnesium brines for titration with base because of precipitation of Mg(OH)2]. Correction factors A (pC{sub H}{sup +} = pH{sub ob} + A) from HCl titrations were similar to those from NaOH titrations where the concentration of free H{sup +} was calculated using a thermodynamic model. These values should be applicable to solns with a very large range in measured pH values (2 to 12). Because a large number of solns were titrated with HCl and the A values are similar for HCl and NaOH titrations, the A values for NaCl and Na2SO4 solns were fit as a function of molality to allow extrapolation. For NaCl solns 0 to 6.0 M, A can be obtained by multiplying the molality by 0.159. For Na2SO4 solns 0 to 2.0 M, the values of A can be obtained from (0.221 {minus} 0.549X + 0.201X{sup 2}), where X is the molality of Na{sub 2}SO{sub 4}. Orion-Ross electrode evaluations indicated that the A values did not differ significantly for different electrodes. Results suggest that the data in this report can be used to estimate A values for different NaCl and Na{sub 2}SO{sub 4} solns even for noncalibrated electrodes.

  1. Temperature-dependent formation of NaCl dihydrate in levitated NaCl and sea salt aerosol particles.

    PubMed

    Peckhaus, Andreas; Kiselev, Alexei; Wagner, Robert; Duft, Denis; Leisner, Thomas

    2016-12-28

    Recent laboratory studies indicate that the hydrated form of crystalline NaCl is potentially important for atmospheric processes involving depositional ice nucleation on NaCl dihydrate particles under cirrus cloud conditions. However, recent experimental studies reported a strong discrepancy between the temperature intervals where the efflorescence of NaCl dihydrate has been observed. Here we report the measurements of the volume specific nucleation rate of crystalline NaCl in the aqueous solution droplets of pure NaCl suspended in an electrodynamic balance at constant temperature and humidity in the range from 250 K to 241 K. Based on these measurements, we derive the interfacial energy of crystalline NaCl dihydrate in a supersaturated NaCl solution and determined its temperature dependence. Taking into account both temperature and concentration dependence of nucleation rate coefficients, we explain the difference in the observed fractions of NaCl dihydrate reported in the previous studies. Applying the heterogeneous classical nucleation theory model, we have been able to reproduce the 5 K shift of the NaCl dihydrate efflorescence curve observed for the sea salt aerosol particles, assuming the presence of super-micron solid inclusions (hypothetically gypsum or hemihydrate of CaSO4). These results support the notion that the phase transitions in microscopic droplets of supersaturated solution should be interpreted by accounting for the stochastic nature of homogeneous and heterogeneous nucleation and cannot be understood on the ground of bulk phase diagrams alone.

  2. Computational Study of Binding of μ-Conotoxin GIIIA to Bacterial Sodium Channels NaVAb and NaVRh.

    PubMed

    Patel, Dharmeshkumar; Mahdavi, Somayeh; Kuyucak, Serdar

    2016-03-29

    Structures of several voltage-gated sodium (NaV) channels from bacteria have been determined recently, but the same feat might not be achieved for the mammalian counterparts in the near future. Thus, at present, computational studies of the mammalian NaV channels have to be performed using homology models based on the bacterial crystal structures. A successful homology model for the mammalian NaV1.4 channel was recently constructed using the extensive mutation data for binding of μ-conotoxin GIIIA to NaV1.4, which was further validated through studies of binding of other μ-conotoxins and ion permeation. Understanding the similarities and differences between the bacterial and mammalian NaV channels is an important issue, and the NaV1.4-GIIIA system provides a good opportunity for such a comparison. To this end, we study the binding of GIIIA to the bacterial channels NaVAb and NaVRh. The complex structures are obtained using docking and molecular dynamics simulations, and the dissociation of GIIIA is studied through umbrella sampling simulations. The results are compared to those obtained from the NaV1.4-GIIIA system, and the differences in the binding modes arising from the changes in the selectivity filters are highlighted.

  3. Empagliflozin decreases myocardial cytoplasmic Na(+) through inhibition of the cardiac Na(+)/H(+) exchanger in rats and rabbits.

    PubMed

    Baartscheer, Antonius; Schumacher, Cees A; Wüst, Rob C I; Fiolet, Jan W T; Stienen, Ger J M; Coronel, Ruben; Zuurbier, Coert J

    2017-03-01

    Empagliflozin (EMPA), an inhibitor of the renal sodium-glucose cotransporter (SGLT) 2, reduces the risk of cardiovascular death in patients with type 2 diabetes. The underlying mechanism of this effect is unknown. Elevated cardiac cytoplasmic Na(+) ([Na(+)]c) and Ca(2+) ([Ca(2+)]c) concentrations and decreased mitochondrial Ca(2+) concentration ([Ca(2+)]m) are drivers of heart failure and cardiac death. We therefore hypothesised that EMPA would directly modify [Na(+)]c, [Ca(2+)]c and [Ca(2+)]m in cardiomyocytes. [Na(+)]c, [Ca(2+)]c, [Ca (2+)]m and Na(+)/H(+) exchanger (NHE) activity were measured fluorometrically in isolated ventricular myocytes from rabbits and rats. An increase in extracellular glucose, from 5.5 mmol/l to 11 mmol/l, resulted in increased [Na(+)]c and [Ca(2+)]c levels. EMPA treatment directly inhibited NHE flux, caused a reduction in [Na(+)]c and [Ca(2+)]c and increased [Ca(2+)]m. After pretreatment with the NHE inhibitor, Cariporide, these effects of EMPA were strongly reduced. EMPA also affected [Na(+)]c and NHE flux in the absence of extracellular glucose. The glucose lowering kidney-targeted agent, EMPA, demonstrates direct cardiac effects by lowering myocardial [Na(+)]c and [Ca(2+)]c and enhancing [Ca(2+)]m, through impairment of myocardial NHE flux, independent of SGLT2 activity.

  4. NMR and IR studies of hydroxyl groups in CaNa and MgNa forms of zeolites A

    NASA Astrophysics Data System (ADS)

    Pruski, M.; Ernst, H.; Pfeifer, H.; Staudte, B.

    1985-09-01

    By measurement of MAS proton magnetic resonance and near-infrared spectra, the existence of bridging hydroxyl groups in MgNaA and CaNaA zeolites is excluded. The MAS proton magnetic resonance lines observed at 2.5-3 ppm for CaNaA and at 3.5 ppm for MgNaA (apart from the small contributions of "terminal" OH groups) and the corresponding bands at 4576 and 4525 cm -1 in the near-infrared spectra are attributed to hydroxyl groups attached to the exchangeable cations.

  5. Temperature-dependent formation of NaCl dihydrate in levitated NaCl and sea salt aerosol particles

    NASA Astrophysics Data System (ADS)

    Peckhaus, Andreas; Kiselev, Alexei; Wagner, Robert; Duft, Denis; Leisner, Thomas

    2016-12-01

    Recent laboratory studies indicate that the hydrated form of crystalline NaCl is potentially important for atmospheric processes involving depositional ice nucleation on NaCl dihydrate particles under cirrus cloud conditions. However, recent experimental studies reported a strong discrepancy between the temperature intervals where the efflorescence of NaCl dihydrate has been observed. Here we report the measurements of the volume specific nucleation rate of crystalline NaCl in the aqueous solution droplets of pure NaCl suspended in an electrodynamic balance at constant temperature and humidity in the range from 250 K to 241 K. Based on these measurements, we derive the interfacial energy of crystalline NaCl dihydrate in a supersaturated NaCl solution and determined its temperature dependence. Taking into account both temperature and concentration dependence of nucleation rate coefficients, we explain the difference in the observed fractions of NaCl dihydrate reported in the previous studies. Applying the heterogeneous classical nucleation theory model, we have been able to reproduce the 5 K shift of the NaCl dihydrate efflorescence curve observed for the sea salt aerosol particles, assuming the presence of super-micron solid inclusions (hypothetically gypsum or hemihydrate of CaSO4). These results support the notion that the phase transitions in microscopic droplets of supersaturated solution should be interpreted by accounting for the stochastic nature of homogeneous and heterogeneous nucleation and cannot be understood on the ground of bulk phase diagrams alone.

  6. Central role of the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) in sodium bioenergetics of Vibrio cholerae.

    PubMed

    Steuber, Julia; Halang, Petra; Vorburger, Thomas; Steffen, Wojtek; Vohl, Georg; Fritz, Günter

    2014-12-01

    Vibrio cholerae is a Gram-negative bacterium that lives in brackish or sea water environments. Strains of V. cholerae carrying the pathogenicity islands infect the human gut and cause the fatal disease cholera. Vibrio cholerae maintains a Na(+) gradient at its cytoplasmic membrane that drives substrate uptake, motility, and efflux of antibiotics. Here, we summarize the major Na(+)-dependent transport processes and describe the central role of the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR), a primary Na(+) pump, in maintaining a Na(+)-motive force. The Na(+)-NQR is a membrane protein complex with a mass of about 220 kDa that couples the exergonic oxidation of NADH to the transport of Na(+) across the cytoplasmic membrane. We describe the molecular architecture of this respiratory complex and summarize the findings how electron transport might be coupled to Na(+)-translocation. Moreover, recent advances in the determination of the three-dimensional structure of this complex are reported.

  7. Expression of diverse Na+ channel messenger RNAs in rat myocardium. Evidence for a cardiac-specific Na+ channel.

    PubMed Central

    Sills, M N; Xu, Y C; Baracchini, E; Goodman, R H; Cooperman, S S; Mandel, G; Chien, K R

    1989-01-01

    This study examined the diversity of Na+ channel gene expression in intact cardiac tissue and purified myocardial cells. The screening of neonatal rat myocardial cell cDNA libraries with a conserved rat brain Na+ channel cDNA probe, resulted in the isolation and characterization of a putative rat cardiac Na+ channel cDNA probe (pCSC-1). The deduced amino acid sequence of pCSC-1 displayed a striking degree of homology with the eel, rat brain-1, and rat brain-2 Na+ channel, thereby identifying pCSC-1 as a related member of the family of Na+ channel genes. Northern blot analysis revealed the expression of a 7-kb CSC-1 transcript in rat cardiac tissue and purified myocardial cells, but little or no detectable expression of CSC-1 in rat brain, skeletal muscle, denervated skeletal muscle, or liver. Using RNase protection and Northern blot hybridization with specific rat brain Na+ channel gene probes, expression of the rat brain-1 Na+ channel was observed in rat myocardium, but no detectable expression of the rat brain-2 gene was found. This study provides evidence for the expression of diverse Na+ channel mRNAs in rat myocardium and presents the initial characterization of a new, related member of the family of Na+ channel genes, which appears to be expressed in a cardiac-specific manner. Images PMID:2544627

  8. Synthesis and characterization of sodium titanates Na 2Ti 3O 7 and Na 2Ti 6O 13

    NASA Astrophysics Data System (ADS)

    Sauvet, A.-L.; Baliteau, S.; Lopez, C.; Fabry, P.

    2004-12-01

    Na 2Ti 3O 7 and Na 2Ti 6O 13 were synthesized by sol-gel method in order to obtain pure phases. Different heat-treatments were applied on powders and pellets of these materials. The effects were studied by XRD, dilatometry, TGA-DTA, SEM and electrochemical impedance spectroscopy. Pure Na 2Ti 3O 7 was obtained at 973 K. Sintering at 1373 K caused a partial decomposition into Na 2Ti 6O 13. The Na 2Ti 3O 7 powder sintered at 1273 K showed polygonal microstructure. Na 2Ti 3O 7 pellets sintered at 1323 K for 10 h exhibited large structures. This latter microstructure decreased the electrical conductivity of Na 2Ti 3O 7. Pure Na 2Ti 6O 13 was obtained at 873 K. Sintering at 1073 K caused a partial decomposition into TiO 2 (rutile). Na 2Ti 6O 13 pellets sintered at 1323 K for 10 h exhibited common shrinkage behavior. This shrinkage process increased the electrical conductivity of this material. The presence of TiO 2 resulted in a oxygen partial pressure dependence of the electrical conductivity.

  9. Density Functional Studies of NaAlH_4, NaH and AlH_3

    NASA Astrophysics Data System (ADS)

    Aguayo, Aaron; Singh, David J.

    2004-03-01

    We report electronic structure investigations of the bonding of the alanate NaAlH4 and the related materials NaH and AlH_3. The results are based on density functional calculations using the LAPW method. All three compounds are insulators. AlH3 has a substantially covalent electronic structure with a band gap of approximately 2 eV, while NaAlH4 and NaH both show larger band gaps of approximately 4 eV and are much more ionic. This ionic character is stabilized by the Madelung energy in the respective crystal structures. We discuss the implications for H storage.

  10. Kinetics and stoichiometry of coupled Na efflux and Ca influx (Na/Ca exchange) in barnacle muscle cells

    PubMed Central

    1989-01-01

    Coupled Na+ exit/Ca2+ entry (Na/Ca exchange operating in the Ca2+ influx mode) was studied in giant barnacle muscle cells by measuring 22Na+ efflux and 45Ca2+ influx in internally perfused, ATP-fueled cells in which the Na+ pump was poisoned by 0.1 mM ouabain. Internal free Ca2+, [Ca2+]i, was controlled with a Ca-EGTA buffering system containing 8 mM EGTA and varying amounts of Ca2+. Ca2+ sequestration in internal stores was inhibited with caffeine and a mitochondrial uncoupler (FCCP). To maximize conditions for Ca2+ influx mode Na/Ca exchange, and to eliminate tracer Na/Na exchange, all of the external Na+ in the standard Na+ sea water (NaSW) was replaced by Tris or Li+ (Tris-SW or LiSW, respectively). In both Na-free solutions an external Ca2+ (Cao)-dependent Na+ efflux was observed when [Ca2+]i was increased above 10(-8) M; this efflux was half-maximally activated by [Ca2+]i = 0.3 microM (LiSW) to 0.7 microM (Tris-SW). The Cao-dependent Na+ efflux was half-maximally activated by [Ca2+]o = 2.0 mM in LiSW and 7.2 mM in Tris-SW; at saturating [Ca2+]o, [Ca2+]i, and [Na+]i the maximal (calculated) Cao-dependent Na+ efflux was approximately 75 pmol#cm2.s. This efflux was inhibited by external Na+ and La3+ with IC50's of approximately 125 and 0.4 mM, respectively. A Nai-dependent Ca2+ influx was also observed in Tris-SW. This Ca2+ influx also required [Ca2+]i greater than 10(-8) M. Internal Ca2+ activated a Nai-independent Ca2+ influx from LiSW (tracer Ca/Ca exchange), but in Tris-SW virtually all of the Cai-activated Ca2+ influx was Nai-dependent (Na/Ca exchange). Half-maximal activation was observed with [Na+]i = 30 mM. The fact that internal Ca2+ activates both a Cao-dependent Na+ efflux and a Nai- dependent Ca2+ influx in Tris-SW implies that these two fluxes are coupled; the activating (intracellular) Ca2+ does not appear to be transported by the exchanger. The maximal (calculated) Nai-dependent Ca2+ influx was -25 pmol/cm2.s. At various [Na+]i between 6 and 106 m

  11. Clinical and therapeutic significance of the Na+,K+ pump*.

    PubMed

    Clausen, T

    1998-07-01

    1. The Na+,K+-ATPase or Na+,K+-pump, mediating the active transport of Na+ and K+, which was first identified 40 years ago, is a central target for acute and long-term regulation, as well as for therapeutic intervention. Acute stimulation of the Na+,K+-pump in skeletal muscle by insulin, catecholamines, beta2-agonists or theophylline increases the intracellular uptake of K+ and accounts for the hypokalaemia elicited by these agents. Conversely, digitalis intoxication elicits hyperkalaemia via acute inhibition of the Na+, K+-pump. 2. Simple and accurate methods have been developed for the quantification of the total concentration of Na+,K+-pumps in small (0.5-5 mg) fresh or frozen biopsies of human skeletal muscle, myocardium or other tissues. This has allowed the identification of several long-term regulatory changes in the concentration of this transport system in human tissues. In skeletal muscle, upregulation is induced by training, thyroid hormones or glucocorticoids. Downregulation is seen in hypothyroidism, cardiac insufficiency, myotonic dystrophy, McArdle disease, K+ deficiency and after muscle inactivity. 3. Since the skeletal muscles contain one of the major pools of Na+,K+-pumps, these changes are important for the ability to counterregulate the hyperkalaemia elicited by exercise or the ingestion of K+. Moreover, downregulation or inhibition of the Na+, K+-pumps in skeletal muscle interferes with contractile performance. Since digitalis glycosides bind to the Na+,K+-pump, the muscles constitute a large distribution volume for these agents and are therefore an important determinant for their plasma level. 4. In cardiac insufficiency, the decrease in the concentration of Na+, K+-pumps in the myocardium is over a wide range correlated to the concomitant reduction in ejection fraction. The regulatory and pathophysiological changes in the activity and concentration of Na+, K+-pumps are important for the contractile function of skeletal muscle and heart as

  12. North America and South America (NA-SA) neuropathy project.

    PubMed

    Pasnoor, Mamatha; Nascimento, Osvaldo J M; Trivedi, Jaya; Wolfe, Gil I; Nations, Sharon; Herbelin, Laura; de Freitas, M G; Quintanilha, Giseli; Khan, Saud; Dimachkie, Mazen; Barohn, Richard

    2013-08-01

    Peripheral neuropathy is a common neurological disorder. There may be important differences and similarities in the diagnosis of peripheral neuropathy between North America (NA) and South America (SA). Neuromuscular databases were searched for neuropathy diagnosis at two North American sites, University of Kansas Medical Center and University of Texas Southwestern Medical Center, and one South American site, Federal Fluminense University in Brazil. All patients were included into one of the six major categories: immune-mediated, diabetic, hereditary, infectious/inflammatory, systemic/metabolic/toxic (not diabetic) and cryptogenic. A comparison of the number of patients in each category was made between North America and South America databases. Total number of cases in North America was 1090 and in South America was 1034 [immune-mediated: NA 215 (19.7%), SA 191 (18%); diabetic: NA 148 (13.5%), SA 236 (23%); hereditary: NA 292 (26.7%), SA 103 (10%); infectious/inflammatory: NA 53 (4.8%), SA 141 (14%); systemic/metabolic/toxic: NA 71 (6.5%), SA 124 (12%); cryptogenic: NA 311 (28.5%), SA 239 (23%)]. Some specific neuropathy comparisons were hereditary neuropathies [Charcot-Marie-Tooth (CMT) cases] in NA 246/292 (84.2%) and SA 60/103 (58%); familial amyloid neuropathy in SA 31/103 (30%) and none in NA. Among infectious neuropathies, cases of human T-lymphotropic virus type 1 (HTLV-1) neuropathy in SA were 36/141(25%), Chagas disease in SA were 13/141(9%) and none for either in NA; cases of neuropathy due to leprosy in NA were 26/53 (49%) and in SA were 39/141(28%). South American tertiary care centers are more likely to see patients with infectious, diabetic and hereditary disorders such as familial amyloid neuropathies. North American tertiary centers are more likely to see patients with CMT. Immune neuropathies and cryptogenic neuropathies were seen equally in North America and South America.

  13. Structural basis for Na(+) transport mechanism by a light-driven Na(+) pump.

    PubMed

    Kato, Hideaki E; Inoue, Keiichi; Abe-Yoshizumi, Rei; Kato, Yoshitaka; Ono, Hikaru; Konno, Masae; Hososhima, Shoko; Ishizuka, Toru; Hoque, Mohammad Razuanul; Kunitomo, Hirofumi; Ito, Jumpei; Yoshizawa, Susumu; Yamashita, Keitaro; Takemoto, Mizuki; Nishizawa, Tomohiro; Taniguchi, Reiya; Kogure, Kazuhiro; Maturana, Andrés D; Iino, Yuichi; Yawo, Hiromu; Ishitani, Ryuichiro; Kandori, Hideki; Nureki, Osamu

    2015-05-07

    Krokinobacter eikastus rhodopsin 2 (KR2) is the first light-driven Na(+) pump discovered, and is viewed as a potential next-generation optogenetics tool. Since the positively charged Schiff base proton, located within the ion-conducting pathway of all light-driven ion pumps, was thought to prohibit the transport of a non-proton cation, the discovery of KR2 raised the question of how it achieves Na(+) transport. Here we present crystal structures of KR2 under neutral and acidic conditions, which represent the resting and M-like intermediate states, respectively. Structural and spectroscopic analyses revealed the gating mechanism, whereby the flipping of Asp116 sequesters the Schiff base proton from the conducting pathway to facilitate Na(+) transport. Together with the structure-based engineering of the first light-driven K(+) pumps, electrophysiological assays in mammalian neurons and behavioural assays in a nematode, our studies reveal the molecular basis for light-driven non-proton cation pumps and thus provide a framework that may advance the development of next-generation optogenetics.

  14. Direct Measurement of {sup 21}Na+{alpha} Stellar Reaction

    SciTech Connect

    Binh, D. N.; Kubono, S.; Yamaguchi, H.; Hayakawa, S.; Hashimoto, T.; Kahl, D.; Teranishi, T.; Iwasa, N.; Kume, N.; Kato, S.; Khiem, L. H.; Tho, N. T.; Wakabayashi, Y.

    2010-08-12

    The measurement of the resonant alpha scattering and the {sup 21}Na({alpha}, p) reaction were performed for the first time in inverse kinematics with the thick target method using a {sup 21}Na radioisotope (RI) beam. This paper reports the current result of alpha scattering measurement and its astrophysics implication.

  15. Hydrothermal Synthesis of (K,Na)NbO3 Particles

    NASA Astrophysics Data System (ADS)

    Zhang, Fan; Han, Lu; Bai, Shan; Sun, Tiedong; Karaki, Tomoaki; Adachi, Masatoshi

    2008-09-01

    (K,Na)NbO3 (KNN) particles were successfully prepared by hydrothermal synthesis. The results showed that Na+ reacted more readily with Nb to form NaNbO3 than K+. For the purpose of obtaining KNN particles with K/Na=1, a mixed alkaline solution with K+/Na+ ratios ranging from 3.5/1 to 4/1 was required as a starting solution. The morphology and size of KNN particles synthesized strongly depended on K/Na ratio in the KNN particles. The KNN particles synthesized from the starting alkaline solution with K+/Na+=3.5/1 were the smallest with a pelletlike morphology affected by NaNbO3- and KNbO3-based particles. Surfactants such as sodium dodecylbenzenesulfonate (SDBS) and sodium hexametaphosphate (SH) were used to synthesize well dispersed and small KNN particles. Platelike KNN particles with 100 nm thickness and 1.5 µm width were obtained in this study.

  16. Naïve Bayes classification in R

    PubMed Central

    2016-01-01

    Naïve Bayes classification is a kind of simple probabilistic classification methods based on Bayes’ theorem with the assumption of independence between features. The model is trained on training dataset to make predictions by predict() function. This article introduces two functions naiveBayes() and train() for the performance of Naïve Bayes classification. PMID:27429967

  17. Resurgent current of voltage-gated Na+ channels

    PubMed Central

    Lewis, Amanda H; Raman, Indira M

    2014-01-01

    Resurgent Na+ current results from a distinctive form of Na+ channel gating, originally identified in cerebellar Purkinje neurons. In these neurons, the tetrodotoxin-sensitive voltage-gated Na+ channels responsible for action potential firing have specialized mechanisms that reduce the likelihood that they accumulate in fast inactivated states, thereby shortening refractory periods and permitting rapid, repetitive, and/or burst firing. Under voltage clamp, step depolarizations evoke transient Na+ currents that rapidly activate and quickly decay, and step repolarizations elicit slower channel reopening, or a ‘resurgent’ current. The generation of resurgent current depends on a factor in the Na+ channel complex, probably a subunit such as NaVβ4 (Scn4b), which blocks open Na+ channels at positive voltages, competing with the fast inactivation gate, and unblocks at negative voltages, permitting recovery from an open channel block along with a flow of current. Following its initial discovery, resurgent Na+ current has been found in nearly 20 types of neurons. Emerging research suggests that resurgent current is preferentially increased in a variety of clinical conditions associated with altered cellular excitability. Here we review the biophysical, molecular and structural mechanisms of resurgent current and their relation to the normal functions of excitable cells as well as pathophysiology. PMID:25172941

  18. Unidirectional Flux Balance of Monovalent Ions in Cells with Na/Na and Li/Na Exchange: Experimental and Computational Studies on Lymphoid U937 Cells.

    PubMed

    Vereninov, Igor A; Yurinskaya, Valentina E; Model, Michael A; Vereninov, Alexey A

    2016-01-01

    Monovalent ion traffic across the cell membrane occurs via various pathways. Evaluation of individual fluxes in whole cell is hampered by their strong interdependence. This difficulty can be overcome by computational analysis of the whole cell flux balance. However, the previous computational studies disregarded ion movement of the self-exchange type. We have taken this exchange into account. The developed software allows determination of unidirectional fluxes of all monovalent ions via the major pathways both under the balanced state and during transient processes. We show how the problem of finding the rate coefficients can be solved by measurement of monovalent ion concentrations and some of the fluxes. Interdependence of fluxes due to the mandatory conditions of electroneutrality and osmotic balance and due to specific effects can be discriminated, enabling one to identify specific changes in ion transfer machinery under varied conditions. To test the effectiveness of the developed approach we made use of the fact that Li/Na exchange is known to be an analogue of the coupled Na/Na exchange. Thus, we compared the predicted and experimental data obtained on U937 cells under varied Li+ concentrations and following inhibition of the sodium pump with ouabain. We found that the coupled Na/Na exchange in U937 cells comprises a significant portion of the entire Na+ turnover. The data showed that the loading of the sodium pump by Li/Na exchange involved in the secondary active Li+ transport at 1-10 mM external Li+ is small. This result may be extrapolated to similar Li+ and Na+ flux relationships in erythrocytes and other cells in patients treated with Li+ in therapeutic doses. The developed computational approach is applicable for studying various cells and can be useful in education for demonstrating the effects of individual transporters and channels on ion gradients, cell water content and membrane potential.

  19. Unidirectional Flux Balance of Monovalent Ions in Cells with Na/Na and Li/Na Exchange: Experimental and Computational Studies on Lymphoid U937 Cells

    PubMed Central

    Vereninov, Igor A.; Yurinskaya, Valentina E.; Model, Michael A.; Vereninov, Alexey A.

    2016-01-01

    Monovalent ion traffic across the cell membrane occurs via various pathways. Evaluation of individual fluxes in whole cell is hampered by their strong interdependence. This difficulty can be overcome by computational analysis of the whole cell flux balance. However, the previous computational studies disregarded ion movement of the self-exchange type. We have taken this exchange into account. The developed software allows determination of unidirectional fluxes of all monovalent ions via the major pathways both under the balanced state and during transient processes. We show how the problem of finding the rate coefficients can be solved by measurement of monovalent ion concentrations and some of the fluxes. Interdependence of fluxes due to the mandatory conditions of electroneutrality and osmotic balance and due to specific effects can be discriminated, enabling one to identify specific changes in ion transfer machinery under varied conditions. To test the effectiveness of the developed approach we made use of the fact that Li/Na exchange is known to be an analogue of the coupled Na/Na exchange. Thus, we compared the predicted and experimental data obtained on U937 cells under varied Li+ concentrations and following inhibition of the sodium pump with ouabain. We found that the coupled Na/Na exchange in U937 cells comprises a significant portion of the entire Na+ turnover. The data showed that the loading of the sodium pump by Li/Na exchange involved in the secondary active Li+ transport at 1–10 mM external Li+ is small. This result may be extrapolated to similar Li+ and Na+ flux relationships in erythrocytes and other cells in patients treated with Li+ in therapeutic doses. The developed computational approach is applicable for studying various cells and can be useful in education for demonstrating the effects of individual transporters and channels on ion gradients, cell water content and membrane potential. PMID:27159324

  20. Deliquescence, efflorescence and ice nucleating ability of NaCl/hydrated NaCl particles under upper tropospheric conditions

    NASA Astrophysics Data System (ADS)

    Wise, M. E.; Baustian, K. J.; Freedman, M. A.; Koop, T.; Tolbert, M. A.

    2010-12-01

    Sea-salt aerosol particles (SSA) are ubiquitous in marine boundary layer and over coastal areas. Therefore SSA have ability to directly and indirectly affect the Earth’s radiation balance. The influence SSA have on the Earth’s radiation balance is related to their water uptake and ice nucleation characteristics. In this study, optical microscopy coupled with Raman spectroscopy was used to determine the deliquescence and efflorescence phase transitions of NaCl particles (a proxy for SSA particles) at temperatures ranging from 233 to 258 K. It was found that NaCl (s) particles deliquesced at 75.7±2.5 % RH and NaCl (aq) particles effloresced at 42.7 ±6.9 % RH. When the temperature of NaCl (aq) particles was held between 236 and 252 K, a mixture of hydrated and non-hydrated particles effloresced. Thus the water uptake characteristics of hydrated NaCl (s) particles were studied. The deliquescence relative humidities (DRH) of hydrated NaCl (s) particles ranged from 75.6 to 94.5 % RH. The DRH values for hydrated NaCl (s) do not agree with the theoretical DRH for the dihydrate form of NaCl (s) particles (the predicted phase using a bulk phase diagram). Additionally, the ice nucleating abilities of NaCl (s) and hydrated NaCl (s) were determined at temperatures ranging from 221 to 230 K. NaCl (s) particles depositionally nucleated ice at an average Sice value of 1.11±0.07. Hydrated NaCl (s) particles depositionally nucleated ice at an average Sice value of 1.01±0.03. When a mixture of hydrated and anhydrous NaCl (s) particles was present in the same sample, ice preferentially nucleated on the hydrated particles 100% of the time. Thus hydrated NaCl (s) particles are better ice nuclei than NaCl (s) particles.

  1. Dissociation of methane hydrate in aqueous NaCl solutions.

    PubMed

    Yagasaki, Takuma; Matsumoto, Masakazu; Andoh, Yoshimichi; Okazaki, Susumu; Tanaka, Hideki

    2014-10-09

    Molecular dynamics simulations of the dissociation of methane hydrate in aqueous NaCl solutions are performed. It is shown that the dissociation of the hydrate is accelerated by the formation of methane bubbles both in NaCl solutions and in pure water. We find two significant effects on the kinetics of the hydrate dissociation by NaCl. One is slowing down in an early stage before bubble formation, and another is swift bubble formation that enhances the dissociation. These effects arise from the low solubility of methane in NaCl solution, which gives rise to a nonuniform spatial distribution of solvated methane in the aqueous phase. We also demonstrate that bubbles form near the hydrate interface in dense NaCl solutions and that the hydrate dissociation proceeds inhomogeneously due to the bubbles.

  2. Feasibility study for a secondary Na/S battery

    NASA Technical Reports Server (NTRS)

    Abraham, K. M.; Schiff, R.; Brummer, S. B.

    1979-01-01

    The feasibility of a moderate temperature Na battery was studied. This battery is to operate at a temperature in the range of 100-150 C. Two kinds of cathode were investigated: (1) a soluble S cathode consisting of a solution of Na2Sn in an organic solvent and (2) an insoluble S cathode consisting of a transition metal dichalcogenide in contact with a Na(+)ion conducting electrolyte. Four amide solvents, dimethyl acetamide, diethyl acetamide, N-methyl acetamide and acetamide, were investigated as possible solvents for the soluble S cathode. Results of stability and electrochemical studies using these solvents are presented. The dialkyl substituted amides were found to be superior. Although the alcohol 1,3-cyclohexanediol was found to be stable in the presence of Na2Sn at 130 C, its Na2Sn solutions did not appear to have suitable electrochemical properties.

  3. Trisodium citrate, Na3(C6H5O7)

    PubMed Central

    Rammohan, Alagappa; Kaduk, James A.

    2016-01-01

    The crystal structure of anhydrous tris­odium citrate, Na3(C6H5O7), has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory (DFT). There are two independent five-coordinate Na+ and one six-coordinate Na+ cations in the asymmetric unit. The [NaO5] and [NaO6] polyhedra share edges and corners to form a three-dimensional framework. There are channels parallel to the a and b axes in which the remainder of the citrate anions reside. The only hydrogen bonds are an intra­molecular one between the hy­droxy group and one of the terminal carboxyl­ate O atoms and an intermolecular one between a methylene group and the hydroxyl O atom. PMID:27308044

  4. Interplanetary dust distribution and temporal variability of Mercury's atmospheric Na

    NASA Astrophysics Data System (ADS)

    Kameda, Shingo; Yoshikawa, Ichiro; Kagitani, Masato; Okano, Shoichi

    2009-08-01

    The interplanetary dust (IPD) distribution in the inner solar system is not yet well understood because of lack of direct dust measurements in the inner solar system and so one needs to rely on zodiacal light observations that are difficult to interpret. Mercury has an unstable atmosphere, and the source processes of Na in its atmosphere are unclear. Results of past observations have revealed that the atmospheric Na density has no or low correlation with the solar flux, sunspot number, heliocentric distance, or solar radiation pressure. We show that the variability of Mercury's atmospheric Na density depends strongly on the IPD distribution. That is, Na density is low (high) when Mercury is far away from (close to) the symmetry plane of IPD, and so one can infer the IPD distribution near Mercury orbit from the temporal variability of Na density in Mercury's atmosphere.

  5. Na-rich layered Na2Ru0.95Zr0.05O3 cathode material for Na-ion batteries

    NASA Astrophysics Data System (ADS)

    Song, Shufeng; Kotobuki, Masashi; Zheng, Feng; Li, Qibin; Xu, Chaohe; Wang, Yu; Li, Wei Dong Z.; Hu, Ning; Lu, Li

    2017-02-01

    Structures and electrochemical performances of Na-rich layered cathode Na2RuO3 are studied by substitution of Zr for Ru. Na2Ru0.95Zr0.05O3 exhibits a combination of disordered and ordered stacking state with a weight fraction of ∼61.57% and 38.43%, respectively. The disordered and ordered Na2Ru0.95Zr0.05O3 exhibits reversible capacity of 137 mAh g-1 that is consistent with the theoretical capacity at a current density of 1 C. In addition, the material shows good cyclability with a capacity retention of 77% after 200 cycles at current density of 1 C, and the Coulombic efficiency remains at about 99% during cycling. The structural evolutions of the Na-rich layered Na2Ru0.95Zr0.05O3 during de(sodiation) have been investigated and found to proceed via a biphasic mechanism.

  6. Role of Na+,K+-pumps and transmembrane Na+,K+-distribution in muscle function. The FEPS lecture - Bratislava 2007.

    PubMed

    Clausen, T

    2008-03-01

    Na(+),K(+)-ATPase situated in the plasma membrane mediates active extrusion of Na(+) and intracellular accumulation of K(+). This transport system the Na(+),K(+)-pump is the major regulator of the transmembrane distribution of Na(+) and K(+), and is itself subject to regulation by a wide variety of factors in skeletal muscles. The excitation of skeletal muscles is elicited by a rapid influx of Na(+), followed by an equivalent efflux of K(+) across sarcolemmal and t-tubular membranes. Due to their size and sudden onset, these events constitute the major transport challenge for the Na(+),K(+)-pumps. Skeletal muscles contain the largest single pool of K(+) in the organism. During intense exercise, the Na(+),K(+)-pumps cannot readily reaccumulate K(+) into the muscle cells. Therefore, the working muscles undergo a net loss of K(+), causing up to a doubling of the K(+) concentration in the arterial blood plasma in less than 1 min and even larger increases in interstitial K(+). This may induce depolarization, loss of excitability and force, in particular in muscles, where the excitation-induced passive Na(+),K(+)-fluxes are large. During continuous stimulation of isolated rat muscles, there is a highly significant correlation between the rise in extracellular K(+) and the rate of force decline. Fortunately, excitation increases the Na(+),K(+)-pumping rate within seconds. Thus, maximum activation of up to 20-fold above the resting transport rate may be reached in 10 s, with utilization of all available Na(+),K(+)-pumps. In muscles, where excitability is reduced by pre-exposure to high [K(+)]o, acute activation of the Na(+),K(+)-pumps by hormones or intermittent electrical stimulation restores excitability and contractility. In working muscles, the Na(+),K(+)-pumps, due to rapid activation of their large transport capacity, play a dynamic regulatory role in the from second to second ongoing restoration and maintenance of excitability and force. Excitation is a self

  7. Single Na+ channels activated by veratridine and batrachotoxin

    PubMed Central

    1987-01-01

    Voltage-sensitive Na+ channels from rat skeletal muscle plasma membrane vesicles were inserted into planar lipid bilayers in the presence of either of the alkaloid toxins veratridine (VT) or batrachotoxin (BTX). Both of these toxins are known to cause persistent activation of Na+ channels. With BTX as the channel activator, single channels remain open nearly all the time. Channels activated with VT open and close on a time scale of 1-10 s. Increasing the VT concentration enhances the probability of channel opening, primarily by increasing the rate constant of opening. The kinetics and voltage dependence of channel block by 21-sulfo-11-alpha-hydroxysaxitoxin are identical for VT and BTX, as is the ionic selectivity sequence determined by bi-ionic reversal potential (Na+ approximately Li+ greater than K+ greater than Rb+ greater than Cs+). However, there are striking quantitative differences in open channel conduction for channels in the presence of the two activators. Under symmetrical solution conditions, the single channel conductance for Na+ is about twice as high with BTX as with VT. Furthermore, the symmetrical solution single channel conductances show a different selectivity for BTX (Na+ greater than Li+ greater than K+) than for VT (Na+ greater than K+ greater than Li+). Open channel current-voltage curves in symmetrical Na+ and Li+ are roughly linear, while those in symmetrical K+ are inwardly rectifying. Na+ currents are blocked asymmetrically by K+ with both BTX and VT, but the voltage dependence of K+ block is stronger with BTX than with VT. The results show that the alkaloid neurotoxins not only alter the gating process of the Na+ channel, but also affect the structure of the open channel. We further conclude that the rate-determining step for conduction by Na+ does not occur at the channel's "selectivity filter," where poorly permeating ions like K+ are excluded. PMID:2435846

  8. New results from the NA48 collaboration

    NASA Astrophysics Data System (ADS)

    NA48 Collaboration

    2003-04-01

    The list of new or recent NA48 results is the following: On CP Violation 1) New CP violation measurement in KS to 3 pi0 decays (eta000 parameter) 2) CP Violation measurement in the KL -> pi+pi-e+e- decay channel, where the violation is the maximal observed in the K system (about 15cross-check, no CP violation has been observed in the KS decay into the same final state. Rare KL, KS decays and Chiral Perturbation Theory (ChPT) 1) First measurement of the BR KS -> pi0 gamma gamma. It gives contraints on ChPT development terms in p**n (see also 2). 2) First precision measurement of KS -> gamma gamma. The result is incompatible with ChPT predictions at p**4 order: it gives indications on the need of a 'big' p**6 contribution. 3) Precision measurement of KL to pi0 gamma gamma; the measurement allows the av parameter (vector coupling constant) extraction used to characterize O(p**6) contributions in ChPT. Other new results from ongoing analyses that might be completed and blessed before your conference: Radiative and S.L. hyperon decays (cascade) KS to pi0 e+e- , KS to pi0 mu+mu- Ke3, Kmu3 form factors KL to 4 leptons Ke3 charge asymmetry

  9. NA-CORDEX: Overview and Sample Results

    NASA Astrophysics Data System (ADS)

    Bukovsky, M. S.; Mearns, L.; Arritt, R. W.; Castro, C. L.; Chang, H. I.; Christensen, J. H.; Christensen, O. B.; Frigon, A.; Gutowski, W. J., Jr.; Kjellstrom, E.; Laprise, R.; McGinnis, S. A.; Nikulin, G.; Scinocca, J. F.; Sushama, L.; Winger, K.

    2016-12-01

    The North American CORDEX program (NA-CORDEX) has produced a good number of projections of climate according to the first phase of the CORDEX program. These simulations are based on a wide range of regional and global climate models, and some matrices of combinations have resulted. The RCMs involved include: WRF, CanRCM4, CRCM5, RegCM4, RCA4, and HirHam5. Driving GCMs include: EC-EARTH, CanESM2, HadGEM2-ES, GFDL-ESM2M, MPI-ESM-LR. These GCMs nicely span the equilibrium climate sensitivity (ECS) of the GCMs making up the CMIP5 suite of models. Simulations have been performed both at .44 and .22 spatial resolutions and often for both RCP8.5 and 4.5. We will present an overview the simulations and their results over North America, focusing on the quality of the baseline climate simulations and the projections of precipitation and temperature.

  10. Endurance testing with Li/Na electrolyte

    SciTech Connect

    Ong, E.T.; Remick, R.J.; Sishtla, C.I.

    1996-12-31

    The Institute of Gas Technology (IGT), under subcontract to M-C Power Corporation under DOE funding, has been operating bench-scale fuel cells to investigate the performance and endurance issues of the Li/Na electrolyte because it offers higher ionic conductivity, higher exchange current densities, lower vapor pressures, and lower cathode dissolution rates than the Li/K electrolyte. These cells have continued to show higher performance and lower decay rates than the Li/K cells since the publication of our two previous papers in 1994. In this paper, test results of two long-term 100-cm{sup 2} bench scale cells are discussed. One cell operated continuously at 160 mA/cm{sup 2} for 17,000 hours with reference gases (60H{sub 2}/20CO{sub 2}/20H{sub 2}O fuel at 75% utilization and 30CO{sub 2}/70 air oxidant humidified at room temperature at 50% utilization). The other cell operated at 160 mA/cm{sup 2} for 6900 hours at 3 atm with system gases (64H{sub 2}/16CO{sub 2}/20H{sub 2}O at 75% utilization and an M-C Power system-defined oxidant at 40% utilization). Both cells have shown the highest performance and longest endurance among IGT cells operated to date.

  11. [SENTIERI-ReNaM: Results].

    PubMed

    Binazzi, Alessandra; Zona, Amerigo; Marinaccio, Alessandro; Bruno, Caterina; Corfiati, Marisa; Fazzo, Lucia; Menegozzo, Simona; Nicita, Carmela; Pasetto, Roberto; Pirastu, Roberta; De Santisi, Marco; Comba, Pietro

    2016-01-01

    Mesothelioma incidence has been analyzed in National Priority Contaminated Sites (NPCSs) to estimate the health impact of asbestos exposure on resident people. The burden of professional and environmental exposures has been identified through data of the Regional Operational Centres (CORs), made available by the Italian National Mesothelioma Registry (ReNaM). An excess of mesothelioma incidence is confirmed in sites with a known past history of direct use of asbestos, such as Balangero, Casale Monferrato, Broni, Bari-Fibronit, and in coastal areas, where shipyards, harbours and other industries that involved a wide use of asbestos are represented (e.g., Trieste, La Spezia, Venice, and Leghorn). An excess of mesothelioma has been observed in settings where the asbestos is not mentioned as contaminant in the decree that included these sites among NPCSs, such as Cengio and Saliceto in Northern Italy; Falconara Marittima and the Bacino Idrografico Fiume Sacco in the Central Italy; the Litorale Domizio Flegreo and Agro Aversano, Milazzo, and Gela in the Southern Italy. Observed excess in the various NPCSs confirms the large-scale occurrence in contaminated Italian sites of a significant amount of total mesothelioma cases observed at national level. The analysis of occupational risk in epidemiological studies with an ecological design helps in defining the contribution of different factors to the overall risk.

  12. A semiclassical study of laser-induced atomic fluorescence from Na2, K2 and NaK

    NASA Technical Reports Server (NTRS)

    Yuan, J.-M.; Bhattacharyya, D. K.; George, T. F.

    1982-01-01

    A semiclassical treatment of laser-induced atomic fluorescence for the alkali-dimer systems Na2, K2 and NaK is presented. The variation of the fluorescence intensity with the frequency of the exciting laser photon is studied and a comparison of theoretical results with a set of experimental data is presented.

  13. Studies of rotationally inelastic collisions of NaK and NaCs with Ar and He perturbers

    NASA Astrophysics Data System (ADS)

    Jones, J.; Faust, C.; Richter, K.; Wolfe, C. M.; Ashman, S.; Malenda, R. F.; Weiser, P.; Carlus, S.; Fragale, A.; Hickman, A. P.; Huennekens, J.

    2013-05-01

    We report studies of rotationally inelastic collisions of Ar and He atoms with the molecules NaK and NaCs prepared in various ro-vibrational levels of the A1Σ+ electronic state. We use laser induced fluorescence (LIF) and polarization labeling (PL) spectroscopy in a pump-probe, two step excitation process. The pump excites the molecule to a ro-vibrational level (v , J) in the A state. The probe laser is scanned over transitions to the 31 Π state in NaK or the 53 Π state in NaCs. In addition to strong direct lines, we observe weak satellite lines that arise from collision-induced transitions of the A state level (v , J) to (v , J + ΔJ) . The ratio of intensities of the satellite line to the direct line in LIF and PL yields information about population and orientation transfer. Preliminary results show a strong propensity for collisions with ΔJ =even for NaK; the propensity is larger for He than for Ar. Collisions of NaCs with He show a similar propensity, but collisions of NaCs with Ar do not. Theoretical calculations are also underway. For He-NaK, we have completed potential surface calculations using GAMESS and coupled channel scattering calculations of rotational energy transfer and transfer of orientation. Work supported by NSF and XSEDE.

  14. In situ fluorescence imaging of glutamate-evoked mitochondrial Na+ responses in astrocytes.

    PubMed

    Bernardinelli, Yann; Azarias, Guillaume; Chatton, Jean-Yves

    2006-10-01

    Astrocytes can experience large intracellular Na+ changes following the activation of the Na+-coupled glutamate transport. The present study investigated whether cytosolic Na+ changes are transmitted to mitochondria, which could therefore influence their function and contribute to the overall intracellular Na+ regulation. Mitochondrial Na+ (Na+(mit)) changes were monitored using the Na+-sensitive fluorescent probe CoroNa Red (CR) in intact primary cortical astrocytes, as opposed to the classical isolated mitochondria preparation. The mitochondrial localization and Na+ sensitivity of the dye were first verified and indicated that it can be safely used as a selective Na+(mit) indicator. We found by simultaneously monitoring cytosolic and mitochondrial Na+ using sodium-binding benzofuran isophthalate and CR, respectively, that glutamate-evoked cytosolic Na+ elevations are transmitted to mitochondria. The resting Na+(mit) concentration was estimated at 19.0 +/- 0.8 mM, reaching 30.1 +/- 1.2 mM during 200 microM glutamate application. Blockers of conductances potentially mediating Na+ entry (calcium uniporter, monovalent cation conductances, K+(ATP) channels) were not able to prevent the Na+(mit) response to glutamate. However, Ca2+ and its exchange with Na+ appear to play an important role in mediating mitochondrial Na+ entry as chelating intracellular Ca2+ with BAPTA or inhibiting Na+/Ca2+ exchanger with CGP-37157 diminished the Na+(mit) response. Moreover, intracellular Ca2+ increase achieved by photoactivation of caged Ca2+ also induced a Na+(mit) elevation. Inhibition of mitochondrial Na/H antiporter using ethylisopropyl-amiloride caused a steady increase in Na+(mit) without increasing cytosolic Na+, indicating that Na+ extrusion from mitochondria is mediated by these exchangers. Thus, mitochondria in intact astrocytes are equipped to efficiently sense cellular Na+ signals and to dynamically regulate their Na+ content.

  15. Tritium separation from Pb-17Li by permeation into Na or NaK and cold trapping

    SciTech Connect

    Reimann, J.

    1988-09-01

    The tritium extraction technique considered for a fusion reactor with a self-cooled Pb-17 Li blanket includes the permeation of the tritium into a Na or NaK intermediate loop and the precipitation as tritide in a cold trap. Tritium is recovered by thermal decomposition under vacuum. Basic kinetic studies of the thermal decomposition of sodium hydride are presented using different types of hydrides. The temperature range investigated was between 280 and 420/sup 0/C. Using fine NaH powder, the rate constants agreed well with those from other authors. For NaH crystals, the rate constants were lower by one order of magnitude and were similar to those obtained previously for coarse NaH powder.

  16. Preparation of Al-La Master Alloy by Thermite Reaction in NaF-NaCl-KCl Molten Salt

    NASA Astrophysics Data System (ADS)

    Jang, Poknam; Li, Hyonmo; Kim, Wenjae; Wang, Zhaowen; Liu, Fengguo

    2015-05-01

    A NaF-NaCl-KCl ternary system containing La2O3 was investigated for the preparation of Al-La master alloy by the thermite reaction method. The solubility of La2O3 in NaF-NaCl-KCl molten salt was determined by the method of isothermal solution saturation. Inductively coupled plasma-optical emission spectroscopy and x-ray diffraction (XRD) analyses were used to consider the content of La2O3 in molten salt and the supernatant composition of molten salt after dissolution of La2O3, respectively. The results showed that the content of NaF had a positive influence on the solubility of La2O3 in NaF-NaCl-KCl molten salts, and the solubility of La2O3 could reach 8.71 wt.% in molten salts of 50 wt.%NaF-50 wt.% (44 wt.%NaCl + 56 wt.%KCl). The XRD pattern of cooling molten salt indicated the formation of LaOF in molten salt, which was probably obtained by the reaction between NaF and La2O3. The kinetic study showed that the thermite reaction was in accord with a first-order reaction model. The main influence factors on La content in the Al-La master alloy product, including molten salt composition, amount of Al, concentration of La2O3, stirring, reduction time and temperature, were investigated by single-factor experimentation. The content of La in the Al-La master alloy could be reached to 10.1 wt.%.

  17. A mutation in Na(+)-NQR uncouples electron flow from Na(+) translocation in the presence of K(+).

    PubMed

    Shea, Michael E; Mezic, Katherine G; Juárez, Oscar; Barquera, Blanca

    2015-01-20

    The sodium-pumping NADH:ubiquinone oxidoreductase (Na(+)-NQR) is a bacterial respiratory enzyme that obtains energy from the redox reaction between NADH and ubiquinone and uses this energy to create an electrochemical Na(+) gradient across the cell membrane. A number of acidic residues in transmembrane helices have been shown to be important for Na(+) translocation. One of these, Asp-397 in the NqrB subunit, is a key residue for Na(+) uptake and binding. In this study, we show that when this residue is replaced with asparagine, the enzyme acquires a new sensitivity to K(+); in the mutant, K(+) both activates the redox reaction and uncouples it from the ion translocation reaction. In the wild-type enzyme, Na(+) (or Li(+)) accelerates turnover while K(+) alone does not activate. In the NqrB-D397N mutant, K(+) accelerates the same internal electron transfer step (2Fe-2S → FMNC) that is accelerated by Na(+). This is the same step that is inhibited in mutants in which Na(+) uptake is blocked. NqrB-D397N is able to translocate Na(+) and Li(+), but when K(+) is introduced, no ion translocation is observed, regardless of whether Na(+) or Li(+) is present. Thus, this mutant, when it turns over in the presence of K(+), is the first, and currently the only, example of an uncoupled Na(+)-NQR. The fact the redox reaction and ion pumping become decoupled from each other only in the presence of K(+) provides a switch that promises to be a useful experimental tool.

  18. Growth and characterization of struvite-Na crystals

    NASA Astrophysics Data System (ADS)

    Chauhan, Chetan K.; Joshi, Mihirkumar J.

    2014-09-01

    Sodium magnesium phosphate heptahydrate [NaMgPO4·7H2O], also known as struvite-Na, is the sodium analog to struvite. Among phosphate containing bio-minerals, struvite has attracted considerable attention, because of its common occurrence in a wide variety of environments. Struvite and family crystals were found as urinary calculi in humans and animals. Struvite-Na crystals were grown by a single diffusion gel growth technique in a silica hydro gel medium. Struvite-Na crystals with different morphologies having transparent to translucent diaphaneity were grown with different growth parameters. The phenomenon of Liesegang rings was also observed with some particular growth parameters. The powder XRD study confirmed the structural similarity of the grown struvite-Na crystals with struvite and found that struvite-Na crystallized in the orthorhombic Pmn21 space group with unit cell parameters such as a= 6.893 Å, b=6.124 Å, c=11.150 Å, and α=β=γ=90°. FT-IR spectra of struvite-Na crystals revealed the presence of functional groups. The TGA, DTA and DSC were carried out simultaneously. The kinetic and thermodynamic parameters of dehydration/decomposition process were calculated. The variation of dielectric constant with frequency of applied field was studied in the range from 400 Hz to 100 kHz.

  19. Voltage dependence of the Na-K pump.

    PubMed

    De Weer, P; Gadsby, D C; Rakowski, R F

    1988-01-01

    Present evidence demonstrates that the Na-K pump rate is voltage dependent, whereas early work was largely inconclusive. The I-V relationship has a positive slope over a wide voltage range, and the existence of a negative slope region is now doubtful. Monotonic voltage dependence is consistent with the reaction cycle containing a single voltage-dependent step. Recent measurements suggest that this voltage-dependent step occurs during Na translocation and may be deocclusion of Na+. In addition, two results suggest that K translocation is voltage insensitive: (a) large positive potentials appear to have no influence on Rb-Rb exchange or associated conformational transitions; and (b) transient currents associated with Na translocation appear to involve movement of a single charge, which is sufficient for a 3Na-2K cycle. The simplest interpretation is that the pump's cation binding sites supply two negative charges. Pre-steady-state measurements demonstrate that Na translocation precedes the pump cycle's rate-limiting step, presumably K translocation. But, because K translocation seems voltage insensitive, the voltage dependence of the steady-state pump rate probably reflects that of the concentration of the intermediate entering this slow step. Further pump current and flux data (both transient and steady-state), carefully determined over a range of conditions, should increase our understanding of the voltage-dependent step(s) in the Na-K pump cycle.

  20. Tetrodotoxin sensitivity of the vertebrate cardiac Na+ current.

    PubMed

    Vornanen, Matti; Hassinen, Minna; Haverinen, Jaakko

    2011-01-01

    Evolutionary origin and physiological significance of the tetrodotoxin (TTX) resistance of the vertebrate cardiac Na(+) current (I(Na)) is still unresolved. To this end, TTX sensitivity of the cardiac I(Na) was examined in cardiac myocytes of a cyclostome (lamprey), three teleost fishes (crucian carp, burbot and rainbow trout), a clawed frog, a snake (viper) and a bird (quail). In lamprey, teleost fishes, frog and bird the cardiac I(Na) was highly TTX-sensitive with EC(50)-values between 1.4 and 6.6 nmol·L(-1). In the snake heart, about 80% of the I(Na) was TTX-resistant with EC(50) value of 0.65 μmol·L(-1), the rest being TTX-sensitive (EC(50) = 0.5 nmol·L(-1)). Although TTX-resistance of the cardiac I(Na) appears to be limited to mammals and reptiles, the presence of TTX-resistant isoform of Na(+) channel in the lamprey heart suggest an early evolutionary origin of the TTX-resistance, perhaps in the common ancestor of all vertebrates.

  1. Hormonal regulation of Na -K -ATPase in cultured epithelial cells

    SciTech Connect

    Johnson, J.P.; Jones, D.; Wiesmann, W.P.

    1986-08-01

    Aldosterone and insulin stimulate Na transport through mechanisms involving protein synthesis. Na -K -ATPase has been implicated in the action of both hormones. The authors examined the effect of aldosterone and insulin on Na -K -ATPase in epithelial cells in culture derived from toad urinary bladder (TB6C) and toad kidney (A6). Aldosterone, but not insulin, increases short-circuit current (I/sub sc/) in TB6C cells. Aldosterone increases Na -K -(TSP)ATPase activity after 18 h of incubation, but no effect can be seen at 3 and 6 h. Amiloride, which inhibits aldosterone-induced increases in I/sub sc/, has no effect on either basal or aldosterone stimulated enzyme activity. Both aldosterone and insulin increase I/sub sc/ in A6 cells and when added together are synergistic. Aldosterone stimulates enzyme activity in A6 cells, but insulin alone has no effect. However, aldosterone and insulin together stimulate enzyme activity more than aldosterone alone. It appears that stimulation of Na -K -ATPase activity is involved in aldosterone action in both cell lines but does not appear to be due to increased Na entry, since enhanced enzyme activity is not inhibited by amiloride. In contrast, insulin alone has no direct effect on Na -K -ATPase, although the increased enzyme activity following both agents in combination may explain their synergism on I/sub sc/.

  2. Electron scattering in graphene with adsorbed NaCl nanoparticles

    SciTech Connect

    Drabińska, Aneta Kaźmierczak, Piotr; Bożek, Rafał; Karpierz, Ewelina; Wysmołek, Andrzej; Kamińska, Maria; Wołoś, Agnieszka; Krajewska, Aleksandra

    2015-01-07

    In this work, the results of contactless magnetoconductance and Raman spectroscopy measurements performed for a graphene sample after its immersion in NaCl solution were presented. The properties of the immersed sample were compared with those of a non-immersed reference sample. Atomic force microscopy and electron spin resonance experiments confirmed the deposition of NaCl nanoparticles on the graphene surface. A weak localization signal observed using contactless magnetoconductance showed the reduction of the coherence length after NaCl treatment of graphene. Temperature dependence of the coherence length indicated a change from ballistic to diffusive regime in electron transport after NaCl treatment. The main inelastic scattering process was of the electron-electron type but the major reason for the reduction of the coherence length at low temperatures was additional, temperature independent, inelastic scattering. We associate it with spin flip scattering, caused by NaCl nanoparticles present on the graphene surface. Raman spectroscopy showed an increase in the D and D′ bands intensities for graphene after its immersion in NaCl solution. An analysis of the D, D′, and G bands intensities proved that this additional scattering is related to the decoration of vacancies and grain boundaries with NaCl nanoparticles, as well as generation of new on-site defects as a result of the decoration of the graphene surface with NaCl nanoparticles. The observed energy shifts of 2D and G bands indicated that NaCl deposition on the graphene surface did not change carrier concentration, but reduced compressive biaxial strain in the graphene layer.

  3. Brush-border tyrosine phosphorylation stimulates ileal neutral NaCl absorption and brush-border Na(+)-H+ exchange.

    PubMed

    Donowitz, M; Montgomery, J L; Walker, M S; Cohen, M E

    1994-04-01

    The drug genistein, a tyrosine (Tyr) kinase inhibitor, was used to define a role for Tyr phosphorylation in regulation of basal and stimulated neutral NaCl absorption in rabbit ileum. Brush-border vesicles contain Tyr-phosphorylated peptides. Genistein freeze-thawed into the vesicles caused a concentration-dependent inhibition of at least three peptides with M(r) 111,000, 83,000, and 80,000. Studied with the Ussing chamber-voltage clamp technique, genistein added to the ileal mucosal surface inhibited neutral NaCl absorption. Direct addition of genistein to brush-border vesicles made from ileal villus cells inhibited brush-border Na(+)-H+ exchange but not D-glucose-stimulated Na+ uptake. These effects were not duplicated by genistin, a drug with similar structure to genistein but lacking Tyr kinase inhibiting properties. Serosal but not mucosal epidermal growth factor (EGF) stimulated NaCl absorption. Mucosal genistein but not genistin also altered second-messenger regulation of neutral NaCl absorption, inhibiting the effect of Ca2+ ionophore A-23187 and of serosal EGF but not affecting the transport changes caused by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). In contrast, the Cl secretory effects indicated by the increase in short-circuit current for all three agents, A-23187, EGF, and 8-BrcAMP, were inhibited by mucosal genistein. These results suggest that 1) a Tyr kinase is involved in basally stimulating ileal neutral NaCl absorption and brush-border Na(+)-H+ exchange; 2) EGF stimulates NaCl absorption by an effect exerted from the serosal surface, but the effect also involves a brush-border Tyr kinase; 3) brush-border Tyr kinase is involved in the ability of Ca2+ ionophore A-23187 to inhibit neutral NaCl absorption but is not involved in the transport effects of cAMP. This study suggests that Tyr kinase(s) acting over short time periods is involved in stimulation of neutral NaCl absorption and brush-border Na(+)-H+ exchange and also in Ca(2

  4. Na+/H+ and Na+/NH4+ exchange activities of zebrafish NHE3b expressed in Xenopus oocytes

    PubMed Central

    Ito, Yusuke; Kato, Akira; Hirata, Taku; Hirose, Shigehisa

    2014-01-01

    Zebrafish Na+/H+ exchanger 3b (zNHE3b) is highly expressed in the apical membrane of ionocytes where Na+ is absorbed from ion-poor fresh water against a concentration gradient. Much in vivo data indicated that zNHE3b is involved in Na+ absorption but not leakage. However, zNHE3b-mediated Na+ absorption has not been thermodynamically explained, and zNHE3b activity has not been measured. To address this issue, we overexpressed zNHE3b in Xenopus oocytes and characterized its activity by electrophysiology. Exposure of zNHE3b oocytes to Na+-free media resulted in significant decrease in intracellular pH (pHi) and intracellular Na+ activity (aNai). aNai increased significantly when the cytoplasm was acidified by media containing CO2-HCO3− or butyrate. Activity of zNHE3b was inhibited by amiloride or 5-ethylisopropyl amiloride (EIPA). Although the activity was accompanied by a large hyperpolarization of ∼50 mV, voltage-clamp experiments showed that Na+/H+ exchange activity of zNHE3b is electroneutral. Exposure of zNHE3b oocytes to medium containing NH3/NH4+ resulted in significant decreases in pHi and aNai and significant increase in intracellular NH4+ activity, indicating that zNHE3b mediates the Na+/NH4+ exchange. In low-Na+ (0.5 mM) media, zNHE3b oocytes maintained aNai of 1.3 mM, and Na+-influx was observed when pHi was decreased by media containing CO2-HCO3− or butyrate. These results provide thermodynamic evidence that zNHE3b mediates Na+ absorption from ion-poor fresh water by its Na+/H+ and Na+/NH4+ exchange activities. PMID:24401990

  5. Proposed decommissioning of radioactively contaminated NaK

    SciTech Connect

    Brown, B.W.; Geimer, R.M.; LaRue, D.M.; Stoll, F.E.; Meservey, R.H.; Maggart, C.L.

    1987-10-01

    This paper deals with a proposed method for stabilizing radioactively contaminated eutectic sodium/potassium (NaK) liquid metal. Approximately 680 liters (180 gal) of contaminated liquid NaK were generated in 1955 during testing with the Experimental Breeder Reactor (EBR-I) at the Idaho National Engineering Laboratory (INEL). Reaction of the NaK with chlorine gas to produce solid salts of sodium and potassium is proposed as a means to stabilize this waste. Preliminary testing was initiated to determine the reaction conditions required for this process. It was found that reaction with chlorine is feasible for safely treating the liquid metal.

  6. Phyla- and Subtype-Selectivity of CgNa, a Na Channel Toxin from the Venom of the Giant Caribbean Sea Anemone Condylactis Gigantea.

    PubMed

    Billen, Bert; Debaveye, Sarah; Béress, Lászlo; Garateix, Anoland; Tytgat, Jan

    2010-01-01

    Because of their prominent role in electro-excitability, voltage-gated sodium (Na(V)) channels have become the foremost important target of animal toxins. These toxins have developed the ability to discriminate between closely related Na(V) subtypes, making them powerful tools to study Na(V) channel function and structure. CgNa is a 47-amino acid residue type I toxin isolated from the venom of the Giant Caribbean Sea Anemone Condylactis gigantea. Previous studies showed that this toxin slows the fast inactivation of tetrodotoxin-sensitive Na(V) currents in rat dorsal root ganglion neurons. To illuminate the underlying Na(V) subtype-selectivity pattern, we have assayed the effects of CgNa on a broad range of mammalian isoforms (Na(V)1.2-Na(V)1.8) expressed in Xenopus oocytes. This study demonstrates that CgNa selectively slows the fast inactivation of rNa(V)1.3/β(1), mNa(V)1.6/β(1) and, to a lesser extent, hNa(V)1.5/β(1), while the other mammalian isoforms remain unaffected. Importantly, CgNa was also examined on the insect sodium channel DmNa(V)1/tipE, revealing a clear phyla-selectivity in the efficacious actions of the toxin. CgNa strongly inhibits the inactivation of the insect Na(V) channel, resulting in a dramatic increase in peak current amplitude and complete removal of fast and steady-state inactivation. Together with the previously determined solution structure, the subtype-selective effects revealed in this study make of CgNa an interesting pharmacological probe to investigate the functional role of specific Na(V) channel subtypes. Moreover, further structural studies could provide important information on the molecular mechanism of Na(V) channel inactivation.

  7. (23)Na multiple-quantum MAS NMR of the perovskites NaNbO(3) and NaTaO(3).

    PubMed

    Ashbrook, Sharon E; Le Pollès, Laurent; Gautier, Régis; Pickard, Chris J; Walton, Richard I

    2006-08-07

    The distorted perovskites NaTaO(3) and NaNbO(3) have been studied using (23)Na multiple-quantum (MQ) MAS NMR. NaTaO(3) was prepared by high temperature solid state synthesis and the NMR spectra are consistent with the expected room temperature structure of the material (space group Pbnm), with a single crystallographic sodium site. Two samples of NaNbO(3) were studied. The first, a commercially available sample which was annealed at 900 degrees C, showed two crystallographic sodium sites, as expected for the room temperature structure of the material (space group Pbcm). The second sample, prepared by a low temperature hydrothermal method, showed the presence of four sodium sites, two of which match the expected room temperature structure and the second pair, another polymorph of the material (space group P21ma). This is consistent with powder X-ray diffraction data which showed weak extra peaks which can be accounted for by the presence of this second polymorph. Density functional theory (DFT) calculations support our conclusions, and aid assignment of the NMR spectra. Finally, we discuss the measured NMR parameters in relation to other studies of sodium in high coordination sites in the solid state.

  8. 23 Na and 17O NMR studies of hyperkagome Na4Ir3O8

    NASA Astrophysics Data System (ADS)

    Shockley, Abigail; Bert, Fabrice; Orain, Jean-Christophe; Okamoto, Yoshihiko; Mendels, Philippe

    2015-03-01

    Na4Ir3O8 is a unique case of a 3D corner sharing triangular lattice which can be decorated with quantum spins. It has spurred a lot of theoretical interest as a spin liquid candidate of a new kind where the Hamiltonian might not be thought in terms of a simple Heisenberg case because of spin orbit coupling on the Ir 5d element. We present a comprehensive set of NMR data taken on both the 23Na and 17O sites. We have found that magnetic freezing of all Ir sites sets in below Tf ~ 7.5K ~ 0 . 019 J with a clear hyperfine field transferred from Ir moments and a drastic decrease of 1 /T1 . Above Tf, physical properties are expected to be a landmark of frustration in this exotic geometry. We will discuss our shift and relaxation data in the temperature range of 300K to 7.5 K in the light of published thermodynamic measurements (Y. Okamotoa et al, PRL 99 137207, 2007 and Y. Singh et al, PRB 88 220413(R), 2013) and comment on their implications for the already existing large body of theoretical work.

  9. Structure determination in 55-atom Li-Na and Na-K nanoalloys.

    PubMed

    Aguado, Andrés; López, José M

    2010-09-07

    The structure of 55-atom Li-Na and Na-K nanoalloys is determined through combined empirical potential (EP) and density functional theory (DFT) calculations. The potential energy surface generated by the EP model is extensively sampled by using the basin hopping technique, and a wide diversity of structural motifs is reoptimized at the DFT level. A composition comparison technique is applied at the DFT level in order to make a final refinement of the global minimum structures. For dilute concentrations of one of the alkali atoms, the structure of the pure metal cluster, namely, a perfect Mackay icosahedron, remains stable, with the minority component atoms entering the host cluster as substitutional impurities. At intermediate concentrations, the nanoalloys adopt instead a core-shell polyicosahedral (p-Ih) packing, where the element with smaller atomic size and larger cohesive energy segregates to the cluster core. The p-Ih structures show a marked prolate deformation, in agreement with the predictions of jelliumlike models. The electronic preference for a prolate cluster shape, which is frustrated in the 55-atom pure clusters due to the icosahedral geometrical shell closing, is therefore realized only in the 55-atom nanoalloys. An analysis of the electronic densities of states suggests that photoelectron spectroscopy would be a sufficiently sensitive technique to assess the structures of nanoalloys with fixed size and varying compositions.

  10. Desensitization by external Na of the cyclic AMP-dependent Na+/H+ antiporter in trout red blood cells

    PubMed Central

    1988-01-01

    The erythrocytes of the trout, Salmo gairdneri, react to beta- adrenergic stimulation by activating a cyclic AMP-dependent and amiloride-sensitive Na+/H+ antiporter (see Borgese, F., F. Garcia- Romeu, and R. Motais, Journal of General Physiology, 1986, 87:551-566). The present study traces the kinetic behavior of the unidirectional Na fluxes after stimulation by isoproterenol. A very considerable increase (100-fold) of the unidirectional Na influx (JNa(in)) follows the addition of isoproterenol to the erythrocyte suspension. After 1.5 min, JNa(in) falls suddenly, and asymptotically diminishes toward the nonstimulated flux level. The unidirectional Na efflux (JNa(out)) proceeds according to similar kinetics. The decrease of JNa(in) and JNa(out)is not linked to either a change in the driving forces of the transported ions or a decrease of the cyclic AMP concentration but to a desensitization of the Na+/H+ antiporter. This desensitization is dependent on the external Na concentration and is not controlled by internal Na, cell swelling, or external Ca. PMID:2839593

  11. Robust NaO2 Electrochemistry in Aprotic Na-O2 Batteries Employing Ethereal Electrolytes with a Protic Additive.

    PubMed

    Abate, Iwnetim I; Thompson, Leslie E; Kim, Ho-Cheol; Aetukuri, Nagaphani B

    2016-06-16

    Aprotic metal-oxygen batteries, such as Li-O2 and Na-O2 batteries, are of topical research interest as high specific energy alternatives to state-of-the-art Li-ion batteries. In particular, Na-O2 batteries with NaO2 as the discharge product offer higher practical specific energy with better rechargeability and round-trip energy efficiency when compared to Li-O2 batteries. In this work, we show that the electrochemical deposition and dissolution of NaO2 in Na-O2 batteries is unperturbed by trace water impurities in Na-O2 battery electrolytes, which is desirable for practical battery applications. We find no evidence for the formation of other discharge products such as Na2O2·H2O. Furthermore, the electrochemical efficiency during charge remains near ideal in the presence of trace water in electrolytes. Although sodium anodes react with trace water leading to the formation of a high-impedance solid electrolyte interphase, the increase in discharge overpotential is only ∼100 mV when compared to cells employing nominally anhydrous electrolytes.

  12. Hole Doping Effects on Spin-gapped Na2Cu2TeO6 via Topochemical Na Deficiency

    NASA Astrophysics Data System (ADS)

    Morimoto, Kumiko; Itoh, Yutaka; Yoshimura, Kazuyoshi; Kato, Masaki; Hirota, Ken

    2006-08-01

    We report the magnetic susceptibility and NMR studies of a spin-gapped layered compound Na2Cu2TeO6 (the spin gap Δ˜ 250 K), the hole doping effect on the Cu2TeO6 plane via a topochemical Na deficiency by soft chemical treatment, and the static spin vacancy effect by nonmagnetic impurity Zn substitution for Cu. A finite Knight shift at the 125Te site was observed for pure Na2Cu2TeO6. The negative hyperfine coupling constant 125Atr is an evidence for the existence of a superexchange pathway of the Cu-O-Te-O-Cu bond. It turned out that both the Na deficiency and Zn impurities induce a Curie-type magnetism in the uniform spin susceptibility in an external magnetic field of 1 T, but only the Zn impurities enhance the low-temperature 23Na nuclear spin-lattice relaxation rate whereas the Na deficiency suppresses it. A spin glass behavior was observed for the Na-deficient samples but not for the Zn-substituted samples. The dynamics of the unpaired moments of the doped holes are different from that of the spin vacancy in the spin-gapped Cu2TeO6 planes.

  13. Desensitization by external Na of the cyclic AMP-dependent Na+/H+ antiporter in trout red blood cells.

    PubMed

    Garcia-Romeu, F; Motais, R; Borgese, F

    1988-04-01

    The erythrocytes of the trout, Salmo gairdneri, react to beta-adrenergic stimulation by activating a cyclic AMP-dependent and amiloride-sensitive Na+/H+ antiporter (see Borgese, F., F. Garcia-Romeu, and R. Motais, Journal of General Physiology, 1986, 87:551-566). The present study traces the kinetic behavior of the unidirectional Na fluxes after stimulation by isoproterenol. A very considerable increase (100-fold) of the unidirectional Na influx (JNa(in)) follows the addition of isoproterenol to the erythrocyte suspension. After 1.5 min, JNa(in) falls suddenly, and asymptotically diminishes toward the nonstimulated flux level. The unidirectional Na efflux (JNa(out)) proceeds according to similar kinetics. The decrease of JNa(in) and JNa(out)is not linked to either a change in the driving forces of the transported ions or a decrease of the cyclic AMP concentration but to a desensitization of the Na+/H+ antiporter. This desensitization is dependent on the external Na concentration and is not controlled by internal Na, cell swelling, or external Ca.

  14. (−)-Englerin A-evoked Cytotoxicity Is Mediated by Na+ Influx and Counteracted by Na+/K+-ATPase*

    PubMed Central

    Ludlow, Melanie J.; Gaunt, Hannah J.; Rubaiy, Hussein N.; Musialowski, Katie E.; Blythe, Nicola M.; Vasudev, Naveen S.; Muraki, Katsuhiko; Beech, David J.

    2017-01-01

    (−)-Englerin A ((−)-EA) has a rapid and potent cytotoxic effect on several types of cancer cell that is mediated by plasma membrane ion channels containing transient receptor potential canonical 4 (TRPC4) protein. Because these channels are Ca2+-permeable, it was initially thought that the cytotoxicity arose as a consequence of Ca2+ overload. Here we show that this is not the case and that the effect of (−)-EA is mediated by a heteromer of TRPC4 and TRPC1 proteins. Both TRPC4 and TRPC1 were required for (−)-EA cytotoxicity; however, although TRPC4 was necessary for the (−)-EA-evoked Ca2+ elevation, TRPC1 was not. TRPC1 either had no role or was a negative regulator of Ca2+ entry. By contrast, both TRPC4 and TRPC1 were necessary for monovalent cation entry evoked by (−)-EA, and (−)-EA-evoked cell death was dependent upon entry of the monovalent cation Na+. We therefore hypothesized that Na+/K+-ATPase might act protectively by counteracting the Na+ load resulting from sustained Na+ entry. Indeed, inhibition of Na+/K+-ATPase by ouabain potently and strongly increased (−)-EA-evoked cytotoxicity. The data suggest that (−)-EA achieves cancer cell cytotoxicity by inducing sustained Na+ entry through heteromeric TRPC1/TRPC4 channels and that the cytotoxic effect of (−)-EA can be potentiated by Na+/K+-ATPase inhibition. PMID:27875305

  15. Encapsulation of Metallic Na in an Electrically Conductive Host with Porous Channels as a Highly Stable Na Metal Anode.

    PubMed

    Luo, Wei; Zhang, Ying; Xu, Shaomao; Dai, Jiaqi; Hitz, Emily; Li, Yiju; Yang, Chunpeng; Chen, Chaoji; Liu, Boyang; Hu, Liangbing

    2017-06-14

    Room-temperature Na ion batteries (NIBs) have attracted great attention because of the widely available, abundant sodium resources and potentially low cost. Currently, the challenge of the NIB development is due primarily to the lack of a high-performance anode, while the Na metal anode holds great promise considering its highest specific capacity of 1165 mA h/g and lowest anodic potential. However, an uneven deposit, relatively infinite volume change, and dendritic growth upon plating/stripping cycles cause a low Coulombic efficiency, poor cycling performance, and severe safety concerns. Here, a stable Na carbonized wood (Na-wood) composite anode was fabricated via a rapid melt infusion (about 5 s) into channels of carbonized wood by capillary action. The channels function as a high-surface-area, conductive, mechanically stable skeleton, which lowers the effective current density, ensures a uniform Na nucleation, and restricts the volume change over cycles. As a result, the Na-wood composite anode exhibited flat plating/stripping profiles with smaller overpotentials and stable cycling performance over 500 h at 1.0 mA/cm(2) in a common carbonate electrolyte system. In sharp comparison, the planar Na metal electrode showed a much shorter cycle life of 100 h under the same test conditions.

  16. (-)-Englerin A-evoked Cytotoxicity Is Mediated by Na+ Influx and Counteracted by Na+/K+-ATPase.

    PubMed

    Ludlow, Melanie J; Gaunt, Hannah J; Rubaiy, Hussein N; Musialowski, Katie E; Blythe, Nicola M; Vasudev, Naveen S; Muraki, Katsuhiko; Beech, David J

    2017-01-13

    (-)-Englerin A ((-)-EA) has a rapid and potent cytotoxic effect on several types of cancer cell that is mediated by plasma membrane ion channels containing transient receptor potential canonical 4 (TRPC4) protein. Because these channels are Ca(2+)-permeable, it was initially thought that the cytotoxicity arose as a consequence of Ca(2+) overload. Here we show that this is not the case and that the effect of (-)-EA is mediated by a heteromer of TRPC4 and TRPC1 proteins. Both TRPC4 and TRPC1 were required for (-)-EA cytotoxicity; however, although TRPC4 was necessary for the (-)-EA-evoked Ca(2+) elevation, TRPC1 was not. TRPC1 either had no role or was a negative regulator of Ca(2+) entry. By contrast, both TRPC4 and TRPC1 were necessary for monovalent cation entry evoked by (-)-EA, and (-)-EA-evoked cell death was dependent upon entry of the monovalent cation Na(+) We therefore hypothesized that Na(+)/K(+)-ATPase might act protectively by counteracting the Na(+) load resulting from sustained Na(+) entry. Indeed, inhibition of Na(+)/K(+)-ATPase by ouabain potently and strongly increased (-)-EA-evoked cytotoxicity. The data suggest that (-)-EA achieves cancer cell cytotoxicity by inducing sustained Na(+) entry through heteromeric TRPC1/TRPC4 channels and that the cytotoxic effect of (-)-EA can be potentiated by Na(+)/K(+)-ATPase inhibition. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Determinants of substrate and cation transport in the human Na+/dicarboxylate cotransporter NaDC3.

    PubMed

    Schlessinger, Avner; Sun, Nina N; Colas, Claire; Pajor, Ana M

    2014-06-13

    Metabolic intermediates, such as succinate and citrate, regulate important processes ranging from energy metabolism to fatty acid synthesis. Cytosolic concentrations of these metabolites are controlled, in part, by members of the SLC13 gene family. The molecular mechanism underlying Na(+)-coupled di- and tricarboxylate transport by this family is understood poorly. The human Na(+)/dicarboxylate cotransporter NaDC3 (SLC13A3) is found in various tissues, including the kidney, liver, and brain. In addition to citric acid cycle intermediates such as α-ketoglutarate and succinate, NaDC3 transports other compounds into cells, including N-acetyl aspartate, mercaptosuccinate, and glutathione, in keeping with its dual roles in cell nutrition and detoxification. In this study, we construct a homology structural model of NaDC3 on the basis of the structure of the Vibrio cholerae homolog vcINDY. Our computations are followed by experimental testing of the predicted NaDC3 structure and mode of interaction with various substrates. The results of this study show that the substrate and cation binding domains of NaDC3 are composed of residues in the opposing hairpin loops and unwound portions of adjacent helices. Furthermore, these results provide a possible explanation for the differential substrate specificity among dicarboxylate transporters that underpin their diverse biological roles in metabolism and detoxification. The structural model of NaDC3 provides a framework for understanding substrate selectivity and the Na(+)-coupled anion transport mechanism by the human SLC13 family and other key solute carrier transporters. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. K+-induced natriuresis is preserved during Na+ depletion and accompanied by inhibition of the Na+-Cl- cotransporter.

    PubMed

    van der Lubbe, Nils; Moes, Arthur D; Rosenbaek, Lena L; Schoep, Sharon; Meima, Marcel E; Danser, Alexander H J; Fenton, Robert A; Zietse, Robert; Hoorn, Ewout J

    2013-10-15

    During hypovolemia and hyperkalemia, the kidneys defend homeostasis by Na(+) retention and K(+) secretion, respectively. Aldosterone mediates both effects, but it is unclear how the same hormone can evoke such different responses. To address this, we mimicked hypovolemia and hyperkalemia in four groups of rats with a control diet, low-Na(+) diet, high-K(+) diet, or combined diet. The low-Na(+) and combined diets increased plasma and kidney ANG II. The low-Na(+) and high-K(+) diets increased plasma aldosterone to a similar degree (3-fold), whereas the combined diet increased aldosterone to a greater extent (10-fold). Despite similar Na(+) intake and higher aldosterone, the high-K(+) and combined diets caused a greater natriuresis than the control and low-Na(+) diets, respectively (P < 0.001 for both). This K(+)-induced natriuresis was accompanied by a decreased abundance but not phosphorylation of the Na(+)-Cl(-) cotransporter (NCC). In contrast, the epithelial Na(+) channel (ENaC) increased in parallel with aldosterone, showing the highest expression with the combined diet. The high-K(+) and combined diets also increased WNK4 but decreased Nedd4-2 in the kidney. Total and phosphorylated Ste-20-related kinase were also increased but were retained in the cytoplasm of distal convoluted tubule cells. In summary, high dietary K(+) overrides the effects of ANG II and aldosterone on NCC to deliver sufficient Na(+) to ENaC for K(+) secretion. K(+) may inhibit NCC through WNK4 and help activate ENaC through Nedd4-2.

  19. Characterization and antibacterial activity of silver exchanged regenerated NaY zeolite from surfactant-modified NaY zeolite.

    PubMed

    Salim, Mashitah Mad; Malek, Nik Ahmad Nizam Nik

    2016-02-01

    The antibacterial activity of regenerated NaY zeolite (thermal treatment from cetyltrimethyl ammonium bromide (CTAB)-modified NaY zeolite and pretreatment with Na ions) loaded with silver ions were examined using the broth dilution minimum inhibitory concentration (MIC) method against Escherichia coli (E. coli ATCC 11229) and Staphylococcus aureus (S. aureus ATCC 6538). X-ray diffraction (XRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy dispersive X-ray (EDX) and chemical elemental analyses were used to characterize the regenerated NaY and AgY zeolites. The XRD patterns indicated that the calcination and addition of silver ions on regenerated NaY zeolite did not affect the structure of the regenerated NaY zeolite as the characteristic peaks of the NaY zeolite were retained, and no new peaks were observed. The regenerated AgY zeolite showed good antibacterial activity against both bacteria strains in distilled water, and the antibacterial activity of the samples increased with increasing Ag loaded on the regenerated AgY zeolite; the regenerated AgY zeolite was more effective against E. coli than S. aureus. However, the antibacterial activity of the regenerated AgY was not effective in saline solution for both bacteria. The study showed that CTAB-modified NaY zeolite materials could be regenerated to NaY zeolite using thermal treatment (550°C, 5h) and this material has excellent performance as an antibacterial agent after silver ions loading. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Regulation of the cardiac Na+ channel NaV1.5 by post-translational modifications.

    PubMed

    Marionneau, Céline; Abriel, Hugues

    2015-05-01

    The cardiac voltage-gated Na(+) channel, Na(V)1.5, is responsible for the upstroke of the action potential in cardiomyocytes and for efficient propagation of the electrical impulse in the myocardium. Even subtle alterations of Na(V)1.5 function, as caused by mutations in its gene SCN5A, may lead to many different arrhythmic phenotypes in carrier patients. In addition, acquired malfunctions of Na(V)1.5 that are secondary to cardiac disorders such as heart failure and cardiomyopathies, may also play significant roles in arrhythmogenesis. While it is clear that the regulation of Na(V)1.5 protein expression and function tightly depends on genetic mechanisms, recent studies have demonstrated that Na(V)1.5 is the target of various post-translational modifications that are pivotal not only in physiological conditions, but also in disease. In this review, we examine the recent literature demonstrating glycosylation, phosphorylation by Protein Kinases A and C, Ca(2+)/Calmodulin-dependent protein Kinase II, Phosphatidylinositol 3-Kinase, Serum- and Glucocorticoid-inducible Kinases, Fyn and Adenosine Monophosphate-activated Protein Kinase, methylation, acetylation, redox modifications, and ubiquitylation of Na(V)1.5. Modern and sensitive mass spectrometry approaches, applied directly to channel proteins that were purified from native cardiac tissues, have enabled the determination of the precise location of post-translational modification sites, thus providing essential information for understanding the mechanistic details of these regulations. The current challenge is first, to understand the roles of these modifications on the expression and the function of Na(V)1.5, and second, to further identify other chemical modifications. It is postulated that the diversity of phenotypes observed with Na(V)1.5-dependent disorders may partially arise from the complex post-translational modifications of channel protein components.

  1. On the Structure and Chemical Bonding of Si62- and Si62- in NaSi6- Upon Na+ Coordination

    SciTech Connect

    Zubarev, Dmitry Y.; Alexandrova, Anastassia N.; Boldyrev, Alexander I.; Cui, Lifeng; Li, Xi; Wang, Lai S.

    2006-03-23

    Photoelectron spectroscopy was combined with ab initio calculations to elucidate the structure and bonding in Si62- and NaSi6-. Well-resolved electronic transitions were observed in the photoelectron spectra of Si6- and NaSi6- at three photon energies (355, 266, and 193 nm). The spectra of NaSi6- were observed to be similar to those of Si6- except that the electron binding energies of the former are lower, suggesting that the Si6 motif in NaSi6- is structurally and electronically similar to that of Si6-. The electron affinity of Si6 and NaSi6 were measured fairly accurately to be 2.23 ± 0.03 eV and 1.80 ± 0.05 eV, respectively. Global minimum structure searches for Si62- and NaSi6- were performed using Gradient Embedded Genetic Algorithm followed by B3LYP, MP2 and CCSD(T) calculations. Vertical electron detachment energies (VDEs) were calculated for the lowest Si6- and NaSi6- structures at the CCSD(T)/6-311+G(2df), ROVGF/6-311+G(2df), UOVGF/6-311+G(2d), TD B3LYP/6-311+G(2df) levels of theory. Experimental VDEs were used to verify the global minimum structure for NaSi6-. Though the octahedral Si62-, analogous to the closo-form of borane B6H62-, is the most stable form for the bare hexa-silicon dianion, it is not the kernel for the NaSi6- global minimum. The most stable isomer of NaSi6- is based on a Si62- motif, which is distorted into C2v symmetry similar to the ground state structure of Si6-. The octahedral Si62- coordinated by a Na+ is a low-lying isomer and was also observed experimentally. The chemical bonding in Si62- and NaSi6- was understood using NBO, molecular orbital, and ELF analysis.

  2. Beyond lithium-ion batteries: A computational study on Na-S and Na-O batteries

    NASA Astrophysics Data System (ADS)

    Masedi, M. C.; Ngoepe, P. E.; Sithole, H. M.

    2017-02-01

    The first principle pseudopotential calculations based on the Perdew-Burke-Ernzerhof (PBE) form of generalized gradient approximation (GGA) within density functional theory (DFT) has been utilized to investigate the stabilities of insoluble discharge products of oxygen and sulphur in the Na-O and Na-S batteries. Their structural, mechanical and electronic properties were determined. The lattice parameters were well reproduced and agree with the available experimental data. The heats of formation predict that all structures are generally stable and Na2S has the lowest value. The elastic constants suggest that all the structures are mechanically stable which in good agreement with the calculated phonon dispersions.

  3. Na double-edge magneto-optic filter for Na lidar profiling of wind and temperature in the lower atmosphere.

    PubMed

    Huang, Wentao; Chu, Xinzhao; Williams, B P; Harrell, S D; Wiig, Johannes; She, C-Y

    2009-01-15

    A Na double-edge magneto-optic filter is proposed for incorporation into the receiver of a three-frequency Na Doppler lidar to extend its wind and temperature measurements into the lower atmosphere. Two prototypes based on cold- and hot-cell designs were constructed and tested with laser scanning and quantum mechanics modeling. The hot-cell filter exhibits superior performances over the cold-cell filter containing buffer gas. Lidar simulations, metrics, and error analyses show that simultaneous wind and temperature measurements are feasible in the altitude range of 20-50 km using the hot-cell filter and reasonable Na lidar parameters.

  4. A Comparative Investigation on the JT Effect in Triangular Compounds of NaMnO2, NaNiO2 and NaTiO2

    NASA Astrophysics Data System (ADS)

    Ouyang, Sheng-De; Quan, Ya-Min; Liu, Da-Yong; Zou, Liang-Jian

    2011-06-01

    We present a study on the Jahn—Teller (JT) distortions of the TiO6, NiO6 and MnO6 complexes in NaTiO2, NaNiO2 and NaMnO2 triangular compounds with a C2/m structure. The JT vibronic normal modes are found to be Q3, Q'4 and Q6 by the group symmetry on the C2/m structure. The magnitude of the normal coordinates (Q3, Q'4, Q6) and the structural parameters of distorted octahedra MO6 (M=Ti, Ni, Mn) are obtained and in good agreement with experimental data. The energy level splitting of 3d orbitals and the highest occupied molecular orbital (HOMO) character in the MO6 complex are also calculated in accordance with the JT distortions. These results provide a first insight into the groundstate and magnetic properties of distorted triangular compounds AMO2.

  5. Infrared and SEM analyses of polyethyleneglycol-400 adsorbed on zeolites NaA, CaA, NaX and NaY

    NASA Astrophysics Data System (ADS)

    Öztürk, Nuri; Ucun, Fatih; Didem Muhtar, A.; Bahçeli, Semiha

    2009-03-01

    The adsorption of polyethyleneglycol-400 (PEG-400) on zeolites NaA, CaA, NaX and NaY have been investigated by using FT-IR spectroscopy and scanning electron microscopic (SEM) analyses. The spectral data have indicated that the source of adsorption of the PEG-400 on the mentioned zeolites is the interaction between the (OH) group of the liquid adsorbent and the surface silanol groups of the zeolites by means of a hydrogen bond. Shortly, the PEG binds with the silanol groups through the hydrogen bonding where the ethereal oxygen acts as a hydrogen bond accepter. A part of the PEG molecule remains adsorbed on the surface and the rest part remains protruded. So, the most of the silanol groups on the zeolites are masked by the PEG-400.

  6. Mg and Na clusters in a helium matrix

    NASA Astrophysics Data System (ADS)

    Höller, Johannes; Krotscheck, Eckhard; Zillich, Robert E.

    2015-08-01

    We have studied the adsorption properties of liquid 4He on small Mg and Na clusters. The calculation requires three components: a calculation of the cluster structure, a path-integral Monte Carlo calculation of the structure of the surrounding helium, and the determination of the cluster-helium interaction. The two types of clusters are examples for two physically very different situations: small Mg clusters are insulating and their interaction with the surrounding helium is relatively strong. We find for all cases considered here that these clusters are submersed in the helium droplet and reside basically at its center. Na clusters, on the other hand, are conducting down to very small particle numbers. More important, however, is the fact that the Na-He interaction is much weaker than the He-He attraction which causes small Na clusters to reside at the cluster surface.

  7. Tb/Na tobermorite: Thermal behaviour and high temperature products

    SciTech Connect

    Garra, Walter; Marchetti, Fabio; Merlino, Stefano

    2009-06-15

    By heating a sample of Tb/Na tobermorite we obtained a phase which was identified through its X-ray diffraction (XRD) pattern, as terbium silicate apatite. Subsequently this compound has been directly prepared by solid state reaction and we carried out a structural refinement from XRD data in space group P6{sub 3}/m obtaining cell parameters a=9.39199(4) A and c=6.84041(5) A. Terbium silicate apatite heated in melted NaF led to Tb{sub 4}O{sub 7} crystals. - Graphical Abstract: By heating over 900 deg. C Tb/Na tobermorite a terbium silicate apatite was obtained. The same product has been independently prepared and structurally characterized from powder diffraction data. Attempts of crystallizing terbium silicate apatite from melted NaF led to Tb{sub 4}O{sub 7} crystals.

  8. Na2MoO2As2O7

    PubMed Central

    Jouini, Raja; Zid, Mohamed Faouzi; Driss, Ahmed

    2012-01-01

    Disodium molybdenum dioxide diarsenate, Na2MoO2As2O7, has been synthesized by a solid-state reaction. The structure is built up from MoAs2O12 linear units sharing corners to form a three-dimensional framework containing tunnels running along the a-axis direction in which the Na+ cations are located. In this framework, the AsV atoms are tetra­hedrally coordinated and form an As2O7 group. The MoVI atom is displaced from the center of an octa­hedron of O atoms. Two Na+ cations are disordered about inversion centres. Structural relationships between different compounds: A 2MoO2As2O7 (A = K, Rb), AMOP2O7 (A = Na, K, Rb; M = Mo, Nb) and MoP2O7 are discussed. PMID:23468669

  9. Stellar (n ,γ ) cross sections of 23Na

    NASA Astrophysics Data System (ADS)

    Uberseder, E.; Heil, M.; Käppeler, F.; Lederer, C.; Mengoni, A.; Bisterzo, S.; Pignatari, M.; Wiescher, M.

    2017-02-01

    The cross section of the 23Na(n ,γ )24Na reaction was measured via the activation method at the Karlsruhe 3.7 MV Van de Graaff accelerator. NaCl samples were exposed to quasistellar neutron spectra at k T =5.1 and 25 keV produced via the 18O(p ,n )18F and 7Li(p ,n )7Be reactions, respectively. The derived capture cross sections <σ> kT =5 keV=9.1 ±0.3 mb and <σ> kT =25 keV=2.03 ±0.05 mb are significantly lower than reported in literature. These results were used to substantially revise the radiative width of the first 23Na resonance and to establish an improved set of Maxwellian average cross sections. The implications of the lower capture cross section for current models of s -process nucleosynthesis are discussed.

  10. Interpretation of Na-K-Mg relations in geothermal waters

    USGS Publications Warehouse

    Fournier, R.O.

    1990-01-01

    When using a Na-K-???Mg triangular diagram as an aid in the interpretation of a geothermal water, the estimated temperature of last water-rock equilibration may change by as much as 50??C, depending on which of the many Na/K geothermometers one assumes is correct. A particular geothermometer may work well in one place and not in another because of differences in the mineralogy of the phases that are in contact with the reservoir fluid. The position of the full equilibrium line that is used for geothermometry and for assessing degrees of departure from equilibrium also changes as the assumed K/???Mg geothermometer equation changes. The degree of ambiguity can be evaluated by utilizing the results of all the recently published Na/K geothermometers on a single Na-K-???Mg triangular plot.

  11. VIEW OF CEMETERY SECTION NA (NEW ADDITION), WITH NORTHERN PERIMETER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF CEMETERY SECTION NA (NEW ADDITION), WITH NORTHERN PERIMETER FENCE ALONG LINCOLN BOULEVARD IN FOREGROUND. VIEW TO SOUTH. - San Francisco National Cemetery, 1 Lincoln Boulevard, San Francisco, San Francisco County, CA

  12. VIEW OF CEMETERY SECTIONS NA (NEW ADDITION) AND NAWS (NEW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF CEMETERY SECTIONS NA (NEW ADDITION) AND NAWS (NEW ADDITION WEST SIDE) ALONG NORTH DRIVE, WITH MAINTENANCE COMPLEX AT LEFT BACKGROUND. VIEW TO SOUTHEAST. - San Francisco National Cemetery, 1 Lincoln Boulevard, San Francisco, San Francisco County, CA

  13. Reactions of NaCl with gaseous SO3, SO2, and O2

    NASA Technical Reports Server (NTRS)

    Fielder, W. L.; Stearns, C. A.; Kohl, F. J.

    1984-01-01

    Hot corrosion of gas turbine engine components involves deposits of Na2SO4 which are produced by reactions between NaCl and oxides of sulfur. For the present investigation, NaCl single crystals were exposed at 100 to 850 C to gaseous mixtures of SO3, SO2, and O2. The products formed during this exposure depend, primarily, on the temperatures. The four product films were: NaCl-SO3; Na2S2O7; Na2SO4; and NaCl-Na2SO4. The kinetics of the reactions were measured.

  14. Structural, electronic, sodium diffusion and elastic properties of Na-P alloy anode for Na-ion batteries: Insight from first-principles calculations

    NASA Astrophysics Data System (ADS)

    Lu, Huansheng; Xu, Bo; Shi, Jing; Wu, Musheng; Hu, Yinquan; Ouyang, Chuying

    2016-11-01

    Sodium-ion batteries (NIBs) as an alternative to lithium-ion batteries (LIBs) have recently received great attentions because of the relatively high abundance of sodium. Searching for suitable anode materials has always been a hot topic in the field of NIB study. Recent reports show that phosphorus-based materials are potential as the anode materials for NIBs. Using first-principles calculations, herein, we study the atomic and electronic structures, diffusion dynamics and intrinsic elastic properties of various Na-P alloy compounds (NaP5, Na3P11, NaP and Na3P) as the intermediate phases during Na extraction/insertion in phosphorus-based anode materials. It is found that all the crystalline phases of Na-P alloy phases considered in our study are semiconductors with band gaps larger than that of black phosphorus (BP). The calculations of Na diffusion dynamics indicate a relatively fast Na diffusion in these materials, which is important for good rate performance. In addition, the diffusion channels of sodium ions are one-dimensional in NaP5 phase and three-dimensional in other three phases (Na3P11, NaP and Na3P). Elastic constant calculations indicate that all four phases are mechanically stable. Among them, however, NaP5, Na3P11 and NaP alloy phases are ductile, while the fully sodiated phase Na3P is brittle. In order to improve the electrochemical performance of Na-P alloy anodes for NIBs, thus, promoting ductility of Na-P phase with high sodium concentration may be an effective way.

  15. In search of synaptosomal Na+,K(+)-ATPase regulators.

    PubMed

    Rodríguez de Lores Arnaiz, G

    1992-01-01

    The arrival of the nerve impulse to the nerve endings leads to a series of events involving the entry of sodium and the exit of potassium. Restoration of ionic equilibria of sodium and potassium through the membrane is carried out by the sodium/potassium pump, that is the enzyme Na+,K(+)-ATPase. This is a particle-bound enzyme that concentrates in the nerve ending or synaptosomal membranes. The activity of Na+,K(+)-ATPase is essential for the maintenance of numerous reactions, as demonstrated in the isolated synaptosomes. This lends interest to the knowledge of the possible regulatory mechanisms of Na+,K(+)-ATPase activity in the synaptic region. The aim of this review is to summarize the results obtained in the author's laboratory, that refer to the effect of neurotransmitters and endogenous substances on Na+,K(+)-ATPase activity. Mention is also made of results in the field obtained in other laboratories. Evidence showing that brain Na+,K(+)-ATPase activity may be modified by certain neurotransmitters and insulin have been presented. The type of change produced by noradrenaline, dopamine, and serotonin on synaptosomal membrane Na+,K(+)-ATPase was found to depend on the presence or absence of a soluble brain fraction. The soluble brain fraction itself was able to stimulate or inhibit the enzyme, an effect that was dependent in turn on the time elapsed between preparation and use of the fraction. The filtration of soluble brain fraction through Sephadex G-50 allowed the separation of two active subfractions: peaks I and II. Peak I increased Na+,K(+)- and Mg(2+)-ATPases, and peak II inhibited Na+,K(+)-ATPase. Other membrane enzymes such as acetylcholinesterase and 5'-nucleotidase were unchanged by peaks I or II. In normotensive anesthetized rats, water and sodium excretion were not modified by peak I but were increased by peak II, thus resembling ouabain effects. 3H-ouabain binding was unchanged by peak I but decreased by peak II in some areas of the CNS assayed by

  16. High Capacity Na+/H+ Exchange Activity in Mineralizing Osteoblasts

    PubMed Central

    Liu, Li; Schlesinger, Paul H.; Slack, Nicole M.; Friedman, Peter A.; Blair, Harry C.

    2015-01-01

    Osteoblasts synthesize bone in polarized groups of cells sealed by tight junctions. Large amounts of acid are produced as bone mineral is precipitated. We addressed the mechanism by which cells manage this acid load by measuring intracellular pH (pHi) in non-transformed osteoblasts in response to weak acid or bicarbonate loading. Basal pHi in mineralizing osteoblasts was ∼7.3 and decreased by ∼ 1.4 units upon replacing extracellular Na+ with N-methyl-d-glucamine. Loading with 40 mM acetic or propionic acids, in normal extracellular Na+, caused only mild cytosolic acidification. In contrast, in Na+-free solutions, weak acids reduced pHi dramatically. After Na+ reintroduction, pHi recovered rapidly, in keeping with Na+/H+exchanger (NHE) activity. Sodium-dependent pHi recovery from weak acid loading was inhibited by amiloride with the Ki consistent with NHEs. NHE1 and NHE6 were expressed strongly, and expression was upregulated highly, by mineralization, in human osteoblasts. Antibody labeling of mouse bone showed NHE1 on basolateral surfaces of all osteoblasts. NHE6 occurred on basolateral surfaces of osteoblasts mainly in areas of mineralization. Conversely, elevated HCO3- alkalinized osteoblasts, and pH recovered in medium containing CI-, with or without Na+, in keeping with Na+-independent CI-/HCO3- exchange. The exchanger AE2 also occurred on the basolateral surface of osteoblasts, consistent with CI-/HCO3- exchange for elimination of metabolic carbonate. Overexpression of NHE6 or knockdown of NHE1 in MG63 human osteosarcoma cells confirmed roles of NHE1 and NHE6 in maintaining pHi. We conclude that in mineralizing osteoblasts, slightly basic basal pHi is maintained, and external acid load is dissipated, by high-capacity Na+/H+ exchange via NHE1 and NHE6. PMID:21413028

  17. Na+ and K+ ion imbalances in Alzheimer’s disease

    PubMed Central

    Vitvitsky, Victor M.; Garg, Sanjay K.; Keep, Richard F.; Albin, Roger L.; Banerjee, Ruma

    2012-01-01

    Alzheimer’s disease (AD) is associated with impaired glutamate clearance and depressed Na+/K+ ATPase levels in AD brain that might lead to a cellular ion imbalance. To test this hypothesis, [Na+] and [K+] were analyzed in postmortem brain samples of 12 normal and 16 AD individuals, and in cerebrospinal fluid (CSF) from AD patients and matched controls. Statistically significant increases in [Na+] in frontal (25%) and parietal cortex (20%) and in cerebellar [K+] (15%) were observed in AD samples compared to controls. CSF from AD patients and matched controls exhibited no differences, suggesting that tissue ion imbalances reflected changes in the intracellular compartment. Differences in cation concentrations between normal and AD brain samples were modeled by a 2-fold increase in intracellular [Na+] and an 8–15% increase in intracellular [K+]. Since amyloid beta peptide (Aβ) is an important contributor to AD brain pathology, we assessed how Aβ affects ion homeostasis in primary murine astrocytes, the most abundant cells in brain tissue. We demonstrate that treatment of astrocytes with the Aβ 25–35 peptide increases intracellular levels of Na+ (~2–3-fold) and K+ (~1.5-fold), which were associated with reduced levels of Na+/K+ ATPase and the Na+-dependent glutamate transporters, GLAST and GLT-1. Similar increases in astrocytic Na+ and K+ levels were also caused by Aβ 1–40, but not by Aβ 1–42 treatment. Our study suggests a previously unrecognized impairment in AD brain cell ion homeostasis that might be triggered by Aβ and could significantly affect electrophysiological activity of brain cells, contributing to the pathophysiology of AD. PMID:22820549

  18. Photoassociation spectroscopy of ultracold highly excited NaCs molecules

    NASA Astrophysics Data System (ADS)

    Jayaseelan, Maitreyi; Haruza, Marek; Bigelow, Nicholas

    2013-05-01

    We report on our spectroscopic investigations of translationally ultracold NaCs molecules. Photoassociation from laser cooled mixtures of ground state sodium and excited cesium atoms creates molecules in excited states detuned from the Na(3s) + Cs(6d) dissociation asymptote. This is an as yet unexplored asymptote for molecule formation. We infer properties of the scattering wave from the PA spectra, and investigate the populated ground states using photoionization and depletion spectroscopy.

  19. The β-γ decay of 21Na

    NASA Astrophysics Data System (ADS)

    Achouri, N. L.; Angélique, J. C.; Ban, G.; Bastin, B.; Blank, B.; Dean, S.; Dendooven, P.; Giovinazzo, J.; Grévy, S.; Jungmann, K.; Laurent, B.; Liénard, E.; Naviliat-Cuncic, O.; Orr, N. A.; Rogachevskiy, A.; Sohani, M.; Traykov, E.; Wilschut, H.

    2010-04-01

    A new and independent determination of the Gamow-Teller branching ratio in the β-decay of 21Na is reported. The value 5.13 ± 0.43% obtained is in agreement with the currently adopted value and the most recent measurement. In contrast to previous experiments, the present method was based on the counting of the parent 21Na ions and the resulting 351 keV γ-rays without coincident β-particle detection.

  20. Metal Fluoride Complexes of Na,K-ATPase

    PubMed Central

    Cornelius, Flemming; Mahmmoud, Yasser A.; Toyoshima, Chikashi

    2011-01-01

    The Na,K-ATPase belongs to the P-type ATPase family of primary active cation pumps. Metal fluorides like magnesium-, beryllium-, and aluminum fluoride act as phosphate analogues and inhibit P-type ATPases by interacting with the phosphorylation site, stabilizing conformations that are analogous to specific phosphoenzyme intermediates. Cardiotonic steroids like ouabain used in the treatment of congestive heart failure and arrhythmias specifically inhibit the Na,K-ATPase, and the detailed structure of the highly conserved binding site has recently been described by the crystal structure of the shark Na,K-ATPase in a state analogous to E2·2K+·Pi with ouabain bound with apparently low affinity (1). In the present work inhibition, and subsequent reactivation by high Na+, after treatment of shark Na,K-ATPase with various metal fluorides are characterized. Half-maximal inhibition of Na,K-ATPase activity by metal fluorides is in the micromolar range. The binding of cardiotonic steroids to the metal fluoride-stabilized enzyme forms was investigated using the fluorescent ouabain derivative 9-anthroyl ouabain and compared with binding to phosphorylated enzyme. The fastest binding was to the Be-fluoride stabilized enzyme suggesting a preformed ouabain binding cavity, in accord with results for Ca-ATPase where Be-fluoride stabilizes the E2-P ground state with an open luminal ion access pathway, which in Na,K-ATPase could be a passage for ouabain. The Be-fluoride stabilized enzyme conformation closely resembles the E2-P ground state according to proteinase K cleavage. Ouabain, but not its aglycone ouabagenin, prevented reactivation of this metal fluoride form by high Na+ demonstrating the pivotal role of the sugar moiety in closing the extracellular cation pathway. PMID:21708939

  1. Na + Xe collisions in the presence of two nonresonant lasers

    NASA Technical Reports Server (NTRS)

    De Vries, P. L.; Chang, C. H.; George, T. F.; Laskowski, B.; Stallcop, J. R.

    1980-01-01

    Na+Xe collisions in the presence of two distinct laser fields (rhodamine 110 and Nd:glass) are investigated with reference to the response to nonresonant radiation of alkali metals collisionally perturbed by a buffer gas. It is found that the excited Na-asterisk (4s)+Xe state is produced with a measurable cross section due to two-photon absorption with field intensities as low as 10 MW/sq cm.

  2. An empirical NaKCa geothermometer for natural waters

    USGS Publications Warehouse

    Fournier, R.O.; Truesdell, A.H.

    1973-01-01

    An empirical method of estimating the last temperature of water-rock interaction has been devised. It is based upon molar Na, K and Ca concentrations in natural waters from temperature environments ranging from 4 to 340??C. The data for most geothermal waters cluster near a straight line when plotted as the function log ( Na K) + ?? log [ ??? (Ca) Na] vs reciprocal of absolute temperature, where ?? is either 1 3 or 4 3 depending upon whether the water equilibrated above or below 100??C. For most waters tested, the method gives better results than the Na K methods suggested by other workers. The ratio Na K should not be used to estimate temperature if ??? ( MCa) MNa is greater than 1. The Na K values of such waters generally yield calculated temperatures much higher than the actual temperature at which water interacted with the rock. A comparison of the composition of boiling hot-spring water with that obtained from a nearby well (170??C) in Yellowstone Park shows that continued water-rock reactions may occur during ascent of water even though that ascent is so rapid that little or no heat is lost to the country rock, i.e. the water cools adiabatically. As a result of such continued reaction, waters which dissolve additional Ca as they ascend from the aquifer to the surface will yield estimated aquifer temperatures that are too low. On the other hand, waters initially having enough Ca to deposit calcium carbonate during ascent may yield estimated aquifer temperatures that are too high if aqueous Na and K are prevented from further reaction with country rock owing to armoring by calcite or silica minerals. The Na-K-Ca geothermometer is of particular interest to those prospecting for geothermal energy. The method also may be of use in interpreting compositions of fluid inclusions. ?? 1973.

  3. 23Na and (1)H NMR microimaging of intact plants.

    PubMed

    Olt, S; Krötz, E; Komor, E; Rokitta, M; Haase, A

    2000-06-01

    (23)Na NMR microimaging is described to map, for the first time, the sodium distribution in living plants. As an example, the response of 6-day-old seedlings of Ricinus communis to exposure to sodium chloride concentrations from 5 to 300 mM was observed in vivo using (23)Na as well as (1)H NMR microimaging. Experiments were performed at 11.75 T with a double resonant (23)Na-(1)H probehead. The probehead was homebuilt and equipped with a climate chamber. T(1) and T(2) of (23)Na were measured in the cross section of the hypocotyl. Within 85 min (23)Na images with an in-plane resolution of 156 x 156 micrometer were acquired. With this spatial information, the different types of tissue in the hypocotyl can be discerned. The measurement time appears to be short compared to the time scale of sodium uptake and accumulation in the plant so that the kinetics of salt stress can be followed. In conclusion, (23)Na NMR microimaging promises great potential for physiological studies of the consequences of salt stress on the macroscopic level and thus may become a unique tool for characterizing plants with respect to salt tolerance and salt sensitivity. Copyright 2000 Academic Press.

  4. 23Na and 1H NMR Microimaging of Intact Plants

    NASA Astrophysics Data System (ADS)

    Olt, Silvia; Krötz, Eva; Komor, Ewald; Rokitta, Markus; Haase, Axel

    2000-06-01

    23Na NMR microimaging is described to map, for the first time, the sodium distribution in living plants. As an example, the response of 6-day-old seedlings of Ricinus communis to exposure to sodium chloride concentrations from 5 to 300 mM was observed in vivo using 23Na as well as 1H NMR microimaging. Experiments were performed at 11.75 T with a double resonant 23Na-1H probehead. The probehead was homebuilt and equipped with a climate chamber. T1 and T2 of 23Na were measured in the cross section of the hypocotyl. Within 85 min 23Na images with an in-plane resolution of 156 × 156 μm were acquired. With this spatial information, the different types of tissue in the hypocotyl can be discerned. The measurement time appears to be short compared to the time scale of sodium uptake and accumulation in the plant so that the kinetics of salt stress can be followed. In conclusion, 23Na NMR microimaging promises great potential for physiological studies of the consequences of salt stress on the macroscopic level and thus may become a unique tool for characterizing plants with respect to salt tolerance and salt sensitivity.

  5. The paranodal cytoskeleton clusters Na+ channels at nodes of Ranvier

    PubMed Central

    Amor, Veronique; Zhang, Chuansheng; Vainshtein, Anna; Zhang, Ao; Zollinger, Daniel R; Eshed-Eisenbach, Yael; Brophy, Peter J; Rasband, Matthew N; Peles, Elior

    2017-01-01

    A high density of Na+ channels at nodes of Ranvier is necessary for rapid and efficient action potential propagation in myelinated axons. Na+ channel clustering is thought to depend on two axonal cell adhesion molecules that mediate interactions between the axon and myelinating glia at the nodal gap (i.e., NF186) and the paranodal junction (i.e., Caspr). Here we show that while Na+ channels cluster at nodes in the absence of NF186, they fail to do so in double conditional knockout mice lacking both NF186 and the paranodal cell adhesion molecule Caspr, demonstrating that a paranodal junction-dependent mechanism can cluster Na+ channels at nodes. Furthermore, we show that paranode-dependent clustering of nodal Na+ channels requires axonal βII spectrin which is concentrated at paranodes. Our results reveal that the paranodal junction-dependent mechanism of Na+channel clustering is mediated by the spectrin-based paranodal axonal cytoskeleton. DOI: http://dx.doi.org/10.7554/eLife.21392.001 PMID:28134616

  6. Na+ conductance and the threshold for repetitive neuronal firing.

    PubMed

    Matzner, O; Devor, M

    1992-11-27

    The Hodgkin-Huxley equation for electrogenesis in the voltage clamped squid giant axon was used to predict the effect of altering maximal Na+ conductance (gNa+max) on the repetitive firing process. The main finding was that increasing gNa+max, without changing any other membrane parameter, reduced the threshold current required to evoke repetitive firing. That is, it rendered the membrane hyperexcitable. Threshold for evoking single action potentials was also affected, but much less so. Other consequences of increasing gNa+max were a decrease in the minimum sustainable rhythmic firing frequency (mRFF), a monotonic increase in firing frequency at any given suprathreshold stimulus intensity, an increase in the current value at which intense depolarizing stimuli block rhythmogenesis, an increase in the maximal sustainable firing frequency using intense currents (MRFF), and the consequent expansion of the dynamic range for stimulus encoding. Thus, the control of gNa+max through the regulation of Na+ channel synthesis and membrane incorporation at sites of rhythmogenesis (e.g. axon hillock-initial segment region, or peripheral sensory endings) is a potential regulatory mechanism for neuronal excitability and stimulus encoding.

  7. Xenon adsorption in NaA zeolite cavities

    NASA Astrophysics Data System (ADS)

    McCormick, A. V.; Chmelka, B. F.

    Adsorption of xenon atoms in the α-cages of NaA zeolite has been studied using 129Xe NMR spectroscopy to probe directly the distribution and configuration of molecules in confined, microporous environments. The 129Xe NMR spectrum is sensitive to subtle changes in xenon environment, so relative populations of α-cages containing different numbers of xenon guests can be determined and the effects of other co-adsorbed species monitored. On the basis of 129Xe NMR spectra, the distribution of xenon atoms among NaA α-cages is shown to exhibit a marked dependence on the pressure at which the xenon guests are introduced. 129Xe NMR spectra recorded at 200 K reveal that xenon atoms in the NaA α-cages experience diminished mobility (resembling condensation phenomena) at higher temperatures than in the bulk gas of equivalent density. Thus, the chemical potential of adsorbed xenon can be investigated experimentally as a function of both temperature and guest density. The density dependence of the 129Xe chemical shift in Xe/NaA and in bulk xenon gas shows that Xe-Xe interactions in the proximity of the NaA cage wall are important in α-cages containing more than five xenon guests. This trend is linked to entropic effects which may enhance xenon adsorption in the confined environment of the NaA α-cages.

  8. NaChBac: The Long Lost Sodium Channel Ancestor

    PubMed Central

    2011-01-01

    In excitable cells, the main mediators of sodium conductance across membranes are voltage-gated sodium channels (NaVs). Eukaryotic NaVs are essential elements in neuronal signaling and muscular contraction and in humans have been causally related to a variety of neurological and cardiovascular channelopathies. They are complex heavily glycosylated intrinsic membrane proteins present in only trace quantities that have proven to be challenging objects of study. However, in recent years, a number of simpler prokaryotic sodium channels have been identified, with NaChBac from Bacillus halodurans being the most well-characterized to date. The availability of a bacterial NaV that is amenable to heterologous expression and functional characterization in both bacterial and mammalian systems has provided new opportunities for structure–function studies. This review describes features of NaChBac as an exemplar of this class of bacterial channels, compares prokaryotic and eukaryotic NaVs with respect to their structural organization, pharmacological profiling, and functional kinetics, and discusses how voltage-gated ion channels may have evolved to deal with the complex functional demands of higher organisms. PMID:21770445

  9. High performance MCFC using Li/Na electrolyte

    SciTech Connect

    Donado, R.A.; Ong, E.T.; Sishtla, C.I.

    1995-08-01

    The substitution of a lithium/ sodium carbonate (Li/Na) mixture for the lithium/potassium carbonate (Li/K) electrolyte used in MCFCs holds the promise of higher ionic conductivity, higher exchange current density at both electrodes, lower vapor pressure, and lower cathode dissolution rates. However, when the substitution is made in cells optimized for use with the Li/K electrolyte, the promised increase in performance is not realized. As a consequence the literature contains conflicting data with regard to the performance, compositional stability, and chemical reactivity of the Li/Na electrolyte. Experiments conducted at the Institute of Gas Technology (IGT) concluded that the source of the problem is the different wetting characteristics of the two electrolytes. Electrode pore structures optimized for use with Li/K do not work well with Li/Na. Using proprietary methods and materials, IGT was able to optimize a set of electrodes for the Li/Na electrolyte. Experiments conducted in bench-scale cells have confirmed the superior performance of the Li/Na electrolyte compared to the Li/K electrolyte. The Li/Na cells exhibited a 5 to 8 percent improvement in overall performance, a substantial decrease in the rate of cathode dissolution, and a decreased decay rate. The longest running cell has logged over 13,000 hours of operation with a decay rate of less than 2 mV/1000 hours.

  10. Voltage dependence of Na-Ca exchanger conformational currents.

    PubMed Central

    Niggli, E; Lipp, P

    1994-01-01

    Properties of a transient current (Icont) believed to reflect a conformational change of the Na-Ca exchanger molecules after Ca2+ binding were investigated. Intracellular Ca2+ concentration jumps in isolated cardiac myocytes were generated with flash photolysis of caged Ca2+ dimethoxynitrophenamine, and membrane currents were simultaneously measured using the whole-cell variant of the patch-clamp technique. A previously unresolved shallow voltage dependence of Icont was revealed after developing an experimental protocol designed to compensate for the photoconsumption of the caged compound. This voltage dependence can be interpreted to reflect the distribution of Na-Ca exchanger conformational states with the Ca2+ binding site exposed to the inside of the cell immediately before the flash. Analysis performed by fitting a Boltzmann distribution to the observed data suggests that under control conditions most exchanger molecules reside in states with the Ca2+ binding site facing the outside of the cell. Dialysis of the cytosol with 3',4'-dichlorobenzamil, an organic inhibitor of the Na-Ca exchange, increased the magnitude of Icont and changed the voltage dependence, consistent with a parallel shift of the charge/voltage curve. This shift may result from intracellular DCB interfering with an Na(+)-binding or Na(+)-translocating step. These observations are consistent with Icont arising from a charge movement mediated by the Na-Ca exchanger molecules after binding of Ca2+. PMID:7819485

  11. Deliquescence of NaCl–NaNO3, KNO3–NaNO3, and NaCl–KNO3 salt mixtures from 90 to 120°C

    PubMed Central

    Carroll, Susan; Craig, Laura; Wolery, Thomas J

    2005-01-01

    We conducted reversed deliquescence experiments in saturated NaCl–NaNO3–H2O, KNO3–NaNO3–H2O, and NaCl–KNO3–H2O systems from 90 to 120°C as a function of relative humidity and solution composition. NaCl, NaNO3, and KNO3 represent members of dust salt assemblages that are likely to deliquesce and form concentrated brines on high-level radioactive waste package surfaces in a repository environment at Yucca Mountain, NV. Discrepancy between model prediction and experiment can be as high as 8% for relative humidity and 50% for dissolved ion concentration. The discrepancy is attributed primarily to the use of 25°C models for Cl–NO3 and K–NO3 ion interactions in the current Yucca Mountain Project high-temperature Pitzer model to describe the nonideal behavior of these highly concentrated solutions.

  12. The enhancement of neutral metal Na layer above thunderstorms

    NASA Astrophysics Data System (ADS)

    Yu, Bingkun; Xue, Xianghui; Lu, Gaopeng; Kuo, Chengling; Dou, Xiankang; Gao, Qi; Qie, Xiushu; Wu, Jianfei; Tang, Yihuan

    2017-04-01

    Na (sodium) exists as layers of atoms in the mesosphere/lower thermosphere (MLT) at altitudes between 80 and 105 km. It has lower ionization potential of 5.139 eV than atmospheric species, such as O2 (12.06 eV). Tropospheric thunderstorms affect the lower ionosphere and the ionospheric sporadic E (Es) at 100 km can also be influenced by lightning. The mechanism is expected to be associated with transient luminous events (TLE) as red sprites and gigantic jets at upper atmosphere. However, measurements of ionospheric electric fields of 20mV·m-1 above thunderstorms are less than estimated value (>48 0mV·m-1) to excite ionization in the lower ionosphere. We found an enhancement of Na layer above thunderstorms. The increase of Na density in the statistical result can be as much as 500 cm-3 and it will have an impact on ionospheric chemistry and modify the conductivity properties of the MLT region. The ionospheric observations made with two digisondes near the Na lidar, the thunderstorm model, ionosphere model, and Na chemistry model are all used to discuss the possible mechanisms responsible for the enhancement of Na layer after thunderstorms.

  13. Theoretical considerations underlying Na(+) uptake mechanisms in freshwater fishes.

    PubMed

    Parks, Scott K; Tresguerres, Martin; Goss, Greg G

    2008-11-01

    Ion and acid-base regulating mechanisms have been studied at the fish gill for almost a century. Original models proposed for Na(+) and Cl(-) uptake, and their linkage with H(+) and HCO(3)(-) secretion have changed substantially with the development of more sophisticated physiological techniques. At the freshwater fish gill, two dominant mechanisms for Na(+) uptake from dilute environments have persisted in the literature. The use of an apical Na(+)/H(+) exchanger driven by a basolateral Na(+)/K(+)-ATPase versus an apical Na(+) channel electrogenically coupled to an apical H(+)-ATPase have been the source of debate for a number of years. Advances in molecular biology have greatly enhanced our understanding of the basic ion transport mechanisms at the fish gill. However, it is imperative to ensure that thermodynamic principles are followed in the development of new models for gill ion transport. This review will focus on the recent molecular advances for Na(+) uptake in freshwater fish. Emphasis will be placed on thermodynamic constraints that prevent electroneutral apical NHE function in most freshwater environments. By combining recent advances in molecular and functional physiology of fish gills with thermodynamic considerations of ion transport, our knowledge in the field should continue to grow in a logical manner.

  14. Regulation of the paracellular Na+ and Cl- conductances by the NaCl-generated osmotic gradient in a manner dependent on the direction of osmotic gradients.

    PubMed

    Tokuda, Shinsaku; Niisato, Naomi; Nakajima, Ken-Ichi; Marunaka, Yoshinori

    2008-02-08

    In the present study, we investigated the effect of osmolality on the paracellular ion conductance (Gp) composed of the Na(+) conductance (G(Na)) and the Cl(-) conductance (G(Cl)). An osmotic gradient generated by NaCl with relatively apical hypertonicity (NaCl-absorption-direction) induced a large increase in the G(Na) associated with a small increase in the G(Cl), whereas an osmotic gradient generated by NaCl with relatively basolateral hypertonicity (NaCl-secretion-direction) induced small increases in the G(Na) and the G(Cl). These increases in the Gp caused by NaCl-generated osmotic gradients were diminished by the application of sucrose canceling the NaCl-generated osmotic gradient. The osmotic gradient generated by apical [corrected] application of sucrose without any NaCl gradients had little effects on the Gp. However, this apical [corrected] application of sucrose produced a precondition drastically quickening the time course of the action of the NaCl-generated osmotic gradient on the Gp. Further, we found that application of the basolateral hypotonicity generated by reduction of NaCl concentration shifted the localization of claudin-1 to the apical from the lateral [corrected] side. These results indicate that the osmotic gradient regulates the paracellular ion conductive pathway of tight junctions via a mechanism dependent on the direction of NaCl gradients associated with a shift of claudin-1 localization to the apical side in renal A6 epithelial cells.

  15. NaNaX 4--4th event of the international conference series "Nanoscience with Nanocrystals".

    PubMed

    Reiss, Peter

    2010-07-27

    The conference "NaNaX 4--Nanoscience with Nanocrystals" held near Munich (April 11-15, 2010) brought together a wide range of scientists discussing the most important current issues in the field of colloidal nanoparticles. Chemical synthesis gives access to nanocrystals of controlled size, shape, composition, and surface functionalization. Past research mainly concentrated on cadmium and lead chalcogenide nanocrystals as well as on gold and iron oxide nanoparticles. Today, there is a trend toward the development of nanoscale heterostructures, which combine different classes of materials and exhibit unique optical, magnetic, and electronic properties. Beside their interest for fundamental science, colloidal nanoparticles hold great promise for a wide range of applications. To this end, speakers and poster presenters showed routes for designing and using nanocrystals in biological imaging and sensing, in energy-related applications, and in catalysis. This report gives a nonexhaustive overview of selected "hot topics" in nanoparticle research discussed at NaNaX 4.

  16. Crystallization kinetics from mixture Na2SO4/glycerol droplets of Na2SO4 by FTIR-ATR

    NASA Astrophysics Data System (ADS)

    Tan, Dan-Ting; Cai, Chen; Zhang, Yun; Wang, Na; Pang, Shu-Feng; Zhang, Yun-Hong

    2016-08-01

    The efflorescence of mixed Na2SO4/glycerol aerosols on the ZnSe substrate with various mole ratios (Na2SO4/glycerol = 1:1, 1:2, 1:4) has been studied in the relative humidity (RH) linearly decline process, using a situ Fourier transform infrared attenuated total reflection (FTIR-ATR) technique. The crystal ratio at a given RH can be gained by the absorbance of the band at 1132 cm-1, which shows the incomplete nucleation for mixed Na2SO4/glycerol aerosols and the decreased amount of the droplets crystallized at the lowest RH with the glycerol increase. Using the volume fraction of droplets that have yet to crystallize, the heterogeneous nucleation kinetics has been gained. By the Extended Aerosol Inorganics Model (E-AIM), the nucleation rate as the function of solute saturation degree has been gained for various mixed Na2SO4/glycerol aerosols.

  17. The discharge properties of Na/Ni 3S 2 cell at ambient temperature

    NASA Astrophysics Data System (ADS)

    Kim, Jong-Seon; Ahn, Hyo-Jun; Ryu, Ho-Suk; Kim, Dong-Ju; Cho, Gyu-Bong; Kim, Ki-Won; Nam, Tae-Hyun; Ahn, Jou Hyeon

    The discharge properties of a Na/Ni 3S 2 cell using 1 M NaCF 3SO 3 in tetra(ethylene glycol)dimethyl ether liquid electrolyte were investigated at room temperature. The products were characterized by X-ray diffraction, scanning electron microscopy and energy dispersive spectroscopy. Electrochemical properties of Na/Ni 3S 2 cells were also presented by cyclic voltammetry and the galvanostatic current method. Na/Ni 3S 2 cells have an initial discharge capacity of 420 mAh g -1 with a plateau potential at 0.94 V versus Na/Na +. After the first discharge, Ni 3S 2 and Na react at room temperature and then form sodium sulfide (Na 2S) and nickel. Sodium ion can be partially deintercalated from Na 2S charge reaction. The discharge process can be explained as follows: Ni 3S 2 + 4Na ↔ 3Ni + 2Na 2S.

  18. Drift tube measurements on Na+ ions and clusters using the 24mNa+ tracer

    NASA Astrophysics Data System (ADS)

    Kasuya, A.; Abmayr, B.; Ohtsuki, T.; Masumoto, K.; Kotajima, H.; Huenges, E.; Morinaga, H.

    1997-06-01

    Mobilities of sodium ions and their clusters in different gases have been measured by gamma-ray spectrometry using the 20 ms isomeric state of 24Na as tracer. This isomer is obtained through the β-decay of 24Ne, which was produced by bombarding 22Ne with the 7 MeV triton beam of a cyclotron. This new technique of measurement allows us to determine the mobility of sodium ions in non-reacting gases of a pressure above 1 mbar. Measurements have been carried out in gases of pressures ranging from 6 mbar to 1000 mbar under an electric field up to 250 V/cm at room temperature. The measured mobility of 24Na+ in pure neon gas at 1000 mbar was determined to be 3.2 cm2/Vs. This value is lower than the zero field mobility of about 8.5 cm2/Vs measured by Tyndall and Akridge. A small amount of polar molecules such as water or ethanol introduced into the drift tube causes their clustering with the sodium ions through monopole-dipole interaction, resulting in a strong decrease in the mobility. This clustering effect has been studied for various combinations of polar molecules and inert gases. The usable pressure range from 1 mbar to high pressures in the range of some hundred bars is interesting because most other methods for cluster studies cannot be done at such high pressures. With this method it is possible to measure the mobility change of sodium ions towards the condensation point and eventually even towards the critical point.

  19. Na(+) transport, and the E(1)P-E(2)P conformational transition of the Na(+)/K(+)-ATPase.

    PubMed Central

    Babes, A; Fendler, K

    2000-01-01

    We have used admittance analysis together with the black lipid membrane technique to analyze electrogenic reactions within the Na(+) branch of the reaction cycle of the Na(+)/K(+)-ATPase. ATP release by flash photolysis of caged ATP induced changes in the admittance of the compound membrane system that are associated with partial reactions of the Na(+)/K(+)-ATPase. Frequency spectra and the Na(+) dependence of the capacitive signal are consistent with an electrogenic or electroneutral E(1)P <--> E(2)P conformational transition which is rate limiting for a faster electrogenic Na(+) dissociation reaction. We determine the relaxation rate of the rate-limiting reaction and the equilibrium constants for both reactions at pH 6.2-8.5. The relaxation rate has a maximum value at pH 7.4 (approximately 320 s(-1)), which drops to acidic (approximately 190 s(-1)) and basic (approximately 110 s(-1)) pH. The E(1)P <--> E(2)P equilibrium is approximately at a midpoint position at pH 6.2 (equilibrium constant approximately 0.8) but moves more to the E(1)P side at basic pH 8.5 (equilibrium constant approximately 0.4). The Na(+) affinity at the extracellular binding site decreases from approximately 900 mM at pH 6.2 to approximately 200 mM at pH 8.5. The results suggest that during Na(+) transport the free energy supplied by the hydrolysis of ATP is mainly used for the generation of a low-affinity extracellular Na(+) discharge site. Ionic strength and lyotropic anions both decrease the relaxation rate. However, while ionic strength does not change the position of the conformational equilibrium E(1)P <--> E(2)P, lyotropic anions shift it to E(1)P. PMID:11053130

  20. Comparative study of NaTiO2 and NaNiO2 using first principle calculations

    NASA Astrophysics Data System (ADS)

    Dhariwal, Monika; Maitra, T.; Singh, Ishwar

    2013-02-01

    The electronic band structure of NaTiO2 and NaNiO2 in their low temperature phase is studied using full potential LAPW method within LSDA+U approach. Magnetic and orbital order is studied for both the compounds in their low temperature phase. Various energy scales such as crystal field splitting, Jahn Teller splitting, exchange splitting etc. are estimated and compared for these two systems.

  1. Carbon dioxide sequestration using NaHSO4 and NaOH: A dissolution and carbonation optimisation study.

    PubMed

    Sanna, Aimaro; Steel, Luc; Maroto-Valer, M Mercedes

    2017-03-15

    The use of NaHSO4 to leach out Mg fromlizardite-rich serpentinite (in form of MgSO4) and the carbonation of CO2 (captured in form of Na2CO3 using NaOH) to form MgCO3 and Na2SO4 was investigated. Unlike ammonium sulphate, sodium sulphate can be separated via precipitation during the recycling step avoiding energy intensive evaporation process required in NH4-based processes. To determine the effectiveness of the NaHSO4/NaOH process when applied to lizardite, the optimisation of the dissolution and carbonation steps were performed using a UK lizardite-rich serpentine. Temperature, solid/liquid ratio, particle size, concentration and molar ratio were evaluated. An optimal dissolution efficiency of 69.6% was achieved over 3 h at 100 °C using 1.4 M sodium bisulphate and 50 g/l serpentine with particle size 75-150 μm. An optimal carbonation efficiency of 95.4% was achieved over 30 min at 90 °C and 1:1 magnesium:sodium carbonate molar ratio using non-synthesised solution. The CO2 sequestration capacity was 223.6 g carbon dioxide/kg serpentine (66.4% in terms of Mg bonded to hydromagnesite), which is comparable with those obtained using ammonium based processes. Therefore, lizardite-rich serpentinites represent a valuable resource for the NaHSO4/NaOH based pH swing mineralisation process.

  2. Na(+)-translocating cytochrome bo terminal oxidase from Vitreoscilla: some parameters of its Na+ pumping and orientation in synthetic vesicles.

    PubMed

    Park, C; Moon, J Y; Cokic, P; Webster, D A

    1996-09-10

    Vitreoscilla cytochrome bo ubiquinol oxidase is similar in some properties to the Escherichia coli enzyme, but unlike the latter, the Vitreoscilla oxidase functions as a primary Na+ pump. When purified Vitreoscilla cytochrome bo is incorporated into liposomes made from Vitreoscilla phospholipids and energized with a quinol substrate, it translocates Na+, not H+, across the vesicle membrane. Since protonophores CCCP (carbonyl cyanide m-chlorophenylhydrazone) and DTHB (3,5-di-tert-butyl-4-hydroxybenzaldehyde) stimulated the Na+ pumping, it is unlikely that it is a secondary effect due to the presence of Na+/H+ antiporter activity in the preparations. The efficiency of the Na+ pumping was 3.93 Na+ pumped per O2 consumed when ascorbate/TMPD was used as the substrate. The cytochrome has a K(m) and Kcat for Na+ of 2.9 mM and 277 s-1, respectively. When ferricytochrome c was entrapped within liposomes prepared from Vitreoscilla phospholipids, it was reduced by Q1H2 (ubiquinol-1) but not by ascorbate/TMPD (N,N,N',N'-tetramethyl-1,4-phenylenediamine). Although Q1H2 was oxidized by cytochrome bo in solution at a rate approximately 14 times that of the latter substrate, the rate of accumulation of Na+ within cytochrome bo vesicles driven by the membrane impermeable ascorbate/TMPD was 1.23 times that of the membrane permeable ubiquinol. These data allowed a calculation that in these synthetic proteoliposomes the cytochrome bo molecules are only 51% directed inward; a value of 61% inward-directed was estimated by measuring the ascorbate/TMPD oxidase activity of the proteoliposomes before and after disrupting them with Triton X-100. A random orientation of the E. coli cytochrome bo oxidase in proteoliposomes has also been reported.

  3. Effect of NaCl and NaHCO3 on serum ionised calcium and blood gas status during sprinting.

    PubMed

    Beard, L A; Hinchcliff, K W

    2002-09-01

    Sodium bicarbonate is often administered to horses before racing in an attempt to delay fatigue and improve performance. We examined the effect of acid-base status on serum ionised calcium concentration (iCa) during high intensity exercise in 8 Standardbred mares. In a randomised, blinded, cross-over study, mares were administered each of 3 treatments, NaCl (0.7 g/kg bwt), NaHCO3 (1 g/kg bwt) in 3 l water, or 3 l of water only, 4 h before performing a standardised exercise test to fatigue on a treadmill. Mixed venous blood samples were collected as the horses ran for 5 min at 3 m/s, to fatigue at a predetermined speed (approxim